“Relationships between accelerometry and general compensatory movements of the upper limb after stroke” (2020) Journal of NeuroEngineering and Rehabilitation
Relationships between accelerometry and general compensatory movements of the upper limb after stroke
(2020) Journal of NeuroEngineering and Rehabilitation, 17 (1), art. no. 138, .
Barth, J.a , Klaesner, J.W.a d , Lang, C.E.a b c
a Washington University School of Medicine, Program in Physical Therapy, St. Louis, MO, United States
b Washington University School of Medicine, Program in Occupational Therapy, St. Louis, MO, United States
c Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
d Department in Biomedical Engineering, Washington University, St. Louis, MO, United States
Abstract
Background: Standardized assessments are used in rehabilitation clinics after stroke to measure restoration versus compensatory movements of the upper limb. Accelerometry is an emerging tool that can bridge the gap between in- and out-of-clinic assessments of the upper limb, but is limited in that it currently does not capture the quality of a person’s movement, an important concept to assess compensation versus restoration. The purpose of this analysis was to characterize how accelerometer variables may reflect upper limb compensatory movement patterns after stroke. Methods: This study was a secondary analysis of an existing data set from a Phase II, single-blind, randomized, parallel dose–response trial (NCT0114369). Sources of data utilized were: (1) a compensatory movement score derived from video analysis of the Action Research Arm Test (ARAT), and (2) calculated accelerometer variables quantifying time, magnitude and variability of upper limb movement from the same time point during study participation for both in-clinic and out-of-clinic recording periods. Results: Participants had chronic upper limb paresis of mild to moderate severity. Compensatory movement scores varied across the sample, with a mean of 73.7 ± 33.6 and range from 11.5 to 188. Moderate correlations were observed between the compensatory movement score and each accelerometer variable. Accelerometer variables measured out-of-clinic had stronger relationships with compensatory movements, compared with accelerometer variables in-clinic. Variables quantifying time, magnitude, and variability of upper limb movement out-of-clinic had relationships to the compensatory movement score. Conclusions: Accelerometry is a tool that, while measuring movement quantity, can also reflect the use of general compensatory movement patterns of the upper limb in persons with chronic stroke. Individuals who move their limbs more in daily life with respect to time and variability tend to move with less movement compensations and more typical movement patterns. Likewise, individuals who move their paretic limbs less and their non-paretic limb more in daily life tend to move with more movement compensations at all joints in the paretic limb and less typical movement patterns. © 2020, The Author(s).
Author Keywords
Accelerometry; Cerebrovascular disease; Stroke rehabilitation; Upper extremity
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Brain function distinguishes female carriers and non-carriers of familial risk for autism” (2020) Molecular Autism
Brain function distinguishes female carriers and non-carriers of familial risk for autism
(2020) Molecular Autism, 11 (1), art. no. 82, .
Eggebrecht, A.T.a e , Dworetsky, A.b , Hawks, Z.c , Coalson, R.b , Adeyemo, B.b , Davis, S.d , Gray, D.d , McMichael, A.b , Petersen, S.E.b , Constantino, J.N.d , Pruett, J.R., Jrd
a Mallinckrodt Institute of Radiology, Washington University School of Medicine, 660 S. Euclid Ave, St Louis, MO 63110, United States
b Department of Neurology, Washington University School of Medicine, 660 S. Euclid Ave, St Louis, MO 63110, United States
c Department of Psychological and Brain Sciences, Washington University in St. Louis, 1 Brookings Dr., St Louis, MO 63130, United States
d Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid Ave, St Louis, MO 63110, United States
e Washington University School of Medicine, C.B. 8225, 4515 McKinley Ave., St. Louis, MO 63110, United States
Abstract
Background: Autism spectrum disorder (ASD) is characterized by high population-level heritability and a three-to-one male-to-female ratio that occurs independent of sex linkage. Prior research in a mixed-sex pediatric sample identified neural signatures of familial risk elicited by passive viewing of point light motion displays, suggesting the possibility that both resilience and risk of autism might be associated with brain responses to biological motion. To confirm a relationship between these signatures and inherited risk of autism, we tested them in families enriched for genetic loading through undiagnosed (“carrier”) females. Methods: Using functional magnetic resonance imaging, we examined brain responses to passive viewing of point light displays—depicting biological versus non-biological motion—in a sample of undiagnosed adult females enriched for inherited susceptibility to ASD on the basis of affectation in their respective family pedigrees. Brain responses in carrier females were compared to responses in age-, SRS-, and IQ-matched non-carrier-females—i.e., females unrelated to individuals with ASD. We conducted a hypothesis-driven analysis focused on previously published regions of interest as well as exploratory, brain-wide analyses designed to characterize more fully the rich responses to this paradigm. Results: We observed robust responses to biological motion. Notwithstanding, the 12 regions implicated by prior research did not exhibit the hypothesized interaction between group (carriers vs. controls) and point light displays (biological vs. non-biological motion). Exploratory, brain-wide analyses identified this interaction in three novel regions. Post hoc analyses additionally revealed significant variations in the time course of brain activation in 20 regions spanning occipital and temporal cortex, indicating group differences in response to point light displays (irrespective of the nature of motion) for exploration in future studies. Limitations: We were unable to successfully eye-track all participants, which prevented us from being able to control for potential differences in eye gaze position. Conclusions: These methods confirmed pronounced neural signatures that differentiate brain responses to biological and scrambled motion. Our sample of undiagnosed females enriched for family genetic loading enabled discovery of numerous contrasts between carriers and non-carriers of risk of ASD that may index variations in visual attention and motion processing related to genetic susceptibility and inform our understanding of mechanisms incurred by inherited liability for ASD. © 2020, The Author(s).
Author Keywords
Biological motion; Endophenotype; Familial risk; Sex ratio; Silent transmission
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“HLA-A alleles including HLA-A29 affect the composition of the gut microbiome: a potential clue to the pathogenesis of birdshot retinochoroidopathy” (2020) Scientific Reports
HLA-A alleles including HLA-A29 affect the composition of the gut microbiome: a potential clue to the pathogenesis of birdshot retinochoroidopathy
(2020) Scientific Reports, 10 (1), art. no. 17636, .
Sternes, P.R.a , Martin, T.M.b , Paley, M.c , Diamond, S.d , Asquith, M.J.d , Brown, M.A.e , Rosenbaum, J.T.d f
a Australian Translational Genomics Centre, Institute of Health and Biomedical Innovation At Translational Research Institute, Queensland University of Technology, Brisbane, Australia
b Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, OR, United States
c Department of Medicine, Washington University, St. Louis, MO, United States
d Department of Medicine, Oregon Health & Science University, Portland, OR, United States
e Guy’s and St Thomas’ NHS Foundation Trust and King’s College London NIHR Biomedical Research Centre, London, United States
f Legacy Devers Eye Institute, Portland, OR, United States
Abstract
Birdshot retinochoroidopathy occurs exclusively in individuals who are HLA-A29 positive. The mechanism to account for this association is unknown. The gut microbiome has been causally implicated in many immune-mediated diseases. We hypothesized that HLA-A29 would affect the composition of the gut microbiome, leading to a dysbiosis and immune-mediated eye disease. Fecal and intestinal biopsy samples were obtained from 107 healthy individuals from Portland, Oregon environs, 10 of whom were HLA-A29 positive, undergoing routine colonoscopy. Bacterial profiling was achieved via 16S rRNA metabarcoding. Publicly available whole meta-genome sequencing data from the Human Microbiome Project (HMP), consisting of 298 healthy controls mostly of US origin, were also interrogated. PERMANOVA and sparse partial least squares discriminant analysis (sPLSDA) demonstrated that subjects who were HLA-A29 positive differed in bacterial species composition (beta diversity) compared to HLA-A29 negative subjects in both the Portland (p = 0.019) and HMP cohorts (p = 0.0002). The Portland and HMP cohorts evidenced different subsets of bacterial species associated with HLA-A29 status, likely due to differences in the metagenomic techniques employed. The functional composition of the HMP cohort did not differ overall (p = 0.14) between HLA-A29 positive and negative subjects, although some distinct pathways such as heparan sulfate biosynthesis showed differences. As we and others have shown for various HLA alleles, the HLA allotype impacts the composition of the microbiome. We hypothesize that HLA-A29 may predispose chorioretinitis via an altered gut microbiome. © 2020, The Author(s).
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Safety enforcement in closed-loop anesthesia—A comparison study” (2020) Control Engineering Practice
Safety enforcement in closed-loop anesthesia—A comparison study
(2020) Control Engineering Practice, 105, art. no. 104653, .
Hosseinzadeh, M.a , van Heusden, K.b , Yousefi, M.b , Dumont, G.A.b , Garone, E.c
a Department of Electrical and Systems Engineering, Washington University in St. Louis, St. Louis, MO, United States
b Department of Electrical and Computer Engineering, The University of British Columbia, Vancouver, Canada
c Service d’Automatique et d’Analyse des Systèmes, Université Libre de Bruxelles, Brussels, Belgium
Abstract
This paper studies application of different constrained control concepts for the control of Depth of Hypnosis (DOH) in closed-loop anesthesia to guarantee patient safety, while ensuring acceptable tracking performance. The core idea is to formulate Overdosing (OD) prevention and Blood Pressure Decrease (BPD) prevention as operational constraints, and then use a constrained control scheme to enforce the constraints satisfaction at all times. In this paper, three methods are studied: (1) Explicit Reference Governor (ERG), (2) Safety Preserving Control (SPC), and (3) Model Predictive Control (MPC). The performance of the methods is assessed with respect to a simulated surgical procedure for 44 patients whose models have been identified using clinical data. In particular, three realistic clinical scenarios are studied in this paper: (1) normal mode, (2) stimulation, and (3) low clearance. The results demonstrate cons and pros of each method in closed-loop anesthesia according to clinically relevant assessments. © 2020 Elsevier Ltd
Author Keywords
Automated drug delivery; Closed-loop anesthesia; Constrained control; Depth of hypnosis; Safety enforcement
Document Type: Article
Publication Stage: Final
Source: Scopus
“Cortical thinning in preschoolers with maladaptive guilt” (2020) Psychiatry Research – Neuroimaging
Cortical thinning in preschoolers with maladaptive guilt
(2020) Psychiatry Research – Neuroimaging, 305, art. no. 111195, .
Donohue, M.R.a , Tillman, R.a , Barch, D.M.a b , Luby, J.a , Gaffrey, M.S.c
a Department of Psychiatry, Washington University School of Medicine, 4444 Forest Park Avenue, Suite 2500, St. Louis, MO 63110, United States
b Department of Psychology, Washington University, St. Louis, MO, United States
c Department of Psychology and Neuroscience, Duke University, Durham, NC, United States
Abstract
Maladaptive guilt is a central symptom of preschool-onset depression associated with severe psychopathology in adolescence and adulthood. Although studies have found that maladaptive guilt is associated with structural alterations in the anterior insula (AI) and dorsomedial prefrontal cortex (dmPFC) in middle childhood and adolescence, no study has examined structural neural correlates of maladaptive guilt in preschool, when this symptom first emerges. This study examined a pooled sample of 3-to 6-year-old children (N = 76; 40.8% female) from two studies, both which used the same type of magnetic resonance imaging scanner and conducted diagnostic interviews for depression that included clinician ratings of whether children met criteria for maladaptive guilt. Preschoolers with maladaptive guilt displayed significantly thinner dmPFC than children without this symptom. Neither children’s depressive severity nor their vegetative or other emotional symptoms of depression were associated with dmPFC thickness, suggesting that dmPFC thinning is specific to maladaptive guilt. Neither AI gray matter volume or thickness nor dmPFC gray matter volume differed between children with and without maladaptive guilt. This study is the first to identify a structural biomarker for a specific depressive symptom in preschool. Findings may inform neurobiological models of the development of depression and aid in detection of this symptom. © 2020
Author Keywords
Brain development; Cortical thickness; dmPFC; MRI; Self-conscious emotion
Document Type: Article
Publication Stage: Final
Source: Scopus
“Mindfulness-based stress reduction for HIV-associated neurocognitive disorder: Rationale and protocol for a randomized controlled trial in older adults” (2020) Contemporary Clinical Trials
Mindfulness-based stress reduction for HIV-associated neurocognitive disorder: Rationale and protocol for a randomized controlled trial in older adults
(2020) Contemporary Clinical Trials, 98, art. no. 106150, .
