“Characterization of focused ultrasound-mediated brainstem delivery of intranasally administered agents” (2020) Journal of Controlled Release
Characterization of focused ultrasound-mediated brainstem delivery of intranasally administered agents
(2020) Journal of Controlled Release, 328, pp. 276-285.
Ye, D.a , Luan, J.a , Pang, H.b , Yang, Y.b , Nazeri, A.c , Rubin, J.B.d e , Chen, H.b f
a Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, Saint Louis, MO 63130, United States
b Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO 63130, United States
c Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, United States
d Departments of Pediatrics and Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, United States
e Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, United States
f Department of Radiation Oncology, Washington University School of Medicine, Saint Louis, MO 63108, United States
Abstract
Focused ultrasound-mediated intranasal (FUSIN) delivery is a recently proposed technique that bypasses the blood-brain barrier to achieve noninvasive and localized brain drug delivery. The goal of this study was to characterize FUSIN drug delivery outcome in mice with regard to its dependency on several critical experimental factors, including the time interval between IN administration and FUS sonication (Tlag1), the FUS pressure, and the time for sacrificing the mice post-FUS (Tlag2). Wild-type mice were treated by FUSIN delivery of near-infrared fluorescent dye-labeled bovine serum albumin (800CW-BSA, used as a model agent). 800CW-BSA was intranasally administered to the mice in vivo, followed by intravenous injection of microbubbles and FUS sonication at the brainstem. Fluorescence imaging of ex vivo mouse brain slices was used to quantify the delivery outcomes of 800CW-BSA. Major organs, along with the nasal tissue and trigeminal nerve, were harvested to assess the biodistribution of 800CW-BSA. The delivery outcome of 800CW-BSA was the highest at the brainstem when Tlag1 was 0.5 h, which was on average 24.5-fold, 5.4-fold, and 21.6-fold higher than those of the IN only, Tlag1 = 1.5 h, and Tlag1 = 4.0 h, respectively. The FUSIN delivery outcome at the lowest pressure level, 0.43 MPa, was on average 1.8-fold and 3.7-fold higher than those at 0.56 MPa and 0.70 MPa, respectively. The mean concentration of 800CW-BSA in the brainstem after FUSIN delivery decreased from 0.5 h to 4.0 h post-FUS. The accumulation of 800CW-BSA was low in the heart, lung, spleen, kidneys, and liver, but high in the stomach and intestines. This study revealed the unique characteristics of FUSIN as a noninvasive, efficient, and localized brain drug delivery technique. © 2020 Elsevier B.V.
Author Keywords
Blood-brain barrier; Brain drug delivery; Brainstem; Focused ultrasound; Intranasal delivery
Document Type: Article
Publication Stage: Final
Source: Scopus
“Cortical midline structures associated with rumination in women with PTSD” (2020) Journal of Psychiatric Research
Cortical midline structures associated with rumination in women with PTSD
(2020) Journal of Psychiatric Research, 131, pp. 69-76.
Philippi, C.L.a , Pessin, S.a , Reyna, L.a , Floyd, T.b , Bruce, S.E.a c
a Department of Psychological Sciences, University of Missouri-St. Louis, St. Louis, MO, United States
b Washington University in St. Louis, St. Louis, MO, United States
c Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
Abstract
Elevated rumination, characterized by repetitive, negative self-focused cognition, is common in posttraumatic stress disorder (PTSD) and has been shown to predict the onset and maintenance of the disorder. Neuroimaging research has implicated cortical midline brain structures, including the rostral anterior cingulate cortex (rACC), posterior cingulate cortex (PCC), and isthmus cingulate (IsthCing), in rumination in healthy and depressed populations. While past research has revealed dysfunction in cortical midline regions in PTSD, no studies have yet investigated the structural and functional neural mechanisms underlying rumination in women with PTSD. In the current study, we used structural MRI and resting-state fMRI to examine relationships between rumination and brain volume, as well as resting-state functional connectivity (rsFC) of cortical midline structures in women with PTSD due to interpersonal trauma (N = 71). We performed multiple linear regression analyses to relate brain volume in rACC, PCC, and IsthCing regions to self-reported rumination, after controlling for age and total intracranial volume. We also conducted standard seed-based voxelwise rsFC analyses for significant regions identified in the structural analysis. We found a significant relationship between greater rumination and volume in the left IsthCing (p =.025). Results from the rsFC analyses revealed a significant relationship between greater rumination and diminished rsFC between the left IsthCing and left precuneus (pFWE <.05). These findings provide novel support for alterations in the neural substrates of ruminative thought in women with PTSD. More broadly, we discuss clinical implications for targeted interventions to reduce rumination through psychotherapy or non-invasive brain stimulation. © 2020 Elsevier Ltd
Author Keywords
Cortical midline structures; Default mode network; Isthmus cingulate; Posttraumatic stress disorder; Precuneus; Rumination
Document Type: Article
Publication Stage: Final
Source: Scopus
“Structure-activity relationship studies and bioactivity evaluation of 1,2,3-triazole containing analogues as a selective sphingosine kinase-2 inhibitors” (2020) European Journal of Medicinal Chemistry
Structure-activity relationship studies and bioactivity evaluation of 1,2,3-triazole containing analogues as a selective sphingosine kinase-2 inhibitors
(2020) European Journal of Medicinal Chemistry, 206, art. no. 112713, .
Tangadanchu, V.K.R.a , Jiang, H.a , Yu, Y.a , Graham, T.J.A.b , Liu, H.c , Rogers, B.E.d , Gropler, R.a , Perlmutter, J.a e , Tu, Z.a
a Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, United States
b Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States
c Department of Surgery, University of Cincinnati, Cincinnati, OH 45267, United States
d Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110, United States
e Departments of Neurology, Neuroscience, Physical Therapy and Occupational Therapy, Washington University School of Medicine, St Louis, MO 63110, United States
Abstract
Sphingosine kinase (SphK) is primarily responsible for the production of Sphingosine-1-phosphate (S1P) that plays an important role in many biological and pathobiological processes including cancer, inflammation, neurological and cardiovascular disorders. Most research has focused on developing inhibitors of SphK1 rather than inhibitors of the other isoform SphK2 which has great importance in several pathophysiologic pathways. Exploration of new analogues for improving the potency and selectivity of SphK2 inhibitors is critical. We now have designed, synthesized, and evaluated eighteen new 1,2,3-triazole analogues for their SphK2 inhibitory activity using a ADP-Glo kinase assay, and explored their in vivo anti-tumor bioactivity. Several compounds including 21c, 21e, 21g, 25e-h, 29a-c have high selectivity for SphK2 over SphK1; compound 21g displayed the highest potency with an IC50 value of 0.23 μM. In addition, three compounds 21a, 21b, and 25b have high anti-tumor activity against U-251 MG human glioblastoma cells. Molecular modeling study was performed to elucidate the polar head group and 1,2,3-triazole pharmacophore impact on the SphK2 selectivity. © 2020 Elsevier Masson SAS
Author Keywords
1,2,3-Triazole hybrids; ADP-Glo; Molecular docking; Selectivity; Sphingosine kinase 2 inhibitors; U-251 MG Human glioblastoma cell
Document Type: Article
Publication Stage: Final
Source: Scopus
“Day-to-Day Variability of Walking Performance Measures in Individuals Poststroke and Individuals With Parkinson Disease” (2020) Journal of Neurologic Physical Therapy: JNPT
Day-to-Day Variability of Walking Performance Measures in Individuals Poststroke and Individuals With Parkinson Disease
(2020) Journal of Neurologic Physical Therapy: JNPT, 44 (4), pp. 241-247.
