“A PIP2 substitute mediates voltage sensor-pore coupling in KCNQ activation” (2020) Communications Biology
A PIP2 substitute mediates voltage sensor-pore coupling in KCNQ activation
(2020) Communications Biology, 3 (1), art. no. 385, .
Liu, Y.a , Xu, X.b , Gao, J.c , Naffaa, M.M.a , Liang, H.a , Shi, J.a , Wang, H.Z.c , Yang, N.-D.a , Hou, P.a , Zhao, W.a , White, K.M.F.a , Kong, W.a , Dou, A.a , Cui, A.a , Zhang, G.a , Cohen, I.S.c , Zou, X.b , Cui, J.a
a Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Disorders, Cardiac Bioelectricity and Arrhythmia Center, Washington University in Saint Louis, Saint Louis, MO 63130, United States
b Dalton Cardiovascular Research Center, Department of Physics and Astronomy, Department of Biochemistry, Institute for Data Science & Informatics, University of Missouri, Columbia, MO 65211, United States
c Department of Physiology and Biophysics, and Institute for Molecular Cardiology, Stony Brook University, Stony Brook, NY 11794, United States
Abstract
KCNQ family K+ channels (KCNQ1-5) in the heart, nerve, epithelium and ear require phosphatidylinositol 4,5-bisphosphate (PIP2) for voltage dependent activation. While membrane lipids are known to regulate voltage sensor domain (VSD) activation and pore opening in voltage dependent gating, PIP2 was found to interact with KCNQ1 and mediate VSD-pore coupling. Here, we show that a compound CP1, identified in silico based on the structures of both KCNQ1 and PIP2, can substitute for PIP2 to mediate VSD-pore coupling. Both PIP2 and CP1 interact with residues amongst a cluster of amino acids critical for VSD-pore coupling. CP1 alters KCNQ channel function due to different interactions with KCNQ compared with PIP2. We also found that CP1 returned drug-induced action potential prolongation in ventricular myocytes to normal durations. These results reveal the structural basis of PIP2 regulation of KCNQ channels and indicate a potential approach for the development of anti-arrhythmic therapy. © 2020, The Author(s).
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Assessing the accuracy of automatic speech recognition for psychotherapy” (2020) NPJ Digital Medicine
Assessing the accuracy of automatic speech recognition for psychotherapy
(2020) NPJ Digital Medicine, 3 (1), art. no. 82, .
Miner, A.S.a b c , Haque, A.d , Fries, J.A.c , Fleming, S.L.e , Wilfley, D.E.f , Terence Wilson, G.g , Milstein, A.h , Jurafsky, D.d i , Arnow, B.A.a , Stewart Agras, W.a , Fei-Fei, L.d , Shah, N.H.c
a Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States
b Department of Health Research and Policy, Stanford UniversityCA, United States
c Center for Biomedical Informatics Research, Stanford University, Stanford, CA, United States
d Department of Computer Science, Stanford University, Stanford, CA, United States
e Department of Biomedical Data Science, Stanford University, Stanford, CA, United States
f Departments of Psychiatry, Medicine, Pediatrics, and Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States
g Graduate School of Applied and Professional Psychology, Rutgers, the State University of New Jersey, New Brunswick, NJ, United States
h Clinical Excellence Research Center, Stanford University, Stanford, CA, United States
i Department of Linguistics, Stanford University, Stanford, CA, United States
Abstract
Accurate transcription of audio recordings in psychotherapy would improve therapy effectiveness, clinician training, and safety monitoring. Although automatic speech recognition software is commercially available, its accuracy in mental health settings has not been well described. It is unclear which metrics and thresholds are appropriate for different clinical use cases, which may range from population descriptions to individual safety monitoring. Here we show that automatic speech recognition is feasible in psychotherapy, but further improvements in accuracy are needed before widespread use. Our HIPAA-compliant automatic speech recognition system demonstrated a transcription word error rate of 25%. For depression-related utterances, sensitivity was 80% and positive predictive value was 83%. For clinician-identified harm-related sentences, the word error rate was 34%. These results suggest that automatic speech recognition may support understanding of language patterns and subgroup variation in existing treatments but may not be ready for individual-level safety surveillance. © 2020, The Author(s).
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Cognitive plausibility in voice-based AI health counselors” (2020) NPJ Digital Medicine
Cognitive plausibility in voice-based AI health counselors
(2020) NPJ Digital Medicine, 3 (1), art. no. 72, .
Kannampallil, T.a b , Smyth, J.M.c , Jones, S.d , Payne, P.R.O.b , Ma, J.e
a Department of Anesthesiology, Washington University School of Medicine, St Louis, MO, United States
b Institute for Informatics, Washington University School of Medicine, St Louis, MO, United States
c Department of Biobehavioral Health, The Pennsylvania State University, University Park, PA, United States
d Department of Communication, University of Illinois at Chicago, Chicago, IL, United States
e Department of Medicine, University of Illinois at Chicago, Chicago, IL, United States
Abstract
Voice-based personal assistants using artificial intelligence (AI) have been widely adopted and used in home-based settings. Their success has created considerable interest for its use in healthcare applications; one area of prolific growth in AI is that of voice-based virtual counselors for mental health and well-being. However, in spite of its promise, building realistic virtual counselors to achieve higher-order maturity levels beyond task-based interactions presents considerable conceptual and pragmatic challenges. We describe one such conceptual challenge—cognitive plausibility, defined as the ability of virtual counselors to emulate the human cognitive system by simulating how a skill or function is accomplished. An important cognitive plausibility consideration for voice-based agents is its ability to engage in meaningful and seamless interactive communication. Drawing on a broad interdisciplinary research literature and based on our experiences with developing two voice-based (voice-only) prototypes that are in the early phases of testing, we articulate two conceptual considerations for their design and use—conceptualizing voice-based virtual counselors as communicative agents and establishing virtual co-presence. We discuss why these conceptual considerations are important and how it can lead to the development of voice-based counselors for real-world use. © 2020, The Author(s).
Document Type: Note
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Estimation and validation of individualized dynamic brain models with resting state fMRI” (2020) NeuroImage,
Estimation and validation of individualized dynamic brain models with resting state fMRI
(2020) NeuroImage, 221, art. no. 117046, .
Singh, M.F.a b c , Braver, T.S.b , Cole, M.W.d , Ching, S.c e
a Department of Neuroscience, Washington University in St. Louis, St. Louis, MO, United States
b Department of Psychology, Washington University in St. Louis, St. Louis, MO, United States
c Department of Electrical and Systems Engineering, Washington University in St. Louis, St. Louis, MO, United States
d Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, NJ 07102, United States
e Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States
Abstract
A key challenge for neuroscience is to develop generative, causal models of the human nervous system in an individualized, data-driven manner. Previous initiatives have either constructed biologically-plausible models that are not constrained by individual-level human brain activity or used data-driven statistical characterizations of individuals that are not mechanistic. We aim to bridge this gap through the development of a new modeling approach termed Mesoscale Individualized Neurodynamic (MINDy) modeling, wherein we fit nonlinear dynamical systems models directly to human brain imaging data. The MINDy framework is able to produce these data-driven network models for hundreds to thousands of interacting brain regions in just 1–3 min per subject. We demonstrate that the models are valid, reliable, and robust. We show that MINDy models are predictive of individualized patterns of resting-state brain dynamical activity. Furthermore, MINDy is better able to uncover the mechanisms underlying individual differences in resting state activity than functional connectivity methods. © 2020 The Author(s)
Author Keywords
Causal modeling; Dynamic functional connectivity; Neural dynamics; Recurrent neural networks; Resting state fMRI
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Clinical and laboratory features distinguishing MOG antibody disease from multiple sclerosis and AQP4 antibody-positive neuromyelitis optica” (2020) Multiple Sclerosis and Related Disorders
Clinical and laboratory features distinguishing MOG antibody disease from multiple sclerosis and AQP4 antibody-positive neuromyelitis optica
(2020) Multiple Sclerosis and Related Disorders, 45, art. no. 102399, .
