"Oral and maxillofacial surgeons’ assessment of the role of Pernkopf's atlas in surgical practice" (2021) Annals of Anatomy
Oral and maxillofacial surgeons’ assessment of the role of Pernkopf’s atlas in surgical practice
(2021) Annals of Anatomy, 234, art. no. 151614, .
Yee, A.a , Li, J.b , Lilly, J.b , Hildebrandt, S.c , Seidelman, W.E.d , Brown, D.e , Kopar, P.e , Coert, J.H.f , Mackinnon, S.E.a , Israel, H.A.b
a Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States
b Oral and Maxillofacial Surgery, Touro College of Dental Medicine, New York Medical College, Hawthorne, NY, United States
c Division of General Pediatrics, Department of Pediatrics, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
d Department of Family and Community Medicine, University of Toronto, Toronto, Canada
e Center for Humanism and Ethics in Surgical Specialties, Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States
f Department of Plastic-, Reconstructive- and Hand Surgery, Utrecht University Medical Center, Utrecht, Netherlands
Abstract
Background: The use of the Pernkopf atlas of human anatomy in surgery presents ethical challenges due to the author’s association with the Nazi regime and the potential depiction of victims of this regime. The atlas was of particular utility to two surgical specialties: nerve surgeons and oral and maxillofacial surgeons. The representation of peripheral nerves and complex head and neck anatomy is probably unequaled in any other atlas of anatomy. While the ethical implications of the use of Pernkopf’s atlas among nerve surgeons have been previously assessed, this study focuses on the volume dedicated to detailed images of head and neck dissections, and the ethical implications of using this atlas by oral and maxillofacial surgeons. Objective: To (1) assess the role of the Pernkopf atlas in oral and maxillofacial surgeons’ current practice and (2) determine whether a proposal of four conditions would provide ethical guidance for use in surgery and education. Methods: Members of three American oral and maxillofacial surgical societies (ACOMS, ASTMJS, AAOMS) were surveyed and 181 responses collected. The survey introduced the historical origin of the Pernkopf atlas, and respondents were asked whether they would use the atlas under specific conditions that could be a recommendation for its ethical handling. An anatomical plate comparison between Netter’s and Pernkopf’s atlases was performed to compare accuracy and surgical utility. Results: Forty-nine percent of respondents were aware of the Pernkopf atlas, and 9% of respondents were currently using it. Amongst those aware of the historical facts, 42% were comfortable using the atlas, 33% uncomfortable, and 25% undecided. The four conditions involving disclosure, bioethical and religious considerations, and remembrance led to 75% of those “uncomfortable” and “undecided” becoming “comfortable” with use. Conclusions: Amid recent developments and controversy regarding the Pernkopf atlas, a proposal detailing conditions for an ethical approach may provide guidance in surgical planning and education. Furthermore, this approach has implications for the future preparation and publication of anatomical atlases and their use. © 2020 Elsevier GmbH
Author Keywords
Anatomy; Medical ethics; Oral and maxillofacial surgery; Pernkopf atlas
Document Type: Article
Publication Stage: Final
Source: Scopus
"Multi-modal biomarkers of low back pain: A machine learning approach" (2021) NeuroImage: Clinical
Multi-modal biomarkers of low back pain: A machine learning approach
(2021) NeuroImage: Clinical, 29, art. no. 102530, .
Lamichhane, B.a , Jayasekera, D.b , Jakes, R.b , Glasser, M.F.c d , Zhang, J.a , Yang, C.d , Grimes, D.a , Frank, T.L.a , Ray, W.Z.a b , Leuthardt, E.C.a b d , Hawasli, A.H.a e
a Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO 63110, United States
b Department of Biomedical Engineering, Washington University in St. Louis McKelvey School of Engineering, St. Louis, MO 63130, United States
c Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, United States
d Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, United States
e Meritas Health Neurosurgery, North Kansas City, 64116, United States
Abstract
Chronic low back pain (LBP) is a very common health problem worldwide and a major cause of disability. Yet, the lack of quantifiable metrics on which to base clinical decisions leads to imprecise treatments, unnecessary surgery and reduced patient outcomes. Although, the focus of LBP has largely focused on the spine, the literature demonstrates a robust reorganization of the human brain in the setting of LBP. Brain neuroimaging holds promise for the discovery of biomarkers that will improve the treatment of chronic LBP. In this study, we report on morphological changes in cerebral cortical thickness (CT) and resting-state functional connectivity (rsFC) measures as potential brain biomarkers for LBP. Structural MRI scans, resting state functional MRI scans and self-reported clinical scores were collected from 24 LBP patients and 27 age-matched healthy controls (HC). The results suggest widespread differences in CT in LBP patients relative to HC. These differences in CT are correlated with self-reported clinical summary scores, the Physical Component Summary and Mental Component Summary scores. The primary visual, secondary visual and default mode networks showed significant age-corrected increases in connectivity with multiple networks in LBP patients. Cortical regions classified as hubs based on their eigenvector centrality (EC) showed differences in their topology within motor and visual processing regions. Finally, a support vector machine trained using CT to classify LBP subjects from HC achieved an average classification accuracy of 74.51%, AUC = 0.787 (95% CI: 0.66–0.91). The findings from this study suggest widespread changes in CT and rsFC in patients with LBP while a machine learning algorithm trained using CT can predict patient group. Taken together, these findings suggest that CT and rsFC may act as potential biomarkers for LBP to guide therapy. © 2020 The Authors
Author Keywords
Cortical thickness; Emotion processing; Low back pain; Pain processing; Resting state connectivity; Support vector machine
Funding details
Cervical Spine Research SocietyCSRS
Neurosurgery Research and Education FoundationNREF
Foundation for Barnes-Jewish Hospital
Document Type: Article
Publication Stage: Final
Source: Scopus
"Amygdala Functional Connectivity Is Associated With Emotion Regulation and Amygdala Reactivity in 4- to 6-Year-Olds" (2021) Journal of the American Academy of Child and Adolescent Psychiatry
Amygdala Functional Connectivity Is Associated With Emotion Regulation and Amygdala Reactivity in 4- to 6-Year-Olds
(2021) Journal of the American Academy of Child and Adolescent Psychiatry, 60 (1), pp. 176-185. Cited 2 times.
Gaffrey, M.S.a , Barch, D.M.b , Luby, J.L.b , Petersen, S.E.b
a Duke University, Durham, NC, United States
b Washington University in St. LouisMO, United States
Abstract
Objective: Emotion dysregulation has been suggested to be a potent risk factor for multiple psychiatric conditions. Altered amygdala−prefrontal cortex (PFC) connectivity has been consistently linked to emotion dysregulation. Recent data indicate that amygdala−PFC functional connectivity undergoes a prolonged period of development, with amygdala reactivity during early childhood potentially shaping this unfolding process. Little is known about the relationships between amygdala−PFC functional connectivity, amygdala reactivity, and emotion regulation during early childhood. This information is likely critical for understanding early emotion dysregulation as a transdiagnostic risk factor for psychopathology. The current study examined the relationships between amygdala functional connectivity, amygdala reactivity, and emotion regulation in preschoolers. Method: A total of 66 medication-naive 4- to 6-year-olds participated in a study where resting-state functional magnetic resonance imaging (rs-fMRI) and parent-reported child emotion regulation ability data were collected. fMRI data collected during a face viewing task was also available for 24 children. Results: Right amygdala−medial PFC (mPFC) functional connectivity was positively associated with child emotion regulation ability and negatively associated with child negative affect and right amygdala reactivity to facial expressions of emotion. Right amygdala−mPFC functional connectivity also statistically mediated the relationship between heightened right amygdala reactivity and elevated child negative affect. Conclusion: Study findings suggest that amygdala−mPFC functional connectivity during early childhood, and its relationships with amygdala reactivity and emotion regulation during this highly sensitive developmental period, may play an important role in early emotional development. These results inform the neurodevelopmental biology of emotion regulation and its potential relationship with risk for psychopathology. © 2020 American Academy of Child and Adolescent Psychiatry
Author Keywords
amygdala; emotion regulation; functional connectivity; irritability; pediatric
Funding details
Klingenstein Third Generation FoundationKTGF
National Institute of Mental HealthNIMHK23 MH098176, R01 MH110488
Document Type: Article
Publication Stage: Final
Source: Scopus
"Optogenetic Methods for the Study of Circadian Rhythms" (2021) Methods in Molecular Biology (Clifton, N.J.)
