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| 2. |
- Al-Delaimy, WK, et al.
(författare)
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Plasma carotenoids as biomarkers of intake of fruits and vegetables: ecological-level correlations in the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2005
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 1476-5640 .- 0954-3007. ; 59:12, s. 1397-1408
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to assess the ability of a single 24-h dietary recall (24HDR) and food questionnaires (FQ) to predict plasma carotenoid levels at the ecological level by assessing the relationship between mean plasma carotenoid levels and mean intake of fruit and vegetables measured by 24HDR and FQ across 16 European regions. Design: A random subsample of 3089 subjects was included, stratified by age and gender. They provided blood samples and dietary information between 1992 and 2000 as part of the European Prospective Investigation into Cancer and Nutrition. Results: Using Spearman's correlation coefficients, the correlations between mean regional 24HDR fruit and vegetable variables and corresponding mean plasma carotenoid levels were generally higher than the correlations using FQ means. The highest correlation was between the 24HDR citrus fruit variable and beta-cryptoxanthin (r = 0.90). For 24HDR, total fruits and vegetables were highly correlated with lutein, zeaxanthin, and beta-cryptoxanthin (r = 0.83-0.87), while vegetables were more closely related with lutein (r = 0.69) and zeaxanthin (r = 0.68), and fruits correlated with zeaxanthin (r = 0.87) and beta-cryptoxanthin (r = 0.84). Root vegetables (r = 0.81) and total carrots (r = 0.71) were well correlated with alpha-carotene. In the multivariate models adjusting for age, body mass index, and season, and using observations of means stratified by sex and region, the association was generally higher for 24HDR compared to FQ. Conclusion: Mean regional intakes of fruits and vegetables in several European countries were closely correlated with corresponding mean plasma levels of individual carotenoids. Fruits and vegetables measured by 24HDR were generally better able to predict plasma carotenoids at the ecological level.
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| 3. |
- Carreras-Torres, Robert, et al.
(författare)
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Obesity, metabolic factors and risk of different histological types of lung cancer : a Mendelian randomization study
- 2017
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Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer. Methods and findings: We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01-1.43] and for small cell lung cancer (OR [95% CI] = 1.52 [1.15-2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m(2)]), but not for adenocarcinoma (OR [95% CI] = 0.93 [0.79-1.08]) (P-heterogeneity = 4.3x10(-3)). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10(-3)), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95% CI] = 0.90 [0.84-0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95% CI] = 1.63 [1.25-2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results. Conclusions: Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously unrecognized effect of obesity on smoking behavior.
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| 4. |
- Ji, Xuemei, et al.
(författare)
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Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk
- 2018
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer.
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| 5. |
- Johansson, Yvonne A., 1956-
(författare)
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Delirium hos äldre patienter som vårdas på sjukhus : identifiering av symtom, tecken och riskfaktorer samt journalförda vårdåtgärder
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- I samband med sjukhusvård kan äldre patienter riskera försämrad hälsa, inklusive delirium. Delirium, som är vanligt hos äldre patienter på sjukhus, är ett akut och allvarligt tillstånd med svåra konsekvenser för såväl patienten som för närstående, vårdpersonal och hälso- och sjukvård. Det är viktigt att delirium förebyggs, identifieras och behandlas. Forskning visar dock på brister i vården, vilket kan påverka patienternas hälsa och välbefinnande negativt. Det övergripande syftet med avhandlingen var att identifiera och beskriva symtom, tecken, riskfaktorer och vårdåtgärder vid delirium hos äldre patienter som vårdas på sjukhus samt att utvärdera tillämpbarheten av ett bedömningsinstrument för att identifiera delirium. Alla deltagande patienter var 65 år och äldre och rekryterades från ett länssjukhus (I-IV) och ett universitetssjukhus (III, IV). Dessutom ingick de bedömare som bedömt delirium med bedömningsinstrumentet 4AT i delarbete IV. Delarbetena bestod av en kvantitativ subgruppsanalys (n=25) av en punktprevalensstudie (n=210), en retrospektiv journalgranskning (n=78) med kvalitativ analys och två tvärsnittsstudier baserade på samma urval (n=200) med kvantitativa (III, IV) och kvalitativa analyser (IV). Data samlades in genom strukturerade intervjuer, validerade instrument, patientjournaler, frågeformulär och en öppen intervjufråga.Patienterna rapporterade svåra och besvärande symtom vilka hade journalförts i begränsad omfattning (14%). Även kognitiv funktionsnedsättning och patienternas beskrivningar av sitt välbefinnande hade journalförts i liten utsträckning. Patienternas tecken på delirium ledde till nedsatt förmåga att såväl delta i sin egen vård som att undvika skada. Vårdpersonalen svarade delvis på patienternas tecken på delirium då åtgärderna kunde vara både anpassade, bristfälliga och utöver vanlig vård. Skörhet var den starkaste riskfaktorn för delirium. Andelen patienter med delirium ökade med svårighetsgraden av skörhet. Den svenska versionen av bedömningsinstrumentet 4AT för att identifiera delirium hade diagnostisk precision och klinisk användbarhet med hög interbedömarreliabilitet. Bedömningsinstrumentet 4AT tolererades väl av patienterna, var lätt att använda och tog några minuter att genomföra. Detta innebär att det nu finns ett enkelt bedömningsinstrument för delirium på svenska som kan användas för att bedöma delirium hos äldre patienter som vårdas på sjukhus.Endast en mindre del av den studerade vården kan ses som personcentrerad och patientsäker. Struktur, systematik och ett helhetsperspektiv tycktes saknas, liksom ett personcentrerat förhållnings- och arbetssätt. För att minska incidensen av delirium, lidande och kostnader behöver vården förbättras. Det finns behov av att öka kunskapen om delirium och att se delirium som en vårdskada inom all vård. Vidare finns behov av att utveckla vården genom att tydligt integrera ett personcentrerat och patientsäkert förhållnings- och arbetssätt för att nå en helhetssyn på patienten. Målet är att främja hälsa och välbefinnande genom att förebygga delirium. För att möjliggöra identifiering av individuella vårdbehov är det en förutsättning att etablera en tillitsfull vårdrelation med den äldre patienten, där patientens perspektiv tillvaratas. Individuella vårdbehov behöver identifieras strukturerat och systematiskt genom bedömning med bedömningsinstrument av symtom, tecken, välbefinnande, delirium och riskfaktorer för delirium innefattande skörhet samt kognitiv funktionsnedsättning. Detta möjliggör individuellt anpassade vårdåtgärder.Ett individuellt anpassat omhändertagande som överensstämmer med ett integrerat personcentrerat och patientsäkert förhållnings- och arbetssätt skulle kunna bidra till att minska incidensen av delirium vilket kan skapa positiva effekter för såväl patienter som för vårdpersonal och hälso- och sjukvård.