Ciotti, J.R.a , Eby, N.S.b , Wu, G.F.a , Naismith, R.T.a , Chahin, S.a , Cross, A.H.a
a Washington University in St. Louis, Department of Neurology, St. Louis, MO, United States
b Washington University Medical School, St. Louis, MO, United States
Abstract
Background: Antibodies to myelin oligodendrocyte glycoprotein (MOG) are associated with a CNS inflammatory disorder distinct from multiple sclerosis (MS) and aquaporin-4 antibody-positive neuromyelitis optica (NMO). Knowledge of the clinical spectrum of MOG antibody disease (MOGAD) remains incomplete, particularly in comparison to two related inflammatory demyelinating diseases, MS and NMO. Objective: Compare demographics, clinical characteristics, estimated disability, laboratory results, and treatment responses of a U.S. MOGAD cohort with age- and sex-matched MS and NMO patients. Design, setting, and participants: This observational, case-control, single-center study identified each group via ICD-10 diagnosis code searches through the electronic medical records of adult patients seen at the John L. Trotter MS Center between January 1, 2019 and January 1, 2020. MOGAD and NMO patients were confirmed to have at least one positive antibody test; those in the MS group had a confirmed diagnosis by a physician with MS subspecialty training. Data were collected after IRB approval. Results: Twenty-six patients were included in each group. MOGAD patients were predominantly Caucasian (88.5%) with mean onset age of 43.9 years. MOGAD patients had no comorbid other autoimmune diseases and comparatively lower rates of family members with autoimmune disease (20.0%) than either MS (40.0%) or NMO (34.6%) matched cohorts. 91% of MOGAD attacks were monofocal, and over 70% presented with optic neuritis. Severity of MOGAD attacks was similar to that of seropositive NMO, but the robust degree of recovery was more similar to MS. Four MOGAD patients converted to negative antibody status, with no attacks occurring after conversion. Serum ANA and ENA were less frequently elevated in MOGAD (21.7%, 5.0%) than in seropositive NMO patients (66.7%, 42.9%). Elevated IgG synthesis rate and positive CSF-restricted oligoclonal bands were not seen in our MOGAD cohort, and only one MOGAD patient had an elevated IgG index. Despite anti-CD20 therapy, 28.6% of MOGAD patients continued to suffer relapses. Conclusions: MOGAD was characterized by a predominantly monofocal presentation (typically optic neuritis) and severe attacks with better recovery than seen with seropositive NMO attacks. Lack of CSF-restricted oligoclonal bands distinguished MOGAD from MS. © 2020 Elsevier B.V.
Author Keywords
Clinical presentation; Demyelinating disease; MOG antibody disease; Multiple sclerosis; Neuromyelitis optica
Document Type: Article
Publication Stage: Final
Source: Scopus
“The role of glia in protein aggregation” (2020) Neurobiology of Disease
The role of glia in protein aggregation
(2020) Neurobiology of Disease, 143, art. no. 105015, .
Li, Q.a b c , Haney, M.S.d
a Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, United States
b Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, United States
c Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, United States
d Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, United States
Abstract
Protein aggregation diseases involve intracellular accumulation or extracellular deposition of certain protein species in neuronal or glial cells, leading to neurodegeneration and shortened lifespan. Prime examples include Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), which are affected by overlapping or specific aggregation-prone proteins. Mounting evidence suggests that dysfunctional glial cells may be major drivers for some diseases, and when they are not causal factors, they could still significantly exacerbate or alleviate disease progression by playing a plethora of detrimental or beneficial roles. Here we review the diverse functions performed by glial cells in a variety of protein aggregation diseases, highlighting the complexity of the issue and the interconnected relationships between these multifaceted effects. © 2020
Author Keywords
Alzheimer’s disease; Amyotrophic lateral sclerosis; Astrocytes; Aβ; Glia; Microglia; Oligodendrocytes; Parkinson’s disease; Protein aggregation; α-Syn
Document Type: Review
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“The effect of thermal therapy on the blood-brain barrier and blood-tumor barrier” (2020) International Journal of Hyperthermia
The effect of thermal therapy on the blood-brain barrier and blood-tumor barrier
(2020) International Journal of Hyperthermia, 37 (2), pp. 35-43. Cited 1 time.
Patel, B., Yang, P.H., Kim, A.H.
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, United States
Abstract
The blood-brain and blood-tumor barriers represent highly specialized structures responsible for tight regulation of molecular transit into the central nervous system. Under normal circumstances, the relative impermeability of the blood-brain barrier (BBB) protects the brain from circulating toxins and contributes to a brain microenvironment necessary for optimal neuronal function. However, in the context of tumors and other diseases of central nervous system, the BBB and the more recently appreciated blood-tumor barrier (BTB) represent barriers that prevent effective drug delivery. Overcoming both barriers to optimize treatment of central nervous system diseases remains the subject of intense scientific investigation. Although many newer technologies have been developed to overcome these barriers, thermal therapy, which dates back to the 1890 s, has been known to disrupt the BBB since at least the early 1980s. Recently, as a result of several technological advances, laser interstitial thermal therapy (LITT), a method of delivering targeted thermal therapy, has gained widespread use as a surgical technique to ablate brain tumors. In addition, accumulating evidence indicates that laser ablation may also increase local BBB/BTB permeability after treatment. We herein review the structure and function of the BBB and BTB and the impact of thermal injury, including LITT, on barrier function. © 2020, © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.
Author Keywords
blood-brain barrier; blood-tumor barrier; brain tumors; glioblastoma; Laser interstitial thermal therapy
Document Type: Review
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Stable readout of observed actions from format-dependent activity of monkey’s anterior intraparietal neurons” (2020) Proceedings of the National Academy of Sciences of the United States of America
Stable readout of observed actions from format-dependent activity of monkey’s anterior intraparietal neurons
(2020) Proceedings of the National Academy of Sciences of the United States of America, 117 (28), pp. 16596-16605.
Lanzilotto, M.a b , Maranesi, M.b , Livi, A.b c , Ferroni, C.G.b , Orban, G.A.b , Bonini, L.d
a Department of Psychology, University of Turin, 10124 Turin, Italy; luca.bonini@unipr.it
b Department of Medicine and Surgery, University of Parma, Parma, 43125, Italy
c Department of Neuroscience, Washington University in St. Louis, St. Louis, MO 63110
d Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy; marco.lanzilotto@unito.it luca.bonini@unipr.it
Abstract
Humans accurately identify observed actions despite large dynamic changes in their retinal images and a variety of visual presentation formats. A large network of brain regions in primates participates in the processing of others’ actions, with the anterior intraparietal area (AIP) playing a major role in routing information about observed manipulative actions (OMAs) to the other nodes of the network. This study investigated whether the AIP also contributes to invariant coding of OMAs across different visual formats. We recorded AIP neuronal activity from two macaques while they observed videos portraying seven manipulative actions (drag, drop, grasp, push, roll, rotate, squeeze) in four visual formats. Each format resulted from the combination of two actor’s body postures (standing, sitting) and two viewpoints (lateral, frontal). Out of 297 recorded units, 38% were OMA-selective in at least one format. Robust population code for viewpoint and actor’s body posture emerged shortly after stimulus presentation, followed by OMA selectivity. Although we found no fully invariant OMA-selective neuron, we discovered a population code that allowed us to classify action exemplars irrespective of the visual format. This code depends on a multiplicative mixing of signals about OMA identity and visual format, particularly evidenced by a set of units maintaining a relatively stable OMA selectivity across formats despite considerable rescaling of their firing rate depending on the visual specificities of each format. These findings suggest that the AIP integrates format-dependent information and the visual features of others’ actions, leading to a stable readout of observed manipulative action identity. Copyright © 2020 the Author(s). Published by PNAS.
