Iron Donor Research Articles

Whole Blood Donor Iron Management Across Europe: Experiences and Challenges in Four Blood Establishments

Whole blood donors lose iron while donating and frequent blood donation is therefore known to induce a risk of iron deficiency and/or anemia. In this review we present, compare and discuss the pros and cons of 4 distinctive donor iron management strategies in England, Finland, the Netherlands, and Denmark. Donor iron management policies in the countries concerned are described for the year 2021, and data on donor and donation numbers, low hemoglobin (Hb) deferral rates and Hb levels are presented. In England Hb levels were only measured in donors failing a copper sulphate test, while in the other 3 countries Hb is measured at every donation. In Finland, donors considered at risk of iron deficiency receive iron supplements, while in the Netherlands, ferritin-guided donation intervals without iron supplementation are in place. In Denmark, iron supplementation is provided to donors with low ferritin levels. Low-Hb deferral rates and average Hb levels are quite similar across the included countries, with the exception of higher deferral rates in England. To conclude, despite significant diversity in donor iron management approaches, low Hb deferral rates and average Hb levels are similar among the included countries except for England, where higher deferral rates were observed that are likely attributed to the absence of iron supplementation or ferritin-guided deferral. Achieving an optimal, more tailored iron management strategy requires further research and a nuanced understanding of both donor demographics and physiological responses to optimize the effectiveness and safety of blood donation practices.

Donor knowledge and perceptions regarding donation-induced iron depletion and iron supplementation as a blood service policy.

Regular whole blood donations are associated with an increased risk of iron deficiency. Iron supplementation is an effective strategy to prevent donation-induced iron deficiency. However, research on donor perceptions towards such a policy is limited. Therefore, we aim to evaluate donors' knowledge on donation-induced iron depletion and their perceptions regarding iron supplementation as a blood service policy. Three thousand Dutch whole blood donors were invited to complete a survey assessing their knowledge of donation-induced iron depletion and attitudes and perceptions towards iron supplementation as a policy. Linear regression modelling was used to evaluate associations between explanatory variables and perceptions. In total, 1093 (77.1%) donors were included in the analysis. Donors had poor knowledge of current iron management policies, but a better understanding of iron metabolism and supplementation. Iron supplementation as a policy was perceived mainly positive by donors, and the majority were willing to use iron supplements if provided. Iron supplementation was not perceived as invasive or negatively affecting donors' motivation to continue donating. Additional iron monitoring, information and donor physician involvement were regarded as important conditions for implementation. Male sex, trust in the blood service, prior experience with iron supplements and openness towards dietary supplements were strongly positively associated with willingness to use iron supplementation. Donors' knowledge regarding donation-induced iron depletion is limited, but not associated with their perceptions regarding iron supplementation. Donors do not consider iron supplementation as invasive, deterring or demotivating, and a majority are willing to take supplements if offered.

External electron donor and transporter of iron triggers the paths to enhancing collaboration of anammox and denitrification in granular sludge: Bacterial resilience and synergetic promotion mechanism

Autotrophic nitrogen removal via anaerobic ammonium oxidation (anammox) technology currently faces significant challenges in treating low-strength wastewater due to inefficient retention of bacteria and unstable activity under fluctuating conditions. This study demonstrates enhanced resilience and stability of anammox coupled with partial denitrification (PD) in granular sludge, assisted by ferric iron (Fe(III)) and nano zero-valent iron (nZVI). The systems treated wastewater with low concentrations of ammonia (NH4+-N of 50 ∼ 80 mg/L) and nitrate (NO3−-N of 60 ∼ 100 mg/L). Fe(III) and nZVI were intermittently added to two PD coupled with anammox (PD/A) systems, which were subjected to increasing nitrogen loading rates (NLRs) and decreasing temperature. Remarkably, both Fe(III)- and nZVI-assisted systems achieved satisfactory total nitrogen (TN) removal efficiencies of 98.1 % and 96.6 %, respectively, even as the temperature dropped from 28.5℃ to 13.4℃ and the NLR increased from 0.22 to 0.72 kgN/m3/d. Significantly, these two systems exhibited pronounced resilience under the shocking effect of excessive organic load, extremely low pH, and high salinity. The presence of iron, acting as an accelerated electron transporter, enhanced anammox activity and microbial NH4+-N oxidation. Additionally, iron reduced the requirement for an organic carbon source, further stimulating the competitiveness of anammox for nitrite (NO2−-N) against denitrification. Interestingly, metagenomic analysis revealed that the functional bacteria Thauera, responsible for PD, employed versatile metabolic pathways for NO3−-N reduction to NO2−-N using Fe(II) as an electron donor. Overall, this study provides new insights into microbial interactions and versatile metabolism in iron-assisted anammox systems, contributing to more energy-efficient wastewater treatment.

