“The Influence of Surgical Intervention and Sagittal Alignment on Frailty in Adult Cervical Deformity” (2020) Operative Neurosurgery (Hagerstown, Md.)
The Influence of Surgical Intervention and Sagittal Alignment on Frailty in Adult Cervical Deformity
(2020) Operative Neurosurgery (Hagerstown, Md.), 18 (6), pp. 583-589.
Segreto, F.A.a b , Passias, P.G.a b , Brown, A.E.a b , Horn, S.R.a b , Bortz, C.A.a b , Pierce, K.E.a b , Alas, H.a b , Lafage, V.c , Lafage, R.c , Smith, J.S.d , Line, B.G.e , Diebo, B.G.f , Kelly, M.P.g , Mundis, G.M.h , Protopsaltis, T.S.a b , Soroceanu, A.i , Kim, H.J.c , Klineberg, E.O.j , Burton, D.C.k , Hart, R.A.l , Schwab, F.J.c , Bess, S.m , Shaffrey, C.I.d , Ames, C.P.n
a Division of Spine Surgery, Department of Orthopedic Surgery, NYU Hospital for Joint Diseases, New York UniversityNY
b Department of Neurosurgery, NYU Hospital for Joint Diseases, New York UniversityNY
c Department of Orthopedic Surgery, Hospital for Special SurgeryNY
d Department of Neurosurgery, University of Virginia Medical Center, University of Virginia, Charlottesville, VA, United States
e Department of Orthopedic Surgery, Rocky Mountain Scoliosis and Spine Center, Denver, CO, United States
f Department of Orthopedic Surgery, SUNY Downstate Health Sciences UniversityNY
g Department of Orthopedic Surgery, Washington University, St. Louis, MO, United States
h San Diego Center for Spinal Disorders, La JollaCA
i Department of Orthopaedic Surgery, University of Calgary, Calgary, Canada
j Department of Orthopaedic Surgery, University of California, Davis, CA, United States
k Department of Orthopedic Surgery, University of Kansas Medical Center, University of Kansas, Kansas City, KS, United States
l Department of Orthopaedic Surgery, Swedish Neuroscience Institute, Seattle, WA, United States
m Rocky Mountain Scoliosis and Spine, Denver, CO, United States
n Department of Neurological Surgery, University of California, San Francisco, CA, Mexico
Abstract
BACKGROUND: Frailty is a relatively new area of study for patients with cervical deformity (CD). As of yet, little is known of how operative intervention influences frailty status for patients with CD. OBJECTIVE: To investigate drivers of postoperative frailty score and variables within the cervical deformity frailty index (CD-FI) algorithm that have the greatest capacity for change following surgery. METHODS: Descriptive analysis of the cohort were performed, paired t-tests determined significant baseline to 1 yr improvements of factors comprising the CD-FI. Pearson bivariate correlations identified significant associations between postoperative changes in overall CD-FI score and CD-FI score components. Linear regression models determined the effect of successful surgical intervention on change in frailty score. RESULTS: A total of 138 patients were included with baseline frailty scores of 0.44. Following surgery, mean 1-yr frailty score was 0.27. Of the CD-FI variables, 13/40 (32.5%) were able to improve with surgery. Frailty improvement was found to significantly correlate with baseline to 1-yr change in CBV, PI-LL, PT, and SVA C7-S1. HRQL CD-FI components reading, feeling tired, feeling exhausted, and driving were the greatest drivers of change in frailty. Linear regression analysis determined successful surgical intervention and feeling exhausted to be the greatest significant predictors of postoperative change in overall frailty score. CONCLUSION: Complications, correction of sagittal alignment, and improving a patient’s ability to read, drive, and chronic exhaustion can significantly influence postoperative frailty. This analysis is a step towards a greater understanding of the relationship between disability, frailty, and surgery in CD. Copyright © 2019 by the Congress of Neurological Surgeons.
Author Keywords
Adult cervical deformity; Ames modifier; Cervical deformity frailty index; Frailty; Frailty drivers; Health-related quality of life; Postoperative frailty; Sagittal alignment; Surgical intervention; Surgical outcomes
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“No Brain Is an Island” (2020) Anesthesia and Analgesia
No Brain Is an Island
(2020) Anesthesia and Analgesia, 130 (6), pp. 1568-1571.
Guay, C.S., Avidan, M.S.
From the Department of Anesthesiology, Washington University School of Medicine, St Louis, MO, United States
Document Type: Article
Publication Stage: Final
Source: Scopus
“Preoperative Cognitive Abnormality, Intraoperative Electroencephalogram Suppression, and Postoperative Delirium: A Mediation Analysis” (2020) Anesthesiology
Preoperative Cognitive Abnormality, Intraoperative Electroencephalogram Suppression, and Postoperative Delirium: A Mediation Analysis
(2020) Anesthesiology, 132 (6), pp. 1458-1468.
Fritz, B.A., King, C.R., Ben Abdallah, A., Lin, N., Mickle, A.M., Budelier, T.P., Oberhaus, J., Park, D., Maybrier, H.R., Wildes, T.S., Avidan, M.S., Apakama, G., Aranake-Chrisinger, A., Bolzenius, J., Burton, J., Cui, V., Emmert, D.A., Goswami, S., Graetz, T.J., Gupta, S., Jordan, K., Kronzer, A., McKinnon, S.L., Muench, M.R., Murphy, M.R., Palanca, B.J., Patel, A., Spencer, J.W., Stevens, T.W., Strutz, P., Tedeschi, C.M., Torres, B.A., Trammel, E.R., Upadhyayula, R.T., Winter, A.C., Jacobsohn, E., Fong, T., Gallagher, J., Inouye, S.K., Schmitt, E.M., Somerville, E., Stark, S., Lenze, E.J., Melby, S.J., Tappenden, J., ENGAGES Research Group
From the Department of Anesthesiology (B.A.F., C.R.K., A.B., A.M.M., T.P.B., J.O., D.P., H.R.M., T.S.W., M.S.A) the Division of Biostatistics (N.L.), Washington University School of Medicine, St. Louis, Missouri the Department of Mathematics and Statistics, Washington University in St. Louis, St. Louis, Missouri (N.L.). Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri Department of Anesthesiology, Washington University School of Medicine
Abstract
BACKGROUND: Postoperative delirium is a common complication that hinders recovery after surgery. Intraoperative electroencephalogram suppression has been linked to postoperative delirium, but it is unknown if this relationship is causal or if electroencephalogram suppression is merely a marker of underlying cognitive abnormalities. The hypothesis of this study was that intraoperative electroencephalogram suppression mediates a nonzero portion of the effect between preoperative abnormal cognition and postoperative delirium. METHODS: This is a prespecified secondary analysis of the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) randomized trial, which enrolled patients age 60 yr or older undergoing surgery with general anesthesia at a single academic medical center between January 2015 and May 2018. Patients were randomized to electroencephalogram-guided anesthesia or usual care. Preoperative abnormal cognition was defined as a composite of previous delirium, Short Blessed Test cognitive score greater than 4 points, or Eight Item Interview to Differentiate Aging and Dementia score greater than 1 point. Duration of intraoperative electroencephalogram suppression was defined as number of minutes with suppression ratio greater than 1%. Postoperative delirium was detected via Confusion Assessment Method or chart review on postoperative days 1 to 5. RESULTS: Among 1,113 patients, 430 patients showed evidence of preoperative abnormal cognition. These patients had an increased incidence of postoperative delirium (151 of 430 [35%] vs.123 of 683 [18%], P < 0.001). Of this 17.2% total effect size (99.5% CI, 9.3 to 25.1%), an absolute 2.4% (99.5% CI, 0.6 to 4.8%) was an indirect effect mediated by electroencephalogram suppression, while an absolute 14.8% (99.5% CI, 7.2 to 22.5%) was a direct effect of preoperative abnormal cognition. Randomization to electroencephalogram-guided anesthesia did not change the mediated effect size (P = 0.078 for moderation). CONCLUSIONS: A small portion of the total effect of preoperative abnormal cognition on postoperative delirium was mediated by electroencephalogram suppression. Study precision was too low to determine if the intervention changed the mediated effect.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Update on Circumscribed Gliomas and Glioneuronal Tumors” (2020) Surgical Pathology Clinics
Update on Circumscribed Gliomas and Glioneuronal Tumors
(2020) Surgical Pathology Clinics, 13 (2), pp. 249-266.
Chen, J.a , Dahiya, S.M.b
a Department of Pathology and Microbiology, University of Nebraska Medical Center, 983135 Nebraska Medical Center, Omaha, NE 68198, USA
b Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
Abstract
Well-circumscribed intra-axial CNS tumors encompass a wide variety of gliomas and glioneuronal tumors, usually corresponding to WHO grades I and II. Nonetheless, sometimes high-grade ‘diffuse’ gliomas such as gliosarcoma and giant cell glioblastoma can be relatively circumscribed but are often found to have foci of diffuse infiltration on careful examination, harboring distinct molecular alterations. These tumors are excluded from the discussion in this chapter with the current review emphasizing on lower-grade entities to include a brief description of their histology and associated molecular findings. Like elsewhere in brain biopsy evaluation, imaging is crucial and acts as a surrogate to gross examination. Given the circumscribed nature of these tumors, surgery alone is the mainstay treatment in most entities. Copyright © 2020 Elsevier Inc. All rights reserved.
Author Keywords
Benign; Glioma; Glioneuronal tumor; Low-grade; Well-circumscribed
Document Type: Review
Publication Stage: Final
Source: Scopus
“Loss- or Gain-of-Function Mutations in ACOX1 Cause Axonal Loss via Different Mechanisms” (2020) Neuron
Loss- or Gain-of-Function Mutations in ACOX1 Cause Axonal Loss via Different Mechanisms
(2020) Neuron, 106 (4), pp. 589-606.e6. Cited 1 time.
