Parental preconception stress in zebrafish induces long-lasting anxiety in offspring
(2024) Physiology and Behavior, 277, art. no. 114477, .
Yeramilli, V.a , Rizek, C.S.a , Graham, J.a , Taylor, C.b , Cheddadi, R.a , Patterson, S.b , Watts, S.b , Martin, C.a
a Dept of Surgery, Washington University School of Medicine, Saint Louis, MO, United States
b Dept of Biology, University of Alabama at Birmingham, Birmingham, AL, United States
Abstract
The growth and function of the vertebrate brain are impacted by environmental stimuli and early life stress. Adults who experience chronic stress during early life are more likely to suffer various neurodevelopmental and health issues. However, our understanding of how these specific environmental signals at different developmental stages affect brain development is poorly understood. In this study, we investigated if stress in parents prior to conception modulates neurodevelopment in offspring. We used a chronic unpredictable stress model adapted to zebrafish, which is an increasingly popular vertebrate model in neuroscience research to investigate the effects of both maternal and paternal preconception stress on offspring behavior. We evaluated the responsiveness of three anxiety-related behavioral paradigms in zebrafish: the novel tank test, thigmotaxis, and shoaling behavior. We found larvae from stressed females exhibited anxiety-like behavior in a thigmotaxis assay. As these larvae matured into adults, they continued to exhibit anxiety-like behavior in a novel tank and shoaling behavioral assay. These studies indicate preconception stress exposure in parents can induce life-long alterations in offspring neurodevelopment. Further, these results expand the hypothesis that chronically elevated glucocorticoid signaling not only in stressed mothers, but also stressed dads can affect neurodevelopment in offspring. We propose that zebrafish may be a useful model to study the transgenerational effects of chronic stress mediated via the maternal and paternal line. © 2024
Author Keywords
Depression; HPA axis; Neurodevelopment; Stress; Zebrafish
Funding details
American Surgical Association FoundationASAF
Document Type: Article
Publication Stage: Final
Source: Scopus
The association of pain with gait spatiotemporal parameters in children with hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder
(2024) Gait and Posture, 109, pp. 271-276.
Jeong, H.-J.a b c , Engel, J.M.b , Muriello, M.f , Basel, D.f , Slavens, B.A.b d e
a Orthopaedic and Rehabilitation Engineering Center, Marquette University, Milwaukee, WI, United States
b Department of Rehabilitation Sciences & Technology, University of Wisconsin-Milwaukee, Milwaukee, WI, United States
c Program in Physical Therapy, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
d Department of Mechanical Engineering, College of Engineering and Applied Science, University of Wisconsin-Milwaukee, Milwaukee, WI, United States
e Department of Biomedical Engineering, College of Engineering and Applied Science, University of Wisconsin-Milwaukee, Milwaukee, WI, United States
f Division of Genetics, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United States
Abstract
Background: Children with hypermobility spectrum disorder/hypermobile Ehlers-Danlos syndrome (HSD/hEDS) have a high prevalence of chronic pain, which may influence gait dynamics. However, little is known about pain outcomes and their association with gait spatiotemporal parameters in children with HSD/hEDS. Research question: Does pain correlate with gait spatiotemporal parameters in children with HSD/hEDS? Methods: Eighteen children with HSD/hEDS and eighteen typically developing (TD) children participated in the study. The current level of pain (0–10 on the numeric rating scale), modified Brief Pain Inventory, and Pain Catastrophizing Scale-Child version were implemented to assess pain in children with HSD/hEDS. All children completed a gait analysis at a self-selected speed. Mean and variability (measured using the coefficient of variation) of gait spatiotemporal parameters were analyzed. Gait parameters included stride length, stride time, gait speed, percent stance time, and step width. A Mann-Whitney U-test was used to compare the gait parameters between children with HSD/hEDS and TD children. Spearman correlations were used to examine the relationships between pain and gait spatiotemporal parameters in children with HSD/hEDS. Results: Children with HSD/hEDS had a longer percent stance time compared to TD children (p = 0.03). Lower pain interference in relationships with other people was significantly associated with faster gait speeds (ρ = −0.55, p = 0.03). Children with HSD/hEDS also had greater pain interference during mobility (ρ = 0.5, p = 0.05) and going to school (ρ = 0.65, p = 0.01), which were significantly correlated with greater stride length variability. Greater pain interference during enjoyment of life was significantly associated with greater percent stance time variability (ρ = 0.5, p = 0.05). Greater pain catastrophizing was correlated with decreased step width variability in children with HSD/hEDS (ρ = −0.49, p = 0.05). Significance: Pain interference and catastrophe were significantly associated with gait spatiotemporal variability. Our findings suggest that assessing pain-associated gait alterations may help understand the clinical features and gait kinematics of children with HSD/hEDS. © 2024 Elsevier B.V.
Author Keywords
Gait, Kinematics; Hypermobile Ehlers-Danlos syndrome; Hypermobile joints; Hypermobility spectrum disorder
Funding details
U.S. Department of Health and Human ServicesHHS
Administration for Community LivingACL
National Institute on Disability, Independent Living, and Rehabilitation ResearchNIDILRR90ARHF0006
College of Health Sciences, University of Wyoming
Document Type: Article
Publication Stage: Final
Source: Scopus
Fast and slow: Recording neuromodulator dynamics across both transient and chronic time scales
(2024) Science Advances, 10 (8), p. eadi0643.
