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| 3. |
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| 4. |
- Dumanski, Jan P., et al.
(författare)
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Mosaic Loss of Chromosome Y in Blood Is Associated with Alzheimer Disease
- 2016
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 98:6, s. 1208-1219
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Tidskriftsartikel (refereegranskat)abstract
- Men have a shorter life expectancy compared with women but the underlying factor(s) are not clear. Late-onset, sporadic Alzheimer disease (AD) is a common and lethal neurodegenerative disorder and many germline inherited variants have been found to influence the risk of developing AD. Our previous results show that a fundamentally different genetic variant, i.e., lifetime-acquired loss of chromosome Y (LOY) in blood cells, is associated with all-cause mortality and an increased risk of non-hematological tumors and that LOY could be induced by tobacco smoking. We tested here a hypothesis that men with LOY are more susceptible to AD and show that LOY is associated with AD in three independent studies of different types. In a case-control study, males with AD diagnosis had higher degree of LOY mosaicism (adjusted odds ratio = 2.80, p = 0.0184, AD events = 606). Furthermore, in two prospective studies, men with LOY at blood sampling had greater risk for incident AD diagnosis during follow-up time (hazard ratio [HR] = 6.80, 95% confidence interval [95% CI] = 2.16-21.43, AD events = 140, p = 0.0011). Thus, LOY in blood is associated with risks of both AD and cancer, suggesting a role of LOY in blood cells on disease processes in other tissues, possibly via defective immunosurveillance. As a male-specific risk factor, LOY might explain why males on average live shorter lives than females.
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| 5. |
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| 6. |
- Dumanski, Jan P., et al.
(författare)
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Smoking is associated with mosaic loss of chromosome Y
- 2015
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 347:6217, s. 81-83
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Tidskriftsartikel (refereegranskat)abstract
- Tobacco smoking is a risk factor for numerous disorders, including cancers affecting organs outside the respiratory tract. Epidemiological data suggest that smoking is a greater risk factor for these cancers in males compared to females. This observation, together with the fact that males have a higher incidence of and mortality from most non-sex-specific cancers, remains unexplained. Loss of chromosome Y (LOY) in blood cells is associated with increased risk of nonhematological tumors. We demonstrate here that smoking is associated with LOY in blood cells in three independent cohorts [TwinGene: odds ratio (OR) = 4.3, 95% CI = 2.8-6.7; ULSAM: OR = 2.4, 95% CI = 1.6-3.6; and PIVUS: OR = 3.5, 95% CI = 1.4-8.4] encompassing a total of 6014 men. The data also suggest that smoking has a transient and dose-dependent mutagenic effect on LOY status. The finding that smoking induces LOY thus links a preventable risk factor with the most common acquired human mutation.
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| 7. |
- Eriksson, Jan W., et al.
(författare)
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Hydrochlorothiazide, but not Candesartan, aggravates insulin resistance and causes visceral and hepatic fat accumulation : the mechanisms for the diabetes preventing effect of Candesartan (MEDICA) Study
- 2008
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Ingår i: Hypertension. - : American Heart Association. - 0194-911X .- 1524-4563. ; 52:6, s. 1030-1037
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Tidskriftsartikel (refereegranskat)abstract
- Treatment with angiotensin II receptor blockers is associated with lower risk for the development of type 2 diabetes mellitus compared with thiazide diuretics. The Mechanisms for the Diabetes Preventing Effect of Candesartan Study addressed insulin action and secretion and body fat distribution after treatment with candesartan, hydrochlorothiazide, and placebo. Twenty-six nondiabetic, abdominally obese, hypertensive patients were included in a multicenter 3-way crossover trial, and 22 completers (by predefined criteria; 10 men and 12 women) were included in the analyses. They underwent 12-week treatment periods with candesartan (C; 16 to 32 mg), hydrochlorothiazide (H; 25 to 50 mg), and placebo (P), respectively, and the treatment order was randomly assigned and double blinded. Intravenous glucose tolerance tests and euglycemic hyperinsulinemic (56 mU/m(2) per minute) clamps were performed. Intrahepatic and intramyocellular and extramyocellular lipid content and subcutaneous and visceral abdominal adipose tissue were measured using proton magnetic resonance spectroscopy and MRI. Insulin sensitivity (M-value) was reduced following H versus C and P (6.07+/-2.05, 6.63+/-2.04, and 6.90+/-2.10 mg/kg of body weight per minute, mean+/-SD; P
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| 8. |
- Ferreira, Daniel, et al.