Addington, E.L.a b , Javandel, S.c , De Gruttola, V.d , Paul, R.e , Milanini, B.c , Ances, B.M.f , Moskowitz, J.T.a b , Valcour, V.c
a Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
b Osher Center for Integrative Medicine, Northwestern University, Chicago, IL, United States
c Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, United States
d Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, United States
e Missouri Institute of Mental Health, University of Missouri-St. Louis, St. Louis, MO, United States
f Department of Neurology, Washington University in St. Louis, School of Medicine, St. Louis, MO, United States
Abstract
The symptom burden of HIV-associated neurocognitive disorder (HAND) is high among older individuals, and treatment options are limited. Mindfulness-based stress reduction (MBSR) has potential to improve neurocognitive performance, psychosocial wellbeing, and quality of life, but empirical studies in this growing vulnerable population are lacking. In this trial, participants (N = 180) age 55 and older who are living with HIV infection, are on combination antiretroviral therapy with suppressed viral loads, and yet continue to experience behavioral and cognitive symptoms of HAND, are randomized to MBSR or to a waitlist control arm that receives MBSR following a 16-week period of standard care. Primary outcomes (attention, executive function, stress, anxiety, depression, everyday functioning, quality of life) and potential mediators (affect, mindfulness) and moderators (social support, loneliness) are assessed at baseline and weeks 8, 16, and 48 in both groups, with an additional assessment at week 24 (post-MBSR) in the crossover control group. Assessments include self-report and objective measures (e.g., neuropsychological assessment, neurological exam, clinical labs). In addition, a subset of participants (n = 30 per group) are randomly selected to undergo fMRI to evaluate changes in functional connectivity networks and their relationship to changes in neuropsychological outcomes. Forthcoming findings from this randomized controlled trial have the potential to contribute to a growing public health need as the number of older adults with HAND is expected to rise © 2020 Elsevier Inc.
Author Keywords
Cognition; HIV; HIV-associated neurocognitive disorder; Mindfulness; Older adults; Stress
Document Type: Article
Publication Stage: Final
Source: Scopus
“A prospective multicenter study of laser ablation for drug resistant epilepsy – One year outcomes” (2020) Epilepsy Research
A prospective multicenter study of laser ablation for drug resistant epilepsy – One year outcomes
(2020) Epilepsy Research, 167, art. no. 106473, .
Landazuri, P.a , Shih, J.b , Leuthardt, E.c , Ben-Haim, S.d , Neimat, J.e , Tovar-Spinoza, Z.f , Chiang, V.g , Spencer, D.g , Sun, D.h , Fecci, P.i , Baumgartner, J.j
a Department of Neurology, University of Kansas Medical Center, Kansas City, KS, United States
b Department of Neurosciences, University of California San Diego, San Diego, CA, United States
c Department of Neurosurgery, Washington University, St. Louis, MO, United States
d Department of Neurosurgery, University of California San Diego, San Diego, CA, United States
e Department of Neurosurgery, University of Louisville, Louisville, KY, United States
f Department of Neurosurgery, SUNY Upstate Medical University, Syracuse, NY, United States
g Yale University School of Medicine, Yale University, New Haven, CT, United States
h Norton Neuroscience Institute, Norton Health Care, Louisville, KY, United States
i Department of Neurosurgery, Duke University Medical Center, Durham, NC, United States
j Department of Neurosurgery, Florida Hospital Advent Health, Orlando, FL, United States
Abstract
Objective: To report one-year seizure outcomes, procedural data, and quality of life scores following laser interstitial thermal therapy (LITT) of epileptogenic foci. Methods: Data from an ongoing prospective, multi-center registry were assessed. Procedural information, Engel seizure outcomes, and quality of life (QoL) scores were analyzed. A responder analysis was performed to better understand potential clinical characteristics that could influence seizure outcome. Results: Sixty patients have been enrolled into LAANTERN (Laser Ablation of Abnormal Neurological Tissue Using Robotic NeuroBlate System) specifically for epilepsy treatment, of which 42 reached one year follow up. Engel I outcome was achieved in 64.3 % at one year follow up. Patients with mesial temporal lobe epilepsy (MTLE) comprised 56.7 % of this cohort of multiple epilepsy types. Other significant etiologies included focal cortical dysplasia, hypothalamic hamartoma, cavernoma, heterotopias, and tuberous sclerosis. Median length of stay was 32.7 h. At discharge, head pain score averaged 1.4 ± 2.1 on a scale from 1 to 10. Five adverse events were reported, one categorized as serious. Seizure worry and social functioning scores improved significantly in quality of life measures. Significance: Surgical treatment with LITT for epileptic foci is a safe and effective treatment option for people with drug resistant epilepsy. Our multicenter prospective seizure outcomes continue to expand published LITT experience in MTLE as well as non-MTLE epilepsies. The minimally invasive nature allows for short hospitalizations with minimal reported pain and discomfort. © 2020 The Authors
Author Keywords
Epilepsy surgery; Extratemporal lobe epilepsy; Laser ablation; Mesial temporal lobe epilepsy; Minimally invasive
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Plasma Aβ and neurofilament light chain are associated with cognitive and physical function decline in non-dementia older adults” (2020) Alzheimer’s Research and Therapy
Plasma Aβ and neurofilament light chain are associated with cognitive and physical function decline in non-dementia older adults
(2020) Alzheimer’s Research and Therapy, 12 (1), art. no. 128, .
He, L.a , De Souto Barreto, P.a b , Aggarwal, G.c d , Nguyen, A.D.c d , Morley, J.E.c , Li, Y.e , Bateman, R.J.e , Vellas, B.a b , Vellas, B.f , Guyonnet, S.f , Carrié, I.f , Brigitte, L.f , Faisant, C.f , Lala, F.f , Delrieu, J.f , Villars, H.f , Combrouze, E.f , Badufle, C.f , Zueras, A.f , Andrieu, S.f , Cantet, C.f , Morin, C.f , Van Kan, G.A.f , Dupuy, C.f , Rolland, Y.f , Caillaud, C.f , Ousset, P.-J.f , Lala, F.f , Willis, S.f , Belleville, S.f , Gilbert, B.f , Dartigues, J.-F.f , Marcet, I.f , Delva, F.f , Foubert, A.f , Cerda, S.f , Costes, C.f , Rouaud, O.f , Manckoundia, P.f , Quipourt, V.f , Marilier, S.f , Franon, E.f , Bories, L.f , Pader, M.-L.f , Basset, M.-F.f , Lapoujade, B.f , Faure, V.f , Tong, M.L.Y.f , Malick-Loiseau, C.f , Cazaban-Campistron, E.f , Desclaux, F.f , Blatge, C.f , Dantoine, T.f , Laubarie-Mouret, C.f , Saulnier, I.f , Clément, J.-P.f , Picat, M.-A.f , Bernard-Bourzeix, L.f , Willebois, S.f , Désormais, I.f , Cardinaud, N.f , Bonnefoy, M.f , Livet, P.f , Rebaudet, P.f , Gédéon, C.f , Burdet, C.f , Terracol, F.f , Pesce, A.f , Roth, S.f , Chaillou, S.f , Louchart, S.f , Sudres, K.f , Lebrun, N.f , Barro-Belaygues, N.f , Touchon, J.f , Bennys, K.f , Gabelle, A.f , Romano, A.f , Touati, L.f , Marelli, C.f , Pays, C.f , Robert, P.f , Le Duff, F.f , Gervais, C.f , Gonfrier, S.f , Gasnier, Y.f , Bordes, S.f , Begorre, D.f , Carpuat, C.f , Khales, K.f , Lefebvre, J.-F.f , El Idrissi, S.M.f , Skolil, P.f , Salles, J.-P.f , Dufouil, C.f , Lehéricy, S.f , Chupin, M.f , Mangin, J.-F.f , Bouhayia, A.f , Allard, M.f , Ricolfi, F.f , Dubois, D.f , Martel, M.P.B.f , Cotton, F.f , Bonafé, A.f , Chanalet, S.f , Hugon, F.f , Bonneville, F.f , Cognard, C.f , Chollet, F.f , Payoux, P.f , Voisin, T.f , Delrieu, J.f , Peiffer, S.f , Hitzel, A.f , Allard, M.f , Zanca, M.f , Monteil, J.f , Darcourt, J.f , Molinier, L.f , Derumeaux, H.f , Costa, N.f , Perret, B.f , Vinel, C.f , Caspar-Bauguil, S.f , Olivier-Abbal, P.f , Andrieu, S.f , Cantet, C.f , Coley, N.f , MAPT/DSA Groupf
a Gérontopôle de Toulouse, Institut du Vieillissement, Centre Hospitalo-Universitaire de Toulouse, 37 allées Jules Guesdes, Toulouse, 31000, France
b Umr UPS/INSERM, 1027 University of Toulouse Iii, Toulouse, France
c Division of Geriatric Medicine, Saint Louis University School of Medicine, St. Louis, MO, United States
d Henry and Amelia Nasrallah Center for Neuroscience, Saint Louis University, St. Louis, MO, United States
e Department of Neurology, Washington University School of Medicine Box 8111, 660 South Euclid Avenue, St. Louis, MO 63110, United States
Abstract
Background: Cognition is closely associated with physical function. Although high brain amyloid-β (Aβ) deposition and neurofilament light chain (NfL) are associated with cognitive and gait speed decline, relationships of combined plasma Aβ and NfL profiles with cognitive and physical functions in older adults remain unknown. The research aim of this study was to investigate the prospective associations of combined plasma Aβ and NfL profiles with cognitive and physical functions in older adults. Methods: Participants (n = 452, aged 76 ± 5 years) who had both plasma Aβ and NfL data collected from the Multidomain Alzheimer’s Preventive Trial (MAPT, May 2008 to April 2016) were included in the current study. These participants were from four MAPT groups (multidomain interventions [physical activity and nutritional counselling, and cognitive training], omega-3 supplementation, multidomain plus omega-3 supplementation and control group) and had received a 3-year intervention, followed by a 2-year observational follow-up. Cognitive function was evaluated as Mini-Mental State Examination and composite cognitive score (CCS, a mean Z-score combining four cognitive tests). Physical function was evaluated as gait speed (4-m usual-pace walk test) and chair-stand time (5-time maximal chair-stand test). Cognitive and physical function data measured at the time of and after blood Aβ and NfL tests were used for analysis. Participants with plasma Aβ42/Aβ40 ratios lower than 0.107 and NfL levels greater than 93.04 pg/ml were classified as Aβ+ and NfL+. Multivariable regressions and mixed-effects linear models were used for the analysis. Results: At the cross-sectional level, no significant association was found between Aβ+NfL+ and cognitive or physical function after controlling for age, sex, body mass index, education level and MAPT group. Evaluating longitudinal changes, participants with Aβ+NfL+ had greater annual declines in the CCS (β =-0.11, 95%CI [-0.17,-0.05]) and gait speed (β =-0.03, 95%CI [-0.05,-0.005]). After adjusting for APOE ϵ4 genotype, Aβ+NfL+ was associated with a greater decline only in the CCS (β =-0.09, 95%CI [-0.15,-0.02]). Conclusions: Combined low plasma Aβ42/Aβ40 ratio and high plasma NfL level was associated with greater declines in cognition and gait speed over time, providing further evidence of the links between cognitive and physical function. Trial registration: www.clinicaltrials.gov [NCT00672685]. © 2020 The Author(s).
Author Keywords
Amyloid-β; Cognitive function; Neurofilament light chain; Physical function
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Lesion evolution and neurodegeneration in RVCL-S: A monogenic microvasculopathy” (2020) Neurology
Lesion evolution and neurodegeneration in RVCL-S: A monogenic microvasculopathy
(2020) Neurology, 95 (14), pp. e1918-e1931.
Ford, A.L., Chin, V.W., Fellah, S., Binkley, M.M., Bodin, A.M., Balasetti, V., Taiwo, Y., Kang, P., Lin, D., Jen, J.C., Grand, M.G., Bogacki, M., Liszewski, M.K., Hourcade, D., Chen, Y., Hassenstab, J., Lee, J.-M., An, H., Miner, J.J., Atkinson, J.P.