Ma, P.a b , Chen, P.a c , Tilden, E.I.a b , Aggarwal, S.a , Oldenborg, A.a , Chen, Y.a
a Department of Neuroscience, Washington University, St. Louis, MO 63110, United States
b Ph.D. Program in Neuroscience, Washington University, St. Louis, MO 63110, United States
c Master’s Program in Biomedical Engineering, Washington University, St. Louis, MO 63110, United States
Abstract
Neuromodulators transform animal behaviors. Recent research has demonstrated the importance of both sustained and transient change in neuromodulators, likely due to tonic and phasic neuromodulator release. However, no method could simultaneously record both types of dynamics. Fluorescence lifetime of optical reporters could offer a solution because it allows high temporal resolution and is impervious to sensor expression differences across chronic periods. Nevertheless, no fluorescence lifetime change across the entire classes of neuromodulator sensors was previously known. Unexpectedly, we find that several intensity-based neuromodulator sensors also exhibit fluorescence lifetime responses. Furthermore, we show that lifetime measures in vivo neuromodulator dynamics both with high temporal resolution and with consistency across animals and time. Thus, we report a method that can simultaneously measure neuromodulator change over transient and chronic time scales, promising to reveal the roles of multi-time scale neuromodulator dynamics in diseases, in response to therapies, and across development and aging.
Document Type: Article
Publication Stage: Final
Source: Scopus
Perceptions of tech-based mental health screening
(2024) Trauma Surgery and Acute Care Open, 9 (1), art. no. e001198, .
McBain, S.A.a , Cleavenger, K.b , Bull, C.a , Payakachat, N.c , Greer, M.d
a Psychiatry, University of Arkansas for Medical Sciences, Little Rock, AR, United States
b Department of Internal Medicine, Washington University in St Louis School of Medicine, St Louis, MO, United States
c College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR, United States
d Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR, United States
Abstract
Background An estimated one-third of patients experience post-traumatic stress disorder (PTSD) or depression in the year following a traumatic injury. The American College of Surgeons requires postinjury PTSD and depression screening in trauma centers, although implementation has been limited. Tech-based solutions have been proposed to improve uptake of postinjury mental health screening. The goals of this pilot study were to assess the usability and acceptability of Blueprint, a tech-based mental health screening platform, and explore attitudes toward tech-based screening and intervention. Methods This pilot study included trauma patients (n=10) admitted to the trauma service. Participants completed the PTSD Checklist-5 and Patient Health Questionnaire-9 using Blueprint to test usability and acceptability of the platform. Participants completed the System Usability Scale (SUS) and a semi-structured interview to assess several domains including attitudes toward tech-based screening, potential barriers to implementation, and its usefulness in a postinjury context. Summative Template Analysis, a data abstraction procedure, was used to analyze qualitative data. Results Blueprint received an average SUS score of 93.25/100 suggesting participants found the interface to be an’excellent’ means to assess postinjury mental health concerns. Participants were supportive of universal screening and identified several benefits to engaging in tech-based routine monitoring of postinjury PTSD and depressive symptoms including convenience, personalization, and trauma-informed care. Regarding intervention, patients valued web-based psychoeducation on topics related to their overall care and local resources. Conclusions Tech-based mental health screening was highly usable and valuable to trauma patients at risk for postinjury PTSD and depression. Participants valued web-based psychoeducation and resources, but overall preferred Blueprint be used to facilitate access to in-person mental health services. Further evaluation of Blueprint as a means of assessment, intervention, and referral is needed. © 2024 BMJ Publishing Group. All rights reserved.
Funding details
National Center for Advancing Translational SciencesNCATSUL1 TR003107
Document Type: Article
Publication Stage: Final
Source: Scopus
Dysregulated Salience Network Control over Default-Mode and Central-Executive Networks in Schizophrenia Revealed Using Stochastic Dynamical Causal Modeling
(2024) Brain Connectivity, 14 (1), pp. 70-79.
Thakuri, D.S.a b , Bhattarai, P.a , Wong, D.F.a c d , Chand, G.B.a d e f
a Department of Radiology, Mallinckrodt Institute of Radiology, Washington University, School of Medicine, St. Louis, MO, United States
b Departments of Medicine and Radiology, University of Missouri, School of Medicine, Columbia, MO, United States
c Departments of Neuroscience Psychiatry and Neurology, Washington University, School of Medicine, St. Louis, MO, United States
d Imaging Core, Knight Alzheimer Disease Research Center, Washington University, School of Medicine, St. Louis, MO, United States
e Institute of Clinical and Translational Sciences, Washington University, School of Medicine, St. Louis, MO, United States
f NeuroGenomics and Informatics Center, Washington University, School of Medicine, St. Louis, MO, United States
Abstract
Introduction: Neuroimaging studies suggest that the human brain consists of intrinsically organized, large-scale neural networks. Among these networks, the interplay among the default-mode network (DMN), salience network (SN), and central-executive network (CEN) has been widely used to understand the functional interaction patterns in health and disease. This triple network model suggests that the SN causally controls over the DMN and CEN in healthy individuals. This interaction is often referred to as SN’s dynamic regulating mechanism. However, such interactions are not well understood in individuals with schizophrenia. Methods: In this study, we leveraged resting-state functional magnetic resonance imaging data from schizophrenia (n = 67) and healthy controls (n = 81) and evaluated the directional functional interactions among DMN, SN, and CEN using stochastic dynamical causal modeling methodology. Results: In healthy controls, our analyses replicated previous findings that SN regulates DMN and CEN activities (Mann-Whitney U test; p < 10-8). In schizophrenia, however, our analyses revealed a disrupted SN-based controlling mechanism over the DMN and CEN (Mann-Whitney U test; p < 10-16). Conclusions: These results indicate that the disrupted controlling mechanism of SN over the other two neural networks may be a candidate neuroimaging phenotype in schizophrenia. © 2024 Mary Ann Liebert Inc.. All rights reserved.