(författare)
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The interactive effect of demographic and clinical factors on hippocampal volume : A multicohort study on 1958 cognitively normal individuals
- 2017
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Ingår i: Hippocampus. - : Wiley. - 1050-9631 .- 1098-1063. ; 27:6, s. 653-667
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease is characterized by hippocampal atrophy. Other factors also influence the hippocampal volume, but their interactive effect has not been investigated before in cognitively healthy individuals. The aim of this study is to evaluate the interactive effect of key demographic and clinical factors on hippocampal volume, in contrast to previous studies frequently investigating these factors in a separate manner. Also, to investigate how comparable the control groups from ADNI, AIBL, and AddNeuroMed are with five population-based cohorts. In this study, 1958 participants were included (100 AddNeuroMed, 226 ADNI, 155 AIBL, 59 BRC, 295 GENIC, 279 BioFiNDER, 398 PIVUS, and 446 SNAC-K). ANOVA and random forest were used for testing between-cohort differences in demographic-clinical variables. Multiple regression was used to study the influence of demographic-clinical variables on hippocampal volume. ANCOVA was used to analyze whether between-cohort differences in demographic-clinical variables explained between-cohort differences in hippocampal volume. Age and global brain atrophy were the most important variables in explaining variability in hippocampal volume. These variables were not only important themselves but also in interaction with gender, education, MMSE, and total intracranial volume. AddNeuroMed, ADNI, and AIBL differed from the population-based cohorts in several demographic-clinical variables that had a significant effect on hippocampal volume. Variability in hippocampal volume in individuals with normal cognition is high. Differences that previously tended to be related to disease mechanisms could also be partly explained by demographic and clinical factors independent from the disease. Furthermore, cognitively normal individuals especially from ADNI and AIBL are not representative of the general population. These findings may have important implications for future research and clinical trials, translating imaging biomarkers to the general population, and validating current diagnostic criteria for Alzheimer's disease and predementia stages.
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| 9. |
- Forsberg, Lars A., 1974-, et al.
(författare)
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Mosaic loss of chromosome Y in leukocytes matters
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:1, s. 4-7
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Forsberg, Lars A., et al.
(författare)
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Mosaic loss of chromosome Y in peripheral blood is associated with shorter survival and higher risk of cancer
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:6, s. 624-628
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Tidskriftsartikel (refereegranskat)abstract
- Incidence and mortality for sex-unspecific cancers are higher among men, a fact that is largely unexplained(1,2). Furthermore, age-related loss of chromosome Y (LOY) is frequent in normal hematopoietic cells(3,4), but the phenotypic consequences of LOY have been elusive(5-10). From analysis of 1,153 elderly men, we report that LOY in peripheral blood was associated with risks of all-cause mortality (hazards ratio (HR) = 1.91, 95% confidence interval (CI) = 1.17-3.13; 637 events) and non-hematological cancer mortality (HR = 3.62, 95% CI = 1.56-8.41; 132 events). LOY affected at least 8.2% of the subjects in this cohort, and median survival times among men with LOY were 5.5 years shorter. Association of LOY with risk of all-cause mortality was validated in an independent cohort (HR = 3.66) in which 20.5% of subjects showed LOY. These results illustrate the impact of post-zygotic mosaicism on disease risk, could explain why males are more frequently affected by cancer and suggest that chromosome Y is important in processes beyond sex determination. LOY in blood could become a predictive biomarker of male carcinogenesis.
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| 11. |
- Fridén, Michael, et al.
(författare)
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Effects of a low-carbohydrate high polyunsaturated fat diet or a healthy Nordic diet versus usual care on liver fat content and cardiometabolic risk factors in people with type 2 diabetes and prediabetes: a randomized controlled trial (NAFLDiet)
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Previous trials have shown that plant-derived polyunsaturated fatty acids (PUFA) in place of saturated fat reduces liver fat, a prerequisite for non-alcoholic fatty liver disease (NAFLD). The effect on liver fat from a novel “anti-lipogenic diet” replacing carbohydrates with PUFA or a healthy Nordic diet (HND) higher in whole-grains but lower in saturated fat has not yet been examined. Objectives: To investigate the effects on changes in liver fat (primary outcome) and other cardiometabolic risk factors after 12 months of follow-up in individuals with prediabetes or T2D from three different diet comparisons: a low carbohydrate high PUFA (LCPUFA) diet versus a HND, a LCPUFA diet versus usual care (UC) and a HND versus UC. Methods: A three-arm parallel ad libitum randomized trial was conducted. Adult men and women (n=148) were randomized to one of the three diet groups. Participants in all groups received key food items on a monthly/bimonthly basis. Liver fat and cardiometabolic risk factors were assessed at baseline and after 12 months. Dietary adherence was assessed using weighed food diaries and objective biomarkers. General linear models were employed to estimate the intention-to-treat (ITT) effect. Results: Dietary adherence was high for all diet groups. Liver fat was reduced to a similar extent in the LCPUFA and the HND group compared to UC (-1.46% (95% CI: -2.42, -0.51)) and -1.76 % (95% CI: -2.96, -0.57), respectively. No difference in liver fat between LCPUFA and HND was observed. Body weight and HbA1c decreased more in the HND compared to the other diet groups whereas no differences were observed between LCPUFA and UC. Similar reductions in LDL-cholesterol were observed for the HND and the LCPUFA group compared to UC, but only the HND reduced triglycerides and C-reactive protein (CRP) compared with UC. No differences were observed for any other secondary outcomes.Conclusions: A LCPUFA diet and a HND both reduced liver fat as compared with UC. Given the sustained weight loss after the HND compared to the other groups, together with improvements in other cardiometabolic markers, the HND in particular seems to be useful for the treatment of T2D and NAFLD.