From the Department of Neurology (A.L.F., V.W.C., S.F., M.B.M., A.M.B., V.B., Y.T., P.K., Y.C., J.H., J.-M.L.), Mallinckrodt Institute of Radiology (A.L.F., J.-M.L., H.A.), Department of Ophthalmology (M.G.G.), and Department of Medicine (M.B., M.K.L., D.H., J.J.M., J.P.A.), Division of Rheumatology, Washington University School of Medicine, St. Louis, MO; Department of Radiology (D.L.), The Johns Hopkins University School of Medicine, Baltimore, MD; and Department of Neurology (J.C.J.), Icahn School of Medicine at Mount Sinai, New York, NY
Abstract
OBJECTIVE: To characterize lesion evolution and neurodegeneration in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) using multimodal MRI. METHODS: We prospectively performed MRI and cognitive testing in RVCL-S and healthy control cohorts. Gray and white matter volume and disruption of white matter microstructure were quantified. Asymmetric spin echo acquisition permitted voxel-wise oxygen extraction fraction (OEF) calculation as an in vivo marker of microvascular ischemia. The RVCL-S cohort was included in a longitudinal analysis of lesion subtypes in which hyperintense lesions on fluid-attenuated inversion recovery (FLAIR), T1-postgadolinium, and diffusion-weighted imaging were delineated and quantified volumetrically. RESULTS: Twenty individuals with RVCL-S and 26 controls were enrolled. White matter volume and microstructure declined faster in those with RVCL-S compared to controls. White matter atrophy in RVCL-S was highly linear (ρ = -0.908, p < 0.0001). Normalized OEF was elevated in RVCL-S and increased with disease duration. Multiple cognitive domains, specifically those measuring working memory and processing speed, were impaired in RVCL-S. Lesion volumes, regardless of subtype, progressed/regressed with high variability as a function of age, while FLAIR lesion burden increased near time to death (p < 0.001). CONCLUSION: RVCL-S is a monogenic microvasculopathy affecting predominantly the white matter with regard to atrophy and cognitive impairment. White matter volumes in RVCL-S declined linearly, providing a potential metric against which to test the efficacy of future therapies. Progressive elevation of white matter OEF suggests that microvascular ischemia may underlie neurodegeneration in RVCL-S. Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Document Type: Note
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“The effect of insomnia on development of Alzheimer’s disease” (2020) Journal of Neuroinflammation
The effect of insomnia on development of Alzheimer’s disease
(2020) Journal of Neuroinflammation, 17 (1), art. no. 289, .
Sadeghmousavi, S.a b , Eskian, M.a c d , Rahmani, F.a c e , Rezaei, N.a c d f
a Neuroimaging Network (NIN), Universal Scientific Education and Research Network (USERN), Tehran, Iran
b School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
c Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
d Network of Immunity in Infection Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
e Department of Radiology, Washington University in St. Louis, St. Louis, MO, United States
f Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Abstract
Alzheimer’s disease (AD) is the most common type of dementia and a neurodegenerative disorder characterized by memory deficits especially forgetting recent information, recall ability impairment, and loss of time tracking, problem-solving, language, and recognition difficulties. AD is also a globally important health issue but despite all scientific efforts, the treatment of AD is still a challenge. Sleep has important roles in learning and memory consolidation. Studies have shown that sleep deprivation (SD) and insomnia are associated with the pathogenesis of Alzheimer’s disease and may have an impact on the symptoms and development. Thus, sleep disorders have decisive effects on AD; this association deserves more attention in research, diagnostics, and treatment, and knowing this relation also can help to prevent AD through screening and proper management of sleep disorders. This study aimed to show the potential role of SD and insomnia in the pathogenesis and progression of AD. © 2020 The Author(s).
Author Keywords
Alzheimer’s disease; Inflammatory processes; Insomnia; Sleep; Sleep deprivation
Document Type: Review
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“A Novel Method for High-Dimensional Anatomical Mapping of Extra-Axial Cerebrospinal Fluid: Application to the Infant Brain” (2020) Frontiers in Neuroscience
A Novel Method for High-Dimensional Anatomical Mapping of Extra-Axial Cerebrospinal Fluid: Application to the Infant Brain
(2020) Frontiers in Neuroscience, 14, art. no. 561556, .
Mostapha, M.a , Kim, S.H.b , Evans, A.C.c , Dager, S.R.d , Estes, A.M.e , McKinstry, R.C.f , Botteron, K.N.f g , Gerig, G.h , Pizer, S.M.a , Schultz, R.T.i , Hazlett, H.C.b j , Piven, J.b j , Girault, J.B.b j , Shen, M.D.b j k , Styner, M.A.a b
a Department of Computer Science, University of North Carolina, Chapel Hill, NC, United States
b Department of Psychiatry, UNC School of Medicine, University of North Carolina, Chapel Hill, NC, United States
c Montreal Neurological Institute, McGill University, Montreal, QC, Canada
d Department of Radiology, University of Washington, Seattle, WA, United States
e Department of Speech and Hearing Sciences, University of Washington, Seattle, WA, United States
f Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO, United States
g Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
h Department of Computer Science and Engineering, New York University, New York, NY, United States
i Department of Pediatrics, Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, United States
j Carolina Institute for Developmental Disabilities, UNC School of Medicine, University of North Carolina-Chapel Hill, Chapel Hill, NC, United States
k UNC Neuroscience Center, University of North Carolina-Chapel Hill, Chapel Hill, NC, United States
Abstract
Cerebrospinal fluid (CSF) plays an essential role in early postnatal brain development. Extra-axial CSF (EA-CSF) volume, which is characterized by CSF in the subarachnoid space surrounding the brain, is a promising marker in the early detection of young children at risk for neurodevelopmental disorders. Previous studies have focused on global EA-CSF volume across the entire dorsal extent of the brain, and not regionally-specific EA-CSF measurements, because no tools were previously available for extracting local EA-CSF measures suitable for localized cortical surface analysis. In this paper, we propose a novel framework for the localized, cortical surface-based analysis of EA-CSF. The proposed processing framework combines probabilistic brain tissue segmentation, cortical surface reconstruction, and streamline-based local EA-CSF quantification. The quantitative analysis of local EA-CSF was applied to a dataset of typically developing infants with longitudinal MRI scans from 6 to 24 months of age. There was a high degree of consistency in the spatial patterns of local EA-CSF across age using the proposed methods. Statistical analysis of local EA-CSF revealed several novel findings: several regions of the cerebral cortex showed reductions in EA-CSF from 6 to 24 months of age, and specific regions showed higher local EA-CSF in males compared to females. These age-, sex-, and anatomically-specific patterns of local EA-CSF would not have been observed if only a global EA-CSF measure were utilized. The proposed methods are integrated into a freely available, open-source, cross-platform, user-friendly software tool, allowing neuroimaging labs to quantify local extra-axial CSF in their neuroimaging studies to investigate its role in typical and atypical brain development. © Copyright © 2020 Mostapha, Kim, Evans, Dager, Estes, McKinstry, Botteron, Gerig, Pizer, Schultz, Hazlett, Piven, Girault, Shen and Styner.
Author Keywords
autism; brain development; EA-CSF; extra-axial cerebrospinal fluid; Laplacian PDE; neurodevelopmental disorders; structural MRI; surface analysis
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Implementation of wearable sensing technology for movement: Pushing forward into the routine physical rehabilitation care field” (2020) Sensors (Switzerland)
Implementation of wearable sensing technology for movement: Pushing forward into the routine physical rehabilitation care field
(2020) Sensors (Switzerland), 20 (20), art. no. 5744, pp. 1-21.
Lang, C.E.a b c , Barth, J.a , Holleran, C.L.a c , Konrad, J.D.a , Bland, M.D.a b c
a Program in Physical Therapy, Washington University School of Medicine, St. Louis, MO 63122, United States
b Program in Occupational Therapy, Washington University School of Medicine, St. Louis, MO 63122, United States
c Department of Neurology, Washington University School of Medicine, St. Louis, MO 63122, United States
Abstract
While the promise of wearable sensor technology to transform physical rehabilitation has been around for a number of years, the reality is that wearable sensor technology for the measurement of human movement has remained largely confined to rehabilitation research labs with limited ventures into clinical practice. The purposes of this paper are to: (1) discuss the major barriers in clinical practice and available wearable sensing technology; (2) propose benchmarks for wearable device systems that would make it feasible to implement them in clinical practice across the world and (3) evaluate a current wearable device system against the benchmarks as an example. If we can overcome the barriers and achieve the benchmarks collectively, the field of rehabilitation will move forward towards better movement interventions that produce improved function not just in the clinic or lab, but out in peoples’ homes and communities. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Author Keywords
Implementation; Measurement; Motor function; Outcomes; Rehabilitation; Wearable sensors
Document Type: Note
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Beyond aggregation: Pathological phase transitions in neurodegenerative disease” (2020) Science (New York, N.Y.)
Beyond aggregation: Pathological phase transitions in neurodegenerative disease
(2020) Science (New York, N.Y.), 370 (6512), pp. 56-60.
Mathieu, C.a , Pappu, R.V.b c , Taylor, J.P.a
a Howard Hughes Medical Institute, Department of Cell and Molecular Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, United States
b Department of Biomedical Engineering, Washington University, St. Louis, MO 63130, USA
c Center for Science and Engineering of Living Systems, Washington University, St. Louis, MO 63130, USA
Abstract
Over the past decade, phase transitions have emerged as a fundamental mechanism of cellular organization. In parallel, a wealth of evidence has accrued indicating that aberrations in phase transitions are early events in the pathogenesis of several neurodegenerative diseases. We review the key evidence of defects at multiple levels, from phase transition of individual proteins to the dynamic behavior of complex, multicomponent condensates in neurodegeneration. We also highlight two concepts, dynamical arrest and heterotypic buffering, that are key to understanding how pathological phase transitions relate to pleiotropic defects in cellular functions and the accrual of proteinaceous deposits at end-stage disease. These insights not only illuminate disease etiology but also are likely to guide the development of therapeutic interventions to restore homeostasis. Copyright © 2020, American Association for the Advancement of Science.
Document Type: Review
Publication Stage: Final
Source: Scopus
“Higher iron stores and the HFE 187C>G variant delay onset of peripheral neuropathy during combination antiretroviral therapy” (2020) PLoS ONE
Higher iron stores and the HFE 187C>G variant delay onset of peripheral neuropathy during combination antiretroviral therapy
(2020) PLoS ONE, 15 (10 October), art. no. e0239758, .
Kallianpur, A.R.a b c , Wen, W.d , Erwin, A.L.a , Clifford, D.B.e , Hulgan, T.f , Robbins, G.K.g
a Genomic Medicine Institute, Cleveland Clinic/Lerner Research Institute, Cleveland, OH, United States
b Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, United States
c Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, United States
d Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
e Division of Infectious Diseases, Departments of Medicine and Neurology, Washington University School of Medicine, Saint Louis, MO, United States
f Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
g Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, United States
Abstract
Objective People with HIV (PWH) continue to experience sensory neuropathy and neuropathic pain in the combination antiretroviral therapy (cART) era for unclear reasons. This study evaluated the role of iron in a previously reported association of iron-loading hemochromatosis (HFE) gene variants with reduced risk of neuropathy in PWH who received more neurotoxic cART, since an iron-related mechanism also might be relevant to neuropathic symptoms in PWH living in low-resource settings today. Design This time-to-event analysis addressed the impact of systemic iron levels on the rapidity of neuropathy onset in PWH who initiated cART. Methods Soluble transferrin receptor (sTFR), the sTFR-ferritin index of iron stores, and high-sensitivity C-reactive protein (hsCRP) levels were determined in stored baseline sera from participants of known HFE genotype from AIDS Clinical Trials Group (ACTG) Study 384, a multicenter randomized clinical trial that evaluated cART strategies. Associations with incident neuropathy were evaluated in proportional-hazards, time-to-event regression models, adjusting for potential confounders. Results Of 151 eligible participants with stored serum who were included in the original genetic study, 43 had cART-associated neuropathy; 108 had sufficient serum for analysis, including 30 neuropathy cases. Carriers of HFE variants had higher systemic iron (lower sTFR and sTFR-ferritin index) and lower hsCRP levels than non-carriers (all p<0.05). Higher sTFR or iron stores, the HFE 187C>G variant, and lower baseline hsCRP were associated with significantly delayed neuropathy in self-reported whites (n = 28; all p-values<0.05), independent of age, CD4+ T-cell count, plasma HIV RNA, and cART regimen. Conclusions Higher iron stores, the HFE 187C>G variant, and lower hsCRP predicted delayed onset of neuropathy among self-reported white individuals initating cART. These findings require confirmation but may have implications for cART in HIV+ populations in areas with high endemic iron deficiency, especially those PWH in whom older, more neurotoxic antiretroviral drugs are occasionally still used. Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“American Neurogastroenterology and Motility Society Task Force Recommendations for Resumption of Motility Laboratory Operations During the COVID-19 Pandemic” (2020) The American Journal of Gastroenterology
American Neurogastroenterology and Motility Society Task Force Recommendations for Resumption of Motility Laboratory Operations During the COVID-19 Pandemic
(2020) The American Journal of Gastroenterology, 115 (10), pp. 1575-1583. Cited 1 time.