Chung, H.-L.a b c , Wangler, M.F.a b d , Marcogliese, P.C.a b , Jo, J.b e , Ravenscroft, T.A.a b , Zuo, Z.a b , Duraine, L.c , Sadeghzadeh, S.f , Li-Kroeger, D.a b , Schmidt, R.E.g , Pestronk, A.g , Rosenfeld, J.A.a , Burrage, L.a , Herndon, M.J.g , Chen, S.a , Shillington, A.h i , Vawter-Lee, M.i j , Hopkin, R.h i , Rodriguez-Smith, J.i k , Henrickson, M.i k , Lee, B.a , Moser, A.B.l , Jones, R.O.l , Watkins, P.l , Yoo, T.m , Mar, S.n , Choi, M.m o , Bucelli, R.C.p , Yamamoto, S.a b d q , Lee, H.K.b d e q , Prada, C.E.h i , Chae, J.-H.o , Vogel, T.P.r , Bellen, H.J.a b c d q , Members of Undiagnosed Diseases Networks
a Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, United States
b Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030, United States
c Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, United States
d Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, United States
e Department of Pediatrics, Section of Neurology, Baylor College of Medicine, Houston, TX 77030, United States
f Department of Psychology, Harvard University, Cambridge, MA 02138, United States
g Department of Pathology and Immunology, Division of Neuropathology, Washington University School of Medicine, St. Louis, MO 63110, United States
h Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, United States
i Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, United States
j Division of Neurology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, United States
k Division of Rheumatology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, United States
l Division of Neurogenetics, Kennedy Krieger Institute, Johns Hopkins School of Medicine, Baltimore, MD 21205, United States
m Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea
n Department of Neurology, St. Louis Children’s Hospital, Washington University School of Medicine, St. Louis, MO 63110, United States
o Department of Pediatrics, Seoul National University College of Medicine, Seoul, South Korea
p Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United States
q Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, United States
r Department of Pediatrics, Section of Rheumatology, Baylor College of Medicine, Center for Human Immunobiology, Texas Children’s Hospital, Houston, TX 77030, United States
Abstract
Chung et al. show that ACOX1, a peroxisomal protein required for degrading VLCFA, is mostly expressed in glial cells. Its loss causes an accumulation of VLCFA and glial loss. An ACOX1 gain-of-function mutation identified in three individuals leads to elevated ROS and glial loss and is potently suppressed by antioxidants. © 2020
ACOX1 (acyl-CoA oxidase 1) encodes the first and rate-limiting enzyme of the very-long-chain fatty acid (VLCFA) β-oxidation pathway in peroxisomes and leads to H2O2 production. Unexpectedly, Drosophila (d) ACOX1 is mostly expressed and required in glia, and loss of ACOX1 leads to developmental delay, pupal death, reduced lifespan, impaired synaptic transmission, and glial and axonal loss. Patients who carry a previously unidentified, de novo, dominant variant in ACOX1 (p.N237S) also exhibit glial loss. However, this mutation causes increased levels of ACOX1 protein and function resulting in elevated levels of reactive oxygen species in glia in flies and murine Schwann cells. ACOX1 (p.N237S) patients exhibit a severe loss of Schwann cells and neurons. However, treatment of flies and primary Schwann cells with an antioxidant suppressed the p.N237S-induced neurodegeneration. In summary, both loss and gain of ACOX1 lead to glial and neuronal loss, but different mechanisms are at play and require different treatments. © 2020
Author Keywords
ACOX1 deficiency; antioxidant NACA; axonal dystrophy; Drosophila; fatty acid peroxidation; NACA; ROS; Schwann cells; very long chain fatty acids; wrapping glia
Document Type: Article
Publication Stage: Final
Source: Scopus
“The Value of Beliefs” (2020) Neuron
The Value of Beliefs
(2020) Neuron, 106 (4), pp. 561-565.
Bromberg-Martin, E.S.a , Sharot, T.b
a Department of Neuroscience, Washington University in St. Louis, St. Louis, MO 63110, United States
b Affective Brain Lab, Department of Experimental Psychology, University College London, London, WC1H 0AP, United Kingdom
Abstract
We construct our beliefs to meet two sometimes conflicting goals: forming accurate beliefs to inform our decisions and forming desirable beliefs that we value for their own sake. In this NeuroView, we consider emerging neuroscience evidence on how the brain motivates itself to form particular beliefs and why it does so. © 2020 Elsevier Inc.
We construct our beliefs to meet two sometimes conflicting goals: forming accurate beliefs to inform our decisions and forming desirable beliefs that we value for their own sake. In this NeuroView, we consider emerging neuroscience evidence on how the brain motivates itself to form particular beliefs and why it does so. © 2020 Elsevier Inc.
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Itch: A Paradigm of Neuroimmune Crosstalk” (2020) Immunity
Itch: A Paradigm of Neuroimmune Crosstalk
(2020) Immunity, 52 (5), pp. 753-766.
Wang, F.a b c , Kim, B.S.a b d e
a Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States
b Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO 63110, United States
c Department of Dermatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China
d Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, United States
e Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
Wang and Kim highlight new discoveries in neuroscience and immunology that have directly informed emerging therapeutic approaches to itch. They outline how classical immunologic pathways integrate with newly identified itch circuits to form a paradigm of sensory neuroimmunology. © 2020 Elsevier Inc.
Although the medical definition of itch has been in existence for 360 years, only in the last 20 years have we begun to understand the basic mechanisms that underlie this unique sensation. Therapeutics that specifically target chronic itch as a pathologic entity are currently still not available. Recent seminal advances in itch circuitry within the nervous system have intersected with discoveries in immunology in unexpected ways to rapidly inform emerging treatment strategies. The current review aims to introduce these basic concepts in itch biology and highlight how distinct immunologic pathways integrate with recently identified itch-sensory circuits in the nervous system to inform a major new paradigm of neuroimmunology and therapeutic development for chronic itch. © 2020 Elsevier Inc.
Document Type: Review
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Single-Cell Analysis of Human Retina Identifies Evolutionarily Conserved and Species-Specific Mechanisms Controlling Development” (2020) Developmental Cell
Single-Cell Analysis of Human Retina Identifies Evolutionarily Conserved and Species-Specific Mechanisms Controlling Development
(2020) Developmental Cell, 53 (4), pp. 473-491.e9.
Lu, Y.a b , Shiau, F.c , Yi, W.d , Lu, S.e , Wu, Q.a b f , Pearson, J.D.e , Kallman, A.g , Zhong, S.a b , Hoang, T.h , Zuo, Z.a , Zhao, F.i , Zhang, M.d f , Tsai, N.j , Zhuo, Y.a , He, S.a , Zhang, J.i , Stein-O’Brien, G.L.h , Sherman, T.D.k , Duan, X.j , Fertig, E.J.k l m n o p q , Goff, L.A.h l r , Zack, D.J.g h l s , Handa, J.T.g , Xue, T.d f t , Bremner, R.e , Blackshaw, S.g h r u v w , Wang, X.a b f t x , Clark, B.S.c y
a State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
b University of Chinese Academy of Sciences, Beijing, 100049, China
c John F. Hardesty, MD, Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, United States
d Hefei National Laboratory for Physical Sciences, at the Microscale, Neurodegenerative Disorder Research Center, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, University of Science and Technology of China, Hefei, 230026, China
e Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Sinai Health Systems, Department of Ophthalmology and Vision Science, and Department of Lab Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 1X5, Canada
f CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China
g Department of Ophthalmology, Wilmer Eye Institute Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
h Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
i Obstetrics and Gynecology Medical Center of Severe Cardiovascular of Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
j Departments of Ophthalmology and Physiology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, United States
k Department of Oncology, Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
l McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
m Institute for Data Intensive Engineering and Science, Johns Hopkins University, Baltimore, MD 21218, United States
n Institute for Computational Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
o Mathematical Institute for Data Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
p Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD 21218, United States
q Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
r Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD 21218, United States
s Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
t Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China
u Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
v Center for Human Systems Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
w Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
x Beijing Institute for Brain Disorders, Beijing, 100069, China
y Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
The development of single-cell RNA sequencing (scRNA-seq) has allowed high-resolution analysis of cell-type diversity and transcriptional networks controlling cell-fate specification. To identify the transcriptional networks governing human retinal development, we performed scRNA-seq analysis on 16 time points from developing retina as well as four early stages of retinal organoid differentiation. We identified evolutionarily conserved patterns of gene expression during retinal progenitor maturation and specification of all seven major retinal cell types. Furthermore, we identified gene-expression differences between developing macula and periphery and between distinct populations of horizontal cells. We also identified species-specific patterns of gene expression during human and mouse retinal development. Finally, we identified an unexpected role for ATOH7 expression in regulation of photoreceptor specification during late retinogenesis. These results provide a roadmap to future studies of human retinal development and may help guide the design of cell-based therapies for treating retinal dystrophies. Lu et al. performed scRNA-seq on the developing human retina and retinal organoids. Using comprehensive analyses, they deduced mechanisms regulating human retinal cell-fate specification and foveagenesis and contrasted these with murine retinal development. The data are a valuable resource for understanding human retinal development and disease. © 2020 Elsevier Inc.
Author Keywords
cell fate; fovea; gene regulatory networks; neurogenesis; neurogenic bHLH factor; organoid; patterning; retina; single cell RNA-seq; transcription factors
Document Type: Article
Publication Stage: Final
Source: Scopus
“Homeostatic Plasticity Shapes the Retinal Response to Photoreceptor Degeneration” (2020) Current Biology
Homeostatic Plasticity Shapes the Retinal Response to Photoreceptor Degeneration
(2020) Current Biology, 30 (10), pp. 1916-1926.e3.
Shen, N.a , Wang, B.a , Soto, F.a , Kerschensteiner, D.a b c d
a John F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, United States
b Department of Neuroscience, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, United States
c Department of Biomedical Engineering, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, United States
d Hope Center for Neurological Disorders, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, United States
Abstract
Homeostatic plasticity stabilizes input and activity levels during neural development, but whether it can restore connectivity and preserve circuit function during neurodegeneration is unknown. Photoreceptor degeneration is the most common cause of blindness in the industrialized world. Visual deficits are dominated by cone loss, which progresses slowly, leaving a window during which rewiring of second-order neurons (i.e., bipolar cells) could preserve function. Here we establish a transgenic model to induce cone degeneration with precise control and analyze bipolar cell responses and their effects on vision through anatomical reconstructions, in vivo electrophysiology, and behavioral assays. In young retinas, we find that three bipolar cell types precisely restore input synapse numbers when 50% of cones degenerate but one does not. Of the three bipolar cell types that rewire, two contact new cones within stable dendritic territories, whereas one expands its dendrite arbors to reach new partners. In mature retinas, only one of four bipolar cell types rewires homeostatically. This steep decline in homeostatic plasticity is accompanied by reduced light responses of bipolar cells and deficits in visual behaviors. By contrast, light responses and behavioral performance are preserved when cones degenerate in young mice. Our results reveal unexpected cell type specificity and a steep maturational decline of homeostatic plasticity. The effect of homeostatic plasticity on functional outcomes identify it as a promising therapeutic target for retinal and other neurodegenerative diseases. © 2020 Elsevier Inc.
Shen et al. find that homeostatic plasticity in young retinas differs between closely related bipolar cell types in the retina, that homeostatic plasticity of bipolar cells declines steeply with age, and that it determines the visual deficits incurred from photoreceptor degeneration. © 2020 Elsevier Inc.
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“A randomized controlled phase III study of VB-111 combined with bevacizumab vs bevacizumab monotherapy in patients with recurrent glioblastoma (GLOBE)” (2020) Neuro-oncology
A randomized controlled phase III study of VB-111 combined with bevacizumab vs bevacizumab monotherapy in patients with recurrent glioblastoma (GLOBE)
(2020) Neuro-oncology, 22 (5), pp. 705-717. Cited 1 time.
