Hope Center Member Publications

A multi- and mixed-method adaptation study of a patient-centered perioperative mental health intervention bundle
(2023) BMC Health Services Research, 23 (1), art. no. 1175, . 

Abraham, J.^a b c , Meng, A.^a , Baumann, A.^d , Holzer, K.J.^a , Lenard, E.^e , Freedland, K.E.^e , Lenze, E.J.^e , Avidan, M.S.^a , Politi, M.C.^d

^a Department of Anesthesiology, School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
^b Institute for Informatics, Data Science and Biostatistics, School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
^c Division of Biology and Biomedical Sciences, School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
^d Division of Public Health Sciences, Department of Surgery, School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
^e Department of Psychiatry, School of Medicine, Washington University in St. Louis, St. Louis, MO, United States

Abstract
Background: Anxiety and depression are common among older adults and can intensify during perioperative periods, but few mental health interventions are designed for older surgical patients’ unique needs. As part of the feasibility trial, we developed and adapted a perioperative mental health (PMH) bundle for older patients comprised of behavioral activation (BA) and medication optimization (MO) to ameliorate anxiety and depressive symptoms before, during, and after cardiac, orthopedic, and oncologic surgery. Methods: We used mixed-methods including workshop studios with patients, caregivers, clinicians, researchers, and interventionists; intervention refinement and reflection meetings; patient case review meetings; intervention session audio-recordings and documentation forms; and patient and caregiver semi-structured interviews. We used the results to refine our PMH bundle. We used multiple analytical approaches to report the nature of adaptations, including hybrid thematic analysis and content analysis informed by the Framework for Reporting Adaptations and Modifications – Expanded. Results: Adaptations were categorized by content (intervention components), context (how the intervention is delivered, based on the study, target population, intervention format, intervention delivery mode, study setting, study personnel), training, and evaluation. Of 51 adaptations, 43.1% involved content, 41.2% involved context, and 15.7% involved training and evaluation. Several key adaptations were noted: (1) Intervention content was tailored to patient preferences and needs (e.g., rewording elements to prevent stigmatization of mental health needs; adjusting BA techniques and documentation forms to improve patient buy-in and motivation). (2) Cohort-specific adaptations were recommended based on differing patient needs. (3) Compassion was identified by patients as the most important element. Conclusions: We identified evidence-based mental health intervention components from other settings and adapted them to the perioperative setting for older adults. Informed by mixed-methods, we created an innovative and pragmatic patient-centered intervention bundle that is acceptable, feasible, and responsive to the needs of older surgical populations. This approach allowed us to identify implementation strategies to improve the reach, scalability, and sustainability of our bundle, and can guide future patient-centered intervention adaptations. Clinical trials Registration: NCT05110690 (11/08/2021). © 2023, The Author(s).

Author Keywords
Anesthesia;  Anxiety;  Depression;  Geriatric;  Psychiatry;  Surgery;  Tailoring;  Wellness

Funding details
National Institute of Mental HealthNIMHP50MH122351

Document Type: Article
Publication Stage: Final
Source: Scopus

Cognitive impact of multidomain intervention and omega 3 according to blood Aβ42/40 ratio: a subgroup analysis from the randomized MAPT trial
(2023) Alzheimer’s Research and Therapy, 15 (1), art. no. 183, . 

Delrieu, J.^a , Vellas, B.^a , Guyonnet, S.^a , Cantet, C.^a , Ovod, V.^b , Li, Y.^b , Bollinger, J.^b , Bateman, R.^b c , Andrieu, S.^d

^a Maintain Aging Research team, CERPOP, Université de Toulouse, Inserm, Université Paul Sabatier, Toulouse, France; Gérontopôle, Department of Geriatrics, Toulouse CHU, Toulouse, France
^b Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
^c Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO, United States
^d Maintain Aging Research team, CERPOP, Université de Toulouse, Inserm, Université Paul Sabatier, Toulouse, France; Department of Epidemiology and Public Health, Toulouse CHU, Toulouse, France

