| 1. |
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| 2. |
- Andersson, Malte, 1941, et al.
(author)
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”Minskande befolkning är inte problemet”
- 2020
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In: Dagens Nyheter. ; :1 augusti, DN-debatt
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Journal article (pop. science, debate, etc.)abstract
- Nätverket Population Matters Sweden: En uppmärksammad studie i The Lancet pekar mot en lägre befolkningsökning i världen än tidigare prognoser. Men en miljard människor till är fortfarande långt över vad jorden klarar. Befolkningstrenden måste snarare vända neråt, och det kräver åtgärder för att stärka kvinnors rättigheter världen över.
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| 3. |
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| 4. |
- Do, Ron, et al.
(author)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Journal article (peer-reviewed)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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| 5. |
- Ekström, Lars, 1959, et al.
(author)
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In vivo porcine intradiscal pressure as a function of external loading
- 2004
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In: J Spinal Disord Tech. - 1536-0652. ; 17:4, s. 312-6
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Journal article (peer-reviewed)abstract
- BACKGROUND: Spinal loading during daily activity as it relates to the ability of the intervertebral disc to sustain its integrity has been a major issue in spinal research. The purpose of this investigation was to establish the relationship between the intervertebral disc pressure in the nucleus and the load applied to the motion segment in an in vivo porcine model. METHODS: Nine domestic pigs were used in this study. A miniaturized servohydraulic testing machine was affixed to the lumbar spine via four intrapedicular screws, which were inserted bilaterally into the L2 and L3 vertebrae. A pressure needle was inserted through the lateral part of the L2-L3 disc annulus and into the nucleus pulposus. Force, deformation, and intradiscal pressure data were collected during a loading scheme that consisted of applying a set of constant loads in increasing order, that is, 50, 100, 150, 200, and 250 N. Each load was applied for 30 seconds followed by 30-second restitution. RESULTS: Intradiscal nucleus pressure was found to correlate to the applied load in all cases. Linear regression analyses resulted in the following equation: intradiscal pressure (MPa) = 0.08 + 1.25E(-3)(load, N), r(2) = 0.81, n = 8. Intradiscal pressure was also highly linearly dependent on the stress. The intrinsic intradiscal pressure was found to be 81 +/- 5 kPa. The results also indicated that the pressure within the disc exhibited a creep behavior. CONCLUSION: In conclusion, pressure in the nucleus of the porcine intervertebral disc was linearly related to the applied load and stress.
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| 6. |
- Ekström, Lars, 1959, et al.
(author)
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Intervertebral disc response to cyclic loading--an animal model.
- 1996
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In: Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine. - 0954-4119. ; 210:4, s. 249-58
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Journal article (peer-reviewed)abstract
- The viscoelastic response of a lumbar motion segment loaded in cyclic compression was studied in an in vivo porcine model (N = 7). Using surgical techniques, a miniaturized servohydraulic exciter was attached to the L2-L3 motion segment via pedicle fixation. A dynamic loading scheme was implemented, which consisted of one hour of sinusoidal vibration at 5 Hz, 50 N peak load, followed by one hour of restitution at zero load and one hour of sinusoidal vibration at 5 Hz, 100 N peak load. The force and displacement responses of the motion segment were sampled at 25 Hz. The experimental data were used for evaluating the parameters of two viscoelastic models: a standard linear solid model (three-parameter) and a linear Burger's fluid model (four-parameter). In this study, the creep behaviour under sinusoidal vibration at 5 Hz closely resembled the creep behaviour under static loading observed in previous studies. Expanding the three-parameter solid model into a four-parameter fluid model made it possible to separate out a progressive linear displacement term. This deformation was not fully recovered during restitution and is therefore an indication of a specific effect caused by the cyclic loading. High variability was observed in the parameters determined from the 50 N experimental data, particularly for the elastic modulus E1. However, at the 100 N load level, significant differences between the models were found. Both models accurately predicted the creep response under the first 800 s of 100 N loading, as displayed by mean absolute errors for the calculated deformation data from the experimental data of 1.26 and 0.97 percent for the solid and fluid models respectively. The linear Burger's fluid model, however, yielded superior predictions particularly for the initial elastic response.
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| 7. |
- Gorski, Mathias, et al.
(author)
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Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies
- 2022
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In: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 102:3, s. 624-639
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Journal article (peer-reviewed)abstract
- Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genomewide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR- baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant- by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with agedependency of genetic cross- section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in- silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03- 1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
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| 8. |
- Grövdal, Michael, et al.
(author)
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Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy
- 2010
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In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 150:3, s. 293-302
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Journal article (peer-reviewed)abstract
- This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction chemotherapy. Sixty patients were enrolled and treated by standard induction chemotherapy. Patients that reached CR started maintenance therapy with subcutaneous azacytidine, 5/28 d until relapse. Promoter-methylation status of CDKN2B (P15 ink4b), CDH1 and HIC1 was examined pre-induction, in CR and 6, 12 and 24 months post CR. Twenty-four (40%) patients achieved CR after induction chemotherapy and 23 started maintenance treatment with azacytidine. Median CR duration was 13.5 months, >24 months in 17% of the patients, and 18-30.5 months in the four patients with trisomy 8. CR duration was not associated with CDKN2B methylation status or karyotype. Median overall survival was 20 months. Hypermethylation of CDH1 was significantly associated with low CR rate, early relapse, and short overall survival (P = 0.003). 5-azacytidine treatment, at a dose of 60 mg/m(2) was well tolerated. Grade III-IV thrombocytopenia and neutropenia occurred after 9.5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients.