Holleran, C.L., Bland, M.D., Reisman, D.S., Ellis, T.D., Earhart, G.M., Lang, C.E.
Program in Physical Therapy (C.L.H., M.D.B., G.M.E., C.E.L.), Program in Occupational Therapy (M.D.B., C.E.L.), Department of Neurology (C.L.H., M.D.B., G.M.E., C.E.L.), and Department of Neuroscience (G.M.E.), Washington University School of Medicine, St Louis, Missouri; Department of Physical Therapy, University of Delaware, Newark (D.S.R.); and Department of Physical Therapy & Athletic Training, College of Health & Rehabilitation Sciences: Sargent, Boston University, Boston, Massachusetts (T.D.E.)
Abstract
BACKGROUND AND PURPOSE: Improvement of walking performance is a primary goal for individuals poststroke or with Parkinson disease (PD) who receive physical therapy. More data about day-to-day variability of walking performance are critical for determining if changes in performance have occurred. METHODS: Baseline assessments were utilized from an ongoing, observational, prospective cohort study including 84 individuals poststroke (n = 37) or with PD (n = 47) receiving outpatient physical therapy services to improve mobility. Participants wore step activity monitors for up to 7 days to measure walking performance (steps per day, walking duration, maximum 30-minute output, and peak activity index) in daily life. Correlation analyses evaluated relationships between both capacity and performance measures as well as the relationships between mean performance variables and day-to-day variability. Regression analyses explored factors that contribute to variability in day-to-day performance variables. RESULTS: Mean steps per day for participants poststroke (5376 ± 2804) and with PD (8149 ± 4490) were consistent with previously reported cohorts. Greater amounts of walking were related to more day-to-day variability, with moderate correlations found between the mean and day-to-day variability of each performance measure, regardless of medical diagnosis or walking speed. Day-to-day variability is large (upwards of 50% of the mean), with the amount of walking performance serving as the primary predictor of day-to-day variability in walking performance. DISCUSSION AND CONCLUSIONS: The results of this study elucidate the factors that are related to and predict day-to-day variability of performance. Walking performance metrics should be evaluated over multiple days and greater variability should be anticipated with greater amounts of performance.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A319).
Document Type: Article
Publication Stage: Final
Source: Scopus
“Correlates of 1-Year Change in Quality of Life in Patients with Urologic Chronic Pelvic Pain Syndrome: Findings from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network” (2020) The Journal of Urology
Correlates of 1-Year Change in Quality of Life in Patients with Urologic Chronic Pelvic Pain Syndrome: Findings from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network
(2020) The Journal of Urology, 204 (4), pp. 754-759.
Clemens, J.Q.a , Stephens-Shields, A.J.b , Newcomb, C.c , Rodriguez, L.V.d , Lai, H.H.e , Bradley, C.S.f , Naliboff, B.D.g , Griffith, J.W.h , Taple, B.J.h , Gupta, P.a , Afari, N.i , Harte, S.E.j , Strachan, E.k , Guo, W.b , Landis, J.R.b
a Department of Urology, Michigan Medicine, Ann Arbor, MI, United States
b Department of Biostatistics, Epidemiology & Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
c Center for Clinical Epidemiology & Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
d Departments of Urology & Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, Mexico
e Division of Urologic Surgery, Department of Surgery, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
f Departments of Obstetrics & Gynecology, Carver College of Medicine, University of Iowa, Iowa City, IA, United States
g Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, Mexico
h Department of Medical Social Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, Mexico
i Department of Psychiatry, University of California, San Diego & Virginia San Diego Healthcare System, San Diego, CA, Mexico
j Chronic Pain and Fatigue Research Center, Department of Anesthesiology, University of Michigan, Ann Arbor, MI, United States
k Department of Psychiatry & Behavioral Sciences, Advance Community Health, University of Washington, Seattle, WA, United States
Abstract
PURPOSE: We evaluated and identified baseline factors associated with change in health related quality of life among patients with interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS: A total of 191 men and 233 women with interstitial cystitis/bladder pain syndrome or chronic prostatitis/chronic pelvic pain syndrome (collectively referred to as urologic chronic pelvic pain syndrome) were followed for 12 months with bimonthly completion of the Short Form 12 to assess general mental and physical health related quality of life, and with biweekly assessment of condition specific health related quality of life using the Genitourinary Pain Index. A functional clustering algorithm was used to classify participants as improved, stable or worsened for each health related quality of life measure. Ordinal logistic regression was used to determine baseline factors associated with change. RESULTS: Physical health related quality of life improved in 22% of the participants, mental health related quality of life improved in 25% and condition specific health related quality of life improved in 47%. Better baseline physical health related quality of life, older age and the presence of nonurological symptoms were associated with lower likelihood of improvement in physical health related quality of life. Better baseline mental health related quality of life, female sex, and greater baseline depression and stress were associated with a lower likelihood of improvement in mental health related quality of life. Better baseline condition specific health related quality of life and more severe baseline urologic chronic pelvic pain syndrome pain symptoms were associated with a lower likelihood of improvement in condition specific health related quality of life. CONCLUSIONS: While several nonurologic chronic pelvic pain syndrome factors influenced the trajectory of general health related quality of life over time, only condition specific baseline health related quality of life and urologic chronic pelvic pain syndrome symptoms were associated with urologic chronic pelvic pain syndrome specific health related quality of life change. Significant differences in how urologic chronic pelvic pain syndrome impacts various aspects of health related quality of life suggest a multidisciplinary approach to assessment and treatment of these patients.
Author Keywords
cystitis; interstitial; prostatitis
Document Type: Article
Publication Stage: Final
Source: Scopus
“People with Parkinson disease with and without freezing of gait respond similarly to external and self-generated cues” (2020) Gait and Posture
People with Parkinson disease with and without freezing of gait respond similarly to external and self-generated cues
(2020) Gait and Posture, 82, pp. 161-166.