Optogenetic Methods for the Study of Circadian Rhythms
(2021) Methods in Molecular Biology (Clifton, N.J.), 2130, pp. 325-336.
Jones, J.R.a b , Tackenberg, M.C.a , McMahon, D.G.a c
a Vanderbilt Brain Institute, Vanderbilt University, TN, Nashville, United States
b Department of Biology, Washington University, St. Louis, MO, USA
c Department of Biological Sciences, Vanderbilt University, TN, Nashville, United States
Abstract
A fundamental feature of circadian clock neurons across species is that they express circadian rhythms in spontaneous spike frequency. Spike frequency rhythms serve as both output timing signals of clock neurons as well as resonant elements of rhythms generation. Importantly, optogenetics, as applied to clock neurons, can enable investigation of the roles of clock neuron electrical activity in circadian timing. Here we describe protocols for using both in vitro and in vivo optogenetics directed to mammalian clock neurons in the suprachiasmatic nucleus to study circadian physiology and behavior. Optogenetic stimulation via channelrhodopsin, or inhibition via halorhodopsin, allows for the precise manipulation of neuronal firing rates across the SCN, and within specific neuronal subpopulations thereof, and can be combined with actigraphy and gene expression analysis.
Author Keywords
Behavior; Bioluminescence; Channelrhodopsin; Circadian; Firing rate; In vivo; Optogenetics
Document Type: Article
Publication Stage: Final
Source: Scopus
"Macrophage-Derived Vascular Endothelial Growth Factor-A Is Integral to Neuromuscular Junction Reinnervation after Nerve Injury" (2020) The Journal of Neuroscience: The Official Journal of the Society for Neuroscience
Macrophage-Derived Vascular Endothelial Growth Factor-A Is Integral to Neuromuscular Junction Reinnervation after Nerve Injury
(2020) The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 40 (50), pp. 9602-9616.
Lu, C.-Y.a b , Santosa, K.B.a c , Jablonka-Shariff, A.a , Vannucci, B.a , Fuchs, A.d , Turnbull, I.d , Pan, D.a , Wood, M.D.a , Snyder-Warwick, A.K.e
a Division of Plastic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110-1093, United States
b Division of Reconstructive Microsurgery, Department of Plastic Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan City, Taiwan
c Section of Plastic and Reconstructive Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan 48109-4217, United States
d Division of General Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110-1093, United States
e Division of Plastic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110-1093, United States
Abstract
Functional recovery in the end target muscle is a determinant of outcome after peripheral nerve injury. The neuromuscular junction (NMJ) provides the interface between nerve and muscle and includes non-myelinating terminal Schwann cells (tSCs). After nerve injury, tSCs extend cytoplasmic processes between NMJs to guide axon growth and NMJ reinnervation. The mechanisms related to NMJ reinnervation are not known. We used multiple mouse models to investigate the mechanisms of NMJ reinnervation in both sexes, specifically whether macrophage-derived vascular endothelial growth factor-A (Vegf-A) is crucial to establishing NMJ reinnervation at the end target muscle. Both macrophage number and Vegf-A expression increased in end target muscles after nerve injury and repair. In mice with impaired recruitment of macrophages and monocytes (Ccr2-/- mice), the absence of CD68+ cells (macrophages) in the muscle resulted in diminished muscle function. Using a Vegf-receptor 2 (VegfR2) inhibitor (cabozantinib; CBZ) via oral gavage in wild-type (WT) mice resulted in reduced tSC cytoplasmic process extension and decreased NMJ reinnervation compared with saline controls. Mice with Vegf-A conditionally knocked out in macrophages (Vegf-Afl/fl; LysMCre mice) demonstrated a more prolonged detrimental effect on NMJ reinnervation and worse functional muscle recovery. Together, these results show that contributions of the immune system are integral for NMJ reinnervation and functional muscle recovery after nerve injury.SIGNIFICANCE STATEMENT This work demonstrates beneficial contributions of a macrophage-mediated response for neuromuscular junction (NMJ) reinnervation following nerve injury and repair. Macrophage recruitment occurred at the NMJ, distant from the nerve injury site, to support functional recovery at the muscle. We have shown hindered terminal Schwann cell (tSC) injury response and NMJ recovery with inhibition of: (1) macrophage recruitment after injury; (2) vascular endothelial growth factor receptor 2 (VegfR2) signaling; and (3) Vegf secretion from macrophages. We conclude that macrophage-derived Vegf is a key component of NMJ recovery after injury. Determining the mechanisms active at the end target muscle after motor nerve injury reveals new therapeutic targets that may translate to improve motor recovery following nerve injury. Copyright © 2020 the authors.
Author Keywords
muscle recovery; nerve injury; neuromuscular junction; reinnervation; terminal Schwann cell; vascular endothelial growth factor
Document Type: Article
Publication Stage: Final
Source: Scopus
"Chemical mutagenesis of a GPCR ligand: Detoxifying "inflammo-attraction" to direct therapeutic stem cell migration" (2020) Proceedings of the National Academy of Sciences of the United States of America
Chemical mutagenesis of a GPCR ligand: Detoxifying “inflammo-attraction” to direct therapeutic stem cell migration
(2020) Proceedings of the National Academy of Sciences of the United States of America, 117 (49), pp. 31177-31188.