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| 9. |
- Henriksnäs, Johanna, 1973-
(author)
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Helicobacter pylori and Gastric Protection Mechanisms : An in vivo Study in Mice and Rats
- 2005
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Doctoral thesis (other academic/artistic)abstract
- The stomach is frequently exposed to hazardous agents and to resist this harsh environment, several protective mechanisms exist. Of special interest is the gastric pathogen Helicobacter pylori which causes gastritis, ulcers and cancer but the mechanism leading to these diseases are still unclear. However it is very likely that H. pylori negatively influence the protection mechanisms that exist in the stomach. The aims of the present investigation were first to develop an in vivo mouse model in which different protection mechanisms could be studied, and second to investigate the influence of H. pylori on these mechanisms. An in vivo preparation of the gastric mucosa in mice was developed. This preparation allows studies of different gastric mucosal variables and can also be applied for studies in other gastro-intestinal organs. Mice chronically infected with H. pylori, were shown to have a reduced ability of the mucosa to maintain a neutral pH at the epithelial cell surface. This could be due to the thinner inner, firmly adherent mucus gel layer, and/or to defective bicarbonate transport across the epithelium. The Cl-/HCO3- exchanger SLC26A9 was inhibited by NH4+, which also is produced by H. pylori. The mRNA levels of SLC26A9 were upregulated in infected mice, suggesting a way to overcome the inhibition of the transporter. Furthermore, the hyperemic response to acid pH 2 and 1.5 was abolished in these mice. The mechanisms by which the bacteria could alter the blood flow response might involve inhibition of the epithelial iNOS.Water extracts of H. pylori (HPE) reduces the blood flow acutely through an iNOS and nerve-mediated pathway, possibly through the endogenous iNOS inhibitor ADMA. Furthermore, HPE alters the blood flow response to acid as the hyperemic response to acid pH 0.8 is accentuated in mice treated with HPE.
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| 10. |
- Hodges, Paul, et al.
(author)
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Intervertebral stiffness of the spine is increased by evoked contraction of transversus abdominis and the diaphragm : in vivo porcine studies.
- 2003
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In: Spine. - 1528-1159. ; 28:23, s. 2594-601
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Journal article (peer-reviewed)abstract
- STUDY DESIGN: In vivo porcine study of intervertebral kinematics. OBJECTIVES: This study investigated the effect of transversus abdominis and diaphragm activity, and increased intra-abdominal pressure on intervertebral kinematics in porcine lumbar spines. BACKGROUND: Studies of trunk muscle recruitment in humans suggest that diaphragm and transversus abdominis activity, and the associated intra-abdominal pressure contribute to the control of intervertebral motion. However, this has not been tested in vivo. METHODS: Relative intervertebral motion of the L3 and L4 vertebrae and the stiffness at L4 were measured in response to displacements of the L4 vertebra imposed via a device fixed to the L4 vertebral body. In separate trials, diaphragm and transversus abdominis activity was evoked by stimulation of the phrenic nerves and via electrodes threaded through the abdominal wall. RESULTS: When intra-abdominal pressure was increased by diaphragm or transversus abdominis stimulation, the relative intervertebral displacement of the L3 and L4 vertebrae was reduced and the stiffness of L4 was increased for caudal displacements. There was no change in either parameter for rostral displacements. In separate trials, the diaphragm crurae and the fascial attachments of transversus abdominis were cut, but intra-abdominal pressure was increased. In these trials, the reduction in intervertebral motion was similar to trials with intact attachments for caudal motion, but was increased for rostral trials. CONCLUSIONS: The results of these studies indicate that elevated intra-abdominal pressure, and contraction of diaphragm and transversus abdominis provide a mechanical contribution to the control of spinal intervertebral stiffness. Furthermore, the effect is modified by the muscular attachments to the spine.
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| 11. |
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| 12. |
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| 13. |
- Holm, Sten, 1948, et al.
(author)
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Experimental disc degeneration due to endplate injury
- 2004
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In: J Spinal Disord Tech. - 1536-0652. ; 17:1, s. 64-71
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Journal article (peer-reviewed)abstract
- The aim of this study was to create an experimental model of disc degeneration that closely mimicked human disc degeneration. In six domestic pigs, an L4 cranial endplate perforation into the nucleus pulposus was made. Three months postoperatively, compressive testing was performed on the L2-L4 motion segments, and intradiscal pressure was measured in the intervening discs. Histochemical and morphologic examinations were made on the excised degenerated and adjacent discs. A significant reduction in water content was observed in the outer anterior annulus of the degenerated disc. In the nucleus, the proteoglycan content was significantly reduced, as well as the cellularity, although not significantly. The nucleus lost its gel-like structure and was discolored, and there was delamination of annular layers. Intradiscal pressure in the nucleus was significantly lower in the degenerated disc. In conclusion, experimental degeneration of the intervertebral disc induced by endplate penetration resembled human disc degeneration, as exemplified by biochemical and structural changes.
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| 14. |
- Holm, Sten, 1948, et al.
(author)
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Intradiscal pressure in the degenerated porcine intervertebral disc
- 2007
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In: Vet Comp Orthop Traumatol. - 0932-0814. ; 20:1, s. 29-33
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Journal article (peer-reviewed)abstract
- Measuring intradiscal pressure is one way of mechanically assessing the discs degenerative state. In this study, the load-bearing capacity of degenerated and their adjacent lumbar intervertebral discs was evaluated using two different injury models. Seventeen adolescent pigs were divided into two groups, an annulus injury group and an endplate injury group. The annulus injury group was subjected to a stab incision in the L3-L4 disc, whereas the endplate injury group received a cranial endplate perforation of the L4 vertebral body. Both groups were biomechanically evaluated three months later using a miniaturized servohydraulic testing machine across L2-L4 and with two pressure needles inserted into the nucleus pulposus of the L2-L3 and L3-L4 discs. Linear relationships between the intradiscal pressure and the applied load were determined within the load range studied. When comparing the ratio of the injured to the adjacent disc pressure, the endplate injury was lower (mean value 0.31) than the annulus injury (mean value 0.51). The pressures in the discs adjacent to the degenerated level were found to be slightly higher. This increase can be expected due to a redistribution in mobility demands in segments adjacent to those with increased stiffness, i.e. degenerated intervertebral discs.
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| 15. |
- Holm, Sten, 1948, et al.