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, St Louis, MO, 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: Gait deficits in Parkinson disease (PD), including freezing of gait (FOG), can be among the most debilitating symptoms. Rhythmic auditory cueing has been used to alleviate some gait symptoms. However, different cue types, such as externally-generated and self-generated cues, affect gait variability differently. The differential effects of these cue types on people with PD with FOG (PD + FOG), who often have higher gait variability, and those with PD without FOG (PD-FOG) is unknown. Given the relationship of gait variability to fall risk, this is an important area to address. Research question: This study aims to 1) confirm the association between falls and gait variability measures in PD-FOG, PD + FOG and age-matched Controls; 2) investigate the effects of different cue types on gait variability in PD-FOG and PD + FOG; and 3) determine whether baseline gait characteristics are associated with response to cues. Methods: This cross-sectional study investigated PD-FOG (n = 24), PD + FOG (n = 20), and Controls (n = 24). Gait trials were collected during use of externally-generated and self-generated cues for all participants. Gait variability measures were the primary outcomes to assess the effects of rhythmic auditory cues. Results: Logistic regression models showed increased gait variability was associated with falls across groups. Repeated measures ANOVAs showed externally-generated cues increased gait variability, whereas self-generated cues did not, for all groups. Pearson’s correlations showed participants with higher baseline gait variability had greater reduction in gait variability with rhythmic auditory cueing. Significance: Higher gait variability is associated with falls. This study demonstrates that PD + FOG are capable of using self-generated cues without increasing gait variability measures, thereby stabilizing gait. People with higher baseline gait variability are likely to experience the largest reductions in variability with the addition of external cues. © 2020 Elsevier B.V.
Author Keywords
Falls; Freezing; Gait variability; Parkinson disease
Document Type: Article
Publication Stage: Final
Source: Scopus
“The Mind of a Mouse” (2020) Cell
The Mind of a Mouse
(2020) Cell, 182 (6), pp. 1372-1376.
Abbott, L.F.a , Bock, D.D.b , Callaway, E.M.c , Denk, W.d , Dulac, C.e , Fairhall, A.L.f , Fiete, I.g , Harris, K.M.h , Helmstaedter, M.i , Jain, V.j , Kasthuri, N.k , LeCun, Y.l , Lichtman, J.W.m , Littlewood, P.B.n , Luo, L.o , Maunsell, J.H.R.p , Reid, R.C.q , Rosen, B.R.r , Rubin, G.M.s , Sejnowski, T.J.c t , Seung, H.S.u , Svoboda, K.s , Tank, D.W.v , Tsao, D.w , Van Essen, D.C.x
a Zuckerman Mind, Brain and Behavior Institute, Department of Neuroscience, Department of Physiology and Cellular Biophysics, Columbia University, New York, NY, United States
b Larner College of Medicine, University of Vermont, Burlington, VT, United States
c Salk Institute for Biological Studies, La Jolla, CA, United States
d Max Planck Institute of Neurobiology, Martinsried, Germany
e Howard Hughes Medical Institute and Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, MA, United States
f Department of Physiology and Biophysics and Computational Neuroscience Center, University of Washington, Seattle, WA, United States
g Department of Brain and Cognitive Sciences and McGovern Institute, MIT, Cambridge, MA, United States
h Center for Learning and Memory, Institute for Neuroscience, University of Texas – Austin, Austin, TX, United States
i Department of Connectomics, Max Planck Institute for Brain Research, Frankfurt, Germany
j Google Research, Mountain View, CA, United States
k Argonne National Laboratory and Department of Neurobiology, University of Chicago, Chicago, IL, United States
l Courant Institute, Center for Data Science and Center for Neural Science, New York University and Facebook AI Research, New York, NY, United States
m Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, United States
n Department of Physics and James Franck Institute, University of Chicago, Chicago, IL, United States
o Howard Hughes Medical Institute, Department of Biology, Stanford University, Stanford, CA, United States
p Department of Neurobiology and Grossman Institute for Neuroscience, Quantitative Biology and Human Behavior, University of Chicago, Chicago, IL, United States
q Allen Institute for Brain Science, Seattle, WA, United States
r Athinoula A. Martinos Center for Biomedical Imaging and Department of Radiology, Harvard Medical School, Boston, MA, United States
s Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, United States
t Division of Biological Sciences, University of California, San Diego, San Diego, CA, United States
u Department of Computer Science and Princeton Neuroscience Institute, Princeton University, Princeton, NJ, United States
v Princeton Neuroscience Institute, Princeton University, Princeton, NJ, United States
w Division of Biology and Biological Engineering, Tianqiao and Chrissy Chen Institute for Neuroscience and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA, United States
x Neuroscience Department, Washington University School of Medicine, St. Louis, MO, United States
Abstract
Large scientific projects in genomics and astronomy are influential not because they answer any single question but because they enable investigation of continuously arising new questions from the same data-rich sources. Advances in automated mapping of the brain’s synaptic connections (connectomics) suggest that the complicated circuits underlying brain function are ripe for analysis. We discuss benefits of mapping a mouse brain at the level of synapses. © 2020 Elsevier Inc.
Large scientific projects in genomics and astronomy are influential not because they answer any single question but because they enable investigation of continuously arising new questions from the same data-rich sources. Advances in automated mapping of the brain’s synaptic connections (connectomics) suggest that the complicated circuits underlying brain function are ripe for analysis. We discuss benefits of mapping a mouse brain at the level of synapses. © 2020 Elsevier Inc.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Photoreceptor responses to light in the pathogenesis of diabetic retinopathy” (2020) Visual Neuroscience
Photoreceptor responses to light in the pathogenesis of diabetic retinopathy
(2020) Visual Neuroscience, 37, p. E007.
Majidi, S.P.a b , Rajagopal, R.a
a Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, United States
b MD-PhD Program, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
Vision loss, among the most feared complications of diabetes, is primarily caused by diabetic retinopathy, a disease that manifests in well-recognized, characteristic microvascular lesions. The reasons for retinal susceptibility to damage in diabetes are unclear, especially considering that microvascular networks are found in all tissues. However, the unique metabolic demands of retinal neurons could account for their vulnerability in diabetes. Photoreceptors are the first neurons in the visual circuit and are also the most energy-demanding cells of the retina. Here, we review experimental and clinical evidence linking photoreceptors to the development of diabetic retinopathy. We then describe the influence of retinal illumination on photoreceptor metabolism, effects of light modulation on the severity of diabetic retinopathy, and recent clinical trials testing the treatment of diabetic retinopathy with interventions that impact photoreceptor metabolism. Finally, we introduce several possible mechanisms that could link photoreceptor responses to light and the development of retinal vascular disease in diabetes. Collectively, these concepts form the basis for a growing body of investigative efforts aimed at developing novel pharmacologic and nonpharmacologic tools that target photoreceptor physiology to treat a very common cause of blindness across the world.
Author Keywords
Diabetic retinopathy; light deprivation; metabolism; photoreceptor; phototransduction; visual cycle
Document Type: Article
Publication Stage: Final
Source: Scopus
“Testosterone and hippocampal trajectories mediate relationship of poverty to emotion dysregulation and depression” (2020) Proceedings of the National Academy of Sciences of the United States of America
Testosterone and hippocampal trajectories mediate relationship of poverty to emotion dysregulation and depression
(2020) Proceedings of the National Academy of Sciences of the United States of America, 117 (36), pp. 22015-22023.