Lee, J.-P.a b , Zhang, R.a , Yan, M.a , Duggineni, S.a , Wakeman, D.R.a , Niles, W.L.a , Feng, Y.a , Chen, J.b , Hamblin, M.H.c , Han, E.B.d , Gonzalez, R.a , Fang, X.e , Zhu, Y.e , Wang, J.e , Xu, Y.e , Wenger, D.A.f , Seyfried, T.N.g , An, J.h , Sidman, R.L.i , Huang, Z.a h , Snyder, E.Y.a j
a Center for Stem Cells and Regenerative Medicine, Sanford Burnham Prebys Medical Discovery Institute, San Diego, CA 92037, United States
b Department of Physiology, Tulane University School of Medicine, New Orleans, LA 70112, United States
c Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, United States
d Department of Neuroscience, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, United States
e School of Life Sciences, Tsinghua University, Beijing, 100084, China
f Department of Neurology, Jefferson Medical College, Philadelphia, PA 19107, United States
g Biology Department, Boston College, Chestnut Hill, MA 02467, United States
h Department of Medicine, University of California San Diego, San Diego, CA 92037, United States
i Department of Neurology, Harvard Medical School, Boston, MA 02115, United States
j Sanford Consortium for Regenerative Medicine, San Diego, CA 92037, United States
Abstract
A transplanted stem cell’s engagement with a pathologic niche is the first step in its restoring homeostasis to that site. Inflammatory chemokines are constitutively produced in such a niche; their binding to receptors on the stem cell helps direct that cell’s “pathotropism.” Neural stem cells (NSCs), which express CXCR4, migrate to sites of CNS injury or degeneration in part because astrocytes and vasculature produce the inflammatory chemokine CXCL12. Binding of CXCL12 to CXCR4 (a G protein-coupled receptor, GPCR) triggers repair processes within the NSC. Although a tool directing NSCs to where needed has been long-sought, one would not inject this chemokine in vivo because undesirable inflammation also follows CXCL12-CXCR4 coupling. Alternatively, we chemically “mutated” CXCL12, creating a CXCR4 agonist that contained a strong pure binding motif linked to a signaling motif devoid of sequences responsible for synthetic functions. This synthetic dual-moity CXCR4 agonist not only elicited more extensive and persistent human NSC migration and distribution than did native CXCL 12, but induced no host inflammation (or other adverse effects); rather, there was predominantly reparative gene expression. When coadministered with transplanted human induced pluripotent stem cell-derived hNSCs in a mouse model of a prototypical neurodegenerative disease, the agonist enhanced migration, dissemination, and integration of donor-derived cells into the diseased cerebral cortex (including as electrophysiologically-active cortical neurons) where their secreted cross-corrective enzyme mediated a therapeutic impact unachieved by cells alone. Such a “designer” cytokine receptor-agonist peptide illustrates that treatments can be controlled and optimized by exploiting fundamental stem cell properties (e.g., “inflammo-attraction”). © 2020 National Academy of Sciences. All rights reserved.
Author Keywords
CXCR4; Homing; Human induced pluripotent stem cells; Neural stem cells; Neurodegeneration
Funding details
California Institute for Regenerative MedicineCIRMRS1-00225-1
National Institutes of HealthNIHR01-GM057761
U.S. Department of DefenseDODW81XWH-16-1-0087-02
Document Type: Article
Publication Stage: Final
Source: Scopus
"Design of a multivalent bifunctional chelator for diagnostic 64Cu PET imaging in Alzheimer's disease" (2020) Proceedings of the National Academy of Sciences of the United States of America
Design of a multivalent bifunctional chelator for diagnostic 64Cu PET imaging in Alzheimer’s disease
(2020) Proceedings of the National Academy of Sciences of the United States of America, 117 (49), pp. 30928-30933.
Cho, H.-J.a , Huynh, T.T.b c , Rogers, B.E.b , Mirica, L.M.a d
a Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States
b Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63108, United States
c Department of Chemistry, Washington University, St. Louis, MO 63130, United States
d Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
Herein, we report a 64Cu positron emission tomography (PET) imaging agent that shows appreciable in vivo brain uptake and exhibits high specific affinity for beta-amyloid (Aβ) aggregates, leading to the successful PET imaging of amyloid plaques in the brains of 5xFAD mice versus those of wild-type mice. The employed approach uses a bifunctional chelator with two Aβ-interacting fragments that dramatically improves the Aβ-binding affinity and lipophilicity for favorable blood-brain barrier penetration, while the use of optimized-length spacers between the Cuchelating group and the Aβ-interacting fragments further improves the in vivo Aβ-binding specificity and brain uptake of the corresponding 64Cu PET imaging agent. © 2020 National Academy of Sciences. All rights reserved.
Author Keywords
Alzheimer’s disease; Amyloid beta (Aβ) peptide; Blood-brain barrier; Multivalent effect; Positron emission tomography imaging
Funding details
National Institutes of HealthNIHR01GM114588
Alzheimer’s Disease Research Center, University of WashingtonADRC, UWP50AG05681
Document Type: Article
Publication Stage: Final
Source: Scopus
"Sequence of Alzheimer disease biomarker changes in cognitively normal adults: A cross-sectional study" (2020) Neurology
Sequence of Alzheimer disease biomarker changes in cognitively normal adults: A cross-sectional study
(2020) Neurology, 95 (23), pp. e3104-e3116.
Luo, J., Agboola, F., Grant, E., Masters, C.L., Albert, M.S., Johnson, S.C., McDade, E.M., Vöglein, J., Fagan, A.M., Benzinger, T., Massoumzadeh, P., Hassenstab, J., Bateman, R.J., Morris, J.C., Perrin, R.J., Chhatwal, J., Jucker, M., Ghetti, B., Cruchaga, C., Graff-Radford, N.R., Schofield, P.R., Mori, H., Xiong, C.
From the Division of Public Health Sciences (J.L.), Department of Surgery, Siteman Cancer Center Biostatistics Core (J.L.), Division of Biostatistics (J.L., F.A., E.G., C.X.), Knight Alzheimer Disease Research Center (F.A., E.G., A.M.F., T.B., P.M., J.H., R.J.B., J.C.M., R.J.P., C.X.), Department of Neurology (E.M.M., A.M.F., J.H., R.J.B., J.C.M., R.J.P.), Department of Radiology (T.B., P.M.), Department of Pathology (J.C.M., R.J.P.), Department of Immunology (J.C.M., R.J.P.), and Department of Psychiatry (C.C.), Washington University School of Medicine, St. Louis, MO; The Florey Institute (C.L.M.), University of Melbourne, Australia; Department of Neurology (M.S.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Wisconsin Alzheimer’s Institute and Alzheimer’s Disease Research Center (S.C.J.), University of Wisconsin-Madison School of Medicine and Public Health; Geriatric Research Education and Clinical Center (S.C.J.), William S. Middleton Veterans Memorial Hospital, Madison, WI; German Center for Neurodegenerative Diseases (J.V.); Department of Neurology (J.V.), Ludwig-Maximilians-Universität München, Munich, Germany; Department of Neurology (J.C.), Massachusetts General Hospital, Harvard Medical School, Boston; Hertie-Institute for Clinical Brain Research (M.J.), University of Tübingen; German Center for Neurodegenerative Diseases (M.J.), Tübingen, Germany; Department of Pathology and Laboratory Medicine (B.G.), Indiana University, Indianapolis; Department of Neurology (N.R.G.-R.), Mayo Clinic, Jacksonville, FL; Neuroscience Research Australia (P.R.S.), Randwick; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney, Australia; and Department of Clinical Neuroscience (H.M.), Osaka City University Medical School, Abenoku, Osaka, Japan
Abstract
OBJECTIVE: To determine the ordering of changes in Alzheimer disease (AD) biomarkers among cognitively normal individuals. METHODS: Cross-sectional data, including CSF analytes, molecular imaging of cerebral fibrillar β-amyloid (Aβ) with PET using the [11C] benzothiazole tracer Pittsburgh compound B (PiB), MRI-based brain structures, and clinical/cognitive outcomes harmonized from 8 studies, collectively involving 3,284 cognitively normal individuals 18 to 101 years of age, were analyzed. The age at which each marker exhibited an accelerated change (called the change point) was estimated and compared across the markers. RESULTS: Accelerated changes in CSF Aβ1-42 (Aβ42) occurred at 48.28 years of age and in Aβ42/Aβ40 ratio at 46.02 years, followed by PiB mean cortical standardized uptake value ratio (SUVR) with a change point at 54.47 years. CSF total tau (Tau) and tau phosphorylated at threonine 181 (Ptau) had a change point at ≈60 years, similar to those for MRI hippocampal volume and cortical thickness. The change point for a cognitive composite occurred at 62.41 years. The change points for CSF Aβ42 and Aβ42/Aβ40 ratio, albeit not significantly different from that for PiB SUVR, occurred significantly earlier than that for CSF Tau, Ptau, MRI markers, and the cognitive composite. Adjusted analyses confirmed that accelerated changes in CSF Tau, Ptau, MRI markers, and the cognitive composite occurred at ages not significantly different from each other. CONCLUSIONS: Our findings support the hypothesized early changes of amyloid in preclinical AD and suggest that changes in neuronal injury and neurodegeneration markers occur close in time to cognitive decline. © 2020 American Academy of Neurology.
