Relaxin-2 (RLX) is a peptide hormone that exerts beneficial anti-fibrotic and anti-inflammatory effects in diverse models of cardiovascular disease. The goal of this study was to determine the ...effects of RLX treatment on the susceptibility to atrial fibrillation (AF) after myocardial infarction (MI).
Mice with cryoinfarction of the left anterior ventricular wall were treated for two weeks with either RLX (75 μg/kg/d) or vehicle (sodium acetate) delivered via subcutaneously implanted osmotic minipumps.
RLX treatment significantly attenuated the increase in AF-inducibility following cryoinfarction and reduced the mean duration of AF episodes. Furthermore, epicardial mapping of both atria revealed an increase in conduction velocity. In addition to an attenuation of atrial hypertrophy, chronic application of RLX reduced atrial fibrosis, which was linked to a significant reduction in atrial mRNA expression of connective tissue growth factor. Transcript levels of the pro-inflammatory cytokines interleukin-6 and interleukin-1β were reduced in RLX treated mice, but macrophage infiltration into atrial myocardium was similar in the vehicle and RLX treated groups.
Treatment with RLX in mice after MI reduces susceptibility to AF due to anti-inflammatory and anti-fibrotic properties. Because to these favorable actions, RLX may become a new therapeutic option in the treatment of AF, even when complicating MI.
•Relaxin-2 reduces susceptibility to atrial fibrillation after myocardial infarction.•Relaxin-2 attenuates atrial fibrosis and hypertrophy.•Atrial expression of pro-inflammatory cytokines is reduced by relaxin-2.•Relaxin-2 might become a reasonable drug for patients with atrial fibrillation.
A meta-analysis using data from seven German population-based cohorts was performed by the German Epidemiological consortium of Peripheral Arterial Disease (GEPArD) to investigate whether one ...question about claudication is more efficient for PAD screening than established questionnaires. Claudication was defined on the basis of the answer to one question asking for pain in the leg during normal walking. This simple question was compared with established questionnaires, including the Edinburgh questionnaire. The associations of claudication with continuous ABI values and decreased ABI were analyzed by linear and logistic regression analysis, respectively. The results of the studies were pooled in a random effect meta-analysis, which included data from 27,945 individuals (14,052 women, age range 20-84 years).
Meta-analysis revealed a significant negative association between claudication and ABI, which was stronger in men (β = -0.07; 95%CI -0.10, -0.04) than in women (β = -0.02; 95%CI -0.02, -0.01). Likewise, the presence of claudication symptoms was related to an increased odds of a decreased ABI in both men (Odds ratio = 5.40; 95%CI 4.20, 6.96) and women (Odds ratio = 1.99; 95%CI 1.58, 2.51).
Asking only one question about claudication was able to identify many individuals with a high likelihood of a reduced ABI with markedly higher sensitivity and only slightly reduced specificity compared to more complex questionnaires. At least in men, this question should be established as first screening step.
Red blood cell transfusions are commonly administered to infants weighing less than 1000 g at birth. Evidence-based transfusion thresholds have not been established. Previous studies have suggested ...higher rates of cognitive impairment with restrictive transfusion thresholds.
To compare the effect of liberal vs restrictive red blood cell transfusion strategies on death or disability.
Randomized clinical trial conducted in 36 level III/IV neonatal intensive care units in Europe among 1013 infants with birth weights of 400 g to 999 g at less than 72 hours after birth; enrollment took place between July 14, 2011, and November 14, 2014, and follow-up was completed by January 15, 2018.
Infants were randomly assigned to liberal (n = 492) or restrictive (n = 521) red blood cell transfusion thresholds based on infants' postnatal age and current health state.
The primary outcome, measured at 24 months of corrected age, was death or disability, defined as any of cognitive deficit, cerebral palsy, or severe visual or hearing impairment. Secondary outcome measures included individual components of the primary outcome, complications of prematurity, and growth.