Abstract
Background: In MAPT (Multidomain Alzheimer Preventive Trial), a cognitive effect of multidomain intervention (MI) was showed in non-demented subjects with positive amyloid PET. However, screening eligible patients for multidomain intervention by PET is difficult to generalize in real-world settings. Methods: MAPT study was a 3-year, randomized, placebo-controlled trial followed by a 2-year observational and optional extension. All participants were non-demented and randomly assigned (1:1:1:1) to the MI plus omega 3, MI plus placebo, omega 3 alone, or placebo alone group. The objectives were to assess the cognitive effect of MAPT interventions (omega 3 supplementation, MI, combined intervention) in non-demented subjects according to amyloid blood status at 12, 36, and 60 months. In this subgroup analysis (n = 483), amyloid status was defined by plasma Aβ42/40 ratio (cutoff ≤ 0.0107). The primary outcome measure was the change in cognitive composite score after a 1, 3, and 5-year clinical follow-up. Results: The intention-to-treat (ITT) population included 483 subjects (161 positive and 322 negative amyloid participants based on plasma Aβ42/40 ratio). In the positive amyloid ITT population, we showed a positive effect of MI plus omega 3 on the change in composite cognitive score in 12 (raw p =.0350, 0.01917, 95% CI = [0.0136 to 0.3699]) and 36 months (raw p =.0357, 0.2818, 95% CI = [0.0190 to 0.5446]). After correction of multiple comparisons and adjustments, these differences were not significant (adjusted p =.1144 and.0690). In the per-protocol positive amyloid group (n = 154), we observed a significant difference between the combined intervention and placebo groups at 12 (p =.0313, 0.2424, 0.0571 to 0.4276) and 36 months (p =.0195, 0.3747, 0.1055 to 0.6439) persisting after adjustment. In the ITT and per-protocol analyses, no cognitive effect was observed in the positive and negative amyloid group at 60-month visit. Conclusions: These findings suggest a benefit of MI plus omega 3 in positive blood amyloid subjects. This promising trend needs to be confirmed before using blood biomarkers for screening in preventive trials. Trial registration: ClinicalTrials.gov Identifier: NCT01513252 . © 2023, BioMed Central Ltd., part of Springer Nature.

Author Keywords
Alzheimer’s disease;  Amyloid blood biomarker;  Clinical trial;  Prevention

Funding details
UMR 1027
National Institute on AgingNIAR56AG061900
Avid Radiopharmaceuticals
Institut de Recherche Pierre FabreIRPF
Ministère des Affaires Sociales et de la Santé
Centre Hospitalier Universitaire de Toulouse

Document Type: Article
Publication Stage: Final
Source: Scopus

Focused Ultrasound-Mediated Delivery of Anti-Programmed Cell Death-Ligand 1 Antibody to the Brain of a Porcine Model
(2023) Pharmaceutics, 15 (10), art. no. 2479, . 

Fadera, S.^a , Chukwu, C.^a , Stark, A.H.^a , Yue, Y.^a , Xu, L.^a , Chien, C.-Y.^a , Yuan, J.^a , Chen, H.^a b

^a Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, United States
^b Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO 63110, United States

Abstract
Immune checkpoint inhibitor (ICI) therapy has revolutionized cancer treatment by leveraging the body’s immune system to combat cancer cells. However, its effectiveness in brain cancer is hindered by the blood-brain barrier (BBB), impeding the delivery of ICIs to brain tumor cells. This study aimed to assess the safety and feasibility of using focused ultrasound combined with microbubble-mediated BBB opening (FUS-BBBO) to facilitate trans-BBB delivery of an ICI, anti-programmed cell death-ligand 1 antibody (aPD-L1) to the brain of a large animal model. In a porcine model, FUS sonication of targeted brain regions was performed after intravenous microbubble injection, which was followed by intravenous administration of aPD-L1 labeled with a near-infrared fluorescent dye. The permeability of the BBB was evaluated using contrast-enhanced MRI in vivo, while fluorescence imaging and histological analysis were conducted on ex vivo pig brains. Results showed a significant 4.8-fold increase in MRI contrast-enhancement volume in FUS-targeted regions compared to nontargeted regions. FUS sonication enhanced aPD-L1 delivery by an average of 2.1-fold, according to fluorescence imaging. In vivo MRI and ex vivo staining revealed that the procedure did not cause significant acute tissue damage. These findings demonstrate that FUS-BBBO offers a noninvasive, localized, and safe delivery approach for ICI delivery in a large animal model, showcasing its potential for clinical translation. © 2023 by the authors.

Author Keywords
blood-brain barrier;  brain drug delivery;  focused ultrasound;  immune checkpoint inhibitors;  immunotherapy

Funding details
National Institutes of HealthNIHR01CA276174, R01EB027223, R01EB030102, R01MH116981, R01NS128461
Charlie Teo FoundationCTF

Document Type: Article
Publication Stage: Final
Source: Scopus

A Drosophila glial cell atlas reveals a mismatch between transcriptional and morphological diversity
(2023) PLoS Biology, 21 (10), art. no. e3002328, . 