Document Type: Article
Publication Stage: Final
Source: Scopus
"Depression and nicotine withdrawal associations with combustible and electronic cigarette use" (2020) International Journal of Environmental Research and Public Health
Depression and nicotine withdrawal associations with combustible and electronic cigarette use
(2020) International Journal of Environmental Research and Public Health, 17 (24), art. no. 9334, pp. 1-5.
Pergadia, M.L.a , Newcomer, J.W.a b , Gilbert, D.G.c
a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, United States
b Thriving Mind South Florida, Miami, FL 33126, United States
c Department of Psychology, Southern Illinois University, Carbondale, IL 62901, United States
Abstract
Depression is a risk factor for nicotine use and withdrawal. Population level epidemiologic studies that include users of either combustible or electronic cigarette (NICUSER) could inform interventions to reduce nicotine dependence in vulnerable populations. The current study examined the relationship between depression diagnosis (DEPDX), NICUSER, and lifetime rates of DSM-V nicotine withdrawal (NW) symptoms in a nationally representative sample of US adults (N = 979), who answered related questions in surveys administered through GfK’s KnowledgePanel. Over 42% of the sample reported lifetime ever combustible cigarette use, 15.6% electronic-cigarette use, and 45.9% either (NICUSER). Weighted logistic regression analyses (controlling for age and gender) found that DEPDX was associated with 2.3 times increased odds (ratio (OR); 95% Confidence Interval (CI): 1.5–3.5) of being a NICUSER. Regarding risks of NW symptoms among NICUSER, models that additionally controlled for frequency of nicotine use found that DEPDX was significantly associated with increased odds of concentration problems (OR = 2.4; 95% CI: 1.3–4.5) and depressed mood (OR = 2.2; 95% CI: 1.1–4.1) when quitting or cutting down on nicotine use. Results highlight the consistent comorbidity between depression, nicotine use, and symptomatic nicotine withdrawal in a population-based sample of combustible and electronic cigarette users. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Author Keywords
Depression; Nicotine; Withdrawal symptoms
Funding details
Florida Atlantic UniversityFAUCC0877-TAG001796
Substance Abuse and Mental Health Services AdministrationSAMHSAH79SM080142
National Institutes of HealthNIH
National Institutes of HealthNIHMH106682, MH118395
Document Type: Article
Publication Stage: Final
Source: Scopus
"Fetal Cortical Plate Segmentation Using Fully Convolutional Networks With Multiple Plane Aggregation" (2020) Frontiers in Neuroscience
Fetal Cortical Plate Segmentation Using Fully Convolutional Networks With Multiple Plane Aggregation
(2020) Frontiers in Neuroscience, 14, art. no. 591683, .
Hong, J.a b , Yun, H.J.b c , Park, G.d , Kim, S.a , Laurentys, C.T.b , Siqueira, L.C.b , Tarui, T.e f , Rollins, C.K.g , Ortinau, C.M.h , Grant, P.E.b c , Lee, J.-M.d , Im, K.b c
a Department of Electronic Engineering, Hanyang University, Seoul, South Korea
b Fetal-Neonatal Neuroimaging and Developmental Science Center, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
c Division of Newborn Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
d Department of Biomedical Engineering, Hanyang University, Seoul, South Korea
e Mother Infant Research Institute, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, United States
f Department of Pediatrics, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, United States
g Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
h Department of Pediatrics, Washington University in St. Louis, St. Louis, MO, United States
Abstract
Fetal magnetic resonance imaging (MRI) has the potential to advance our understanding of human brain development by providing quantitative information of cortical plate (CP) development in vivo. However, for a reliable quantitative analysis of cortical volume and sulcal folding, accurate and automated segmentation of the CP is crucial. In this study, we propose a fully convolutional neural network for the automatic segmentation of the CP. We developed a novel hybrid loss function to improve the segmentation accuracy and adopted multi-view (axial, coronal, and sagittal) aggregation with a test-time augmentation method to reduce errors using three-dimensional (3D) information and multiple predictions. We evaluated our proposed method using the ten-fold cross-validation of 52 fetal brain MR images (22.9–31.4 weeks of gestation). The proposed method obtained Dice coefficients of 0.907 ± 0.027 and 0.906 ± 0.031 as well as a mean surface distance error of 0.182 ± 0.058 mm and 0.185 ± 0.069 mm for the left and right, respectively. In addition, the left and right CP volumes, surface area, and global mean curvature generated by automatic segmentation showed a high correlation with the values generated by manual segmentation (R2 > 0.941). We also demonstrated that the proposed hybrid loss function and the combination of multi-view aggregation and test-time augmentation significantly improved the CP segmentation accuracy. Our proposed segmentation method will be useful for the automatic and reliable quantification of the cortical structure in the fetal brain. © Copyright © 2020 Hong, Yun, Park, Kim, Laurentys, Siqueira, Tarui, Rollins, Ortinau, Grant, Lee and Im.
Author Keywords
cortical plate; deep learning; fetal brain; hybrid loss; MRI; segmentation
Funding details
HI19C0755
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHD
National Institutes of HealthNIHR01HD100009, K23HD079605, U01HD087211, R21HD094130
National Institute of Biomedical Imaging and BioengineeringNIBIBR01EB017337
Ministry of Science and ICT, South KoreaMSIT2020-0-01373
Korea Health Industry Development InstituteKHIDI
Institute for Information and Communications Technology PromotionIITP
American Heart AssociationAHA19IPLOI34660336
National Institute of Neurological Disorders and StrokeNINDSR01NS114087
National Heart, Lung, and Blood InstituteNHLBIK23HL141602, K23-NS101120
Document Type: Article
Publication Stage: Final
Source: Scopus
"Association Between Benzodiazepine Use With or Without Opioid Use and All-Cause Mortality in the United States, 1999-2015" (2020) JAMA Network Open
Association Between Benzodiazepine Use With or Without Opioid Use and All-Cause Mortality in the United States, 1999-2015
(2020) JAMA Network Open, 3 (12), p. e2028557.