Author Keywords
action observation; neural decoding; parietal cortex; visual invariance
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Molecular and clinicopathologic features of gliomas harboring NTRK fusions” (2020) Acta Neuropathologica Communications
Molecular and clinicopathologic features of gliomas harboring NTRK fusions
(2020) Acta Neuropathologica Communications, 8 (1), p. 107.
Torre, M.a b , Vasudevaraja, V.c , Serrano, J.c , DeLorenzo, M.c , Malinowski, S.d , Blandin, A.-F.d , Pages, M.e , Ligon, A.H.a f , Dong, F.a , Meredith, D.M.a , Nasrallah, M.P.g , Horbinski, C.h i , Dahiya, S.j , Ligon, K.L.a b d , Santi, M.g k , Ramkissoon, S.H.l m , Filbin, M.G.n , Snuderl, M.c , Alexandrescu, S.a b
a Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, MA, 75 Francis Street, Boston, 02115, United States
b Department of Pathology, Boston Children’s Hospital and Harvard Medical School, Bader Building, MA, 300 Longwood Ave, Boston, 02115, United States
c Department of Pathology, NYU Langone Health, 550 First Avenue, NY, NY 10016, United States
d Department of Oncologic Pathology, Dana-Farber Cancer Institute, MA, 450 Brookline Avenue, Boston, 02115, United States
e Department of Neuropathology, GHU Paris Sainte-Anne Hospital, 1 Rue Cabanis, Paris, 75014, France
f Center for Advanced Molecular Diagnostics, Brigham and Women’s Hospital and Harvard Medical School, MA, 75 Francis Street, Boston, 02115, United States
g Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street 34th St, Philadelphia, 19104, United States
h Department of Neurological Surgery, Northwestern University, Chicago, United States
i Department of Pathology, Northwestern University, 303 East Chicago Avenue, Chicago, 60611, United States
j Division of Neuropathology, Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8118, St. Louis, MO, 63110, USA
k Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, Philadelphia, United States
l Foundation Medicine, 7010 Kit Creek Road, Morrisville, 27560, United States
m Wake Forest Comprehensive Cancer Center and Department of Pathology, Wake Forest School of Medicine, Winston-Salem27157, United States
n Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, MA, 450 Brookline Avenue, Boston, 02215, United States
Abstract
Fusions involving neurotrophic tyrosine receptor kinase (NTRK) genes are detected in ≤2% of gliomas and can promote gliomagenesis. The remarkable therapeutic efficacy of TRK inhibitors, which are among the first Food and Drug Administration-approved targeted therapies for NTRK-fused gliomas, has generated significant clinical interest in characterizing these tumors. In this multi-institutional retrospective study of 42 gliomas with NTRK fusions, next generation DNA sequencing (n = 41), next generation RNA sequencing (n = 1), RNA-sequencing fusion panel (n = 16), methylation profile analysis (n = 18), and histologic evaluation (n = 42) were performed. All infantile NTRK-fused gliomas (n = 7) had high-grade histology and, with one exception, no other significant genetic alterations. Pediatric NTRK-fused gliomas (n = 13) typically involved NTRK2, ranged from low- to high-histologic grade, and demonstrated histologic overlap with desmoplastic infantile ganglioglioma, pilocytic astrocytoma, ganglioglioma, and glioblastoma, among other entities, but they rarely matched with high confidence to known methylation class families or with each other; alterations involving ATRX, PTEN, and CDKN2A/2B were present in a subset of cases. Adult NTRK-fused gliomas (n = 22) typically involved NTRK1 and had predominantly high-grade histology; genetic alterations involving IDH1, ATRX, TP53, PTEN, TERT promoter, RB1, CDKN2A/2B, NF1, and polysomy 7 were common. Unsupervised principal component analysis of methylation profiles demonstrated no obvious grouping by histologic grade, NTRK gene involved, or age group. KEGG pathway analysis detected methylation differences in genes involved in PI3K/AKT, MAPK, and other pathways. In summary, the study highlights the clinical, histologic, and molecular heterogeneity of NTRK-fused gliomas, particularly when stratified by age group.
Author Keywords
Glioma; Methylation; NGS sequencing; NTRK
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Why stop at two opinions? Reply to McCrae” (2020) (2020) American Psychologist
Why stop at two opinions? Reply to McCrae (2020)
(2020) American Psychologist, 75 (5), pp. 731-732.
Bleidorn, W.a , Hill, P.L.b , Back, M.D.c , Denissen, J.J.A.d , Hennecke, M.e , Hopwood, C.J.a , Jokela, M.f , Kandler, C.g , Lucas, R.E.h , Luhmann, M.i , Orth, U.j , Wagner, J.k , Wrzus, C.l , Zimmermann, J.m , Roberts, B.n
a University of California, Davis, United States
b Washington University, St. Louis, United States
c Westfälische Wilhems-University Münster, Germany
d Utrecht University, Netherlands
e University of Siegen, Germany
f University of Helsinki, Finland
g University of Bremen, Germany
h Michigan State University, United States
i Ruhr University Bochum, Germany
j University of Bern, Switzerland
k University of Hamburg, Germany
l University of Heidelberg, Germany
m University of Kassel, Germany
n University of Illinois at Urbana-Champaign, United States
Abstract
McCrae (2020) argues that it is premature to explore interventions focused on personality change. In his commentary, he suggests that interventions should be promoted only if their effects in self-report data are confirmed by the additional opinion of informants. We agree with the essence of his position and would go further by envisioning a new framework for rigorous collaborative research on personality change (Bleidorn et al., 2020). We nevertheless maintain that policymakers would benefit from considering the additional opinion of personality scientists. © 2020 American Psychological Association.
Author Keywords
Development; Interventions; Longitudinal; Personality; Policy
Document Type: Letter
Publication Stage: Final
Source: Scopus
“Recurrent Closed Funnel Retinal Detachment Associated With Optic Nerve Coloboma” (2020) JAMA Ophthalmology
Recurrent Closed Funnel Retinal Detachment Associated With Optic Nerve Coloboma
(2020) JAMA Ophthalmology, 138 (7), p. e194102.
Li, A.S.a b
a John F. Hardesty, MD, Department of Ophthalmology and Visual Sciences, Washington University School of Medicine in St Louis, St Louis, MO, United States
b Now with Department of Ophthalmology and Visual Sciences, University of Maryland School of Medicine, Baltimore, United States
Document Type: Article
Publication Stage: Final
Source: Scopus
“Letter to the Editor Regarding ‘Treatment of Atlantoaxial Tuberculosis with Neurological Impairment: A Systematic Review'” (2020) World Neurosurgery
Letter to the Editor Regarding “Treatment of Atlantoaxial Tuberculosis with Neurological Impairment: A Systematic Review”
(2020) World Neurosurgery, 139, p. 667.
Shenoy, S.a b , Shenoy, V.S.b
a Brown School, Washington University, St. Louis, MO, United States
b Tarun Neuro Clinic, Mumbai, India
Document Type: Note
Publication Stage: Final
Source: Scopus
“Evidence for a conditioning effect of inhalational anesthetics on angiographic vasospasm after aneurysmal subarachnoid hemorrhage” (2020) Journal of Neurosurgery
Evidence for a conditioning effect of inhalational anesthetics on angiographic vasospasm after aneurysmal subarachnoid hemorrhage
(2020) Journal of Neurosurgery, 133 (1), pp. 152-158.