Author Keywords
dynamical causal modeling; functional magnetic resonance imaging; large-scale neural networks; neuroimaging
Funding details
5P20RR021938/P20GM103472
National Institutes of HealthNIHK01AG083230, R01AG040282, R01MH10719705, U01HL096812
National Institute of Mental HealthNIMH1U01 MH097435
University of WashingtonUW
Institute of Clinical and Translational SciencesICTS
Mallinckrodt Institute of RadiologyMIR
Document Type: Article
Publication Stage: Final
Source: Scopus
Demyelination and Na+ Channel Redistribution Underlie Auditory and Vestibular Dysfunction in PMP22-Null Mice
(2024) eNeuro, 11 (2), .
Lee, J.H.a , Park, S.a b , Perez-Flores, M.C.a , Chen, Y.a , Kang, M.a b , Choi, J.a , Levine, L.c , Gratton, M.A.d , Zhao, J.a , Notterpek, L.e , Yamoah, E.N.f
a Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno, NV 89557, United States
b Busan 67264, South Korea
c Program in Audiology and Communication Sciences, Washington University, St. Louis, MO 63110, United States
d Boys Town National Research Hospital, Omaha, NE 68131, United States
e Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno, NV 89557, United States
f Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno, NV 89557, United States
Abstract
Altered expression of peripheral myelin protein 22 (PMP22) results in demyelinating peripheral neuropathy. PMP22 exhibits a highly restricted tissue distribution with marked expression in the myelinating Schwann cells of peripheral nerves. Auditory and vestibular Schwann cells and the afferent neurons also express PMP22, suggesting a unique role in hearing and balancing. Indeed, neuropathic patients diagnosed with PMP22-linked hereditary neuropathies often present with auditory and balance deficits, an understudied clinical complication. To investigate the mechanism by which abnormal expression of PMP22 may cause auditory and vestibular deficits, we studied gene-targeted PMP22-null mice. PMP22-null mice exhibit an unsteady gait, have difficulty maintaining balance, and live for only ∼3-5 weeks relative to unaffected littermates. Histological analysis of the inner ear revealed reduced auditory and vestibular afferent nerve myelination and profound Na+ channel redistribution without PMP22. Yet, Na+ current density was unaltered, in stark contrast to increased K+ current density. Atypical postsynaptic densities and a range of neuronal abnormalities in the organ of Corti were also identified. Analyses of auditory brainstem responses (ABRs) and vestibular sensory-evoked potential (VsEP) revealed that PMP22-null mice had auditory and vestibular hypofunction. These results demonstrate that PMP22 is required for hearing and balance, and the protein is indispensable for the formation and maintenance of myelin in the peripheral arm of the eighth nerve. Our findings indicate that myelin abnormalities and altered signal propagation in the peripheral arm of the auditory nerve are likely causes of auditory deficits in patients with PMP22-linked neuropathies. Copyright © 2024 Lee et al.
Author Keywords
demylination; hearing loss; neuropathy; PMP22; sodium channels; vestibular hypofunction
Document Type: Article
Publication Stage: Final
Source: Scopus
Functional parcellation of the neonatal cortical surface
(2024) Cerebral Cortex, 34 (2), art. no. bhae047, .
Myers, M.J.a , Labonte, A.K.a b , Gordon, E.M.c , Laumann, T.O.a , Tu, J.C.b c , Wheelock, M.D.c , Nielsen, A.N.a , Schwarzlose, R.F.a , Camacho, M.C.a , Alexopoulos, D.d , Warner, B.B.e , Raghuraman, N.f , Luby, J.L.a , Barch, D.M.a g , Fair, D.A.h i j , Petersen, S.E.c d , Rogers, C.E.a , Smyser, C.D.c d e , Sylvester, C.M.a c k
a Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63110, United States
b Neurosciences Graduate Program, Washington University in St. Louis, St. Louis, MO 63110, United States
c Department of Radiology, Washington University in St. Louis, St. Louis, MO 63110, United States
d Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United States
e Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, United States
f Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO 63110, United States
g Department of Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO 63110, United States
h Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN 55414, United States
i Institute of Child Development, University of Minnesota, Minneapolis, MN 55455, United States
j Department of Pediatrics, University of Minnesota, Minneapolis, MN 55454, United States
k Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
The cerebral cortex is organized into distinct but interconnected cortical areas, which can be defined by abrupt differences in patterns of resting state functional connectivity (FC) across the cortical surface. Such parcellations of the cortex have been derived in adults and older infants, but there is no widely used surface parcellation available for the neonatal brain. Here, we first demonstrate that existing parcellations, including surface-based parcels derived from older samples as well as volume-based neonatal parcels, are a poor fit for neonatal surface data. We next derive a set of 283 cortical surface parcels from a sample of n = 261 neonates. These parcels have highly homogenous FC patterns and are validated using three external neonatal datasets. The Infomap algorithm is used to assign functional network identities to each parcel, and derived networks are consistent with prior work in neonates. The proposed parcellation may represent neonatal cortical areas and provides a powerful tool for neonatal neuroimaging studies. © The Author(s) 2024. Published by Oxford University Press. All rights reserved.