Effectiveness of ferritin-guided donation intervals in whole-blood donors in the Netherlands (FIND'EM): a stepped-wedge cluster-randomised trial

Whole-blood donors are at increased risk for iron deficiency and anaemia. The current standard of haemoglobin monitoring is insufficient to ensure the maintenance of proper iron reserves and donor health. We aimed to determine the effects of ferritin-guided donation intervals for blood donor health and blood supply in the Netherlands. In this stepped-wedge cluster-randomised trial (FIND'EM), the 138 fixed and mobile donation centres in the Netherlands are organised into 29 geographical clusters and the clusters were randomly assigned to four treatment groups, with two groups being further split into two per a protocol amendment. Eligible donors were whole-blood donors who consented for use of their leftover material in the study. Each group was sequentially crossed over from the existing policy (haemoglobin-based screening; control) to a ferritin-guided donation interval policy over a 3-year period. In the intervention groups, in addition to the existing haemoglobin screening, ferritin was measured in all new donors and at every fifth donation in repeat donors. Subsequent donation intervals were extended to 6 months if ferritin concentrations were 15-30 ng/mL and to 12 months if they were less than 15 ng/mL. Outcomes were measured cross-sectionally across all donation centres at four timepoints. Primary outcomes were ferritin and haemoglobin concentrations, iron deficiency, and haemoglobin-based deferrals. We assessed all outcomes by sex and menopausal status and significance for primary outcomes was indicated by a p value of less than 0·0125. This trial is registered in the Dutch trial registry, NTR6738, and is complete. Between Sept 11, 2017, and Nov 27, 2020, 412 888 whole-blood donors visited a donation centre, and we did measurements on samples from 37 621 donations from 36 099 donors. Over 38 months, ferritin-guided donation intervals increased mean ferritin concentrations (by 0·18 log10 ng/mL [95% CI 0·15-0·22; p<0·0001] in male donors, 0·10 log10 ng/mL [0·06-0·15; p<0·0001] in premenopausal female donors, and 0·17 log10 ng/mL [0·12-0·21; p<0·0001] in postmenopausal female donors) and mean haemoglobin concentrations (by 0·30 g/dL [95% CI 0·22-0·38; p<0·0001] in male donors, 0·12 g/dL [0·03-0·20; p<0·0074] in premenopausal female donors, and 0·16 g/dL [0·05-0·27; p<0·0044] in postmenopausal female donors). Iron deficiency decreased by 36-38 months (odds ratio [OR] 0·24 [95% CI 0·18-0·31; p<0·0001] for male donors, 0·49 [0·37-0·64; p<0·0001] for premenopausal female donors, and 0·24 [0·15-0·37; p<0·0001] for postmenopausal female donors). At 36-38 months, haemoglobin-based deferral decreased significantly in male donors (OR at 36-38 months 0·21 [95% CI 0·10-0·40, p<0·0001]) but not significantly in premenopausal or postmenopausal female donors (0·81 [0·54-1·20; p=0·29] and 0·50 [95% CI 0·25-0·98; p=0·051], respectively). Ferritin-guided donation intervals significantly improved haemoglobin and ferritin concentrations and significantly decreased iron deficiency over the study period. Haemoglobin-based deferrals decreased significantly for male donors, but not female donors. Although this intervention is overall beneficial for maintenance of iron and haemoglobin concentrations in donors, increased efforts are needed to recruit and retain donors. The Sanquin Research Programming Committee.