Baker, J.R.a , Moshiree, B.a , Rao, S.b , Neshatian, L.c , Nguyen, L.c , Chey, W.D.d , Saad, R.d , Garza, J.M.e , Waseem, S.f , Khan, A.R.g , Pandolfino, J.E.h , Gyawali, C.P.i
a Atrium Health, University of North Carolina, Charlotte, North Carolina, USA
b Augusta University, Augusta, GA, United States
c Stanford University, Stanford, CA, United States
d University of Michigan, Ann Arbor, MI, United States
e GI Care for Kids, Children’s Healthcare of Atlanta, Atlanta, GA, United States
f Indiana University, Indianapolis, IN, United States
g New York University Langone HealthNY, United States
h Northwestern University, Chicago, IL, United States
i Washington University, St. Louis, MO, United States
Abstract
The American Neurogastroenterology and Motility Society Task Force recommends that gastrointestinal motility procedures should be performed in motility laboratories adhering to the strict recommendations and personal protective equipment (PPE) measures to protect patients, ancillary staff, and motility allied health professionals. When available and within constraints of institutional guidelines, it is preferable for patients scheduled for motility procedures to complete a coronavirus disease 2019 (COVID-19) test within 48 hours before their procedure, similar to the recommendations before endoscopy made by gastroenterology societies. COVID-19 test results must be documented before performing procedures. If procedures are to be performed without a COVID-19 test, full PPE use is recommended, along with all social distancing and infection control measures. Because patients with suspected motility disorders may require multiple procedures, sequential scheduling of procedures should be considered to minimize need for repeat COVID-19 testing. The strategies for and timing of procedure(s) should be adapted, taking into consideration local institutional standards, with the provision for screening without testing in low prevalence areas. If tested positive for COVID-19, subsequent negative testing may be required before scheduling a motility procedure (timing is variable). Specific recommendations for each motility procedure including triaging, indications, PPE use, and alternatives to motility procedures are detailed in the document. These recommendations may evolve as understanding of virus transmission and prevalence of COVID-19 infection in the community changes over the upcoming months.
Document Type: Article
Publication Stage: Final
Source: Scopus
“11C dihydrotetrabenazine Positron Emission Tomography in Manganese-Exposed Workers” (2020) Journal of Occupational and Environmental Medicine
11C]dihydrotetrabenazine Positron Emission Tomography in Manganese-Exposed Workers
(2020) Journal of Occupational and Environmental Medicine, 62 (10), pp. 788-794.
Criswell, S.R., Nielsen, S.S., Warden, M.N., Perlmutter, J.S., Moerlein, S.M., Sheppard, L., Lenox-Krug, J., Checkoway, H., Racette, B.A.
Department of Neurology (Dr Criswell, Dr Nielsen, Mr Warden, Dr Perlmutter, Mr Lenox-Krug, Dr Racette); Department of Radiology (Dr Perlmutter, Dr Moerlein); Department of Neuroscience (Dr Perlmutter); Program in Physical Therapy (Dr Perlmutter); Program in Occupational Therapy (Dr Perlmutter); Department of Biochemistry and Molecular Biophysics (Dr Moerlein), Washington University School of Medicine, St. Louis, Missouri ; Department of Environmental and Occupational Health Sciences (Dr Sheppard); Department of Biostatistics (Dr Sheppard), School of Public Health, University of Washington, Seattle, Washington; Department of Family Medicine and Public Health (Dr Checkoway); Department of Neurosciences (Dr Checkoway), School of Medicine, University of California, San Diego, La Jolla, California; Faculty of Health Sciences, School of Public Health, University of the Witwatersrand, Parktown, South Africa (Dr Racette)
Abstract
OBJECTIVE: To understand the neurotoxic effects of manganese (Mn) exposure on monoaminergic function, utilizing [C]dihydrotetrabenazine (DTBZ) positron emission tomography (PET) to measure vesicular monoamine transporter 2 (VMAT2). METHODS: Basal ganglia and thalamic DTBZ binding potentials (BPND) were calculated on 56 PETs from 41 Mn-exposed workers. Associations between cumulative Mn exposure, regional BPND, and parkinsonism were examined by mixed linear regression. RESULTS: Thalamic DTBZ BPND was inversely associated with exposure in workers with less than 3 mg Mn/m-yrs, but subsequently remained stable. Pallidal DTBZ binding increased in workers with less than 2 mg Mn/m-yrs of exposure, but decreased thereafter. Thalamic DTBZ binding was inversely associated with parkinsonism (P = 0.003). CONCLUSION: Mn-dose-dependent associations with thalamic and pallidal DTBZ binding indicate direct effects on monoaminergic VMAT2. Thalamic DTBZ binding was also associated with parkinsonism, suggesting potential as an early biomarker of Mn neurotoxicity.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Relationship Between Trait Mindfulness and Sleep Quality in College Students: A Conditional Process Model” (2020) Frontiers in Psychology
Relationship Between Trait Mindfulness and Sleep Quality in College Students: A Conditional Process Model
(2020) Frontiers in Psychology, 11, art. no. 576319, .
Ding, X.a , Wang, X.a , Yang, Z.b , Tang, R.c , Tang, Y.-Y.d
a College of Psychology, Liaoning Normal University, Dalian, China
b Department of Gastroenterology, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
c Department of Psychological Brain Sciences, Washington University in St. Louis, St. LouisMO, United States
d Department of Psychological Sciences, Texas Tech University, Lubbock, TX, United States
Abstract
Sleep quality can affect the physical and mental health, as well as the personal development of college students. Mindfulness practices are known to ameliorate sleep disorder and improve sleep quality. Trait mindfulness, an innate capacity often enhanced by mindfulness training, has been shown to relate to better sleep quality and different aspects of psychological well-being. However, how individual difference factors such as trait mindfulness relate to sleep quality remains largely unclear, which limits the optimization and further application of mindfulness-based intervention schemes targeting the improvement of sleep quality. In this study, we aimed to investigate how negative emotions and neuroticism may influence the relationship between trait mindfulness and sleep quality. A conditional process model was built to examine these relationships in 1,423 Chinese young adults. Specifically, the conditional process model was constructed with trait mindfulness as the independent variable, sleep quality as the dependent variable, negative emotions as the mediating variable, and neuroticism as the moderating variable. Our results showed that negative emotions mediated the link between mindfulness and sleep quality and that neuroticism had a moderating effect on the relationship between mindfulness and sleep quality. Together, these findings suggested a potential mechanism of how trait mindfulness influences sleep quality, provided a therapeutic target for which mindfulness-based interventions may act upon to improve sleep quality, and offered a basis for prediction of different intervention effects among individuals. © Copyright © 2020 Ding, Wang, Yang, Tang and Tang.
Author Keywords
conditional process model; mindfulness; negative emotions; neuroticism; sleep quality
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Coprescribed Benzodiazepines in Older Adults Receiving Antidepressants for Anxiety and Depressive Disorders: Association With Treatment Outcomes” (2020) The Journal of Clinical Psychiatry
Coprescribed Benzodiazepines in Older Adults Receiving Antidepressants for Anxiety and Depressive Disorders: Association With Treatment Outcomes
(2020) The Journal of Clinical Psychiatry, 81 (6), .
Altmann, H.a , Stahl, S.T.a b , Gebara, M.A.a , Lenze, E.J.c , Mulsant, B.H.d , Blumberger, D.M.d , Reynolds, C.F., 3rda , Karp, J.F.a
a Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
b Department of Psychiatry, University of Pittsburgh, 3811 O’Hara St, Pittsburgh, United States
c Department of Psychiatry, Washington University School of Medicine, St Louis, MO, United States
d Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada
Abstract
OBJECTIVE: There is a paucity of data on the effects of coprescribed benzodiazepines on treatment response variability and adherence to antidepressant pharmacotherapy for depression and anxiety in late life. The objective of this transdiagnostic analysis was to examine the effect of benzodiazepines on treatment outcomes in older patients with generalized anxiety disorder (GAD) or major depressive disorder (MDD). METHODS: Secondary analyses of data from 2 clinical trials of antidepressant pharmacotherapy for GAD (escitalopram vs placebo, 2006-2009) or MDD (open treatment with venlafaxine, 2009-2014) were conducted. Participants included 640 adults aged 60+ years with DSM-IV-defined GAD (n = 177) or MDD (n = 463). Benzodiazepine data were collected at baseline. Adherence and treatment response were assessed over 12 weeks. The analysis addressed whether coprescribed benzodiazepines are associated with treatment response, antidepressant medication adherence, dropout, final dose of antidepressant medication, and report of antidepressant-related adverse effects. RESULTS: Participants with GAD and coprescribed benzodiazepines were treated with a lower mean dosage of escitalopram and were less likely to complete the trial; there was no difference in adherence or treatment response. Participants with MDD and coprescribed benzodiazepines were less likely to tolerate a therapeutic dose of venlafaxine and reported more medication-related adverse effects; there was no difference in adherence, dropout, or treatment response. CONCLUSIONS: Coprescription of benzodiazepines was associated with increased dropout in older patients with GAD and more medication-related adverse effects in older patients with MDD. However, with the systematic clinical attention offered in a clinical trial, they do not impede treatment response. Clinicians should be aware that a coprescribed benzodiazepine may be a marker of a more challenging treatment course. © Copyright 2020 Physicians Postgraduate Press, Inc.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Video chatting and appearance satisfaction during COVID-19: Appearance comparisons and self-objectification as moderators” (2020) International Journal of Eating Disorders
Video chatting and appearance satisfaction during COVID-19: Appearance comparisons and self-objectification as moderators
(2020) International Journal of Eating Disorders, .
Pfund, G.N.a , Hill, P.L.a , Harriger, J.b
a Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States
b Social Science Division, Pepperdine University, Malibu, CA, United States
Abstract
Objective: As video chatting has emerged as a leading form of communication for work, education, and socialization during the COVID-19 pandemic, it is important to investigate the association between video chatting and appearance satisfaction. Method: Participants included women from the United States (n = 438; age: M = 31.3, SD = 12.71) who completed measures examining their use of video chatting services, self-objectification, video chatting appearance comparison, and appearance satisfaction. Results: The total time spent on video chatting services was not associated with appearance satisfaction; however, self-objectification moderated the relationship between total hours of video chatting and appearance satisfaction. In addition, participants who engaged in more video chatting appearance comparisons reported lower face and body satisfaction. Furthermore, video chatting appearance comparison was associated with more frequent usage of certain Zoom features, such as the “touch up my appearance” feature, and more time spent looking at oneself on video calls. Finally, those who spent more time engaged with their families over video chatting services reported greater face and body satisfaction. Discussion: The results of the current study demonstrate that time spent video chatting is not predictive of appearance satisfaction, but that self-objectification can exacerbate these associations. © 2020 Wiley Periodicals LLC
Author Keywords
appearance comparison; appearance concerns; appearance satisfaction; self-objectification; video chatting
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Curbing the Cough: Multimodal Treatments for Neurogenic Cough: A Systematic Review and Meta-Analysis” (2020) Laryngoscope
Curbing the Cough: Multimodal Treatments for Neurogenic Cough: A Systematic Review and Meta-Analysis
(2020) Laryngoscope, .
