Pain sensitivity, negative affect, and alcohol use disorder status: A moderated mediation study of emotion dysregulation

Previous work suggests that the association between pain and emotional processes among individuals with alcohol use disorder (AUD) may differ from healthy controls. This study inves-tigates whether pain sensitivity mediates the association between negative affect and emotional dysregulation and whether this association differs across AUD status using moderated mediation. The sample included 165 individuals diagnosed with AUD and 110 healthy controls. Of interest was pain sensitivity, as assessed with the Pain Sensitivity Questionnaire, negative affect, as assessed with the Beck Depression Inventory, and emotional dysregulation, as assessed with the Difficulties in Emotional regulation Scale. Age, biological sex, and current pain severity were included as covariates. The results support a moderated partial mediation model that explained 44% of the variance in emotional dysregulation. The findings indicate that negative affect is related to higher pain sensitivity across groups. Moreover, pain sensitivity partially mediated the association between negative affect and emotional dysregulation, but in opposite directions depending on AUD status. Among healthy controls, greater pain sensitivity was related to better emotional regulation, while greater pain sensitivity led to greater emotional dysregulation among individuals with AUD. The potential parallels in the underlying neurobiological mechanisms of emotionality, pain, and AUD suggest that interventions targeting pain may improve adaptive affect regulation skills, which in turn could reduce negative affect and its effect on pain sensitivity among individuals with AUD

High-pressure optical floating-zone growth of Li2FeSiO4 single crystals

We report the growth of mm-sized Pmnb-Li2FeSiO4 single crystals by means of the optical floating-zone method at high argon pressure and describe the conditions required for a stable growth process. The crystal structure is determined and refined by single-crystal X-ray diffraction. The lattice constants amount to a = 6.27837(3) A, b = 10.62901(6) A and c = 5.03099(3) A at 100 K. In addition, we present high-resolution neutron powder diffraction data that suggest that the slight Li-Fe site exchange seems to be intrinsic to this material. High quality of the crystal is confirmed by very sharp anomalies in the static magnetic susceptibility and in the specific heat associated with the onset of long-range antiferromagnetic order at TN = 17.0(5) K and pronounced magnetic anisotropy for the three crystallographic axes. Furthermore, magnetic susceptibility excludes the presence of sizable amounts of magnetic impurity phases

Interoception, alexithymia, and anxiety among individuals with alcohol use disorder

BackgroundInteroception (i.e., the ability to recognize bodily signals), alexithymia (i.e., the inability to recognize emotional states) and negative affect (i.e., unpleasant feelings such as anxiety) have been associated with alcohol use disorder (AUD). Previous research suggests that interoception may underlie alexithymia, which in turn may be associated with negative affectivity. However, this remains to be empirically tested. This study investigates whether alexithymia mediates the association between interoception and anxiety and whether this association differs across individuals with AUD and a healthy control (HC) comparison group.MethodsThe AUD group consisted of 99 participants enrolled in an 8-week abstinence-based inpatient treatment program. The HC group included 103 healthy individuals. The heartbeat counting task (HCT) was used to assess interoception (cardiac interoceptive accuracy). The Toronto Alexithymia Scale (TAS-20) was used to assess alexithymia. The Brief Symptom Inventory (BSI) was used to assess anxiety.ResultsThe moderated mediation model with interoception as the predictor, alexithymia as the mediator, and negative affect (i.e., state anxiety) as the dependent variable was tested. The analysis showed that the conditional indirect effect of interoception on anxiety via alexithymia was significant for individuals with AUD [ab = −0.300, bootstrap 95% CI = (−0.618, −0.088)], as well as for HCs [ab = −0.088, bootstrap 95% CI = (−0.195, −0.014)]; however, the conditional indirect effect significantly differed across HCs and individuals with AUD. Namely, the mediated effect was greater among individuals with AUD compared to the HC group.ConclusionThe results suggests that interoceptive impairment contributes to greater negative affect (i.e., state anxiety) via alexithymia especially for individuals with AUD. Improving emotion recognition via therapeutic methods focused on strengthening interoceptive abilities could improve outcomes for individuals receiving treatment for AUD

Role of the CX3C chemokine receptor CX3CR1 in the pathogenesis of atherosclerosis after aortic transplantation

Background: The CX3C chemokine receptor CX3CR1 is expressed on monocytes as well as tissue resident cells, such as smooth muscle cells ( SMCs). Its role in atherosclerotic tissue remodeling of the aorta after transplantation has not been investigated. Methods: We here have orthotopically transplanted infrarenal Cx3cr1(-/-) Apoe(-/-) and Cx3cr1(+/+) Apoe(-/-)aortic segments into Apoe(-/-) mice, as well as Apoe(-/-) aortic segments into Cx3cr1(-/-) Apoe(-/-)mice. The intimal plaque size and cellular plaque composition of the transplanted aortic segment were analyzed after four weeks of atherogenic diet. Results: Transplantation of Cx3cr(-/-) Apoe(-/-) aortic segments into Apoe(-/-) mice resulted in reduced atherosclerotic plaque formation compared to plaque size in Apoe(-/-) or Cx3cr1(-/-) Apoe(-/-) mice after transplantation of Apoe(-/-) aortas. This reduction in lesion formation was associated with reduced numbers of lesional SMCs but not macrophages within the transplanted Cx3cr(-/-) Apoe(-/-) aortic segment. No differences in frequencies of proliferating and apoptotic cells could be observed. Conclusion These results indicate that CX3CR1 on resident vessel wall cells plays a key role in atherosclerotic plaque formation in transplanted aortic grafts. Targeting of vascular CX3CL1/ CX3CR1 may therefore be explored as a therapeutic option in vascular transplantation procedures

