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| 2. |
- Bogie, JFJ, et al.
(författare)
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Stearoyl-CoA desaturase-1 impairs the reparative properties of macrophages and microglia in the brain
- 2020
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 217:5
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Tidskriftsartikel (refereegranskat)abstract
- Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis. Macrophages and microglia are crucially involved in the formation and repair of demyelinated lesions. Here we show that myelin uptake temporarily skewed these phagocytes toward a disease-resolving phenotype, while sustained intracellular accumulation of myelin induced a lesion-promoting phenotype. This phenotypic shift was controlled by stearoyl-CoA desaturase-1 (SCD1), an enzyme responsible for the desaturation of saturated fatty acids. Monounsaturated fatty acids generated by SCD1 reduced the surface abundance of the cholesterol efflux transporter ABCA1, which in turn promoted lipid accumulation and induced an inflammatory phagocyte phenotype. Pharmacological inhibition or phagocyte-specific deficiency of Scd1 accelerated remyelination ex vivo and in vivo. These findings identify SCD1 as a novel therapeutic target to promote remyelination.
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| 3. |
- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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- Marien, E., et al.
(författare)
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Non-small cell lung cancer is characterized by dramatic changes in phospholipid profiles
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 137:7, s. 1539-1548
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Tidskriftsartikel (refereegranskat)abstract
- Non-small cell lung cancer (NSCLC) is the leading cause of cancer death globally. To develop better diagnostics and more effective treatments, research in the past decades has focused on identification of molecular changes in the genome, transcriptome, proteome, and more recently also the metabolome. Phospholipids, which nevertheless play a central role in cell functioning, remain poorly explored. Here, using a mass spectrometry (MS)-based phospholipidomics approach, we profiled 179 phospholipid species in malignant and matched non-malignant lung tissue of 162 NSCLC patients (73 in a discovery cohort and 89 in a validation cohort). We identified 91 phospholipid species that were differentially expressed in cancer versus non-malignant tissues. Most prominent changes included a decrease in sphingomyelins (SMs) and an increase in specific phosphatidylinositols (PIs). Also a decrease in multiple phosphatidylserines (PSs) was observed, along with an increase in several phosphatidylethanolamine (PE) and phosphatidylcholine (PC) species, particularly those with 40 or 42 carbon atoms in both fatty acyl chains together. 2D-imaging MS of the most differentially expressed phospholipids confirmed their differential abundance in cancer cells. We identified lipid markers that can discriminate tumor versus normal tissue and different NSCLC subtypes with an AUC (area under the ROC curve) of 0.999 and 0.885, respectively. In conclusion, using both shotgun and 2D-imaging lipidomics analysis, we uncovered a hitherto unrecognized alteration in phospholipid profiles in NSCLC. These changes may have important biological implications and may have significant potential for biomarker development. What's new? Cellular membranes are subject to extensive modification in cancer, often with marked alterations in phospholipid metabolism. The extent and nature of those changes are not fully known, however, particularly for non-small cell lung cancer (NSCLC). In this study, lipidomics analysis of phospholipid profiles uncovered dramatic differences between NSCLC and normal lung tissue. The differences were confirmed via 2D-imaging lipidomics in tissue sections. Lipid markers capable of discriminating between tumor and normal tissue and between different NSCLC subtypes were identified. The observed alterations in NSCLC phospholipid profiles may be biologically significant.
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| 5. |
- Sim, Thomas G., et al.