Lago-Baldaia, I.^a , Cooper, M.^a , Seroka, A.^b , Trivedi, C.^a , Powell, G.T.^a , Wilson, S.W.^a , Ackerman, S.D.^c d , Fernandes, V.M.^a

^a Department of Cell and Developmental Biology, University College London, London, United Kingdom
^b Institute of Neuroscience, Howard Hughes Medical Institute, University of Oregon, Eugene, OR, United States
^c Department of Pathology and Immunology, Brain Immunology and Glia Center, Washington University School of Medicine, Saint Louis, MO, United States
^d Department of Developmental Biology, Washington University School of Medicine, Saint Louis, MO, United States

Abstract
Morphology is a defining feature of neuronal identity. Like neurons, glia display diverse morphologies, both across and within glial classes, but are also known to be morphologically plastic. Here, we explored the relationship between glial morphology and transcriptional signature using the Drosophila central nervous system (CNS), where glia are categorised into 5 main classes (outer and inner surface glia, cortex glia, ensheathing glia, and astrocytes), which show within-class morphological diversity. We analysed and validated single-cell RNA sequencing data of Drosophila glia in 2 well-characterised tissues from distinct developmental stages, containing distinct circuit types: the embryonic ventral nerve cord (VNC) (motor) and the adult optic lobes (sensory). Our analysis identified a new morphologically and transcriptionally distinct surface glial population in the VNC. However, many glial morphological categories could not be distinguished transcriptionally, and indeed, embryonic and adult astrocytes were transcriptionally analogous despite differences in developmental stage and circuit type. While we did detect extensive within-class transcriptomic diversity for optic lobe glia, this could be explained entirely by glial residence in the most superficial neuropil (lamina) and an associated enrichment for immune-related gene expression. In summary, we generated a single-cell transcriptomic atlas of glia in Drosophila, and our extensive in vivo validation revealed that glia exhibit more diversity at the morphological level than was detectable at the transcriptional level. This atlas will serve as a resource for the community to probe glial diversity and function. © 2023 Lago-Baldaia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding details
210472/Z/18/Z
National Institutes of HealthNIHK99/R00NS121137
Wellcome TrustWT104682/Z/14/Z

Document Type: Article
Publication Stage: Final
Source: Scopus

Controversies and progress on standardization of large-scale brain network nomenclature
(2023) Network Neuroscience, 7 (3), pp. 864-905. Cited 1 time.

Uddin, L.Q.^a , Betzel, R.F.^b , Cohen, J.R.^c , Damoiseaux, J.S.^d , De Brigard, F.^e , Eickhoff, S.B.^f , Fornito, A.^g , Gratton, C.^h , Gordon, E.M.ⁱ , Laird, A.R.^j , Larson-Prior, L.^k , McIntosh, A.R.^l , Nickerson, L.D.^m , Pessoa, L.ⁿ , Pinho, A.L.^o , Poldrack, R.A.^p , Razi, A.^g , Sadaghiani, S.^q , Shine, J.M.^r , Yendiki, A.^s , Yeo, B.T.T.^t , Spreng, R.N.^u

^a Department of Psychiatry and Biobehavioral Sciences and Department of Psychology, University of California, Los Angeles, Los Angeles, CA, United States
^b Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, United States
^c Department of Psychology and Neuroscience, University of North Carolina, Chapel Hill, NC, United States
^d Institute of Gerontology and Department of Psychology, Wayne State University, Detroit, MI, United States
^e Department of Philosophy, Duke University, Durham, NC, United States
^f Institute of Systems Neuroscience, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
^g Turner Institute for Brain and Mental Health, Monash University, Melbourne, Australia
^h Department of Psychology, Northwestern University, Evanston, IL, United States
ⁱ Mallinckrodt Institute of Radiology, Washington University, St. Louis, MO, United States
^j Department of Physics, Florida International University, Miami, FL, United States
^k Deptartment of Psychiatry and Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little RockAR, United States
^l Institute for Neuroscience and Neurotechnology, Simon Fraser University, Vancouver, BC, Canada
^m Department of Psychiatry, McLean Hospital, Boston, MA, United States
ⁿ Department of Psychology, University of Maryland, College Park, MD, United States
^o Brain and Mind Institute, Western University, London, ON, Canada
^p Department of Psychology, Stanford University, Stanford, CA, United States
^q Department of Psychology, University of Illinois, Urbana Champaign, IL, United States
^r Brain and Mind Center, University of Sydney, Sydney, Australia
^s Department of Radiology, Massachusetts General Hospital, Boston, MA, United States
^t Department of Electrical and Computer Engineering, National University of Singapore, Singapore
^u Department of Neurology and Neurosurgery, McGill University, Montreal, Canada

Author Keywords
Brain network;  Cognitive neuroscience;  Diffusion weighted imaging;  EEG;  Functional connectivity;  MEG;  Network neuroscience;  Parcellation;  Resting-state fMRI;  Structural connectivity

Funding details
National Science FoundationNSF2048066, FAIN 2218556, R01MH116226, R01MH118370, R01MH119091, R21NS104603, U01DA050987
National Institutes of HealthNIHP50MH106435, R01EB021265, R01NS119911, U01EB026996
National Institute of Mental HealthNIMHMH071589, MH112517
National Institute on AgingNIAR01AG068563
Canadian Institutes of Health ResearchIRSC
Natural Sciences and Engineering Research Council of CanadaNSERC
Fonds de Recherche du Québec – SantéFRQS
Western UniversityUWO
Canada First Research Excellence FundCFREF

Document Type: Article
Publication Stage: Final
Source: Scopus