Among 1013 patients randomized (median gestational age at birth, 26.3 interquartile range {IQR}, 24.9-27.6 weeks; 509 50.2% females), 928 (91.6%) completed the trial. Among infants in the liberal vs restrictive transfusion thresholds groups, respectively, incidence of any transfusion was 400/492 (81.3%) vs 315/521 (60.5%); median volume transfused was 40 mL (IQR, 16-73 mL) vs 19 mL (IQR, 0-46 mL); and weekly mean hematocrit was 3 percentage points higher with liberal thresholds. Among infants in the liberal vs restrictive thresholds groups, the primary outcome occurred in 200/450 (44.4%) vs 205/478 (42.9%), respectively, for a difference of 1.6% (95% CI, -4.8% to 7.9%; P = .72). Death by 24 months occurred in 38/460 (8.3%) vs 44/491 (9.0%), for a difference of -0.7% (95% CI, -4.3% to 2.9%; P = .70), cognitive deficit was observed in 154/410 (37.6%) vs 148/430 (34.4%), for a difference of 3.2% (95% CI, -3.3% to 9.6%; P = .47), and cerebral palsy occurred in 18/419 (4.3%) vs 25/443 (5.6%), for a difference of -1.3% (95% CI, -4.2% to 1.5%; P = .37), in the liberal vs the restrictive thresholds groups, respectively. In the liberal vs restrictive thresholds groups, necrotizing enterocolitis requiring surgical intervention occurred in 20/492 (4.1%) vs 28/518 (5.4%); bronchopulmonary dysplasia occurred in 130/458 (28.4%) vs 126/485 (26.0%); and treatment for retinopathy of prematurity was required in 41/472 (8.7%) vs 38/492 (7.7%). Growth at follow-up was also not significantly different between groups.
Among infants with birth weights of less than 1000 g, a strategy of liberal blood transfusions compared with restrictive transfusions did not reduce the likelihood of death or disability at 24 months of corrected age.
ClinicalTrials.gov Identifier: NCT01393496.
The ectonucleoside triphosphate diphosphohydrolase (CD39)/5′ ectonuclotidase (CD73)-dependent purinergic pathway emerges as promising cancer target. Yet, except for own previous work revealing a ...pathogenic role of CD73 and adenosine in radiation-induced lung fibrosis, the role of purinergic signaling for radiotherapy outcome remained elusive. Here we used C57BL/6 wild-type (WT), CD39 knockout (CD39
−/−
), and CD73 knockout (CD73
−/−
) mice and hind-leg tumors of syngeneic murine Lewis lung carcinoma cells (LLC1) to elucidate how host purinergic signaling shapes the growth of LLC1 tumors to a single high-dose irradiation with 10 Gy
in vivo
. In complementary
in vitro
experiments, we examined the radiation response of LLC1 cells in combination with exogenously added ATP or adenosine, the proinflammatory and anti-inflammatory arms of purinergic signaling. Finally, we analyzed the impact of genetic loss of CD39 on pathophysiologic lung changes associated with lung fibrosis induced by a single-dose whole-thorax irradiation (WTI) with 15 Gy. Loss of CD73 in the tumor host did neither significantly affect tumor growth nor the radiation response of the CD39/CD73-negative LLC1 tumors. In contrast, LLC1 tumors exhibited a tendency to grow faster in CD39
−/−
mice compared to WT mice. Even more important, tumors grown in the CD39-deficient background displayed a significantly reduced tumor growth delay upon irradiation when compared to irradiated tumors grown on WT mice. CD39 deficiency caused only subtle differences in the immune compartment of irradiated LLC1 tumors compared to WT mice. Instead, we could associate the tumor growth and radioresistance-promoting effects of host CD39 deficiency to alterations in the tumor endothelial compartment. Importantly, genetic deficiency of CD39 also augmented the expression level of fibrosis-associated osteopontin in irradiated normal lungs and exacerbated radiation-induced lung fibrosis at 25 weeks after irradiation. We conclude that genetic loss of host CD39 alters the tumor microenvironment, particularly the tumor microvasculature, and thereby promotes growth and radioresistance of murine LLC1 tumors. In the normal tissue loss of host, CD39 exacerbates radiation-induced adverse late effects. The suggested beneficial roles of host CD39 on the therapeutic ratio of radiotherapy suggest that therapeutic strategies targeting CD39 in combination with radiotherapy have to be considered with caution.
