| 1. |
- Jones, Lesley, et al.
(författare)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Tidskriftsartikel (refereegranskat)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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| 2. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 3. |
- Tedersoo, Leho, et al.
(författare)
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Global diversity and geography of soil fungi
- 2014
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6213, s. artikel nr 1256688-
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Tidskriftsartikel (refereegranskat)abstract
- Fungi play major roles in ecosystem processes, but the determinants of fungal diversity and biogeographic patterns remain poorly understood. Using DNA metabarcoding data from hundreds of globally distributed soil samples, we demonstrate that fungal richness is decoupled from plant diversity. The plant-to-fungus richness ratio declines exponentially toward the poles. Climatic factors, followed by edaphic and spatial variables, constitute the best predictors of fungal richness and community composition at the global scale. Fungi show similar latitudinal diversity gradients to other organisms, with several notable exceptions. These findings advance our understanding of global fungal diversity patterns and permit integration of fungi into a general macroecological framework.
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| 4. |
- Hallgren, Mats, et al.
(författare)
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Associations of device-measured and self-reported physical activity with alcohol consumption : Secondary analyses of a randomized controlled trial (FitForChange).
- 2024
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Ingår i: Drug And Alcohol Dependence. - : Elsevier. - 0376-8716 .- 1879-0046. ; 259
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Physical activity (PA) is increasingly used as an adjunct treatment for alcohol use disorder (AUD). Previous studies have relied on self-report measures of PA, which are prone to measurement error. In the context of a randomized controlled trial of PA for AUD, we examined: (1) associations between device-measured and self-reported PA, (2) associations between PA measurements and alcohol use, and (3) the feasibility of obtaining device-measured PA data in this population.METHOD: One-hundred and forty individuals with clinician-diagnosed AUD participated in a 12-week intervention comparing usual care (phone counselling) to yoga-based exercise and aerobic exercise. Device-measured PA (Actigraph GT3x), self-reported PA (International Physical Activity Questionnaire) and alcohol consumption (Timeline Follow Back Method) were assessed before and after the trial. Effects of the interventions on PA levels were assessed using linear mixed models.RESULTS: In total, 42% (n=59) of participants returned usable device-measured PA data (mean age= 56±10 years, 73% male). Device-measured and self-reported vigorous-intensity PA were correlated (β= -0.02, 95%CI= -0.03, -0.00). No associations were found for moderate-intensity PA. Compared to usual care, time spent in device-measured light-intensity PA increased in the aerobic exercise group (∆= 357, 95%CI= 709, 5.24). Increases in device-measured light-intensity PA were associated with fewer standard drinks (∆= -0.24, 95%CI= -0.03, -0.44), and fewer heavy drinking days (∆= -0.06, 95%CI=-0.01, -0.10).CONCLUSION: Increases in light-intensity/habitual PA were associated with less alcohol consumption in adults with AUD. Self-reported PA data should be interpreted with caution. Incentives are needed to obtain device-measured PA data in AUD populations.
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| 5. |
- Hallgren, Mats, et al.
(författare)
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Associations of interruptions to leisure-time sedentary behaviour with symptoms of depression and anxiety.
- 2020
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Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Interruptions to time spent sitting can ameliorate detrimental metabolic-health consequences of high volumes of sedentary time, but their potential mental health benefits have not been examined. We used the Swedish Health Profile Assessment database, a general health assessment offered to all employees working for companies or organisations connected to occupational and health services. Cross-sectional analyses examined data from 40,550 employees (60% male, mean age = 42 years), collected in 2017-2019. Participants reported the proportion of time (almost always; 75% of the time; 50% of the time; 25% of the time; and almost never) usually spent in leisure-time sedentary behaviours; and, separately, the frequency (never; rarely; sometimes; often; and very often) of interruptions (every 30 min) to sedentary time. Logistic regression models assessed associations of sedentary time, and the frequency of interruptions to sedentary time, with depression/anxiety symptoms. Fully adjusted models included physical exercise. Compared to those in the lowest sedentary time category, those in the medium and high categories had 1.52 (95% confidence interval (CI) = 1.40-1.66) and 3.11 (95% CI = 2.82-3.42) higher odds of frequent depression/anxiety symptoms, respectively. Compared to those who never/rarely interrupted their sedentary time, those who reported interruptions sometimes, often and very often had 0.72 (95% CI = 0.65-0.80), 0.59 (95% CI = 0.53-0.65), and 0.53 (95% CI = 0.46-0.59) lower odds of depression/anxiety symptoms, respectively. In stratified analyses, more frequent interruptions to sedentary time were associated with lower odds of depression/anxiety symptoms, except among those in the lowest interruptions categories (never/25% of the time). More regularly interrupting sitting during leisure-time may reduce the odds of experiencing symptoms of depression and anxiety.