Athiraman, U.a , Aum, D.b , Vellimana, A.K.b , Osbun, J.W.b , Dhar, R.c , Tempelhoff, R.a , Zipfel, G.J.b
a Departments of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
b Departments of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
c Department of Neurology, Washington University, St. Louis, MO, United States
Abstract
OBJECTIVE Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) is characterized by large-artery vasospasm, distal autoregulatory dysfunction, cortical spreading depression, and microvessel thrombi. Large-artery vasospasm has been identified as an independent predictor of poor outcome in numerous studies. Recently, several animal studies have identified a strong protective role for inhalational anesthetics against secondary brain injury after SAH including DCI-a phenomenon referred to as anesthetic conditioning. The aim of the present study was to assess the potential role of inhalational anesthetics against cerebral vasospasm and DCI in patients suffering from an SAH. METHODS After IRB approval, data were collected retrospectively for all SAH patients admitted to the authors’ hospital between January 1, 2010, and December 31, 2013, who received general anesthesia with either inhalational anesthetics only (sevoflurane or desflurane) or combined inhalational (sevoflurane or desflurane) and intravenous (propofol) anesthetics during aneurysm treatment. The primary outcomes were development of angiographic vasospasm and development of DCI during hospitalization. Univariate and logistic regression analyses were performed to identify independent predictors of these endpoints. RESULTS The cohort included 157 SAH patients whose mean age was 56 ± 14 (± SD). An inhalational anesthetic-only technique was employed in 119 patients (76%), while a combination of inhalational and intravenous anesthetics was employed in 34 patients (22%). As expected, patients in the inhalational anesthetic-only group were exposed to significantly more inhalational agent than patients in the combination anesthetic group (p < 0.05). Multivariate logistic regression analysis identified inhalational anesthetic-only technique (OR 0.35, 95% CI 0.14-0.89), Hunt and Hess grade (OR 1.51, 95% CI 1.03-2.22), and diabetes (OR 0.19, 95% CI 0.06-0.55) as significant predictors of angiographic vasospasm. In contradistinction, the inhalational anesthetic-only technique had no significant impact on the incidence of DCI or functional outcome at discharge, though greater exposure to desflurane (as measured by end-tidal concentration) was associated with a lower incidence of DCI. CONCLUSIONS These data represent the first evidence in humans that inhalational anesthetics may exert a conditioning protective effect against angiographic vasospasm in SAH patients. Future studies will be needed to determine whether optimized inhalational anesthetic paradigms produce definitive protection against angiographic vasospasm; whether they protect against other events leading to secondary brain injury after SAH, including microvascular thrombi, autoregulatory dysfunction, blood-brain barrier breakdown, neuroinflammation, and neuronal cell death; and, if so, whether this protection ultimately improves patient outcome. © 2020 AANS.
Author Keywords
Aneurysmal subarachnoid hemorrhage; Angiographic vasospasm; DCI; Delayed cerebral ischemia; Inhalational anesthetics; Vascular disorders
Document Type: Article
Publication Stage: Final
Source: Scopus
“Multi-excitation magnetic resonance elastography of the brain: Wave propagation in anisotropic white matter” (2020) Journal of Biomechanical Engineering
Multi-excitation magnetic resonance elastography of the brain: Wave propagation in anisotropic white matter
(2020) Journal of Biomechanical Engineering, 142 (7), art. no. 071005-1, .
Smith, D.R.a , Guertler, C.A.b , Okamoto, R.J.b , Romano, A.J.c , Bayly, P.V.b , Johnson, C.L.a
a Department of Biomedical Engineering, University of Delaware, Newark, DE 19716, United States
b Department of Mechanical Engineering and Material Science, Washington University, St. Louis, MO 63130, United States
c Naval Research Laboratory, Code 7160, Washington, DC 20375, United States
Abstract
Magnetic resonance elastography (MRE) has emerged as a sensitive imaging technique capable of providing a quantitative understanding of neural microstructural integrity. However, a reliable method for the quantification of the anisotropic mechanical properties of human white matter is currently lacking, despite the potential to illuminate the pathophysiology behind neurological disorders and traumatic brain injury. In this study, we examine the use of multiple excitations in MRE to generate wave displacement data sufficient for anisotropic inversion in white matter. We show the presence of multiple unique waves from each excitation which we combine to solve for parameters of an incompressible, transversely isotropic (ITI) material: shear modulus, μ, shear anisotropy, φ, and tensile anisotropy, ζ. We calculate these anisotropic parameters in the corpus callosum body and find the mean values as μ = 3.78 kPa, φ = 0.151, and ζ = 0.099 (at 50 Hz vibration frequency). This study demonstrates that multi-excitation MRE provides displacement data sufficient for the evaluation of the anisotropic properties of white matter. © 2020 American Society of Mechanical Engineers (ASME). All rights reserved.
Author Keywords
Anisotropy; Brain; Magnetic resonance elastography; Stiffness; White matter
Document Type: Article
Publication Stage: Final
Source: Scopus
“Aromatic interactions with membrane modulate human BK channel activation” (2020) eLife
Aromatic interactions with membrane modulate human BK channel activation
(2020) eLife, 9, art. no. e55571, pp. 1-52.
Yazdani, M.a , Zhang, G.c , Jia, Z.a , Shi, J.c , Cui, J.c , Chen, J.a b
a Department of Chemistry, University of Massachusetts, Amherst, MA 01003, United States
b Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA 01003, United States
c Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Disorders, Cardiac Bioelectricity and Arrhythmia Center, Washington University, St Louis, MO 63130, United States
Abstract
Large-conductance potassium (BK) channels are transmembrane (TM) proteins that can be synergistically and independently activated by membrane voltage and intracellular Ca2+. The only covalent connection between the cytosolic Ca2+ sensing domain and the TM pore and voltage sensing domains is a 15-residue “C-linker”. To determine the linker’s role in human BK activation, we designed a series of linker sequence scrambling mutants to suppress potential complex interplay of specific interactions with the rest of the protein. The results revealed a surprising sensitivity of BK activation to the linker sequence. Combining atomistic simulations and further mutagenesis experiments, we demonstrated that nonspecific interactions of the linker with membrane alone could directly modulate BK activation. The C-linker thus plays more direct roles in mediating allosteric coupling between BK domains than previously assumed. Our results suggest that covalent linkers could directly modulate TM protein function and should be considered an integral component of the sensing apparatus. © 2020, eLife Sciences Publications Ltd. All rights reserved.
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Precommitment Devices: A Defensible Treatment for Opioid Addiction?” (2020) American Journal of Law & Medicine
Precommitment Devices: A Defensible Treatment for Opioid Addiction?
(2020) American Journal of Law & Medicine, 46 (2-3), pp. 189-202.
Dresser, R.
Washington University in St. Louis. I am grateful to Travis Rieder and an anonymous reviewer for helpful comments on an earlier draft
Document Type: Article
Publication Stage: Final
Source: Scopus
“Pro-Con Debate: Use of Wake-Promoting Agents for the Treatment of Daytime Fatigue in OSA Patients with Curtailed CPAP Use (Less than 6 h)” (2020) Current Sleep Medicine Reports
Pro-Con Debate: Use of Wake-Promoting Agents for the Treatment of Daytime Fatigue in OSA Patients with Curtailed CPAP Use (Less than 6 h)
(2020) Current Sleep Medicine Reports, .
Malhotra, R.K.