Central venous catheters (CVC) placed either via the internal jugular vein (IJV) or the subclavian vein (SCV) are routinely used in patients with hematologic malignancies. In this retrospective ...study, we systematically compared CVC‐associated complications for both insertion sites, IJV and SCV. Between January 2011 and June 2013, all consecutive patients (n = 87) were included with at least one CVC (n = 153; n = 94 IJV; n = 59 SCV) at our institution due to induction/consolidation for AML/ALL or autologous hematopoietic cell transplantation (HCT). Primary study endpoints were central line‐associated (CLABSI), catheter‐related (CRBSI) blood stream infections and local inflammation (LI) at the insertion site. CRBSI occurred earlier and more frequently in the IJV‐ versus the SCV‐group with an incidence rate of CRBSI at day 15 of 10% versus 0% (p = .04) and a rate of CRBSI per 1000 CVC days of 5.7 versus 1.2. In addition, CLABSI was detected more often in IJV‐ compared to SCV‐CVC (26% vs. 8%, p = .009). Conversely, LI occurred more frequently and earlier in SCV‐ versus IJV‐CVC (88% vs. 56%, p < .0001) with a median time to LI of 9 versus 14 days (p < .0001). The strongest risk factor for the endpoints CRBSI, CLABSI, and LI was the insertion site. However, SCV insertion was a risk factor for LI (p = .001, HR: 2.0), insertion in the IJV a risk factor for CLABSI (p = .044, HR: 2.7) and CRBSI (p = .036, HR: 5.4). These results demonstrate a differential effect of the insertion site of CVC in neutropenic patients with a significantly reduced frequency of CVC‐related blood stream infections in SCV‐CVC.
Dynamic Coronary Roadmap (DCR) is a software tool that creates a real-time dynamic coronary artery overlay on fluoroscopic images. The efficacy of DCR in significantly reducing contrast medium use ...during percutaneous coronary interventions (PCI) has previously been shown. In this study, we aimed to determine if DCR is equally effective irrespective of the performing investigator's experience level.
In this sub-analysis of a monocentric, open-label, randomized trial, 130 patients with hemodynamic relevant coronary type A and B lesions were randomized and contrast medium use was conducted with (+) or without (-) DCR software. PCI was randomly allocated and performed by an investigator with high (A) or medium (B) experience level.
Overall, contrast medium use was significantly reduced by both investigators in the +DCR group, and Investigator B used significantly less contrast medium with the software than Investigator A. The DCR software was not accompanied by increased radiation exposure for the patients or the teams. On the contrary, dose area product was reduced by both investigators, but was significantly reduced by the highly experienced investigator when using DCR. Fluoroscopy time was not different between investigators. Procedural success was 100%. Serious in-hospital adverse events were not observed. One of Investigator A's patients suffered from post-procedural acute kidney injury in the -DCR group.
DCR significantly reduces contrast medium use during PCI irrespective of investigator's experience level.
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•The TUM-WelChem Cell Model is applied in liquid distributor design.•Optimum design for minimized material usage and high free space for gas flow.•The optimum drip point density ...increases with the nominal size of random packing.•For a perfectly square grid, the highest possible is also the optimum wall spacing.•The optimum drip point density increases for smaller column diameters.
Liquid distributors are the second most important internal in packed columns, as they ensure sufficient initial distribution, which is crucial to achieve optimum separation performance. In this work, a liquid distributor design method is presented, which applies the TUM–WelChem Cell Model to consider the interaction between the liquid distributor and the packing. Liquid distribution in the packing is estimated in dependence of the liquid distributor design. An overall maldistribution quality is determined as a characteristic value for evaluation. Two common methods, the coefficient of variation and the liquid distribution quality by Moore and Rukovena, are implemented for reference. A parameter study with an exemplary column design provides optimum drip point densities for different types of packing. Moreover, the spacing between the outermost drip points and the column wall is considered in detail, suggesting an optimum distribution quality for high wall spacing. Further application of the method suggests an increase of the optimum drip point density for smaller column diameters. Application of the TUM–WelChem Cell Model to liquid distributor design provides a potent tool for an optimized distributor layout with sufficient initial distribution at minimized material usage and high free space for the gas flow.