Barch, D.M.a b c , Shirtcliff, E.A.d , Elsayed, N.M.e , Whalen, D.b , Gilbert, K.b , Vogel, A.C.b , Tillman, R.b , Luby, J.L.b
a Department of Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO 63130;
b Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63130
c Department of Radiology, Washington University in St. Louis, St. Louis, MO 63130
d Department of Human Development Family Studies, Iowa State University, Ames, IA 50011, United States
e Department of Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO 63130
Abstract
There is robust evidence that early poverty is associated with poor developmental outcomes, including impaired emotion regulation and depression. However, the specific mechanisms that mediate this risk are less clear. Here we test the hypothesis that one pathway involves hormone mechanisms (testosterone and DHEA) that contribute to disruption of hippocampal brain development, which in turn contributes to perturbed emotion regulation and subsequent risk for depression. To do so, we used data from 167 children participating in the Preschool Depression Study, a longitudinal study that followed children from preschool (ages 3 to 5 y) to late adolescence, and which includes prospective assessments of poverty in preschool, measures of testosterone, DHEA, and hippocampal volume across school age and adolescence, and measures of emotion regulation and depression in adolescence. Using multilevel modeling and linear regression, we found that early poverty predicted shallower increases of testosterone, but not DHEA, across development, which in turn predicted shallower trajectories of hippocampal development. Further, we found that early poverty predicted both impaired emotion regulation and depression. The relationship between early poverty and self-reported depression in adolescence was explained by serial mediation through testosterone to hippocampus to emotion dysregulation. There were no significant interactions with sex. These results provide evidence about a hormonal pathway by which early poverty may contribute to disrupted brain development and risk for mental health problems later in life. Identification of such pathways provide evidence for potential points of intervention that might help mitigate the impact of early adversity on brain development.
Author Keywords
development; emotion regulation; hippocampus; poverty; testosterone
Document Type: Article
Publication Stage: Final
Source: Scopus
“A Critical, Event-Related Appraisal of Denoising in Resting-State fMRI Studies” (2020) Cerebral Cortex (New York, N.Y. : 1991)
A Critical, Event-Related Appraisal of Denoising in Resting-State fMRI Studies
(2020) Cerebral Cortex (New York, N.Y. : 1991), 30 (10), pp. 5544-5559.
Power, J.D.a , Lynch, C.J.b , Adeyemo, B.c , Petersen, S.E.c
a Sackler Institute for Developmental Psychobiology, Department of Psychiatry, Weill Cornell Medicine, 1300 York Avenue, NY, NY 10065, United States
b Brain and Mind Research Institute, Weill Cornell Medicine, 1300 York Avenue, NY, NY 10065, United States
c Departments of Neurology and Psychology, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, USA
Abstract
This article advances two parallel lines of argument about resting-state functional magnetic resonance imaging (fMRI) signals, one empirical and one conceptual. The empirical line creates a four-part organization of the text: (1) head motion and respiration commonly cause distinct, major, unwanted influences (artifacts) in fMRI signals; (2) head motion and respiratory changes are, confoundingly, both related to psychological and clinical and biological variables of interest; (3) many fMRI denoising strategies fail to identify and remove one or the other kind of artifact; and (4) unremoved artifact, due to correlations of artifacts with variables of interest, renders studies susceptible to identifying variance of noninterest as variance of interest. Arising from these empirical observations is a conceptual argument: that an event-related approach to task-free scans, targeting common behaviors during scanning, enables fundamental distinctions among the kinds of signals present in the data, information which is vital to understanding the effects of denoising procedures. This event-related perspective permits statements like “Event X is associated with signals A, B, and C, each with particular spatial, temporal, and signal decay properties”. Denoising approaches can then be tailored, via performance in known events, to permit or suppress certain kinds of signals based on their desirability. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.
Author Keywords
censoring; functional connectivity; global signal; multiecho; validity
Document Type: Article
Publication Stage: Final
Source: Scopus
“Association between supratentorial pediatric high-grade gliomas involved with the subventricular zone and decreased survival: A multi-institutional retrospective study” (2020) Journal of Neurosurgery: Pediatrics
Association between supratentorial pediatric high-grade gliomas involved with the subventricular zone and decreased survival: A multi-institutional retrospective study
(2020) Journal of Neurosurgery: Pediatrics, 26 (3), pp. 288-294.
Mistry, A.M.a , Mummareddy, N.b , CreveCoeur, T.S.c , Lillard, J.C.d , Vaughn, B.N.d , Gallant, J.-N.e , Hale, A.T.e , Griffin, N.c , Wellons, J.C., Iiia f , Limbrick, D.D., Jr.g , Klimo, P., Jr.d , Naftel, R.P.a f
a Department of Neurological Surgery, Vanderbilt University Medical Center, United States
b School of Medicine, Vanderbilt University, Nashville, TN, United States
c School of Medicine, Washington University, St. Louis, MI, United States
d Department of Neurological Surgery, University of Tennessee Health Science Center, Memphis, United States
e Medical Scientist Training Program, School of Medicine, Vanderbilt University, Nashville, United States
f Vanderbilt Children’s Hospital, Nashville, TN, United States
g Department of Neurosurgery, Washington University, St. Louis, MI, United States
Abstract
OBJECTIVE The subventricular zone (SVZ), housed in the lateral walls of the lateral ventricles, is the largest neurogenic niche in the brain. In adults, high-grade gliomas in contact or involved with the SVZ are associated with decreased survival. Whether this association holds true in the pediatric population remains unexplored. To address this gap in knowledge, the authors conducted this retrospective study in a pediatric population with high-grade gliomas treated at three comprehensive centers in the United States. METHODS The authors retrospectively identified 63 patients, age = 21 years, with supratentorial WHO grade III-IV gliomas treated at three academic centers. Basic demographic and clinical data regarding presenting signs and symptoms and common treatment variables were obtained. Preoperative MRI studies were evaluated to assess SVZ contact by tumor and to quantify tumor volume. RESULTS Sixty-three patients, including 34 males (54%), had a median age of 12.3 years (IQR 6.50-16.2) and a median tumor volume of 39.4 ml (IQR 19.4-65.8). Tumors contacting the SVZ (SVZ+) were noted in 34 patients (54%) and overall were larger than those not in contact with the SVZ (SVZ-; 51.1 vs 27.3, p = 0.002). The SVZ+ tumors were also associated with decreased survival. However, age, tumor volume, tumor grade, and treatment with chemotherapy and/or radiation were not associated with survival in the 63 patients. In the univariable analysis, near-total resection, gross-total resection, and seizure presentation were associated with increased survival (HR = 0.23, 95% CI 0.06-0.88, p = 0.03; HR = 0.26, 95% CI 0.09-0.74, p = 0.01; and HR = 0.46, 95% CI 0.22-0.97, p = 0.04, respectively). In a multivariable stepwise Cox regression analysis, only SVZ+ tumors remained significantly associated with decreased survival (HR = 1.94, 95% CI 1.03-3.64, p = 0.04). CONCLUSIONS High-grade glioma contact with the SVZ neural stem cell niche was associated with a significant decrease in survival in the pediatric population, as it is in the adult population. This result suggests that tumor contact with the SVZ is a general negative prognosticator in high-grade glioma independent of age group and invites biological investigations to understand the SVZ’s role in glioma pathobiology. © 2020 American Association of Neurological Surgeons. All rights reserved.