Wamkpah, N.S.a , Peterson, A.M.b , Lee, J.J.a , Jia, L.c , Hardi, A.d , Stoll, C.e , Huston, M.f
a Department of Otolaryngology-Head and Neck Surgery, Washington University in St. Louis, St. Louis, MO, United States
b University of Missouri-Kansas City School of Medicine, Kansas City, MO, United States
c Washington University School of Medicine, St. Louis, MO, United States
d Bernard Becker Medical Library, Washington University in St. Louis, St. Louis, MO, United States
e Washington University Division of Public Health Sciences, St. Louis, MO, United States
f Division of Laryngology, Department of Otolaryngology–Head and Neck Surgery, Washington University in St Louis, St. Louis, MO, United States
Abstract
Objectives/Hypothesis: Neurogenic cough affects 11% of Americans and causes significant detriment to quality of life. With the advent of novel therapies, the objective of this review is to determine how procedural therapies (e.g., superior laryngeal nerve block) compare to other established pharmacologic and non-pharmacologic treatments for neurogenic cough. Methods: With the assistance of a medical librarian, a systematic review was performed using PICOS (patients, interventions, comparator, outcome, study design) format: adults with neurogenic cough receiving any pharmacologic or non-pharmacologic treatment for neurogenic cough compared to adults with neurogenic cough receiving any other relevant interventions, or treated as single cohorts, assessed with cough-specific quality of life outcomes, in all study designs and case series with ≥ 10 cases. Case reports, review articles, non-human studies, non-English language articles, and unavailable full-text articles were excluded. Results: There were 2408 patients with neurogenic cough in this review, treated with medical therapy (77%), speech therapy (19%), both medical and speech therapy (1%), and procedural therapy (3%). The included studies ranged from low to intermediate quality. Overall, most interventions demonstrated successful improvement in cough. However, the heterogeneity of included study designs precluded direct comparisons between intervention types. Conclusion: This meta-analysis compared various treatments for neurogenic cough. Procedural therapy should be considered in the armamentarium of neurogenic cough treatments, particularly in patients refractory to, or intolerant of, the side effects of medical therapy. Lastly, this review illuminates key areas for improving neurogenic cough diagnosis, such as strict adherence to diagnostic and treatment guidelines, sophisticated reflux testing, and standardized, consistent outcome reporting. Laryngoscope, 2020. © 2020 American Laryngological, Rhinological and Otological Society Inc, “The Triological Society” and American Laryngological Association (ALA)
Author Keywords
chronic cough; idiopathic cough; laryngeal hypersensitivity; Neurogenic cough; neuromodulator; superior laryngeal nerve block
Document Type: Review
Publication Stage: Article in Press
Source: Scopus
“Socio-demographic and trauma-related predictors of PTSD within 8 weeks of a motor vehicle collision in the AURORA study” (2020) Molecular Psychiatry
Socio-demographic and trauma-related predictors of PTSD within 8 weeks of a motor vehicle collision in the AURORA study
(2020) Molecular Psychiatry, .
Kessler, R.C.a , Ressler, K.J.b c , House, S.L.d , Beaudoin, F.L.e f g h , An, X.i , Stevens, J.S.j , Zeng, D.k , Neylan, T.C.l m , Linnstaedt, S.D.i , Germine, L.T.b n o , Musey, P.I., Jr.p , Hendry, P.L.q , Sheikh, S.q , Storrow, A.B.r , Jones, C.W.s , Punches, B.E.t u , Datner, E.M.v w , Mohiuddin, K.x y , Gentile, N.T.z , McGrath, M.E.aa , van Rooij, S.J.j , Hudak, L.A.ab ac , Haran, J.P.ad , Peak, D.A.ae , Domeier, R.M.af , Pearson, C.ag , Sanchez, L.D.ah ai , Rathlev, N.K.aj , Peacock, W.F.ak , Bruce, S.E.al , Miller, M.W.am an , Joormann, J.ao , Barch, D.M.ap , Pizzagalli, D.A.b , Sheridan, J.F.aq ar as , Smoller, J.W.at au av , Pace, T.W.W.j , Harte, S.E.aw ax ay , Elliott, J.M.az ba bb , Harnett, N.G.b c , Lebois, L.A.M.b c , Hwang, I.a , Sampson, N.A.a , Koenen, K.C.bc , McLean, S.A.i bd
a Department of Health Care Policy, Harvard Medical School, Boston, MA, United States
b Department of Psychiatry, Harvard Medical School, Boston, MA, United States
c Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA, United States
d Department of Emergency Medicine, Washington University School of Medicine, St. Louis, MO, United States
e Department of Emergency Medicine, The Alpert Medical School of Brown University, Providence, RI, United States
f Department of Health Services, Policy and Practice, Brown University School of Public Health, Providence, RI, United States
g Rhode Island Hospital, Providence, RI, United States
h The Miriam Hospital, Providence, RI, United States
i Institute for Trauma Recovery, Department of Anesthesiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
j Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States
k Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, United States
l San Francisco VA Healthcare System, San Francisco, CA, United States
m Departments of Psychiatry and Neurology, University of California, San Francisco, CA, United States
n Institute for Technology in Psychiatry, McLean Hospital, Belmont, MA, United States
o The Many Brains Project, Acton, MA, United States
p Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN, United States
q Department of Emergency Medicine, University of Florida College of Medicine -Jacksonville, Jacksonville, FL, United States
r Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
s Department of Emergency Medicine, Cooper Medical School of Rowan University, Camden, NJ, United States
t Department of Emergency Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States
u University of Cincinnati College of Nursing, Cincinnati, OH, United States
v Department of Emergency Medicine, Einstein Healthcare Network, Philadelphia, PA, United States
w Department of Emergency Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States
x Department of Internal Medicine, Einstein Medical Center, Philadelphia, PA, United States
y Department of Emergency Medicine, Einstein Medical Center, Philadelphia, PA, United States
z Department of Emergency Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
aa Department of Emergency Medicine, Boston Medical Center, Boston, MA, United States
ab Department of Emergency Medicine, Emory University School of Medicine, Atlanta, GA, United States
ac Emergency Medicine, Grady Memorial Hospital, Atlanta, GA, United States
ad Department of Emergency Medicine, University of Massachusetts Medical School, Worcester, MA, United States
ae Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, United States
af Department of Emergency Medicine, Saint Joseph Mercy Hospital, Ann Arbor, MI, United States
ag Wayne State University Department of Emergency Medicine, Ascension St. John Hospital, Detroit, MI, United States
ah Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States
ai Department of Emergency Medicine, Harvard Medical School, Boston, MA, United States
aj Department of Emergency Medicine, University of Massachusetts Medical School-Baystate, Springfield, MA, United States
ak Henry JN Taub Department of Emergency Medicine, Baylor College of Medicine, Houston, TX, United States
al Department of Psychological Sciences, University of Missouri – St. Louis, St. Louis, MO, United States
am National Center for PTSD at VA Boston Healthcare System, Boston, MA, United States
an Department of Psychiatry, Boston University School of Medicine, Boston, MA, United States
ao Department of Psychology, Yale University, New Haven, CT, United States
ap Departments of Psychological & Brain Sciences, Psychiatry, and Radiology, Washington University in St. Louis, St. Louis, MO, United States
aq Department of Neuroscience, Ohio State University Wexner Medical Center, Columbus, OH, United States
ar College of Dentistry Division of Bioscience, Ohio State University, Columbus, OH, United States
as Institute for Behavioral Medicine Research, Ohio State University Wexner Medical Center, Columbus, OH, United States
at Department of Psychiatry, Massachusetts General Hospital, Boston, MA, United States
au Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, United States
av Stanley Center for Psychiatric Research, Broad Institute, Boston, MA, United States
aw Chronic Pain and Fatigue Research Center, University of Michigan Medical School, Ann Arbor, MI, United States
ax Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI, United States
ay Department of Internal Medicine-Rheumatology, University of Michigan Medical School, Ann Arbor, MI, United States
az The Kolling Institute of Medical Research, Northern Clinical School, University of Sydney, St Leonards, NSW, Australia
ba Faculty of Health Sciences, University of Sydney, St Leonards, NSW, Australia
bb Physical Therapy & Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
bc Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
bd Department of Emergency Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
Abstract
This is the initial report of results from the AURORA multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience. We focus on n = 666 participants presenting to EDs following a motor vehicle collision (MVC) and examine associations of participant socio-demographic and participant-reported MVC characteristics with 8-week posttraumatic stress disorder (PTSD) adjusting for pre-MVC PTSD and mediated by peritraumatic symptoms and 2-week acute stress disorder (ASD). Peritraumatic Symptoms, ASD, and PTSD were assessed with self-report scales. Eight-week PTSD prevalence was relatively high (42.0%) and positively associated with participant sex (female), low socioeconomic status (education and income), and several self-report indicators of MVC severity. Most of these associations were entirely mediated by peritraumatic symptoms and, to a lesser degree, ASD, suggesting that the first 2 weeks after trauma may be a uniquely important time period for intervening to prevent and reduce risk of PTSD. This observation, coupled with substantial variation in the relative strength of mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated with more in-depth analyses of the rich and evolving AURORA data. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus” (2020) Nature Medicine
Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus
(2020) Nature Medicine, .
Jin, S.C.a b c , Dong, W.a b , Kundishora, A.J.d , Panchagnula, S.d , Moreno-De-Luca, A.e , Furey, C.G.d f , Allocco, A.A.d , Walker, R.L.g , Nelson-Williams, C.b , Smith, H.d , Dunbar, A.d , Conine, S.d , Lu, Q.h , Zeng, X.a b , Sierant, M.C.a b , Knight, J.R.b i , Sullivan, W.d , Duy, P.Q.d , DeSpenza, T.d , Reeves, B.C.d , Karimy, J.K.d , Marlier, A.d , Castaldi, C.i , Tikhonova, I.R.i , Li, B.j , Peña, H.P.k , Broach, J.R.l , Kabachelor, E.M.m , Ssenyonga, P.m , Hehnly, C.n , Ge, L.h , Keren, B.o , Timberlake, A.T.p , Goto, J.q , Mangano, F.T.q , Johnston, J.M.r , Butler, W.E.s , Warf, B.C.t , Smith, E.R.t , Schiff, S.J.n , Limbrick, D.D., Jr.u , Heuer, G.v w , Jackson, E.M.x , Iskandar, B.J.y , Mane, S.b i , Haider, S.k , Guclu, B.z , Bayri, Y.aa , Sahin, Y.aa , Duncan, C.C.d , Apuzzo, M.L.J.d , DiLuna, M.L.d , Hoffman, E.J.ab , Sestan, N.ac , Ment, L.R.ad ae , Alper, S.L.af , Bilguvar, K.b i , Geschwind, D.H.ag , Günel, M.b d , Lifton, R.P.a b , Kahle, K.T.b d ah
a Laboratory of Human Genetics and Genomics, The Rockefeller University, New York, NY, United States
b Department of Genetics, Yale University School of Medicine, New Haven, CT, United States
c Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States
d Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, United States
e Autism & Developmental Medicine Institute, Genomic Medicine Institute, Department of Radiology, Geisinger, Danville, PA, United States
f Department of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ, United States
g Department of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States
h Department of Biostatistics & Medical Informatics, University of Wisconsin, Madison, WI, United States
i Yale Center for Genome Analysis, Yale University, New Haven, CT, United States
j Department of Biostatistics, Yale School of Public Health, New Haven, CT, United States
k Department of Pharmaceutical and Biological Chemistry, University College London School of Pharmacy, London, United Kingdom
l Institute for Personalized Medicine, The Penn State College of Medicine, Hershey, PA, United States
m CURE Children’s Hospital of Uganda, Mbale, Uganda
n Departments of Neurosurgery, Engineering Science & Mechanics, and Physics; Center for Neural Engineering and Infectious Disease Dynamics, The Pennsylvania State University, University Park, PA, United States
o Département de Génétique, Centre de Référence Déficiences Intellectuelles de Causes Rares, Groupe Hospitalier Pitié Salpêtrière et GHUEP Hôpital Trousseau, Sorbonne Université, GRC “Déficience Intellectuelle et Autisme”, Paris, France
p Hansjörg Wyss Department of Plastic Surgery, New York University Langone Medical Center, New York, NY, United States
q Division of Pediatric Neurosurgery, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States
r Department of Neurosurgery, University of Alabama School of Medicine, Birmingham, AL, United States
s Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
t Department of Neurosurgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
u Department of Neurological Surgery and Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
v Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, PA, United States
w Division of Neurosurgery, Children’s Hospital of Philadelphia, Philadelphia, PA, United States
x Department of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, MD, United States
y Department of Neurological Surgery, University of Wisconsin Medical School, Madison, WI, United States
z Kartal Dr. Lutfi Kirdar Research and Training Hospital, Istanbul, Turkey
aa Department of Neurosurgery, Marmara University School of Medicine, Istanbul, Turkey
ab Yale Child Study Center, Yale University School of Medicine, New Haven, CT, United States
ac Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT, United States
ad Department of Pediatrics, Yale University School of Medicine, New Haven, CT, United States
ae Department of Neurology, Yale University School of Medicine, New Haven, CT, United States
af Division of Nephrology and Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, MA, United States
ag Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States
ah Department of Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, CT, United States
Abstract
Congenital hydrocephalus (CH), characterized by enlarged brain ventricles, is considered a disease of excessive cerebrospinal fluid (CSF) accumulation and thereby treated with neurosurgical CSF diversion with high morbidity and failure rates. The poor neurodevelopmental outcomes and persistence of ventriculomegaly in some post-surgical patients highlight our limited knowledge of disease mechanisms. Through whole-exome sequencing of 381 patients (232 trios) with sporadic, neurosurgically treated CH, we found that damaging de novo mutations account for >17% of cases, with five different genes exhibiting a significant de novo mutation burden. In all, rare, damaging mutations with large effect contributed to ~22% of sporadic CH cases. Multiple CH genes are key regulators of neural stem cell biology and converge in human transcriptional networks and cell types pertinent for fetal neuro-gliogenesis. These data implicate genetic disruption of early brain development, not impaired CSF dynamics, as the primary pathomechanism of a significant number of patients with sporadic CH. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Hierarchical Geodesic Modeling on the Diffusion Orientation Distribution Function for Longitudinal DW-MRI Analysis” (2020) Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Hierarchical Geodesic Modeling on the Diffusion Orientation Distribution Function for Longitudinal DW-MRI Analysis
(2020) Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), 12267 LNCS, pp. 311-321.