Author Keywords
cortical areas; fMRI; functional connectivity; neonate; parcellation
Funding details
National Institute of Mental HealthNIMHR01MH122389, R01MH131584
National Institute on Drug AbuseNIDAR01DA046224, U24DA055330
National Institute of Child Health and Human DevelopmentNICHDK99HD109454
Intellectual and Developmental Disabilities Research Center, Washington University School of Medicine in St. LouisIDDRCP50 HD103525
Document Type: Article
Publication Stage: Final
Source: Scopus
Catalytic isoforms of AMP-activated protein kinase differentially regulate IMPDH activity and photoreceptor neuron function
(2024) JCI Insight, 9 (4), art. no. e173707, .
Lee, T.J.a b , Sasaki, Y.c , Ruzycki, P.A.a c , Ban, N.d , Lin, J.B.a , Wu, H.-T.b , Santeford, A.a , Apte, R.S.a b e
a John F. Hardesty, MD Department of Ophthalmology and Visual Sciences, St. Louis, MO, United States
b Department of Developmental Biology
c Department of Genetics, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
d Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan
e Department of Medicine, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
Abstract
AMP-activated protein kinase (AMPK) plays a crucial role in maintaining ATP homeostasis in photoreceptor neurons. AMPK is a heterotrimeric protein consisting of α, β, and γ subunits. The independent functions of the 2 isoforms of the catalytic α subunit, PRKAA1 and PRKAA2, are uncharacterized in specialized neurons, such as photoreceptors. Here, we demonstrate in mice that rod photoreceptors lacking PRKAA2, but not PRKAA1, showed altered levels of cGMP, GTP, and ATP, suggesting isoform-specific regulation of photoreceptor metabolism. Furthermore, PRKAA2-deficient mice displayed visual functional deficits on electroretinography and photoreceptor outer segment structural abnormalities on transmission electron microscopy consistent with neuronal dysfunction, but not neurodegeneration. Phosphoproteomics identified inosine monophosphate dehydrogenase (IMPDH) as a molecular driver of PRKAA2-specific photoreceptor dysfunction, and inhibition of IMPDH improved visual function in Prkaa2 rod photoreceptor–knockout mice. These findings highlight a therapeutically targetable PRKAA2 isoform–specific function of AMPK in regulating photoreceptor metabolism and function through a potentially previously uncharacterized mechanism affecting IMPDH activity. © 2024, Lee et al.
Funding details
National Institutes of HealthNIHEY02687, R01 EY019287
Research to Prevent BlindnessRPB1T32GM1397740-1
BrightFocus FoundationBFF
Harvard Medical SchoolHMS
Washington University in St. LouisWUSTLRF1 AG013730, T32 GM07200
Diabetes Research Center, University of WashingtonDRC, UW5 P30 DK020579
Starr FoundationTSF
Carl Marshall and Mildred Almen Reeves Foundation
VitreoRetinal Surgery FoundationVRSFF30 DK130282, VGR0023118
Document Type: Article
Publication Stage: Final
Source: Scopus
Sarm1 knockout prevents type 1 diabetic bone disease in females independent of neuropathy
(2024) JCI insight, 9 (4), .
Brazill, J.M.a , Shen, I.R.a , Craft, C.S.a , Magee, K.L.a , Park, J.S.a , Lorenz, M.a , Strickland, A.b , Wee, N.K.a , Zhang, X.a c , Beeve, A.T.a c , Meyer, G.A.d , Milbrandt, J.b , DiAntonio, A.e , Scheller, E.L.a c e f
a Division of Bone and Mineral Diseases, Department of Medicine
b Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States
c Department of Biomedical Engineering, McKelvey School of Engineering, Washington University, St. Louis, MO, United States
d Program in Physical Therapy
e Department of Developmental Biology
f Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, United States
Abstract
Patients with diabetes have a high risk of developing skeletal diseases accompanied by diabetic peripheral neuropathy (DPN). In this study, we isolated the role of DPN in skeletal disease with global and conditional knockout models of sterile-α and TIR-motif-containing protein-1 (Sarm1). SARM1, an NADase highly expressed in the nervous system, regulates axon degeneration upon a range of insults, including DPN. Global knockout of Sarm1 prevented DPN, but not skeletal disease, in male mice with type 1 diabetes (T1D). Female wild-type mice also developed diabetic bone disease but without DPN. Unexpectedly, global Sarm1 knockout completely protected female mice from T1D-associated bone suppression and skeletal fragility despite comparable muscle atrophy and hyperglycemia. Global Sarm1 knockout rescued bone health through sustained osteoblast function with abrogation of local oxidative stress responses. This was independent of the neural actions of SARM1, as beneficial effects on bone were lost with neural conditional Sarm1 knockout. This study demonstrates that the onset of skeletal disease occurs rapidly in both male and female mice with T1D completely independently of DPN. In addition, this reveals that clinical SARM1 inhibitors, currently being developed for treatment of neuropathy, may also have benefits for diabetic bone through actions outside of the nervous system.