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| 12. |
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| 13. |
- Joshi, Peter K, et al.
(författare)
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Directional dominance on stature and cognition in diverse human populations
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
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Tidskriftsartikel (refereegranskat)abstract
- Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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| 14. |
- Kullberg, Joel, et al.
(författare)
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Practical approach for estimation of subcutaneous and visceral adipose tissue
- 2007
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Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961 .- 1475-097X. ; 27:3, s. 148-153
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The first objective was to investigate the correlations between anthropometrical measurements and visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) in two cohorts differing in age using magnetic resonance imaging (MRI) as reference. A second objective was to investigate the potential usage of abdominal diameters in practical estimation of adipose tissue compartments using these cohorts. Methods: Measurements of body mass index, waist circumference, sagittal abdominal diameter (sagittal AD) and transverse abdominal diameter (transverse AD) were obtained from 336 volunteers of age 14-70 years. Manual measurements of VAT and SAT from single slice MRI at the L4-L5 level were used as reference. The abdominal diameters were measured from the MR images. Linear correlations between the anthropometrical measurements and the reference were studied. Results: Sagittal AD showed the strongest correlation to VAT (r > 0·780, P<0·0001) and transverse AD was found to give information about the amount of SAT (r > 0·866, P<0·0001). The ellipse spanned by the sagittal AD and the transverse AD was strongly correlated to the total amount of adipose tissue (r ≥ 0·962 P<0·0001). Conclusion: Strong correlations were found between sagittal and transverse abdominal diameters, assessed using MRI, and VAT and SAT, respectively. These results suggest the use of abdominal diameters in practical estimations of VAT and SAT depots.
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| 15. |
- Lind, Johanna, et al.
(författare)
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Reduced functional brain activity response in cognitively intact apolipoprotein E ε4 carriers
- 2006
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Ingår i: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 129:5, s. 1240-1248
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Tidskriftsartikel (refereegranskat)abstract
- The apolipoprotein E epsilon4 (APOE epsilon4) is the main known genetic risk factor for Alzheimer's disease. Genetic assessments in combination with other diagnostic tools, such as neuroimaging, have the potential to facilitate early diagnosis. In this large-scale functional MRI (fMRI) study, we have contrasted 30 APOE epsilon4 carriers (age range: 49-74 years; 19 females), of which 10 were homozygous for the epsilon4 allele, and 30 non-carriers with regard to brain activity during a semantic categorization task. Test groups were closely matched for sex, age and education. Critically, both groups were cognitively intact and thus symptom-free of Alzheimer's disease. APOE epsilon4 carriers showed reduced task-related responses in the left inferior parietal cortex, and bilaterally in the anterior cingulate region. A dose-related response was observed in the parietal area such that diminution was most pronounced in homozygous compared with heterozygous carriers. In addition, contrasts of processing novel versus familiar items revealed an abnormal response in the right hippocampus in the APOE epsilon4 group, mainly expressed as diminished sensitivity to the relative novelty of stimuli. Collectively, these findings indicate that genetic risk translates into reduced functional brain activity, in regions pertinent to Alzheimer's disease, well before alterations can be detected at the behavioural level.
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| 16. |
- Lind, Johanna, et al.
