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- Azevedo, Carla, et al.
(författare)
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Parkinsons disease and multiple system atrophy patient iPSC-derived oligodendrocytes exhibit alpha-synuclein-induced changes in maturation and immune reactive properties
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:12
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Tidskriftsartikel (refereegranskat)abstract
- Limited evidence has shed light on how aSYN proteins affect the oligodendrocyte phenotype and pathogenesis in synucleinopathies that include Parkinsons disease (PD) and multiple system atrophy (MSA). Here, we investigated early transcriptomic changes within PD and MSA O4(+) oligodendrocyte lineage cells (OLCs) generated from patient-induced pluripotent stem cells (iPSCs). We found impaired maturation of PD and MSA O4(+) OLCs compared to controls. This phenotype was associated with changes in the human leukocyte antigen (HLA) genes, the immunoproteasome subunit PSMB9, and the complement component C4b for aSYN p.A53T and MSA O4(+) OLCs, but not in SNCA(trip) O4(+) OLCs despite high levels of aSYN assembly formation. Moreover, SNCA overexpression resulted in the development of O4(+) OLCs, whereas exogenous treatment with aSYN species led to significant toxicity. Notably, transcriptome profiling of genes encoding proteins forming Lewy bodies and glial cytoplasmic inclusions revealed clustering of PD aSYN p.A53T O4(+) OLCs with MSA O4(+) OLCs. Our work identifies early phenotypic and pathogenic changes within human PD and MSA O4(+) OLCs.
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- Eék, Niels, 1980, et al.
(författare)
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Efficacy of an Internet-Based Community Reinforcement and Family Training Program to Increase Treatment Engagement for AUD and to Improve Psychiatric Health for CSOs: A Randomized Controlled Trial
- 2020
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Ingår i: Alcohol and alcoholism (Oxford, Oxfordshire). - : Oxford University Press (OUP). - 1464-3502 .- 0735-0414. ; 55:2, s. 187-195
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Community Reinforcement Approach and Family Training (CRAFT) is a support program for concerned significant others (CSOs) to identified persons (IPs) with alcohol use disorders, with the purpose of engaging IPs to treatment and to improve CSO functioning. The purpose of the present study was to investigate the efficacy of an internet-based version of CRAFT (iCRAFT). METHODS: Randomized controlled trial comparing iCRAFT with a wait-list (WL) condition with a nation-wide uptake in Sweden. A total of 94 CSOs to a treatment refusing IP, who described the IP according to DSM-IV criteria for alcohol dependence or abuse, were included in the study. iCRAFT consisted of five weekly administered therapist-guided modules with the following content: (a) improve CSOs' own mental health, (b) improve the CSOs skills in asking the IP to seek treatment, (c) positive communication skills training, (d) contingency management of IP drinking behavior. Main outcome measure was IPs initiative to seek treatment measured at 24weeks. Secondary outcomes were IP's daily alcohol consumption, CSOs mental health, quality of life and relational satisfaction. RESULTS: Of 94 participants, 15 CSOs reported IP treatment initiative during the study period. Of these, 10 belonged to the iCRAFT condition and five to the WL condition. The difference between conditions was nonsignificant, and the results were inconclusive. Participants in iCRAFT showed short-term improvements regarding depressive symptoms, quality of life and relational happiness. CONCLUSION: This study was unable to demonstrate substantial changes in the iCRAFT program regarding IP treatment seeking or CSO mental health. © The Author(s) 2020. Medical Council on Alcohol and Oxford University Press.
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