Cloughesy, T.F.a , Brenner, A.b , de Groot, J.F.c , Butowski, N.A.d , Zach, L.e , Campian, J.L.f , Ellingson, B.M.g , Freedman, L.S.h , Cohen, Y.C.i , Lowenton-Spier, N.i , Rachmilewitz Minei, T.i , Fain Shmueli, S.i , Patrick Y, W.j , GLOBE Study Investigatorsk
a Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States
b University of Texas Health San Antonio Cancer Center, San Antonio, TX, United States
c Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, United States
d Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, United States
e Oncology Institute, Chaim Sheba Medical Center, Tel HaShomer, Israel
f Division of Medical Oncology, Washington University School of Medicine, St Louis, MO, United States
g UCLA Brain Tumor Imaging Laboratory, Center for Computer Vision and Imaging Biomarkers, Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States
h Biostatistics and Biomathematics Unit, Gertner Institute for Epidemiology and Health Policy Research, Chaim Sheba Medical Center, Tel HaShomer, Israel
i VBL Therapeutics, Modi’in, Israel, Israel
j Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, United States
Abstract
BACKGROUND: Ofranergene obadenovec (VB-111) is an anticancer viral therapy that demonstrated in a phase II study a survival benefit for patients with recurrent glioblastoma (rGBM) who were primed with VB-111 monotherapy that was continued after progression with concomitant bevacizumab. METHODS: This pivotal phase III randomized, controlled trial compared the efficacy and safety of upfront combination of VB-111 and bevacizumab versus bevacizumab monotherapy. Patients were randomized 1:1 to receive VB-111 1013 viral particles every 8 weeks in combination with bevacizumab 10 mg/kg every 2 weeks (combination arm) or bevacizumab monotherapy (control arm). The primary endpoint was overall survival (OS), and secondary endpoints were objective response rate (ORR) by Response Assessment in Neuro-Oncology (RANO) criteria and progression-free survival (PFS). RESULTS: Enrolled were 256 patients at 57 sites. Median exposure to VB-111 was 4 months. The study did not meet its primary or secondary goals. Median OS was 6.8 versus 7.9 months in the combination versus control arm (hazard ratio, 1.20; 95% CI: 0.91-1.59; P = 0.19) and ORR was 27.3% versus 21.9% (P = 0.26). A higher rate of grades 3-5 adverse events was reported in the combination arm (67% vs 40%), mainly attributed to a higher rate of CNS and flu-like/fever events. Trends for improved survival with combination treatment were seen in the subgroup of patients with smaller tumors and in patients who had a posttreatment febrile reaction. CONCLUSIONS: In this study, upfront concomitant administration of VB-111 and bevacizumab failed to improve outcomes in rGBM. Change of treatment regimen, with the lack of VB-111 monotherapy priming, may explain the differences from the favorable phase II results. CLINICAL TRIALS REGISTRATION: NCT02511405. © The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.
Author Keywords
anti-angiogenesis; gene therapy; glioblastoma; VB-111; viral immuno-oncology
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“A Mobile Health App for the Collection of Functional Outcomes After Inpatient Stroke Rehabilitation: Pilot Randomized Controlled Trial” (2020) JMIR mHealth and uHealth
A Mobile Health App for the Collection of Functional Outcomes After Inpatient Stroke Rehabilitation: Pilot Randomized Controlled Trial
(2020) JMIR mHealth and uHealth, 8 (5), p. e17219.
Li, L.a , Huang, J.a b , Wu, J.a , Jiang, C.a , Chen, S.a , Xie, G.a , Ren, J.a , Tao, J.a b c , Chan, C.C.H.d , Chen, L.a b c , Wong, A.W.K.e f g
a College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China
b Key Laboratory of Orthopedics & Traumatology of Traditional Chinese Medicine and Rehabilitation, Fujian University of Traditional Chinese Medicine, Ministry of Education, Fuzhou, China
c Traditional Chinese Medicine Rehabilitation Research Center of State Administration of Traditional Chinese Medicine, Fuzhou, China
d Department of Rehabilitation Sciences, Hong Kong Polytechnic University, Hong Kong
e Program in Occupational Therapy, Washington University School of Medicine, St. Louis, MO, United States
f Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
g Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
Abstract
BACKGROUND: Monitoring the functional status of poststroke patients after they transition home is significant for rehabilitation. Mobile health (mHealth) technologies may provide an opportunity to reach and follow patients post discharge. However, the feasibility and validity of functional assessments administered by mHealth technologies are unknown. OBJECTIVE: This study aimed to evaluate the feasibility, validity, and reliability of functional assessments administered through the videoconference function of a mobile phone-based app compared with administration through the telephone function in poststroke patients after rehabilitation hospitalization. METHODS: A randomized controlled trial was conducted in a rehabilitation hospital in Southeast China. Participants were randomly assigned to either a videoconference follow-up (n=60) or a telephone follow-up (n=60) group. We measured the functional status of participants in each group at 2-week and 3-month follow-up periods. Half the participants in each group were followed by face-to-face home visit assessments as the gold standard. Validity was assessed by comparing any score differences between videoconference follow-up and home visit assessments, as well as telephone follow-up and home visit assessments. Reliability was assessed by computing agreements between videoconference follow-up and home visit assessments, as well as telephone follow-up and home visit assessments. Feasibility was evaluated by the levels of completion, satisfaction, comfort, and confidence in the 2 groups. RESULTS: Scores obtained from the videoconference follow-up were similar to those of the home visit assessment. However, most scores collected from telephone administration were higher than those of the home visit assessment. The agreement between videoconference follow-up and home visit assessments was higher than that between telephone follow-up and home visit assessments at all follow-up periods. In the telephone follow-up group, completion rates were 95% and 82% at 2-week and 3-month follow-up points, respectively. In the videoconference follow-up group, completion rates were 95% and 80% at 2-week and 3-month follow-up points, respectively. There were no differences in the completion rates between the 2 groups at all follow-up periods (X21=1.6, P=.21 for 2-week follow-up; X21=1.9, P=.17 for 3-month follow-up). Patients in the videoconference follow-up group perceived higher confidence than those in the telephone follow-up group at both 2-week and 3-month follow-up periods (X23=6.7, P=.04 for 2-week follow-up; X23=8.0, P=.04 for 3-month follow-up). The videoconference follow-up group demonstrated higher satisfaction than the telephone follow-up group at 3-month follow-up (X23=13.9; P=.03). CONCLUSIONS: The videoconference follow-up assessment of functional status demonstrates higher validity and reliability, as well as higher confidence and satisfaction perceived by patients, than the telephone assessment. The videoconference assessment provides an efficient means of assessing functional outcomes of patients after hospital discharge. This method provides a novel solution for clinical trials requiring longitudinal assessments. TRIAL REGISTRATION: chictr.org.cn: ChiCTR1900027626; http://www.chictr.org.cn/edit.aspx?pid=44831&htm=4. ©Li Li, Jia Huang, Jingsong Wu, Cai Jiang, Shanjia Chen, Guanli Xie, Jinxin Ren, Jing Tao, Chetwyn C H Chan, Lidian Chen, Alex W K Wong. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 13.05.2020.
Author Keywords
activities of daily living; cell phone; health care; outcome and process assessment; rehabilitation; stroke; telemedicine
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Transcriptional analyses of adult and pediatric adamantinomatous craniopharyngioma reveals similar expression signatures regarding potential therapeutic targets” (2020) Acta Neuropathologica Communications
Transcriptional analyses of adult and pediatric adamantinomatous craniopharyngioma reveals similar expression signatures regarding potential therapeutic targets
(2020) Acta Neuropathologica Communications, 8 (1), p. 68.
Prince, E.a b , Whelan, R.c , Donson, A.b d , Staulcup, S.a , Hengartner, A.a b , Vijmasi, T.a b , Agwu, C.e , Lillehei, K.O.c , Foreman, N.K.b d , Johnston, J.M.f , Massimi, L.g h , Anderson, R.C.E.i , Souweidane, M.M.j k , Naftel, R.P.l , Limbrick, D.D.m n , Grant, G.o , Niazi, T.N.p , Dudley, R.q , Kilburn, L.r s , Jackson, E.M.t , Jallo, G.I.u , Ginn, K.v , Smith, A.w , Chern, J.J.x y , Lee, A.z aa , Drapeau, A.ab , Krieger, M.D.ac , Handler, M.H.a , Hankinson, T.C.a b , Advancing Treatment for Pediatric Craniopharyngioma Consortiumad
a Division of Pediatric Neurosurgery, Children’s Hospital Colorado, Aurora, United States
b Morgan Adams Foundation Pediatric Brain Tumor Research Program, Aurora, United States
c Department of Neurosurgery, University of Colorado School of Medicine, Aurora, United States
d Division of Pediatric Neurooncology, Children’s Hospital Colorado, Aurora, United States
e Washington University in St. Louis, St. Louis, United States
f Division of Pediatric Neurosurgery, Department of Neurosurgery, University of Alabama at Birmhingham, Birmingham, United States
g Neurochirurgia Pediatrica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
h Istituto di Neurochirurgia, Università Cattolica del Sacro Cuore, Roma, Italy
i Department of Neurosurgery, Columbia University, Morgan Stanley Children’s Hospital of NewYork-PresbyterianNY, United States
j Department of Neurosurgery, Memorial Sloan Kettering Cancer CenterNY, United States
k Department of Neurological Surgery, Weill Cornell Medical CollegeNY, United States
l Department of Neurological Surgery, Vanderbilt University Medical Center, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, United States
m Department of Pediatrics, Washington University School of Medicine, St. Louis, United States
n Department of Neurosurgery, Washington University School of Medicine, St. Louis, United States
o Department of Pediatric Neurosurgery, Lucile Packard Children’s Hospital at Stanford University, Palo Alto, United States
p Department of Pediatric Neurosurgery, Nicklaus Children’s Hospital, Miami, United States
q Department of Neurosurgery, McGill University, Montreal, Canada
r Children’s National Health System, Center for Cancer and Blood Disorders, DCWA, United States
s Children’s National Health System, Brain Tumor Institute, DCWA, United States
t Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, United States
u Johns Hopkins All Children’s Hospital, Institute of Brain Protection Sciences, St Petersburg, United States
v Division of Pediatric Hematology and Oncology, Department of Pediatrics, Children’s Mercy Hospital, Kansas City, United States
w Department of Pediatric Hematology-Oncology, Arnold Palmer Hospital, Orlando, United States
x Departments of Pediatrics and Neurosurgery, Emory University School of Medicine, Atlanta, United States
y Department of Pediatric Neurosurgery, Children’s Healthcare of Atlanta, Atlanta, United States
z Department of Pediatric Neurosurgery, Seattle Children’s Hospital, Seattle, United States
aa Department of Neurological Surgery, University of Washington School of Medicine, Seattle, United States
ab Division of Pediatric Neurosurgery, Nationwide Children’s Hospital, Columbus, United States
ac Department of Neurosurgery, Children’s Hospital Los Angeles, Los Angeles, United States
Abstract
Adamantinomatous craniopharyngioma (ACP) is a biologically benign but clinically aggressive lesion that has a significant impact on quality of life. The incidence of the disease has a bimodal distribution, with peaks occurring in children and older adults. Our group previously published the results of a transcriptome analysis of pediatric ACPs that identified several genes that were consistently overexpressed relative to other pediatric brain tumors and normal tissue. We now present the results of a transcriptome analysis comparing pediatric to adult ACP to identify biological differences between these groups that may provide novel therapeutic insights or support the assertion that potential therapies identified through the study of pediatric ACP may also have a role in adult ACP. Using our compiled transcriptome dataset of 27 pediatric and 9 adult ACPs, obtained through the Advancing Treatment for Pediatric Craniopharyngioma Consortium, we interrogated potential age-related transcriptional differences using several rigorous mathematical analyses. These included: canonical differential expression analysis; divisive, agglomerative, and probabilistic based hierarchical clustering; information theory based characterizations; and the deep learning approach, HD Spot. Our work indicates that there is no therapeutically relevant difference in ACP gene expression based on age. As such, potential therapeutic targets identified in pediatric ACP are also likely to have relvance for adult patients.