HLA-DRB3/4/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation

The HLA-DRB3/4/5 loci are closely linked to the HLA-DRB1 gene. Mismatches in these loci occur with a frequency of about 8%–12% in otherwise 10/10 HLA-matched transplant pairs. There is preliminary evidence that these disparities may associate with increased acute graft-versus-host disease (GvHD) rates. The aim of this study was to analyze a large cohort of German patients and their donors for HLA-DRB3/4/5 compatibility and to correlate the HLA-DRB3/4/5 matching status with the outcome of unrelated hematopoietic stem cell transplantation (uHSCT). To this end, 3,410 patients and their respective donors were HLA-DRB3/4/5 and HLA-DPB1 typed by amplicon-based nextgeneration sequencing (NGS). All patients included received their first allogeneic transplant for malignant hematologic diseases between 2000 and 2014. Mismatches in the antigen recognition domain (ARD) of HLA-DRB3/4/5 genes were correlated with clinical outcome. HLA-DRB3/4/5 incompatibility was seen in 12.5% (n = 296) and 17.8% (n = 185) of the 10/10 and 9/10 HLA-matched cases, respectively. HLA-DRB3/4/5 mismatches in the ARD associated with a worse overall survival (OS), as shown in univariate (5-year OS: 46.1% vs. 39.8%, log-rank p = 0.038) and multivariate analyses [hazard ratio (HR) 1.25, 95% CI 1.02–1.54, p = 0.034] in the otherwise 10/10 HLAmatched subgroup. The worse outcome was mainly driven by a significantly higher nonrelapse mortality (HR 1.35, 95% CI 1.05–1.73, p = 0.017). In the 9/10 HLA-matched cases, the effect was not statistically significant. Our study results suggest that mismatches within the ARD of HLA-DRB3/4/5 genes significantly impact the outcome of otherwise fully matched uHSCT and support their consideration upon donor selection in the future

HLA-DRB3/4/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation

The HLA-DRB3/4/5 loci are closely linked to the HLA-DRB1 gene. Mismatches in these loci occur with a frequency of about 8%–12% in otherwise 10/10 HLA-matched transplant pairs. There is preliminary evidence that these disparities may associate with increased acute graft-versus-host disease (GvHD) rates. The aim of this study was to analyze a large cohort of German patients and their donors for HLA-DRB3/4/5 compatibility and to correlate the HLA-DRB3/4/5 matching status with the outcome of unrelated hematopoietic stem cell transplantation (uHSCT). To this end, 3,410 patients and their respective donors were HLA-DRB3/4/5 and HLA-DPB1 typed by amplicon-based nextgeneration sequencing (NGS). All patients included received their first allogeneic transplant for malignant hematologic diseases between 2000 and 2014. Mismatches in the antigen recognition domain (ARD) of HLA-DRB3/4/5 genes were correlated with clinical outcome. HLA-DRB3/4/5 incompatibility was seen in 12.5% (n = 296) and 17.8% (n = 185) of the 10/10 and 9/10 HLA-matched cases, respectively. HLA-DRB3/4/5 mismatches in the ARD associated with a worse overall survival (OS), as shown in univariate (5-year OS: 46.1% vs. 39.8%, log-rank p = 0.038) and multivariate analyses [hazard ratio (HR) 1.25, 95% CI 1.02–1.54, p = 0.034] in the otherwise 10/10 HLAmatched subgroup. The worse outcome was mainly driven by a significantly higher nonrelapse mortality (HR 1.35, 95% CI 1.05–1.73, p = 0.017). In the 9/10 HLA-matched cases, the effect was not statistically significant. Our study results suggest that mismatches within the ARD of HLA-DRB3/4/5 genes significantly impact the outcome of otherwise fully matched uHSCT and support their consideration upon donor selection in the future

RENEB intercomparison exercises analyzing micronuclei (Cytokinesis-block Micronucleus Assay)

Purpose: In the framework of the ‘Realizing the European Network of Biodosimetry’ (RENEB) project, two intercomparison exercises were conducted to assess the suitability of an optimized version of the cytokinesis-block micronucleus assay, and to evaluate the capacity of a large laboratory network performing biodosimetry for radiation emergency triages. Twelve European institutions participated in the first exercise, and four non-RENEB labs were added in the second one. Materials and methods: Irradiated blood samples were shipped to participating labs, whose task was to culture these samples and provide a blind dose estimate. Micronucleus analysis was performed by automated, semi-automated and manual procedures. Results: The dose estimates provided by network laboratories were in good agreement with true administered doses. The most accurate estimates were reported for low dose points (== 2.7 Gy) a larger variation in estimates was observed, though in the second exercise the number of acceptable estimates increased satisfactorily. Higher accuracy was achieved with the semi-automated method. Conclusion: The results of the two exercises performed by our network demonstrate that the micronucleus assay is a useful tool for large-scale radiation emergencies, and can be successfully implemented within a large network of laboratories