Oral iron supplementation: new formulations, old questions.

Iron-deficiency anemia and pre-anemic iron deficiency are the most frequent pathologies. The first line of treatment involves oral iron supplementation. The simplest, least expensive, and most commonly prescribed drug is ferrous sulfate, while other ferrous salts and ferric complexes with polysaccharides or succinylated milk proteins are also widely used. In recent years, novel iron formulations have been developed, such as the lipophilic iron donor ferric maltol, or nanoparticle encapsulated sucrosomial® iron. Oral iron supplementation is usually efficacious in correcting iron-deficiency anemia and replenishing iron stores but causes gastrointestinal side effects that reduce compliance. When oral iron supplementation is contraindicated, intravenous iron therapy can rapidly achieve therapeutic targets without gastrointestinal complications. Herein, we critically review literature on relative efficacy and tolerability of currently available oral iron supplements, and summarize recent data on optimal dosage and frequency.

Dps Functions as a Key Player in Bacterial Iron Homeostasis.

Iron plays a vital role in the maintenance of life, being central to various cellular processes, from respiration to gene regulation. It is essential for iron to be stored in a nontoxic and readily available form. DNA binding proteins under starvation (Dps) belong to the ferritin family of iron storage proteins and are adept at storing iron in their hollow protein shells. Existing solely in prokaryotes, these proteins have the additional functions of DNA binding and protection from oxidative stress. Iron storage proteins play a functional role in storage, release, and transfer of iron and therefore are central to the optimal functioning of iron homeostasis. Here we review the multifarious properties of Dps through relevant biochemical and structural studies with a focus on iron storage and ferroxidation. We also examine the role of Dps as a possible candidate as an iron donor to iron-sulfur (Fe-S) clusters, which are ubiquitous to many biological processes.

Examining Prenatal Dietary Factors in Association with Child Autism-Related Traits Using a Bayesian Mixture Approach: Results from 2 United States Cohorts

BackgroundPrior work has suggested relationships between prenatal intake of certain nutrients and autism. ObjectivesWe examined a broad set of prenatal nutrients and foods using a Bayesian modeling approach. MethodsParticipants were drawn from the Early Autism Risks Longitudinal Investigation (n = 127), a cohort following women with a child with autism through a subsequent pregnancy. Participants were also drawn from the Nurses’ Health Study II (NHSII, n = 713), a cohort of United States female nurses, for comparison analyses. In both studies, information on prospectively reported prenatal diet was drawn from food frequency questionnaires, and child autism-related traits were measured by the Social Responsiveness Scale (SRS). Bayesian kernel machine regression was used to examine the combined effects of several nutrients with neurodevelopmental relevance, including polyunsaturated fatty acids (PUFAs), iron, zinc, vitamin D, folate, and other methyl donors, and separately, key food sources of these, in association with child SRS scores in crude and adjusted models. ResultsIn adjusted analyses, the overall mixture effects of nutrients in Early Autism Risks Longitudinal Investigation and foods in both cohorts on SRS scores were not observed, though there was some suggestion of decreasing SRS scores with increasing overall nutrient mixture in NHSII. No associations were observed with folate within the context of this mixture, but holding other nutrients fixed, n–6 PUFAs were associated with lower SRS scores in NHSII. In both cohorts, lower SRS scores were observed with higher intake of some groupings of vegetables, though for differing types of vegetables across cohorts, and some vegetable groups were associated with higher SRS scores in NHSII. ConclusionsOur work extends prior research and suggests the need to further consider prenatal dietary factors from a combined effects perspective. In addition, findings here point to potential differences in nutrient associations based on a family history of autism, which suggests the need to consider gene interactions in future work.

