Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

The Control of Heparanase Through the Use of Small Molecules

Despite the enormous progress made in recent years with antibodies, vaccines, antisense oligonucleotides, etc., the so-called “biological” approaches for tackling the control of various diseases, medicinal chemistry remains a bulwark to refer to for the development of new drugs. Also in the case of heparanase, medicinal chemistry has always been in the forefront to identify new inhibitors, through modification of natural macromolecules, e.g., sulfated polysaccharides like heparin, or of natural compounds isolated from bacteria or plants, or through rational design. In this chapter, the reader will find a detailed description of the most relevant small-molecule heparanase inhibitors reported so far in the scientific literature and in patent applications, with mention to the design strategy and to structure-activity relationships. Starting from heparanase inhibitors of natural origin and the attempts to improve their potency and selectivity, the reader will be guided through the major chemical classes of synthetic inhibitors, with representation of the structure of the most relevant compounds. The last paragraph is dedicated to a brief description of inhibitors that have reached clinical trials, highlighting their structure, mechanism, and improved derivatives

Low night temperature at veraison enhances the accumulation of anthocyanins in Corvina grapes (Vitis Vinifera L.)

Climate change is a major concern in grape production worldwide. Nights have been warming much faster than the days, raising attention on the effect of night temperatures on grape and wine composition. In this study we evaluated the effect of night temperatures on grape coloration in the cv. Corvina (Vitis vinifera L.). In 2015 and 2016 potted plants were cooled overnight (10-11 \ub0C) during two berry ripening phases, veraison (TV) or post-veraison (TPV), and compared to control vines (C) grown at ambient night temperature (15-20 \ub0C on average). Cooling treatment around veraison (TV) hastened berry anthocyanin accumulation, while the same treatment applied after veraison (TPV) was ineffective. Molecular analysis revealed an increased transcription of four key genes in anthocyanin biosynthesis (CHS3, F3H1, MYBA1 and UFGT) in TV treatment. These results suggest that the anthocyanin biosynthesis capacity was enhanced by cool nights during veraison. However, since the gene expression was not always temporally correlated to the increase in anthocyanin concentration, we speculate on the presence of mechanisms, such as enzymatic regulation or anthocyanin transport, which may contribute in determining the anthocyanin accumulation under low night temperatures