Sleep Medicine Section, Department of Neurology, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
Abstract
Purpose of Review: Positive airway pressure (PAP) is the most common treatment for obstructive sleep apnea (OSA) in adults and typically improves excessive daytime sleepiness and quality of sleep. Unfortunately, a certain portion of patients (6–14%) continue to have residual hypersomnia with treated OSA. Many of these patients regularly use PAP for treatment, but not for the entire night every night. This review critically evaluates the appropriate use of wake-promoting agents in patients with residual hypersomnia with less than 6 h of PAP use. Recent Findings: Trials of wake-promoting agents such as modafinil, armodafinil, and solriamfetol to treat residual daytime sleepiness in patients with OSA have demonstrated improvement in symptoms despite some of the patients not using PAP for greater than 6 h per night. Residual hypersomnia may be related to permanent damage to the central nervous system from chronic intermittent hypoxia related to sleep apnea and may not improve with PAP therapy alone. Summary: Many patients may benefit from use of wake-promoting agents to treat residual hypersomnia in OSA, including patients with curtailed PAP treatment of less than 6 h per night. © 2020, Springer Nature Switzerland AG.
Author Keywords
Armodafinil; Modafinil; Obstructive sleep apnea; Positive airway pressure; Residual hypersomnia; Solriamfetol
Document Type: Review
Publication Stage: Article in Press
Source: Scopus
“Finger tapping as a proxy for gait: Similar effects on movement variability during external and self-generated cueing in people with Parkinson’s disease and healthy older adults” (2020) Annals of Physical and Rehabilitation Medicine
Finger tapping as a proxy for gait: Similar effects on movement variability during external and self-generated cueing in people with Parkinson’s disease and healthy older adults
(2020) Annals of Physical and Rehabilitation Medicine, .
Horin, A.P.a , Harrison, E.C.b , Rawson, K.S.a , Earhart, G.M.a b c
a Program in Physical Therapy, Washington University School of Medicine, Campus Box 8502, 4444 Forest Park Ave., St. Louis, MO, 63108, United States
b Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
c Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United States
Abstract
Background: Rhythmic auditory cueing has been widely studied for gait rehabilitation in Parkinson’s disease (PD). Our research group previously showed that externally generated cues (i.e., music) increased gait variability measures from uncued gait, whereas self-generated cues (i.e., mental singing) did not. These different effects may be due to differences in underlying neural mechanisms that could be discerned via neuroimaging; however, movement types that can be studied with neuroimaging are limited. Objective: The primary aim of the present study was to investigate the effects of different cue types on gait, finger tapping, and foot tapping, to determine whether tapping can be used as a surrogate for gait in future neuroimaging studies. The secondary aim of this study was to investigate whether rhythm skills or auditory imagery abilities are associated with responses to these different cue types. Methods: In this cross-sectional study, controls (n = 24) and individuals with PD (n = 33) performed gait, finger tapping, and foot tapping at their preferred pace (UNCUED) and to externally generated (MUSIC) and self-generated (MENTAL) cues. Spatiotemporal parameters of gait and temporal parameters of finger tapping and foot tapping were collected. The Beat Alignment Task (BAT) and Bucknell Auditory Imagery Scale (BAIS) were also administered. Results: The MUSIC cues elicited higher movement variability than did MENTAL cues across all movements. The MUSIC cues also elicited higher movement variability than the UNCUED condition for gait and finger tapping. Conclusions: This study shows that different cue types affect gait and finger tapping similarly. Finger tapping may be an adequate proxy for gait in studying the underlying neural mechanisms of these cue types. © 2020 Elsevier Masson SAS
Author Keywords
Auditory cues; Gait; Parkinson’s; Rehabilitation; Tapping
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Amygdalostriatal coupling underpins positive but not negative coloring of ambiguous affect” (2020) Cognitive, Affective and Behavioral Neuroscience
Amygdalostriatal coupling underpins positive but not negative coloring of ambiguous affect
(2020) Cognitive, Affective and Behavioral Neuroscience, .
Kim, M.J.a , Mattek, A.M.b , Shin, J.c
a Department of Psychology, Sungkyunkwan University, Seoul, South Korea
b Department of Psychology, University of Oregon, Eugene, OR, United States
c Department of Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States
Abstract
Humans routinely integrate affective information from multiple sources. For example, we rarely interpret an emotional facial expression devoid of context. In this paper, we describe the neural correlates of an affective computation that involves integrating multiple sources, by leveraging the ambiguity and subtle feature-based valence signals found in surprised faces. Using functional magnetic resonance imaging, participants reported the valence of surprised faces modulated by positive or negative sentences. Amygdala activity corresponded to the valence value assigned to each contextually modulated face, with greater activity reflecting more negative ratings. Amygdala activity did not track the valence of the faces or sentences per se. Moreover, the amygdala was functionally coupled with the nucleus accumbens only during face trials preceded by positive contextual cues. These data suggest 1) valence-related amygdala activity reflects the integrated valence values rather than the valence values of each individual component, and 2) amygdalostriatal coupling underpins positive but not negative coloring of ambiguous affect. © 2020, The Psychonomic Society, Inc.
Author Keywords
Ambiguity; Amygdala; Context; Emotion; Feature; Valence
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Franz Joseph Gall on the “deaf and dumb” and the complexities of mind” (2020) Journal of the History of the Neurosciences
Franz Joseph Gall on the “deaf and dumb” and the complexities of mind
(2020) Journal of the History of the Neurosciences, pp. 1-13.
Eling, P.a , Finger, S.b
a Department of Psychology, Radboud University, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands
b Department of Psychological and Brain Sciences, and Program in History of Medicine, Washington University, St. Louis, MO, United States
Abstract
Franz Joseph Gall used a broad variety of phenomena in support of his organology. Well known are his observations on anatomical features of the brain, species-specific behavioral patterns, the observation that some individuals may excel in one faculty while being mediocre in others, changes in the organs with development and aging, and how the organs associated with the faculties might be affected by diseases and acute brain lesions. We here present a widely overlooked source: his observations on individuals then classified as “deaf and dumb.” We discuss how these observations were presented by Gall in support of his organology and in his disputes with empiricists and sensationalists about the nature of mind. © 2020, © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.
Author Keywords
empiricism; feral children; Franz Joseph Gall; language learning; organology; phrenology; sensualism; “deaf and dumb”
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Positive information facilitates response inhibition in older adults only when emotion is task-relevant” (2020) Cognition and Emotion
Positive information facilitates response inhibition in older adults only when emotion is task-relevant
(2020) Cognition and Emotion, pp. 1-14.
Williams, S.E.a , Lenze, E.J.b , Waring, J.D.a
a Department of Psychology, Saint Louis University, St. Louis, MO, United States
b Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
Abstract
Emotional information is integral to everyday life and impacts a variety of cognitive abilities including response inhibition, a critical skill for maintaining appropriate and flexible behaviour. However, reported effects of emotion on response inhibition are inconsistent in younger adults, and very limited in older adults. Effects of aging are especially relevant because emotion regulation improves with aging despite declining inhibitory control over neutral information. Across three studies, we assessed the impact of emotional facial expressions on response inhibition in younger and older adults while manipulating attention to task stimuli. Emotional faces (versus neutral faces) altered response inhibition only when task instructions required explicit attention to emotional attributes of the faces. When directly comparing fear faces to happy faces, both age groups had better response inhibition to happy faces. Age further influenced differences across conditions, in that happy faces enhanced response inhibition relative to neutral faces in older adults but not younger adults. Thus, emotional response inhibition for task-relevant (but not task-irrelevant) positive information is enhanced in late life compared to early adulthood. The present work extends the nascent literature on emotional response inhibition in aging, and proffers a framework to reconcile the mixed literature on this topic in younger adults. © 2020, © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
Author Keywords
aging; Emotion; executive function; response inhibition; stop-signal task
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“The Effects of Intraoperative Electrical Stimulation on Regeneration and Recovery After Nerve Isograft Repair in a Rat Model” (2020) Hand
The Effects of Intraoperative Electrical Stimulation on Regeneration and Recovery After Nerve Isograft Repair in a Rat Model
(2020) Hand, .