Kim, H.a , Hong, S.b , Styner, M.c d , Piven, J.c , Botteron, K.e , Gerig, G.a
a Department of Computer Science and Engineering, New York University, New York, NY, United States
b Department of Neurology, MGH, Harvard Medical School, Boston, MA, United States
c Department of Psychiatry, University of North Carolina, Chapel Hill, NC, United States
d Department of Computer Science, University of North Carolina, Chapel Hill, NC, United States
e Department of Psychiatry, Washington University, St. Louis, MO, United States
Abstract
The analysis of anatomy that undergoes rapid changes, such as neuroimaging of the early developing brain, greatly benefits from spatio-temporal statistical analysis methods to represent population variations but also subject-wise characteristics over time. Methods for spatio-temporal modeling and for analysis of longitudinal shape and image data have been presented before, but, to our knowledge, not for diffusion weighted MR images (DW-MRI) fitted with higher-order diffusion models. To bridge the gap between rapidly evolving DW-MRI methods in longitudinal studies and the existing frameworks, which are often limited to the analysis of derived measures like fractional anisotropy (FA), we propose a new framework to estimate a population trajectory of longitudinal diffusion orientation distribution functions (dODFs) along with subject-specific changes by using hierarchical geodesic modeling. The dODF is an angular profile of the diffusion probability density function derived from high angular resolution diffusion imaging (HARDI) and we consider the dODF with the square-root representation to lie on the unit sphere in a Hilbert space, which is a well-known Riemannian manifold, to respect the nonlinear characteristics of dODFs. The proposed method is validated on synthetic longitudinal dODF data and tested on a longitudinal set of 60 HARDI images from 25 healthy infants to characterize dODF changes associated with early brain development. © 2020, Springer Nature Switzerland AG.
Author Keywords
Diffusion weighted imaging; Hierarchical geodesic modeling; Longitudinal analysis
Document Type: Conference Paper
Publication Stage: Final
Source: Scopus
“MAGIC: Multi-scale Heterogeneity Analysis and Clustering for Brain Diseases” (2020) Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
MAGIC: Multi-scale Heterogeneity Analysis and Clustering for Brain Diseases
(2020) Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), 12267 LNCS, pp. 678-687.
Wen, J.a , Varol, E.b , Chand, G.a c , Sotiras, A.d , Davatzikos, C.a
a Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
b Department of Statistics, Center for Theoretical Neuroscience, Zuckerman Institute, Columbia University, New York, United States
c Department of Radiology, School of Medicine, Washington University in St. Louis, St. Louis, United States
d Department of Radiology and Institute for Informatics, Washington University School of Medicine, St. Louis, United States
Abstract
There is a growing amount of clinical, anatomical and functional evidence for the heterogeneous presentation of neuropsychiatric and neurodegenerative diseases such as schizophrenia and Alzheimer’s Disease (AD). Elucidating distinct subtypes of diseases allows a better understanding of neuropathogenesis and enables the possibility of developing targeted treatment programs. Recent semi-supervised clustering techniques have provided a data-driven way to understand disease heterogeneity. However, existing methods do not take into account that subtypes of the disease might present themselves at different spatial scales across the brain. Here, we introduce a novel method, MAGIC, to uncover disease heterogeneity by leveraging multi-scale clustering. We first extract multi-scale patterns of structural covariance (PSCs) followed by a semi-supervised clustering with double cyclic block-wise optimization across different scales of PSCs. We validate MAGIC using simulated heterogeneous neuroanatomical data and demonstrate its clinical potential by exploring the heterogeneity of AD using T1 MRI scans of 228 cognitively normal (CN) and 191 patients. Our results indicate two main subtypes of AD with distinct atrophy patterns that consist of both fine-scale atrophy in the hippocampus as well as large-scale atrophy in cortical regions. The evidence for the heterogeneity is further corroborated by the clinical evaluation of two subtypes, which indicates that there is a subpopulation of AD patients that tend to be younger and decline faster in cognitive performance relative to the other subpopulation, which tends to be older and maintains a relatively steady decline in cognitive abilities. © 2020, Springer Nature Switzerland AG.
Author Keywords
Clustering; Multi-scale; Semi-supervised
Document Type: Conference Paper
Publication Stage: Final
Source: Scopus
“Optical coherence tomography outcomes from SPRINT-MS, a multicenter, randomized, double-blind trial of ibudilast in progressive multiple sclerosis” (2020) Multiple Sclerosis Journal
Optical coherence tomography outcomes from SPRINT-MS, a multicenter, randomized, double-blind trial of ibudilast in progressive multiple sclerosis
(2020) Multiple Sclerosis Journal, .
Bermel, R.A.a , Fedler, J.K.b , Kaiser, P.c , Novalis, C.d , Schneebaum, J.d , Klingner, E.A.b , Williams, D.d , Yankey, J.W.b , Ecklund, D.J.b , Chase, M.e , Naismith, R.T.f , Klawiter, E.C.g , Goodman, A.D.h , Coffey, C.S.b , Fox, R.J.a
a Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH, United States
b Data Coordinating Center, Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT), University of Iowa, Iowa City, IA, United States
c Cole Eye Institute, Cleveland Clinic, Cleveland, OH, United States
d Digital Angiography Reading Center, Great Neck, NY, United States
e Clinical Coordinating Center, Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT), Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
f Department of Neurology, Washington University, St. Louis, MI, United States
g Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
h Department of Neurology, University of Rochester Medical Center, Rochester, NY, United States
Abstract
Background: The SPRINT-MS trial demonstrated benefit of ibudilast on brain atrophy over 96 weeks in progressive multiple sclerosis (MS). Optical coherence tomography (OCT) was performed in all trial participants. Objective: Report the OCT results of the SPRINT-MS trial. Methods: OCT was obtained at baseline and every 6 months using spectral domain OCT and analyzed by an OCT reading center. Change in each OCT outcome measure by treatment group was estimated using linear mixed models. Results: Change in pRNFL thickness was +0.0424 uM/year (95% confidence interval (CI): −0.3091 to 0.3939) for ibudilast versus −0.2630 uM (95% CI: −0.5973 to 0.0714) for placebo (n = 244, p = 0.22). Macular volume change was −0.00503 mm3/year (−0.02693 to 0.01688) with ibudilast versus −0.03659 mm3/year (−0.05824 to −0.01494) for placebo in the Spectralis cohort (n = 61, p = 0.044). For the Cirrus cohort, macular volume change was −0.00040 mm3/year (−0.02167, 0.020866) with ibudilast compared to −0.02083 mm3/year (−0.04134 to −0.00033) for placebo (n = 183, p = 0.1734). Ganglion cell-inner plexiform layer thickness change, available from Cirrus, was −0.4893 uM/year (−0.9132, −0.0654) with ibudilast versus −0.9587 uM/year (−1.3677, −0.5498) with placebo (n = 183, p = 0.12). Conclusion: Retinal thinning in MS may be attenuated by ibudilast. Sample size estimates suggest OCT can be a viable outcome measure in progressive MS trials if a therapy has a large treatment effect. Trial registration: NN102/SPRINT-MS ClinicalTrials.gov number, NCT01982942. © The Author(s), 2020.
Author Keywords
ibudilast; multiple sclerosis; neuroprotection; Optical coherence tomography
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Dosimetric feasibility of brain stereotactic radiosurgery with a 0.35 T MRI-guided linac and comparison vs a C-arm-mounted linac” (2020) Medical Physics
Dosimetric feasibility of brain stereotactic radiosurgery with a 0.35 T MRI-guided linac and comparison vs a C-arm-mounted linac
(2020) Medical Physics, .
Slagowski, J.M.a , Redler, G.b , Malin, M.J.c , Cammin, J.d , Lobb, E.C.e , Lee, B.H.f , Sethi, A.f , Roeske, J.C.f , Flores-Martinez, E.a , Stevens, T.g , Yenice, K.M.a , Green, O.d , Mutic, S.d , Aydogan, B.a
a Radiation and Cellular Oncology, University of Chicago, Chicago, IL 60637, United States
b Radiation Oncology, Moffitt Cancer Center, Tampa, FL 33607, United States
c Radiation Oncology, Langone Medical Center & Laura and Issac Perlmutter Cancer Center, New York University, New York, NY 10016, United States
d Radiation Oncology, Washington University School of Medicine, Barnes-Jewish Hospital, St. Louis, MO 63110, United States
e Radiation Oncology, St. Elizabeth Hospital, Appleton, WI 54915, United States
f Radiation Oncology, Loyola University Medical Center, Maywood, IL 60153, United States
g Medical Physics, Dalhousie University, Halifax, B3H 4R2, Canada
Abstract
Purpose: MRI is the gold-standard imaging modality for brain tumor diagnosis and delineation. The purpose of this work was to investigate the feasibility of performing brain stereotactic radiosurgery (SRS) with a 0.35 T MRI-guided linear accelerator (MRL) equipped with a double-focused multileaf collimator (MLC). Dosimetric comparisons were made vs a conventional C-arm-mounted linac with a high-definition MLC. Methods: The quality of MRL single-isocenter brain SRS treatment plans was evaluated as a function of target size for a series of spherical targets with diameters from 0.6 cm to 2.5 cm in an anthropomorphic head phantom and six brain metastases (max linear dimension = 0.7-1.9 cm) previously treated at our clinic on a conventional linac. Each target was prescribed 20 Gy to 99% of the target volume. Step-and-shoot IMRT plans were generated for the MRL using 11 static coplanar beams equally spaced over 360° about an isocenter placed at the center of the target. Couch and collimator angles are fixed for the MRL. Two MRL planning strategies (VR1 and VR2) were investigated. VR1 minimized the 12 Gy isodose volume while constraining the maximum point dose to be within ±1 Gy of 25 Gy which corresponded to normalization to an 80% isodose volume. VR2 minimized the 12 Gy isodose volume without the maximum dose constraint. For the conventional linac, the TB1 method followed the same strategy as VR1 while TB2 used five noncoplanar dynamic conformal arcs. Plan quality was evaluated in terms of conformity index (CI), conformity/gradient index (CGI), homogeneity index (HI), and volume of normal brain receiving ≥12 Gy (V12Gy). Quality assurance measurements were performed with Gafchromic EBT-XD film following an absolute dose calibration protocol. Results: For the phantom study, the CI of MRL plans was not significantly different compared to a conventional linac (P > 0.05). The use of dynamic conformal arcs and noncoplanar beams with a conventional linac spared significantly more normal brain (P = 0.027) and maximized the CGI, as expected. The mean CGI was 95.9 ± 4.5 for TB2 vs 86.6 ± 3.7 (VR1), 88.2 ± 4.8 (VR2), and 88.5 ± 5.9 (TB1). Each method satisfied a normal brain V12Gy ≤ 10.0 cm3 planning goal for targets with diameter ≤2.25 cm. The mean V12Gy was 3.1 cm3 for TB2 vs 5.5 cm3, 5.0 cm3 and 4.3 cm3, for VR1, VR2, and TB1, respectively. For a 2.5-cm diameter target, only TB2 met the V12Gy planning objective. The MRL clinical brain plans were deemed acceptable for patient treatment. The normal brain V12Gy was ≤6.0 cm3 for all clinical targets (maximum target volume = 3.51 cm3). CI and CGI ranged from 1.12–1.65 and 81.2–88.3, respectively. Gamma analysis pass rates (3%/1mm criteria) exceeded 97.6% for six clinical targets planned and delivered on the MRL. The mean measured vs computed absolute dose difference was −0.1%. Conclusions: The MRL system can produce clinically acceptable brain SRS plans for spherical lesions with diameter ≤2.25 cm. Large lesions (>2.25 cm) should be treated with a linac capable of delivering noncoplanar beams. © 2020 American Association of Physicists in Medicine
Author Keywords
brain metastases; MR-linac; MRI-guided radiotherapy; stereotactic radiosurgery; ViewRay
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Cognitive-affective drivers of fixation in threat assessment” (2020) Behavioral Sciences and the Law
Cognitive-affective drivers of fixation in threat assessment
(2020) Behavioral Sciences and the Law, .