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| 6. |
- McKay, James D., et al.
(författare)
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Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes
- 2017
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 49:7, s. 1126-1132
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Tidskriftsartikel (refereegranskat)abstract
- Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genomewide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer.
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| 7. |
- Al-Delaimy, WK, et al.
(författare)
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Plasma carotenoids as biomarkers of intake of fruits and vegetables: individual-level correlations in the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2005
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 1476-5640 .- 0954-3007. ; 59:12, s. 1387-1396
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim in this study was to assess the association between individual plasma carotenoid levels (alpha-carotene, beta-carotene, lycopene, beta-cryptoxanthin, lutein, zeaxanthin) and fruit and vegetable intakes recorded by a calibrated food questionnaire (FQ) and 24- h dietary recall records (24HDR) in nine different European countries with diverse populations and widely varying intakes of plant foods. Design: A stratified random subsample of 3089 men and women from nine countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC), who had provided blood samples and dietary and other lifestyle information between 1992 and 2000, were included. Results: beta-Cryptoxanthin was most strongly correlated with total fruits (FQ r = 0.52, 24HDR r = 0.39), lycopene with tomato and tomato products (FQ r = 0.38, 24HDR r = 0.25), and alpha-carotene with intake of root vegetables (r = 0.39) and of total carrots (r = 0.38) for FQ only. Based on diet measured by FQ and adjusting for possible confounding by body mass index (BMI), age, gender, smoking status, alcohol intake, and energy intake, the strongest predictors of individual plasma carotenoid levels were fruits (R-partial(2) = 17.2%) for beta-cryptoxanthin, total carrots (R-partial(2) = 13.4%) and root vegetables (R-partial(2) = 13.3%) for alpha-carotene, and tomato products (R-partial(2) = 13.8%) for lycopene. For 24HDR, the highest R-partial(2) was for fruits in relation to beta-cryptoxanthin (7.9%). Conclusions: Intakes of specific fruits and vegetables as measured by food questionnaires are good predictors of certain individual plasma carotenoid levels in our multicentre European study. At individual subject levels, FQ measurements of fruits, root vegetables and carrots, and tomato products are, respectively, good predictors of beta-cryptoxanthin, alpha-carotene, and lycopene in plasma.
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| 10. |
- Andersson, Irene, 1978, et al.
(författare)
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Endothelial dysfunction in growth hormone transgenic mice
- 2006
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Ingår i: Clinical Science. - 0143-5221 .- 1470-8736. ; 110:2, s. 217-25
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Tidskriftsartikel (refereegranskat)abstract
- Acromegaly [overproduction of GH (growth hormone)] is associated with cardiovascular disease. Transgenic mice overexpressing bGH (bovine GH) develop hypertension and hypercholesterolaemia and could be a model for cardiovascular disease in acromegaly. The aims of the present study were to investigate the effects of excess GH on vascular function and to test whether oxidative stress affects endothelial function in bGH transgenic mice. We studied the ACh (acetylcholine)-induced relaxation response in aortic and carotid rings of young (9-11 weeks) and aged (22-24 weeks) female bGH transgenic mice and littermate control mice, without and with the addition of a free radical scavenger {MnTBAP [Mn(III)tetrakis(4-benzoic acid)porphyrin chloride]}. We also measured mRNA levels of eNOS (endothelial nitric oxide synthase) and EC-SOD (extracellular superoxide dismutase). Intracellular superoxide anion production in the vascular wall was estimated using a dihydroethidium probe. Carotid arteries from bGH transgenic mice had an impaired ACh-induced relaxation response (young, 46 +/- 7% compared with 69 +/- 8%; aged, 52 +/- 5% compared with 80 +/- 3%; P < 0.05), whereas endothelial function in aorta was intact in young but impaired in aged bGH transgenic mice. Endothelial dysfunction was corrected by addition of MnTBAP in carotid arteries from young mice and in aortas from aged mice; however, MnTBAP did not correct endothelial dysfunction in carotid arteries from aged bGH transgenic mice. There was no difference in intracellular superoxide anion production between bGH transgenic mice and control mice, whereas mRNA expression of EC-SOD and eNOS was increased in aortas from young bGH transgenic mice compared with control mice (P < 0.05). We interpret these data to suggest that bGH overexpression is associated with a time- and vessel-specific deterioration in endothelial function, initially caused by increased oxidative stress and later by other alterations in vascular function.
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