| 11. |
- Nylander, Ruta, et al.
(författare)
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Relation between cardiovascular disease risk markers and brain infarcts detected by magnetic resonance imaging in an elderly population
- 2015
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Ingår i: Journal of Stroke & Cerebrovascular Diseases. - : Elsevier BV. - 1052-3057 .- 1532-8511. ; 24:2, s. 312-318
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Established cardiovascular risk markers, such as hypertension, are associated with increased risk of brain infarcts. The newer markers N-terminal pro-brain natriuretic peptide, troponin I, C-reactive protein, and cystatin C may affect the risk of cardiovascular events and potentially, thereby, also stroke. We investigated the association between established and new risk markers for cardiovascular disease and brain infarcts detected by magnetic resonance imaging (MRI) at age 75.METHODS: Four hundred six randomly selected subjects from the Prospective Investigation of the Vasculature in Uppsala Seniors study were examined with MRI of the brain at age 75. Blood samples, measurements, and dedicated questionnaires at age 70 were used for analysis of risk markers. A history of diseases had been obtained at age 70 and 75. MRI was evaluated regarding lacunar and cortical infarcts. Univariate associations between outcomes and risk markers were assessed with logistic regression models.RESULTS: One or more infarcts were seen in 23% of the subjects (20% had only lacunar infarcts, 1% had only cortical infarcts, and 2% had both). Hypertension (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.4, 4.7) and obesity (OR 1.3; CI 1.0, 1.8) were significantly associated with increased risk of brain infarction. The newer risk markers were not significantly associated with the brain infarcts.CONCLUSIONS: The new markers were not associated with the predominantly lacunar infarcts in our 75-year-old population, why troponin I and NT-proBNP may be associated mainly with cardioembolic infarcts as shown recently.
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| 12. |
- Pattaro, Cristian, et al.
(författare)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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| 13. |
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| 14. |
- Aga, Cathrine, et al.
(författare)
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Risk of Revision Was Not Reduced by a Double-bundle ACL Reconstruction Technique: Results From the Scandinavian Registers
- 2017
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Ingår i: Clinical Orthopaedics and Related Research. - : Ovid Technologies (Wolters Kluwer Health). - 0009-921X .- 1528-1132. ; 475:10, s. 2503-2512
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Tidskriftsartikel (refereegranskat)abstract
- © 2017, The Association of Bone and Joint Surgeons®. Background: Double-bundle anterior cruciate ligament (ACL) reconstruction has demonstrated improved biomechanical properties and moderately better objective outcomes compared with single-bundle reconstructions. This could make an impact on the rerupture rate and reduce the risk of revisions in patients undergoing double-bundle ACL reconstruction compared with patients reconstructed with a traditional single-bundle technique. The National Knee Ligament Registers in Scandinavia provide information that can be used to evaluate the revision outcome after ACL reconstructions. Questions/purposes: The purposes of the study were (1) to compare the risk of revision between double-bundle and single-bundle reconstructions, reconstructed with autologous hamstring tendon grafts; (2) to compare the risk of revision between double-bundle hamstring tendon and single-bundle bone-patellar tendon-bone autografts; and (3) to compare the hazard ratios for the same two research questions after Cox regression analysis was performed. Methods: Data collection of primary ACL reconstructions from the National Knee Ligament Registers in Denmark, Norway, and Sweden from July 1, 2005, to December 31, 2014, was retrospectively analyzed. A total of 60,775 patients were included in the study; 994 patients were reconstructed with double-bundle hamstring tendon grafts, 51,991 with single-bundle hamstring tendon grafts, and 7790 with single-bundle bone-patellar tendon-bone grafts. The double-bundle ACL-reconstructed patients were compared with the two other groups. The risk of revision for each research question was detected by the risk ratio, hazard ratio, and the corresponding 95% confidence intervals. Kaplan-Meier analysis was used to estimate survival at 1, 2, and 5 years for the three different groups. Furthermore, a Cox proportional hazard regression model was applied and the hazard ratios were adjusted for country, age, sex, meniscal or chondral injury, and utilized fixation devices on the femoral and tibial sides. Results: There were no differences in the crude risk of revision between the patients undergoing the double-bundle