Opposite fates of the purine metabolite allantoin under water and nitrogen limitations in bread wheat

The metabolite allantoin is an intermediate of the catabolism of purines (components of nucleotides) and is known for its housekeeping role in nitrogen (N) recycling and also for its function in N transport and storage in nodulated legumes. Allantoin was also shown to differentially accumulate upon abiotic stress in a range of plant species but little is known about its role in cereals. To address this, purine catabolic pathway genes were identified in hexaploid bread wheat and their chromosomal location was experimentally validated. A comparative study of two Australian bread wheat genotypes revealed a highly significant increase of allantoin (up to 29-fold) under drought. In contrast, allantoin significantly decreased (up to 22-fold) in response to N deficiency. The observed changes were accompanied by transcriptional adjustment of key purine catabolic genes, suggesting that the recycling of purine-derived N is tightly regulated under stress. We propose opposite fates of allantoin in plants under stress: the accumulation of allantoin under drought circumvents its degradation to ammonium (NH4+) thereby preventing N losses. On the other hand, under N deficiency, increasing the NH4+ liberated via allantoin catabolism contributes towards the maintenance of N homeostasis

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)