Prognostic significance of miR-34a in Ewing sarcoma is associated with cyclin D1 and ki-67 expression

BACKGROUND: At diagnosis, identification of reliable biological indicators of prognosis to allow stratification of patients according to different risks is an important but still unresolved aspect in the treatment of Ewing sarcoma (EWS) patients. This study aimed to explore the role of miR-34A expression on prognosis of EWS patients.PATIENTS AND METHODS: Specimens from 109 patients with non-metastatic EWS treated at the Rizzoli Institute with neoadjuvant chemotherapy (protocols ISG/SSGIII, EW-1, EW-2, EW-REN2, EW-REN3, EW-PILOT) and 17 metastases were studied. Sixty-eight patients (62%) remained disease-free and 41 (38%) relapsed (median follow-up: 67 months, range 9-241 months). Expression of miR-34a and of some of its targets (cyclin D1, bcl-2, SIRT1 and YY1) was evaluated by qRT-PCR using TaqMan MicroRNA Assays and/or by immunohistochemistry on tissue microarrays from the same patients.RESULTS: High expression of miR-34a in localized tumors was significantly related to better event-free and overall survival (P = 0.004). Relevance of miR-34a was confirmed by using different calibrators (normal mesenchymal stem cells and different normal tissues). By multivariate Cox regression analysis, low miR-34a expression as well as nontotal necrosis and high levels of lactate dehydrogenase were all confirmed as independent risk factors associated with poor outcome. Expression of miR-34a was lower in metastases than in primary tumors. It inversely correlated with expression of cyclin D1 and Ki-67.CONCLUSIONS: By demonstrating its relationship with clinical outcome, we propose evaluation of miR-34a at diagnosis of EWS patients to allow early risk stratification. Validation of these results would nonetheless ultimately need a prospective assessment

High sedimentary oxygen consumption indicates that sewage input from small islands drives benthic community shifts on overfished reefs

Small-island coral reef ecosystems are usually closely coupled to the activities of human inhabitants. Ahus Island (Papua New Guinea) is an isolated Pacific island with a rapidly growing population, heavy reliance on marine resources and limited infrastructure. We hypothesized that untreated sewage was driving distinct benthic assemblages around Ahus and neighbouring uninhabited Onetah. At sites with varying proximities to beach toilets, fore-reef herbivorous fish biomass and benthic composition were measured alongside reef-flat sedimentary oxygen consumption (SOC); a high SOC rate reflects high organic input into coastal waters, thus serving as a potential indicator of sewage input. Fish biomass was low (17.1–20.1 g m–2), but consistent between sites. However, cyanobacteria dominated the fore-reef closest to toilets (62 ± 3%) with highest reef-flat SOC, whereas hard corals dominated furthest away (63 ± 1%), where SOC was lowest. To our knowledge, this is the first study that used SOC to detect local differences in sewage pollution. The results indicate that whilst corals can maintain their dominance on overfished reefs, additional sewage stress may drive pronounced benthic shifts, highlighting the urgency to improve small-island waste management

La movimentazione manual edei pazienti: un metodo sintetico per la valutazione del rischio.

La movimentazione manuale dei carichi e le patologie ad essa correlate sono oggetto di crescente interesse da parte degli addetti alla prevenzione negli ambienti di lavoro. Gli operatori sanitari rappresentano una delle categorie a rischio, in quanto adibiti alla movimentazione manuale dei pazienti che rappresentano un “carico "tipico”. È necessaria, quindi, la valutazione del rischio relativo alla movimentazione manuale, ai movimenti ripetuti degli arti superiori ed a posture incongrue e frequentemente instabili. Lo studio prevede il confronto di un metodo integrato con i tre metodi maggiormente utilizzati (MAPO, REBA, OCRA). I risultati evidenziano la possibilità e la convenienza dell’utilizzare un unico metodo integrato nella valutazione della movimentazione manuale dei pazienti

Human-mediated loss of phylogenetic and functional diversity in coral reef fishes

Beyond the loss of species richness [1, 2 and 3], human activities may also deplete the breadth of evolutionary history (phylogenetic diversity) and the diversity of roles (functional diversity) carried out by species within communities, two overlooked components of biodiversity. Both are, however, essential to sustain ecosystem functioning and the associated provision of ecosystem services, particularly under fluctuating environmental conditions [1, 2, 3, 4, 5, 6 and 7]. We quantified the effect of human activities on the taxonomic, phylogenetic, and functional diversity of fish communities in coral reefs, while teasing apart the influence of biogeography and habitat along a gradient of human pressure across the Pacific Ocean. We detected nonlinear relationships with significant breaking points in the impact of human population density on phylogenetic and functional diversity of parrotfishes, at 25 and 15 inhabitants/km^2, respectively, while parrotfish species richness decreased linearly along the same population gradient. Over the whole range, species richness decreased by 11.7%, while phylogenetic and functional diversity dropped by 35.8% and 46.6%, respectively. Our results call for caution when using species richness as a benchmark for measuring the status of ecosystems since it appears to be less responsive to variation in human population densities than its phylogenetic and functional counterparts, potentially imperiling the functioning of coral reef ecosystems

Enoxacin extends lifespan of C. elegans by inhibiting miR-34-5p and promoting mitohormesis

Alterations in microRNA (miRNA) processing have been previously linked to aging. Here we used the small molecule enoxacin to pharmacologically interfere with miRNA biogenesis and study how it affects aging in C. elegans. Enoxacin extended worm lifespan and promoted survival under normal and oxidative stress conditions. Enoxacin-induced longevity required the transcription factor SKN-1/Nrf2 and was blunted by the antioxidant N-acetyl-cysteine, suggesting a prooxidant-mediated mitohormetic response. The longevity effects of enoxacin were also dependent on the miRNA pathway, consistent with changes in miRNA expression elicited by the drug. Among these differentially expressed miRNAs, the widely conserved miR-34-5p was found to play an important role in enoxacin-mediated longevity. Enoxacin treatment down-regulated miR-34-5p and did not further extend lifespan of long-lived mir-34 mutants. Moreover, N-acetyl-cysteine abrogated mir-34(gk437)-induced longevity. Evidence also points to double-stranded RNA-specific adenosine deaminases (ADARs) as new targets of enoxacin since ADAR loss-of-function abrogates enoxacin-induced lifespan extension. Thus, enoxacin increases lifespan by reducing miR-34-5p levels, interfering with the redox balance and promoting healthspan. Keywords: Enoxacin, MicroRNA, Aging, miR-34, Mitohormesis, ADA