(author)
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Reactive changes in the adolescent porcine spine with disc degeneration due to endplate injury
- 2007
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In: Vet Comp Orthop Traumatol. - 0932-0814. ; 20:1, s. 12-7
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Journal article (peer-reviewed)abstract
- Degenerative and reactive structural alterations occurring after experimentally-induced disc degeneration were evaluated using a porcine model. A cranial perforation was made through the L4 vertebral endplate into the nucleus pulposus. Three months later, the lumbar intervertebral disc and adjacent vertebrae were dissected, fixed in formalin and further processed for histopathological analyses. The results showed that there were nucleus pulposus fragments, rather than a distinct border between the nucleus and annulus fibrosus. The central lamellae were distorted and delamination of the outer anterior layers was observed. Blood vessels emerged from the adjacent tissue, penetrated the annulus and branched into the residues of the nucleus. Nerve fibres accompanying the blood vessels could be recognized in the disc within the connective scar tissue. The epiphyseal cartilage plates in the vertebrae were hypertrophic in several areas and there was bone formation directed towards the centre of the vertebral body and the disc. Hypertrophic hyaline cartilage, newly formed bone and scar tissue filled the injury canal. A slight chronic inflammatory reaction was evident along vascular buds. The reactive changes dominated over the degenerated features in the operated disc. Physiological loading enhanced the infiltration of various tissue types characterizing immature cartilage formation. Prominent neovascularisation of the central parts of the disc is likely to be of key importance in turning the degenerative features of the remaining tissue into reactive healthy structures.
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| 16. |
- Hult, E, et al.
(author)
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In vivo measurement of spinal column viscoelasticity--an animal model.
- 1995
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In: Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine. - 0954-4119. ; 209:2
-
Journal article (peer-reviewed)abstract
- The goal of this study was to measure the in vivo viscoelastic response of spinal motion segments loaded in compression using a porcine model. Nine pigs were used in the study. The animals were anaesthetized and, using surgical techniques, four intrapedicular screws were inserted into the vertebrae of the L2-L3 motion segment. A miniaturized servohydraulic exciter capable of compressing the motion segment was mounted on to the screws. In six animals, a loading scheme consisting of 50 N and 100 N of compression, each applied for 10 min, was used. Each loading period was followed by 10 min restitution with zero load. The loading scheme was repeated four times. Three animals were examined for stiffening effects by consecutively repeating eight times 50 N loading for 5 min followed by 5 min restitution with zero load. This loading scheme was repeated using a 100 N load level. The creep-recovery behavior of the motion segment was recorded continuously. Using non-linear regression techniques, the experimental data were used for evaluating the parameters of a three-parameter standard linear solid model. Correlation coefficients of the order of 0.85 or higher were obtained for the three independent parameters of the model. A survey of the data shows that the viscous deformation rate was a function of the load level. Also, repeated loading at 100 N seemed to induce long-lasting changes in the viscoelastic properties of the porcine lumbar motion segment.
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| 17. |
- Håkanson, Ulf, et al.
(author)
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Photon mapping of single quantum dots by scanning tunneling microscopy induced luminescence spectroscopy
- 2002
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In: 7th International Conference on Nanometer-Scale Science and Technology and 21st European Conference on Surface Science.
-
Conference paper (peer-reviewed)abstract
- Scanning tunneling microscopy induced luminescence (STML) has been used to investigate individual self-assembled InP quantum dots overgrown with GaInP. We will present results correlating the surface morphology with the optical properties of single dots. In particular, the strain induced energy-shift of the dot emission with increasing cap layer thickness and its relation to the overgrowth will be discussed. Effects of the dots on the properties of the overgrown GaInP will also be treated. STML spectra and monochromatic photon maps are compared with results from photoluminescence and transmission electron microscopy measurements. Furthermore, a comparison with theoretical calculations is made
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| 18. |
- Johansson, Mikael, et al.
(author)
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Correlation between overgrowth morphology and optical properties of single self-assembled InP quantum dots
- 2003
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In: Physical Review B (Condensed Matter and Materials Physics). - 1098-0121. ; 68:12
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Journal article (peer-reviewed)abstract
- We have studied the early stages of GaInP overgrowth on InP quantum dots (QD's) experimentally and theoretically. A direct correlation between the surface morphology and the optical properties of individual InP QD's is made using scanning tunneling microscopy (STM) and scanning tunneling luminescence. The geometric structure of the islands is further investigated using cross-sectional transmission electron microscopy (TEM). The overgrowth occurs in three stages; initially the InP QD's act as seeding points for the overgrowth, where the GaInP grows laterally from the side facets of the QD. The growth occurs preferentially in the [110] direction and elongated GaInP/InP islands are formed. As the overgrowth continues the islands increase laterally in size and GaInP also starts to grow between the islands, but not covering the top of the InP QD's. The growth of GaInP on top of the QD's commences once the islands have begun to coalesce. Using a model based on the STM and TEM results the electronic structures of the QD's have been calculated by eight-band k.p theory. The calculations are in good agreement with the experimental results. Our findings unravel the details of the strain induced energy shift of the QD luminescence previously reported [Pistol , Appl. Phys. Lett. 67, 1438 (1995)].
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| 19. |
- Kaigle Holm, Allison, 1964, et al.
(author)
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In vivo dynamic stiffness of the porcine lumbar spine exposed to cyclic loading: influence of load and degeneration.
- 1998
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In: Journal of spinal disorders. - 0895-0385. ; 11:1, s. 65-70
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Journal article (peer-reviewed)abstract
- The dynamic axial stiffness of the L2-3 motion segment subjected to vibratory loading under intact and injured states of the intervertebral disc was studied using an in vivo porcine model. Three groups of animals with the following states of the intervertebral discs were studied: intact disc, acutely injured disc, and degenerated disc. A miniaturized servo-hydraulic exciter was used to sinusoidally vibrate the motion segment from 0.05 to 25 Hz under a compressive load with a peak value of either 100 or 200 N. The dynamic axial stiffness of the intervertebral disc was calculated at 1-Hz intervals over the frequency range. The results showed that the dynamic axial stiffness was frequency dependent. A positive relationship was found between an increase in mean dynamic stiffness and load magnitude. An increase in mean stiffness with successive exposures at the same load magnitude was observed, despite the allowance of a recovery period between loading. The greatest difference was noted between the first and second load sets. No significant change in stiffness was found due to an acute disc injury, whereas a significant increase in mean stiffness was found for the degenerated disc group as compared with the intact group. The form of the frequency response curve, however, remained relatively unaltered regardless of the degenerated state of the disc. With heavier loads, repeated loading, and/or disc degeneration, the stiffness of the intervertebral disc increases. An increase in stiffness can mean a reduction in the amount of allowable motion within the motion segment or a potentially harmful increase in force to obtain the desired motion. This may locally result in greater stresses due to an altered ability of the disc to distribute loads.
