Interaction between polymorphisms in the OCT1 and MATE1 transporter and metformin response

Introduction: The transporter OCT1 is involved in the influx of metformin into the liver and the transporter MATE1 is involved in the efflux of metformin out of the liver. Recently, we identified that the polymorphism rs622342 in the gene coding for OCT1, and the polymorphism rs2289669 in the gene coding for MATE1, are associated with the degree of glucose-lowering effect by metformin. In this study, we analysed the existence of interaction between these two polymorphisms. Design and methods: We identified all incident metformin users in the Rotterdam Study, a population-based cohort study. Interaction between these two polymorphisms and change in HbA1c levels was analyzed. Results: In incident metformin users with the OCT1 rs622342 AA genotype, no association was found between the MATE1 rs2289669 genotype and the HbA1c-lowering effect (p = 0.39). In users with the OCT1 rs622342 AC genotype a non-significant tendency was found between the MATE1 rs2289669 genotype and the HbA1c-lowering effect (p = 0.070), and in users with the OCT1 rs622342 CC genotype a significant association was found between the MATE1 rs2289669 genotype and the glucose-lowering effect of metformin (p = 0.005). Conclusion: The effect of the MATE1 rs2289669 genotype on the glucose-lowering effect of metformin is stronger in incident users with the rs622342 CC genotype than in incident users with the rs622342 AA genotype. In most patients, metformin will lower HbA1c levels sufficiently, except in patients with a reduced function of the OCT1 transporter and a normal function of the MATE1 transporter.</p

Interaction between polymorphisms in the OCT1 and MATE1 transporter and metformin response

Introduction: The transporter OCT1 is involved in the influx of metformin into the liver and the transporter MATE1 is involved in the efflux of metformin out of the liver. Recently, we identified that the polymorphism rs622342 in the gene coding for OCT1, and the polymorphism rs2289669 in the gene coding for MATE1, are associated with the degree of glucose-lowering effect by metformin. In this study, we analysed the existence of interaction between these two polymorphisms. Design and methods: We identified all incident metformin users in the Rotterdam Study, a population-based cohort study. Interaction between these two polymorphisms and change in HbA1c levels was analyzed. Results: In incident metformin users with the OCT1 rs622342 AA genotype, no association was found between the MATE1 rs2289669 genotype and the HbA1c-lowering effect (p = 0.39). In users with the OCT1 rs622342 AC genotype a non-significant tendency was found between the MATE1 rs2289669 genotype and the HbA1c-lowering effect (p = 0.070), and in users with the OCT1 rs622342 CC genotype a significant association was found between the MATE1 rs2289669 genotype and the glucose-lowering effect of metformin (p = 0.005). Conclusion: The effect of the MATE1 rs2289669 genotype on the glucose-lowering effect of metformin is stronger in incident users with the rs622342 CC genotype than in incident users with the rs622342 AA genotype. In most patients, metformin will lower HbA1c levels sufficiently, except in patients with a reduced function of the OCT1 transporter and a normal function of the MATE1 transporter.</p

The Longitudinal Interplay Between Attention Bias and Interpretation Bias in Social Anxiety in Adolescents

Background: Cognitive biases are found to play a role in the onset and maintenance of social anxiety. However, particularly in adolescence, the link between different biases and their role in predicting social anxiety is far from clear. This study therefore investigated the interplay between attention bias and interpretation bias in relation to social anxiety in adolescence across three years. Methods: 816 adolescents in grade 7 to 9 participated at three yearly waves (52.8% boys, Mage grade7 = 12.60). Social anxiety was measured with a self-report questionnaire. Attention bias was measured with a visual search task with emotional faces. Textual vignettes assessed interpretation bias. Results: Cross-lagged models showed that negative interpretation bias at grade 7 predicted an increase in social anxiety at grade 8. This effect was not found from grade 8 to 9. Attention bias did not predict social anxiety. Attention bias and interpretation bias were not longitudinally related to each other, nor did they interact with each other in predicting social anxiety. Conclusions: Thus, no evidence was found for the Combined Cognitive Bias Hypothesis in social anxiety in adolescents. Instead, our results suggest that interpretation bias rather than attention bias contributes to the increase of social anxiety over time

Association Between Bilirubin, Atazanavir, and Cardiovascular Disease Events Among People Living With HIV Across the United States