Author Keywords
Adamantinomatous Craniopharyngioma; Age-related therapy; Pediatric Craniopharyngioma; Suprasellar tumor; Transcriptional analysis
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Neonatal CSF vasopressin concentration predicts later medical record diagnoses of autism spectrum disorder” (2020) Proceedings of the National Academy of Sciences of the United States of America
Neonatal CSF vasopressin concentration predicts later medical record diagnoses of autism spectrum disorder
(2020) Proceedings of the National Academy of Sciences of the United States of America, 117 (19), pp. 10609-10613.
Oztan, O.a , Garner, J.P.a b , Constantino, J.N.c d , Parker, K.J.a
a Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, United States
b Department of Comparative Medicine, Stanford University, Stanford, CA 94305, United States
c Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63110, United States
d Department of Pediatrics, Washington University in St. Louis, St. Louis, MO 63110, United States
Abstract
Autism spectrum disorder (ASD) is a brain disorder characterized by social impairments. ASD is currently diagnosed on the basis of behavioral criteria because no robust biomarkers have been identified. However, we recently found that cerebrospinal fluid (CSF) concentration of the “social” neuropeptide arginine vasopressin (AVP) is significantly lower in pediatric ASD cases vs. controls. As an initial step in establishing the direction of causation for this association, we capitalized upon a rare biomaterials collection of newborn CSF samples to conduct a quasi-prospective test of whether this association held before the developmental period when ASD first manifests. CSF samples had been collected in the course of medical care of 0- to 3-mo-old febrile infants (n = 913) and subsequently archived at -70 °C. We identified a subset of CSF samples from individuals later diagnosed with ASD, matched them 1:2 with appropriate controls (n = 33 total), and quantified their AVP and oxytocin (OXT) concentrations. Neonatal CSF AVP concentrations were significantly lower among ASD cases than controls and individually predicted case status, with highest precision when cases with comorbid attention-deficit/hyperactivity disorder were removed from the analysis. The associations were specific to AVP, as ASD cases and controls did not differ in neonatal CSF concentrations of the structurally related neuropeptide, OXT. These preliminary findings suggest that a neurochemical marker of ASD may be present very early in life, and if replicated in a larger, prospective study, this approach could transform how ASD is detected, both in behaviorally symptomatic children, and in infants at risk for developing it. © 2020 National Academy of Sciences. All rights reserved.
Author Keywords
Autism; Cerebrospinal fluid; Oxytocin; Social; Vasopressin
Document Type: Article
Publication Stage: Final
Source: Scopus
“mHealth Assessment and Intervention of Depression and Anxiety in Older Adults” (2020) Harvard Review of Psychiatry
mHealth Assessment and Intervention of Depression and Anxiety in Older Adults
(2020) Harvard Review of Psychiatry, 28 (3), pp. 203-214.
Grossman, J.T., Frumkin, M.R., Rodebaugh, T.L., Lenze, E.J.
From the Department of Psychological and Brain Sciences, Washington University in St. Louis (Mr. Grossman, Ms. Frumkin, and Dr. Rodebaugh); Department of Psychiatry, Washington University School of Medicine (Dr. Lenze)
Abstract
Mobile technology is increasingly being used to enhance health and wellness, including in the assessment and treatment of psychiatric disorders. Such applications have been referred to collectively as mHealth, and this article provides a comprehensive review and clinical perspective of research regarding mHealth in late-life mood and anxiety disorders. The novel data collection offered by mHealth has contributed to a broader understanding of psychopathology, to an increased diversity of psychological interventions, and to novel methods of assessment that may ultimately provide individually adaptive mental health care for this population. Older adults face challenges (e.g., transportation, mobility) that limit their ability to receive medical and mental health care services, and mHealth may improve the capacity to reach this population. Although several mobile interventions exist for health-related issues in older adults (e.g., balance, diabetes, medication management), mHealth targeting psychiatric disorders is limited and most often focuses on problems related to dementia, cognitive dysfunction, and memory loss. Given that depression and anxiety are two of the most common mental health concerns among this population, mHealth has strong potential for broad public health interventions that may improve effectiveness of mental health care via individualized assessments and treatments.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Rev-erbα heterozygosity produces a dose-dependent phenotypic advantage in mice” (2020) PLoS ONE
Rev-erbα heterozygosity produces a dose-dependent phenotypic advantage in mice
(2020) PLoS ONE, 15 (5), art. no. e0227720, .
Welch, R.D.a , Billon, C.b , Kameric, A.c , Burris, T.P.b , Flaveny, C.A.c d e
a Salk Institute for Biological Sciences, San diego, CA, United States
b Center for Clinical Pharmacology, Saint Louis College of Pharmacy, Saint Louis, MO, United States
c Department of Pharmacology and Physiology, Saint Louis University School of Medicine, Saint Louis, MO, United States
d Alvin J. Siteman Cancer Center at Barnes-Jewish, Washington University School of Medicine in Saint Louis, Saint Louis, MO, United States
e Saint Louis University Henry, Amelia Nasrallah Center for Neuroscience, Saint Louis, MO, United States
Abstract
Numerous mutational studies have demonstrated that circadian clock proteins regulate behavior and metabolism. Nr1d1(Rev-erbα) is a key regulator of circadian gene expression and a pleiotropic regulator of skeletal muscle homeostasis and lipid metabolism. Loss of Rev-erbα expression induces muscular atrophy, high adiposity, and metabolic syndrome in mice. Here we show that, unlike knockout mice, Nr1d1 heterozygous mice are not susceptible to muscular atrophy and in fact paradoxically possess larger myofiber diameters and improved neuromuscular function, compared to wildtype mice. Heterozygous mice lacked dyslipidemia, a characteristic of Nr1d1 knockout mice and displayed increased whole-body fatty-acid oxidation during periods of inactivity (light cycle). Heterozygous mice also exhibited higher rates of glucose uptake when fasted, and had elevated basal rates of gluconeogenesis compared to wildtype and knockout littermates. Rev-erbα ablation suppressed glycolysis and fatty acid-oxidation in white-adipose tissue (WAT), whereas partial Rev-erbα loss, curiously stimulated these processes. Our investigations revealed that Rev-erbα dose-dependently regulates glucose metabolism and fatty acid oxidation in WAT and muscle. © 2020 Welch 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
“Mechanical Thrombectomy in the Era of the COVID-19 Pandemic: Emergency Preparedness for Neuroscience Teams: A Guidance Statement From the Society of Vascular and Interventional Neurology” (2020) Stroke
Mechanical Thrombectomy in the Era of the COVID-19 Pandemic: Emergency Preparedness for Neuroscience Teams: A Guidance Statement From the Society of Vascular and Interventional Neurology
(2020) Stroke, pp. STROKEAHA120030100.
Nguyen, T.N.a b c , Abdalkader, M.b , Jovin, T.G.d , Nogueira, R.G.e , Jadhav, A.P.f g , Haussen, D.C.e , Hassan, A.E.h , Novakovic, R.i , Sheth, S.A.j , Ortega-Gutierrez, S.k , Panagos, P.D.l , Cordina, S.M.m , Linfante, I.n , Mansour, O.Y.o , Malik, A.M.p , Narayanan, S.f , Masoud, H.E.q , Chou, S.H.-Y.f g r , Khatri, R.s , Janardhan, V.t , Yavagal, D.R.p , Zaidat, O.O.u , Greer, D.M.a , Liebeskind, D.S.v
a From the Department of Neurology, Boston Medical Center, Boston University School of Medicine
b Department of Radiology, Boston Medical Center, Boston University School of Medicine
c Department of Neurosurgery, Boston Medical Center, Boston University School of Medicine
d Department of Neurology, Cooper University Health Care, Camden
e Department of Neurology, Grady Memorial Hospital/Emory University, Atlanta, United States
f Department of Neurology, University of Pittsburgh Medical Center, S.N.
g Department of Neurosurgery, University of Pittsburgh Medical Center
h Department of Neuroscience
i Department of Neurology, UT Southwestern Medical Center, Dallas, United States
j Department of Neurology, UT Health McGovern Medical School, Houston
k Departments of Neurology, Neurosurgery, Radiology, University of Iowa Hospitals and Clinics (S.O.-G.)
l Department of Emergency Medicine, Washington University School of Medicine, St. Louis, United States
m Departments of Neurology, Neurosurgery, Radiology, University of Southern Alabama, Mobile, United States
n Departments of Interventional Neuroradiology and Endovascular Neurosurgery, Miami Cardiac and Vascular Institute, FL (I.L.)
o Departments of Neurology and Neuroradiology, Alexandria University Hospital
p Department of Neurology, University of Miami, FL (A.M.M.
q Departments of Neurology, Neurosurgery, Radiology, SUNY Upstate Medical University Hospital
r Department of Critical Care Medicine, University of Pittsburgh Medical Center
s Department of Neurointerventional Surgery, Texas Tech University
t Department of Neurology
u Neuroscience Institute, Bon Secours Mercy Health System, St. Vincent HospitalToledo, Belize
v Department of Neurology, UCLA Comprehensive Stroke Center
Author Keywords
coronavirus; COVID-19; Italy; personal protective equipment; stroke
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access
“Multiple Network Disconnection in Anosognosia for Hemiplegia” (2020) Frontiers in Systems Neuroscience
Multiple Network Disconnection in Anosognosia for Hemiplegia
(2020) Frontiers in Systems Neuroscience, 14, art. no. 21, .
Monai, E.a b , Bernocchi, F.a b , Bisio, M.a b , Bisogno, A.L.a b , Salvalaggio, A.a b , Corbetta, M.a b c
a Department of Neuroscience, Neurological Clinic, University of Padua, Padua, Italy
b Padova Neuroscience Center, University of Padua, Padua, Italy
c Department of Neurology, Radiology, and Neuroscience, Washington University in St. Louis, St. Louis, MO, United States
Abstract
Anosognosia for hemiplegia (AHP) is a complex syndrome whose neural correlates are still under investigation. One hypothesis, mainly based on lesion mapping studies, is that AHP reflects a breakdown of neural systems of the right hemisphere involved in motor function. However, more recent theories have suggested that AHP may represent a disorder of cognitive systems involved in belief updating, self-referential or body processing. Two recent studies, using a method to estimate the degree of white matter disconnection from lesions, have indeed shown that patients with AHP suffer from damage of several long-range white matter pathways in association cortex. Here, we use a similar indirect disconnection approach to study a group of patients with motor deficits without anosognosia (hemiparesis or hemiplegia, HP, n = 35), or motor deficits with AHP (n = 28). The HP lesions came from a database of stroke patients, while cases of AHP were selected from the published literature. Lesions were traced into an atlas from illustrations of the publications using a standard method. There was no region in the brain that was more damaged in AHP than HP. In terms of structural connectivity, AHP patients had a similar pattern of disconnection of motor pathways to HP patients. However, AHP patients also showed significant disconnection of the right temporo-parietal junction, right insula, right lateral and medial prefrontal cortex. These associative cortical regions were connected through several white matter tracts, including superior longitudinal fasciculus III, arcuate, fronto-insular, frontal inferior longitudinal, and frontal aslant. These tracts connected regions of different cognitive networks: default, ventral attention, and cingulo-opercular. These results were not controlled for clinical variables as concomitant symptoms and other disorders of body representation were not always available for co-variate analysis. In conclusion, we confirm recent studies of disconnection demonstrating that AHP is not limited to dysfunction of motor systems, but involves a much wider set of large-scale cortical networks. © Copyright © 2020 Monai, Bernocchi, Bisio, Bisogno, Salvalaggio and Corbetta.