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| 20. |
- Kawchuk, G. N., et al.
(author)
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Bulging of the inner and outer annulus during in vivo axial loading of normal and degenerated discs
- 2009
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In: Journal of Spinal Disorders & Techniques. - 1539-2465. ; 22:3, s. 214-8
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Journal article (peer-reviewed)abstract
- STUDY DESIGN: Comparison of in vivo biomechanical outcomes between experimental and control group animals. OBJECTIVE: To quantify the in vivo bulging response of the inner and outer annulus in animals with and without disc degeneration. SUMMARY OF BACKGROUND DATA: Prior attempts to quantify the load-deformation response of the inner annulus have most often relied on in vitro preparations. Unfortunately, to visualize the inner annulus, these in vitro approaches rely on disc modifications that may result in nonphysiologic behaviors. In response to this problem, in vivo techniques were developed to quantify regional bulging of the inner and outer annulus during applied axial loading. METHODS: Two groups of pigs were tested: a normal group and a group having disc degeneration that was induced surgically 3 months earlier. Eight adolescent pigs were evaluated and for each animal, a miniature servohydraulic actuator was attached to the third and fourth lumbar vertebrae to deliver a cyclic axial loading protocol (300 N, 1 Hz, 10 cycles) whereas regional deformations of the annulus were visualized ultrasonically via retroperitoneal access. RESULTS: For the normal animals, image analysis demonstrated a significantly greater bulging of the inner annular region when compared with the outer annular region. In animals with disc degeneration, the inner and outer annular regions were equal in their bulging response, which ranged from 0 bulging to 37% greater than the average response of the normal animals. CONCLUSIONS: This work supports prior in vitro studies that observed maximal disc bulging in the inner annulus and minimal bulging in the external annulus. Results for this in vivo study suggest that this normal bulging gradient is lost with degenerative disc disease. Compared with in vitro approaches, this new in vivo technique has the potential to demonstrate disc behavior in a variety of loading conditions and/or with a variety of induced disc pathologies.
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| 21. |
- Mannerås Holm, Louise, 1980, et al.
(author)
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Adipose tissue has aberrant morphology and function in PCOS: enlarged adipocytes and low serum adiponectin, but not circulating sex steroids, are strongly associated with insulin resistance.
- 2011
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In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 96:2
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Journal article (peer-reviewed)abstract
- Context: Comprehensive characterization of the adipose tissue in women with polycystic ovary syndrome (PCOS), over a wide range of body mass indices (BMIs), is lacking. Mechanisms behind insulin resistance in PCOS are unclear. Objective: To characterize the adipose tissue of women with PCOS and controls matched pair-wise for age and BMI, and to identify factors, among adipose tissue characteristics and serum sex steroids, that are associated with insulin sensitivity in PCOS. Design/Outcome Measures: Seventy-four PCOS women and 31 controls were included. BMI was 18-47 (PCOS) and 19-41 kg/m2 (controls). Anthropometric variables, volumes of subcutaneous/visceral adipose tissue (magnetic resonance imaging; MRI), and insulin sensitivity (clamp) were investigated. Adipose tissue biopsies were obtained to determine adipocyte size, lipoprotein lipase (LPL) activity, and macrophage density. Circulating testosterone, free testosterone, free 17β-estradiol, SHBG, glycerol, adiponectin, and serum amyloid A were measured/calculated. Results: Comparison of 31 pairs revealed lower insulin sensitivity, hyperandrogenemia, and higher free 17β-estradiol in PCOS. Abdominal adipose tissue volumes/distribution did not differ in the groups, but PCOS women had higher waist-to-hip ratio, enlarged adipocytes, reduced adiponectin, and lower LPL activity. In regression analysis, adipocyte size, adiponectin, and waist circumference were the factors most strongly associated with insulin sensitivity in PCOS (R2=0.681, P < 0.001). Conclusions: In PCOS, adipose tissue has aberrant morphology/function. Increased waist-to-hip ratio indicates abdominal/visceral fat accumulation, but this is not supported by MRI. Enlarged adipocytes and reduced serum adiponectin, together with a large waistline, rather than androgen excess, may be central factors in the pathogenesis/maintenance of insulin resistance in PCOS.
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| 22. |
- Melke, Jonas, 1971, et al.
(author)
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A polymorphism in the serotonin receptor 3A (HTR3A) gene and its association with harm avoidance in women.
- 2003
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In: Archives of general psychiatry. - : American Medical Association (AMA). - 0003-990X. ; 60:10, s. 1017-23
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Journal article (peer-reviewed)abstract
- BACKGROUND: The brain neurotransmitter serotonin is known to affect various aspects of human behavior, including personality traits. Serotonin receptor type 3 is a ligand-gated channel encoded by 2 different subunit genes, HTR3A and HTR3B. A polymorphism (C178T) in the 5' region of the HTR3A gene has recently been identified and suggested to be of functional importance. OBJECTIVE: To elucidate the possible association between the C178T polymorphism in the HTR3A gene and personality traits in women. DESIGN: Two independent samples of 35- to 45-year-old Swedish women were recruited using the population register. Sample 1 (n = 195) was assessed via the Karolinska Scales of Personality and the Temperament and Character Inventory; sample 2 (n = 175) was assessed using the latter only. Both samples were genotyped with respect to the C178T polymorphism in the HTR3A gene. The A1596G polymorphism in the same gene was also investigated. RESULTS: A significant association between C178T genotype and the Temperament and Character Inventory factor harm avoidance was observed in sample 1 (corrected for multiple comparisons P =.04); this finding was subsequently replicated in sample 2 (P =.004) (pooled populations: P<.001). In the pooled sample, all harm avoidance subscales were found to be significantly associated with the C178T polymorphism: anticipatory worry (P =.001), fear of uncertainty (P<.001), shyness (P<.001), and fatigability and asthenia (P =.008). In addition, a significant association was found in sample 1 between the C178T polymorphism and the Karolinska Scales of Personality nonconformity factor (corrected P =.002), including the subscales of social desirability (P<.001), indirect aggression (P =.002), verbal aggression (P =.05), and irritability (P<.001). Participants homozygous for the less common T allele (<4%) differed from the remaining women by displaying lower ratings on harm avoidance and nonconformity. CONCLUSION: The C178T polymorphism in the HTR3A gene may affect the personality trait of harm avoidance in women.
