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- Klasson-Heggebø, L., et al.
(författare)
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Graded associations between cardiorespiratory fitness, fatness, and blood pressure in children and adolescents
- 2006
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Ingår i: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 40:1, s. 25-29; discussion 25
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:To measure the graded relation between cardiorespiratory fitness and sum of skinfolds, waist circumference, and blood pressure in children and adolescents participating in the European youth heart study.METHODS:The participants were 4072 children and adolescents (aged 9 and 15) from Denmark, Portugal, Estonia, and Norway. Cardiorespiratory fitness was indirectly determined using a maximal ergometer cycle test. The sum of four skinfolds, waist circumference, and blood pressure were assessed with a standardised protocol. Linear regression analysis was used to test the graded relation between cardiorespiratory fitness and the dependent variables adjusted for pubertal stage, sex, and country.RESULTS:A significant curvilinear graded relation was found between cardiorespiratory fitness and waist circumference and sum of skinfolds (partial r2 for cardiorespiratory fitness was 0.09-0.26 for the different sexes and age groups). Systolic and diastolic blood pressure also showed a curvilinear relation with cardiorespiratory fitness, and fitness explained 2% of the variance in systolic blood pressure. The difference in systolic blood pressure between the least and most fit was 6 mm Hg.CONCLUSION:A curvilinear graded relation was found between cardiorespiratory fitness and waist circumference, sum of skinfolds, and systolic blood pressure. The greatest difference in these health variables was observed between low and moderate fitness levels.
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| 2. |
- Hagmar, L, et al.
(författare)
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Plasma concentrations of persistent organochlorines in relation to thyrotropin and thyroid hormone levels in women
- 2001
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 0340-0131 .- 1432-1246. ; 74:3, s. 8-184
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: There is a concern that persistent organohalogen toxicants, such as polychlorinated biphenyls (PCBs), might display endocrine-disrupting effects in exposed populations. In this study the correlations between PCBs and thyrotropin (TSH) and thyroid hormone concentrations in plasma were assessed in adult women.METHODS: The study group consisted of 182 fishermen's wives from the Swedish east coast, with a median age of 42 years (range 23-62) and a median current consumption of contaminated fatty fish from the Baltic Sea of two meals per month (range 0-12). TSH, free (FT3) and total (TT3) triiodothyronine and free (FT4) and total (TT4) thyroxin in plasma were analyzed by immunofluorometric assays, and 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) in plasma was analyzed by gas chromatography with electron capture detection. Twenty other PCB and two hydroxy-PCB congeners were analyzed in subgroups of the women. Plasma lipid analyses were performed with enzymatic techniques.RESULTS: The CB-153 concentration in plasma (range 16-776 ng/g lipid) was negatively correlated with the TT3 concentrations (range 1.0-3.0 nmol/l, rs = -0.29, P < 0.001). This association remained after age adjustment.CONCLUSIONS: The present study gives some support for the notion that dietary exposure to persistent organochlorine compounds (POCs) might weakly affect peripheral thyroid hormone concentrations in adult women.
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| 6. |
- Frankling, MH, et al.
(författare)
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'Palliative-D'-Vitamin D Supplementation to Palliative Cancer Patients: A Double Blind, Randomized Placebo-Controlled Multicenter Trial
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:15
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the ‘Palliative-D’ study was to test the hypothesis that correction of vitamin D deficiency reduces opioid use in cancer patients admitted to palliative care. A multicenter randomized, placebo-controlled, double-blind trial in three home-based palliative care facilities in Sweden was performed. Patients with advanced cancer and 25-hydroxyvitamin D < 50 nmol/L were randomized to vitamin D3 4000 IU/day or placebo for 12 weeks. The primary endpoint was the difference of long-acting opioid use (fentanyl ug/h) between the groups during 12 weeks, based on four time points. Secondary outcomes included changes in antibiotic use, fatigue and Quality of Life (QoL). A total of 244 patients were randomized, and 150 patients completed the 12 weeks. The major reason for drop-out was death due to cancer. The vitamin D-group had a significantly smaller increase of opioid doses compared to the placebo-group; beta coefficient −0.56 (p = 0.03), i.e., 0.56 µg less fentanyl/h per week with vitamin D treatment. Vitamin D-reduced fatigue assessed with ESAS was −1.1 points after 12 weeks (p < 0.01). Antibiotic use or QoL did not differ significantly between the groups. The treatment was safe and well-tolerated. In conclusion, correction of vitamin D deficiency may have positive effects on opioid use and fatigue in palliative cancer patients, but only in those with a survival time more than 12 weeks.
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| 7. |
- Olsson Lindvall, Martina, et al.
