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- Yaghootkar, Hanieh, et al.
(författare)
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Mendelian randomization studies do not support a causal role for reduced circulating adiponectin levels in insulin resistance and type 2 diabetes.
- 2013
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 62:10, s. 3589-3598
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Tidskriftsartikel (refereegranskat)abstract
- Adiponectin is strongly inversely associated with insulin resistance and type 2 diabetes, but its causal role remains controversial. We used a Mendelian randomization approach to test the hypothesis that adiponectin causally influences insulin resistance and type 2 diabetes. We used genetic variants at the ADIPOQ gene as instruments to calculate a regression slope between adiponectin levels and metabolic traits (up to 31,000 individuals) and a combination of instrumental variables and summary statistics-based genetic risk scores to test the associations with gold-standard measures of insulin sensitivity (2,969 individuals) and type 2 diabetes (15,960 case subjects and 64,731 control subjects). In conventional regression analyses, a 1-SD decrease in adiponectin levels was correlated with a 0.31-SD (95% CI 0.26-0.35) increase in fasting insulin, a 0.34-SD (0.30-0.38) decrease in insulin sensitivity, and a type 2 diabetes odds ratio (OR) of 1.75 (1.47-2.13). The instrumental variable analysis revealed no evidence of a causal association between genetically lower circulating adiponectin and higher fasting insulin (0.02 SD; 95% CI -0.07 to 0.11; N = 29,771), nominal evidence of a causal relationship with lower insulin sensitivity (-0.20 SD; 95% CI -0.38 to -0.02; N = 1,860), and no evidence of a relationship with type 2 diabetes (OR 0.94; 95% CI 0.75-1.19; N = 2,777 case subjects and 13,011 control subjects). Using the ADIPOQ summary statistics genetic risk scores, we found no evidence of an association between adiponectin-lowering alleles and insulin sensitivity (effect per weighted adiponectin-lowering allele: -0.03 SD; 95% CI -0.07 to 0.01; N = 2,969) or type 2 diabetes (OR per weighted adiponectin-lowering allele: 0.99; 95% CI 0.95-1.04; 15,960 case subjects vs. 64,731 control subjects). These results do not provide any consistent evidence that interventions aimed at increasing adiponectin levels will improve insulin sensitivity or risk of type 2 diabetes.
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- Chaturvedi, Swasti, et al.
(författare)
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Slit2 Prevents Neutrophil Recruitment and Renal Ischemia-Reperfusion Injury : english
- 2013
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673. ; 24:8, s. 1274-1287
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophils recruited to the postischemic kidney contribute to the pathogenesis of ischemia-reperfusion injury (IRI), which is the most common cause of renal failure among hospitalized patients. The Slit family of secreted proteins inhibits chemotaxis of leukocytes by preventing activation of Rho-family GTPases, suggesting that members of this family might modulate the recruitment of neutrophils and the resulting IRI. Here, in static and microfluidic shear assays, Slit2 inhibited multiple steps required for the infiltration of neutrophils into tissue. Specifically, Slit2 blocked the capture and firm adhesion of human neutrophils to inflamed vascular endothelial barriers as well as their subsequent transmigration. To examine whether these observations were relevant to renal IRI, we administered Slit2 to mice before bilateral clamping of the renal pedicles. Assessed at 18 hours after reperfusion, Slit2 significantly inhibited renal tubular necrosis, neutrophil and macrophage infiltration, and rise in plasma creatinine. In vitro, Slit2 did not impair the protective functions of neutrophils, including phagocytosis and superoxide production, and did not inhibit neutrophils from killing the extracellular pathogen Staphylococcus aureus. In vivo, administration of Slit2 did not attenuate neutrophil recruitment or bacterial clearance in mice with ascending Escherichia coli urinary tract infections and did not increase the bacterial load in the livers of mice infected with the intracellular pathogen Listeria monocytogenes. Collectively, these results suggest that Slit2 may hold promise as a strategy to combat renal IRI without compromising the protective innate immune response.
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- O'Mahen, Heather A., et al.
(författare)
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Internet-based behavioral activation—Treatment for postnatal depression (Netmums): A randomized controlled trial
- 2013
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Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 150:3, s. 814-822
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite the high prevalence of postnatal depression (PND), few women seek help. The internet may increase timely access to treatment. We report a randomized controlled trial of a minimal intervention internet Behavioral Activation (iBA) treatment modified to address postnatal specific concerns (Postnatal-iBA).Methods: Women (n=910) recruited via a popular UK parenting site, Netmums.com, scoring above 12 on the Edinburgh Postnatal Depression Scale (EPDS) were randomly assigned to receive either Postnatal-iBA delivered or treatment-as-usual (TAU). We investigated the feasibility (recruitment, trial and treatment adherence) and effectiveness (depression status EPDS >12) of the intervention.Results: Recruitment was excellent; 1261 women, 961 of whom met inclusion criteria, signed up to the trial within two 2-week recruitment periods. Thirty-eight percent (343/910) of women completed the 15-week outcome assessment. Of those who completed 15-week assessment, fewer exceeded the depression cutoff in the Postnatal-iBA group (n=66/181) compared to TAU (n=91/162). Assuming all non-respondents remained depressed, the Postnatal-iBA effect was reduced.Limitations: The study suffered from high attrition and future trials need to consider strategies for improving outcome completion. Some women reported struggles "keeping up" with the treatment.Conclusions: A minimal support, widely accessible internet Behavioral Activation program for PND is feasible to deliver to community populations when embedded within popular parenting sites. For women who provide outcome data, postnatal-iBA offers promise as an effective treatment for PND. The addition of support may reduce women's struggles to keep pace with the treatment.Keywords: Behavioral activation; Cognitive behavioral therapy; Depression; Online cbt; Postnatal depression; Randomized controlled trial.