Author Keywords
Glioblastoma; Glioma; Oncology; Pediatric brain tumors; Subventricular zone; Survival
Document Type: Article
Publication Stage: Final
Source: Scopus
“Blood Pressure Profiles in Infants With Hypoxic Ischemic Encephalopathy (HIE), Response to Dopamine, and Association With Brain Injury” (2020) Frontiers in Pediatrics
Blood Pressure Profiles in Infants With Hypoxic Ischemic Encephalopathy (HIE), Response to Dopamine, and Association With Brain Injury
(2020) Frontiers in Pediatrics, 8, art. no. 512, .
Pazandak, C.a , McPherson, C.a , Abubakar, M.b , Zanelli, S.b , Fairchild, K.b , Vesoulis, Z.a
a Division of Newborn Medicine, Department of Pediatrics, Washington University School of Medicine, Saint Louis, MO, United States
b Department of Pediatrics, University of Virginia, Charlottesville, VA, United States
Abstract
Objective: To describe mean arterial blood pressure (MABP), responsiveness to dopamine, and relationship to brain injury in infants with moderate/severe hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). We hypothesized that, when utilized, dopamine would rapidly and effectively increase MABP in treated patients. Methods: Continuous arterial blood pressure measurements were prospectively recorded from infants with moderate/severe HIE undergoing TH in a multi-institutional cohort from 2010 to 2018. Treatment with dopamine was at the discretion of the medical team for hypotension/hypoperfusion. MABP values of treated infants were compared to those obtained at an equivalent time period in control infants receiving TH but not dopamine (24 h after birth). MRI was obtained per unit protocols and included T1/T2/DWI sequences. Injury was classified as no injury/mild injury or moderate/severe injury using a standardized scoring system. Seizures were confirmed with conventional EEG. Results: Eighteen infants were treated with dopamine and were similar to untreated controls (n = 36) with the exception of lower cord gas pH (6.92 ± 0.2 vs. 7.07 ± 0.2, p < 0.05). Dopamine was initiated at a mean of 24 h after birth. MABP was significantly lower in the dopamine group at the start of therapy (39.9 ± 2.0 vs. 49.1 ± 1.3, p < 0.01) and 1 h later (44.3 ± 2.0 vs. 49.8 ± 1.1, p < 0.05). However, after 9 h of treatment, dopamine increased the MABP by an average of 9 mmHg and MABP values were similar to untreated controls for the remainder of the observation period. There were no significant differences in rates of seizures, brain injury, or death. Conclusion: Neonates with moderate/severe HIE treated with dopamine during TH had MABP significantly lower than controls. The majority of infants responded to dopamine monotherapy following adequate volume resuscitation. An association between requirement for dopamine and severity of brain injury was not detected. © Copyright © 2020 Pazandak, McPherson, Abubakar, Zanelli, Fairchild and Vesoulis.
Author Keywords
blood pressure; brain injury; dopamine; hypoxic ischemic encephalopathy; neonate; neurology; seizures; therapeutic hypothermia
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Abnormal preoperative cognitive screening in aged surgical patients: a retrospective cohort analysis” (2020) British Journal of Anaesthesia
Abnormal preoperative cognitive screening in aged surgical patients: a retrospective cohort analysis
(2020) British Journal of Anaesthesia, .
Gregory, S.H., King, C.R., Ben Abdallah, A., Kronzer, A., Wildes, T.S.
Department of Anesthesiology, Washington University in St. Louis, St. Louis, MO, United States
Abstract
Background: Preoperative cognitive dysfunction has been associated with adverse postoperative outcomes. There are limited data characterising the epidemiology of preoperative cognitive dysfunction in older surgical patients. Methods: This retrospective cohort included all patients ≥65 yr old seen at the Washington University preoperative clinic between January 2013 and June 2018. Cognitive screening was performed using the Short-Blessed Test (SBT) and Eight-Item Interview to Differentiate Aging and Dementia (AD8) screen. The primary outcome of abnormal cognitive screening was defined as SBT score ≥5 or AD8 score ≥2. Multivariable logistic regression was used to identify associated factors. Results: Overall, 21 666 patients ≥65 yr old completed screening during the study period; 23.5% (n=5099) of cognitive screens were abnormal. Abnormal cognitive screening was associated with increasing age, decreasing BMI, male sex, non-Caucasian race, decreased functional independence, and decreased metabolic functional capacity. Patients with a history of stroke or transient ischaemic attack, chronic obstructive pulmonary disease, diabetes mellitus, hepatic cirrhosis, and heavy alcohol use were also more likely to have an abnormal cognitive screen. Predictive modelling showed no combination of patient factors was able to reliably identify patients who had a <10% probability of abnormal cognitive screening. Conclusions: Routine preoperative cognitive screening of unselected aged surgical patients often revealed deficits consistent with cognitive impairment or dementia. Such deficits were associated with increased age, decreased function, decreased BMI, and several common medical comorbidities. Further research is necessary to characterise the clinical implications of preoperative cognitive dysfunction and identify interventions that may reduce related postoperative complications. © 2020 British Journal of Anaesthesia
Author Keywords
cognitive screening; dementia screening; geriatric surgery; neurocognitive dysfunction; perioperative medicine; preoperative assessment
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Sleep and self-regulation in early childhood” (2020) Advances in Child Development and Behavior
Sleep and self-regulation in early childhood
(2020) Advances in Child Development and Behavior, .
Breitenstein, R.S.a , Hoyniak, C.P.b , McQuillan, M.E.c , Bates, J.E.a
a Department of Psychological and Brain Sciences, Indiana University—Bloomington, Bloomington, IN, United States
b Department of Psychiatry, Washington University, School of Medicine, St. Louis, MO, United States
c Department of Pediatrics, Indiana University, School of Medicine, Indianapolis, IN, United States
Abstract
What is the role of sleep in children’s behavioral, emotional, and cognitive regulation? This chapter considers theoretical and conceptual links between sleep and self-regulation, with special attention to sleep and self-regulation in early childhood. We selectively review the growing body of research on associations between sleep and self-regulation, mentioning some methodological issues. We also consider how child characteristics and sociocontextual factors may interact with sleep in the development of self-regulation in early childhood. We provide some relevant empirical examples from our own research. © 2020 Elsevier Inc.
Author Keywords
Early childhood; Executive functioning; Self-regulation; Sleep; Sleep problems
Document Type: Book Chapter
Publication Stage: Article in Press
Source: Scopus
“The Brain Chart of Aging: Machine-learning analytics reveals links between brain aging, white matter disease, amyloid burden, and cognition in the iSTAGING consortium of 10,216 harmonized MR scans” (2020) Alzheimer’s and Dementia
The Brain Chart of Aging: Machine-learning analytics reveals links between brain aging, white matter disease, amyloid burden, and cognition in the iSTAGING consortium of 10,216 harmonized MR scans
(2020) Alzheimer’s and Dementia, .