Xu, K.Y.a , Hartz, S.M.a , Borodovsky, J.T.a , Bierut, L.J.a b , Grucza, R.A.a c
a Health and Behavior Research Center, Department of Psychiatry, Washington University School of Medicine in St Louis, St Louis, MO, United States
b Alvin J. Siteman Cancer Center, Barnes Jewish Hospital, Washington University School of Medicine in St Louis, St Louis, MO, United States
c Center for Health Outcomes Research, St Louis University, St Louis, MO, United States
Abstract
Importance: Although overall rates of opioid use have been plateauing, coprescriptions of benzodiazepines and opioids have increased greatly in recent years. It is unknown whether this combination is an independent risk factor for all-cause mortality as opposed to being more frequently used by persons with a baseline elevated risk of death. Objective: To evaluate whether benzodiazepine use, with or without opioid use, is associated with increased all-cause mortality relative to the use of low-risk antidepressants. Design, Setting, and Participants: This retrospective cohort study used a large, nationally representative US data set (the National Health and Nutrition Examination Surveys [NHANES]) from 1999 to 2015. Eight cycles of NHANES data were used, spanning 37 610 person-years of follow-up time among 5212 individuals. Statistical analysis was performed from August 24, 2019, through May 23, 2020. Exposures: The primary exposure variable was benzodiazepine and opioid coprescriptions. Individuals taking selective serotonin reuptake inhibitors (SSRIs) served as an active comparator reference group. Main Outcomes and Measures: All-cause mortality was obtained via linkage of NHANES to the National Death Index. Propensity scores were calculated from covariates associated with sociodemographic factors, comorbidities, and medication use for more than 1000 prescription types. Propensity score-weighted mortality hazards were calculated from Cox proportional hazards regression models. Results: Of 5212 participants aged 20 years or older (1993 men [38.2%]; mean [SD] age, 54.8 [16.9] years) followed up for a median of 6.7 years (range, 0.2-16.8 years), 101 deaths (33.0 per 1000 person-years) occurred among those receiving cotreatment, 236 deaths (26.5 per 1000 person-years) occurred among those receiving only benzodiazepines, and 227 deaths (20.2 per 1000 person-years) occurred among SSRI recipients taking neither opioids nor benzodiazepines. After propensity score weighting, a significant increase in all-cause mortality was associated with benzodiazepine and opioid cotreatment (hazard ratio, 2.04 [95% CI, 1.65-2.52]) and benzodiazepines without opioids (hazard ratio, 1.60 [95% CI, 1.33-1.92]). Subgroup analyses revealed an increased risk of mortality for individuals receiving cotreatment who were 65 years or younger but not for those older than 65 years; similar findings were observed for those receiving benzodiazepines without opioids. Conclusions and Relevance: This study found a significant increase in all-cause mortality associated with benzodiazepine use with or without opioid use in comparison with SSRI use. Benzodiazepine and opioid cotreatment, in particular, was associated with a 2-fold increase in all-cause mortality even after taking into account medical comorbidities and polypharmacy burden.
Document Type: Article
Publication Stage: Final
Source: Scopus
"Joint reconstruction of initial pressure distribution and spatial distribution of acoustic properties of elastic media with application to transcranial photoacoustic tomography" (2020) Inverse Problems
Joint reconstruction of initial pressure distribution and spatial distribution of acoustic properties of elastic media with application to transcranial photoacoustic tomography
(2020) Inverse Problems, 36 (12), art. no. 124007, .
Poudel, J.a , Anastasio, M.A.b
a Department of Biomedical Engineering, Washington University in St. Louis, 1 Brookings Dr., St. Louis, MO 63130, United States
b Department of Bioengineering, University of Illinois at Urbana-Champaign, 1406 W Green St, Urbana, IL 61801, United States
Abstract
Photoacoustic computed tomography (PACT) is an emerging computed imaging modality that exploits optical contrast and ultrasonic detection principles to form images of the photoacoustically induced initial pressure distribution within tissue. The PACT reconstruction problem corresponds to a time-domain inverse source problem, where the initial pressure distribution is recovered from the measurements recorded on an aperture outside the support of the source. A major challenge in transcranial PACT brain imaging is to compensate for aberrations in the measured acoustic data that are induced by propagation of the photoacoustic wavefields through the skull. To properly account for these effects, previously proposed image reconstruction methods for transcranial PACT require knowledge of the spatial distribution of the elastic parameters of the skull. However, estimating the spatial distribution of these parameters prior to the PACT experiment remains challenging. To circumvent this issue, in this work a method to jointly reconstruct the initial pressure distribution and a low-dimensional representation of the elastic parameters of the skull is developed and investigated. The joint reconstruction (JR) problem is solved by use of a proximal optimization method that allows constraints and non-smooth regularization terms. The proposed method is evaluated by use of large-scale three-dimensional (3D) computer-simulation studies that mimic transcranial PACT experiments. © 2020 The Author(s).
Author Keywords
Elastic wave equation; Image reconstruction; Joint image reconstruction; Photoacoustic computed tomography; Transcranial imaging
Document Type: Article
Publication Stage: Final
Source: Scopus
"Longitudinal assessment of neuroradiologic features in wolfram syndrome" (2020) American Journal of Neuroradiology
Longitudinal assessment of neuroradiologic features in wolfram syndrome
(2020) American Journal of Neuroradiology, 41 (12), pp. 2364-2369.
Samara, A.a , Lugar, H.M.a , Hershey, T.b c , Shimony, J.S.c
a Department of Psychiatry, Washington University, School of Medicine, St. Louis, MO, United States
b Department of Neurology, Washington University, School of Medicine, St. Louis, MO, United States
c Department of Mallinckrodt, Institute of Radiology, Washington University, School of Medicine, St. Louis, MO, United States
Abstract
BACKGROUND AND PURPOSE: Wolfram syndrome is a rare genetic disease with characteristic brain involvement. We reviewed the brain MR images of patients with Wolfram syndrome to determine the frequency and characteristics of common neuroradiologic findings. MATERIALS AND METHODS: We retrospectively reviewed the imaging data of patients with genetically-confirmed Wolfram syndrome who had been recruited to the Washington University Wolfram Syndrome Research Clinic. These patients were evaluated between 2010 and 2019 with annual MRIs, along with other measures. MR images were assessed for clinical neuroradiologic signs at each individual’s first and last follow-up visits to characterize the frequency, rate of progression, and clinical correlations of these signs. RESULTS: We included 30 patients (13 males/17 females; average age at first visit, 14 years; average age at last visit, 19 years). The median duration of follow-up was 5 years (range, 2-9 years). The most common findings were an absent or diminished posterior pituitary bright spot (first, 53%; last, 70%), T1/T2 pons signal abnormalities (first, 53%; last, 67%), optic nerve atrophy (first, 30%; last, 80%), white matter T2 hyperintensities (first, 27%; last, 35%), and cerebellar atrophy (first, 23%; last, 70%). CONCLUSIONS: Patients with Wolfram syndrome present characteristic neuroradiologic findings that involve the posterior pituitary gland, optic nerves, white matter, brain stem, and cerebellum. These abnormal findings appear at an early age and tend to increase in frequency with time. However, the neurologic significance and neuropathologic mechanisms of each sign require more investigation. Neuroradiologists should be aware of the pattern of these features in Wolfram syndrome. © 2020 American Society of Neuroradiology. All rights reserved.
Funding details
American Diabetes AssociationADA
McDonnell Center for Systems Neuroscience
National Institute on Drug AbuseNIDA5T32DA007261–27, HD070855, U54 HD087011
DK020579, UL1 RR024992
National Institutes of HealthNIH
National Institute on Drug AbuseNIDA5T32DA007261–27
Document Type: Article
Publication Stage: Final
Source: Scopus
"Validation of Hearing Loss Prediction Tool for Cisplatin Chemotherapy and Radiation in Head and Neck Cancer Treatment" (2020) JAMA Otolaryngology – Head and Neck Surgery
Validation of Hearing Loss Prediction Tool for Cisplatin Chemotherapy and Radiation in Head and Neck Cancer Treatment
(2020) JAMA Otolaryngology – Head and Neck Surgery, .