Author Keywords
anosognosia; awareness; hemiplegia; network; stroke; structural disconnection
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Associations between racial and socioeconomic discrimination and risk behaviors among African-American adolescents and young adults: a latent class analysis” (2020) Social Psychiatry and Psychiatric Epidemiology
Associations between racial and socioeconomic discrimination and risk behaviors among African-American adolescents and young adults: a latent class analysis
(2020) Social Psychiatry and Psychiatric Epidemiology, .
Xie, T.H.a b , Ahuja, M.a c , McCutcheon, V.V.a , Bucholz, K.K.a
a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
b Indiana University, Bloomington, IN, United States
c Brown School of Social Work, Washington University in St. Louis, St. Louis, United States
Abstract
Purpose: Discrimination is a common stressor among African Americans and may increase vulnerability to risk behaviors, such as early initiation of substance use, substance use problems, and physical aggression; however, few studies have examined different types of discrimination and their associations with patterns of risk behaviors. This study examines the relationship between experiences of racial and socioeconomic discrimination and risk behaviors in African-American adolescents and young adults. Methods: We investigated associations of two discrimination types with risk behavior patterns identified with latent class analysis in a high-risk sample of African Americans (N = 797, Mage = 17.9 years, 50.2% female). Results: Four distinct classes of risk behaviors were characterized by High Use and Aggression (10%), Moderate Use and Aggression (10%), High Alcohol (17%), and Low Use and Aggression (63%). Classes that exhibit general risk behaviors, including substance use and aggression, were significantly associated with racial and socioeconomic discrimination, even in the fully adjusted model. Relative to other classes, the High Use and Aggression class demonstrated an elevated likelihood of experiencing both racial and socioeconomic discrimination. Conclusions: Findings support a link between racial and socioeconomic discrimination and risk behavior in African-American youth, which may be stronger for socioeconomic discrimination. Understanding the relationship between discrimination and risk behavior can inform future interventions to prevent substance misuse and conduct problems in youth. Further study is needed to elucidate the relationship between discrimination and other risk behaviors. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.
Author Keywords
Aggression; Black/African American; Discrimination; Latent class analysis; Substance use
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Utstein recommendation for emergency stroke care” (2020) International Journal of Stroke
Utstein recommendation for emergency stroke care
(2020) International Journal of Stroke, .
Rudd, A.G.a , Bladin, C.b , Carli, P.c , De Silva, D.A.d , Field, T.S.e , Jauch, E.C.f , Kudenchuk, P.g , Kurz, M.W.h , Lærdal, T.i , Ong, M.E.H.j , Panagos, P.k , Ranta, A.l , Rutan, C.m , Sayre, M.R.n , Schonau, L.o , Shin, S.D.p , Waters, D.q , Lippert, F.r , on behalf of the Utstein Stroke working groupr
a NHS England and King’s College, London, United Kingdom
b Eastern Health Monash University, Melbourne, Australia
c Emergency Medical Services, Paris, France
d National Neuroscience Institute, Singapore General Hospital, Singapore
e University of British Columbia, Vancouver, Canada
f Mission Health System, Asheville, United States
g University of Washington School of Medicine, Seattle, WA, United States
h Stavanger University Hospital, Stavanger, Norway
i The Laerdal Foundation, Stavanger, Norway
j Singapore General Hospital and Duke-NUS Medical School, Singapore, Singapore
k Washington University School of Medicine, St. Louis, MO, United States
l University of Otago, Dunedin, New Zealand
m American Heart Association, Dallas, TX, United States
n University of Washington, United States
o Danish Resuscitation Council, Copenhagen, Denmark
p Seoul National University College of Medicine, Seoul, South Korea
q Ambulance New Zealand, Wellington, New Zealand
r Copenhagen Emergency Medical Services, Copenhagen, Denmark
Abstract
Background: Recent advances in treatment for stroke give new possibilities for optimizing outcomes. To deliver these prehospital care needs to become more efficient. Aim: To develop a framework to support improved delivery of prehospital care. The recommendations are aimed at clinicians involved in prehospital and emergency health systems who will often not be stroke specialists but need clear guidance as to how to develop and deliver safe and effective care for acute stroke patients. Methods: Building on the successful implementation program from the Global Resuscitation Alliance and the Resuscitation Academy, the Utstein methodology was used to define a generic chain of survival for Emergency Stroke Care by assembling international expertise in Stroke and Emergency Medical Services (EMS). Ten programs were identified for Acute Stroke Care to improve survival and outcomes, with recommendations for implementation of best practice. Conclusions: Efficient prehospital systems for acute stroke will be improved through public awareness, optimized prehospital triage and timely diagnostics, and quick and equitable access to acute treatments. Documentation, use of metrics and transparency will help to build a culture of excellence and accountability. © 2020 World Stroke Organization.
Author Keywords
emergency medical services; prehospital care; Stroke
Document Type: Review
Publication Stage: Article in Press
Source: Scopus
“Sustained remission of child depression despite drift in parent emotion management skills 18 weeks following Parent Child Interaction Therapy: emotion development” (2020) European Child and Adolescent Psychiatry
Sustained remission of child depression despite drift in parent emotion management skills 18 weeks following Parent Child Interaction Therapy: emotion development
(2020) European Child and Adolescent Psychiatry, .
Luby, J.a , Donohue, M.R.a , Gilbert, K.a , Tillman, R.a , Barch, D.M.b
a Washington University School of Medicine, Child Psychiatry, St. Louis, MO 63130, United States
b Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO 63130, United States
Abstract
Whether effects of psychotherapies for depression are sustained after treatment is an important clinical issue. In older depressed children and adolescents such treatments have been shown to be sustained for several months. Rates of remission ranged from 62–69% at 3 months–1 year in one large scale study. To date there has been no data to inform whether the effects of earlier interventions for depression in the preschool period are sustained. To address this, we used data from a randomized controlled trial of a novel early intervention for depression called “Parent Child Interaction Therapy Emotion Development” (PCIT-ED) that has shown efficacy for depression, parenting stress and parenting practices. Participants and their caregivers were re-assessed 18 weeks after treatment completion. All study procedures were approved by the Washington University School of Medicine Internal Review Board prior to data collection. Study findings demonstrated a high rate of sustained gains in remission from depression, decreased parenting stress and parental depression 18 weeks after completion of a trial of PCIT-ED in a population of young children. Parental response to the child expression of emotion, a key treatment target drifted back towards baseline after 3 months. Relapse rates were 17% and predictors of relapse were the presence of an externalizing disorder, a higher number of co-morbid disorders and poorer guilt reparation and emotion regulation measured at treatment completion. This extends the body of literature demonstrating parent–child interaction therapy (PCIT) to have sustained effects on targeted disruptive symptom profiles to early childhood depression. This relatively low relapse rate after 18 weeks is comparable or better than many empirically proven treatments for depression in older children. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.
Author Keywords
Child psychopathology; Childhood depression; Parenting; PCIT
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Split-Brain: What We Know Now and Why This is Important for Understanding Consciousness” (2020) Neuropsychology Review
Split-Brain: What We Know Now and Why This is Important for Understanding Consciousness
(2020) Neuropsychology Review, .
de Haan, E.H.F.a , Corballis, P.M.b , Hillyard, S.A.c , Marzi, C.A.d , Seth, A.e , Lamme, V.A.F.a , Volz, L.f , Fabri, M.g , Schechter, E.h , Bayne, T.i , Corballis, M.b , Pinto, Y.a
a Department of Psychology, University of Amsterdam, Amsterdam, Netherlands
b School of Psychology, University of Auckland, Auckland, New Zealand
c School of Health Sciences, University of California Dan Diego, La Jolla, CA, United States
d School of Medicine and Surgery, University of Verona, Verona, Italy
e Sackler Centre for Consciousness Science, Sussex University, Brighton, United Kingdom
f Klinik für Neurologie, Universitätsklinikum Köln, Kerpener Str, Köln, 62, Germany
g Dipartimento di Medicina Sperimentale e Clinica, Via Tronto 10/A, Ancona, 60020, Italy
h Department of Philosophy, Washington University, St. Louis, MO, United States
i Department of Philosophy, Monash University, Melbourne, Australia
Abstract
Recently, the discussion regarding the consequences of cutting the corpus callosum (“split-brain”) has regained momentum (Corballis, Corballis, Berlucchi, & Marzi, Brain, 141(6), e46, 2018; Pinto et al., Brain, 140(5), 1231–1237, 2017a; Pinto, Lamme, & de Haan, Brain, 140(11), e68, 2017; Volz & Gazzaniga, Brain, 140(7), 2051–2060, 2017; Volz, Hillyard, Miller, & Gazzaniga, Brain, 141(3), e15, 2018). This collective review paper aims to summarize the empirical common ground, to delineate the different interpretations, and to identify the remaining questions. In short, callosotomy leads to a broad breakdown of functional integration ranging from perception to attention. However, the breakdown is not absolute as several processes, such as action control, seem to remain unified. Disagreement exists about the responsible mechanisms for this remaining unity. The main issue concerns the first-person perspective of a split-brain patient. Does a split-brain harbor a split consciousness or is consciousness unified? The current consensus is that the body of evidence is insufficient to answer this question, and different suggestions are made with respect to how future studies might address this paucity. In addition, it is suggested that the answers might not be a simple yes or no but that intermediate conceptualizations need to be considered. © 2020, The Author(s).
Author Keywords
Consciousness agents; Epilepsy; Lateralization; Split-brain; Visual perception
Document Type: Review
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access
“Author Correction: Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease (Nature Medicine, (2020), 26, 1, (131-142), 10.1038/s41591-019-0695-9)” (2020) Nature Medicine
Author Correction: Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease (Nature Medicine, (2020), 26, 1, (131-142), 10.1038/s41591-019-0695-9)
(2020) Nature Medicine, .