(författare)
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Regional variability in peatland burning at mid-to high-latitudes during the Holocene
- 2023
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Ingår i: Quaternary Science Reviews. - : Elsevier. - 0277-3791 .- 1873-457X. ; 305
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Tidskriftsartikel (refereegranskat)abstract
- Northern peatlands store globally-important amounts of carbon in the form of partly decomposed plant detritus. Drying associated with climate and land-use change may lead to increased fire frequency and severity in peatlands and the rapid loss of carbon to the atmosphere. However, our understanding of the patterns and drivers of peatland burning on an appropriate decadal to millennial timescale relies heavily on individual site-based reconstructions. For the first time, we synthesise peatland macrocharcoal re-cords from across North America, Europe, and Patagonia to reveal regional variation in peatland burning during the Holocene. We used an existing database of proximal sedimentary charcoal to represent regional burning trends in the wider landscape for each region. Long-term trends in peatland burning appear to be largely climate driven, with human activities likely having an increasing influence in the late Holocene. Warmer conditions during the Holocene Thermal Maximum (similar to 9e6 cal. ka BP) were associated with greater peatland burning in North America's Atlantic coast, southern Scandinavia and the Baltics, and Patagonia. Since the Little Ice Age, peatland burning has declined across North America and in some areas of Europe. This decline is mirrored by a decrease in wider landscape burning in some, but not all sub-regions, linked to fire-suppression policies, and landscape fragmentation caused by agricultural expansion. Peatlands demonstrate lower susceptibility to burning than the wider landscape in several instances, probably because of autogenic processes that maintain high levels of near-surface wetness even during drought. Nonetheless, widespread drying and degradation of peatlands, particularly in Europe, has likely increased their vulnerability to burning in recent centuries. Consequently, peatland restoration efforts are important to mitigate the risk of peatland fire under a changing climate. Finally, we make recommendations for future research to improve our understanding of the controls on peatland fires.(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 8. |
- Guimaraes, V, et al.
(författare)
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An Exergame Solution for Personalized Multicomponent Training in Older Adults
- 2021
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Ingår i: APPLIED SCIENCES-BASEL. - : MDPI AG. - 2076-3417. ; 11:17
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In addition to contributing to increased training motivation, exergames are a promising approach to counteract age-related impairments. Mobility limitations, cognitive impairment, and urinary incontinence are very common in older adults. To optimally address these conditions, exergames should include interventions for strength, balance, cognition, and pelvic floor muscle training. In this study, we develop a personalized multicomponent exergame solution for the geriatric rehabilitation of age-related impairments. The exergame can provide interventions for balance, strength, cognition, and urinary incontinence in one single session, accommodating the needs of older adults with multiple disabilities. For its development, we involved a multidisciplinary team that helped us to specify the structure and contents of the exergame considering training requirements, game design principles, and end-user characteristics. In addition to allowing the customization of the training components, the exergame includes automatic adaptation of difficulty/load, in line with player progress over time. The game mechanics ensures the fulfilment of training needs as defined by the therapist. The exergame is cross-platform compatible (web-based) and includes novel means of interaction with wearable sensors.
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| 10. |
- Kwakkel, G., et al.
(författare)
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Motor rehabilitation after stroke: European Stroke Organisation (ESO) consensus-based definition and guiding framework
- 2023
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Ingår i: European Stroke Journal. - 2396-9873. ; 8:4, s. 880-894
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Forskningsöversikt (refereegranskat)abstract
- Purpose: To propose a consensus-based definition and framework for motor rehabilitation after stroke. Methods: An expert European working group reviewed the literature, attaining internal consensus after external feedback. Findings: Motor rehabilitation is defined as a process that engages people with stroke to benefit their motor function, activity capacity and performance in daily life. It is necessary for people with residual motor disability whose goal is to enhance their functioning, independence and participation. Motor rehabilitation operates through learning- and use-dependent mechanisms. The trajectory of motor recovery varies across patients and stages of recovery. Early behavioral restitution of motor function depends on spontaneous biological mechanisms. Further improvements in activities of daily living are achieved by compensations. Motor rehabilitation is guided by regular assessment of motor function and activity using consensus-based measures, including patient-reported outcomes. Results are discussed with the patient and their carers to set personal goals. During motor rehabilitation patients learn to optimize and adapt their motor, sensory and cognitive functioning through appropriately dosed repetitive, goal-oriented, progressive, task- and context-specific training. Motor rehabilitation supports people with stroke to maximize health, well-being and quality of life. The framework describes the International Classification of Functioning, Disability and Health in the context of stroke, describes neurobiological mechanisms of behavioral restitution and compensation, and summarizes recommendations for clinical assessment, prediction tools, and motor interventions with strong recommendations from clinical practice guidelines (2016-2022). Conclusions: This definition and framework may guide clinical educators, inform clinicians on current recommendations and guidelines, and identify gaps in the evidence base.
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