(författare)
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A Comprehensive Sequencing-Based Analysis of Allelic Methylation Patterns in Hemostatic Genes in Human Liver
- 2020
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Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 120:2, s. 229-242
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Tidskriftsartikel (refereegranskat)abstract
- Characterizing the relationship between genetic, epigenetic (e.g., deoxyribonucleic acid [DNA] methylation), and transcript variation could provide insights into mechanisms regulating hemostasis and potentially identify new drug targets. Several hemostatic factors are synthesized in the liver, yet high-resolution DNA methylation data from human liver tissue is currently lacking for these genes. Single-nucleotide polymorphisms (SNPs) can influence DNA methylation in cis which can affect gene expression. This can be analyzed through allele-specific methylation (ASM) experiments. We performed targeted genomic DNA- and bisulfite-sequencing of 35 hemostatic genes in human liver samples for SNP and DNA methylation analysis, respectively, and integrated the data for ASM determination. ASM-associated SNPs (ASM-SNPs) were tested for association to gene expression in liver using in-house generated ribonucleic acid-sequencing data. We then assessed whether ASM-SNPs associated with gene expression, plasma proteins, or other traits relevant for hemostasis using publicly available data. We identified 112 candidate ASM-SNPs. Of these, 68% were associated with expression of their respective genes in human liver or in other human tissues and 54% were associated with the respective plasma protein levels, activity, or other relevant hemostatic genome-wide association study traits such as venous thromboembolism, coronary artery disease, stroke, and warfarin dose maintenance. Our study provides the first detailed map of the DNA methylation landscape and ASM analysis of hemostatic genes in human liver tissue, and suggests that methylation regulated by genetic variants in cis may provide a mechanistic link between noncoding SNPs and variation observed in circulating hemostatic proteins, prothrombotic diseases, and drug response.
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| 8. |
- Olsson Lindvall, Martina, et al.
(författare)
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Hemostatic Genes Exhibit a High Degree of Allele-Specific Regulation in Liver
- 2019
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Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 119:7, s. 1072-1083
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Tidskriftsartikel (refereegranskat)abstract
- Objective Elucidating the genetic basis underlying hepatic hemostatic gene expression variability may contribute to unraveling genetic factors contributing to thrombotic or bleeding disorders. We aimed to identify novel cis-regulatory variants involved in regulating hemostatic genes by analyzing allele-specific expression (ASE) in human liver samples. Study Design Biopsies of human liver tissue and blood were collected from adults undergoing liver surgery at the Sahlgrenska University Hospital (n =20). Genomic deoxyribonucleic acid (gDNA) and total ribonucleic acid (RNA) were isolated. A targeted approach was used to enrich and sequence 35 hemostatic genes for single nucleotide polymorphism (SNP) analysis (gDNAseq) and construct individualized genomes for transcript alignment. The allelic ratio of transcripts from targeted RNAseq was determined via ASE analysis. Public expression quantitative trait loci (eQTL) and genome-wide association study (GWAS) data were used to assess novelty and importance of the ASE SNPs (and proxies, r(2) >= 0.8) for relevant traits/diseases. Results Sixty percent of the genes studied showed allelic imbalance across 53 SNPs. Of these, 7 SNPs were previously validated in liver eQTL studies. For 32 with eQTLs in other cell/tissue types, this is the first time genotype-specific expression is demonstrated in liver, and for 14 ASE SNPs, this is the first ever reported genotype-expression association. A total of 29 ASE SNPs were previously associated with the respective plasma protein levels and 17 ASE SNPs to other relevant GWAS traits including venous thromboembolism, coronary artery disease, and stroke. Conclusion Our study provides a comprehensive ASE analysis of hemostatic genes and insights into the regulation of hemostatic genes in human liver.
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| 9. |
- Repetto, Linda, et al.
(författare)
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Genetic mechanisms of 184 neuro-related proteins in human plasma.
- 2023
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Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Understanding the genetic basis of neuro-related proteins is essential for dissecting the disease etiology of neuropsychiatric disorders and other complex traits and diseases. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-related proteins in human plasma. The analysis identified 117 cis-regulatory protein quantitative trait loci (cis-pQTL) and 166 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. Mendelian randomization analyses revealed multiple proteins showing potential causal effects on neuro-related traits as well as complex diseases such as hypertension, high cholesterol, immune-related disorders, and psychiatric disorders. Integrating with established drug information, we validated 13 combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets for diseases and comorbidities. This consortium effort provides a large-scale proteogenomic resource for biomedical research.
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| 10. |
- Repetto, Linda, et al.
(författare)
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Unraveling Neuro-Proteogenomic Landscape and Therapeutic Implications for Human Behaviors and Psychiatric Disorders.
- 2023
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Ingår i: Nature Portfolio. - : Research Square Platform LLC.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioral traits and the disease etiology of neuropsychiatric disorders. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-related proteins in human plasma. The analysis identified 117 cis-regulatory protein quantitative trait loci (cis-pQTL) and 166 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. Mendelian randomization analyses revealed multiple proteins showing potential causal effects on neuro-related traits such as sleeping, smoking, feelings, alcohol intake, mental health, and psychiatric disorders. Integrating with established drug information, we validated 13 out of 13 matched combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets. This consortium effort provides a large-scale proteogenomic resource for biomedical research on human behaviors and other neuro-related phenotypes.
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