| 21. |
- Dahl, Åslög, 1955, et al.
(författare)
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Pollen, luftföroreningar och väderlek
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Pollenallergiker kan få ett bättre liv om de får information om tillståndet i luften. Det är till och med deras medborgerliga rättighet, enligt EU-direktiv, att få det. Därmed kan de förebygga symptom och planera sina aktiviteter. Avsikten med vår rapport är att bidra till underlaget för sådan en information, och att belysa hur de allergiska symptomen varierar med miljöfaktorer. Informationen bör innehålla en rapport om situationen innevarande dag. Vi ger ett förslag på hur den kan presenteras i form av ett luftkvalitetsindex. Dessutom bör informationen innehålla en prognos för de kommande dagarna. Pollenallergi, inklusive allergisk astma, är ett vanligt problem i vårt samhälle. Var fjärde till femte person är drabbad. Under sommarhalvåret bidrar allergin inte bara till att allergikerna får symptom från ögon och näsa, utan också till en totalt sett sänkt livskvalitet (Kiotseridis et al. 2013a, b). Ett flertal studier visar att luftföroreningar också påverkar luftvägarna. De kan orsaka en inflammation som kan förstärka allergiska besvär och som kan sänka tröskeln för att den skall uppstå. Våra resultat visar att ozon, kvävedioxid och partiklar bidrar till behovet av allergiläkemedel, när halterna överskrider ett visst tröskelvärde. Myndigheter med ansvar för miljö och folkhälsa på statlig, regional och kommunal nivå bör garantera att det finns förutsättningar för att förmedla informationen till allmänhet och sjukvård. Pollenövervakning saknas i flera regioner. I de fall sådan övervakning finns, är expertisen på området och nvändig infrastruktur inte långsiktigt tryggade. Verksamheten har hittills aldrig garanterats mer än ett år i taget. Detta innebär en ständig risk för bristande kontinuitet, att kompetens skall gå förlorad, och att underlaget till informationen är otillräcklig. I rapporten vill vi visa att allergibesvär beror av en kombination av faktorer, och bara kan förstås genom samarbete mellan experter från olika ämnesdiscipliner. Det är myndigheternas ås uppgift att tillhandahålla förutsättningar för att kompetens inom dessa områden kan samordnas. Föreliggande rapport är resultatet av ett regionalt utvecklingsprojekt i regi av länsstyrelserna i Västra Götaland och Skåne, inom ramen för Naturvårdsverkets programområde Hälsorelaterad Miljöpåverkan.
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| 22. |
- Eskelund, Christian W., et al.
(författare)
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TP53 mutations identify younger mantle cell lymphoma patients who do not benefit from intensive chemoimmunotherapy
- 2017
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 130:17, s. 1903-1910
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Tidskriftsartikel (refereegranskat)abstract
- Despite recent advances in lymphoma treatment, mantle cell lymphoma (MCL) remains incurable, and we are still unable to identify patients who will not benefit from the current standard of care. Here, we explore the prognostic value of recurrent genetic aberrations in diagnostic bone marrow (BM) specimens from 183 younger patients with MCL from the Nordic MCL2 and MCL3 trials, which represent current standard-of-care regimens. In the univariate model, mutations of TP53 (11%) and NOTCH1 (4%), and deletions of TP53 (16%) andCDKN2A(20%),weresignificantly associatedwithinferioroutcomes(togetherwithMIPI, MIPI-c, blastoidmorphology, and Ki67 > 30%); however, inmultivariate analyses, only TP53 mutations (HR, 6.2; P <.0001) retained prognostic impact for overall survival (OS), whereas TP53 mutations (HR, 6.9; P <.0001) andMIPI-c high-risk (HR, 2.6; P5.003) had independent prognostic impact on time to relapse. TP53-mutated cases had a dismal outcome, with a median OS of 1.8 years, and 50% relapsed at 1.0 years, compared to a median OS of 12.7 years for TP53-unmutated cases (P <.0001). TP53 mutations were significantly associated with Ki67 > 30%, blastoid morphology, MIPI high-risk, and inferior responses to both induction- and high-dose chemotherapy. In conclusion, we show that TP53mutations identify a phenotypically distinct and highly aggressive form of MCL with poor or no response to regimens including cytarabine, rituximab, and autologous stem-cell transplant (ASCT). We suggest patients with MCL should be stratified according to TP53 status, and that patients with TP53 mutations should be considered for experimental frontline trials exploring novel agents.
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| 23. |
- Fahnehjelm, Kristina, et al.