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| 23. |
- Nilsson-Ehle, Herman, et al.
(author)
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Quality of life, physical function and MRI T2*in elderly low-risk MDS patients treated to a haemoglobin level of andgt;= 120 g/L with darbepoetin alfa +/- filgrastim or erythrocyte transfusions
- 2011
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In: European Journal of Haematology. - : John Wiley and Sons. - 0902-4441 .- 1600-0609. ; 87:3, s. 244-252
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Journal article (peer-reviewed)abstract
- Objective: Anaemia in low-risk myelodysplastic syndromes (MDS) is associated with reduced quality of life (QoL). Response to treatment with erythropoietin +/- granulocyte colony-stimulating factor (G-CSF) is associated with improved QoL, but whether transfusion therapy with higher haemoglobin (Hb) target levels has similar effects is unknown. The objective for this prospective phase II Nordic multicentre trial was to assess QoL, response rate and physical function in elderly anaemic MDS patients treated to a target Hb level of andgt; 120 g /L. Methods: Thirty-six elderly patients with low-and intermediate-1 risk MDS received darbepoetin (DA) 300 mu g/wk, with the addition of G-CSF if no response. If the Hb target was reached at 16 wk, treatment was maintained until week 26. Remaining patients were transfused to reach the target level for at least 8 wk. Results: Twenty-seven patients completed the study. Response rate to DA +/- G-CSF was 67% in evaluable patients and 56% according to intention to treat. Eighteen patients reached the target Hb level according to protocol. QoL scores for fatigue, dyspnoea, constipation, and physical, role and social functioning improved significantly during study, with similar results for transfused and untransfused patients. Maintaining Hb andgt; 120 g /L did not confer a higher transfusion rate, once the target was reached. In two of fourteen patients, magnetic resonance imaging T2* indicated cardiac iron overload, however, without association with ferritin levels. Conclusions: In elderly anaemic MDS patients, an increment in haemoglobin is associated with improved QoL, whether induced by growth factor treatment or transfusion therapy.
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| 24. |
- Oddsson, Asmundur, et al.
(author)
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Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality
- 2023
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Journal article (peer-reviewed)abstract
- Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million individuals from six European populations. In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785.
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| 25. |
- Surendran, Praveen, et al.
(author)
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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
-
In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
-
Journal article (peer-reviewed)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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| 26. |
- Willer, Cristen J., et al.
(author)
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Discovery and refinement of loci associated with lipid levels
- 2013
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
-
Journal article (peer-reviewed)abstract
- Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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| 27. |
- Winkler, TW, et al.
(author)
-
Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
- 2022
-
In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 580-
-
Journal article (peer-reviewed)abstract
- Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
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| 28. |
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| 29. |
- Abdi, Abdulhakim M., et al.
(author)
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Biodiversity decline with increasing crop productivity in agricultural fields revealed by satellite remote sensing
- 2021
-
In: Ecological Indicators. - : Elsevier BV. - 1470-160X. ; 130
-
Journal article (peer-reviewed)abstract
- Increasing land-use intensity is a main driver of biodiversity loss in farmland, but measuring proxies for land-use intensity across entire landscapes is challenging. Here, we develop a novel method for the assessment of the impact of land-use intensity on biodiversity in agricultural landscapes using remote sensing parameters derived from the Sentinel-2 satellites. We link crop phenology and productivity parameters derived from time-series of a two-band enhanced vegetation index with biodiversity indicators (insect pollinators and insect-pollinated vascular plants) in agricultural fields in southern Sweden, with contrasting land management (i.e. conventional and organic farming). Our results show that arable land-use intensity in cereal systems dominated by spring-sown cereals can be approximated using Sentinel-2 productivity parameters. This was shown by the significant positive correlations between the amplitude and maximum value of the enhanced vegetation index on one side and farmer reported yields on the other. We also found that conventional cereal fields had 17% higher maximum and 13% higher amplitude of their enhanced vegetation index than organic fields. Sentinel-2 derived parameters were more strongly correlated with the abundance and species richness of bumblebees and the richness of vascular plants than the abundance and species richness of butterflies. The relationships we found between biodiversity and crop production proxies are consistent with predictions that increasing agricultural land-use intensity decreases field biodiversity. The newly developed method based on crop phenology and productivity parameters derived from Sentinel-2 data serves as a proof of concept for the assessment of the impact of land-use intensity on biodiversity over cereal fields across larger areas. It enables the estimation of arable productivity in cereal systems, which can then be used by ecologists and develop tools for land managers as a proxy for land-use intensity. Coupled with spatially explicit databases on agricultural land-use, this method will enable crop-specific cereal productivity estimation across large geographical regions.
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| 30. |
- Abelev, Betty, et al.
(author)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
-
In: Journal of High Energy Physics. - 1029-8479. ; :11
-
Journal article (peer-reviewed)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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| 31. |
- Abelev, Betty, et al.
(author)
-
Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
-
In: Journal of High Energy Physics. - 1029-8479. ; :7
-
Journal article (peer-reviewed)abstract
- We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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| 32. |
- Adler, Mats, et al.