Keane, G.C.a , Pan, D.a , Roh, J.a , Larson, E.L.a , Schellhardt, L.a , Hunter, D.A.a , Snyder-Warwick, A.K.a , Moore, A.M.b , Mackinnon, S.E.a , Wood, M.D.a
a Washington University in St. LouisMO, United States
b The Ohio State University, Columbus, United States
Abstract
Background: Therapeutic electrical stimulation (ES) applied to repaired nerve is a promising treatment option to improve regeneration. However, few studies address the impact of ES following nerve graft reconstruction. The purpose of this study was to determine if ES applied to a nerve repair using nerve isograft in a rodent model could improve nerve regeneration and functional recovery. Methods: Adult rats were randomized to 2 groups: “ES” and “Control.” Rats received a tibial nerve transection that was repaired using a tibial nerve isograft (1.0 cm length), where ES was applied immediately after repair in the applicable group. Nerve was harvested 2 weeks postrepair for immunohistochemical analysis of axon growth and macrophage accumulation. Independently, rats were assessed using walking track and grid-walk analysis for up to 21 weeks. Results: At 2 weeks, more robust axon regeneration and greater macrophage accumulation was observed within the isografts for the ES compared to Control groups. Both walking track and grid-walk analysis revealed that return of functional recovery was accelerated by ES. The ES group demonstrated improved functional recovery over time, as well as improved recovery compared to the Control group at 21 weeks. Conclusions: ES improved early axon regeneration into a nerve isograft and was associated with increased macrophage and beneficial M2 macrophage accumulation within the isograft. ES ultimately improved functional recovery compared to isograft repair alone. This study supports the clinical potential of ES to improve the management of nerve injuries requiring a nerve graft repair. © The Author(s) 2020.
Author Keywords
autograft; basic science; diagnosis; microsurgery; muscle; nerve; nerve regeneration; specialty
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“COVID-19 in people with multiple sclerosis: A global data sharing initiative” (2020) Multiple Sclerosis Journal
COVID-19 in people with multiple sclerosis: A global data sharing initiative
(2020) Multiple Sclerosis Journal, .
Peeters, L.M.a , Parciak, T.b , Walton, C.c , Geys, L.a , Moreau, Y.d , De Brouwer, E.d , Raimondi, D.d , Pirmani, A.e , Kalincik, T.f aq , Edan, G.g , Simpson-Yap, S.h ao , De Raedt, L.i , Dauxais, Y.i , Gautrais, C.i , Rodrigues, P.R.j , McKenna, L.j , Lazovski, N.j , Hillert, J.k , Forsberg, L.k , Spelman, T.k , McBurney, R.l , Schmidt, H.l , Bergmann, A.m , Braune, S.m , Stahmann, A.n , Middleton, R.o , Salter, A.p am , Bebo, B.F.q , Rojas, J.I.r ap , van der Walt, A.s , Butzkueven, H.s , van der Mei, I.t , Ivanov, R.u , Hellwig, K.v , Sciascia do Olival, G.w , Cohen, J.A.x , Van Hecke, W.y , Dobson, R.z , Magyari, M.aa , Brum, D.G.ab , Alonso, R.ac al , Nicholas, R.ad aj ak , Bauer, J.ae , Chertcoff, A.af , de Sèze, J.ag an , Louapre, C.ah ar , Comi, G.ai , Rijke, N.c
a Biomedical Research Institute and Data Science Institute, Hasselt University, Diepenbeek, Belgium
b Department of Medical Informatics, University Medical Center Göttingen, Göttingen, Germany
c MS International Federation, London, United Kingdom
d ESAT-STADIUS, KU Leuven, Leuven, Belgium
e Biomedical Research Institute and Data Science Institute, Hasselt University, Diepenbeek, Belgium/ESAT-STADIUS, KU Leuven, Leuven, Belgium
f Clinical Outcomes Research (CORe) Unit, The University of Melbourne, Melbourne, VIC, Australia
g Department of Neurology, CHU Pontchaillou, Rennes, France
h Neuroepidemiology Unit, Melbourne School of Population Global Health, The University of Melbourne, Melbourne, VIC, Australia
i Department of Computer Science and Leuven.AI, KU Leuven, Leuven, Belgium
j QMENTA, Barcelona, Spain
k Department of Clinical Neuroscience, Swedish MS Registry, Stockholm, Sweden
l iConquerMS People-Powered Research Network, Accelerated Cure Project for MS, Waltham, MA, United States
m NeuroTransData Study Group, NeuroTransData, Neuburg, Germany
n MS Forschungs- und Projektentwicklungs-gGmbH, Hannover, Germany
o UK MS Register, Swansea, United Kingdom
p COViMS, St Louis, United States
q COViMS, USA/National Multiple Sclerosis Society, Portland, OR, United States
r Neurology Department, Hospital Universitario de CEMIC, Buenos Aires, Argentina
s MSBase Registry, Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia
t The Australian MS Longitudinal Study (AMSLS), Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia
u Bulgarian SmartMS COVID-19 Dataset, Sofia, Bulgaria
v LEOSS, Department of Neurology, Katholisches Klinikum Bochum, Bochum, Germany
w Brazilian Multiple Sclerosis Association (ABEM), São Paulo, Brazil
x Cleveland Clinic MS COVID-19 Registry, Mellen MS Center, Cleveland Clinic, Cleveland, OH, United States
y Icometrix – Icompanion, Leuven, Belgium
z OptimiseMS, Preventive Neurology Unit, Queen Mary University of, London, London, United Kingdom
aa The Danish Multiple Sclerosis Registry, Department of Neurology, University Hospital Rigshospitalet, Glostrup, Denmark
ab Universidade Estadual Paulista (Unesp), Faculdade de Medicina, Botucatu/REDONE – Brazilian Registry of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders, São Paulo, Brazil
ac RELACOEM, Buenos Aires, Argentina
ad UK MS Register, Swansea, United Kingdom
ae Mental Health Area, EMA, Buenos Aires, Argentina
af MS and Demyelinating Diseases, Hospital Británico de Buenos Aires – EMA, Buenos Aires, Argentina
ag Department of Neurology, Strasbourg University Hospital, Strasbourg, France
ah COVISEP, France
ai Institute of Experimental Neurology, Ospedale San Raffaele, Milan, Italy
aj Imperial College London, London, United Kingdom
ak Swansea University, Swansea, United Kingdom
al Multiple Sclerosis University Center, Ramos Mejia Hospital – EMA, Buenos Aires, Argentina
am Division of Biostatistics, Washington University in St. Louis, St. Louis, MO, United States
an COVISEP, France
ao Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia
ap RELACOEM, Buenos Aires, Argentina
aq Melbourne MS Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia
ar Institut du Cerveau ICM, APHP – Hôpital Pitié Salpêtrière, Sorbonne University, Paris, France
Abstract
Background: We need high-quality data to assess the determinants for COVID-19 severity in people with MS (PwMS). Several studies have recently emerged but there is great benefit in aligning data collection efforts at a global scale. Objectives: Our mission is to scale-up COVID-19 data collection efforts and provide the MS community with data-driven insights as soon as possible. Methods: Numerous stakeholders were brought together. Small dedicated interdisciplinary task forces were created to speed-up the formulation of the study design and work plan. First step was to agree upon a COVID-19 MS core data set. Second, we worked on providing a user-friendly and rapid pipeline to share COVID-19 data at a global scale. Results: The COVID-19 MS core data set was agreed within 48 hours. To date, 23 data collection partners are involved and the first data imports have been performed successfully. Data processing and analysis is an on-going process. Conclusions: We reached a consensus on a core data set and established data sharing processes with multiple partners to address an urgent need for information to guide clinical practice. First results show that partners are motivated to share data to attain the ultimate joint goal: better understand the effect of COVID-19 in PwMS. © The Author(s), 2020.