Zhou, Y.a , Song, W.M.a , Andhey, P.S.a , Swain, A.a , Levy, T.b , Miller, K.R.c , Poliani, P.L.d , Cominelli, M.d , Grover, S.e , Gilfillan, S.a , Cella, M.a , Ulland, T.K.f , Zaitsev, K.a k , Miyashita, A.g , Ikeuchi, T.g , Sainouchi, M.h , Kakita, A.h , Bennett, D.A.i , Schneider, J.A.i , Nichols, M.R.e , Beausoleil, S.A.b , Ulrich, J.D.j , Holtzman, D.M.j , Artyomov, M.N.a , Colonna, M.a
a Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
b Bluefin Biomedicine, Beverly, MA, United States
c NanoString, Seattle, WA, United States
d Pathology Unit, Molecular and Translational Medicine Department, University of Brescia, Brescia, Italy
e Department of Chemistry & Biochemistry, University of Missouri-St. Louis, St. Louis, MO, United States
f Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI, United States
g Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan
h Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan
i Rush Alzheimer’s Disease Center and Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, United States
j Department of Neurology, Hope Center for Neurological Disorders, Knight ADRC, Washington University School of Medicine, St. Louis, MO, United States
k Computer Technologies Department, ITMO University, Saint Petersburg, Russian Federation
Abstract
In the version of this article initially published, the ‘Data availability’ statement indicated that the data had been deposited to Synapse; however, the data have since been relocated to the AD Knowledge Portal under study snRNAseqAD_TREM2. The statement has been updated to reflect this relocation and to include revised information on requests for data. The errors have been corrected in the HTML and PDF versions of the article. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
Document Type: Erratum
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access
“Idiographic Traits: A Return to Allportian Approaches to Personality” (2020) Current Directions in Psychological Science
Idiographic Traits: A Return to Allportian Approaches to Personality
(2020) Current Directions in Psychological Science, .
Beck, E.D., Jackson, J.J.
Department of Psychological & Brain Sciences, Washington University in St. Louis, United States
Abstract
Since its beginnings, personality psychology has focused on both nomothetic and idiographic questions, but nomothetic approaches have captured the majority of attention in the past century. In this article, we demonstrate how recent measurement and modeling techniques provide an avenue for testing idiographic propositions about the dynamic features of a personality system. Findings indicate that people have unique structures of personality and that these structures are sensitive to situations people encounter. At the same time, these unique, mutable systems show longitudinal consistency for some but not all people. © The Author(s) 2020.
Author Keywords
dynamics; idiographic; personality; structure; traits
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“AADC deficiency from infancy to adulthood: Symptoms and developmental outcome in an international cohort of 63 patients” (2020) Journal of Inherited Metabolic Disease
AADC deficiency from infancy to adulthood: Symptoms and developmental outcome in an international cohort of 63 patients
(2020) Journal of Inherited Metabolic Disease, .
Pearson, T.S.a , Gilbert, L.a , Opladen, T.b , Garcia-Cazorla, A.c , Mastrangelo, M.d , Leuzzi, V.d , Tay, S.K.H.e , Sykut-Cegielska, J.f , Pons, R.g , Mercimek-Andrews, S.h , Kato, M.i , Lücke, T.j , Oppebøen, M.k , Kurian, M.A.l , Steel, D.l , Manti, F.d , Meeks, K.D.a , Jeltsch, K.b , Flint, L.m
a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b Division of Child Neurology & Metabolic Medicine, University Children’s Hospital, Heidelberg, Germany
c Inborn Errors of Metabolism Unit, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, Barcelona, Spain
d Unit of Child Neurology and Psychiatry, Department of Human Neuroscience, Sapienza University of Rome, Rome, Italy
e KTP-National University Children’s Medical Institute, National University Health System, Singapore, Singapore
f Department of Inborn Errors of Metabolism and Pediatrics, Institute of Mother and Child, Warsaw, Poland
g First Department of Pediatrics, Aghia Sofia Hospital, University of Athens, Athens, Greece
h Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, ON, Canada
i Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan
j University Children’s Hospital, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
k Division of Child Neurology, Oslo University Hospital, Oslo, Norway
l Developmental Neurosciences, UCL Great Ormond Street-Institute of Child Health and Department of Neurology, Great Ormond Street Hospital, London, United Kingdom
m AADC Research Trust, Caterham, United Kingdom
Abstract
Aromatic l-amino acid decarboxylase deficiency (AADCD) is a rare, autosomal recessive neurodevelopmental disorder characterized by impaired synthesis of dopamine, noradrenaline, adrenaline and serotonin, leading to a complex syndrome of motor, behavioral, and autonomic symptoms. This retrospective study assessed the symptoms and developmental outcome of a large international cohort of patients with AADCD via physician and/or caregiver responses to a detailed, standardized questionnaire. Sixty-three patients (60% female; ages 6 months-36 years, median 7 years; 58 living) from 23 individual countries participated. Common symptoms at onset (median age 3 months, range 0-12 months) were hypotonia, developmental delay, and/or oculogyric crises. Oculogyric crises were present in 97% of patients aged 2 to 12 years, occurred in the majority of patients in all age groups, and tended to be most severe during early childhood. Prominent non-motor symptoms were sleep disturbance, irritable mood, and feeding difficulties. The majority of subjects (70%) had profound motor impairment characterized by absent head control and minimal voluntary movement, while 17% had mild motor impairment and were able to walk independently. Dopamine agonists were the medications most likely to produce some symptomatic benefit, but were associated with dose-limiting side effects (dyskinesia, insomnia, irritability, vomiting) that led to discontinuation 25% of the time. The age distribution of our cohort (70% of subjects under age 13 years) and the observation of a greater proportion of patients with a more severe disease phenotype in the younger compared to the older patients, both suggest a significant mortality risk during childhood for patients with severe disease. © 2020 SSIEM
Author Keywords
dystonia-parkinsonism; gene therapy; natural history; neurotransmitter disorders; rare diseases
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access
“Real-World Effectiveness of Initial Disease-Modifying Therapies in Pediatric Multiple Sclerosis” (2020) Annals of Neurology
Real-World Effectiveness of Initial Disease-Modifying Therapies in Pediatric Multiple Sclerosis
(2020) Annals of Neurology, .
Krysko, K.M.a , Graves, J.S.a b , Rensel, M.c , Weinstock-Guttman, B.d , Rutatangwa, A.a , Aaen, G.e , Belman, A.f , Benson, L.g , Chitnis, T.h , Gorman, M.g , Goyal, M.S.i , Harris, Y.j , Krupp, L.f , Lotze, T.k , Mar, S.l , Moodley, M.m , Ness, J.n , Rodriguez, M.o , Rose, J.p , Schreiner, T.q , Tillema, J.-M.o , Waltz, M.r , Casper, T.C.r , Waubant, E.a , the US Network of Pediatric MS Centerss
a UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, United States
b Department of Neurology, University of California, San Diego, La Jolla, CA, United States
c Department of Neurology, Cleveland Clinic, Cleveland, OH, United States
d Department of Neurology, State University of New York at Buffalo, Buffalo, NY, United States
e Department of Pediatrics, Loma Linda University, San Bernardino, CA, United States
f Department of Neurology, New York University Langone Medical Center, New York, NY, United States
g Department of Neurology, Boston Children’s Hospital, Boston, MA, United States
h Department of Pediatric Neurology, Massachusetts General Hospital, Boston, MA, United States
i Mallinckrodt Institute of Radiology, Washington University in Saint Louis, St Louis, MO, United States
j Department of Nursing, University of Alabama at Birmingham, Birmingham, AL, United States
k Department of Neurology, Texas Children’s Hospital, Houston, TX, United States
l Department of Neurology, Washington University in Saint Louis, St Louis, MO, United States
m Department of Pediatrics and Neurology, Dell Children’s Hospital, University of Texas, Austin, TX, United States
n Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, United States
o Department of Neurology, Mayo Clinic, Rochester, MN, United States
p Department of Neurology, University of Utah, Salt Lake City, UT, United States
q Departments of Neurology and Pediatrics, University of Colorado, Aurora, CO, United States
r Department of Pediatrics, University of Utah, Salt Lake City, UT, United States
Abstract
Objective: To assess real-world effectiveness of initial treatment with newer compared to injectable disease-modifying therapies (DMTs) on disease activity in pediatric multiple sclerosis (MS) and clinically isolated syndrome (CIS). Methods: This is a cohort study of children with MS/CIS followed at 12 clinics in the US Network of Pediatric MS Centers, who received initial therapy with newer (fingolimod, dimethyl fumarate, teriflunomide, natalizumab, rituximab, ocrelizumab) or injectable (interferon-β, glatiramer acetate) DMTs. Propensity scores (PSs) were computed, including preidentified confounders. Relapse rate while on initial DMT was modeled with negative binomial regression, adjusted for PS-quintile. Time to new/enlarging T2-hyperintense and gadolinium-enhancing lesions on brain magnetic resonance imaging were modeled with midpoint survival analyses, adjusted for PS-quintile. Results: A total of 741 children began therapy before 18 years, 197 with newer and 544 with injectable DMTs. Those started on newer DMTs were older (15.2 vs injectable 14.4 years, p = 0.001) and less likely to have a monofocal presentation. In PS-quintile–adjusted analysis, those on newer DMTs had a lower relapse rate than those on injectables (rate ratio = 0.45, 95% confidence interval (CI) = 0.29–0.70, p < 0.001; rate difference = 0.27, 95% CI = 0.14–0.40, p = 0.004). One would need to treat with newer rather than injectable DMTs for 3.7 person-years to prevent 1 relapse. Those started on newer DMTs had a lower rate of new/enlarging T2 (hazard ratio [HR] = 0.51, 95% CI = 0.36–0.72, p < 0.001) and gadolinium-enhancing lesions (HR = 0.38, 95% CI = 0.23–0.63, p < 0.001) than those on injectables. Interpretation: Initial treatment of pediatric MS/CIS with newer DMTs led to better disease activity control compared to injectables, supporting greater effectiveness of newer therapies. Long-term safety data for newer DMTs are required. ANN NEUROL 2020. © 2020 American Neurological Association
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Inherited Risk for Autism Through Maternal and Paternal Lineage” (2020) Biological Psychiatry
Inherited Risk for Autism Through Maternal and Paternal Lineage
(2020) Biological Psychiatry, .
Bai, D.a , Marrus, N.b , Yip, B.H.K.a d , Reichenberg, A.e f g h , Constantino, J.N.b c , Sandin, S.a d e f
a Jockey Club School of Public Health and Primary Care, Chinese University of Hong Kong, Hong Kong
b Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
c Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
d Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
e Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States
f Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, United States
g Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
h Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
Abstract
Background: Autism spectrum disorder (ASD) is highly familial, with a positively skewed male-to-female ratio that is purported to arise from the so-called female protective effect. A serious implication of a female protective effect is that familial ASD liability would be expected to aggregate asymptomatically in sisters of affected probands, who would incur elevated rates of ASD among their offspring. Currently, there exist no data on second-generation recurrence rates among families affected by ASD. Methods: We analyzed data from the Swedish National Patient Register and the Multi-Generation Register for a cohort of children born between 2003 and 2012. ASD was ascertained in both the child and parental generations. Results: Among 847,732 children, 13,103 (1.55%) children in the cohort were diagnosed with ASD. Among their maternal/paternal aunts and uncles, 1744 (0.24%) and 1374 (0.18%) were diagnosed with ASD, respectively. Offspring of mothers with a sibling(s) diagnosed with ASD had higher rates of ASD than the general population (relative risk, 3.05; 95% confidence interval, 2.52–3.64), but not more than would be predicted for second-degree relatives within a generation, and only slightly more than was observed for fathers with siblings with ASD (relative risk, 2.08; 95% confidence interval, 1.53–2.67). Models adjusting for temporal trends and for psychiatric history in the parental generation did not alter the results. Conclusions: These findings establish a robust general estimate of ASD transmission risk for siblings of individuals affected by ASD, the first ever reported. Our findings do not suggest female protective factors as the principal mechanism underlying the male sex bias in ASD. © 2020 Society of Biological Psychiatry
Author Keywords
Autism; Epidemiology; Female protective effect; Population-based; Psychiatry; Sex bias
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access
“Improvements in Neck Pain and Disability Following C1-C2 Posterior Cervical Instrumentation and Fusion for Atlanto-Axial Osteoarthritis” (2020) World Neurosurgery
Improvements in Neck Pain and Disability Following C1-C2 Posterior Cervical Instrumentation and Fusion for Atlanto-Axial Osteoarthritis
(2020) World Neurosurgery, .
