| 1. |
- Sarwar, Nadeem, et al.
(författare)
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Interleukin-6 receptor pathways in coronary heart disease : a collaborative meta-analysis of 82 studies
- 2012
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Ingår i: The Lancet. - New York, NY, USA : Elsevier. - 0140-6736 .- 1474-547X. ; 379:9822, s. 1205-1213
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Tidskriftsartikel (refereegranskat)abstract
- Background: Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling. Methods: In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125 222 participants. We also compared the frequency of Asp358Ala in 51 441 patients with coronary heart disease and in 136 226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6. Findings: The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele >= 0.04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34.3% (95% CI 30.4-38.2) and of interleukin 6 by 14.6% (10.7-18.4), and mean concentration of C-reactive protein was reduced by 7.5% (5.9-9.1) and of fibrinogen by 1.0% (0.7-1.3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3.4% (1.8-5.0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes. Interpretation: Large-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease.
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| 2. |
- Jansson, Jan-Håkan, et al.
(författare)
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Snus (Swedish smokeless tobacco) use and risk of stroke: pooled analyses of incidence and survival
- 2014
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 276:1, s. 87-95
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Tidskriftsartikel (refereegranskat)abstract
- Background. Snus is a moist smokeless tobacco product with high nicotine content. Its use has a short-term effect on the cardiovascular system, but the relationship between snus use and stroke is unclear. Objective. The aim of this study was to assess the associations between use of snus and incidence of and survival after stroke, both overall and according to subtypes. Methods. Pooled analyses of eight Swedish prospective cohort studies were conducted, including 130 485 men who never smoked. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of incidence and death after diagnosis using Cox proportional hazard regression models and case fatality and survival using logistic regression and Kaplan-Meier methods, respectively. Results. No associations were observed between the use of snus and the risk of overall stroke (HR 1.04, 95% CI 0.92-1.17) or of any of the stroke subtypes. The odds ratio (OR) of 28-day case fatality was 1.42 (95% CI 0.99-2.04) amongst users of snus who had experienced a stroke, and the HR of death during the follow-up period was 1.32 (95% CI 1.08-1.61). Conclusion. Use of snus was not associated with the risk of stroke. Hence, nicotine is unlikely to contribute importantly to the pathophysiology of stroke. However, case fatality was increased in snus users, compared with nonusers, but further studies are needed to determine any possible causal mechanisms.
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| 3. |
- Eeg-Olofsson, Måns, 1967, et al.
(författare)
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Evaluation of bone tissue formation in a flat surface attachment of a Bone Conduction Implant - A pilot study in a sheep model
- 2014
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Ingår i: Audiology & Neurotology Extra. - : S. Karger AG. - 1664-5537. ; 4:3, s. 62-76
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Tidskriftsartikel (refereegranskat)abstract
- The Bone Conduction Implant (BCI) is a new bone conduction hearing device implanted under intact skin. The transducer has a flat direct contact to the mastoid part of the temporal bone and no screws are used. The sound signal is transmitted from the external audio processor to the implant by means of magnetic induction. In this study, osseointegration of a flat passive BCI transducer dummy in sheep skulls was assessed using quantitative and qualitative histology as well as Cone Beam Computed Tomography (CBCT) and Computed Tomography (CT). The histology results were also related to the mechanical properties of the bone to implant interface. Eight months after the surgical implantation, histology sections of the bone close to the implant showed bone remodelling, compact bone and some degree of osseointegration. The histological findings corresponded well to the mechanical measurements indicating stiffer bone close to the implant, and unaffected skull vibration transmission. Neither CBCT nor CT had enough resolution to visualize the bone to implant interface in detail. In this study, using an animal model, it is shown that a flat implant in contact with bone, can be a feasible method for efficient vibration transmission to the skull bone.
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| 4. |
- Speliotes, Elizabeth K., et al.
(författare)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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| 5. |
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| 6. |
- Heid, Iris M, et al.
(författare)
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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
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Tidskriftsartikel (refereegranskat)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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| 7. |
- Paul-Visse, Gesine, et al.
(författare)
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The adult human brain harbors multipotent perivascular mesenchymal stem cells.
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- Blood vessels and adjacent cells form perivascular stem cell niches in adult tissues. In this perivascular niche, a stem cell with mesenchymal characteristics was recently identified in some adult somatic tissues. These cells are pericytes that line the microvasculature, express mesenchymal markers and differentiate into mesodermal lineages but might even have the capacity to generate tissue-specific cell types. Here, we isolated, purified and characterized a previously unrecognized progenitor population from two different regions in the adult human brain, the ventricular wall and the neocortex. We show that these cells co-express markers for mesenchymal stem cells and pericytes in vivo and in vitro, but do not express glial, neuronal progenitor, hematopoietic, endothelial or microglial markers in their native state. Furthermore, we demonstrate at a clonal level that these progenitors have true multilineage potential towards both, the mesodermal and neuroectodermal phenotype. They can be epigenetically induced in vitro into adipocytes, chondroblasts and osteoblasts but also into glial cells and immature neurons. This progenitor population exhibits long-term proliferation, karyotype stability and retention of phenotype and multipotency following extensive propagation. Thus, we provide evidence that the vascular niche in the adult human brain harbors a novel progenitor with multilineage capacity that appears to represent mesenchymal stem cells and is different from any previously described human neural stem cell. Future studies will elucidate whether these cells may play a role for disease or may represent a reservoir that can be exploited in efforts to repair the diseased human brain.
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| 8. |
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| 9. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 10. |
- Bäck, Maria, 1978, et al.
(författare)
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What variables predict participation in exercise-based cardiac rehabilitation in patients with coronary artery disease?
- 2014
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Ingår i: European Heart Journal. European Society of Cardiology, 30 August - 3 September 2014, Barcelona. ; 35:Suppl 1
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Purpose Despite the well-established positive effects of exercise-based cardiac rehabilitation (CR) participation has been shown to be sub-optimal. A significant association between kinesiophobia (fear of movement) and participation in CR has previously been found. Therefore, the aim of this study was to identify predictors of participation in CR in patients with coronary artery disease (CAD), with a special reference to kinesiophobia. Methods In all, 332 patients (75 women; mean age 65±9.1 years) with a diagnosis of CAD were recruited between 2007 and 2009 at Sahlgrenska University Hospital/Sahlgrenska. The patients were tested regarding muscle endurance, level of physical activity, health related quality of life, anxiety, depression and kinesiophobia. A path model with direct and indirect effects via kinesiophobia was used to predict participation in CR. An explorative selection of significant predictors was performed. Results Kinesiophobia (p=.012), waist circumference (p=.023), and a previous history of PCI (p=.037) had direct negative effects on participation in CR, while current incidence of CABG (p<.001), PCI (p=.005) and BMI (p=.008) had positive effects. Compared to patients diagnosed with unstable angina, a diagnosis of myocardial infarction (p=.004) had a positive effect on participation in CR. The following indirect effects on participation in CR were found. Anxiety (p=.001) and previous PCI (p=.025) increased kinesiophobia, while muscle endurance (p=.003), perceptions of general health (p<.001) and physical functioning (p=.009) decreased kinesiophobia. Moreover, men had higher kinesiophobia compared to women (p=.031) and smoking was found to reduce kinesiophobia (p=.004). Conclusions Several important variables with an influence on participation in CR were identified and should be further analysed in relation to clinical practice. A reduction of kinesiophobia can be an efficient way to increase participation in CR and should therefore be given priority in future research.
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