Deutsch, B.C.a , Collopy, C.b , Kallogjeri, D.a , Piccirillo, J.F.a
a Department of Otolaryngology-Head and Neck Surgery, Washington University, School of Medicine, St Louis, MO, United States
b Division of Adult Audiology, Department of Otolaryngology-Head and Neck Surgery, Washington University, School of Medicine, St Louis, MO, United States
Abstract
Importance: Hearing loss affects up to 88% of patients undergoing head and neck cancer treatment; however, there are few validated models to predict this outcome. A predictive posttreatment model for hearing loss will allow clinicians and patients to make well-informed decisions about treatment with cisplatin-based chemotherapies and radiotherapy. Objective: To validate a previously created predictive model for objective hearing outcomes and to assess barriers to using the prediction nomogram in general practice for patients newly diagnosed with head and neck cancer. Design, Setting, and Participants: This cohort study includes an evaluation of 105 patients (208 ears) and interviews with 6 clinicians. The patients were treated at a high-volume tertiary care hospital. Patient participants were newly diagnosed with head and neck cancer and treated at Siteman Cancer Center from July 1, 2018, to December 31, 2019, with radiotherapy both with and without cisplatin-based chemotherapy. Additionally, the clinicians involved in the care of patients with head and neck cancer were interviewed to assess implementation strategies. Exposures: Radiotherapy with and without cisplatin-based chemotherapy. Main Outcomes and Measures: Hearing defined by the audiometric pure-tone average of 1, 2, and 4 kHz. Results: A total of 105 patients (208 ears; mean [SD] age, 61 [11] years; 82 men [78%]) were compared with the development cohort to assess the similarities and differences in case mix. All patients underwent radiation therapy, 50 (48%) received cisplatin-based chemotherapy, and 67 (64%) had a surgical resection. The mean (SD) cochlear dose of radiation was 13 (12) Gy, and the mean (SD) total cisplatin dose was 238 (83) mg/m2for those undergoing cisplatin therapy. A calibration curve demonstrated that predicted and observed posttreatment pure-tone average were not significantly different. The model predicted a posttreatment pure-tone average greater than 35 dB (a common threshold for hearing aid consideration) with a sensitivity of 73% and specificity of 67% with an area under the curve of 0.71, showing good discrimination. Clinician interviews suggest the nomogram requires careful integration into patient counseling to clarify risks and benefits for treatment. Conclusions and Relevance: The findings of this cohort study confirm this model’s ability to predict posttreatment hearing outcomes in a unique population of patients. This model has the potential to inform pretreatment counseling and posttreatment hearing evaluations for this patient population. © 2020 American Medical Association. All rights reserved.
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
"Predicted Mode of Binding to and Allosteric Modulation of the μ-Opioid Receptor by Kratom's Alkaloids with Reported Antinociception in Vivo" (2020) Biochemistry
Predicted Mode of Binding to and Allosteric Modulation of the μ-Opioid Receptor by Kratom’s Alkaloids with Reported Antinociception in Vivo
(2020) Biochemistry, .
Zhou, Y.a , Ramsey, S.a , Provasi, D.a , El Daibani, A.b c , Appourchaux, K.b c , Chakraborty, S.b c , Kapoor, A.a , Che, T.b c , Majumdar, S.b c , Filizola, M.a
a Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1677, New York, NY 10029-6574, United States
b Department of Anesthesiology, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, United States
c Center for Clinical Pharmacology, University of Health Sciences and Pharmacy, St. Louis and Washington University, School of Medicine, St. Louis, MO 63110, United States
Abstract
Pain management devoid of serious opioid adverse effects is still far from reach despite vigorous research and development efforts. Alternatives to classical opioids have been sought for years, and mounting reports of individuals finding pain relief with kratom have recently intensified research on this natural product. Although the composition of kratom is complex, the pharmacological characterization of its most abundant alkaloids has drawn attention to three molecules in particular, owing to their demonstrated antinociceptive activity and limited side effects in vivo. These three molecules are mitragynine (MG), its oxidized active metabolite, 7-hydroxymitragynine (7OH), and the indole-to-spiropseudoindoxy rearrangement product of MG known as mitragynine pseudoindoxyl (MP). Although these three alkaloids have been shown to preferentially activate the G protein signaling pathway by binding and allosterically modulating the μ-opioid receptor (MOP), a molecular level understanding of this process is lacking and yet important for the design of improved therapeutics. The molecular dynamics study and experimental validation reported here provide an atomic level description of how MG, 7OH, and MP bind and allosterically modulate the MOP, which can eventually guide structure-based drug design of improved therapeutics. © 2020 American Chemical Society.
Funding details
National Institutes of HealthNIHDA045884, DA046487, DA034049
MCB080077
National Science FoundationNSFACI-1548562
National Institutes of HealthNIHS10OD026880, S10OD018522
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
"Dopamine D1 + D3 receptor density may correlate with parkinson disease clinical features" (2020) Annals of Clinical and Translational Neurology
Dopamine D1 + D3 receptor density may correlate with parkinson disease clinical features
(2020) Annals of Clinical and Translational Neurology, .
Yang, P.a , Knight, W.C.a , Li, H.a , Guo, Y.a , Perlmutter, J.S.a b c d e , Benzinger, T.L.S.a , Morris, J.C.b , Xu, J.a
a Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, United States
b Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United States
c Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, United States
d Department of Physical Therapy, Washington University School of Medicine, St. Louis, MO 63110, United States
e Department of Occupational Therapy, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
Objective: Dopamine D2-like receptors – mainly dopamine D2 receptors (D2R) and dopamine D3 receptors (D3R) – are believed to be greatly involved in the pathology of Parkinson disease (PD) progression. However, these receptors have not been precisely examined in PD patients. Our aim was to quantitatively calculate the exact densities of dopamine D1 receptors (D1R), D2R, and D3R in control, Alzheimer disease (AD), and Lewy body disease (LBD) patients (including PD, Dementia with Lewy bodies, and Parkinson disease dementia); and analyze the relationship between dopamine receptors and clinical PD manifestations. Methods: We analyzed the densities of D1R, D2R, and D3R in the striatum and substantia nigra (SN) using a novel quantitative autoradiography procedure previously developed by our group. We also examined the expression of D2R and D3R mRNA in the striatum by in situ hybridization. Results: The results showed that although no differences of striatal D1R were found among all groups; D2R was significantly decreased in the striatum of PD patients when compared with control and AD patients. Some clinical manifestations: age of onset, PD stage, dopamine responsiveness, and survival time after onset; showed a better correlation with striatal D1R + D3R densities combined compared to D1R or D3R alone. Interpretation: There is a possibility that we may infer the results in diagnosis, treatment, and prognosis of PD by detecting D1R + D3R as opposed to using dopamine D1 or D3 receptors alone. This is especially true for elderly patients with low D2R expression as is common in this disease. © 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association
Funding details
National Institutes of HealthNIHR01 NS092865, P50 AG06644, R01 AG052550
National Institutes of HealthNIHR01 NS092865, P50 AG06644, R01 AG052550
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
"Visual outcomes following everolimus targeted therapy for neurofibromatosis type 1-associated optic pathway gliomas in children" (2020) Pediatric Blood and Cancer
Visual outcomes following everolimus targeted therapy for neurofibromatosis type 1-associated optic pathway gliomas in children
(2020) Pediatric Blood and Cancer, .