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- Shirer, K. R., et al.
(författare)
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Nuclear magnetic resonance studies of pseudospin fluctuations in URu2Si2
- 2013
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 88:9, s. 094436-
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Tidskriftsartikel (refereegranskat)abstract
- We report Si-29 nuclear magnetic resonance measurements in single crystals and aligned powders of URu2Si2 in the hidden order and paramagnetic phases. The spin-lattice relaxation data reveal evidence of pseudospin fluctuations of U moments in the paramagnetic phase. We find evidence for partial suppression of the density of states below 30 K and analyze the data in terms of a two-component spin-fermion model. We propose that this behavior is a realization of a pseudogap between the hidden-order transition T-HO and 30 K. This behavior is then compared to other materials that demonstrate precursor fluctuations in a pseudogap regime above a ground state with long-range order.
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- Schouten, Stefan, et al.
(författare)
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An interlaboratory study of TEX86 and BIT analysis of sediments, extracts, and standard mixtures
- 2013
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Ingår i: Geochemistry Geophysics Geosystems. - 1525-2027. ; 14:12, s. 5263-5285
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Tidskriftsartikel (refereegranskat)abstract
- Two commonly used proxies based on the distribution of glycerol dialkyl glycerol tetraethers (GDGTs) are the TEX86 (TetraEther indeX of 86 carbon atoms) paleothermometer for sea surface temperature reconstructions and the BIT (Branched Isoprenoid Tetraether) index for reconstructing soil organic matter input to the ocean. An initial round-robin study of two sediment extracts, in which 15 laboratories participated, showed relatively consistent TEX86 values (reproducibility +/- 3-4 degrees C when translated to temperature) but a large spread in BIT measurements (reproducibility +/- 0.41 on a scale of 0-1). Here we report results of a second round-robin study with 35 laboratories in which three sediments, one sediment extract, and two mixtures of pure, isolated GDGTs were analyzed. The results for TEX86 and BIT index showed improvement compared to the previous round-robin study. The reproducibility, indicating interlaboratory variation, of TEX86 values ranged from 1.3 to 3.0 degrees C when translated to temperature. These results are similar to those of other temperature proxies used in paleoceanography. Comparison of the results obtained from one of the three sediments showed that TEX86 and BIT indices are not significantly affected by interlaboratory differences in sediment extraction techniques. BIT values of the sediments and extracts were at the extremes of the index with values close to 0 or 1, and showed good reproducibility (ranging from 0.013 to 0.042). However, the measured BIT values for the two GDGT mixtures, with known molar ratios of crenarchaeol and branched GDGTs, had intermediate BIT values and showed poor reproducibility and a large overestimation of the true (i.e., molar-based) BIT index. The latter is likely due to, among other factors, the higher mass spectrometric response of branched GDGTs compared to crenarchaeol, which also varies among mass spectrometers. Correction for this different mass spectrometric response showed a considerable improvement in the reproducibility of BIT index measurements among laboratories, as well as a substantially improved estimation of molar-based BIT values. This suggests that standard mixtures should be used in order to obtain consistent, and molar-based, BIT values.
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- ter Haar, C. Cato, et al.
(författare)
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Difference vectors to describe dynamics of the ST segment and the ventricular gradient in acute ischemia
- 2013
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Ingår i: Journal of Electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 46:4, s. 302-311
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Tidskriftsartikel (refereegranskat)abstract
- Background: The ECG is important in the diagnosis and triage of the acute coronary syndrome (ACS), especially in the hyperacute phase, the "golden hours," during which myocardial salvage possibilities are largest. An important triaging decision to be taken is whether or not a patient requires primary PCI, for which, as mentioned in the guidelines, the presence of an ST elevation (STE) pattern in the ECG is a major criterion. However, preexisting non-zero ST amplitudes (diagnostic, but also non-diagnostic) can obscure or even preclude this diagnosis. Methods: In this study, we investigated the potential diagnostic possibilities of ischemia detection by means of changes in the ST vector, Delta ST, and changes in the VG (QRST integral) vector, Delta VG. We studied the vectorcardiograms (VCGs) synthesized of the ECGs of 84 patients who underwent elective PTCA. Mean +/- SD balloon occlusion times were 260 +/- 76 s. The ECG ischemia diagnosis (ST elevation, STE, or non-ST-elevation, NSTE), magnitudes and orientations of the ST and VG vectors, and the differences Delta ST and Delta VG with the baseline ECG were measured after 3 min of balloon occlusion. Results: Planar angles between the Delta ST and Delta VG vectors were 14.9 +/- 14.0 degrees. Linear regression of Delta VG on Delta ST yielded Delta VG = 324. Delta ST (r = 0.85; P < 0.0001, Delta ST in mV). We adopted Delta ST > 0.05 mV, and the corresponding Delta VG > 16.2 mV.ms as ischemia thresholds. The classical criteria characterized the ECGs of 46/84 (55%) patients after 3 min of occlusion as STE ECGs. Combined application of the Delta ST and Delta VG criteria identified 73/84 (87%) of the patients as ischemic. Conclusion: Differential diagnosis by Delta ST and Delta VG (requiring an earlier made non-ischemic baseline ECG) could dramatically improve ECG guided detection of patients who urgently require catheter intervention. (C) 2013 Elsevier Inc. All rights reserved.
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