Meloy, J.R.a , Rahman, T.b
a Department of Psychiatry, University of California, San Diego, CA, United States
b Department of Psychiatry, Washington University at St Louis, St Louis, MO, United States
Abstract
Pathological fixation – preoccupation with a person or a cause that is accompanied by deterioration in social and occupational functioning – has been found to precede most cases of targeted violence. It is clinically observed and theorized to have three different cognitive-affective drivers: delusion, obsession, or extreme overvalued belief. Each driver is explained, and case examples are provided in the context of threat assessment. Extreme overvalued belief as a new concept is discussed in detail, both its historical provenance and its demarcation from delusions and obsessions. Threat management for each separate cognitive-affective driver is briefly summarized, based upon current clinical findings and research. Emphasis is placed upon understanding both the categorical and dimensional nature (intensity) of these cognitive-affective drivers, and suggested guidelines are offered for the assessment of such in a clinical examination by a forensic psychiatrist or psychologist. © 2020 John Wiley & Sons Ltd.
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Optimizing Use of Neuroimaging Tools in Evaluation of Prodromal Alzheimer’s Disease and Related Disorders” (2020) Journal of Alzheimer’s Disease
Optimizing Use of Neuroimaging Tools in Evaluation of Prodromal Alzheimer’s Disease and Related Disorders
(2020) Journal of Alzheimer’s Disease, 77 (3), pp. 935-947.
Raji, C.A.a b , Torosyan, N.a , Silverman, D.H.S.a
a Ahmanson Translational Imaging Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, United States
b Mallinckrodt Institute of Radiology, Division of Neuroradiology, Washington University in St. Louis, St. Louis, MO, United States
Abstract
Alzheimer’s disease (AD) is the most common neurodegenerative disease and is characterized by preclinical, pre-dementia, and dementia phases. Progression of the disease leads to cognitive decline and is associated with loss of functional independence, personality changes, and behavioral disturbances. Current guidelines for AD diagnosis include the use of neuroimaging tools as biomarkers for identifying and monitoring pathological changes. Various imaging modalities, namely magnetic resonance imaging (MRI), fluorodeoxyglucose-positron emission tomography (FDG-PET) and PET with amyloid-beta tracers are available to facilitate early accurate diagnoses. Enhancing diagnosis in the early stages of the disease can allow for timely interventions that can delay progression of the disease. This paper will discuss the characteristic findings associated with each of the imaging tools for patients with AD, with a focus on FDG-PET due to its established accuracy in assisting with the differential diagnosis of dementia and discussion of other methods including MRI. Diagnostically-relevant features to aid clinicians in making a differential diagnosis will also be pointed out and multimodal imaging will be reviewed. We also discuss the role of quantification software in interpretation of brain imaging. Lastly, to guide evaluation of patients presenting with cognitive deficits, an algorithm for optimal integration of these imaging tools will be shared. Molecular imaging modalities used in dementia evaluations hold promise toward identifying AD-related pathology before symptoms are fully in evidence. The work describes state of the art functional and molecular imaging methods for AD. It will also overview a clinically applicable quantitative method for reproducible assessments of such scans in the early identification of AD. © 2020 – IOS Press and the authors. All rights reserved.
Author Keywords
Alzheimer’s disease; brain imaging; FDG-PET
Document Type: Review
Publication Stage: Final
Source: Scopus
“Predicting alcohol dependence from multi-site brain structural measures” (2020) Human Brain Mapping
Predicting alcohol dependence from multi-site brain structural measures
(2020) Human Brain Mapping, .
Hahn, S.a , Mackey, S.a , Cousijn, J.b , Foxe, J.J.c , Heinz, A.d , Hester, R.e , Hutchinson, K.f , Kiefer, F.g , Korucuoglu, O.h , Lett, T.d , Li, C.-S.R.i , London, E.j , Lorenzetti, V.k l m , Maartje, L.n , Momenan, R.o , Orr, C.a , Paulus, M.p q , Schmaal, L.r s , Sinha, R.i , Sjoerds, Z.t u , Stein, D.J.v , Stein, E.w , van Holst, R.J.x , Veltman, D.y , Walter, H.d , Wiers, R.W.b , Yucel, M.j z , Thompson, P.M.aa , Conrod, P.ab , Allgaier, N.a , Garavan, H.a
a Department of Psychiatry, University of Vermont College of Medicine, Burlington, VT, United States
b Department of Psychology, University of Amsterdam, Amsterdam, Netherlands
c Department of Neuroscience & The Ernest J. Del Monte Institute for Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States
d Department of Psychiatry and Psychotherapy, Charité—Universitätsmedizin Berlin, Berlin, Germany
e Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Australia
f Department of Psychology and Neuroscience, University of Colorado, Boulder, CO, United States
g Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, Heidelberg University, Mannheim, Germany
h Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
i Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States
j David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, United States
k Monash Institute of Cognitive and Clinical Neurosciences & School of Psychological Sciences, Monash University, Melbourne, Australia
l School of Psychology, Faculty of Health Sciences, Australian Catholic University, Melbourne, Australia
m Department of Psychological Sciences, the University of Liverpool, Liverpool, United Kingdom
n Behavioural Science Institute, Radboud University, Nijmegen, Netherlands
o Clinical NeuroImaging Research Core, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, United States
p VA San Diego Healthcare System and Department of Psychiatry, University of California San Diego, La Jolla, CA, United States
q Laureate Institute for Brain Research, Tulsa, OK, United States
r Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, Australia
s Centre for Youth Mental Health, The University of Melbourne, Melbourne, Australia
t Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
u Institute of Psychology, Cognitive Psychology Unit & Leiden Institute for Brain and Cognition, Leiden University, Leiden, Netherlands
v SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa
w Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, United States
x Department of Psychiatry, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, Netherlands
y Department of Psychiatry, VU University Medical Center, Amsterdam, Netherlands
z Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Melbourne, Australia
aa Imaging Genetics Center, Stevens Institute for Neuroimaging & Informatics, Keck School of Medicine, University of Southern CaliforniaCA, United States
ab Department of Psychiatry, Université de Montreal, CHU Ste Justine Hospital, Montreal, QC, Canada
Abstract
To identify neuroimaging biomarkers of alcohol dependence (AD) from structural magnetic resonance imaging, it may be useful to develop classification models that are explicitly generalizable to unseen sites and populations. This problem was explored in a mega-analysis of previously published datasets from 2,034 AD and comparison participants spanning 27 sites curated by the ENIGMA Addiction Working Group. Data were grouped into a training set used for internal validation including 1,652 participants (692 AD, 24 sites), and a test set used for external validation with 382 participants (146 AD, 3 sites). An exploratory data analysis was first conducted, followed by an evolutionary search based feature selection to site generalizable and high performing subsets of brain measurements. Exploratory data analysis revealed that inclusion of case- and control-only sites led to the inadvertent learning of site-effects. Cross validation methods that do not properly account for site can drastically overestimate results. Evolutionary-based feature selection leveraging leave-one-site-out cross-validation, to combat unintentional learning, identified cortical thickness in the left superior frontal gyrus and right lateral orbitofrontal cortex, cortical surface area in the right transverse temporal gyrus, and left putamen volume as final features. Ridge regression restricted to these features yielded a test-set area under the receiver operating characteristic curve of 0.768. These findings evaluate strategies for handling multi-site data with varied underlying class distributions and identify potential biomarkers for individuals with current AD. © 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.
Author Keywords
addiction; alcohol dependence; genetic algorithm; machine learning; multi-site; prediction; structural MRI
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access
“The Cardiovascular Effects of Newer Antidepressants in Older Adults and Those With or At High Risk for Cardiovascular Diseases” (2020) CNS Drugs
The Cardiovascular Effects of Newer Antidepressants in Older Adults and Those With or At High Risk for Cardiovascular Diseases
(2020) CNS Drugs, .
Behlke, L.M., Lenze, E.J., Carney, R.M.
Department of Psychiatry, Washington University School of Medicine, 4320 Forest Park Avenue, Suite 301, Saint Louis, MO 63108, United States
Abstract
Depression is common in older adults and those with cardiovascular disease. Although selective serotonin reuptake inhibitors generally have been shown to be safe to treat depression in these patients, it is important to identify additional antidepressants when selective serotonin reuptake inhibitors are not effective. This qualitative narrative review summarizes what is known about the cardiovascular side effects of some of the newer antidepressants. Twelve novel non-selective serotonin reuptake inhibitor antidepressants were identified from the literature: venlafaxine, desvenlafaxine, duloxetine, milnacipran, levomilnacipran, mirtazapine, bupropion, vilazodone, vortioxetine, agomelatine, moclobemide, and ketamine–esketamine. A search restricted to publications written in English was conducted in PubMed and Google Scholar with the following search criteria: the specific antidepressant AND (QT OR QTc OR “heart rate” OR “heart rate variability” OR “hypertension” OR “orthostatic hypotension” OR “cardiovascular outcomes” OR “arrhythmia” OR “myocardial infarction” OR “cardiovascular mortality”) AND (geriatric OR “older adults” OR “late life depression” OR “cardiovascular disease” OR “hospitalized” OR “hospitalized”). The recommended use, dosing ranges, cardiovascular effects, and general advantages and disadvantages of each of the drugs are discussed. Levomilnacipran and vilazodone have not received enough study to judge their safety in older patients or in those with, or at high risk for, cardiovascular disease. There is at least some evidence for possible adverse events with each of the other newer antidepressants that could be of concern in these patients. Nevertheless, with careful administration and attention to the potential adverse reactions for each drug, these may provide safe effective alternatives for older adults and patients with cardiovascular disease who do not respond to selective serotonin reuptake inhibitor antidepressants. However, more research on the safety and efficacy of these drugs in these specific patient populations is urgently needed. © 2020, Springer Nature Switzerland AG.
Document Type: Review
Publication Stage: Article in Press
Source: Scopus
“Intact microstructure of the right corticostriatal pathway predicts creative ability in healthy adults” (2020) Brain and Behavior
Intact microstructure of the right corticostriatal pathway predicts creative ability in healthy adults
(2020) Brain and Behavior, .