Ullrich, N.J.a l , Prabhu, S.P.b , Packer, R.J.c , Goldman, S.d , Robison, N.J.e , Allen, J.C.f , Viskochil, D.H.g , Gutmann, D.H.h , Perentesis, J.P.i , Korf, B.R.j , Fisher, M.J.k , Kieran, M.W.l , NF Clinical Trials Consortiumm
a Department of Neurology, Boston Children’s Hospital, Boston, MA, United States
b Department of Radiology, Boston Children’s Hospital, Boston, MA, United States
c Center for Neuroscience and Behavioral Medicine, Children’s National Hospital, Washington, DC, United States
d Ann and Robert Lurie Children’s Hospital, Chicago, IL, United States
e Children’s Center for Cancer and Blood Diseases, Children’s Hospital Los Angeles, Los Angeles, CA, United States
f Departments of Pediatrics and Neurology, NYU Langone Medical Center, New York, NY, United States
g Department of Genetics, University of Utah, Salt Lake City, UT, United States
h Department of Neurology, Washington University School of Medicine, St Louis, MO, United States
i Division of Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States
j Department of Medical Genetics, University of Alabama at Birmingham, Birmingham, AL, United States
k Division of Oncology, Children’s Hospital of Philadelphia, Philadelphia, PA, United States
l Dana-Farber/Boston Children’s Cancer and Blood Disorder Center, Boston, MA, United States
Abstract
Data for visual acuity (VA) after treatment of neurofibromatosis type 1-associated optic pathway gliomas (NF1-OPGs) are limited. We retrospectively collected VA, converted to logMAR, before and after targeted therapy with everolimus for NF1-OPG, and compared to radiologic outcomes (14/18 with NF1-OPG, 25 eyes [three without quantifiable vision]). Upon completion of treatment, VA was stable in 19 eyes, improved in four eyes, and worsened in two eyes; visual and radiologic outcomes were discordant. In summary, the majority of children with NF1-OPG exhibited stabilization of their VA after everolimus treatment. A larger, prospective study will help delineate visual outcomes after targeted therapy. © 2020 Wiley Periodicals LLC
Author Keywords
everolimus; neurofibromatosis; optic glioma; visual acuity
Funding details
W81XWH‐05‐01‐0615
Congressionally Directed Medical Research ProgramsCDMRP
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
"Inter- and intra-tract analysis of white matter abnormalities in individuals with early-treated phenylketonuria (PKU)" (2020) Molecular Genetics and Metabolism
Inter- and intra-tract analysis of white matter abnormalities in individuals with early-treated phenylketonuria (PKU)
(2020) Molecular Genetics and Metabolism, .
Clocksin, H.E.a , Hawks, Z.W.b , White, D.A.b , Christ, S.E.a
a Department of Psychological Sciences, University of Missouri, Columbia, MO 65211, United States
b Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO 63130, United States
Abstract
Even with early and continuous treatment, individuals with phenylketonuria (PKU) may exhibit abnormalities of cortical white matter (WM). The present study utilizes a new analysis approach called Automated Fiber-Tract Quantification (AFQ) to advance our understanding of the tract-specific patterns of change in WM abnormalities in individuals with early-treated PKU (ETPKU). Diffusion Tensor Imaging (DTI) data from a sample of 22 individuals with ETPKU and a demographically-matched sample of 21 healthy individuals without PKU was analyzed using AFQ. In addition, a subsample of 8 individuals with ETPKU was reevaluated six months later after demonstrating a significant reduction in blood phe levels following initiation of sapropterin treatment. Within-tract AFQ analyses revealed significant location-by-group interactions for several WM tracts throughout the brain. In most cases, ETPKU-related disruptions in mean diffusivity (MD) were more apparent in posterior (as compared to anterior) aspects of a given tract. Reduction in blood phe levels with the aforementioned ETPKU subsample was associated with a similar pattern of improvement (posterior-to-anterior) within most tracts. Taken together, these findings suggest that there is a systematic pattern of change in WM abnormalities in individuals with ETPKU in a posterior-to-anterior manner along individual WM tracts. © 2020 Elsevier Inc.
Author Keywords
Diffusion tensor imaging; Magnetic resonance imaging; Phenylketonuria; White matter
Funding details
BioMarin Pharmaceutical
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
"The association between post-dural puncture headache and needle type during spinal anaesthesia: a systematic review and network meta-analysis" (2020) Anaesthesia
The association between post-dural puncture headache and needle type during spinal anaesthesia: a systematic review and network meta-analysis
(2020) Anaesthesia, .
Maranhao, B., Liu, M., Palanisamy, A., Monks, D.T., Singh, P.M.
Department of Anaesthesiology, Washington University in Saint LouisMO, United States
Abstract
Post-dural puncture headache is one of the most undesirable complications of spinal anaesthesia. Previous pairwise meta-analyses have either compared groups of needles or ranked individual needles based on the pooled incidence of post-dural puncture headache. These analyses have suggested both the gauge and needle tip design as risk-factors, but failed to provide an unbiased comparison of individual needles. This network meta-analysis compared the odds of post-dural puncture headache with needles of varying gauge and tip design. We searched randomised controlled trials in medical databases. The primary outcome measure of the network meta-analysis was the incidence of post-dural puncture headache. Secondary outcomes were procedural failure, backache and non-specific headache. Overall, we compared 11 different needles in 61 randomised controlled trials including a total of 14,961 participants. The probability of post-dural puncture headache and procedural failure was lowest with 26-G atraumatic needles. The 29-G cutting needle was more likely than three atraumatic needles to have the lowest odds of post-dural puncture headache, although with increased risk of procedural failure. The probability rankings were: 26 atraumatic > 27 atraumatic > 29 cutting > 24 atraumatic > 22 atraumatic > 25 atraumatic > 23 cutting > 22 cutting > 25 cutting > 27 cutting = 26 cutting for post-dural puncture headache; and 26 atraumatic > 25 cutting > 22 cutting > 24 atraumatic > 22 atraumatic > 25 atraumatic > 26 cutting > 29 cutting > 27 atraumatic = 27 cutting for procedural success. Meta-regression by type of surgical population (obstetric/non-obstetric) and participant position (sitting/lateral) did not alter these rank orders. This analysis provides an unbiased comparison of individual needles that does not support the use of simple rules when selecting the optimal needle. The 26-G atraumatic needle is most likely to enable successful insertion while avoiding post-dural puncture headache but, where this is not available, our probability rankings can help clinicians select the best of available options. © 2020 Association of Anaesthetists
Author Keywords
backache; failure; headache; PDPH; spinal anaesthesia
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
"Brief mindfulness meditation induces gray matter changes in a brain hub" (2020) Neural Plasticity
Brief mindfulness meditation induces gray matter changes in a brain hub
(2020) Neural Plasticity, 2020, art. no. 8830005, .
Tang, R.a , Friston, K.J.b , Tang, Y.-Y.c
a Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO 63105, United States
b Wellcome Centre for Human Neuroimaging, UCL Queen Square Institute of Neurology, University College London, London, WC1N 3AR, United Kingdom
c Department of Psychological Sciences, Texas Tech University, Lubbock, TX 79409, United States
Abstract
Previous studies suggest that the practice of long-term (months to years) mindfulness meditation induces structural plasticity in gray matter. However, it remains unknown whether short-term (<30 days) mindfulness meditation in novices could induce similar structural changes. Our previous randomized controlled trials (RCTs) identified white matter changes surrounding the anterior cingulate cortex (ACC) and the posterior cingulate cortex (PCC) within 2 to 4 weeks, following 5-10 h of mindfulness training. Furthermore, these changes were correlated with emotional states in healthy adults. The PCC is a key hub in the functional anatomy implicated in meditation and other perspectival processes. In this longitudinal study using a randomized design, we therefore examined the effect of a 10 h of mindfulness training, the Integrative Body-Mind Training (IBMT) on gray matter volume of the PCC compared to an active control-relaxation training (RT). We found that brief IBMT increased ventral PCC volume and that baseline temperamental trait-an index of individual differences was associated with a reduction in training-induced gray matter increases. Our findings indicate that brief mindfulness meditation induces gray matter plasticity, suggesting that structural changes in ventral PCC-a key hub associated with self-awareness, emotion, cognition, and aging-may have important implications for protecting against mood-related disorders and aging-related cognitive declines. © 2020 Rongxiang Tang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Funding details
Wellcome TrustWT088130/Z/09/Z, F31 AT010422
National Institutes of HealthNIHAT010138
Office of Naval ResearchONR
Office of Naval ResearchONRN000141512148
Document Type: Article
Publication Stage: Final
Source: Scopus
"Delirium Prevention, Detection, and Treatment in Emergency Medicine Settings: A Geriatric Emergency Care Applied Research (GEAR) Network Scoping Review and Consensus Statement" (2020) Academic Emergency Medicine
Delirium Prevention, Detection, and Treatment in Emergency Medicine Settings: A Geriatric Emergency Care Applied Research (GEAR) Network Scoping Review and Consensus Statement
(2020) Academic Emergency Medicine, .
