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  • Zaccardi, Francesco, et al. (författare)
  • Mortality risk comparing walking pace to handgrip strength and a healthy lifestyle : A UK Biobank study
  • 2021
  • Ingår i: European Journal of Preventive Cardiology. - : Sage Publications. - 2047-4873 .- 2047-4881. ; 28:7, s. 704-712
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Brisk walking and a greater muscle strength have been associated with a longer life; whether these associations are influenced by other lifestyle behaviours, however, is less well known.Methods: Information on usual walking pace (self-defined as slow, steady/average, or brisk), dynamometer-assessed handgrip strength, lifestyle behaviours (physical activity, TV viewing, diet, alcohol intake, sleep and smoking) and body mass index was collected at baseline in 450,888 UK Biobank study participants. We estimated 10-year standardised survival for individual and combined lifestyle behaviours and body mass index across levels of walking pace and handgrip strength.Results: Over a median follow-up of 7.0 years, 3808 (1.6%) deaths in women and 6783 (3.2%) in men occurred. Brisk walkers had a survival advantage over slow walkers, irrespective of the degree of engagement in other lifestyle behaviours, except for smoking. Estimated 10-year survival was higher in brisk walkers who otherwise engaged in an unhealthy lifestyle compared to slow walkers who engaged in an otherwise healthy lifestyle: 97.1% (95% confidence interval: 96.9–97.3) vs 95.0% (94.6–95.4) in women; 94.8% (94.7–95.0) vs 93.7% (93.3–94.2) in men. Body mass index modified the association between walking pace and survival in men, with the largest survival benefits of brisk walking observed in underweight participants. Compared to walking pace, for handgrip strength there was more overlap in 10-year survival across lifestyle behaviours.Conclusion: Except for smoking, brisk walkers with an otherwise unhealthy lifestyle have a lower mortality risk than slow walkers with an otherwise healthy lifestyle.
  • Zenker, Frank, et al. (författare)
  • Falsification
  • 2017
  • Ingår i: The Wiley-Blackwell Encyclopedia of Social Theory. - Oxford, UK : John Wiley & Sons, Ltd. - 9781118430866 - 9781118430873
  • Bokkapitel (refereegranskat)
  • Zhai, Guangju, et al. (författare)
  • Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms.
  • 2011
  • Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 7:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands--yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15 × 10(-36)), SULT2A1 (rs2637125; p = 2.61 × 10(-19)), ARPC1A (rs740160; p = 1.56 × 10(-16)), TRIM4 (rs17277546; p = 4.50 × 10(-11)), BMF (rs7181230; p = 5.44 × 10(-11)), HHEX (rs2497306; p = 4.64 × 10(-9)), BCL2L11 (rs6738028; p = 1.72 × 10(-8)), and CYP2C9 (rs2185570; p = 2.29 × 10(-8)). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS.
  • Zillich, Lea, et al. (författare)
  • Biological aging markers in blood and brain tissue indicate age acceleration in alcohol use disorder
  • 2024
  • Ingår i: ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH. - : John Wiley & Sons. - 2993-7175. ; 48:2, s. 250-259
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundAlcohol use disorder (AUD) is associated with increased mortality and morbidity risk. A reason for this could be accelerated biological aging, which is strongly influenced by disease processes such as inflammation. As recent studies of AUD show changes in DNA methylation and gene expression in neuroinflammation-related pathways in the brain, biological aging represents a potentially important construct for understanding the adverse effects of substance use disorders. Epigenetic clocks have shown accelerated aging in blood samples from individuals with AUD. However, no systematic evaluation of biological age measures in AUD across different tissues and brain regions has been undertaken.MethodsAs markers of biological aging (BioAge markers), we assessed Levine's and Horvath's epigenetic clocks, DNA methylation telomere length (DNAmTL), telomere length (TL), and mitochondrial DNA copy number (mtDNAcn) in postmortem brain samples from Brodmann Area 9 (BA9), caudate nucleus, and ventral striatum (N = 63-94), and in whole blood samples (N = 179) of individuals with and without AUD. To evaluate the association between AUD status and BioAge markers, we performed linear regression analyses while adjusting for covariates.ResultsThe majority of BioAge markers were significantly associated with chronological age in all samples. Levine's epigenetic clock and DNAmTL were indicative of accelerated biological aging in AUD in BA9 and whole blood samples, while Horvath's showed the opposite effect in BA9. No significant association of AUD with TL and mtDNAcn was detected. Measured TL and DNAmTL showed only small correlations in blood and none in brain.ConclusionsThe present study is the first to simultaneously investigate epigenetic clocks, telomere length, and mtDNAcn in postmortem brain and whole blood samples in individuals with AUD. We found evidence for accelerated biological aging in AUD in blood and brain, as measured by Levine's epigenetic clock, and DNAmTL. Additional studies of different tissues from the same individuals are needed to draw valid conclusions about the congruence of biological aging in blood and brain.
  • Zuurbier, Susanna M, et al. (författare)
  • Cerebral Venous Thrombosis in Older Patients.
