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- Wolk, David A., et al.
(författare)
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Use of flutemetamol F18-labeled positron emission tomography and other biomarkers to assess risk of clinical progression in patients with amnestic mild cognitive impairment
- 2018
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149. ; 75:9, s. 1114-1123
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Patients with amnestic mild cognitive impairment (aMCI) may progress to clinical Alzheimer disease (AD), remain stable, or revert to normal. Earlier progression to AD among patients who were β-amyloid positive vs those who were β-amyloid negative has been previously observed. Current research now accepts that a combination of biomarkers could provide greater refinement in the assessment of risk for clinical progression. Objective: To evaluate the ability of flutemetamol F 18 and other biomarkers to assess the risk of progression from aMCI to probable AD. Design, Setting, and Participants: In this multicenter cohort study, from November 11, 2009, to January 16, 2014, patients with aMCI underwent positron emission tomography (PET) at baseline followed by local clinical assessments every 6 months for up to 3 years. Patients with aMCI (365 screened; 232 were eligible) were recruited from 28 clinical centers in Europe and the United States. Physicians remained strictly blinded to the results of PET, and the standard of truth was an independent clinical adjudication committee that confirmed or refuted local assessments. Flutemetamol F 18-labeled PET scans were read centrally as either negative or positive by 5 blinded readers with no knowledge of clinical status. Statistical analysis was conducted from February 19, 2014, to January 26, 2018. Interventions: Flutemetamol F 18-labeled PET at baseline followed by up to 6 clinical visits every 6 months, as well as magnetic resonance imaging and multiple cognitive measures. Main Outcomes and Measures: Time from PET to probable AD or last follow-upwas plotted as a Kaplan-Meier survival curve; PET scan results, age, hippocampal volume, and aMCI stage were entered into Cox proportional hazards logistic regression analyses to identify variables associated with progression to probable AD. Results: Of 232 patients with aMCI (118 women and 114 men; mean [SD] age, 71.1 [8.6] years), 98 (42.2%) had positive results detected on PET scan. By 36 months, the rates of progression to probable AD were 36.2% overall (81 of 224 patients), 53.6%(52 of 97) for patients with positive results detected on PET scan, and 22.8% (29 of 127) for patients with negative results detected on PET scan. Hazard ratios for association with progression were 2.51 (95% CI, 1.57-3.99; P < .001) for a positive β-amyloid scan alone (primary outcome measure), 5.60 (95%CI, 3.14-9.98; P < .001) with additional low hippocampal volume, and 8.45 (95%CI, 4.40-16.24; P < .001) when poorer cognitive status was added to the model. Conclusions and Relevance: A combination of positive results of flutemetamol F 18-labeled PET, low hippocampal volume, and cognitive status corresponded with a high probability of risk of progression from aMCI to probable AD within 36 months.
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| 2. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 3. |
- Sasidharan, Kavitha, et al.
(författare)
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IL32 downregulation lowers triglycerides and type I collagen in di-lineage human primary liver organoids.
- 2024
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Ingår i: Cell reports. Medicine. - 2666-3791. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Steatotic liver disease (SLD) prevails as the most common chronic liver disease yet lack approved treatments due to incomplete understanding of pathogenesis. Recently, elevated hepatic and circulating interleukin 32 (IL-32) levels were found in individuals with severe SLD. However, the mechanistic link between IL-32 and intracellular triglyceride metabolism remains to be elucidated. We demonstrate invitro that incubation with IL-32β protein leads to an increase in intracellular triglyceride synthesis, while downregulation of IL32 by small interfering RNA leads to lower triglyceride synthesis and secretion in organoids from human primary hepatocytes. This reduction requires the upregulation of Phospholipase A2 group IIA (PLA2G2A). Furthermore, downregulation of IL32 results in lower intracellular type I collagen levels in di-lineage human primary hepatic organoids. Finally, we identify a genetic variant of IL32 (rs76580947) associated with lower circulating IL-32 and protection against SLD measured by non-invasive tests. These data suggest that IL32 downregulation may be beneficial against SLD.
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| 4. |
- Zengarini, Elisa, et al.
(författare)
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Prognosis and Interplay of Cognitive Impairment and Sarcopenia in Older Adults Discharged from Acute Care Hospitals
- 2019
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 8:10
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Tidskriftsartikel (refereegranskat)abstract
- Sarcopenia and cognitive impairment are associated with an increased risk of negative outcomes, but their prognostic interplay has not been investigated so far. We aimed to investigate the prognostic interaction of sarcopenia and cognitive impairment concerning 12-month mortality among older patients discharged from acute care wards in Italy. Our series consisted of 624 patients (age = 80.1 +/- 7.0 years, 56.1% women) enrolled in a prospective observational study. Sarcopenia was defined following the European Working Group on Sarcopenia in Older People (EWGSOP) criteria. Cognitive impairment was defined as age- and education-adjusted Mini-Mental State Examination (MMSE) score < 24 or recorded diagnosis of dementia. The study outcome was all-cause mortality during 12-month follow-up. The combination of sarcopenia and cognitive ability was tested against participants with intact cognitive ability and without sarcopenia. Overall, 159 patients (25.5%) were identified as having sarcopenia, and 323 (51.8%) were cognitively impaired. During the follow-up, 79 patients (12.7%) died. After adjusting for potential confounders, the combination of sarcopenia and cognitive impairment has been found associated with increased mortality (HR = 2.12, 95% CI = 1.05-4.13). Such association was also confirmed after excluding patients with dementia (HR = 2.13, 95% CI = 1.06-4.17), underweight (HR = 2.18, 95% CI = 1.03-3.91), high comorbidity burden (HR = 2.63, 95% CI = 1.09-6.32), and severe disability (HR = 2.88, 95% CI = 1.10-5.73). The co-occurrence of sarcopenia and cognitive impairment may predict 1-year mortality in older patients discharged from acute care hospitals.
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