(author)
-
Diagnosdiskussion
- 2016
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In: Tidskriften för Svensk Psykiatri. - 1653-8579. ; 2016:1, s. 77-78
-
Journal article (other academic/artistic)abstract
- Senaste halvåret har en arbetsgrupp på Svenska Psykiatriska Föreningens uppdrag arbetat med problem som finns runt psykiatriska diagnoser. En viktig del av arbetet har varit att ta fram ett diskussionsunderlag främst riktat till dem som i sitt arbete sätter psykiatriska diagnoser. Detta underlag syftar till att problematisera, inte till att polemisera. Självklart har vi i gruppen uppfattningar, men vi har inte alltid samma uppfattningar inom detta område. En sak är vi dock helt överens om – psykiatrisk diagnostik är svårt! samt att det idag finns uppenbara problem.
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| 33. |
- Adler, Mats, et al.
(author)
-
Psykiatrisk diagnostik är svårt.
- 2015
-
In: Tidskriften för Svensk Psykiatri. - 1653-8579. ; 2015:4, s. 36-37
-
Journal article (other academic/artistic)
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| 34. |
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| 35. |
- Ahlberg, Joakim, 1966-
(author)
-
Multi-unit common value auctions : theory and experiments
- 2012
-
Doctoral thesis (other academic/artistic)abstract
- Research on auctions that involve more than one identical item for sale was,almost non-existing in the 90’s, but has since then been getting increasing attention. External incentives for this research have come from the US spectrum, sales, the European 3G mobile-phone auctions, and Internet auctions. The policy relevance and the huge amount of money involved in many of them have helped the theory and experimental research advance. But in auctions where values are equal across bidders, common value auctions, that is, when the value depends on some outside parameter, equal to all bidders, the research is still embryonic.This thesis contributes to the topic with three studies. The first uses a Bayesian game to model a simple multi-unit common value auction, the task being to compare equilibrium strategies and the seller’s revenue from three auction formats; the discriminatory, the uniform and the Vickrey auction. The second study conducts an economic laboratory experiment on basis of the first study. The third study comprises an experiment on the multi-unit common value uniform auction and compares the dynamic and the static environments of this format.The most salient result in both experiments is that subjects overbid. They are victims of the winner’s curse and bid above the expected value, thus earning a negative profit. There is some learning, but most bidders continue to earn a negative profit also in later rounds. The competitive effect when participating in an auction seems to be stronger than the rationality concerns. In the first experiment, subjects in the Vickrey auction do somewhat better in small groups than subjects in the other auction types and, in the second experiment, subjects in the dynamic auction format perform much better than subjects in the static auction format; but still, they overbid.Due to this overbidding, the theoretical (but not the behavioral) prediction that the dynamic auction should render more revenue than the static fails inthe second experiment. Nonetheless, the higher revenue of the static auction comes at a cost; half of the auctions yield negative profits to the bidders, and the winner’s curse is more severely widespread in this format. Besides, only a minority of the bidders use the equilibrium bidding strategy.The bottom line is that the choice between the open and sealed-bid formats may be more important than the choice of price mechanism, especially in common value settings.
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| 36. |
- Ahola, Virpi, et al.
(author)
-
The Glanville fritillary genome retains an ancient karyotype and reveals selective chromosomal fusions in Lepidoptera
- 2014
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 4737-
-
Journal article (peer-reviewed)abstract
- Previous studies have reported that chromosome synteny in Lepidoptera has been well conserved, yet the number of haploid chromosomes varies widely from 5 to 223. Here we report the genome (393 Mb) of the Glanville fritillary butterfly (Melitaea cinxia; Nymphalidae), a widely recognized model species in metapopulation biology and eco-evolutionary research, which has the putative ancestral karyotype of n = 31. Using a phylogenetic analyses of Nymphalidae and of other Lepidoptera, combined with orthologue-level comparisons of chromosomes, we conclude that the ancestral lepidopteran karyotype has been n = 31 for at least 140 My. We show that fusion chromosomes have retained the ancestral chromosome segments and very few rearrangements have occurred across the fusion sites. The same, shortest ancestral chromosomes have independently participated in fusion events in species with smaller karyotypes. The short chromosomes have higher rearrangement rate than long ones. These characteristics highlight distinctive features of the evolutionary dynamics of butterflies and moths.
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| 37. |
- Amin, H., et al.
(author)
-
Indoor Airborne Microbiome and Endotoxin: Meteorological Events and Occupant Characteristics Are Important Determinants
- 2023
-
In: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 57:32, s. 11750-11766
-
Journal article (peer-reviewed)abstract
- Minimal research exists onthe factors influencing the indoorbacterial community. Despite their proposed importance for health,here we report environmental factors influencing the composition ofthe indoor bacterial communities. Airborne bacteria and endotoxin may affect asthma andallergies.However, there is limited understanding of the environmental determinantsthat influence them. This study investigated the airborne microbiomesin the homes of 1038 participants from five cities in Northern Europe:Aarhus, Bergen, Reykjavik, Tartu, and Uppsala. Airborne dust particleswere sampled with electrostatic dust fall collectors (EDCs) from theparticipants' bedrooms. The dust washed from the EDCs'clothes was used to extract DNA and endotoxin. The DNA extracts wereused for quantitative polymerase chain (qPCR) measurement and 16SrRNA gene sequencing, while endotoxin was measured using the kineticchromogenic limulus amoebocyte lysate (LAL) assay. The results showedthat households in Tartu and Aarhus had a higher bacterial load anddiversity than those in Bergen and Reykjavik, possibly due to elevatedconcentrations of outdoor bacterial taxa associated with low precipitationand high wind speeds. Bergen-Tartu had the highest difference (ANOSIM R = 0.203) in & beta; diversity. Multivariate regressionmodels showed that & alpha; diversity indices and bacterial and endotoxinloads were positively associated with the occupants' age, numberof occupants, cleaning frequency, presence of dogs, and age of thehouse. Further studies are needed to understand how meteorologicalfactors influence the indoor bacterial community in light of climatechange.