(författare)
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Optic nerve hypoplasia in children and adolescents; prevalence, ocular characteristics and behavioural problems
- 2014
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Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 92:6, s. 563-570
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To report prevalence, ocular characteristics and coexisting behavioural problems in children and adolescents with optic nerve hypoplasia (ONH), which is a common cause of visual impairment in children in western countries, often associated with neurological or endocrinological problems and where autism has been reported in severe cases with blindness. Methods: This is a population-based cross-sectional study of patients <20 years of age who had been diagnosed with ONH and lived in the county of Stockholm in December 2009. Ophthalmological assessments including fundus photographs with optic disc analyses were made. A questionnaire was used to screen for behaviour and development. Results: The prevalence of ONH in all living children <18 years of age in Stockholm was 17.3/100 000 with a prevalence of visual impairment (<0.3) of 3.9/100 000. In total, 66 patients, median age 9.3 years (0.6-19.4), 36 with bilateral and 30 with unilateral ONH, were included in the current study; 53 were re-examined clinically, group A, and 13 agreed to retrospective analyses of existing medical records, group B. Analyses of the optic discs were made in fundus photographs from 53 patients comparing a semi-automated (Retinal Size Tool) and a manual method (Zeki). There was a strong curvilinear correlation (rS = -0.91 p < 0.0001 for both eyes). Behavioural problems were more common (p < 0.05) in bilateral ONH. Conclusion: Opticnerve hypoplasia is a common ocular malformation with a prevalence of 17.3/100 000 children and adolescents <18 years of age in Stockholm. Unilateral ONH seems as common as bilateral.
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| 24. |
- Gabriková, Dana, et al.
(författare)
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Familiar Meniere's disease restricted to 1.48 Mb on chromosome 12p12.3 by allelic and haplotype association
- 2010
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Ingår i: Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1434-5161 .- 1435-232X. ; 55:12, s. 834-837
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Tidskriftsartikel (refereegranskat)abstract
- Meniere's disease (MD) is a disorder of the inner ear characterized by episodes of vertigo, tinnitus and fluctuating sensorineural hearing loss. Most MD cases are sporadic, but 5-15% of patients are familial following an autosomal dominant mode of inheritance with incomplete penetrance. We have previously identified a candidate gene region for MD on chromosome 12p12.3 using linkage analysis. We genotyped 15 Swedish families segregating familial MD (FMD) to further clarify the role of chromosome 12p in a larger cohort of families. Highly polymorphic marker loci were analyzed over the 16-Mb candidate region in affected and healthy family members as well as in control subjects. The results revealed allelic association between FMD and several individual polymorphic marker alleles and single-nucleotide polymorphisms. Moreover, a common three-marker haplotype spanning 1.48 Mb co-segregates with FMD in 60% of the families investigated, forming the core of a possible ancestral haplotype associated with FMD in Sweden.
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| 25. |
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| 26. |
- Hakansson, Sara, et al.
(författare)
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Moderate frequency of BRCA1 and BRCA2 germ-line mutations in Scandinavian familial breast cancer
- 1997
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Ingår i: American Journal of Human Genetics. - 0002-9297. ; 60:5, s. 1068-1078
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies of high-risk breast cancer families have proposed that two major breast cancer-susceptibility genes, BRCA1 and BRCA2, may account for at least two-thirds of all hereditary breast cancer. We have screened index cases from 106 Scandinavian (mainly southern Swedish) breast cancer and breast-ovarian cancer families for germ-line mutations in all coding exons of the BRCA1 and BRCA2 genes, using the protein-truncation test, SSCP analysis, or direct sequencing. A total of 24 families exhibited 11 different BRCA1 mutations, whereas 11 different BRCA2 mutations were detected in 12 families, of which 3 contained cases of male breast cancer. One BRCA2 mutation, 4486delG, was found in two families of the present study and, in a separate study, also in breast tumors from three unrelated males with unknown family history, suggesting that at least one BRCA2 founder mutation exists in the Scandinavian population. We report 1 novel BRCA1 mutation, eight additional cases of 4 BRCA1 mutations described elsewhere, and 11 novel BRCA2 mutations (9 frameshift deletions and 2 nonsense mutations), of which all are predicted to cause premature truncation of the translated products. The relatively low frequency of BRCA1 and BRCA2 mutations in the present study could be explained by insufficient screening sensitivity to the location of mutations in uncharacterized regulatory regions, the analysis of phenocopies, or, most likely, within predisposed families, additional uncharacterized BRCA genes.
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| 27. |
- Karlsson, Ida K., et al.