  • 2018
  • Ingår i: Stroke. - 1524-4628. ; 49:1, s. 197-200
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebral venous thrombosis (CVT) is rare in older patients. We investigated whether clinical features and outcomes differ in older and younger patients.We used data from a multicenter observational registry of consecutive adult patients with CVT admitted between 1987 and 2016. We compared demographics, clinical manifestations, and outcomes between older (upper quartile of the age distribution) and younger (lower 3 quartiles of the age distribution) patients.Data for 843 patients with CVT were available. The median age was 43 years (interquartile range, 30-55 years). Older patients (≥55 years; n=222) were less often women than younger patients (48% versus 71%; P<0.001) and less often reported headache (63% versus 87%; P<0.001). Cancer was more common in older patients (24% versus 9%; P<0.001), especially solid malignancies (19% versus 5%; P<0.001). Outcome at follow-up was worse in older patients (modified Rankin Scale, 3-6; adjusted odds ratio, 2.68; 95% confidence interval, 1.78-4.03; mortality, adjusted odds ratio, 2.13; 95% confidence interval, 1.09-4.19).The sex ratio of CVT is evenly distributed in older patients, probably because of the dissipation of hormonal influences. Malignancy should be considered as a potential precipitant in older patients with CVT.
  • Åslund, Andreas, et al. (författare)
  • Novel Pentameric Thiophene Derivatives for in Vitro and in Vivo Optical Imaging of a Plethora of Protein Aggregates in Cerebral Amyloidoses
  • 2009
  • Ingår i: ACS CHEMICAL BIOLOGY. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 4:8, s. 673-684
  • Tidskriftsartikel (refereegranskat)abstract
    • Molecular probes for selective Identification of protein aggregates are important to advance our understanding of the molecular pathogenesis underlying cerebral amyloidoses. Here we report the chemical design of pentameric thiophene derivatives, denoted luminescent conjugated oligothiophenes (LCOs), which could be used for real-time visualization of cerebral protein aggregates in transgenic mouse models of neurodegenerative diseases by multiphoton microscopy. One of the LCOs, p-FTAA, could be utilized for ex vivo spectral assignment of distinct prion deposits from two, mouse-adapted prion strains. p-FTAA also revealed a transient soluble pre-fibrillar non-thioflavinophilic A beta-assemblies during in vitro fibrillation of A beta peptides. In brain tissue samples, A beta deposits and neurofibrillary tangles (NFTs) were readily identified by a strong fluorescence from p-FTAA and the LCO staining showed complete co-localliation with conventional antibodies (6E10 and AT8). In addition, a patchy islet-like staining of individual A beta plaque was unveiled by the anti-oligomer A11 antibody during co-staining with p-FTAA. The major hallmarks of Alzheimers disease, namely, A beta aggregates versus NFTs, could also be distinguished because of distinct emission spectra from p-FTAA. Overall, we demonstrate that LCOs can be utilized as powerful practical research tools for studying protein aggregation diseases and facilitate the study of amyloid origin, evolution and maturation, A beta-tau interactions, and pathogenesis both ex vivo and in vivo.
  • Öberg, Henrik, et al. (författare)
  • Stability of Pt-Modified Cu(111) in the Presence of Oxygen and Its Implication on the Overall Electronic Structure
  • 2013
  • Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 117:32, s. 16371-16380
  • Tidskriftsartikel (refereegranskat)abstract
    • The electronic structure and stability of Cu(111)-hosted Pt overlayers with and without the presence of atomic oxygen have been studied by means of core-level spectroscopy and density functional theory (DFT). Because of lattice mismatch, Pt(111) overlayers grown on Cu(111) are compressively strained, and hard X-ray photoelectron spectroscopy together with Pt L-3-edge X-ray absorption spectroscopy (XAS) reveals a pronounced downshift of the Pt d-band owing to the increased overlap of the d-orbitals, an effect also reproduced theoretically. Exposure to oxygen severely alters the surface composition; the O-Cu binding energy largely exceeds that of O-Pt, and DFT calculations predict surface segregation of Cu atoms. Comparing the adsorbate electronic structure for O on unstrained Pt(111) with that of O on Pt-modified Cu(111) using O K-edge XAS and X-ray emission spectroscopy salient differences are observed and calculations show that Cu-segregation to the topmost layer is required to reproduce the measured spectra. It is proposed that O is binding in a hollow site constituted by at least two Cu atoms and that up to 75% of the Pt atoms migrate below the surface.
  • Özalp, V Cengiz, et al. (författare)
  • Small molecule detection by lateral flow strips via aptamer-gated silica nanoprobes.
  • 2016
  • Ingår i: The Analyst. - : Royal Society of Chemistry (RSC). - 0003-2654 .- 1364-5528. ; 141:8, s. 2595-9
  • Tidskriftsartikel (refereegranskat)abstract
    • A fast, sensitive and ratiometric biosensor strategy for small molecule detection was developed through nanopore actuation. The new platform engineers together, a highly selective molecular recognition element, aptamers, and a novel signal amplification mechanism, gated nanopores. As a proof of concept, aptamer gated silica nanoparticles have been successfully used as a sensing platform for the detection of ATP concentrations at a wide linear range from 100 μM up to 2 mM.
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