Author Keywords
Bone Biology; Bone disease; Diabetes; Endocrinology; Neurodegeneration
Document Type: Article
Publication Stage: Final
Source: Scopus
A Digital Intervention to Promote Self-Management Self-Efficacy Among Community-Dwelling Individuals With Stroke: Pilot Randomized Controlled Trial
(2024) JMIR Rehabilitation and Assistive Technologies, 11 (1), art. no. e50863, .
Li, Z.a , Lei, Y.b , Bui, Q.c , DePaul, O.d , Nicol, G.E.e , Mohr, D.C.f g , Lee, S.I.h , Fong, M.W.M.i , Metts, C.L.j , Tomazin, S.E.k , Wong, A.W.K.k l m
a Division of Occupational Science and Occupational Therapy, University of North Carolina, School of Medicine, Chapel Hill, NC, United States
b Department of Occupational Therapy, New York University, New York, NY, United States
c Institute for Informatics, Data Science & Biostatistics, Washington University, School of Medicine, St. Louis, MO, United States
d Memorial Hospital Belleville, Belleville, IL, United States
e Department of Psychiatry, Washington University, School of Medicine, St. Louis, MO, United States
f Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
g Center for Behavioral Intervention Technologies, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
h Manning College of Information and Computer Sciences, University of Massachusetts Amherst, Amherst, MA, United States
i Chicago, IL, United States
j Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, United States
k Center for Rehabilitation Outcomes Research, Shirley Ryan AbilityLab, Chicago, IL, United States
l Department of Physical Medicine and Rehabilitation, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
m Department of Medical Social Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
Abstract
Background: Digital interventions provided through smartphones or the internet that are guided by a coach have been proposed as promising solutions to support the self-management of chronic conditions. However, digital intervention for poststroke self-management is limited; we developed the interactive Self-Management Augmented by Rehabilitation Technologies (iSMART) intervention to address this gap. Objective: This study aimed to examine the feasibility and initial effects of the iSMART intervention to improve self-management self-efficacy in people with stroke. Methods: A parallel, 2-arm, nonblinded, randomized controlled trial of 12-week duration was conducted. A total of 24 participants with mild-to-moderate chronic stroke were randomized to receive either the iSMART intervention or a manual of stroke rehabilitation (attention control). iSMART was a coach-guided, technology-supported self-management intervention designed to support people managing chronic conditions and maintaining active participation in daily life after stroke. Feasibility measures included retention and engagement rates in the iSMART group. For both the iSMART intervention and active control groups, we used the Feasibility of Intervention Measure, Acceptability of Intervention Measure, and Intervention Appropriateness Measure to assess the feasibility, acceptability, and appropriateness, respectively. Health measures included the Participation Strategies Self-Efficacy Scale and the Patient-Reported Outcomes Measurement Information System’s Self-Efficacy for Managing Chronic Conditions. Results: The retention rate was 82% (9/11), and the engagement (SMS text message response) rate was 78% for the iSMART group. Mean scores of the Feasibility of Intervention Measure, Acceptability of Intervention Measure, and Intervention Appropriateness Measure were 4.11 (SD 0.61), 4.44 (SD 0.73), and 4.36 (SD 0.70), respectively, which exceeded our benchmark (4 out of 5), suggesting high feasibility, acceptability, and appropriateness of iSMART. The iSMART group showed moderate-to-large effects in improving self-efficacy in managing emotions (r=0.494), symptoms (r=0.514), daily activities (r=0.593), and treatments and medications (r=0.870), but the control group showed negligible-to-small effects in decreasing self-efficacy in managing emotions (r=0.252), symptoms (r=0.262), daily activities (r=0.136), and treatments and medications (r=0.049). In addition, the iSMART group showed moderate-to-large effects of increasing the use of participation strategies for management in the home (r=0.554), work (r=0.633), community (r=0.673), and communication activities (r=0.476). In contrast, the control group showed small-to-large effects of decreasing the use of participation strategies for management in the home (r=0.567), work (r=0.342, community (r=0.215), and communication activities (r=0.379). Conclusions: Our findings support the idea that iSMART was feasible to improve poststroke self-management self-efficacy. Our results also support using a low-cost solution, such as SMS text messaging, to supplement traditional therapeutic patient education interventions. Further evaluation with a larger sample of participants is still needed. ©Zhaoying Li, Yating Lei, Quoc Bui, Olivia DePaul, Ginger E Nicol, David C Mohr, Sunghoon I Lee, Mandy W M Fong, Christopher L Metts, Stephanie E Tomazin, Alex W K Wong. Originally published in JMIR Rehabilitation and Assistive Technology.
Author Keywords
digital intervention; feasibility; mobile health; participation; rehabilitation; self-efficacy; self-management; stroke; technology; telehealth; telemedicine; text messaging
Funding details
National Institutes of HealthNIH
National Institute of Mental HealthNIMHR34 MH118395
Health Resources and Services AdministrationHRSA
American Occupational Therapy FoundationAOTF
Craig H. Neilsen FoundationCHNF
National Center for Advancing Translational SciencesNCATSUL1TR002345
National Center for Medical Rehabilitation ResearchNCMRRK01HD095388
Foundation for Barnes-Jewish HospitalFBJH
University of WashingtonUW
Institute of Clinical and Translational SciencesICTS
Usona Institute
Otsuka AmericaOAI
Mallinckrodt Institute of RadiologyMIR
Document Type: Article
Publication Stage: Final
Source: Scopus
Risk factors for neurocognitive impairment, emotional distress, and poor quality of life in survivors of pediatric rhabdomyosarcoma: A report from the Childhood Cancer Survivor Study
(2024) Cancer, .