(författare)
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Reduced hippocampal volume in non-demented carriers fo the apolipoprotein E ε4 : Relation to chronological age and recognition memory
- 2006
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 396:1, s. 23-27
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein E ε4 (APOE ε4) is the main known genetic risk factor for Alzheimer's disease (AD). Some previous studies have reported structural brain changes as well as cognitive deficits in non-demented APOE ε4 carriers, but the pattern of results is inconsistent and studies with larger sample sizes have been called for. Here we compared hippocampal volume and recognition–memory performance between AD-symptom-free carriers (N = 30) and non-carriers (N = 30) of the APOE ε4 (age range: 49–79 years). We observed reduced right hippocampal volume in APOE ε4 carriers, and found that the difference was most pronounced before the age of 65. Further, the APOE ε4 carriers made significantly more false alarms in the recognition–memory test, and the number of false alarms correlated significantly with right hippocampus volume. These results indicate that relatively young individuals at genetic risk for AD have smaller hippocampal volume and lower performance on hippocampal-dependent cognitive tasks. A question for the future is whether smaller hippocampal volume represents early-onset hippocampal volume reduction or an inherent trait.
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| 17. |
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| 18. |
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| 19. |
- Lind, P. Monica, et al.
(författare)
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Serum concentrations of phthalate metabolites are related to abdominal fat distribution two years later in elderly women
- 2012
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Ingår i: Environmental Health. - 1476-069X. ; 11:1, s. 21-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Phthalates, commonly used to soften plastic goods, are known PPAR-agonists affecting lipid metabolism and adipocytes in the experimental setting. We evaluated if circulating concentrations of phthalates were related to different indices of obesity using data from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Data from both dual-energy X-ray absorptiometry (DXA) and abdominal magnetic resonance imaging (MRI) were used.METHODS: 1,016 subjects aged 70 years were investigated in the PIVUS study. Four phthalate metabolites were detected in the serum of almost all subjects (> 96%) by an API 4000 liquid chromatograph/tandem mass spectrometer. Abdominal MRI was performed in a representative subsample of 287 subjects (28%), and a dual-energy X-ray absorptiometry (DXA)-scan was obtained in 890 (88%) of the subjects two year following the phthalate measurements.RESULTS:In women, circulating concentrations of mono-isobutyl phthalate (MiBP) were positively related to waist circumference, total fat mass and trunk fat mass by DXA, as well as to subcutaneous adipose tissue by MRI following adjustment for serum cholesterol and triglycerides, education, smoking and exercise habits (all p < 0.008). Mono-methyl phthalate (MMP) concentrations were related to trunk fat mass and the trunk/leg-ratio by DXA, but less powerful than MiBP. However, no such statistically significant relationships were seen in men.CONCLUSIONS:The present evaluation shows that especially the phthalate metabolite MiBP was related to increased fat amount in the subcutaneous abdominal region in women measured by DXA and MRI two years later.
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| 20. |
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| 21. |
- Nikpay, Majid, et al.
(författare)
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A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:10, s. 1121-1121
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Tidskriftsartikel (refereegranskat)abstract
- Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of similar to 185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.
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| 22. |
- Nilsson, Bo, et al.
(författare)
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C3 and C4 are strongly related to adipose tissue variables and cardiovascular risk factors
- 2014
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Ingår i: European Journal of Clinical Investigation. - : John Wiley & Sons. - 0014-2972 .- 1365-2362. ; 44:6, s. 587-596
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Tidskriftsartikel (refereegranskat)abstract
- Background In several reports, C3 and C4 have been linked to diabetes and cardiovascular disease (CVD). Here, we investigate this link and the degree of C3 activation in elderly individuals. Methods In this study, C3 and C4 and the activation fragment C3a-desArg were analysed in 1016 subjects aged 70, in which blood pressure, lipid variables and fasting blood glucose were assessed. Results C3 levels were related to all the investigated classical cardiovascular risk factors and the metabolic syndrome (BMI, waist circumference, fat distribution, blood pressure, blood glucose levels, TG) except total cholesterol and LDL cholesterol in a highly significant fashion (Spearman up to 0,5; P<0.0001). C4 and C3a-desArg were associated in the same fashion but less significantly, while the ratios C4/C3 or C3a-desArg/C3 were not, indicating thatthe association was not directly related to complement activation. The levels C3 and to a lesser degree C4 and C3a-desArg were associated particularly with CRP, but also with E-selectin and ICAM-1. In addition, C3 and C4 levels were shown to decline significantly in 15 female subjects enrolled in a weight-reduction programme over 4 months. Conclusion A strong relation between C3, C4 and C3a-desArg levels, adipose tissue and risk factors of CVD was established. The data support that theadipose tissue produces complement components and generates initiators of inflammation, such as C3a and C5a, able to trigger a cyto/chemokine response, in proportion to the amount of adipose tissue. This corroborates the concept that complement contributes to the low-grade inflammation associated with obesity.
