A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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A role for endothelial nitric oxide synthase in intestinal stem cell proliferation and mesenchymal colorectal cancer

Abstract Background Nitric oxide (NO) has been highlighted as an important agent in cancer-related events. Although the inducible nitric oxide synthase (iNOS) isoform has received most attention, recent studies in the literature indicate that the endothelial isoenzyme (eNOS) can also modulate different tumor processes including resistance, angiogenesis, invasion, and metastasis. However, the role of eNOS in cancer stem cell (CSC) biology and mesenchymal tumors is unknown. Results Here, we show that eNOS was significantly upregulated in VilCre ERT2 Apc fl/+ and VilCre ERT2 Apc fl/fl mouse intestinal tissue, with intense immunostaining in hyperproliferative crypts. Similarly, the more invasive VilCre ERT2 Apc fl/+ Pten fl/+ mouse model showed an overexpression of eNOS in intestinal tumors whereas this isoform was not expressed in normal tissue. However, none of the three models showed iNOS expression. Notably, when 40 human colorectal tumors were classified into different clinically relevant molecular subtypes, high eNOS expression was found in the poor relapse-free and overall survival mesenchymal subtype, whereas iNOS was absent. Furthermore, Apc fl/fl organoids overexpressed eNOS compared with wild-type organoids and NO depletion with the scavenger carboxy-PTIO (c-PTIO) decreased the proliferation and the expression of stem-cell markers, such as Lgr5, Troy, Vav3, and Slc14a1, in these intestinal organoids. Moreover, specific NO depletion also decreased the expression of CSC-related proteins in human colorectal cancer cells such as β-catenin and Bmi1, impairing the CSC phenotype. To rule out the contribution of iNOS in this effect, we established an iNOS-knockdown colorectal cancer cell line. NO-depleted cells showed a decreased capacity to form tumors and c-PTIO treatment in vivo showed an antitumoral effect in a xenograft mouse model. Conclusion Our data support that eNOS upregulation occurs after Apc loss, emerging as an unexpected potential new target in poor-prognosis mesenchymal colorectal tumors, where NO scavenging could represent an interesting therapeutic alternative to targeting the CSC subpopulation

Do Investors Value a Firm\u27s Commitment to Social Activities?

Previous empirical research has found mixed results for the impact of corporate social responsibility (CSR) investments on corporate financial performance (CFP). This paper contributes to the literature by exploring in a two stage investor decision-making model the relationship between a firm’s innovation effort, CSR, and financial performance. We simultaneously examine the impact of CSR on both accounting-based (financial health) and market-based (Tobin’s Q) financial performance measures. From a sample of top corporate citizens, we find that: (1) a firm’s social responsibility commitment (CSR) contributes to its financial performance; (2) after controlling for investment in innovation activities, CSR continues to have a positive impact on a firm’s financial performance; (3) the customer dimension of CSR has a positive effect on both CFP measures, whereas the employee dimension indicates a significant impact only on financial heath; and (4) the community relation dimension of CSR only affects the market-based CFP measure of firms with high innovation intensit

An Amphisbaenian Skull from the European Miocene and the Evolution of Mediterranean Worm Lizards

<div><p>The evolution of blanid amphisbaenians (Mediterranean worm lizards) is mainly inferred based on molecular studies, despite their fossils are common in Cenozoic European localities. This is because the fossil record exclusively consists in isolated elements of limited taxonomic value. We describe the only known fossil amphisbaenian skull from Europe – attributed to <i>Blanus mendezi</i> sp. nov. (Amphisbaenia, Blanidae) – which represents the most informative fossil blanid material ever described. This specimen, from the Middle Miocene of Abocador de Can Mata (11.6 Ma, MN7+8) in the Vallès-Penedès Basin (Catalonia, NE Iberian Peninsula), unambiguously asserts the presence of <i>Blanus</i> in the Miocene of Europe. This reinforces the referral to this genus of the previously-known, much more incomplete and poorly-diagnostic material from other localities of the European Neogene. Our analysis – integrating the available molecular, paleontological and biogeographic data – suggests that the new species postdates the divergence between the two main (Eastern and Western Mediterranean) extant clades of blanids, and probably precedes the split between the Iberian and North-Western African subclades. This supports previous paleobiogeographic scenarios for blanid evolution and provides a significant minimum divergence time for calibrating molecular analyses of blanid phylogeny.</p></div

ESICM LIVES 2016: part two : Milan, Italy. 1-5 October 2016.

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