van der Plas, E.a b , Darji, H.c d , Srivastava, D.K.d , Schapiro, M.e , Jeffe, D.f , Perkins, S.g , Howell, R.h , Leisenring, W.i , Armstrong, G.T.j , Oeffinger, K.k , Krull, K.l , Edelstein, K.m , Hayashi, R.J.n
a Department of Hematology/Oncology, Arkansas Children’s Hospital, Little Rock, AR, United States
b Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, United States
c Quantitative Sciences Unit, Department of Medicine, Stanford University, Stanford, CA, United States
d Biostatistics Department, St. Jude Children’s Research Hospital, Memphis, TN, United States
e Department of Pediatrics, SSM Health Cardinal Glennon Children’s Hospital-St. Louis University, St. Louis, MO, United States
f John T. Milliken Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
g Department of Radiation Oncology, Washington University in St. Louis, St. Louis, MO, United States
h Department of Radiation Physics, The MD Anderson Cancer Center, Houston, TX, United States
i Clinical Research Division, Fred Hutch Cancer Center, Seattle, WA, United States
j Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, Memphis, TN, United States
k Department of Medicine, Duke University, Durham, NC, United States
l Psychology and Biobehavioral Sciences, St. Jude Children’s Research Hospital, Memphis, TN, United States
m Department of Supportive Care, Princess Margaret Cancer Center, Toronto, ON, Canada
n Washington University School of Medicine in St. Louis, Department of Pediatrics, St. Louis Childrens Hospital, Siteman Cancer Center, St. Louis, MO, United States
Abstract
Background: Prevalence and risk of poor psychological outcomes following rhabdomyosarcoma (RMS) are not well-established. Methods: Participants in this cross-sectional, case-control study (n = 713 survivors, 42.5% female; mean [SD] age, 30.5 [6.6] years; n = 706 siblings, 57.2% female; mean age, 32.8,[7.9] years) completed measures of neurocognition, emotional distress, and health-related quality of life (HRQOL). Multivariable logistic regression models identified treatments, health behaviors, and chronic conditions associated with impairment. Results: Relative to siblings, more survivors reported neurocognitive impairment (task efficiency: 21.1% vs. 13.7%, emotional regulation: 16.7% vs. 11.0%, memory: 19.3% vs. 15.1%), elevated emotional distress (somatic distress: 12.9% vs. 4.7%, anxiety: 11.7% vs. 5.9%, depression: 22.8% vs. 16.9%) and poorer HRQOL (physical functioning: 11.1% vs. 2.8%, role functioning due to physical problems: 16.8% vs. 8.2%, pain: 17.5% vs. 10.0%, vitality: 22.3% vs. 13.8%, social functioning: 14.4% vs. 6.8%, emotional functioning: 17.1% vs. 10.6%). Cranial radiation increased risk for impaired task efficiency (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.14–4.63), whereas chest and pelvic radiation predicted increased risk of physical functioning (OR, 2.68; 95% CI, 1.16–6.21 and OR, 3.44; 95% CI, 1.70–6.95, respectively). Smoking was associated with impaired task efficiency (OR, 2.06; 95% CI, 1.14–3.70), memory (OR, 2.23; 95% CI, 1.26–3.95), anxiety (OR, 2.71; 95% CI, 1.36–5.41) and depression (OR, 1.77; 95% CI, 1.01–3.11). Neurologic conditions increased risk of anxiety (OR, 2.30; 95% CI, 1.04–5.10), and hearing conditions increased risk of depression (OR, 1.79; 95% CI, 1.05–3.03). Neurologic and hearing conditions, respectively, were associated with impaired memory (OR, 2.44; 95% CI, 1.20–4.95 and OR, 1.87; 95% CI, 1.05–3.35) and poor health perception (OR, 2.62; 95% CI, 1.62–1.28 and OR, 2.33; 95% CI, 1.34–4.06). Conclusions: RMS survivors are at significant risk for poor psychological outcomes. Advancing therapies for local control, smoking cessation, and managing chronic medical conditions may mitigate poor outcomes following RMS. © 2024 American Cancer Society.
Author Keywords
cognition; psychological distress; quality of life; rhabdomyosarcoma; surveys and questionnaires; survivorship
Funding details
P30 CA021765
National Institutes of HealthNIH
National Cancer InstituteNCIU24 CA055727
St. Jude Children’s Research Hospital
Princess Margaret Cancer FoundationPMCF
Washington University School of Medicine in St. LouisWUSM
Canadian Institutes of Health ResearchIRSC
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Presenilin-1 mutation position influences amyloidosis, small vessel disease, and dementia with disease stage
(2024) Alzheimer’s and Dementia, .
