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Oncogenic fusion proteins generated by chromosomal translocations play major roles in cancer. Among them, fusions between EWSR1 and transcription factors generate oncogenes with powerful chromatin regulatory activities, capable of establishing complex gene expression programs in permissive precursor cells. Here we define the epigenetic and 3D connectivity landscape of Clear Cell Sarcoma, an aggressive cancer driven by the EWSR1-ATF1 fusion gene. We find that EWSR1-ATF1 displays a distinct DNA binding pattern that requires the EWSR1 domain and promotes ATF1 retargeting to new distal sites, leading to chromatin activation and the establishment of a 3D network that controls oncogenic and differentiation signatures observed in primary CCS tumors. Conversely, EWSR1-ATF1 depletion results in a marked reconfiguration of 3D connectivity, including the emergence of regulatory circuits that promote neural crest-related developmental programs. Taken together, our study elucidates the epigenetic mechanisms utilized by EWSR1-ATF1 to establish regulatory networks in CCS, and points to precursor cells in the neural crest lineage as candidate cells of origin for these tumors. The relationship between cellular histogenesis and molecular phenotypes for the EWSR1- ATF1 fusion in clear cell sarcoma (CCS) requires further characterization. Here, the authors investigate the EWSR1-ATF1 gene regulation networks in CCS cell lines, primary tumors, and mesenchymal stem cells. [ABSTRACT FROM AUTHOR]

Anabolic androgenic steroids (AAS) are doping agents that are mostly used for improvement of strength and muscle hypertrophy. In some sports, athletes reported that the intake of AAS is associated with a better recovery, a higher training load capacity and therefore an increase in physical and mental performances. The purpose of this study was to evaluate, the effect of multiple doses of AAS on different physiological parameters that could indirectly relate the physical state of athletes during a hard endurance training program. In a double blind settings, three groups (n = 9, 8 and 8) were orally administered placebo, testosterone undecanoate or 19-norandrostenedione, 12 times during 1 month. Serum biomarkers (creatine kinase, ASAT and urea), serum hormone profiles (testosterone, cortisol and LH) and urinary catecholamines (noradrenalin, adrenalin and dopamine) were evaluated during the treatment. Running performance was assessed before and after the intervention phase by means of a standardized treadmill test. None of the measured biochemical variables showed significant impact of AAS on physical stress level. Data from exercise testing on submaximal and maximal level did not reveal any performance differences between the three groups or their response to the treatment. In the present study, no effect of multiple oral doses of AAS on endurance performance or bioserum recovery markers was found. [ABSTRACT FROM AUTHOR]

Copyright of Social & Preventive Medicine is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Social & Preventive Medicine is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Lung volume and alveolar pressure were assessed using inductance plethysmography, airway occlusion and pneumotachography in a child with severe adult respiratory distress syndrome during both conventional mechanical and combined high-frequency ventilation (HFJV). The results suggest that improved oxygenation during combined HFJV is associated with higher end-expiratory lung volume and lower peak and mean lung volume and alveolar pressure. [ABSTRACT FROM AUTHOR]