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| 38. |
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| 39. |
- Andræ, Margareta, 1943-
(author)
-
Facing death : physicians' difficulties and coping strategies in cancer care
- 1994
-
Doctoral thesis (other academic/artistic)abstract
- Even if the treatment of cancer has developed over the last decades 50% of the patients still die of their cancer. The doctor's way of dealing with his and his patient's anxiety must surely be of significance for the treatment the patient receives.In the first part of the thesis earlier studies of physicians' stress and ways of coping are reported. There is a lack of systematic studies which show how doctors working with cancer patients adjust to this work. The aim of this investigation is to study cancer doctors' difficulties and coping strategies. The theoretical frame of the study embraces parts of psychoanalytical theory and coping models, emphasizing that both unconscious and conscious psychological processes play their part in the coping process.The second, empirical part of the study includes 23 physicians strategically selected out of a population of physicians who work with institutional care and who have daily contact with adult cancer patients. The main method of data collection has been a series of recorded interviews. The focus of the interview was the physician's perception of how he reacts, thinks, talks and acts in different phases of the cancer disease. To illustrate the defence strategies of the interviewers, the projective percept-genetic test, the "Defence Mechanism Test" (DMT) is used. The "Structural Analysis of Social Behaviour" (SASB) has been used to study the doctors' self image.The results indicate that the stated difficulties deeply affect the doctor as a human being. The statements reflect conflicting feelings and wishes in relation to authority, conflicting feelings and wishes in relation to frightening and injuring, conflicting feelings and wishes in relation to intimacy/distance. Thirty themes of coping strategies frequently recur and they have been grouped into seven categories. Most of the doctors "seek knowledge" and support from scientific literature. The majority of them state that attempting to "solve a problem" is their main strategy. Most of the doctors "seek support " as a part of their coping strategy. An interesting observation is that the doctors to a higher extent "seek a relation" to their patients rather than to their colleagues. Almost one third use "denial of the severity of a situation" as their main strategy. All the doctors consciously or unconsciously use "diverting strategies", i.e. undertake tasks which are devoid of contact with patients, such as research and administration or other activities which allow them to avoid the patient. One third use "projective manoeuvres" but this is never a main strategy.In the third part of the study the credibility of the results and their pedagogical and practical implications are discussed.
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| 40. |
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| 41. |
- Annerbrink, Kristina, 1974, et al.
(author)
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Association between the catechol-O-methyltransferase Val158Met polymorphism and panic disorder: A replication
- 2010
-
In: Psychiatry Research. - : Elsevier Science B.V., Amsterdam.. - 0165-1781 .- 1872-7123. ; 178:1, s. 196-198
-
Journal article (peer-reviewed)abstract
- The association between the catechol-O-methyltransferase Val158Met polymorphism and panic disorder was studied in a Swedish sample of 211 patients and 452 controls. We found a significant excess of the Val allele in both male and female patients, the latter but not the former finding being in line with previous studies.
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| 42. |
- Annerbrink, Kristina, 1974, et al.
(author)
-
Catechol O-methyltransferase val158-met polymorphism is associated with abdominal obesity and blood pressure in men.
- 2008
-
In: Metabolism. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 57:5, s. 708-711
-
Journal article (peer-reviewed)abstract
- Catechol O-methyltransferase (COMT) degrades catecholamines and estrogens, both of which are of known importance for cardiovascular risk factors such as obesity and hypertension. The gene coding for COMT contains a val158-met polymorphism that exerts a considerable influence on enzymatic activity. We hypothesized that this polymorphism might influence risk factors for cardiovascular disease. Deoxyribonucleic acid samples and data regarding blood pressure and anthropometry were collected from 240 Swedish men, all 51 years old. Subjects homozygous for the low-activity allele (met) displayed higher blood pressure, heart rate, waist-to-hip ratio, and abdominal sagittal diameter as compared with heterozygous subjects, who in turn displayed higher blood pressure, heart rate, waist-to-hip ratio, and abdominal sagittal diameter than subjects homozygous for the high-activity allele (val). All measured variables were significantly correlated; however, the associations between COMT val158-met and cardiovascular variables, and the association between COMT val158-met and anthropometry, respectively, were partly independent of each other, as revealed by multiple linear regression.
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| 43. |
- Annerbrink, Kristina, 1974, et al.
(author)
-
Panic disorder is associated with the Val308Iso polymorphism in the hypocretin receptor gene
- 2011
-
In: PSYCHIATRIC GENETICS. - : Rapid Communications of Oxford Ltd. - 0955-8829 .- 1473-5873. ; 21:2, s. 85-89
-
Journal article (peer-reviewed)abstract
- Background Orexin A and B are neuropeptides influencing, for example, arousal and respiration. Although panic disorder is characterized by both enhanced proneness for arousal and by respiratory abnormalities, the possible influence of orexin-related genes on the risk of developing this disorder has not been studied until now. Methods We have analyzed the Ile408Val polymorphism in the hypocretin receptor 1 (HCRTR1) gene and the Val308Iso (G1246A) polymorphism in the hypocretin receptor 2 (HCRTR2) gene in a sample of 215 panic disorder patients and 454 controls. Results Although the polymorphism in the HCRTR1 did not differ between groups, the Iso allele of the HCRTR2 polymorphism was significantly more frequent in patients than in controls. After the population was divided according to sex, the association between the Iso allele of the Val308Iso polymorphism and panic disorder was observed only in female patients. Conclusion Our results suggest that the HCRTR2 polymorphism may be of importance for the pathophysiology of panic disorder. The results should be regarded as preliminary until replicated in an independent sample. This indicates that further research on the possible role of orexin in panic disorder may prove rewarding.
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| 44. |
- Anthonsen, M W, et al.
