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- Saliba-Gustafsson, P., et al.
(författare)
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Subclinical atherosclerosis and its progression are modulated by PLIN2 through a feed-forward loop between LXR and autophagy
- 2019
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 660-675
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Tidskriftsartikel (refereegranskat)abstract
- Background Hyperlipidaemia is a major risk factor for cardiovascular disease, and atherosclerosis is the underlying cause of both myocardial infarction and stroke. We have previously shown that the Pro251 variant of perilipin-2 reduces plasma triglycerides and may therefore be beneficial to reduce atherosclerosis development. Objective We sought to delineate putative beneficial effects of the Pro251 variant of perlipin-2 on subclinical atherosclerosis and the mechanism by which it acts. Methods A pan-European cohort of high-risk individuals where carotid intima-media thickness has been assessed was adopted. Human primary monocyte-derived macrophages were prepared from whole blood from individuals recruited by perilipin-2 genotype or from buffy coats from the Karolinska University hospital blood central. Results The Pro251 variant of perilipin-2 is associated with decreased intima-media thickness at baseline and over 30 months of follow-up. Using human primary monocyte-derived macrophages from carriers of the beneficial Pro251 variant, we show that this variant increases autophagy activity, cholesterol efflux and a controlled inflammatory response. Through extensive mechanistic studies, we demonstrate that increase in autophagy activity is accompanied with an increase in liver-X-receptor (LXR) activity and that LXR and autophagy reciprocally activate each other in a feed-forward loop, regulated by CYP27A1 and 27OH-cholesterol. Conclusions For the first time, we show that perilipin-2 affects susceptibility to human atherosclerosis through activation of autophagy and stimulation of cholesterol efflux. We demonstrate that perilipin-2 modulates levels of the LXR ligand 27OH-cholesterol and initiates a feed-forward loop where LXR and autophagy reciprocally activate each other; the mechanism by which perilipin-2 exerts its beneficial effects on subclinical atherosclerosis.
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| 2. |
- Bonomi, A, et al.
(författare)
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Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study
- 2020
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Ingår i: Genes and immunity. - : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 21:2, s. 100-108
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Tidskriftsartikel (refereegranskat)abstract
- The genes regulating circulating levels of soluble gp130 (sgp130), the antagonist of the inflammatory response in atherosclerosis driven by interleukin 6, are largely unknown. Aims of the present study were to identify genetic loci associated with circulating sgp130 and to explore the potential association between variants associated with sgp130 and markers of subclinical atherosclerosis. The study is based on IMPROVE (n = 3703), a cardiovascular multicentre study designed to investigate the determinants of carotid intima media thickness, a measure of subclinical atherosclerosis. Genomic DNA was genotyped by the CardioMetaboChip and ImmunoChip. About 360,842 SNPs were tested for association with log-transformed sgp130, using linear regression adjusted for age, gender, and population stratification using PLINK v1.07. A p value of 1 × 10−5 was chosen as threshold for significance value. In an exploratory analysis, SNPs associated with sgp130 were tested for association with c-IMT measures. We identified two SNPs significantly associated with sgp130 levels and 24 showing suggestive association with sgp130 levels. One SNP (rs17688225) on chromosome 14 was positively associated with sgp130 serum levels (β = 0.03 SE = 0.007, p = 4.77 × 10−5) and inversely associated with c-IMT (c-IMTmean–maxβ = −0.001 SE = 0.005, p = 0.0342). Our data indicate that multiple loci regulate sgp130 levels and suggest a possible common pathway between sgp130 and c-IMT measures.
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| 4. |
- Hoppe, J. A., et al.
(författare)
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When do individuals choose care robots over a human caregiver? : Insights from a laboratory experiment on choices under uncertainty
- 2023
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Ingår i: Computers in Human Behavior Reports. - : Elsevier B.V.. - 2451-9588. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Demographic changes and a predicted shortage of nursing staff are progressively putting pressure on the healthcare system. Care robots may represent one part of a possible solution to this problem as they can assist care work. However, large parts of the population are reportedly skeptical about robotics in care, and field studies are difficult to conduct due to the low prevalence of real robotics in the field. Therefore, we follow an experimental approach pertaining to the question of individual decision-making. In this regard, we analyze the aspects that influence the individual's choice between a care robot and a human caregiver for assistance in their daily life. Our economic experiment is conducted in a virtual laboratory to examine specifically how quality uncertainty of care affects individual's decisions for and against robotic care. In the experiment, 162 participants fully completed the experiment in which they were asked to repeatedly choose between a human caregiver and a care robot. Our results reveal that, overall, the care robot is chosen more often than a human caregiver. At the same time, the quality uncertainty of care linked to a human caregiver barely affected the choice of participants. On the other hand, a participant's health status and their attitude toward direct interactions with care robots did partially affect their choice. Additionally, we explored causes for indecisiveness and its effect on the choice. Here, we found indecisive participants tending to choose a human caregiver more often.
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| 5. |
- Johansson-Pajala, Rose-Marie, et al.
(författare)
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Improved Knowledge Changes the Mindset : Older Adults’ Perceptions of Care Robots
- 2019
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Ingår i: Lecture Notes in Computer Science, vol. 11592. - Cham : Springer Verlag. - 9783030220112 ; , s. 212-227
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Konferensbidrag (refereegranskat)abstract
- This paper explores Finnish, German and Swedish older adults’ perceptions of a future welfare service with increased use of welfare technologies, specifically care robots. The issues are the rapid digitalization and development of health and welfare technology, which presently is mainly technology driven (not need or user driven), and the demographic challenge. The aim of the study was to explore older adults’ perception of the future use of welfare technology or care robots. A qualitative approach with focus group discussions was employed, followed by thematic analysis. The results are presented in four overall themes: the impact on daily life for older adults and professional caregivers, codes of practice and terms of use, dissemination of information and knowledge, and conditions for successful implementation. There were significant differences in the informants’ attitudes toward and knowledge about care robots. However, the informants’ attitudes appeared to change during the focus groups and in general, became more positive. Authentic needs, which care robots could support, refer to independence, safety and security, and the ability to manage or ease daily life or working life. The results suggest that older adults, after receiving relevant information, were open to the idea of being supported by care robots in their daily lives.
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