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| 23. |
- 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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| 24. |
- 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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| 25. |
- Penell, Johanna, et al.
(författare)
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Persistent organic pollutants are related to the change in circulating lipid levels during a 5 year follow-up
- 2014
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 134, s. 190-197
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Tidskriftsartikel (refereegranskat)abstract
- When reporting circulating levels of persistent organic pollutants (POPs), usually lipid-normalized values are given. However, animal experiments and some human data indicate that exposure to POPs may change lipid values. The aim of the present study is to investigate if POP levels can predict future changes in levels of circulating lipids. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, lipids were measured at age 70 and at age 75 in 598 subjects without lipid-lowering medication. Twenty-three different POPs, including 16 polychlorinated biphenyls (PCBs), five organochlorine pesticides, one dioxin (OCDD) and one flame retardant brominated compound (BDE47) were analyzed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS) at age 70. Strong relationships were seen among the baseline levels of the non-dioxin-like PCBs 194, 206 and 209 and the degree of increase in total serum cholesterol and LDL-cholesterol during the 5 year follow-up. These relationships were generally stronger when lipidnormalized levels were used compared to wet-weight based levels. On the contrary, for two of the pesticides, hexachlorobenzene and trans-nonachlordane, levels were inversely related to the change in LDL-cholesterol, with strongest associations found using wet-weight based levels. PCBs 194, 206 and 209 were inversely related to the change in HDL-cholesterol, in particular for wet-weight based levels. However, these relationships were only significant for wet-weight PCB 194 following adjustment for multiple testing. None of the POPs was related to the change in serum triglycerides. When investigating the association between the change in total serum cholesterol and LDL-cholesterol across different categories of change in BMI, we noted robust results especially in the group with stable BMI, suggesting that the observed relationships were not due to fluctuations in BMI over time. In conclusion, POPs are related to the change in lipids over time, especially LDL-cholesterol. This may explain why POP exposure previously has been linked to atherosclerosis and cardiovascular disease.
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| 26. |
- Roos, Vendela, et al.
(författare)
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Circulating Levels of Persistent Organic Pollutants in Relation to Visceral and Subcutaneous Adipose Tissue by Abdominal MRI
- 2013
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Ingår i: Obesity. - : Wiley-Blackwell. - 1930-7381 .- 1930-739X. ; 21:2, s. 413-418
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We and others have shown relationships between circulating levels of persistent organic pollutants (POPs) and different measures of obesity in both cross-sectional and prospective studies. Since viscerally located fat seems to be the most harmful type, we investigated whether plasma POP levels were more closely related to visceral adipose tissue (VAT) than to subcutaneous adipose tissue (SAT).Design and Methods: Thousand hundred and sixteen subjects aged 70 years were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study; 23 POPs were analyzed using high-resolution gas chromatography/ high-resolution mass spectrometry. Abdominal magnetic resonance imaging, measuring VAT and SAT, respectively, was performed in a representative subsample of 287 subjects.Results: The less chlorinated polychlorinated biphenyl (PCB) congeners (105 and 118), and the pesticides dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB), and trans-nonachlordane (TNC) were positively related to both VAT and SAT, whereas the more highly chlorinated PCBs (153, 156, 157, 169, 170, 180, 194, 206, and 209) were inversely related to both VAT and SAT. PCB189 was related to the VAT/SAT ratio in an inverted U-shaped manner (P = 0.0008).Conclusions: In conclusion, the results were in accordance with our previous studies using waist circumference and fat mass as obesity measure. However, the novel finding that PCB189 was related to the VAT/SAT ratio deserves further investigation since exposure to this PCB congener, which has previously been linked to diabetes development, might thereby play a role in the distribution of abdominal adipose tissue.
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| 27. |
- Roos, Vendela, et al.
(författare)
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Circulating Levels of Persistent Organic Pollutants in Relation to Visceral and Subcutaneous Adipose Tissue by Abdominal MRI
- 2013
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 21:2, s. 413-418
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Tidskriftsartikel (refereegranskat)abstract
- We and others have shown relationships between circulating levels of persistent organic pollutants (POPs) and different measures of obesity in both cross-sectional and prospective studies. Since viscerally located fat seems to be the most harmful type, we investigated whether plasma POP levels were more closely related to visceral adipose tissue (VAT) than to subcutaneous adipose tissue (SAT). Thousand hundred and sixteen subjects aged 70 years were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study; 23 POPs were analyzed using high-resolution gas chromatography/high-resolution mass spectrometry. Abdominal magnetic resonance imaging, measuring VAT and SAT, respectively, was performed in a representative subsample of 287 subjects. The less chlorinated polychlorinated biphenyl (PCB) congeners (105 and 118), and the pesticides dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB), and trans-nonachlordane (TNC) were positively related to both VAT and SAT, whereas the more highly chlorinated PCBs (153, 156, 157, 169, 170, 180, 194, 206, and 209) were inversely related to both VAT and SAT. PCB189 was related to the VAT/SAT ratio in an inverted U-shaped manner (P = 0.0008). In conclusion, the results were in accordance with our previous studies using waist circumference and fat mass as obesity measure. However, the novel finding that PCB189 was related to the VAT/SAT ratio deserves further investigation since exposure to this PCB congener, which has previously been linked to diabetes development, might thereby play a role in the distribution of abdominal adipose tissue.