Adogwa, O.a , Buchowski, J.M.a , Sielatycki, J.A.b , Shlykov, M.A.a , Theologis, A.A.a , Lin, J.b , CreveCoeur, T.a , Peters, C.a , Riew, K.D.b
a Department of Orthopedic Surgery, Washington University School of Medicine, St Louis, MO, United States
b Department of Orthopedic Surgery, New York Presbyterian Hospital/Columbia University School of Medicine, New York, NY, United States
Abstract
Objective: Symptomatic Atlanto-axial (C1-2) osteoarthritis (AAOA) is a common phenomenon in elderly patients; however, there is a paucity of data on the effectiveness of posterior atlanto-axial fusion (PAAF) for this condition. To this end, here we assess changes in patient-reported outcomes and neck-related disability in adult patients undergoing PAAF for symptomatic C1-2 AAOA. Methods: In this retrospective study, the clinical records of consecutive patients with symptomatic AAOA who underwent PAAF between 2004 and 2017 were reviewed. Patient demographics, comorbidities, intraoperative and postoperative variables, and complication rates were collected. Neck Disability Index (NDI) scores were recorded at baseline and 6 weeks, 6 months, 1 year, and 2 years postoperatively. Results: Forty-two patients (average age, 72.04 ± 8.56 years; 26.19% males) met the study’s inclusion criteria. In this cohort, 19.04% had previous subaxial cervical spine surgery, 35.71% had a history of smoking (all had stopped smoking before surgery), and 11.90% had type II diabetes. At baseline, the majority of patients had a normal neurologic exam. The average preoperative NDI score was 26.88 ± 24.85, which improved to 10.59 ± 14.88 at the 1-year follow-up and 13.20 ± 14.96 at the 2-year follow-up (P = 0.004). At baseline, 18% of the patients reported severe disability based on NDI score; this percentage decreased to 2% at 1 year and 0 at 2 years (P = 0.01). Importantly, a high percentage (11.90%) of patients had undergone previous subaxial cervical fusion for their pain due to a mistaken diagnosis for this condition, without symptom relief. Conclusions: In appropriately selected patients, PAAF may decrease neck pain and improve functional disability in patients with AAOA. Future prospective longitudinal studies are needed to corroborate these findings. © 2020 Elsevier Inc.
Author Keywords
Atlanto-axial osteoarthritis; C1-C2 osteoarthritis; Cervical osteoarthritis; Neck disability; Posterior atlanto-axial fusion
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Counterpoint. Early intervention for psychosis risk syndromes: Minimizing risk and maximizing benefit” (2020) Schizophrenia Research
Counterpoint. Early intervention for psychosis risk syndromes: Minimizing risk and maximizing benefit
(2020) Schizophrenia Research, .
Woods, S.W.a , Bearden, C.E.b ac , Sabb, F.W.c , Stone, W.S.d y , Torous, J.d , Cornblatt, B.A.e , Perkins, D.O.f , Cadenhead, K.S.g , Addington, J.h , Powers, A.R., IIIa ab , Mathalon, D.H.i , Calkins, M.E.j , Wolf, D.H.j , Corcoran, C.M.k , Horton, L.E.l , Mittal, V.A.m ad , Schiffman, J.n , Ellman, L.M.o , Strauss, G.P.p , Mamah, D.q , Choi, J.r , Pearlson, G.D.a r , Shah, J.L.s , Fusar-Poli, P.t u , Arango, C.v , Perez, J.w , Koutsouleris, N.x , Wang, J.y , Kwon, J.S.z , Walsh, B.C.a , McGlashan, T.H.a , Hyman, S.E.aa , Gur, R.E.j , Cannon, T.D.a ab , Kane, J.M.e , Anticevic, A.a ab
a Department of Psychiatry, Yale University, New Haven, CT, United States
b Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, United States
c Lewis Center for Neuroimaging, University of Oregon, Eugene, United States
d Department of Psychiatry, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, United States
e Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, United States
f Department of Psychiatry, University of North Carolina, Chapel Hill, United States
g Department of Psychiatry, University of California, San Diego, United States
h Department of Psychiatry, University of CalgaryAlberta, Canada
i Department of Psychiatry, University of California, San Francisco, United States
j Department of Psychiatry, University of Pennsylvania, Philadelphia, United States
k Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States
l Department of Psychiatry, University of PittsburghPA, United States
m Department of Psychology, Northwestern University, Evanston, IL, United States
n Department of Psychology, University of Maryland, Baltimore County, United States
o Department of Psychology, Temple University, Philadelphia, PA, United States
p Department of Psychology, University of Georgia, Athens, GA, United States
q Department of Psychiatry, Washington University in Saint LouisMO, United States
r Olin Neuropsychiatry Research Center, Institute of Living, Hartford HospitalCT, United States
s Department of Psychiatry, McGill University, Montreal, Canada
t Department of Psychosis Studies, King’s College London, United Kingdom
u Department of Behavioral Sciences, University of Pavia, Pavia, Italy
v Dept. of Child and Adolescent Psychiatry, Universidad Complutense de Madrid, Spain
w Department of Psychiatry, University of Cambridge, United Kingdom
x Department of Psychiatry, Ludwig Maximilian University of Munich, Germany
y Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, China
z Department of Psychiatry, Seoul National University College of Medicine, South Korea
aa Broad Institute of MIT and Harvard, Cambridge, MA, United States
ab Department of Psychology, Yale University, New Haven, CT, United States
ac Department Psychology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, United States
ad Department of Psychology, Northwestern University, Chicago, IL, United States
Abstract
Background: Malhi et al. in this issue critique the clinical high risk (CHR) syndrome for psychosis. Method: Response to points of critique. Results: We agree that inconsistency in CHR nomenclature should be minimized. We respectfully disagree on other points. In our view: a) individuals with CHR and their families need help, using existing interventions, even though we do not yet fully understand disease mechanisms; b) substantial progress has been made in identification of biomarkers; c) symptoms used to identify CHR are specific to psychotic illnesses; d) CHR diagnosis is not “extremely difficult”; e) the pattern of progression, although heterogenous, is discernible; f) “psychosis-like symptoms” are common but are not used to identify CHR; and g) on the point described as ‘the real risk,’ CHR diagnosis does not frequently cause harmful stigma. Discussion: Malhi et al.’s arguments do not fairly characterize progress in the CHR field nor efforts to minimize stigma. That said, much work remains in areas of consistent nomenclature, mechanisms of disease, dissecting heterogeneity, and biomarkers. With regard to what the authors term the “real risk” of stigma associated with a CHR “label,” however, our view is that avoiding words like “risk” and “psychosis” reinforces the stigma that both they and we mean to oppose. Moreover, patients and their families benefit from being given a term that describes what is happening to them. © 2020 Elsevier B.V.
Author Keywords
Autonomy; Beneficence; Biomarkers; Clinical high risk (CHR); Psychosis; Stigma
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Leukocyte Telomere Length Is Unrelated to Cognitive Performance among Non-Demented and Demented Persons: An Examination of Long Life Family Study Participants” (2020) Journal of the International Neuropsychological Society
Leukocyte Telomere Length Is Unrelated to Cognitive Performance among Non-Demented and Demented Persons: An Examination of Long Life Family Study Participants
(2020) Journal of the International Neuropsychological Society, .
Ashrafi, A.a , Cosentino, S.b , Kang, M.S.c , Lee, J.H.a , Schupf, N.a , Andersen, S.L.d , Christensen, K.e , Province, M.A.f , Thyagarajan, B.g , Zmuda, J.M.h , Honig, L.S.b
a Department of Epidemiology, Columbia University, Irving Medical Center, New York, NY, United States
b Department of Neurology, Columbia University, Irving Medical Center, New York, NY, United States
c Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, Irving Medical Center, New York, NY, United States
d Department of Medicine, Boston University, School of Medicine, Boston, MA, United States
e Department of Public Health, University of Southern Denmark, Odense, Denmark
f Department of Genetics, Washington University St. Louis, St. Louis, MO, United States
g Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, United States
h Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, United States
Abstract
Objective:Leukocyte telomere length (LTL) is a widely hypothesized biomarker of biological aging. Persons with shorter LTL may have a greater likelihood of developing dementia. We investigate whether LTL is associated with cognitive function, differently for individuals without cognitive impairment versus individuals with dementia or incipient dementia.Method:Enrolled subjects belong to the Long Life Family Study (LLFS), a multi-generational cohort study, where enrollment was predicated upon exceptional family longevity. Included subjects had valid cognitive and telomere data at baseline. Exclusion criteria were age ≤ 60 years, outlying LTL, and missing sociodemographic/clinical information. Analyses were performed using linear regression with generalized estimating equations, adjusting for sex, age, education, country, generation, and lymphocyte percentage.Results:Older age and male gender were associated with shorter LTL, and LTL was significantly longer in family members than spouse controls (p < 0.005). LTL was not associated with working or episodic memory, semantic processing, and information processing speed for 1613 cognitively unimpaired individuals as well as 597 individuals with dementia or incipient dementia (p < 0.005), who scored significantly lower on all cognitive domains (p < 0.005).Conclusions:Within this unique LLFS cohort, a group of families assembled on the basis of exceptional survival, LTL is unrelated to cognitive ability for individuals with and without cognitive impairment. LTL does not change in the context of degenerative disease for these individuals who are biologically younger than the general population. Copyright © INS. Published by Cambridge University Press, 2020.
Author Keywords
Cognition; Cognitive aging; Cognitive decline; Cognitive function; Cognitive tests; Dementia and longevity; Telomere shortening
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Remembering: Epistemic and Empirical” (2020) Review of Philosophy and Psychology
Remembering: Epistemic and Empirical
(2020) Review of Philosophy and Psychology, .
Craver, C.F.
