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- Vogel, Jacob W., et al.
(author)
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Four distinct trajectories of tau deposition identified in Alzheimer’s disease
- 2021
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:5, s. 871-881
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Journal article (peer-reviewed)abstract
- Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These ‘subtypes’ were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of ‘typical AD’ and a revisiting of tau pathological staging. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
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- Steinacker, J. M., et al.
(author)
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Global Alliance for the Promotion of Physical Activity: the Hamburg Declaration
- 2023
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In: Bmj Open Sport & Exercise Medicine. ; 9:3
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Journal article (peer-reviewed)abstract
- Non-communicable diseases (NCDs), including coronary heart disease, stroke, hypertension, type 2 diabetes, dementia, depression and cancers, are on the rise worldwide and are often associated with a lack of physical activity (PA). Globally, the levels of PA among individuals are below WHO recommendations. A lack of PA can increase morbidity and mortality, worsen the quality of life and increase the economic burden on individuals and society. In response to this trend, numerous organisations came together under one umbrella in Hamburg, Germany, in April 2021 and signed the 'Hamburg Declaration'. This represented an international commitment to take all necessary actions to increase PA and improve the health of individuals to entire communities. Individuals and organisations are working together as the 'Global Alliance for the Promotion of Physical Activity' to drive long-term individual and population-wide behaviour change by collaborating with all stakeholders in the community: active hospitals, physical activity specialists, community services and healthcare providers, all achieving sustainable health goals for their patients/clients. The 'Hamburg Declaration' calls on national and international policymakers to take concrete action to promote daily PA and exercise at a population level and in healthcare settings.
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- Zhou, XP, et al.
(author)
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Non-coding variability at the APOE locus contributes to the Alzheimer's risk
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3310-
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Journal article (peer-reviewed)abstract
- Alzheimer’s disease (AD) is a leading cause of mortality in the elderly. While the coding change of APOE-ε4 is a key risk factor for late-onset AD and has been believed to be the only risk factor in the APOE locus, it does not fully explain the risk effect conferred by the locus. Here, we report the identification of AD causal variants in PVRL2 and APOC1 regions in proximity to APOE and define common risk haplotypes independent of APOE-ε4 coding change. These risk haplotypes are associated with changes of AD-related endophenotypes including cognitive performance, and altered expression of APOE and its nearby genes in the human brain and blood. High-throughput genome-wide chromosome conformation capture analysis further supports the roles of these risk haplotypes in modulating chromatin states and gene expression in the brain. Our findings provide compelling evidence for additional risk factors in the APOE locus that contribute to AD pathogenesis.
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- Bustin, Stephen A., et al.
(author)
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The need for transparency and good practices in the qPCR literature
- 2013
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In: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 10:11, s. 1063-1067
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Journal article (other academic/artistic)abstract
- Two surveys of over 1,700 publications whose authors use quantitative real-time PCR (qPCR) reveal a lack of transparent and comprehensive reporting of essential technical information. Reporting standards are significantly improved in publications that cite the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines, although such publications are still vastly outnumbered by those that do not.
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- Hallgren, Mats, et al.
(author)
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Habitual physical activity levels predict treatment outcomes in depressed adults : A prospective cohort study.
- 2016
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In: Preventive Medicine. - : Elsevier BV. - 0091-7435 .- 1096-0260. ; 88, s. 53-58
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Journal article (peer-reviewed)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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- Hjelle, B, et al.
(author)
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Rapid and specific detection of Sin Nombre virus antibodies in patients with hantavirus pulmonary syndrome by a strip immunoblot assay suitable for field diagnosis.
- 1997
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In: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 35:3, s. 600-8
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Journal article (peer-reviewed)abstract
- To develop a rapid antibody test for Sin Nombre hantavirus (SNV) infection for diagnosis of hantavirus pulmonary syndrome (HPS) in field settings where advanced instrumentation is not available, a strip immunoblot assay bearing four immobilized antigens for SNV and a recombinant nucleocapsid protein antigen of Seoul hantavirus (SEOV) was prepared. The SNV antigens included a full-length recombinant-expressed nucleocapsid (N) protein (rN), a recombinant-expressed G1 protein (residues 35 to 117), and synthetic peptides derived from N (residues 17 to 59) and G1 (residues 55 to 88). On the basis of the observed reactivities of hantavirus-infected patient and control sera, we determined that a positive assay requires reactivity with SNV or SEOV rN antigen and at least one other antigen. Isolated reactivity to either viral rN antigen is indeterminate, and any pattern of reactivity that does not include reactivity to an rN antigen is considered indeterminate but is unlikely to represent hantavirus infection. Fifty-eight of 59 samples from patients with acute SNV-associated HPS were positive according to these criteria, and one was initially indeterminate. Four of four samples from patients with HPS due to other hantaviruses were positive, as were most samples from patients with SEOV and Puumala virus infections. Of 192 control serum samples, 2 (1%) were positive and 2 were indeterminate. Acute SNV infection was distinguishable from remote SNV infection or infection with hantaviruses other than SNV by the presence of G1 peptide antigen reactivities in the former. The strip immunoblot assay shows promise for the detection of SNV antibodies early in the course of HPS.
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