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| 28. |
- Rönn, Monika, et al.
(författare)
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Bisphenol A is related to circulating levels of adiponectin, leptin and ghrelin, but not to fat mass or fat distribution in humans
- 2014
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 112, s. 42-48
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Since bisphenol A (BPA) has been shown to induce obesity in experimental studies, we explored the associations between BPA and fat mass, fat distribution and circulating levels of adiponectin, leptin and ghrelin in humans. Methods: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), fat mass and fat distribution were determined in 70-year-old men and women (n = 890) by dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI) (n = 287). Serum levels of BPA were analyzed using isotope liquid chromatography/tandem mass spectrometer (API4000LC-MS/MS). Hormone levels were analyzed with radioimmunoassays (RIA) or enzyme-linked immunosorbent assay (ELISA). Imaging was performed approximately two years following collection of other data. Results: Serum concentrations of BPA were not related to adipose tissue measurements by DXA or MRI. BPA associated positively with adiponectin and leptin, but negatively with ghrelin, following adjustments for sex, height, fat mass, lean mass, smoking, alcohol consumption, physical activity, energy intake, and educational levels (p < 0.001, p = 0.009, p < 0.001, respectively). The relationship between BPA and ghrelin was stronger in women than in men. Conclusion: Although no relationships between BPA levels and measures of fat mass were seen, BPA associated strongly with the adipokines adiponectin and leptin and with the gut-hormone ghrelin suggesting that BPA may interfere with hormonal control of hunger and satiety.
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| 29. |
- Sjöberg Lind, Ylva, et al.
(författare)
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Circulating levels of persistent organic pollutants (POPs) are associated with left ventricular systolic and diastolic dysfunction in the elderly
- 2013
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Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 123, s. 39-45
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVE:Major risk factors for congestive heart failure (CHF) are myocardial infarction, hypertension, diabetes, atrial fibrillation, smoking, left ventricular hypertrophy (LVH) and obesity. However, since these risk factors only explain part of the risk of CHF, we investigated whether persistent organic pollutants (POPs) might also play a role.METHODS:In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, left ventricular ejection fraction, (EF), E/A-ratio and isovolumic relaxation time (IVRT), were determined by echocardiography and serum samples of 21 POPs were analyzed in serum measured by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS) in 998 subjects all aged 70 years.RESULTS:In this cross-sectional analysis, high levels of several of the polychlorinated biphenyls (PCB congeners 99, 118, 105, 138, 153, and 180) and octachlorodibenzo-p-dioxin (OCDD) were significantly related to a decreased EF. Some POPs were also related to a decreased E/A-ratio (PCBs 206 and 209). All the results were adjusted for gender, hypertension, diabetes, smoking, LVH and BMI, and subjects with myocardial infarction or atrial fibrillation were excluded from the analysis.CONCLUSIONS:Circulating levels of POPs were related to impairments in both left ventricular systolic and diastolic function independently of major congestive heart failure risk factors, suggesting a possible role of POPs in heart failure.
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| 30. |
- Sjöberg Lind, Ylva, et al.
(författare)
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Persistent organic pollutants and abnormal geometry of the left ventricle in the elderly
- 2013
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 31:8, s. 1547-1553
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Tidskriftsartikel (refereegranskat)abstract
- Background:Established risk factors for left ventricular hypertrophy (LVH) are hypertension, diabetes, and obesity. However, as these risk factors explain only part of the variation in left ventricular mass, we investigated whether persistent organic pollutants (POPs) might also play a role in LVH, because exposure to polychlorinated biphenyl 126 induced cardiac growth in rats.Methods:In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), left ventricular mass index (LVMI), relative wall thickness (RWT), and geometric groups of LVH, were determined by echocardiography and 21 POPs were measured by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS) in 1016 individuals aged 70 years. All individuals with a history of myocardial infarction were excluded from analysis (n=72).Results:Several of the POPs were related to abnormal left ventricular geometry before adjustment for established risk factors, but lost in significance following adjustment. However, the pesticide hexachlorobenzene (HCB) levels were significantly related to RWT, and concentric left ventricular remodeling, also following adjustment for sex, blood pressure, antihypertensive treatment, diabetes, and BMI (Pandlt;0.0001).Conclusion:In this cross-sectional study, circulating levels of HCB were related to increased wall thickness of the left ventricle and concentric left ventricular remodeling, independently of LVH risk factors, suggesting a role of this environmental contaminant in abnormal growth of the left ventricle.