Rahmani, F.a b , Sanjari Moghaddam, H.c , Aarabi, M.H.c
a Department of Radiology, Washington University in St. Louis, St. Louis, MO, United States
b NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN), Tehran, Iran
c Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Abstract
Introduction: Creativity is one of the most complex functions of the human brain. The corticostriatal pathways have been implicated in creative thinking, yet few studies have addressed the microstructural underpinnings of creative ability, especially those related to the corticostriatal dopaminergic circuitry. We hypothesized that performance in creativity tests can be predicted based on diffusion metrics of the corticostriatal pathways and basal ganglia. Methods: A total of 37 healthy adults were included. Neuropsychological tests of creativity, including the alternative uses task (AUT), test of creative imagery abilities (TCIA), remote associates test (RAT), and creative achievement questionnaire (CAQ), as well as diffusion MRI data were acquired for each participant. Results: We demonstrated an independent effect of TCIA originality and TCIA transformativeness subscores, and RAT score in predicting the mean diffusivity (MD), mean axial diffusivity (AD), mean fractional anisotropy (FA), and mean generalized FA of the right corticostriatal pathway. We also observed independent effects of AUT elaboration subscore in predicting the AD of the right substantia nigra, and radial diffusivity (RD) of the right globus pallidus. Conclusion: Our results put a further spin on the “creative right brain” notion and question the presence of high-creative and low-creative networks in the brain. © 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC
Author Keywords
corticostriatal pathway; creativity; diffusion MRI; diffusion-weighted imaging
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access
“Cell-type-specific 3D epigenomes in the developing human cortex” (2020) Nature
Cell-type-specific 3D epigenomes in the developing human cortex
(2020) Nature, .
Song, M.a b , Pebworth, M.-P.c d , Yang, X.a , Abnousi, A.e , Fan, C.f g , Wen, J.h , Rosen, J.D.i , Choudhary, M.N.K.f g , Cui, X.a , Jones, I.R.a , Bergenholtz, S.a , Eze, U.C.d j , Juric, I.e , Li, B.a , Maliskova, L.a , Lee, J.a , Liu, W.i , Pollen, A.A.d k , Li, Y.h i l , Wang, T.f g m , Hu, M.e , Kriegstein, A.R.d k , Shen, Y.a k n
a Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, United States
b Pharmaceutical Sciences and Pharmacogenomics Graduate Program, University of California, San Francisco, San Francisco, CA, United States
c Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, United States
d The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, United States
e Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, United States
f Department of Genetics, Washington University School of Medicine, St Louis, MO, United States
g The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO, United States
h Department of Genetics, University of North Carolina, Chapel Hill, NC, United States
i Department of Biostatistics, University of North Carolina, Chapel Hill, NC, United States
j Medical Scientist Training Program, University of California, San Francisco, San Francisco, CA, United States
k Department of Neurology, University of California, San Francisco, San Francisco, CA, United States
l Department of Computer Science, University of North Carolina, Chapel Hill, NC, United States
m McDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, United States
n Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States
Abstract
Lineage-specific epigenomic changes during human corticogenesis have been difficult to study owing to challenges with sample availability and tissue heterogeneity. For example, previous studies using single-cell RNA sequencing identified at least 9 major cell types and up to 26 distinct subtypes in the dorsal cortex alone1,2. Here we characterize cell-type-specific cis-regulatory chromatin interactions, open chromatin peaks, and transcriptomes for radial glia, intermediate progenitor cells, excitatory neurons, and interneurons isolated from mid-gestational samples of the human cortex. We show that chromatin interactions underlie several aspects of gene regulation, with transposable elements and disease-associated variants enriched at distal interacting regions in a cell-type-specific manner. In addition, promoters with increased levels of chromatin interactivity—termed super-interactive promoters—are enriched for lineage-specific genes, suggesting that interactions at these loci contribute to the fine-tuning of transcription. Finally, we develop CRISPRview, a technique that integrates immunostaining, CRISPR interference, RNAscope, and image analysis to validate cell-type-specific cis-regulatory elements in heterogeneous populations of primary cells. Our findings provide insights into cell-type-specific gene expression patterns in the developing human cortex and advance our understanding of gene regulation and lineage specification during this crucial developmental window. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Ecological Momentary Assessment of Social Interactions: Associations With Depression, Anxiety, Pain, and Fatigue in Individuals With Mild Stroke” (2020) Archives of Physical Medicine and Rehabilitation
Ecological Momentary Assessment of Social Interactions: Associations With Depression, Anxiety, Pain, and Fatigue in Individuals With Mild Stroke
(2020) Archives of Physical Medicine and Rehabilitation, .
Neff, A.J.a , Lee, Y.a , Metts, C.L.b , Wong, A.W.K.a c d
a Program in Occupational Therapy, Washington University School of Medicine, St. Louis, MO, United States
b Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, United States
c Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
d Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
Abstract
Objectives: To examine real-time relationships between social interactions and poststroke mood and somatic symptoms in participants’ daily environments. Design: Prospective observational study using smartphone-based ecological momentary assessment (EMA) surveys 5 times a day for 2 weeks. Multilevel models were used to analyze data for concurrent and lagged associations. Setting: Community. Participants: Adults (N=48) with mild stroke. Interventions: Not applicable. Main Outcome Measures: EMA measures of self-appraisal of social interactions (confidence, satisfaction, and success), as well as mood (depression and anxiety) and somatic (pain and fatigue) symptoms. Results: In concurrent associations, increased depressed mood was associated with reduced ratings of all aspects of social interactions. Fatigue was associated with reduced ratings of social satisfaction and success. In lagged associations, increased anxious mood preceded increased subsequent social confidence. Higher average social satisfaction, confidence, and success were related to lower momentary fatigue, anxious mood, and depressed mood at the next time point. Regarding clinicodemographic factors, being employed was concurrently related to increased social interactions. An increased number of comorbidities predicted higher somatic, but not mood, symptoms at the next time point. Conclusions: This study provides preliminary evidence of dynamic relationships between social interactions and somatic and mood symptoms in individuals with mild stroke. Interventions to not only address the sequelae of symptoms, but also to promote participation in social activities in poststroke life should be explored. © 2020 American Congress of Rehabilitation Medicine
Author Keywords
Anxiety; Depression; Ecological momentary assessment; Fatigue; Interpersonal relations; Rehabilitation; Stroke
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“New neurologic deficit and recovery rates in the treatment of complex pediatric spine deformities exceeding 100 degrees or treated by vertebral column resection (VCR)” (2020) Spine Deformity
New neurologic deficit and recovery rates in the treatment of complex pediatric spine deformities exceeding 100 degrees or treated by vertebral column resection (VCR)
(2020) Spine Deformity, .
Boachie-Adjei, O.a , Duah, H.O.a , Yankey, K.P.a , Lenke, L.G.b , Sponseller, P.D.c , Sucato, D.J.d , Samdani, A.F.e , Newton, P.O.f , Shah, S.A.g , Erickson, M.A.h , Akoto, H.i , Sides, B.A.j , Gupta, M.C.j , Fox Pediatric Spinal Deformity Studyj
a FOCOS Orthopaedic Hospital, Accra, Ghana
b New York Presbyterian, The Allen Hospital, New York, United States
c The Johns Hopkins Hospital, Baltimore, MD, United States
d Scottish Rite Hospital for Children, Texas, United States
e Shriners Hospitals for Children- Philadelphia, Philadelphia, PA, United States
f Rady Children’s Hospital -San Diego, San Diego, CA, United States
g Spine and Scoliosis Center, Nemours/Alfred I. duPont Pediatrics, Wilmington, DE, United States
h Children’s Hospital Colorado, Aurora, CO, United States
i Korle-Bu Teaching Hospital, Accra, Ghana
j Department of Orthopedics, Washington University School of Medicine, St. Louis, MO, United States
Abstract
Study design: Prospective multicenter international observational study. Objective: To investigate incidence of new neurologic deficit (NND) and the long-term recovery patterns following complex pediatric spine deformity surgery. Summary of background data: The SRS M&M reports identify pediatric patients as having higher rate of new neurologic deficit compared with adults, while congenital and neuromuscular deformities are associated with higher new neurologic risks. Very few studies have had the large numbers of pediatric patients with curves exceeding 100 deg to ascertain the new neurologic deficit (NND) rates and recovery patterns as it relates to curve laterality and diagnosis. Method: The FOX pediatric database from 17 international sites was queried for New Neurologic Deficit (NND) as characterized by change in American Spinal Injury Association (ASIA) Lower or Upper Extremity Motor Score. Recovery rates at specific intervals were recorded and related to the curve type and etiology. Results: Data of 286 consecutive patients with normal pre-operative neurologic exams were reviewed. There were 160 females vs 125 males with an average age of 14.6 years. NND occurred in 27 patients (9.4%) in the immediate post-operative period. Diagnostic categories included idiopathic scoliosis (3 patients); idiopathic kyphoscoliosis(5 patients); congenital scoliosis (7 patients); congenital kyphoscoliosis (4 patients); congenital kyphosis (6 patients), other kyphosis (1 patient) and syndromic (1 patient). 1 patient was lost to follow-up (f/u) after discharge; 1 had chronic deficits at the first post-operative erect visit (from discharge to 9 months f/u) and was subsequently lost to follow-up; 2 patients were improving at 1-year f/u but lost to subsequent f/u. 16 patients had normal neurologic function by the time of the first post-operative erect visit, 21 patients at 1-year f/u and 21 patients at the 2-year f/u. 2 patients (0.69%) had improved NND at 2-year mark. Conclusion: A significant proportion of patients with complex spine deformity experience NND. However, significant improvement in neurologic function can be expected over time as seen in this study without additional surgical intervention in most cases. Congenital deformities accounted for 63% of the patients experiencing NND. © 2020, Scoliosis Research Society.
Author Keywords
Complex Spine Deformity; Neurologic complications; Neurologic recovery; New Neurologic Deficit
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Deletion of muscarinic acetylcholine receptor 3 in microglia impacts brain ischemic injury” (2020) Brain, Behavior, and Immunity
Deletion of muscarinic acetylcholine receptor 3 in microglia impacts brain ischemic injury
(2020) Brain, Behavior, and Immunity, .
Costa, A.a b , Haage, V.a , Yang, S.a g , Wegner, S.c , Ersoy, B.c , Ugursu, B.g , Rex, A.c , Kronenberg, G.c d , Gertz, K.c , Endres, M.c e f , Wolf, S.A.a g , Kettenmann, H.a
a Cellular Neuroscience, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Str. 10, Berlin, 13051, Germany
b Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United States
c Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Klinik und Hochschulambulanz für Neurologie und Centrum für Schlaganfallforschung Berlin (CSB) und Abteilung für Experimentelle Neurologie, Berlin, 10117, Germany
d College of Life Sciences, University of Leicester, BHF Research Centre, Groby Road, Leicester, Leicester LE3 9Q4, United Kingdom
e German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Germany
f German Center for Neurodegenerative Diseases (DZNE), Partner Site Berlin, Germany
g Department of Ophthalmology, Charité – University Medicine Berlin, Augustenburger Platz 1, Berlin, 13353, Germany
Abstract
Microglia are the immune cells of the brain and become activated during any type of brain injury. In the middle cerebral artery occlusion (MCAo) model, a mouse model for ischemic stroke, we have previously shown that microglia and invaded monocytes upregulate the expression of the muscarinic acetylcholine receptor 3 (M3R) in the ischemic lesion. Here we tested whether this upregulation has an impact on the pathogenesis of MCAo. We depleted the m3R receptor in microglia, but not in circulating monocytes by giving tamoxifen to CX3CR1-CreERT+/+M3Rflox/flox (M3RKOmi) animals 3 weeks prior to MCAo. We found that M3RKOmi male mice had bigger lesions, more pronounced motor deficits after one week and cognitive deficits after about one month compared to control males. The density of Iba1+ cells was lower in the lesions of M3RKO male mice in the early, but not in the late disease phase. In females, these differences were not significant. By giving tamoxifen 1 week prior to MCAo, we depleted m3R in microglia and in circulating monocytes (M3RKOmi/mo). Male M3RKOmi/mo did not differ in lesion size, but had a lower survival rate, showed motor deficits and a reduced accumulation of Iba1+ positive cells into the lesion site. In conclusion, our data suggest that the upregulation of m3R in microglia and monocytes in stroke has a beneficial effect on the clinical outcome in male mice. © 2020 Elsevier Inc.
Author Keywords
Brain macrophages; MCAo model; Microglia; Muscarinic acetylcholine receptor; Stroke
Document Type: Article
Publication Stage: Article in Press
Source: Scopus