Habes, M.a b u v , Pomponio, R.u v , Shou, H.c v v , Doshi, J.u v v , Mamourian, E.u v v , Erus, G.u v v , Nasrallah, I.u v v , Launer, L.J.d , Rashid, T.u v v , Bilgel, M.e , Fan, Y.u v v , Toledo, J.B.f g , Yaffe, K.h , Sotiras, A.i v v , Srinivasan, D.u v v , Espeland, M.j , Masters, C.k , Maruff, P.k , Fripp, J.l , Völzk, H.m , Johnson, S.C.n , Morris, J.C.o , Albert, M.S.p , Miller, M.I.q , Bryan, R.N.r , Grabe, H.J.s t , Resnick, S.M.e , Wolk, D.A.a v v , Davatzikos, C.u v v , for the iSTAGING consortium, the Preclinical AD consortium, the ADNI, and the CARDIA studiesv
a Department of Neurology and Penn Memory Center, University of Pennsylvania, Philadelphia, PA, United States
b Neuroimage Analytics Laboratory and Biggs Institute Neuroimaging Core, Glenn Biggs Institute for Neurodegenerative Disorders, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
c Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, United States
d Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD, United States
e Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD, United States
f Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, United States
g Stanley Appel Department of Neurology, Houston Methodist Hospital, Houston, TX, United States
h Departments of Neurology, Psychiatry and Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, United States
i Department of Radiology, Washington University in St. Louis, St. Louis, MO, United States
j Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC, United States
k Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia
l CSIRO Health and Biosecurity, Australian e-Health Research Centre CSIRO, Australia
m Institute for Community Medicine, University of Greifswald, Greifswald, Germany
n Wisconsin Alzheimer’s Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
o Department of Neurology, Washington University in St. Louis, St. Louis, MO, United States
p Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
q Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States
r Department of Diagnostic Medicine, University of Texas, Austin, TX, United States
s Department of Psychiatry and Psychotherapy, University of Greifswald, Germany
t German Center for Neurodegenerative Diseases (DZNE), Rostock, Greifswald, Germany
u Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States
v Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA, United States
Abstract
Introduction: Relationships between brain atrophy patterns of typical aging and Alzheimer’s disease (AD), white matter disease, cognition, and AD neuropathology were investigated via machine learning in a large harmonized magnetic resonance imaging database (11 studies; 10,216 subjects). Methods: Three brain signatures were calculated: Brain-age, AD-like neurodegeneration, and white matter hyperintensities (WMHs). Brain Charts measured and displayed the relationships of these signatures to cognition and molecular biomarkers of AD. Results: WMHs were associated with advanced brain aging, AD-like atrophy, poorer cognition, and AD neuropathology in mild cognitive impairment (MCI)/AD and cognitively normal (CN) subjects. High WMH volume was associated with brain aging and cognitive decline occurring in an ≈10-year period in CN subjects. WMHs were associated with doubling the likelihood of amyloid beta (Aβ) positivity after age 65. Brain aging, AD-like atrophy, and WMHs were better predictors of cognition than chronological age in MCI/AD. Discussion: A Brain Chart quantifying brain-aging trajectories was established, enabling the systematic evaluation of individuals’ brain-aging patterns relative to this large consortium. © 2020 the Alzheimer’s Association
Author Keywords
Alzheimer’s disease pathology; beta-amyloid; brain aging; brain signatures; cognitive testing; Dementia; harmonized neuroimaging cohorts; Machine Learning; MRI; Neuroimaging; PET; preclinical Alzheimer’s disease; small vessel ischemic disease; tau
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Estrogen, brain structure, and cognition in postmenopausal women” (2020) Human Brain Mapping
Estrogen, brain structure, and cognition in postmenopausal women
(2020) Human Brain Mapping, .
Boyle, C.P.a , Raji, C.A.b , Erickson, K.I.c , Lopez, O.L.d , Becker, J.T.c d e , Gach, H.M.f , Kuller, L.H.g , Longstreth, W., Jr.h , Carmichael, O.T.i , Riedel, B.C.a j , Thompson, P.M.a
a Imaging Genetics Center, Mark & Mary Stevens Institute for Neuroimaging & Informatics, Keck School of Medicine, University of Southern California, Marina del Rey, CA, United States
b Mallinckrodt Institute of Radiology, Washington University, St. Louis, MO, United States
c Department of Psychology, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
d Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
e Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
f Departments of Radiation Oncology, Radiology, and Biomedical Engineering, Washington University, St. Louis, MO, United States
g Department of Epidemiology, University of Pittsburgh, Graduate School of Public Health, Pittsburgh, PA, United States
h Departments of Neurology and Epidemiology, University of Washington, Seattle, WA, United States
i Pennington Biomedical Research Center, Baton Rouge, LA, United States
j Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States
Abstract
Declining estrogen levels before, during, and after menopause can affect memory and risk for Alzheimer’s disease. Undesirable side effects of hormone variations emphasize a role for hormone therapy (HT) where possible benefits include a delay in the onset of dementia—yet findings are inconsistent. Effects of HT may be mediated by estrogen receptors found throughout the brain. Effects may also depend on lifestyle factors, timing of use, and genetic risk. We studied the impact of self-reported HT use on brain volume in 562 elderly women (71–94 years) with mixed cognitive status while adjusting for aforementioned factors. Covariate-adjusted voxelwise linear regression analyses using a model with 16 predictors showed HT use as positively associated with regional brain volumes, regardless of cognitive status. Examinations of other factors related to menopause, oophorectomy and hysterectomy status independently yielded positive effects on brain volume when added to our model. One interaction term, HTxBMI, out of several examined, revealed significant negative association with overall brain volume, suggesting a greater reduction in brain volume than BMI alone. Our main findings relating HT to regional brain volume were as hypothesized, but some exploratory analyses were not in line with existing hypotheses. Studies suggest lower levels of estrogen resulting from oophorectomy and hysterectomy affect brain volume negatively, and the addition of HT modifies the relation between BMI and brain volume positively. Effects of HT may depend on the age range assessed, motivating studies with a wider age range as well as a randomized design. © 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC
Author Keywords
Alzheimer’s disease; Brain volume; hormone therapy
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Association of sex and APOE ∈4 with brain tau deposition and atrophy in older adults with Alzheimer’s disease” (2020) Theranostics
Association of sex and APOE ∈4 with brain tau deposition and atrophy in older adults with Alzheimer’s disease
(2020) Theranostics, 10 (23), pp. 10563-10572.