(författare)
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Adiposity and the risk of dementia : mediating effects from inflammation and lipid levels
- 2022
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Ingår i: European Journal of Epidemiology. - : Springer Nature Switzerland AG.. - 0393-2990 .- 1573-7284. ; 37:12, s. 1261-1271
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Tidskriftsartikel (refereegranskat)abstract
- While midlife adiposity is a risk factor for dementia, adiposity in late-life appears to be associated with lower risk. What drives the associations is poorly understood, especially the inverse association in late-life. Using results from genome-wide association studies, we identified inflammation and lipid metabolism as biological pathways involved in both adiposity and dementia. To test if these factors mediate the effect of midlife and/or late-life adiposity on dementia, we then used cohort data from the Swedish Twin Registry, with measures of adiposity and potential mediators taken in midlife (age 40–64, n = 5999) or late-life (age 65–90, n = 7257). Associations between body-mass index (BMI), waist-hip ratio (WHR), C-reactive protein (CRP), lipid levels, and dementia were tested in survival and mediation analyses. Age was used as the underlying time scale, and sex and education included as covariates in all models. Fasting status was included as a covariate in models of lipids. One standard deviation (SD) higher WHR in midlife was associated with 25% (95% CI 2–52%) higher dementia risk, with slight attenuation when adjusting for BMI. No evidence of mediation through CRP or lipid levels was present. After age 65, one SD higher BMI, but not WHR, was associated with 8% (95% CI 1–14%) lower dementia risk. The association was partly mediated by higher CRP, and suppressed when high-density lipoprotein levels were low. In conclusion, the negative effects of midlife adiposity on dementia risk were driven directly by factors associated with body fat distribution, with no evidence of mediation through inflammation or lipid levels. There was an inverse association between late-life adiposity and dementia risk, especially where the body’s inflammatory response and lipid homeostasis is intact.
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| 28. |
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| 29. |
- Karlsson, Ida K., et al.
(författare)
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Epigenome-wide association study of level and change in cognitive abilities from midlife through late life
- 2021
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Ingår i: Clinical Epigenetics. - : Springer Nature. - 1868-7075 .- 1868-7083. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epigenetic mechanisms are important in aging and may be involved in late-life changes in cognitive abilities. We conducted an epigenome-wide association study of leukocyte DNA methylation in relation to level and change in cognitive abilities, from midlife through late life in 535 Swedish twins. Results: Methylation levels were measured with the Infinium Human Methylation 450 K or Infinium MethylationEPIC array, and all sites passing quality control on both arrays were selected for analysis (n = 250,816). Empirical Bayes estimates of individual intercept (age 65), linear, and quadratic change were obtained from latent growth curve models of cognitive traits and used as outcomes in linear regression models. Significant sites (p < 2.4 × 10–7) were followed up in between-within twin pair models adjusting for familial confounding and full-growth modeling. We identified six significant associations between DNA methylation and level of cognitive abilities at age 65: cg18064256 (PPP1R13L) with processing speed and spatial ability; cg04549090 (NRXN3) with spatial ability; cg09988380 (POGZ), cg25651129 (-), and cg08011941 (ENTPD8) with working memory. The genes are involved in neuroinflammation, neuropsychiatric disorders, and ATP metabolism. Within-pair associations were approximately half that of between-pair associations across all sites. In full-growth curve models, associations between DNA methylation and cognitive level at age 65 were of small effect sizes, and associations between DNA methylation and longitudinal change in cognitive abilities of very small effect sizes. Conclusions: Leukocyte DNA methylation was associated with level, but not change in cognitive abilities. The associations were substantially attenuated in within-pair analyses, indicating they are influenced in part by genetic factors.
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| 30. |
- Karlsson, Ida K., et al.
(författare)
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Replicating associations between DNA methylation and body mass index in a longitudinal sample of older twins
- 2020
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Ingår i: International Journal of Obesity. - : Springer Nature. - 0307-0565 .- 1476-5497. ; 44:6, s. 1397-1405
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Tidskriftsartikel (refereegranskat)abstract
- Background:There is an important interplay between epigenetic factors and body weight, and previous work has identified ten sites where DNA methylation is robustly associated with body mass index (BMI) cross-sectionally. However, interpretation of the associations is complicated by the substantial changes in BMI often occurring in late-life, and the fact that methylation is often driven by genetic variation. This study therefore investigated the longitudinal association between these ten sites and BMI from midlife to late-life, and whether associations persist after controlling for genetic factors.Methods:We used data from 535 individuals (mean age 68) in the Swedish Adoption/Twin Study of Aging (SATSA) with longitudinal measures of both DNA methylation from blood samples and BMI, spanning up to 20 years. Methylation levels were measured with the Infinium Human Methylation 450K or Infinium MethylationEpic array, with seven of the ten sites passing quality control. Latent growth curve models were applied to investigate longitudinal associations between methylation and BMI, and between–within models to study associations within twin pairs, thus adjusting for genetic factors.Results:Baseline DNA methylation levels at five of the seven sites were associated with BMI level at age 65 (cg00574958 [CPT1A]; cg11024682 [SREBF1]), and/or change (cg06192883 [MYO5C]; cg06946797 [RMI2]; cg08857797 [VPS25]). For four of the five sites, the associations remained comparable within twin pairs. However, the effects of cg06192883 were substantially attenuated within pairs. No change in DNA methylation was detected for any of the seven evaluated sites.Conclusion:Five of the seven sites investigated were associated with late-life level and/or change in BMI. The effects for four of the sites remained similar when examined within twin pairs, indicating that the associations are mainly environmentally driven. However, the substantial attenuation in the association between cg06192883 and late-life BMI within pairs points to the importance of genetic factors in this association.
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