Context.
The eROSITA X-ray telescope on board the Spectrum-Roentgen-Gamma satellite has started to detect new X-ray sources over the full sky at an unprecedented rate. Understanding the performance ...and selection function of the source detection is important for the subsequent scientific analysis of the eROSITA catalogs.
Aims.
Through simulations, we test and optimize the eROSITA source detection procedures, and we characterize the detected catalog quantitatively.
Methods.
Taking the eROSITA Final Equatorial-Depth Survey (eFEDS) as an example, we ran extensive photon-event simulations based on our best knowledge of the instrument characteristics, the background spectrum, and the population of astronomical X-ray sources. We introduce a method of analyzing source detection completeness, purity, and efficiency based on the origin of each photon.
Results.
According to the source detection efficiency measured in the simulation, we chose a two-pronged strategy to build eROSITA X-ray catalogs, creating a main catalog using only the most sensitive band (0.2–2.3 keV) and an independent hard-band-selected catalog using multiband detection in a range up to 5 keV. Because our mock data are highly representative of the real eFEDS data, we used the mock catalogs to measure the completeness and purity of the eFEDS catalogs as a function of multiple parameters, such as detection likelihood, flux, and luminosity. These measurements provide a basis for choosing the eFEDS catalog selection thresholds. The mock catalogs (available with this paper) can be used to construct the selection function of active galactic nuclei and galaxy clusters. A direct comparison of the output and input mock catalogs also gives rise to a correction curve that converts the raw point-source flux distribution into the intrinsic number counts distribution.
We show the error in water-limited yields simulated by crop models which is associated with spatially aggregated soil and climate input data. Crop simulations at large scales (regional, national, ...continental) frequently use input data of low resolution. Therefore, climate and soil data are often generated via averaging and sampling by area majority. This may bias simulated yields at large scales, varying largely across models. Thus, we evaluated the error associated with spatially aggregated soil and climate data for 14 crop models. Yields of winter wheat and silage maize were simulated under water-limited production conditions. We calculated this error from crop yields simulated at spatial resolutions from 1 to 100 km for the state of North Rhine-Westphalia, Germany. Most models showed yields biased by <15% when aggregating only soil data. The relative mean absolute error (rMAE) of most models using aggregated soil data was in the range or larger than the inter-annual or inter-model variability in yields. This error increased further when both climate and soil data were aggregated. Distinct error patterns indicate that the rMAE may be estimated from few soil variables. Illustrating the range of these aggregation effects across models, this study is a first step towards an ex-ante assessment of aggregation errors in large-scale simulations.
Abstract
Grasslands are globally distributed and naturally occurring; however, in Europe, most grasslands are anthropogenically created or altered by livestock grazing or mowing. Low‐intensity use ...and management have led to species‐rich communities in European grasslands. The intensification of crop production and livestock farming with stabling throughout the year has led to an abandonment of grasslands that are no longer economically profitable. In this study, we looked at the influence of grassland abandonment on biodiversity. We hypothesized that abandonment of grasslands decreases the overall biodiversity, but has different effects depending on the focal taxonomic group (i.e., vascular plants, insects, or birds). We also hypothesized that the type of management before abandonment, the type of grassland, and the time after abandonment would influence grassland biodiversity. We conducted a Web of Science search, with pre‐defined terms, to find articles that compared biodiversity of managed and abandoned grasslands in Europe. We screened the articles and included 39 studies in a subsequent meta‐analysis. We found that overall biodiversity was reduced after abandonment; however, the biodiversity reduction in the grasslands differed among taxonomic groups. Plant species diversity was significantly lower after abandonment (plant summary effect size: −0.25 −0.34; −0.16), whereas the diversity of insects and birds showed no significant trend, but a visual trend toward an increase. None of the other environmental variables (type of management, type of grassland, or the time after abandonment) had a significant influence on the biodiversity of the grasslands. We conclude that maintaining grassland management is crucial to support biodiversity conservation in European grasslands.
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