Objective: Bilirubin is an antioxidant that may suppress lipid oxidation. Elevated bilirubin is associated with decreased cardiovascular events in HIV-uninfected populations. We examined these associations in people living with HIV (PLWH). Methods: Potential myocardial infarctions (MIs) and strokes were centrally adjudicated. We examined MI types: type 1 MI (T1MI) from atherosclerotic plaque instability and type 2 MI (T2MI) in the setting of oxygen demand/supply mismatch such as sepsis. We used multivariable Cox regression analyses to determine associations between total bilirubin levels and outcomes adjusting for traditional and HIV-specific risk factors. To minimize confounding by hepatobiliary disease, we conducted analyses limited to bilirubin values <2.1 mg/dL; among those with fibrosis-4 values <3.25; and among everyone. We repeated analyses stratified by hepatitis C status and time-updated atazanavir use. Results: Among 25,816 PLWH, there were 392 T1MI and 356 T2MI during follow-up. Adjusted hazard ratios for the association of higher bilirubin levels with T1MI were not significant. Higher bilirubin levels were associated with T2MI. By contrast, among PLWH on atazanavir, higher bilirubin levels were associated with fewer T2MI (hazard ratio 0.56:0.33-1.00). Higher bilirubin levels among those on atazanavir were associated with fewer T1MI combined with ischemic stroke. Limitations: Analyses were conducted with total rather than unconjugated bilirubin. Conclusions: Among PLWH, higher bilirubin levels were associated with T2MI among some subgroups. However, among those on atazanavir, there was a protective association between bilirubin and T2MI. These findings demonstrate different associations between outcomes and elevated bilirubin due to diverse causes and the importance of distinguishing MI types

Transverse momentum spectra of charged particles in proton-proton collisions at s=900\sqrt{s} = 900 GeV with ALICE at the LHC

The inclusive charged particle transverse momentum distribution is measured in proton-proton collisions at $\sqrt{s} = 900$ GeV at the LHC using the ALICE detector. The measurement is performed in the central pseudorapidity region $(|\eta|<0.8)$ over the transverse momentum range $0.15<p_{\rm T}<10$ GeV/$c$. The correlation between transverse momentum and particle multiplicity is also studied. Results are presented for inelastic (INEL) and non-single-diffractive (NSD) events. The average transverse momentum for $|\eta|<0.8$ is $\left<p_{\rm T}\right>_{\rm INEL}=0.483\pm0.001$ (stat.) $\pm0.007$ (syst.) GeV/$c$ and \left_{\rm NSD}=0.489\pm0.001 (stat.) $\pm0.007$ (syst.) GeV/$c$, respectively. The data exhibit a slightly larger $\left<p_{\rm T}\right>$ than measurements in wider pseudorapidity intervals. The results are compared to simulations with the Monte Carlo event generators PYTHIA and PHOJET.Comment: 20 pages, 8 figures, 2 tables, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/390

Measurement of forward charged hadron flow harmonics in peripheral PbPb collisions at √sNN = 5.02 TeV with the LHCb detector

Flow harmonic coefficients, v n , which are the key to studying the hydrodynamics of the quark-gluon plasma (QGP) created in heavy-ion collisions, have been measured in various collision systems and kinematic regions and using various particle species. The study of flow harmonics in a wide pseudorapidity range is particularly valuable to understand the temperature dependence of the shear viscosity to entropy density ratio of the QGP. This paper presents the first LHCb results of the second- and the third-order flow harmonic coefficients of charged hadrons as a function of transverse momentum in the forward region, corresponding to pseudorapidities between 2.0 and 4.9, using the data collected from PbPb collisions in 2018 at a center-of-mass energy of 5.02 TeV . The coefficients measured using the two-particle angular correlation analysis method are smaller than the central-pseudorapidity measurements at ALICE and ATLAS from the same collision system but share similar features

Helium identification with LHCb

The identification of helium nuclei at LHCb is achieved using a method based on measurements of ionisation losses in the silicon sensors and timing measurements in the Outer Tracker drift tubes. The background from photon conversions is reduced using the RICH detectors and an isolation requirement. The method is developed using pp collision data at √(s) = 13 TeV recorded by the LHCb experiment in the years 2016 to 2018, corresponding to an integrated luminosity of 5.5 fb-1. A total of around 105 helium and antihelium candidates are identified with negligible background contamination. The helium identification efficiency is estimated to be approximately 50% with a corresponding background rejection rate of up to O(10^12). These results demonstrate the feasibility of a rich programme of measurements of QCD and astrophysics interest involving light nuclei

Curvature-bias corrections using a pseudomass method

Momentum measurements for very high momentum charged particles, such as muons from electroweak vector boson decays, are particularly susceptible to charge-dependent curvature biases that arise from misalignments of tracking detectors. Low momentum charged particles used in alignment procedures have limited sensitivity to coherent displacements of such detectors, and therefore are unable to fully constrain these misalignments to the precision necessary for studies of electroweak physics. Additional approaches are therefore required to understand and correct for these effects. In this paper the curvature biases present at the LHCb detector are studied using the pseudomass method in proton-proton collision data recorded at centre of mass energy √(s)=13 TeV during 2016, 2017 and 2018. The biases are determined using Z→μ + μ - decays in intervals defined by the data-taking period, magnet polarity and muon direction. Correcting for these biases, which are typically at the 10-4 GeV-1 level, improves the Z→μ + μ - mass resolution by roughly 18% and eliminates several pathological trends in the kinematic-dependence of the mean dimuon invariant mass