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| 6. |
- Hallgren, Mats, et al.
(författare)
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Associations of sedentary behavior in leisure and occupational contexts with symptoms of depression and anxiety.
- 2020
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Ingår i: Preventive Medicine. - : Elsevier. - 0091-7435 .- 1096-0260. ; 133
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Tidskriftsartikel (refereegranskat)abstract
- Sedentary behaviors (SB) can be associated with poorer mental health, but it remains unclear whether contexts for these behaviors may be important. We assessed relationships of SB in leisure-time and occupational contexts with frequent symptoms of depression and anxiety. Data originate from the Swedish Health Profile Assessment (HPA) database, a health assessment offered to employees working for companies or organizations connected to healthcare services. Analyses are based on data from 2017 onwards (N = 23,644; 57% male, mean age = 42 years). Two self-report questions assessed proportions of time spent in SB in leisure contexts and in the occupational setting. Logistic regressions examined relationships of SB in each context with the self-reporting of frequent symptoms of depression/anxiety. A separate model for the leisure plus occupational SB was also generated. Fully-adjusted models included exercise frequency. Compared to those reporting that they were 'almost never' sedentary in leisure-time contexts, a detrimental dose-response with frequent depression/anxiety symptoms was observed with increasing proportions of sedentary time: 50% of the time (OR = 1.44; 1.23-1.70), 75% (OR = 2.95; 2.45-3.54), almost always (OR = 3.85; 2.84-5.22). For occupational SB, the only associations were among those who reported being sedentary almost always, compared to almost never (OR = 1.47; 1.25-1.73). Associations of 'overall' SB with depression/anxiety symptoms mirrored the dose-response relationship for leisure-time SB. Exercise frequency attenuated the association for leisure-time SB only, but it remained statistically significant. Adults who spend ≥50% of their leisure-time in sedentary pursuits experience more frequent symptoms of depression and anxiety, compared to those who are less sedentary in that context.
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| 7. |
- Hallgren, Mats, et al.
(författare)
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Habitual physical activity levels predict treatment outcomes in depressed adults : A prospective cohort study.
- 2016
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Ingår i: Preventive Medicine. - : Elsevier BV. - 0091-7435 .- 1096-0260. ; 88, s. 53-58
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Exercise is an efficacious stand-alone therapy for mild-to-moderate depression, but little is known about the influence of physical activity levels on responses to depression treatment. This study aimed to prospectively assess the association between self-reported habitual physical activity levels and depression severity following a 12-week intervention.METHOD: 629 adults (75% women; aged 18-71years) with mild-to-moderate depression were recruited from primary care centres across Sweden and treated for 12weeks. The interventions included internet-based cognitive behavioural therapy (ICBT) and 'usual care' (CBT or supportive counselling). One third of all participants were taking anti-depressant medication. The primary outcome was the change in depression severity assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). Habitual physical activity levels were self-rated and based on the estimated frequency, duration and intensity of total physical activity, including planned exercise, 'during a typical week'. Prospective associations were explored using linear regression models (percentage change) with 95% confidence intervals (CI's).RESULTS: Following adjustment for relevant covariates, high levels of habitual physical activity were associated with larger relative reductions in depression severity compared to low physical activity (β=-9.19, 95% CI=-18.46, -0.09, p=0.052) and moderate physical activity (β=-10.81, 95% CI=-21.09, -0.53, p<0.05), respectively.CONCLUSION: Adults who routinely engage in high levels of physical activity respond more favourably to CBT-focused depression treatments than adults who engage in low-to-moderate levels of activity. The optimal level of physical activity associated with reductions in depression severity corresponds to consensus recommendations for maximizing general health. One limitation is the use of self-reported physical activity data.
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| 8. |
- Helgadóttir, Björg, et al.
(författare)
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Changes in physical activity and sedentary behavior associated with an exercise intervention in depressed adults
- 2017
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Ingår i: Psychology of Sport And Exercise. - : Elsevier BV. - 1469-0292 .- 1878-5476. ; 30, s. 10-18
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Tidskriftsartikel (refereegranskat)abstract
- Background Exercise is beneficial for depression, but less is known about its impact on post-intervention physical activity and sedentary behavior. The aim of this paper was to determine the extent to which participation in light-, moderate- and vigorous-intensity exercise intervention influenced habitual physical activity and sedentary behavior patterns in depressed adults. Methods Accelerometer data was collected pre- and post-intervention from depressed participants randomized to one of three 12-week intervention groups: light (n = 21), moderate (n = 25) and vigorous (n = 22) exercise. Mixed models examined changes in time spent sedentary and in light and moderate-to-vigorous physical activity (MVPA); time accumulated in sedentary and MVPA bouts; and, number of MVPA bouts and interruptions in sedentary time. Results Overall sedentary time decreased while light activity time increased across all intervention groups but not significantly so. The light exercise intervention group reduced MVPA minutes (−8.22, 95% CI: −16.44, −0.01), time in MVPA bouts (−8.44, 95% CI: −14.27, −2.62), and number of activity bouts (−0.43, 95% CI: −0.77, −0.09). The moderate exercise intervention group reduced time in MVPA bouts (−6.27, 95% CI: −11.71, −0.82) and number of sedentary interruptions (−6.07, 95% CI: −9.30, −2.84). No changes were observed for the vigorous exercise intervention group. Conclusions The exercise intervention led to an increase in overall light physical activity and decrease in sedentary time, though neither change was statistically significant. Participation in the light and moderate exercise intervention groups was associated with reductions of time in MVPA bouts, but this was not evident for the vigorous exercise intervention group.