Joseph-Mathurin, N.a , Feldman, R.L.a , Lu, R.a , Shirzadi, Z.b , Toomer, C.a c , Saint Clair, J.R.a d , Ma, Y.a , McKay, N.S.a , Strain, J.F.a , Kilgore, C.a , Friedrichsen, K.A.a , Chen, C.D.a , Gordon, B.A.a , Chen, G.a , Hornbeck, R.C.a , Massoumzadeh, P.a , McCullough, A.A.a , Wang, Q.a , Li, Y.a , Wang, G.a , Keefe, S.J.a , Schultz, S.A.b , Cruchaga, C.a , Preboske, G.M.e , Jack, C.R., Jr.e , Llibre-Guerra, J.J.a , Allegri, R.F.f , Ances, B.M.a , Berman, S.B.g , Brooks, W.S.h i , Cash, D.M.j , Day, G.S.k , Fox, N.C.j , Fulham, M.l , Ghetti, B.m , Johnson, K.A.b , Jucker, M.n o , Klunk, W.E.g , la Fougère, C.n p , Levin, J.q r s , Niimi, Y.t , Oh, H.u , Perrin, R.J.a , Reischl, G.n p , Ringman, J.M.c , Saykin, A.J.m , Schofield, P.R.h i , Su, Y.v , Supnet-Bell, C.a , Vöglein, J.q r , Yakushev, I.w , Brickman, A.M.x , Morris, J.C.a , McDade, E.a , Xiong, C.a , Bateman, R.J.a , Chhatwal, J.P.b , Benzinger, T.L.S.a , for the Dominantly Inherited Alzheimer Networky
a Washington University School of Medicine in Saint Louis, St. Louis, MO, United States
b Massachusetts General Hospital, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
c Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
d Meharry School of Medicine, Meharry College, Nashville, TN, United States
e Mayo Clinic, Rochester, MN, United States
f Institute for Neurological Research FLENI, Buenos Aires, Montañeses, Argentina
g University of Pittsburgh Medical Center, Pittsburgh, PA, United States
h Neuroscience Research Australia, Sydney, NSW, Australia
i University of New South Wales, Sydney, NSW, Australia
j UK Dementia Research Institute and Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
k Mayo Clinic, Jacksonville, FL, United States
l Royal Prince Alfred Hospital, Camperdown, NSW, Australia
m Indiana University School of Medicine, Indianapolis, IN, United States
n German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
o Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
p University hospital Tübingen, Tübingen, Germany
q German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
r Ludwig Maximilian University of Munich, Munich, Germany
s Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
t The University of Tokyo, Tokyo, Bunkyo City, Japan
u Brown University, Providence, RI, United States
v Banner Alzheimer Institute, Banner Health, Phoenix, AZ, United States
w Department of Nuclear Medicine, Technical University of Munich, Munich, Germany
x Columbia University Medical Center, New York, NY, United States
Abstract
INTRODUCTION: Amyloidosis, including cerebral amyloid angiopathy, and markers of small vessel disease (SVD) vary across dominantly inherited Alzheimer’s disease (DIAD) presenilin-1 (PSEN1) mutation carriers. We investigated how mutation position relative to codon 200 (pre-/postcodon 200) influences these pathologic features and dementia at different stages. METHODS: Individuals from families with known PSEN1 mutations (n = 393) underwent neuroimaging and clinical assessments. We cross-sectionally evaluated regional Pittsburgh compound B-positron emission tomography uptake, magnetic resonance imaging markers of SVD (diffusion tensor imaging-based white matter injury, white matter hyperintensity volumes, and microhemorrhages), and cognition. RESULTS: Postcodon 200 carriers had lower amyloid burden in all regions but worse markers of SVD and worse Clinical Dementia Rating® scores compared to precodon 200 carriers as a function of estimated years to symptom onset. Markers of SVD partially mediated the mutation position effects on clinical measures. DISCUSSION: We demonstrated the genotypic variability behind spatiotemporal amyloidosis, SVD, and clinical presentation in DIAD, which may inform patient prognosis and clinical trials. Highlights: Mutation position influences Aβ burden, SVD, and dementia. PSEN1 pre-200 group had stronger associations between Aβ burden and disease stage. PSEN1 post-200 group had stronger associations between SVD markers and disease stage. PSEN1 post-200 group had worse dementia score than pre-200 in late disease stage. Diffusion tensor imaging-based SVD markers mediated mutation position effects on dementia in the late stage. © 2024 The Authors. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association.
Author Keywords
autosomal dominant Alzheimer’s disease (ADAD); cerebral amyloid angiopathy (CAA); codon 200; dominantly inherited Alzheimer’s disease (DIAD); microbleeds; microhemorrhages; peak width of skeletonized mean diffusivity (PSMD); PiB-PET; presenilin-1; PSEN1; small vessel disease (SVD); white matter hyperintensity (WMH)
Funding details
P30AG072980
A2022013F, AARF‐21‐722077, R01AG074909, R03AG072375, RMS2318, T32AG078117‐01
National Institutes of HealthNIH1K01AG080123‐01
National Institute on AgingNIA
Michael J. Fox Foundation for Parkinson’s ResearchMJFF
Alzheimer’s AssociationAA
BrightFocus FoundationBFFA2023001F
Arizona State UniversityASU
Japan Agency for Medical Research and DevelopmentAMED
UK Research and InnovationUKRIMR/V03863X/1
Korea Dementia Research CenterKDRC
Medical Research CouncilMRC
Alzheimer’s Society
Alzheimer’s Research UKARUKARUK‐PG2017‐1946
Ministry of Science, ICT and Future PlanningMSIPHI21C0066
Ministry of Health and WelfareMOHW
Korea Health Industry Development InstituteKHIDI
Instituto de Salud Carlos IIIISCIIIAARFD‐20‐681815
Deutsches Zentrum für Neurodegenerative ErkrankungenDZNE
Fleni
UK Dementia Research InstituteUK DRI
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
White matter development and language abilities during infancy in autism spectrum disorder
(2024) Molecular Psychiatry, .