Department of Philosophy, Wilson Hall, Washington University St. Louis, St. Louis, MO 63130, United States
Abstract
The construct “remembering” is equivocal between an epistemic sense, denoting a distinctive ground for knowledge, and empirical sense, denoting the typical behavior of a neurocognitive mechanism. Because the same kind of equivocation arises for other psychologistic terms (such as believe, decide, know, judge, decide, infer and reason), the effort to spot and remedy the confusion in the case of remembering might prove generally instructive. The failure to allow these two senses of remembering equal play in their respective domains leads, I argue, to unnecessary confusion about memory externalism, the possibility of episodic memory in non-human species, and the thesis of memory continuism. By distinguishing these equivocal senses of remembering, we thus gain leverage on understanding how the distinctive epistemic norms that define many of our psychologic terms are more plausibly related to the capacities studied by empirical science, given that neither identity nor elimination are possible. © 2020, Springer Nature B.V.
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Factors associated with therapeutic anticoagulation status in patients with ischemic stroke and atrial fibrillation” (2020) Journal of Stroke and Cerebrovascular Diseases
Factors associated with therapeutic anticoagulation status in patients with ischemic stroke and atrial fibrillation
(2020) Journal of Stroke and Cerebrovascular Diseases, art. no. 104888, .
Yaghi, S.a , Liberman, A.L.b , Henninger, N.c d , Grory, B.M.e , Nouh, A.f , Scher, E.a , Giles, J.g , Liu, A.g , Nagy, M.c , Kaushal, A.e , Azher, I.e , Fakhri, H.h , Espaillat, K.B.h , Asad, S.D.f , Pasupuleti, H.i , Martin, H.i , Tan, J.i , Veerasamy, M.i , Esenwa, C.b , Cheng, N.b , Moncrieffe, K.b , Moeini-Naghani, I.j , Siddu, M.j , Trivedi, T.a , Ishida, K.a , Frontera, J.a , Lord, A.a , Furie, K.e , Keyrouz, S.g , de Havenon, A.k , Mistry, E.h , Leon Guerrero, C.R.j , Khan, M.i
a Department of Neurology, New York Langone Health, 150 55th St Suite 3667, Brooklyn, NY 11220, United States
b Department of Neurology, Montefiore Medical Center, New York, NY, United States
c Department of Neurology, University of Massachusetts, Worcester, MA, United States
d Department of Psychiatry, University of Massachusetts, Worcester, MA, United States
e Department of Neurology, Brown University, Providence, RI, United States
f Department of Neurology, Hartford Hospital, Hartford, CT, United States
g Department of Neurology, Washington University, Saint Louis, MO, United States
h Department of Neurology, Vanderbilt University, Nashville, TN, United States
i Department of Neurology, Spectrum Health, Grand Rapids, MI, United States
j Department of Neurology, George Washington University, Washington, DC, United States
k Department of Neurology, University of Utah, Salt Lake City, UT, United States
Abstract
Background and purpose: Understanding factors associated with ischemic stroke despite therapeutic anticoagulation is an important goal to improve stroke prevention strategies in patients with atrial fibrillation (AF). We aim to determine factors associated with therapeutic or supratherapeutic anticoagulation status at the time of ischemic stroke in patients with AF. Methods: The Initiation of Anticoagulation after Cardioembolic stroke (IAC) study is a multicenter study pooling data from stroke registries of eight comprehensive stroke centers across the United States. Consecutive patients hospitalized with acute ischemic stroke in the setting of AF were included in the IAC cohort. For this study, we only included patients who reported taking warfarin at the time of the ischemic stroke. Patients not on anticoagulation and patients who reported use of a direct oral anticoagulant were excluded. Analyses were stratified based on therapeutic (INR ≥2) versus subtherapeutic (INR <2) anticoagulation status. We used binary logistic regression models to determine factors independently associated with anticoagulation status after adjustment for pertinent confounders. In particular, we sought to determine whether atherosclerosis with 50% or more luminal narrowing in an artery supplying the infarct (a marker for a competing atherosclerotic mechanism) and small stroke size (≤ 10 mL; implying a competing small vessel disease mechanism) related to anticoagulant status. Results: Of the 2084 patients enrolled in the IAC study, 382 patients met the inclusion criteria. The mean age was 77.4 ± 10.9 years and 52.4% (200/382) were women. A total of 222 (58.1%) subjects presented with subtherapeutic INR. In adjusted models, small stroke size (OR 1.74 95% CI 1.10–2.76, p = 0.019) and atherosclerosis with 50% or more narrowing in an artery supplying the infarct (OR 1.96 95% CI 1.06–3.63, p = 0.031) were independently associated with INR ≥2 at the time of their index stroke. Conclusion: Small stroke size (≤ 10 ml) and ipsilateral atherosclerosis with 50% or more narrowing may indicate a competing stroke mechanism. There may be important opportunities to improve stroke prevention strategies for patients with AF by targeting additional ischemic stroke mechanisms to improve patient outcomes. © 2020 Elsevier Inc.
Author Keywords
Anticoagulation; Atrial fibrillation; Predictors; Recurrence; Stroke
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Reparative Prosocial Behavior Difficulties across Childhood Predict Poorer Social Functioning and Depression in Adolescence” (2020) Journal of Abnormal Child Psychology
Reparative Prosocial Behavior Difficulties across Childhood Predict Poorer Social Functioning and Depression in Adolescence
(2020) Journal of Abnormal Child Psychology, .
Donohue, M.R., Tillman, R., Luby, J.
Department of Psychiatry, Washington University School of Medicine, 4444 Forest Park Avenue, Suite 2100, St. Louis, MO 63108, United States
Abstract
Difficulty using reparative behaviors (i.e., prosocial behaviors that individuals use after they have transgressed to cause another’s distress) has been concurrently associated with poorer social functioning and both internalizing and externalizing disorders in children and adults. Despite these associations, no study has examined social and psychological outcomes of children who display consistently low levels of reparative behaviors across childhood. This study used established developmental trajectories of reparative behaviors that span preschool through early adolescence (low-stable, moderate-stable, and high-stable) to predict social and psychological outcomes in adolescence (N = 129). Membership in trajectories characterized by lower levels of reparative behaviors predicted greater social rejection, social withdrawal, aggression, and symptoms of depression in adolescence, even when controlling for baseline levels of each outcome. Membership in the low-stable reparative trajectory also significantly mediated the relationship between high levels of guilt in preschool and greater depression severity in adolescence. Findings suggest that children who display persistently low levels of reparative behaviors may be at-risk for a variety of poorer social and emotional outcomes. Further, preschoolers who display both high levels of guilt and low levels of reparative behaviors may be at particularly high risk for depression recurrence in adolescence. Thus, interventions that teach young children reparative skills and/or promote approach rather than avoidance after transgressions may have important implications for preventing a wide range of poorer social and emotional outcomes in adolescence. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.
Author Keywords
Aggression; Depression; Guilt; Prosocial behavior; Reparative behavior; Social functioning
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Cortical activity underlying overt and covert language generation measured using high-density diffuse optical tomography” (2019) Optics InfoBase Conference Papers
Cortical activity underlying overt and covert language generation measured using high-density diffuse optical tomography
(2019) Optics InfoBase Conference Papers, Part F142-ECBO 2019, .
Schroeder, M.L.a , Fishell, A.K.d , Sherafati, A.c , Svoboda, A.M.a , Culver, J.P.a b c , Eggebrecht, A.T.a
a Dept. of Radiology, Washington University School of Medicine, St. Louis, MO 63110, United States
b Dept. of Biomedical Engineering, Washington University, St. Louis, MO 63130, United States
c Dept. of Physics, Washington University, St. Louis, MO 63130, United States
d Division of Biology and Biomedical Sciences, Washington University, St. Louis, MO 63130, United States
Abstract
Using naturalistic language generation tasks (e.g. overt speech) to capture the neural correlates of speech production is important, as less naturalistic (but often used) tasks such as covert language generation are not a reliable substitute for accurately assessing cortical activation associated with naturalistic speech. fMRI poses challenges to implementing naturalistic language tasks, especially in clinical populations, because it is noisy, physically constraining, and contraindicated in populations with metal implants. High-density diffuse optical tomography (HD-DOT) is particularly well-suited for naturalistic language tasks because it is silent, wearable, portable, and metal-compatible. This study investigates cortical activity underlying naturalistic language generation using HD-DOT. Six adult subjects aged 20-26 years completed two scans on two separate days consisting of three different tasks: covert word reading (RW), covert verb generation (CV), and overt verb generation (OV). Cortical responses were apparent in expected anatomical areas for all tasks and RW, CV, and OV evoked responses of increasing strength (peak ?HbO (µMol) = 7.58, 10.3, and 11.0, respectively). Notably, OV recruits additional activation in Broca’s area and right-lateralized primary motor cortex as compared to CV. These findings are consistent with those obtained using fMRI9,10,11 and underscore the need to use naturalistic language tasks when assessing the neural representations of natural speech. These results motivate extension to further investigations of naturalistic language processing of increased complexity, both receptive and productive, such as within-room conversation. © SPIE-OSA 2019
Author Keywords
Brain mapping; Cortical anatomy; Diffuse optical imaging; Naturalistic language; Speech production; Verb generation
Document Type: Conference Paper
Publication Stage: Final
Source: Scopus
“Neurodot: An extensible Matlab toolbox for streamlined optical functional mapping” (2019) Optics InfoBase Conference Papers
Neurodot: An extensible Matlab toolbox for streamlined optical functional mapping
(2019) Optics InfoBase Conference Papers, Part F142-ECBO 2019, .
Eggebrecht, A.T.a , Culver, J.P.a b c
a Department of Radiology, Washington University School of Medicine, St. Louis, MO 63130, United States
b Department of Physics, Washington University School of Medicine, St. Louis, MO 63130, United States
c Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO 63130, United States
Abstract
Multiple challenges exist in standardization of data format and processing pipelines for optical functional neuroimaging. We present here a fully self-contained and end-user-friendly tool that provides the flexibility for multiple array-based imaging modalities, and offers format compatibility, spatial registration, and analytical breadth and sophistication for post-processing. NeuroDOT, available on GitHub, is written in MATLAB in the style of a conventional MATLAB toolbox with functionality distributed across several pipelines with extensive functions for data quality analysis and visualization. To aid in end-user support at multiple levels of familiarity and expertise, beyond the basic functionality, NeuroDOT contains data samples, support files, help sections, appendices, and tutorials. Anonymized and published data samples have been chosen to reflect common experimental paradigms in neuroimaging (e.g., retinotopy and language based tasks), and are provided in both raw and pre-processed versions to aid in troubleshooting and training for the new user. The NeuroDOT toolbox currently supports a wide variety of standard data file formats (e.g., NIFTI, GIFTI, and others). Help sections exist for each function and are searchable from the MATLAB command line, with a Help Viewer version as well. Both are written and formatted in the style of their native MATLAB counterparts for familiarity and ease of use. Several appendices detail data structures, pipelines and their construction, and select visualizations of our pipelines’ results for multiple data samples. Several tutorials are also included, each of which runs a data sample through a given pipeline to help the user harness the power and flexibility of NeuroDOT. © SPIE-OSA 2019
Author Keywords
Analysis; Brain; Diffuse; Function; Pipeline; Tomography; Toolbox; Visualization
Document Type: Conference Paper
Publication Stage: Final
Source: Scopus