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| 9. |
- Howard, Bethany J., et al.
(författare)
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Self-Reported Sitting Time, Physical Activity and Fibrinolytic and Other Novel Cardio-Metabolic Biomarkers in Active Swedish Seniors
- 2016
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Ingår i: PLOS ONE. - San Francisco, USA : Public Library od Scence. - 1932-6203. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Too much sitting is linked with an increased risk of cardiovascular disease and mortality. The mediating mechanisms for these associations are largely unknown, however dysregulated fibrinolysis have emerged as a possible contributor.Objective: We examined the associations of self-reported overall sitting time and physical activity with fibrinolytic and other novel cardio-metabolic biomarkers in older adults.Materials and Methods: Data was analysed for 364 participants (74±7 yrs) of the Active Seniors group (retired, living independently in their own homes). Linear regression analyses examined associations of categories of categories of sitting time (≤3, 3-6, >6 hrs/day) and overall physical activity (Low, Moderate and High) with biomarkers in serum or plasma, adjusting for age, gender and smoking (with further adjustment for either overall physical activity or sitting time and BMI in secondary analyses).Results: Compared to sitting ≤ 3 hrs/day, sitting >6 hrs/day was associated with higher tissue plasminogen activator (tPA) and tissue plasminogen activator/plasminogen activator inhibitor-1 complex (tPA-PAI-1 complex). These associations were not independent of overall physical activity or BMI. Compared to those in the high physical activity, low physical activity was associated with a higher BMI, high-sensitivity C-reactive protein (hs-CRP) and tPA-PAI-1 complex levels. Only the associations of BMI and hs-CRP were independent of sitting time.Conclusions: These findings provide preliminary cross-sectional evidence for the relationships of sitting time with fibrinolytic markers in older adults. They also reinforce the importance of regular physical activity for cardio-metabolic health.
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| 10. |
- Wennberg, Patrik, et al.
(författare)
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Acute effects of breaking up prolonged sitting on fatigue and cognition : a pilot study
- 2016
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To compare the acute effects of uninterrupted sitting with sitting interrupted by brief bouts of light-intensity walking on self-reported fatigue, cognition, neuroendocrine biomarkers and cardiometabolic risk markers in overweight/obese adults.Design: Randomised two-condition crossover trial.Setting: Laboratory study conducted in Melbourne, Australia.Participants: 19 overweight/obese adults (45–75 years).Interventions: After an initial 2 h period seated, participants consumed a meal-replacement beverage and completed (on 2 days separated by a 6-day washout period) each condition over the next 5 h: uninterrupted sitting (sedentary condition) or sitting with 3 min bouts of light-intensity walking every 30 min (active condition).Primary outcome measures: Self-reported fatigue, executive function and episodic memory at 0 h, 4 h and 7 h.Secondary outcome measures: Neuroendocrine biomarkers and cardiometabolic risk markers (blood collections at 0 h, 4 h and 7 h, blood pressure and heart rate measured hourly and interstitial glucose measured using a continuous glucose monitoring system).Results: During the active condition, fatigue levels were lower at 4 h (−13.32 (95% CI −23.48 to −3.16)) and at 7 h (−10.73 (95% CI −20.89 to −0.58)) compared to the sedentary condition. Heart rate was higher at 4 h (4.47 (95% CI 8.37 to 0.58)) and at 7 h (4.32 (95% CI 8.21 to 0.42)) during the active condition compared to the sedentary condition. There were no significant differences between conditions by time for other variables. In the sedentary condition, changes in fatigue scores over time correlated with a decrease in heart rate and plasma dihydroxyphenylalanine (DOPA) and an increase in plasma dihydroxyphenylglycol (DHPG).Conclusions: Interrupting prolonged sitting with light-intensity walking breaks may be an effective fatigue countermeasure acutely. Fatigue levels corresponded with the heart rate and neuroendocrine biomarker changes in uninterrupted sitting in this pilot study. Further research is needed to identify potential implications, particularly for the occupational health context.
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