(author)
-
Identification of novel phosphorylation sites in hormone-sensitive lipase that are phosphorylated in response to isoproterenol and govern activation properties in vitro
- 1998
-
In: Journal of Biological Chemistry. - 1083-351X. ; 273:1, s. 215-221
-
Journal article (peer-reviewed)abstract
- Hormone-sensitive lipase (HSL) is the rate-limiting enzyme in lipolysis. Stimulation of rat adipocytes with isoproterenol results in phosphorylation of HSL and a 50-fold increase in the rate of lipolysis. In this study, we used site-directed mutagenesis and two-dimensional phosphopeptide mapping to show that phosphorylation sites other than the previously identified Ser-563 are phosphorylated in HSL in response to isoproterenol stimulation of 32P-labeled rat adipocytes. Phosphorylation of HSL in adipocytes in response to isoproterenol and in vitro phosphorylation of HSL containing Ser --> Ala mutations in residues 563 and 565 (S563A, S565A) with protein kinase A (PKA), followed by tryptic phosphopeptide mapping resulted in two tryptic phosphopeptides. These tryptic phosphopeptides co-migrated with the phosphopeptides released by the same treatment of F654HPRRSSQGVLHMPLYSSPIVK675 phosphorylated with PKA. Analysis of the phosphorylation site mutants, S659A, S660A, and S659A,S660A disclosed that mutagenesis of both Ser-659 and Ser-660 was necessary to abolish the activation of HSL toward a triolein substrate after phosphorylation with PKA. Mutation of Ser-563 to alanine did not cause significant change of activation compared with wild-type HSL. Hence, our results demonstrate that in addition to the previously identified Ser-563, two other PKA phosphorylation sites, Ser-659 and Ser-660, are present in HSL and, furthermore, that Ser-659 and Ser-660 are the major activity controlling sites in vitro.
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| 45. |
- Arking, D. E., et al.
(author)
-
Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
- 2014
-
In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
-
Journal article (peer-reviewed)abstract
- The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc.
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| 46. |
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| 47. |
- Atuma, Christer, et al.
(author)
-
Extracts of Helicobacter pylori reduce gastric mucosal blood flow through a VacA- and CagA-independent pathway in rats
- 1998
-
In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 33:12, s. 1256-1261
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Helicobacter pylori may interfere with gastroduodenal protective mechanisms. Such effects could be due to a direct interaction with gastric epithelial cells but also to the action of a wide range of secreted and membrane-bound virulence factors. Our aim was to study the acute effects of water extracts produced from H. pylori on gastric mucosal blood flow and acid secretion and to relate them to VacA and CagA activity.METHOD: Extracts were produced from strains 88-23 and A5, both wild type; A5VacA, an isogenic mutant lacking expression of the vacuolating cytotoxin (VacA) and the immunodominant antigen (CagA); and Escherichia coli strain ATCC-25922. Bacterial extracts were applied on the exteriorized gastric corporal mucosa in inactin-anaesthetized rats after removal of as much as possible of the mucus layer, during intravital microscopy. Blood flow was measured by means of laser-Doppler flowmetry.RESULTS: All H. pylori extracts, including the extract from 88-23 heated to 100 degrees C for 30 min, significantly reduced blood flow by 15%-19%, whereas E. coli had no significant effect on blood flow.CONCLUSION: A factor or a combination of factors, other than VacA and CagA released from H. pylori, might compromise the natural defence of the gastric corporal mucosa by reducing mucosal blood flow. The factor is heat-stable and lacking or less potent in E. coli.
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| 48. |
- Atuma, C, et al.
(author)
-
Helicobacter pylori extracts reduce gastric mucosal blood flow by a nitric oxide-independent but mast cell- and platelet-activating factor receptor-dependent pathway in rats
- 1999
-
In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 34:12, s. 1183-1189
-
Journal article (peer-reviewed)abstract
- BACKGROUND: We have previously shown that water extracts from Helicobacter pylori reduce gastric mucosal blood flow by approximately 15%. It has also been suggested that H. pylori can inhibit endogenous nitric oxide (NO) biosynthesis. Our aim was to examine whether the reduction in blood flow induced by H. pylori is the direct consequence of an NO synthase inhibition and the possible involvement of mast cell degranulation.METHODS: A water extract was produced from wildtype strain 88-23. The extract was applied on the exteriorized gastric corporal mucosa in inactin-anesthetized rats, after removing as much as possible of the mucus layer, during intravital microscopy. Blood flow was measured with laser-Doppler flowmetry.RESULTS: In rats pretreated with the NO synthase inhibitor N-nitro-L-arginine there was a 19% +/- 6% reduction in blood flow 40 min after application of the extract, and a 27% +/- 9% reduction after another 20 min with saline. The reduction was abolished by concomitant pretreatment with the mast cell stabilizer ketotifen or the platelet-activating factor (PAF) receptor antagonist WEB2086.CONCLUSION: The reduction in mucosal blood flow induced by the extract was probably mediated through an acute inflammatory response involving mast cell degranulation with consequent PAF secretion. The effect on blood flow was not the result of a decrease in vascular tone due to an inhibition of endogenous NO biosynthesis.
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| 49. |
- Axelsson, Susanna, et al.
(author)
-
Effect of combined caries-preventive methods: a systematic review of controlled clinical trials.
- 2004
-
In: Acta odontologica Scandinavica. - : Informa UK Limited. - 0001-6357 .- 1502-3850. ; 62:3, s. 163-9
-
Research review (peer-reviewed)abstract
- The aim of this systematic review was to evaluate the caries-preventive effect of combined caries-preventive methods, defined as two or more different interventions in combination, each expected to prevent dental caries. The Medline database was searched for articles published in the period January 1966 to June 2003. Twenty-four controlled studies met the inclusion criteria, and their value as evidence was assessed according to predetermined criteria. The level of evidence for the overall conclusion regarding each method was graded according to the protocol of the Swedish Council on Technology Assessment in Health Care. The scientific evidence for the combination of treatments involving fluoride that had a preventive effect on caries in children and adolescents was graded as moderate. However, for elderly patients the scientific evidence for the caries-preventive effect of different combinations of treatments was found to be incomplete. No conclusion could be drawn regarding the evidence for combinations of treatments being effective for groups at high caries risk, as the results from the identified clinical studies were conflicting.
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| 50. |
- Axfors, Cathrine, et al.
(author)
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Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
- 2021
-
In: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
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Research review (peer-reviewed)abstract
- Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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