Author Keywords
coronavirus 2; COVID-19; data collection; humans; Multiple sclerosis; pandemics; registries
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access
“Experiences of American Older Adults with Pre-existing Depression During the Beginnings of the COVID-19 Pandemic: A Multicity, Mixed-Methods Study” (2020) American Journal of Geriatric Psychiatry
Experiences of American Older Adults with Pre-existing Depression During the Beginnings of the COVID-19 Pandemic: A Multicity, Mixed-Methods Study
(2020) American Journal of Geriatric Psychiatry, .
Hamm, M.E.a , Brown, P.J.b , Karp, J.F.c , Lenard, E.d , Cameron, F.a , Dawdani, A.a , Lavretsky, H.e , Miller, J.P.f , Mulsant, B.H.g , Pham, V.T.d , Reynolds, C.F.h , Roose, S.P.b , Lenze, E.J.d
a University of Pittsburgh, Department of General Internal Medicine, Pittsburgh, PA, United States
b Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York, NY, United States
c University of Pittsburgh, Department of Psychiatry, Pittsburgh, PA, United States
d Washington University in St. Louis, School of Medicine, St. Louis, MO, United States
e University of California, Los Angeles, Department of Psychiatry and Biobehavioral Sciences, Los Angeles, CA, United States
f Washington University in St. Louis, Division of Biostatistics, St. Louis, MO, United States
g University of Toronto, Department of Psychiatry, Toronto, ON, Canada
h University of Pittsburgh, School of Medicine, Pittsburgh, PA, United States
Abstract
Objective: To determine the effect of the COVID-19 pandemic on the mental health of older adults with pre-existing major depressive disorder (MDD). Participants: Participants were 73 community-living older adults with pre-existing MDD (mean age 69 [SD 6]) in Los Angeles, New York, Pittsburgh, and St Louis. Design and Measurements: During the first 2 months of the pandemic, the authors interviewed participants with a semistructured qualitative interview evaluating access to care, mental health, quality of life, and coping. The authors also assessed depression, anxiety, and suicidality with validated scales and compared scores before and during the pandemic. Results: Five themes from the interviews highlight the experience of older adults with MDD: 1) They are more concerned about the risk of contracting the virus than the risks of isolation. 2) They exhibit resilience to the stress and isolation of physical distancing. 3) Most are not isolated socially, with virtual contact with friends and family. 4) Their quality of life is lower, and they worry their mental health will suffer with continued physical distancing. 5) They are outraged by an inadequate governmental response to the pandemic. Depression, anxiety, and suicidal ideation symptom scores did not differ from scores before the pandemic. Conclusion: Most older adults with pre-existing MDD show resilience in the first 2 months of the COVID-19 pandemic but have concerns about the future. Policies and interventions to provide access to medical services and opportunities for social interaction are needed to help to maintain mental health and quality of life as the pandemic continues. © 2020 American Association for Geriatric Psychiatry
Author Keywords
anxiety; Covid-19 Pandemic; depression; resilience
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access
“MicroRNA Profiling as a Methodology to Diagnose Ménière’s Disease: Potential Application of Machine Learning” (2020) Otolaryngology – Head and Neck Surgery (United States)
MicroRNA Profiling as a Methodology to Diagnose Ménière’s Disease: Potential Application of Machine Learning
(2020) Otolaryngology – Head and Neck Surgery (United States), .
Shew, M.a , Wichova, H.b , Bur, A.b , Koestler, D.C.c , St Peter, M.d , Warnecke, A.e , Staecker, H.b
a Department of Otolaryngology–Head and Neck Surgery, Washington University School of Medicine in St Louis, St Louis, MO, United States
b Department of Otolaryngology–Head and Neck Surgery, School of Medicine, University of Kansas, Kansas City, KS, United States
c Department of Biostatistics, School of Medicine, University of Kansas, Kansas City, KS, United States
d School of Medicine, University of Kansas, Kansas City, KS, United States
e Department of Otorhinolaryngology, Hannover Medical School, Hannover, Germany
Abstract
Objective: Diagnosis and treatment of Ménière’s disease remains a significant challenge because of our inability to understand what is occurring on a molecular level. MicroRNA (miRNA) perilymph profiling is a safe methodology and may serve as a “liquid biopsy” equivalent. We used machine learning (ML) to evaluate miRNA expression profiles of various inner ear pathologies to predict diagnosis of Ménière’s disease. Study Design: Prospective cohort study. Setting: Tertiary academic hospital. Subjects and Methods: Perilymph was collected during labyrinthectomy (Ménière’s disease, n = 5), stapedotomy (otosclerosis, n = 5), and cochlear implantation (sensorineural hearing loss [SNHL], n = 9). miRNA was isolated and analyzed with the Affymetrix miRNA 4.0 array. Various ML classification models were evaluated with an 80/20 train/test split and cross-validation. Permutation feature importance was performed to understand miRNAs that were critical to the classification models. Results: In terms of miRNA profiles for conductive hearing loss versus Ménière’s, 4 models were able to differentiate and identify the 2 disease classes with 100% accuracy. The top-performing models used the same miRNAs in their decision classification model but with different weighted values. All candidate models for SNHL versus Ménière’s performed significantly worse, with the best models achieving 66% accuracy. Ménière’s models showed unique features distinct from SNHL. Conclusions: We can use ML to build Ménière’s-specific prediction models using miRNA profile alone. However, ML models were less accurate in predicting SNHL from Ménière’s, likely from overlap of miRNA biomarkers. The power of this technique is that it identifies biomarkers without knowledge of the pathophysiology, potentially leading to identification of novel biomarkers and diagnostic tests. © American Academy of Otolaryngology–Head and Neck Surgery Foundation 2020.
Author Keywords
machine learning; miRNA; Ménière’s disease; perilymph sample
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Blurring past and present: Using false memory to better understand false hearing in young and older adults” (2020) Memory and Cognition
Blurring past and present: Using false memory to better understand false hearing in young and older adults
(2020) Memory and Cognition, .
Failes, E., Sommers, M.S., Jacoby, L.L.
Department of Psychological and Brain Sciences, Washington University in St. Louis, 1 Brookings Dr., Campus Box 1125, St. Louis, MO 63130, United States
Abstract
A number of recent studies have shown that older adults are more susceptible to context-based misperceptions in hearing (Rogers, Jacoby, & Sommers, Psychology and Aging, 27, 33–45, 2012; Sommers, Morton, & Rogers, Remembering: Attributions, Processes, and Control in Human Memory [Essays in Honor of Larry Jacoby], pp. 269–284, 2015) than are young adults. One explanation for these age-related increases in what we term false hearing is that older adults are less able than young individuals to inhibit a prepotent response favored by context. A similar explanation has been proposed for demonstrations of age-related increases in false memory (Jacoby, Bishara, Hessels, & Toth, Journal of Experimental Psychology: General, 134, 131–148, 2005). The present study was designed to compare susceptibility to false hearing and false memory in a group of young and older adults. In Experiment 1, we replicated the findings of past studies demonstrating increased frequency of false hearing in older, relative to young, adults. In Experiment 2, we demonstrated older adults’ increased susceptibility to false memory in the same sample. Importantly, we found that participants who were more prone to false hearing also tended to be more prone to false memory, supporting the idea that the two phenomena share a common mechanism. The results are discussed within the framework of a capture model, which differentiates between context-based responding resulting from failures of cognitive control and context-based guessing. © 2020, The Psychonomic Society, Inc.
Author Keywords
Aging; Context effects; False hearing; False memory; Speech perception
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Altered structural connectivity and cytokine levels in Schizophrenia and Genetic high-risk individuals: Associations with disease states and vulnerability” (2020) Schizophrenia Research
Altered structural connectivity and cytokine levels in Schizophrenia and Genetic high-risk individuals: Associations with disease states and vulnerability
(2020) Schizophrenia Research, .