Yan, S.a b , Zheng, C.b , Paranjpe, M.D.c , Li, J.b , Benzinger, T.L.S.b d , Lu, J.a , Zhou, Y.b
a Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing, China
b Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
c Harvard-MIT Program in Health Sciences and Technology, Harvard Medical School, Boston, MA, United States
d Department of Neurology, Washington in St. Louis University School of Medicine, St. Louis, MO, United States
Abstract
The objective of this study was to assess the association of sex and the apolipoprotein E (APOE) ∈4 allele with brain tau deposition and atrophy in older adults with Alzheimer’s disease (AD) using quantitative 18F-AV-1451 positron emission tomography (PET) and magnetic resonance imaging (MRI). Methods: Preprocessed 18F-AV-1451 tau PET, raw T1-weighted structural MR images, demographic information, cerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated tau (p-tau) measurements from 57 elderly individuals with AD were downloaded from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. An iteratively reblurred Van Cittert partial volume correction (PVC) method was applied to all preprocessed PET images. MRI images were used for PET spatial normalization and gray matter volume calculation. 18F-AV-1451 PET standardized uptake value ratio (SUVR) was calculated relative to the cerebellum gray matter. The effect of sex and APOE ∈4 status on SUVR and gray matter volume were assessed at both region of interest (ROI) and voxelwise levels. Results: Female APOE ∈4 carriers (FACs) had significant higher 18F-AV-1451 SUVRs in the lateral temporal, parietal, posterior cingulate, medial temporal, inferior temporal, entorhinal cortex, amygdala and parahippocampal gyrus regions, and exhibited smaller gray matter volumes in the posterior cingulate, medial temporal, inferior temporal and amygdala regions, as compared to the non-FACs (NFACs) comprised of female APOE ∈4 non-carriers, male APOE ∈4 carriers and male APOE ∈4 non-carriers. Voxelwise analysis revealed forebrain and limbic clusters with greater 18F-AV-1451 SUVRs and lower gray matter volume between FACs compared to the NFACs. Negative correlations between ROI 18F-AV-1451 SUVRs and gray matter volumes were significant after adjusting for age and years of education. Conclusions: Among elderly individuals with AD, sex modified the effects of the APOE ∈4 allele on region-specific tau deposition and gray matter volume. FACs had elevated brain region-specific tau PET SUVR and decreased gray matter volume in comparison to NFACs. The study provides a basis for the use of precision medicine in the diagnosis of AD and evaluation of therapeutics using 18F-AV-1451 PET and structural MRI. © 2020 Ivyspring International Publisher. All rights reserved.
Author Keywords
Alzheimer’s disease; APOE; Neurodegeneration; Sex; Tau PET
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Multiscale Mechanobiology of Brain Injury: Axonal Strain Redistribution” (2020) Biophysical Journa
Multiscale Mechanobiology of Brain Injury: Axonal Strain Redistribution
(2020) Biophysical Journal, .
Shakiba, D.a , Zhao, W.b , Ji, S.b
a Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, MO, United States
b Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, United States
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Optimizing hand-function patient outcome measures for inclusion body myositis” (2020) Neuromuscular Disorders
Optimizing hand-function patient outcome measures for inclusion body myositis
(2020) Neuromuscular Disorders, .
Lin, A.Y.a , Siener, C.S.b , Faino, A.V.c , Seiffert, M.b , Weihl, C.C.b , Wang, L.H.d
a Department of Neurology, Stanford University, Stanford Neuroscience Health Center, 213 Quarry Road, M/C 5956, Palo Alto, CA 94305, United States
b Department of Neurology, Washington University in St. Louis, 660 S. Euclid, Campus Box 8111, St. Louis, MO 63110, United States
c Children’s Core for Biomedical Statistics, Seattle Children’s Research Institute, Seattle, WA, United States
d Department of Neurology, University of Washington Medical Center, Box 356465, 1959 NE Pacific Street. SeattleWA 98195-6465, United States
Abstract
Inclusion body myositis is the most commonly acquired myopathy after the age of 45. The slowly progressive and heterogeneous disorder is a challenge for measuring clinical trial efficacy. One current method for measuring progression utilizes the Inclusion Body Myositis-Functional Rating Scale. We have found that the upper extremity domain scores in the Inclusion Body Myositis-Functional Rating Scale do not consistently change until there is extreme loss of grip and finger flexor strength. Therefore, we performed a cross-sectional observational study of 83 inclusion body myositis patients and 38 controls recruited at the 2019 Annual Patient Conference of The Myositis Association. We evaluated new Inclusion Body Myositis Patient-Reported Outcome measures for upper extremity function modified from the NIH Patient-Reported Outcomes Measurement Information System as well as pinch and grip strength. We found that Patient-Reported Outcome measures hand-function have a higher correlation with pinch and grip strength than the Inclusion Body Myositis-Functional Rating Scale. © 2020 Elsevier B.V.
Author Keywords
Functional rating scale; Grip strength; Inclusion body myositis; Outcome measures; Patient reported outcome; Pinch strength
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Baseline Prevalence of Polypharmacy in Older Hypertensive Study Subjects with Elevated Dementia Risk: Findings from the Risk Reduction for Alzheimer’s Disease Study (rrAD)” (2020) Journal of Alzheimer’s Disease: JAD
Baseline Prevalence of Polypharmacy in Older Hypertensive Study Subjects with Elevated Dementia Risk: Findings from the Risk Reduction for Alzheimer’s Disease Study (rrAD)
(2020) Journal of Alzheimer’s Disease: JAD, 77 (1), pp. 175-182.
Vidoni, E.D.a b , Kamat, A.a , Gahan, W.P.c , Ourso, V.c , Woodard, K.c , Kerwin, D.R.d , Binder, E.F.e , Burns, J.M.a b , Cullum, M.d f , Hynan, L.S.d g , Vongpatanasin, W.h , Zhu, D.C.i , Zhang, R.d h , Keller, J.N.c
a KU Alzheimer’s Disease Center, United States
b Department of Neurology, University of Kansas Medical Center, Kansas City, United States
c Pennington Biomedical Research Center, LA, Baton Rouge, United States
d Department of Neurology & Neurotherapeutics, UT Southwestern Medical Center, TX, Dallas, United States
e Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
f Department of Psychiatry, UT Southwestern Medical Center, TX, Dallas, United States
g Department of Population and Data Sciences, UT Southwestern Medical Center, TX, Dallas, United States
h Department of Internal Medicine, UT Southwestern Medical Center, TX, Dallas, United States
i Department of Radiology and Cognitive Imaging Research Center, Michigan State University, MI, East Lansing, United States
Abstract
BACKGROUND: Little is known about the prevalence of polypharmacy, the taking of five or more medications a day, in older adults with specific dementia risk factors. OBJECTIVE: To examine the prevalence of polypharmacy in participants at baseline in a vascular risk reduction focused Alzheimer’s disease (rrAD) trial targeting older patients with hypertension and elevated dementia risk. METHODS: We conducted a detailed review of medications in a cross-sectional study of community-dwelling older adults with hypertension and elevated dementia risk. Medications were identified in a structured interview process with an onsite pharmacist or qualified designee. Polypharmacy was defined as use of five or more medications on a regular basis. Descriptive analyses were conducted on the sample as well as direct comparisons of subgroups of individuals with hypertension, diabetes, and hyperlipidemia. RESULTS: The 514 rrAD participants, mean age 68.8 (standard deviation [sd] 6), reported taking different combinations of 472 unique medications at their baseline visit. The median number of medications taken by participants was eight [Range 0-21], with 79.2% exhibiting polypharmacy (n = 407). Sites differed in their prevalence of polypharmacy, χ2(3) = 56.0, p < 0.001. A nearly identical percentage of the 2,077 prescribed (51.8%) and over the counter (48.2%) medications were present in the overall medication profile. The presence of diabetes (87.5%), hyperlipidemia (88.2%), or both (97.7%) was associated with a higher prevalence of polypharmacy than participants who exhibited hypertension in the absence of either of these conditions (63.2%), χ2(3) = 35.8, p < 0.001. CONCLUSION: Participants in a dementia risk study had high levels of polypharmacy, with the co-existence of diabetes or hyperlipidemia associated with a greater prevalence of polypharmacy as compared to having hypertension alone.
