The combination of carboxy-terminal propeptide of procollagen type I blood levels and late gadolinium enhancement at cardiac magnetic resonance provides additional prognostic information in idiopathic dilated cardiomyopathy - A multilevel assessment of myocardial fibrosis in dilated cardiomyopathy

Aims To determine the prognostic value of multilevel assessment of fibrosis in dilated cardiomyopathy (DCM) patients. Methods and results We quantified fibrosis in 209 DCM patients at three levels: (i) non-invasive late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR); (ii) blood biomarkers [amino-terminal propeptide of procollagen type III (PIIINP) and carboxy-terminal propeptide of procollagen type I (PICP)], (iii) invasive endomyocardial biopsy (EMB) (collagen volume fraction, CVF). Both LGE and elevated blood PICP levels, but neither PIIINP nor CVF predicted a worse outcome defined as death, heart transplantation, heart failure hospitalization, or life-threatening arrhythmias, after adjusting for known clinical predictors [adjusted hazard ratios: LGE 3.54, 95% confidence interval (CI) 1.90-6.60; P < 0.001 and PICP 1.02, 95% CI 1.01-1.03; P = 0.001]. The combination of LGE and PICP provided the highest prognostic benefit in prediction (likelihood ratio test P = 0.007) and reclassification (net reclassification index: 0.28, P = 0.02; and integrated discrimination improvement index: 0.139, P = 0.01) when added to the clinical prediction model. Moreover, patients with a combination of LGE and elevated PICP (LGE+/PICP+) had the worst prognosis (log-rank P < 0.001). RNA-sequencing and gene enrichment analysis of EMB showed an increased expression of pro-fibrotic and pro-inflammatory pathways in patients with high levels of fibrosis (LGE+/PICP+) compared to patients with low levels of fibrosis (LGE-/PICP-). This would suggest the validity of myocardial fibrosis detection by LGE and PICP, as the subsequent generated fibrotic risk profiles are associated with distinct cardiac transcriptomic profiles. Conclusion The combination of myocardial fibrosis at CMR and circulating PICP levels provides additive prognostic value accompanied by a pro-fibrotic and pro-inflammatory transcriptomic profile in DCM patients with LGE and elevated PICP

The impact of soybean expansion on mammal and bird, in the Balsas region, north Brasilian Cerrado

In order to analyse the impact of land use change, it is particularly important to know how organisms use resources distributed across a heterogeneous landscape. The main objective of this study is to analyse the potential impact of land use change on bird and mammal fauna, by using a coupled model approach. The CLUE (Conversion of Land Use and its Effects) model has been applied to obtain the spatial pattern of land use change for a scenario with soybean expansion in the Cerrado of Maranhão State in Brazil. These land use change maps were used as the input for the LEDESS (Landscape Ecological Decision and Evaluation Support System) model to evaluate the impact of habitat fragmentation on mammal and bird species. The scenarios demonstrated that high quality habitat for all studied species will be lost in the future when current trends in agricultural expansion continue, but these changes will have species-specific impacts. The most relevant ecological impact under the explored scenarios was habitat fragmentation expressed by the increase the number of habitat clusters. The coupled model approach of LEDESS and CLUE made it possible to project the spatial impact of soybean expansion on habitat dynamics in the studied region. This model approach can help to design effective ecological infrastructure to facilitate species survival and to implement an effective habitat network in the Balsas region

Remarkably similar migration patterns between different red-backed shrike populations suggest that migration rather than breeding area phenology determines the annual cycle

The regular fluctuation of resources across the Globe guides movements of migratory animals. To ensure sufficient reproductive output and maintain viable population sizes, migratory animals should match arrival at breeding areas with local peaks in resource availability. It is generally assumed that breeding phenology dictates the timing of the annual cycle, but this is poorly studied. Here, we use light-level geolocator tracking data to compare the annual spatiotemporal migration patterns of a long-distance migratory songbird, the red-backed shrike, Lanius collurio, breeding at widely different latitudes within Europe. We find that populations use remarkably similar migration routes and are highly synchronized in time. Additional tracks from populations breeding at the edges of the European range support these similar migration patterns. When comparing timing of breeding and vegetation phenology, as a measure of resource availability across populations, we find that arrival and timing of breeding corresponds to the peak in vegetation greenness at northern latitudes. At lower latitudes birds arrive simultaneously with the more northerly breeding populations, but after the local greenness peak, suggesting that breeding area phenology does not determine the migratory schedule. Rather, timing of migration in red-backed shrikes may be constrained by events in other parts of the annual cycle

In vitro micronucleus assay with Chinese hamster V79 cells - results of a collaborative study with in situ exposure to 26 chemical substances

A collaborative study with 10 participating laboratories was conducted to evaluate a test protocol for the performance of the in vitro micronucleus (MN) test using the V79 cell line with one treatment and one sampling time only. A total of 26 coded substances were tested in this study for MN-inducing properties. Three substances were tested by all 10 laboratories and 23 substances were tested by three or four laboratories in parallel. Six aneugenic, 7 clastogenic and 6 non-genotoxic chemicals were uniformly recognised as such by all laboratories. Three chemicals were tested uniformly negative by three laboratories although also clastogenic properties have been reported for these substances. Another set of three clastogenic substances showed inconsistent results and one non-clastogenic substance was found to be positive by one out of three laboratories. Within the study, the applicability of the determination of a proliferation index (PI) as an internal cytotoxicity parameter in comparison with the determination of the mitotic index (MI) was also evaluated. Both parameters were found to be useful for the interpretation of the MN test result with regard to the control of cell cycle kinetics and the mode of action for MN induction. The MN test in vitro was found to be easy to perform and its results were mainly in accordance with results from chromosomal aberration tests in vitro