McFayden, T.C.a , Rutsohn, J.b , Cetin, G.a , Forsen, E.c , Swanson, M.R.d , Meera, S.S.e , Wolff, J.J.f , Elison, J.T.g , Shen, M.D.a , Botteron, K.c , Dager, S.R.h i , Estes, A.i j , Gerig, G.k , McKinstry, R.C.l , Pandey, J.m , Schultz, R.m , St. John, T.i j , Styner, M.n , Truong, Y.b , Zwaigenbaum, L.o , Hazlett, H.C.a , Piven, J.a , Girault, J.B.a , Pivena , Hazletta , Shena , Giraulta , Dagerh i , Estesi j , St. Johni j , Botteronc , Schultzm , Pandeym , Zwaigenbaumo , Elisong , Wolfff , Stynern , Gerigk , McKinstryl , Truongb
a Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, Carrboro, NC, United States
b Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
c Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
d Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States
e Department of Speech Pathology and Audiology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India
f Department of Educational Psychology, University of Minnesota, Minneapolis, MN, United States
g Institute of Child Development, University of Minnesota, Minneapolis, MN, United States
h Department of Radiology, University of Washington, Seattle, WA, United States
i Institute on Human Development and Disability, University of Washington, Seattle, WA, United States
j Department of Speech and Hearing Sciences, University of Washington, Seattle, WA, United States
k Tandon School of Engineering, New York University, New York, NY, United States
l Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States
m Center for Autism Research, The Children’s Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA, United States
n Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
o Department of Pediatrics, University of Alberta, Edmonton, AB, Canada
Abstract
White matter (WM) fiber tract differences are present in autism spectrum disorder (ASD) and could be important markers of behavior. One of the earliest phenotypic differences in ASD are language atypicalities. Although language has been linked to WM in typical development, no work has evaluated this association in early ASD. Participants came from the Infant Brain Imaging Study and included 321 infant siblings of children with ASD at high likelihood (HL) for developing ASD; 70 HL infants were later diagnosed with ASD (HL-ASD), and 251 HL infants were not diagnosed with ASD (HL-Neg). A control sample of 140 low likelihood infants not diagnosed with ASD (LL-Neg) were also included. Infants contributed expressive language, receptive language, and diffusion tensor imaging data at 6-, 12-, and 24 months. Mixed effects regression models were conducted to evaluate associations between WM and language trajectories. Trajectories of microstructural changes in the right arcuate fasciculus were associated with expressive language development. HL-ASD infants demonstrated a different developmental pattern compared to the HL-Neg and LL-Neg groups, wherein the HL-ASD group exhibited a positive association between WM fractional anisotropy and language whereas HL-Neg and LL-Neg groups showed weak or no association. No other fiber tracts demonstrated significant associations with language. In conclusion, results indicated arcuate fasciculus WM is linked to language in early toddlerhood for autistic toddlers, with the strongest associations emerging around 24 months. To our knowledge, this is the first study to evaluate associations between language and WM development during the pre-symptomatic period in ASD. © The Author(s), under exclusive licence to Springer Nature Limited 2024.
Funding details
National Institutes of HealthNIHK01-MH122779, P30-HD003110, R01-HD055741-S1, U54-EB005149
Simons FoundationSF
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHDT32HD040127
Simons Foundation Autism Research InitiativeSFARI140209
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Social participation mediates the relationship between self-efficacy and loneliness among people with stroke during COVID-19: a cross-sectional study
(2024) Topics in Stroke Rehabilitation, .
Lee, S.a , Randolph, S.B.a , Baum, C.M.a b c , Nicholas, M.L.d , Connor, L.T.a b
a Program in Occupational 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 Brown School of Social Work, Washington University, St. Louis, MO, United States
d Department of Communication Sciences and Disorders, MGH Institute of Health Professions, Boston, MA, United States
Abstract
Background: People post-stroke experience increased loneliness, compared to their healthy peers and loneliness may have increased during COVID due to social distancing. How social distancing affected loneliness among people after stroke is unknown. Bandura’s self-efficacy theory suggests that self-efficacy may be a critical component affecting individuals’ emotions, behaviors, attitudes, and interpretation of everyday situations. Additionally, previous studies indicate that self-efficacy is associated with both loneliness and social participation. This study investigates relationships among self-efficacy, social participation, and loneliness in people with stroke. Objectives: Determine how social participation affects the relationship between self-efficacy and loneliness in people with stroke during the COVID-19 pandemic. Methods: 44 participants were community-dwelling individuals, ≥ 6 months post-stroke who participated in a 2-hour phone interview. A regression-based mediation analysis was conducted using these measures: Participation Strategies Self-Efficacy Scale, Activity Card Sort for social participation, and UCLA Loneliness Scale for loneliness. Results: The total effect of self-efficacy on loneliness was significant (b = -0.36, p =.01). However, social participation fully mediated the relationship between self-efficacy and loneliness (indirect effect, b = -0.11, 95% CI [−0.24, −0.01]; direct effect, b = -0.25, 95% CI [−0.03, 0]). Conclusions: Self-efficacy is associated with both social participation and loneliness in people with stroke in this cross-sectional study. Mediation analysis findings suggest that interventions focused on increasing social participation may prevent or potentially alleviate loneliness in people with stroke who have low self-efficacy. © 2024 Taylor & Francis Group, LLC.
Author Keywords
loneliness; participation; self-efficacy; social activity; Stroke
Document Type: Article
Publication Stage: Article in Press
Source: Scopus