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| 31. |
- T. Tegler, Lotta, et al.
(författare)
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A highly selective polypeptide binder for human Acetylcholine esterase
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- A highly selective high-affinity polypeptide conjugate binder for human Acetylcholine Esterase (hAChE) has been obtained by coupling a derivative of acridine, a known medium-affinity inhibitor of hAChE, to each member of a 16-membered set of 42-residue polypeptide scaffolds. The best candidate, 4-C10L17-Ac, was identified to have a KD of 10 nM or less in an assay where each polypeptide conjugate was titrated with hAChE in 50 mM phosphate buffer at pH 7.0 and 298K. It was found in a sandwich ELISA to have high selectivity for hAChE in cerebrospinal fluid. Targeting the active site of hAChE by a polypeptide conjugate binder presents a special problem as it is buried deep inside the protein in a cavity that is approximately 20 Å deep. In order to permit simultaneous and cooperative binding of the acridine and the polypeptide to the active site and the AChE surface a fourteen atom spacer was needed. The 9-aminoacridine group was linked to the side chain of a lysine residue in each polypeptide via a spacer prepared from two aminohexanoic acid fragments. The results reinforce the impression that polypeptide conjugates are excellent alternatives to currently used protein binder technologies in diagnostic and therapeutic applications and that the conjugation of enzyme inhibitors to polypeptide scaffolds is a strategy of general applicability in the design of high-affinity binders for enzymes.
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| 32. |
- Wallentin, Lars, et al.
(författare)
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GDF-15 for Prognostication of Cardiovascular and Cancer Morbidity and Mortality in Men
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12, s. e78797-
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to evaluate the hypothesis that growth-differentiation factor 15 (GDF-15) is an independent marker of the long-term risk for both cardiovascular disease and cancer morbidity beyond clinical and biochemical risk factors. Plasma obtained at age 71 was available from 940 subjects in the Uppsala Longitudinal Study of Adult Men (ULSAM) cohort. Complete mortality and morbidity data were obtained from public registries. At baseline there were independent associations between GDF-15 and current smoking, diabetes mellitus, biomarkers of cardiac (high-sensitivity troponin-T, NT-proBNP) and renal dysfunction (cystatin-C) and inflammatory activity (C-reactive protein), and previous cardiovascular disease (CVD). During 10 years follow-up there occurred 265 and 131 deaths, 115 and 46 cardiovascular deaths, and 185 and 86 events with coronary heart disease mortality or morbidity in the respective total cohort (n=940) and non-CVD (n=561) cohort. After adjustment for conventional cardiovascular risk factors, one SD increase in log GDF-15 were, in the respective total and non-CVD populations, associated with 48% (95%CI 26 to 73%, p<0.001) and 67% (95%CI 28 to 217%, p<0.001) incremental risk of cardiovascular mortality, 48% (95%CI 33 to 67%, p<0.001) and 61% (95%CI 38 to 89%, p<0.001) of total mortality and 36% (95%CI 19 to 56%, p<0.001) and 44% (95%CI 17 to 76%, p<0.001) of coronary heart disease morbidity and mortality. The corresponding incremental increase for cancer mortality in the respective total and non-cancer disease (n=882) population was 46% (95%CI 21 to 77%, p<0.001) and 38% (95%CI 12 to 70%, p<0.001) and for cancer morbidity and mortality in patients without previous cancer disease 30% (95%CI 12 to 51%, p<0.001). In conclusion, in elderly men, GDF-15 improves prognostication of both cardiovascular, cancer mortality and morbidity beyond established risk factors and biomarkers of cardiac, renal dysfunction and inflammation.
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| 33. |
- Winkler, TW, et al.
(författare)
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Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 580-
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
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| 34. |
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| 35. |
- 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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| 36. |
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| 37. |
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| 38. |
- Andric, Stefan, et al.