Wang, Y.a b , Wei, Y.a b , Edmiston, E.K.c , Womer, F.Y.d , Zhang, X.e , Duan, J.a b , Zhu, Y.a b , Zhang, R.a b , Yin, Z.a b , Zhang, Y.a b , Jiang, X.b f , Wei, S.b f , Liu, Z.g , Zhang, Y.h , Tang, Y.a b , Wang, F.a b f i
a Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
b Brain Function Research Section, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
c Department of Psychiatry, University of Pittsburgh Medical Center, United States
d Department of Psychiatry, Washington University School of Medicine, St. Louis, United States
e School of Computer Science and Engineering, Northeastern University, Shenyang, Liaoning, China
f Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
g School of Public Health, China Medical University, Shenyang, Liaoning, China
h Department of Psychiatry, College of Medicine, University of Saskatchewan, Canada
i Department of Psychiatry, Yale School of Medicine, New Haven, CT, United States
Abstract
Background: Alterations of white matter (WM) integrity have been observed in both schizophrenia (SZ) and individuals at genetic high risk for SZ (GHR-SZ); however, the molecular mechanisms underlying WM disruption remain unclear. Cytokines are chemical messengers of the immune system that are closely related to inflammation and neurogenesis in the brain. This study aimed to identify abnormalities in WM integrity, cytokine levels, and their association in SZ and GHR-SZ. Methods: A total of 355 participants (126 with SZ, 99 GHR-SZ, and 130 healthy controls [HCs]) were recruited. All participants underwent diffusion tensor imaging and blood samples were obtained from 113 participants within 24 h of imaging. Results: In SZ, there was decreased fractional anisotropy(FA) in the genu and body of the corpus callosum (GCC/BCC), anterior corona radiata, anterior and posterior limbs of the internal capsule (ALIC/PLIC), superior fronto-occipital fasciculus, external capsule, and fornix, and elevated IL-6 levels. In both SZ and GHR-SZ, decreased FA in the splenium of the corpus callosum (SCC), posterior corona radiate (PCR), and posterior thalamic radiation (PTR) was observed, and elevated leptin levels were present. Additionally, the IL-6 levels were negatively correlated with FA in the GCC and ALIC in SZ, and leptin levels were negatively correlated with the SCC, PCR, and PTR in SZ and GHR-SZ. Conclusions: Abnormal WM integrity in SZ may reflect the state of disease and is associated with increased IL-6 levels. In addition, these leptin-associated WM integrity abnormalities in both SZ and GHR-SZ may reflect a genetic vulnerability to SZ. © 2020 Elsevier B.V.
Author Keywords
Cytokine; Diffusion tensor imaging; Genetic high-risk individuals; Schizophrenia
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Using a developmental perspective to examine the moderating effects of marriage on heavy episodic drinking in a young adult sample enriched for risk” (2020) Development and Psychopathology
Using a developmental perspective to examine the moderating effects of marriage on heavy episodic drinking in a young adult sample enriched for risk
(2020) Development and Psychopathology, .
Cho, S.B.a b , Smith, R.L.b , Bucholz, K.c , Chan, G.d , Edenberg, H.J.e , Hesselbrock, V.d , Kramer, J.f , Mccutcheon, V.V.c , Nurnberger, J.g , Schuckit, M.h , Zang, Y.i , Dick, D.M.b j , Salvatore, J.E.b k
a Department of Psychology, Pusan National University, Busan, South Korea
b Department of Psychology, Virginia Commonwealth University, Box 842018, Richmond, VA 23284-2018, United States
c Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, United States
d Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, United States
e Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, United States
f Department of Psychiatry, University of Iowa, Iowa City, IA, United States
g Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, United States
h Department of Psychiatry, University of California-San Diego, San Diego, CA, United States
i Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN, United States
j Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, United States
k Virginia Institute for Psychiatric and Behavioral Genetics, Richmond, VA, United States
Abstract
Many studies demonstrate that marriage protects against risky alcohol use and moderates genetic influences on alcohol outcomes; however, previous work has not considered these effects from a developmental perspective or in high-risk individuals. These represent important gaps, as it cannot be assumed that marriage has uniform effects across development or in high-risk samples. We took a longitudinal developmental approach to examine whether marital status was associated with heavy episodic drinking (HED), and whether marital status moderated polygenic influences on HED. Our sample included 937 individuals (53.25% female) from the Collaborative Study on the Genetics of Alcoholism who reported their HED and marital status biennially between the ages of 21 and 25. Polygenic risk scores (PRS) were derived from a genome-wide association study of alcohol consumption. Marital status was not associated with HED; however, we observed pathogenic gene-by-environment effects that changed across young adulthood. Among those who married young (age 21), individuals with higher PRS reported more HED; however, these effects decayed over time. The same pattern was found in supplementary analyses using parental history of alcohol use disorder as the index of genetic liability. Our findings indicate that early marriage may exacerbate risk for those with higher polygenic load. © 2020 Cambridge University Press.
Author Keywords
Alcohol; development; genetics; marital status; young adults
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Validation of a Parent Proxy Quality-of-Life Measure for Young Children With Hearing Loss” (2020) Laryngoscope
Validation of a Parent Proxy Quality-of-Life Measure for Young Children With Hearing Loss
(2020) Laryngoscope, .
Yu, C.Y.a , Jeffe, D.B.b , Kenna, M.A.c , Germiller, J.A.d , Lieu, J.E.C.e
a Washington University School of Medicine, St. Louis, MO, United States
b Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
c Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
d Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA, United States
e Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, United States
Abstract
Objectives: No hearing-related quality of life (QL) questionnaire currently exists for children < 7 years. This study aimed to develop and evaluate the construct validity and reliability of a new parent-proxy Preschool Hearing Environments and Reflection on Quality of Life (HEAR-QL) questionnaire. Methods: Parents of children 2 to 6 years old with any hearing loss (HL) were recruited from multiple sites. To evaluate the new measure’s construct validity, participants completed a 70-item preschool HEAR-QL and validated questionnaires measuring hearing and communication functioning (Parents’ Evaluation of Aural/Oral Performance of Children), generic pediatric QL (Pediatric Quality of Life Inventory Parent Report, PedsQL), family functioning (PedsQL Family Impact Module), and parent well-being (Patient Reported Outcomes Measurement Information System Adult Global Report). Participants completed the preschool HEAR-QL 2 weeks later to measure test–retest reliability. Exploratory principal components analysis was used to reduce the number of items and determine the underlying HEAR-QL factor structure. Analysis of variance examined HEAR-QL differences by HL. Results: Among 205 parents, 144 had children with bilateral HL, 50 had children with unilateral HL, 10 had children with normal hearing (NH), and one child’s hearing status was unspecified. The 70-item questionnaire was reduced to 23 items with five underlying factors: Behavior and Attention, Hearing Environments, New Social Situations, Social Interactions, and Communication. Cronbach’s alpha for each factor ranged from 0.80 to 0.91. Test–retest reliability was 0.93. Moderate-to-strong correlations (r >.300) were observed between each Preschool HEAR-QL factor and previously validated measures. Hearing Environments scores differed significantly between children with NH and any HL. Conclusion: Preschool HEAR-QL correlations with other measures supported its construct validity. Discriminant validity testing requires a larger sample of children with NH. Level of Evidence: NA Laryngoscope, 2020. © 2020 The American Laryngological, Rhinological and Otological Society, Inc.
Author Keywords
child; hearing loss; preschool; proxy; Quality of life; questionnaire; survey; validation study
Document Type: Article
Publication Stage: Article in Press
Source: Scopus