Author Keywords
Alzheimer’s disease; dementia; hypertension; inappropriate medication; polypharmacy; risk factor
Document Type: Article
Publication Stage: Final
Source: Scopus
“The Future of Women in Psychological Science” (2020) Perspectives on Psychological Science
The Future of Women in Psychological Science
(2020) Perspectives on Psychological Science, .
Gruber, J.a , Mendle, J.b , Lindquist, K.A.c , Schmader, T.d , Clark, L.A.e , Bliss-Moreau, E.f , Akinola, M.g , Atlas, L.h , Barch, D.M.i j , Barrett, L.F.k l , Borelli, J.L.m , Brannon, T.N.n , Bunge, S.A.o , Campos, B.m p , Cantlon, J.q , Carter, R.r , Carter-Sowell, A.R.s , Chen, S.o , Craske, M.G.n , Cuddy, A.J.C.t , Crum, A.u , Davachi, L.v , Duckworth, A.L.w , Dutra, S.J.x , Eisenberger, N.I.o , Ferguson, M.y , Ford, B.Q.z , Fredrickson, B.L.c , Goodman, S.H.aa , Gopnik, A.o , Greenaway, V.P.v , Harkness, K.L.ab , Hebl, M.ac , Heller, W.ad , Hooley, J.ae , Jampol, L.af , Johnson, S.L.o , Joormann, J.ag , Kinzler, K.D.y , Kober, H.x ag , Kring, A.M.o , Paluck, E.L.ah , Lombrozo, T.ah , Lourenco, S.F.aa , McRae, K.ai , Monin, J.K.aj , Moskowitz, J.T.ak , Natsuaki, M.N.al , Oettingen, G.am , Pfeifer, J.H.an , Prause, N.ao , Saxbe, D.ap , Smith, P.K.aq , Spellman, B.A.ar , Sturm, V.as , Teachman, B.A.at , Thompson, R.J.i , Weinstock, L.M.au , Williams, L.A.av
a Department of Psychology and Neuroscience, University of Colorado Boulder, United States
b Department of Human Development, Cornell University, United States
c Department of Psychology, University of North Carolina Chapel Hill, United States
d Department of Psychology, University of British Columbia, Canada
e Department of Psychology, University of Notre Dame, United States
f Department of Psychology, University of California, Davis, the California National Primate Research Center, Davis, CA, United States
g Columbia Business School, Columbia University, United States
h National Center for Complementary and Integrative Health and National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States
i Department of Psychological Brain Sciences, Washington University in St. Louis, United States
j Departments of Psychiatry and Radiology, School of Medicine, Washington University in St. Louis, United States
k Department of Psychology, Northeastern University, United States
l Massachusetts General Hospital/Harvard Medical School, United States
m Department of Psychological Science, University of California, Irvine, United States
n Department of Psychology, University of California, Los Angeles, United States
o Department of Psychology, University of California, Berkeley, United States
p Department of Chicano/Latino Studies, University of California, Irvine, United States
q Department of Psychology, Carnegie Mellon University, United States
r Department of Psychology, University of Michigan, United States
s Department of Psychological and Brain Sciences and Africana Studies Program, Texas AM University, United States
t Harvard Business School Executive Education, United States
u Department of Psychology, Stanford University, United States
v Department of Psychology, Columbia University, United States
w Department of Psychology, University of Pennsylvania, United States
x Department of Clinical Psychology, William James College, United States
y Department of Psychology, Cornell University, United States
z Department of Psychology, University of Toronto, United States
aa Department of Psychology, Emory University, United States
ab Department of Psychology, Queen’s University, Canada
ac Department of Psychology, Rice University, United States
ad Department of Psychology, University of Illinois Urbana-Champaign, United States
ae Department of Psychology, Harvard University, United States
af Humu, Inc, Mountain View, CA, United States
ag Department of Psychology, Yale University, United States
ah Department of Psychology, Princeton University, United States
ai Department of Psychology, University of Denver, United States
aj Social and Behavioral Sciences, Yale School of Public Health, United States
ak Northwestern University, Feinberg School of Medicine, United States
al Department of Psychology, University of California, Riverside, United States
am Department of Psychology, New York University, United States
an Department of Psychology, University of Oregon, United States
ao Liberos, LLC, Los Angeles, CA, United States
ap Department of Psychology, University of Southern California, United States
aq Rady School of Management, University of California, San Diego, United States
ar University of Virginia School of Law, United States
as Memory and Aging Center, University of California, San Francisco, United States
at Department of Psychology, University of Virginia, United States
au Department of Psychiatry and Human Behavior, Brown University, United States
av School of Psychology, University of New South Wales, Australia
Abstract
There has been extensive discussion about gender gaps in representation and career advancement in the sciences. However, psychological science itself has yet to be the focus of discussion or systematic review, despite our field’s investment in questions of equity, status, well-being, gender bias, and gender disparities. In the present article, we consider 10 topics relevant for women’s career advancement in psychological science. We focus on issues that have been the subject of empirical study, discuss relevant evidence within and outside of psychological science, and draw on established psychological theory and social-science research to begin to chart a path forward. We hope that better understanding of these issues within the field will shed light on areas of existing gender gaps in the discipline and areas where positive change has happened, and spark conversation within our field about how to create lasting change to mitigate remaining gender differences in psychological science. © The Author(s) 2020.
Author Keywords
bias; gender; gender roles; psychology; science; women
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Semi-automated segmentation of the lateral periventricular regions using diffusion magnetic resonance imaging” (2020) MethodsX
Semi-automated segmentation of the lateral periventricular regions using diffusion magnetic resonance imaging
(2020) MethodsX, 7, art. no. 101023, .
Isaacs, A.M.a b , Han, R.H.c , Smyser, C.D.d e f , Limbrick, D.D., Jr.c , Shimony, J.S.f
a Department of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, MO, United States
b Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada
c Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO, United States
d Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
e Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
f Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States
Abstract
The lateral ventricular perimeter (LVP) of the brain is a critical region because in addition to housing neural stem cells required for brain development, it facilitates cerebrospinal fluid (CSF) bulk flow and functions as a blood-CSF barrier to protect periventricular white matter (PVWM) and other adjacent regions from injurious toxins. LVP injury is common, particularly among preterm infants who sustain intraventricular hemorrhage or post hemorrhagic hydrocephalus and has been associated with poor neurological outcomes. Assessment of the LVP with diffusion MRI has been challenging, primarily due to issues with partial volume artifacts since the LVP region is in close proximity to CSF and other structures of varying signal intensities that may be inadvertently included in LVP segmentation. This research method presents: • A novel MATLAB-based method to segment a homogenous LVP layer using high spatial resolution parameters (voxel size 1.2 × 1.2 × 1.2 mm3) to only capture the innermost layer of the LVP. • The segmented LVP is averaged from three contiguous axial slices to increase signal to noise ratio and reduce the effect of any residual volume averaging effect and eliminates manual and inter/intrarater-related errors. © 2020 The Author(s)
Author Keywords
Diffusion tensor imaging; Hydrocephalus; Intraventricular hemorrhage; Lateral ventricular perimeter; Preterm infant; Segmentation of lateral ventricular perimeter regions of interest; Subventricular zone; Ventricular zone
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access