technique and the two other groups. A total of 3.7% patients were revised in the double-bundle group (37 of 994 patients) versus 3.8% in the single-bundle hamstring tendon group (1952 of 51,991; risk ratio, 1.01; 95% confidence interval (CI), 0.73–1.39; p = 0.96), and 2.8% of the patients were revised in the bone-patellar tendon-bone group (219 of the 7790 bone-patellar tendon-bone patients; risk ratio, 0.76; 95% CI, 0.54–1.06; p = 0.11). Cox regression analysis with adjustment for country, age, sex, menisci or cartilage injury, and utilized fixation device on the femoral and tibial sides, did not reveal any further difference in the risk of revision between the single-bundle hamstring tendon and double-bundle hamstring tendon groups (hazard ratio, 1.18; 95% CI, 0.85–1.62; p = 0.33), but the adjusted hazard ratio showed a lower risk of revision in the single-bundle bone-patellar tendon-bone group compared with the double-bundle group (hazard ratio, 0.62; 95% CI, 0.43–0.90; p = 0.01). Comparisons of the graft revision rates reported separately for each country revealed that double-bundle hamstring tendon reconstructions in Sweden had a lower hazard ratio compared with the single-bundle hamstring tendon reconstructions (hazard ratio, 1.00 versus 1.89; 95% CI, 1.09–3.29; p = 0.02). Survival at 5 years after index surgery was 96.0% for the double-bundle group, 95.4% for the single-bundle hamstring tendon group, and 97.0% for the single-bundle bone-patellar tendon-bone group. Conclusions: Based on the data from all three national registers, the risk of revision was not influenced by the reconstruction technique in terms of using single- or double-bundle hamstring tendons, although national differences in survival existed. Using bone-patellar tendon-bone grafts lowered the risk of revision compared with double-bundle hamstring tendon grafts. These findings should be considered when deciding what reconstruction technique to use in ACL-deficient knees. Future studies identifying the reasons for graft rerupture in single- and double-bundle reconstructions would be of interest to understand the findings of the present study. Level of Evidence: Level III, therapeutic study.
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| 15. |
- Artigas, MS, et al.
(författare)
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Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation
- 2015
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6, s. 8658-
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Tidskriftsartikel (refereegranskat)abstract
- Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10−8) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.
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| 16. |
- Ax, Erika, et al.
(författare)
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Circulating levels of environmental contaminants are associated with dietary patterns in older adults
- 2015
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Ingår i: Environment International. - Oxford, United Kingdom : Elsevier. - 0160-4120 .- 1873-6750. ; 75, s. 93-102
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Tidskriftsartikel (refereegranskat)abstract
- Background: Food intake contributes substantially to our exposure to environmental contaminants. Still, little is known about our dietary habits' contribution to exposure variability.Objective: The aim of this study was to assess circulating levels of environmental contaminants in relation to predefined dietary patterns in an elderly Swedish population.Methods: Dietary data and serum concentrations of environmental contaminants were obtained from 844 70-year-old Swedish subjects (50% women) in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Dietary data from 7-day food records was used to assess adherence to a Mediterranean-like diet, a low carbohydrate-high protein diet and the WHO dietary recommendations. Circulating levels of 6 polychlorinated biphenyl markers, 3 organochlorine pesticides, 1 dioxin and 1 polybrominated diphenyl ether, the metals cadmium, lead, mercury and aluminum and serum levels of bisphenol A and 4 phthalate metabolites were investigated in relation to dietary patterns in multivariate linear regression models.Results: A Mediterranean-like diet was positively associated with levels of several polychlorinated biphenyls (118, 126, 153, and 209), trans-nonachlor and mercury. A low carbohydrate-high protein diet was positively associated with polychlorinated biphenyls 118 and 153, trans-nonachlor, hexachlorobenzene and p, p'-dichlorodiphenyldichloroethylene, mercury and lead. The WHO recommended diet was negatively related to levels of dioxin and lead, and borderline positively to polychlorinated biphenyl 118 and trans-nonachlor.Conclusion: Dietary patterns were associated in diverse manners with circulating levels of environmental contaminants in this elderly Swedish population. Following the WHO dietary recommendations seems to be associated with a lower burden of environmental contaminants.