(författare)
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Lateral III-V Nanowire MOSFETs in Low-Noise Amplifier Stages
- 2022
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Ingår i: IEEE Transactions on Microwave Theory and Techniques. - 0018-9480. ; 70:2, s. 1284-1291
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Tidskriftsartikel (refereegranskat)abstract
- Lateral III-V nanowire (NW) MOSFETs are a promising candidate for high-frequency electronics. However, their circuit performance is not yet assessed. Here, we integrate lateral nanowires (LNWs) in a circuit environment and characterize the transistors and amplifiers. MOSFETs are fabricated in a simple scheme with a dc transconductance of up to 1.3 mS/μm, ON-resistance down to 265 Ω · μ m, and cutoff frequencies up to 250 GHz, measured on the circuit level. The circuit model estimates 25% device parasitic capacitance increase due to back-end-of-line (BEOL) dielectric cladding. A low-noise amplifier input stage is designed with optimum network design for a noise matched input and an inductive peaking output. The input stage shows up to 4-dB gain and 2.5-dB noise figure (NF), at 60 GHz. Utilizing gate-length scaling in the circuit environment, the obtained normalized intrinsic gate capacitance value of 0.34-aF/nm gate length, per NW, corresponds well to the predicted theoretical value, demonstrating the circuit's ability to provide intrinsic device parameters. This is the first mm-wave validation of noise models for III-V LNW MOSFETs. The results demonstrate the potential for utilization of the technology platform for low-noise applications.
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| 39. |
- Arking, D. E., et al.
(författare)
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Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
- 2014
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc.
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| 40. |
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| 41. |
- 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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| 42. |
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| 43. |
- 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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| 44. |
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| 45. |
- Bahls, M., et al.
(författare)
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Progression of conventional cardiovascular risk factors and vascular disease risk in individuals: insights from the PROG-IMT consortium
- 2020
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 27:3
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Averaged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear. Methods and results: An individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration (n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events. Conclusion: Averaged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints. © The European Society of Cardiology 2019.
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| 46. |
- Benedict, Christian, et al.
(författare)
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Association between physical activity and brain health in older adults
- 2013
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 34:1, s. 83-90
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Tidskriftsartikel (refereegranskat)abstract
- In the present cross-sectional study, we examined physical activity (PA) and its possible association with cognitive skills and brain structure in 331 cognitively healthy elderly. Based on the number of self-reported light and hard activities for at least 30 minutes per week, participants were assigned to 4 groups representing different levels of PA. The cognitive skills were assessed by the Mini Mental State Examination score, a verbal fluency task, and the Trail-making test as a measure of visuospatial orientation ability. Participants also underwent a magnetic resonance imaging of the brain. Multiple regression analysis revealed that greater PA was associated with a shorter time to complete the Trail-making test, and higher levels of verbal fluency. Further, the level of self-reported PA was positively correlated with brain volume, white matter, as well as a parietal lobe gray matter volume, situated bilaterally at the precuneus. These present cross-sectional results indicate that PA is a lifestyle factor that is linked to brain structure and function in late life.
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| 47. |
- Benedict, Christian, et al.
(författare)
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Impaired Insulin Sensitivity as Indexed by the HOMA Score Is Associated With Deficits in Verbal Fluency and Temporal Lobe Gray Matter Volume in the Elderly
- 2012
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 35:3, s. 488-494
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVEImpaired insulin sensitivity is linked to cognitive deficits and reduced brain size. However, it is not yet known whether insulin sensitivity involves regional changes in gray matter volume. Against this background, we examined the association between insulin sensitivity, cognitive performance, and regional gray matter volume in 285 cognitively healthy elderly men and women aged 75 years from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study.RESEARCH DESIGN AND METHODSInsulin sensitivity was calculated from fasting serum insulin and plasma glucose determinations using the homeostasis model assessment of insulin resistance (HOMA-IR) method. Cognitive performance was examined by a categorical verbal fluency. Participants also underwent a magnetic resonance imaging (MRI) brain scan. Multivariate analysis using linear regression was conducted, controlling for potential confounders (sex, education, serum LDL cholesterol, mean arterial blood pressure, and abdominal visceral fat volume).RESULTSThe HOMA-IR was negatively correlated with verbal fluency performance, brain size (S1), and temporal lobe gray matter volume in regions known to be involved in speech production (Brodmann areas 21 and 22, respectively). No such effects were observed when examining diabetic (n = 55) and cognitively impaired (n = 27) elderly subjects as separate analyses.CONCLUSIONSThese cross-sectional findings suggest that both pharmacologic and lifestyle interventions improving insulin signaling may promote brain health in late life but must be confirmed in patient studies.
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| 48. |
- 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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| 49. |
- 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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| 50. |
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