Deep denitrification: Stream and groundwater biogeochemistry reveal contrasted but connected worlds above and below

Excess nutrients from agricultural and urban development have created a cascade of ecological crises around the globe. Nutrient pollution has triggered eutrophication in most freshwater and coastal ecosystems, contributing to a loss in biodiversity, harm to human health, and trillions in economic damage every year. Much of the research conducted on nutrient transport and retention has focused on surface environments, which are both easy to access and biologically active. However, surface characteristics of watersheds, such as land use and network configuration, often do not explain the variation in nutrient retention observed in rivers, lakes, and estuaries. Recent research suggests subsurface processes and characteristics may be more important than previously thought in determining watershed-level nutrient fluxes and removal. In a small watershed in western France, we used a multi-tracer approach to compare surface and subsurface nitrate dynamics at commensurate spatiotemporal scales. We combined 3-D hydrological modeling with a rich biogeochemical dataset from 20 wells and 15 stream locations. Water chemistry in the surface and subsurface showed high temporal variability, but groundwater was substantially more spatially variable, attributable to long transport times (10–60 years) and patchy distribution of the iron and sulfur electron donors fueling autotrophic denitrification. Isotopes of nitrate and sulfate revealed fundamentally different processes dominating the surface (heterotrophic denitrification and sulfate reduction) and subsurface (autotrophic denitrification and sulfate production). Agricultural land use was associated with elevated nitrate in surface water, but subsurface nitrate concentration was decoupled from land use. Dissolved silica and sulfate are affordable tracers of residence time and nitrogen removal that are relatively stable in surface and subsurface environments. Together, these findings reveal distinct but adjacent and connected biogeochemical worlds in the surface and subsurface. Characterizing how these worlds are linked and decoupled is critical to meeting water quality targets and addressing water issues in the Anthropocene.

Hsp90 and J-protein family chaperones are not directly involved in cellular iron-sulfur protein assembly and iron regulation in yeast.

Systematic studies have revealed interactions between components of the Hsp90 chaperone system and Fe/S protein biogenesis or iron regulation. In addition, two chloroplast-localized DnaJ-like proteins, DJA5 and DJA6, function as specific iron donors in plastidial Fe/S protein biogenesis. Here, we used Saccharomyces cerevisiae to study the impact of both the Hsp90 chaperone and the yeast DJA5-DJA6 homologs, the essential cytosolic Ydj1 and the mitochondrial Mdj1, on cellular iron-related processes. Despite severe phenotypes induced upon depletion of these crucial proteins, there was no critical in vivo impact on Fe/S protein biogenesis or iron regulation. Importantly, unlike the plant DJA5-DJA6 iron chaperones, Ydj1 and Mdj1 did not bind iron in vivo, suggesting that these proteins use zinc for function under normal physiological conditions.

Molecular typing to personalise donor donation frequency

Blood donors can lose up to 200–250 mg of iron per whole blood donation, significantly increasing their risk of iron deficiency and anaemia. Recovery of donor iron stores following whole blood donation varies considerably. Using genomic DNA from blood donors, we have reported preliminary data for two molecular typing strategies to profile genetic variants associated with iron metabolism and storage.1,2 These studies on small numbers of donors using next generation sequencing (NGS) for a panel of genes associated with iron homeostasis2,3 and TaqMan arrays for 10 selected single-nucleotide polymorphisms (SNP)1 established proof-of-principle. Future work of this nature must consider the advantages of each tool. NGS, is more expensive and time consuming for both testing and data analysis, however, is required for identification of variants of significance in donor iron recovery. TaqMan is a fast, convenient, and less expensive tool to rapidly identify a donor’s variant profile for individual management. A two-stage approach would benefit future studies. First, a large-scale survey using sequencing techniques to identify genetic variants associated with recovery of post-donation iron stores. Second, rapid testing with a less expensive tool such as TaqMan suitable for rapid testing and individual tailoring of blood donation frequency.

Endometriosis-Associated Mesenchymal Stem Cells Support Ovarian Clear Cell Carcinoma through Iron Regulation.

Endometriosis-derived mesenchymal stem cells support ovarian clear cell carcinoma via iron donation necessary for cancer growth, which also confers sensitivity to ferroptosis-inducing therapy.