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| 17. |
- Benedict, Christian, et al.
(författare)
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Self-reported sleep disturbance is associated with Alzheimer's disease risk in men
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:9, s. 1090-1097
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the association between self-reported sleep disturbances and dementia risk.METHODS: Self-reported sleep disturbances and established risk factors for dementia were measured in men at ages 50 (n = 1574) and 70 (n = 1029) years. Dementia incidence was determined by reviewing their patient history between ages 50 and 90 years. In addition, plasma levels of β-amyloid (Aβ) peptides 1-40 and 1-42 were measured at ages 70, 77, and 82 years.RESULTS: Cox regression demonstrated that men with self-reported sleep disturbances had a higher risk of developing dementia (+33%) and Alzheimer's disease (AD, +51%) than men without self-reported sleep disturbances (both P < .05). Binary logistic regression showed the increased risk for both dementia (+114%) and AD (+192%) were highest when sleep disturbance was reported at age 70 years (both P < .001). No group differences were found in Aβ levels.CONCLUSION: Improving sleep quality may help reduce the neurodegenerative risk in older men.
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| 18. |
- Bixby, H., et al.
(författare)
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Rising rural body-mass index is the main driver of the global obesity epidemic in adults
- 2019
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 569:7755, s. 260-4
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Tidskriftsartikel (refereegranskat)abstract
- Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.
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| 19. |
- Chen, X., et al.
(författare)
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A genome-wide association study of IgM antibody against phosphorylcholine: shared genetics and phenotypic relationship to chronic lymphocytic leukemia
- 2018
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 27:10, s. 1809-1818
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Tidskriftsartikel (refereegranskat)abstract
- Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein (oxLDL), apoptotic cells and several pathogens like Streptococcus pneumoniae. Immunoglobulin M against PC (IgM anti-PC) has the ability to inhibit uptake of oxLDL by macrophages and increase clearance of apoptotic cells. From our genome-wide association studies (GWASs) in four European-ancestry cohorts, six single nucleotide polymorphisms (SNPs) in 11q24.1 were discovered (in 3002 individuals) and replicated (in 646 individuals) to be associated with serum level of IgM anti-PC (the leading SNP rs35923643-G, combined beta = 0.19, 95% confidence interval 0.13-0.24, P = 4.3 x 10-11). The haplotype tagged by rs35923643-G (or its proxy SNP rs735665-A) is also known as the top risk allele for chronic lymphocytic leukemia (CLL), and a main increasing allele for general IgM. By using summary GWAS results of IgM anti-PC and CLL in the polygenic risk score (PRS) analysis, PRS on the basis of IgM anti-PC risk alleles positively associated with CLL risk (explained 0.6% of CLL variance, P = 1.2 x 10-15). Functional prediction suggested that rs35923643-G might impede the binding of Runt-related transcription factor 3, a tumor suppressor playing a central role in the immune regulation of cancers. Contrary to the expectations from the shared genetics between IgM anti-PC and CLL, an inverse relationship at the phenotypic level was found in a nested case-control study (30 CLL cases with 90 age- and sex-matched controls), potentially reflecting reverse causation. The suggested function of the top variant as well as the phenotypic association between IgM anti-PC and CLL risk needs replication and motivates further studies.
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| 20. |
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