Increasing zinc (Zn) concentration of cereal grains is a global challenge to alleviate Zn deficiency‐related health problems in humans caused by low dietary Zn intake. This study investigated the effects of soil‐ and foliar‐applied nitrogen (N) and Zn fertilizers on grain Zn accumulation of durum wheat (Triticum durum) grown on a Zn‐deficient soil. In addition, localization of Zn and protein within durum wheat grain was studied by using Bradford reagent for protein and dithizone (diphenyl thiocarbazone) for Zn. Grain Zn concentration was greatly enhanced by soil or foliar applications of Zn. When Zn supply was adequately high, both soil and foliar N applications improved grain Zn concentration. Consequently, there was a significant positive correlation between grain concentrations of Zn and N, when Zn supply was not limiting. Protein and Zn staining studies showed co‐localization of Zn and protein within grain, particularly in the embryo and aleurone. Results indicate that N and Zn fertilization have a synergistic effect on grain Zn concentration. Possibly, increasing N supply contributes to grain Zn concentration by affecting the levels of Zn‐chelating nitrogenous compounds or the abundance of Zn transporters. Our results suggest that nitrogen management can be an effective agronomic tool to improve grain Zn concentration.

Summary• This study focussed on the effect of increasing nitrogen (N) supply on root uptake and root-to-shoot translocation of zinc (Zn) as well as retranslocation of foliar-applied Zn in durum wheat (Triticum durum).• Nutrient solution experiments were conducted to examine the root uptake and root-to-shoot translocation of 65 Zn in seedlings precultured with different N supplies. In additional experiments, the effect of varied N nutrition on retranslocation of foliar-applied 65 Zn was tested at both the vegetative and generative stages.• When N supply was increased, the 65 Zn uptake by roots was enhanced by up to threefold and the 65 Zn translocation from roots to shoots increased by up to eightfold, while plant growth was affected to a much smaller degree. Retranslocation of 65 Zn from old into young leaves and from flag leaves to grains also showed marked positive responses to increasing N supply.• The results demonstrate that the N-nutritional status of wheat affects major steps in the route of Zn from the growth medium to the grain, including its uptake, xylem transport and remobilization via phloem. Thus, N is a critical player in the uptake and accumulation of Zn in plants, which deserves special attention in biofortification of food crops with Zn.

Deficiencies of zinc (Zn) and iron (Fe) are global nutritional problems and caused most often by their limited dietary intake. Increasing Zn and Fe concentrations of staple food crops such as wheat is therefore an important global challenge. This study investigated the effects of varied nitrogen (N) and Zn supply on the total uptake, remobilization and partitioning of Zn, Fe and N in durum wheat throughout its ontogenesis. Plants were grown under greenhouse conditions with high or low supply of N and Zn, and harvested at 8 different developmental stages for analysis of Zn, Fe and N in leaves, stems, husks and grains. The results obtained showed that the Zn and Fe uptake per plant was enhanced up to 4fold by high N supply while the increases in plant growth by high N supply were much less. When both the Zn and N supplies were high, approximately 50% of grain Zn and 80% of grain Fe were provided by post-anthesis shoot uptake, indicating that the contribution of remobilization to grain accumulation was higher for Zn than for Fe. At the high N and Zn application, about 60% of Zn, but only 40% of Fe initially stored in vegetative parts were retranslocated to grains, and nearly 80% of total shoot Zn and 60% of total shoot Fe were harvested with grains. All these values were significantly lower at the low N treatment. Results indicate that N nutrition is a critical factor in both the acquisition and grain allocation of Zn and Fe in wheat.

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BackgroundGenuine uncertainty on superiority of one intervention over the other is called equipoise. Physician-investigators in randomized controlled trials (RCT) need equipoise at least in studies with more than minimal risks. Ideally, this equipoise is also present in patient-participants.In pediatrics, data on equipoise are lacking. We hypothesize that 1) lack of equipoise at enrolment among parents may reduce recruitment; 2) lack of equipoise during participation may reduce retention in patients assigned to a less favoured treatment-strategy.MethodsWe compared preferences of parents/patients at enrolment, documented by a questionnaire (phase 1), with preferences developed during follow-up by an interview-study (phase 2) to investigate equipoise of child-participants and parents in the BeSt-for-Kids-study (NTR 1574). This trial in new-onset Juvenile Idiopathic Arthritis-patients consists of three strategies. One strategy comprises initial treatment with a biological disease-modifying-antirheumatic-drug (DMARD), currently not standard-of-care. Semi-structured interviews were conducted with 23 parents and 7 patients, median 11 months after enrolment.ResultsInitially most parents and children were not in equipoise. Parents/patients who refused participation, regularly declined due to specific preferences. Many participating families preferred the biological-first-strategy. They participated to have a chance for this initial treatment, and would even consider stopping trial-participation when not randomized for it. Their conviction of superiority of the biological-first strategy was based on knowledge from internet and close relations. According to four parents, the physician-investigator preferred the biological-first-strategy, but the majority (n = 19) stated that she had no preferred strategy. In phase 2, preferences tended to change to the treatment actually received.ConclusionsLack of equipoise during enrolment did not reduce study recruitment, mainly due to the fact that preferred treatment was only available within the study. Still, when developing a trial it is important to evaluate whether the physicians’ research question is in line with preferences of the patient-group. By exploring so-called ‘informed patient-group’-equipoise, successful recruitment may be enhanced and bias avoided.In our study, lack of equipoise during trial-participation did not reduce retention in those assigned to a less favoured option. We observed a change for preference towards treatment actually received, possibly explained by comparable outcomes in all three arms.Electronic supplementary materialThe online version of this article (10.1186/s12910-018-0336-8) contains supplementary material, which is available to authorized users.