Fe‐based catalyst with diphenylphosphite as donor for stereopolymerization of butadiene, isoprene, and myrcene

AbstractIron catalyst has been encountered with low activity and stereoselectivity sensitive to the operational conditions for diene polymerization. In this study, diphenylphosphite has been proved as an efficient donor in iron‐based tertiary catalyst for butadiene, isoprene and myrcene stereopolymerizations. Thermal robustness of active species has been demonstrated as the high activity and 1,2 stereoselectivity are survived in a wide temperature scope ranging from 5°C to 80°C. The resultant polybutadienes are found to have 1,2 incorporation up to 92.8% with syndiotactic conformation (rrrr: 95.1%), and more than 65% of irregular 3,4 enchainments are generated for polyisoprene and polymyrcene. The active species are formed preferably following addition sequence of iron compound, donor and activator in the presence of monomer. The development of this highly active and stable catalyst combining cost‐efficient components and mild operation parameters could provide accessible catalyst recipe to produce new types of polydienes.

A randomized trial of blood donor iron repletion on red cell quality for transfusion and donor cognition and well-being

AbstractAlthough altruistic regular blood donors are vital for the blood supply, many become iron deficient from donation-induced iron loss. The effects of blood donation–induced iron deficiency on red cell transfusion quality or donor cognition are unknown. In this double-blind, randomized trial, adult iron-deficient blood donors (n = 79; ferritin < 15 μg/L and zinc protoporphyrin >60 μMol/mol heme) who met donation qualifications were enrolled. A first standard blood donation was followed by the gold-standard measure for red cell storage quality: a 51-chromium posttransfusion red cell recovery study. Donors were then randomized to intravenous iron repletion (1 g low-molecular-weight iron dextran) or placebo. A second donation ∼5 months later was followed by another recovery study. Primary outcome was the within-subject change in posttransfusion recovery. The primary outcome measure of an ancillary study reported here was the National Institutes of Health Toolbox–derived uncorrected standard Cognition Fluid Composite Score. Overall, 983 donors were screened; 110 were iron-deficient, and of these, 39 were randomized to iron repletion and 40 to placebo. Red cell storage quality was unchanged by iron repletion: mean change in posttransfusion recovery was 1.6% (95% confidence interval −0.5 to 3.8) and −0.4% (−2.0 to 1.2) with and without iron, respectively. Iron repletion did not affect any cognition or well-being measures. These data provide evidence that current criteria for blood donation preserve red cell transfusion quality for the recipient and protect adult donors from measurable effects of blood donation–induced iron deficiency on cognition. This trial was registered at www.clinicaltrials.gov as NCT02889133 and NCT02990559.

Exogenous iron impairs the anti-cancer effect of ascorbic acid both in vitro and in vivo

IntroductionThe anti-cancer effect of high concentrations of ascorbic acid (AA) has been well established while its underlying mechanisms remain unclear. The association between iron and AA has attracted great attention but was still controversial due to the complicated roles of iron in tumors. ObjectivesOur study aims to explore the anti-cancer mechanisms of AA and the interaction between AA and iron in cancer. MethodsThe MTT and ATP assays were used to evaluate the cytotoxicity of AA. Reactive oxygen species (ROS) generation, calcium (Ca2+), and lipid peroxidation were monitored with flow cytometry. Mitochondrial dysfunction was assessed by mitochondrial membrane potential (MMP) detection with JC-1 or tetramethylrhodamine methyl ester (TMRM) staining. Mitochondrial swelling was monitored with MitoTracker Green probe. FeSO4 (Fe2+), FeCl3 (Fe3+), Ferric ammonium citrate (Fe3+), hemin chloride (Fe3+) were used as an iron donor to investigate the effects of iron on AA’s anti-tumor activity. The in vivo effects of AA and iron were analyzed in xenograft zebrafish and allograft mouse models. ResultsHigh concentrations of AA exhibited cytotoxicity in a panel of cancer cells. AA triggered ROS-dependent non-apoptotic cell death. AA-induced cell death was essentially mediated by the accumulated intracellular Ca2+, which was partly originated from endoplasmic reticulum (ER). Surprisingly, exogenous iron could significantly reverse AA-induced ROS generation, Ca2+ overloaded, and cell death. Especially, the iron supplements significantly impaired the in vivo anti-tumor activity of AA. ConclusionsOur study elucidated the protective roles of iron in ROS/Ca2+ mediated necrosis triggered by AA both in vitro and in vivo, which might shed novel insight into the anti-cancer mechanisms and provide clinical application strategies for AA in cancer treatment.

