| 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. |
- Ahlström, Christine, et al.
(författare)
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Feedback modeling of non-esterified fatty acids in rats after nicotinic acid infusions
- 2011
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Ingår i: JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS. - 1567-567X. ; 38:1, s. 1-24
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Tidskriftsartikel (refereegranskat)abstract
- A feedback model was developed to describe the tolerance and oscillatory rebound seen in non-esterified fatty acid (NEFA) plasma concentrations following intravenous infusions of nicotinic acid (NiAc) to male Sprague-Dawley rats. NiAc was administered as an intravenous infusion over 30 min (0, 1, 5 or 20 μmol kg(-1) of body weight) or over 300 min (0, 5, 10 or 51 μmol kg(-1) of body weight), to healthy rats (n = 63), and serial arterial blood samples were taken for measurement of NiAc and NEFA plasma concentrations. Data were analyzed using nonlinear mixed effects modeling (NONMEM). The disposition of NiAc was described by a two-compartment model with endogenous turnover rate and two parallel capacity-limited elimination processes. The plasma concentration of NiAc was driving NEFA (R) turnover via an inhibitory drug-mechanism function acting on the formation of NEFA. The NEFA turnover was described by a feedback model with a moderator distributed over a series of transit compartments, where the first compartment (M (1)) inhibited the formation of R and the last compartment (M ( N )) stimulated the loss of R. All processes regulating plasma NEFA concentrations were assumed to be captured by the moderator function. The potency, IC (50), of NiAc was 45 nmol L(-1), the fractional turnover rate k ( out ) was 0.41 L mmol(-1) min(-1) and the turnover rate of moderator k ( tol ) was 0.027 min(-1). A lower physiological limit of NEFA was modeled as a NiAc-independent release (k ( cap )) of NEFA into plasma and was estimated to 0.032 mmol L(-1) min(-1). This model can be used to provide information about factors that determine the time-course of NEFA response following different modes, rates and routes of administration of NiAc. The proposed model may also serve as a preclinical tool for analyzing and simulating drug-induced changes in plasma NEFA concentrations after treatment with NiAc or NiAc analogues.
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| 3. |
- 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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| 4. |
- Bäck, Maria, 1978, et al.
(författare)
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The impact on kinesiophobia (fear of movement) by clinical variables for patients with coronary artery disease
- 2013
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Ingår i: International Journal of Cardiology. - : Elsevier Ireland Ltd. - 0167-5273 .- 1874-1754. ; 167:2, s. 391-397
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Tidskriftsartikel (refereegranskat)abstract
- Background: The impact on kinesiophobia (fear of movement) for patients with coronary artery disease (CAD) is not known. The aims were to describe the occurrence of kinesiophobia in patients with CAD, and to investigate the influence on kinesiophobia by clinical variables. Material and methods: In total, 332 patients, mean age, 65±9.1 years diagnosed with CAD at a university hospital were included in the study. The Tampa Scale for Kinesiophobia Heart (TSK-SV Heart) was used to assess kinesiophobia. Comparisons between high versus low levels of kinesiophobia were measured for each variable. Binary logistic regression analyses were performed with a high level of kinesiophobia (TSK-SV Heart >37) as dependent variable, and with the observed variables as independent. The study had an exploratory, cross-sectional design. Results: A high level of kinesiophobia was found in 20% of the patients. The following variables decreased the odds ratio (OR) for a high level of kinesiophobia: Attending cardiac rehabilitation (yes vs no; -56.7%), level of physical activity (medium vs high; -80.2%), Short Form-36: general health (-4,3%), physical functioning (-1.8%). Two variables increased the OR for a high level of kinesiophobia: heart failure as complication at hospital (yes vs no; 418.7%), anxiety (19.2%). Previous heart failure (yes vs no) was unexpectedly found to reduce kinesiophobia (-88.3%) due to suppression. Conclusions: Several important clinical findings with impact on rehabilitation and prognosis for patients with CAD were found to be associated with a high level of kinesiophobia. Therefore, kinesiophobia needs to be considered in secondary prevention for patients with CAD.
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| 5. |
- Bäck, Maria, 1978, et al.
(författare)
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Validation of a questionnaire to detect kinesiophobia (fear of movement) in patients with coronary artery disease
- 2012
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Ingår i: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1651-2081 .- 1650-1977. ; 44:4, s. 363-369
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the validity and reliability of the Tampa Scale for Kinesiophobia Heart (TSK-SV Heart), which is a brief questionnaire to detect kinesiophobia (fear of movement), in patients with coronary artery disease (CAD). Design: Methodological research (cross-sectional study). Subjects: A total of 332 patients, mean age, 65±9.1 years diagnosed with CAD at a university hospital were included in the study. Methods: The psychometric properties of the TSK-SV Heart were tested. The tests of validity comprised face validity, content validity, and construct validity. The reliability tests included composite reliability, internal consistency and stability over time. Results: In terms of reliability, the TSK-SV Heart was found to be stable over time (Intra Class Correlation coefficient = 0.83), and internally consistent (Cronbach’s alpha = 0.78). A confirmatory factor analysis provided acceptable fit for a hypothesized four-factor model with inclusion of a method factor. Conclusions: These results provide support showing the TSK-SV Heart to be reliable and the questionnaire seems to be valid for use in patients with CAD. However, some items need further investigation due to low influence on some sub-dimensions of the test. The sub-dimensions of kinesiophobia require future studies concerning their implications for the target group.
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| 6. |
- 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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| 7. |
- Eeg-Olofsson, Måns, 1967, et al.
(författare)
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BCI-bone conduction implant.
- 2013
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Ingår i: The Fourth International Symposium on Bone Conduction Hearing – Craniofacial Osseointegration. Newcastle, UK.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 8. |
- 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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| 9. |
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| 10. |
- Fredén Jansson, Karl-Johan, 1988, et al.
(författare)
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MRI Induced Torque and Demagnetization in Retention Magnets for a Bone Conduction Implant
- 2014
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Ingår i: IEEE Transactions on Biomedical Engineering. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9294 .- 1558-2531. ; 61:6, s. 1887-1893
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Tidskriftsartikel (refereegranskat)abstract
- Performing magnetic resonance imaging (MRI) examinations in patients who use implantable medical devices involve safety risks both for the patient and the implant. Hearing implants often use two permanent magnets, one implanted and one external, for the retention of the external transmitter coil to the implanted receiver coil to achieve an optimal signal transmission. The implanted magnet is subjected to both demagnetization and torque, magnetically induced by the MRI scanner. In this paper, demagnetization and a comparison between measured and simulated induced torque is studied for the retention magnet used in a bone conduction implant (BCI) system. The torque was measured and simulated in a uniform static magnetic field of 1.5 T. The magnetic field was generated by a dipole electromagnet and permanent magnets with two different types of coercive fields were tested. Demagnetization and maximum torque for the high coercive field magnets was 7.7% +/- 2.5% and 0.20 +/- 0.01 Nm, respectively and 71.4% +/- 19.1% and 0.18 +/- 0.01 Nm for the low coercive field magnets, respectively. The simulated maximum torque was 0.34 Nm, deviating from the measured torque in terms of amplitude, mainly related to an insufficient magnet model. The BCI implant with high coercive field magnets is believed to be magnetic resonance (MR) conditional up to 1.5 T if a compression band is used around the skull to fix the implant. This is not approved and requires further investigations, and if removal of the implant is needed, the surgical operation is expected to be simple.
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