Carpenter, C.R.a , Hammouda, N.b , Linton, E.A.b c , Doering, M.d , Ohuabunwa, U.K.e , Ko, K.J.f , Hung, W.W.g h , Shah, M.N.i , Lindquist, L.A.j , Biese, K.k , Wei, D.i , Hoy, L.l , Nerbonne, L.l , Hwang, U.m , Dresden, S.M.n , the GEAR Networko
a Department of Emergency Medicine, Washington University in St. Louis School of Medicine, Emergency Care Research Core, St. Louis, MI, United States
b Department of Emergency Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
c Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
d Becker Medical Library, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
e Division of General Medicine and Geriatrics, Emory University School of Medicine, Atlanta, GA, United States
f Clinical Research, West Health Institute, La Jolla, CA, United States
g James J. Peters VA Medical Center, Bronx, NY, United States
h Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
i BerbeeWalsh Department of Emergency Medicine, University of Wisconsin–Madison, Madison, WI, United States
j Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
k Departments of Emergency Medicine and Internal Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
l PFCC Partners, Long Beach, CA, United States
m Department of Emergency Medicine, Yale School of Medicine, New Haven, CT, United States
n Department of Emergency Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
Abstract
Background: Older adult delirium is often unrecognized in the emergency department (ED), yet the most compelling research questions to overcome knowledge-to-practice deficits remain undefined. The Geriatric Emergency care Applied Research (GEAR) Network was organized to identify and prioritize delirium clinical questions. Methods: GEAR identified and engaged 49 transdisciplinary stakeholders including emergency physicians, geriatricians, nurses, social workers, pharmacists, and patient advocates. Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews, clinical questions were derived, medical librarian electronic searches were conducted, and applicable research evidence was synthesized for ED delirium detection, prevention, and management. The scoping review served as the foundation for a consensus conference to identify the highest priority research foci. Results: In the scoping review, 27 delirium detection “instruments” were described in 48 ED studies and used variable criterion standards with the result of delirium prevalence ranging from 6% to 38%. Clinician gestalt was the most common “instrument” evaluated with sensitivity ranging from 0% to 81% and specificity from 65% to 100%. For delirium management, 15 relevant studies were identified, including one randomized controlled trial. Some intervention studies targeted clinicians via education and others used clinical pathways. Three medications were evaluated to reduce or prevent ED delirium. No intervention consistently prevented or treated delirium. After reviewing the scoping review results, the GEAR stakeholders identified ED delirium prevention interventions not reliant on additional nurse or physician effort as the highest priority research. Conclusions: Transdisciplinary stakeholders prioritize ED delirium prevention studies that are not reliant on health care worker tasks instead of alternative research directions such as defining etiologic delirium phenotypes to target prevention or intervention strategies. © 2020 by the Society for Academic Emergency Medicine
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
"Analysis of N-acetyl cysteine modified polydimethylsiloxane shunt for improved treatment of hydrocephalus" (2020) Journal of Biomedical Materials Research – Part B Applied Biomaterials
Analysis of N-acetyl cysteine modified polydimethylsiloxane shunt for improved treatment of hydrocephalus
(2020) Journal of Biomedical Materials Research – Part B Applied Biomaterials, .
Al-Saloum, S.a , Zaranek, M.a , Horbatiuk, J.a , Gopalakrishnan, P.a , Dumitrescu, A.a , McAllister, J.P., IIb , Harris, C.A.a
a Wayne State University Department of Chemical Engineering and Materials Science, Detroit, MI, United States
b Washington University St. Louis, St. Louis, MO, United States
Abstract
A major cause of hydrocephalus shunt failure is cell adhesion and obstruction of shunt catheter holes. An estimated 50% of pediatric shunts fail in the first 2 years of insertion, decreasing cell attachment and catheter obstruction can prolong the lifetime and effectiveness of the device. From previous studies, it was shown that treatment of the polydimethylsiloxane (PDMS) surface of a standard catheter with an N-acetyl-cysteine (NAC/1-ethyl-3-(3-dimethylanimopropyl)carbodiimide hydrochloride/N-hydroxysuccinimide) layer increases the wettability of the surface and has been shown to decrease cell adhesion. Other studies indicate that NAC’s antioxidant behavior induces glutathione and in turn modulates cell inflammatory pathways. The current study explores the longevity of the NAC coating from the surface of the catheter over time and shows its effect on valve function. Using SEM imaging, contact angle testing, and nanodrop spectrophotometry, this release was quantified for shunt samples incubated for 0, 10, 30, 60, and 90 days. Contact angle showed a significant increase in wettability of the surface when shunts were treated with NAC, confirming successful surface modification. Pressure assays determined that if the coating is release it had no detrimental downstream effects, such as on the shunt valve mechanism. SEM imaging revealed slight deformations in surface coating indicative of salt deposition on the modified shunt samples, while nanodrop spectrophotometry and contact angle data trends suggested some discharge of the NAC coating from the catheter surfaces. The effects of NAC on cell activity may transform the way hydrocephalus is treated in the future by increasing the longevity of the shunt to protect from obstruction. © 2020 Wiley Periodicals LLC
Author Keywords
catheter; hydrocephalus; NAC (N-acetyl-L-cysteine); release
Funding details
National Institutes of HealthNIHR01NS094570
Hydrocephalus AssociationHA
National Institute of Neurological Disorders and StrokeNINDS
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
"Author Correction: Fragmented mitochondria released from microglia trigger A1 astrocytic response and propagate inflammatory neurodegeneration (Nature Neuroscience, (2019), 22, 10, (1635-1648), 10.1038/s41593-019-0486-0)" (2020) Nature Neuroscience
Author Correction: Fragmented mitochondria released from microglia trigger A1 astrocytic response and propagate inflammatory neurodegeneration (Nature Neuroscience, (2019), 22, 10, (1635-1648), 10.1038/s41593-019-0486-0)
(2020) Nature Neuroscience, .
Joshi, A.U.a , Minhas, P.S.b , Liddelow, S.A.c f g , Haileselassie, B.a d , Andreasson, K.I.b , Dorn, G.W., IIe , Mochly-Rosen, D.a
a Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, United States
b Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, United States
c Department of Neurobiology, Stanford University School of Medicine, Stanford, CA, United States
d Department of Pediatrics Division of Critical Care Medicine, Stanford University School of Medicine, Stanford, CA, United States
e Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO, United States
f Department of Neuroscience and Physiology and Neuroscience Institute, New York University Langone Medical Center, New York, NY, United States
g Department of Pharmacology and Therapeutics, The University of Melbourne, Melbourne, VIC, Australia
Abstract
In the version of this article initially published, two graphs were inadvertently duplicated in Fig. 2: the left graph in Fig. 2f and the right graph in Fig. 2k. These graphs have been replotted after reviewing the data; results and conclusions were not affected. Source data for the revised figures are provided as Supplementary Data. The error has been corrected in the PDF and HTML versions of this article. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
Document Type: Erratum
Publication Stage: Article in Press
Source: Scopus