Repair of Iron Center Proteins-A Different Class of Hemerythrin-like Proteins.

Repair of Iron Center proteins (RIC) form a family of di-iron proteins that are widely spread in the microbial world. RICs contain a binuclear nonheme iron site in a four-helix bundle fold, two basic features of hemerythrin-like proteins. In this work, we review the data on microbial RICs including how their genes are regulated and contribute to the survival of pathogenic bacteria. We gathered the currently available biochemical, spectroscopic and structural data on RICs with a particular focus on Escherichia coli RIC (also known as YtfE), which remains the best-studied protein with extensive biochemical characterization. Additionally, we present novel structural data for Escherichia coli YtfE harboring a di-manganese site and the protein’s affinity for this metal. The networking of protein interactions involving YtfE is also described and integrated into the proposed physiological role as an iron donor for reassembling of stress-damaged iron-sulfur centers.

The Di-Iron Protein YtfE Is a Nitric Oxide-Generating Nitrite Reductase Involved in the Management of Nitrosative Stress.

Previously characterized nitrite reductases fall into three classes: siroheme-containing enzymes (NirBD), cytochrome c hemoproteins (NrfA and NirS), and copper-containing enzymes (NirK). We show here that the di-iron protein YtfE represents a physiologically relevant new class of nitrite reductases. Several functions have been previously proposed for YtfE, including donating iron for the repair of iron–sulfur clusters that have been damaged by nitrosative stress, releasing nitric oxide (NO) from nitrosylated iron, and reducing NO to nitrous oxide (N2O). Here, in vivo reporter assays confirmed that Escherichia coli YtfE increased cytoplasmic NO production from nitrite. Spectroscopic and mass spectrometric investigations revealed that the di-iron site of YtfE exists in a mixture of forms, including nitrosylated and nitrite-bound, when isolated from nitrite-supplemented, but not nitrate-supplemented, cultures. Addition of nitrite to di-ferrous YtfE resulted in nitrosylated YtfE and the release of NO. Kinetics of nitrite reduction were dependent on the nature of the reductant; the lowest Km, measured for the di-ferrous form, was ∼90 μM, well within the intracellular nitrite concentration range. The vicinal di-cysteine motif, located in the N-terminal domain of YtfE, was shown to function in the delivery of electrons to the di-iron center. Notably, YtfE exhibited very low NO reductase activity and was only able to act as an iron donor for reconstitution of apo-ferredoxin under conditions that damaged its di-iron center. Thus, YtfE is a high-affinity, low-capacity nitrite reductase that we propose functions to relieve nitrosative stress by acting in combination with the co-regulated NO-consuming enzymes Hmp and Hcp.

Physiologically based serum ferritin thresholds for iron deficiency in women of reproductive age who are blood donors

AbstractOur objective is to develop a physiologically based method to determine serum ferritin thresholds for iron deficiency in healthy individuals. The current World Health Organization threshold of <15 µg/L for iron deficiency in women is based on expert opinion. We examined the relationship between serum ferritin and 2 independently measured indicators of iron-deficient erythropoiesis, soluble transferrin receptor (sTfR) and hemoglobin, in baseline data from 286 women, 20 to 49 years, who were first-time or reactivated donors in the Retrovirus Epidemiology Donor Study-II Donor Iron Status Evaluation (REDS-RISE) study. At lower serum ferritin concentrations, median sTfR increased as hemoglobin decreased. Using restricted cubic spline regression analysis to determine thresholds for iron-deficient erythropoiesis, the thresholds identified by sTfR (serum ferritin < 25.4 µg/L) and hemoglobin (serum ferritin < 25.3 µg/L) did not differ significantly. The thresholds found in the REDS-RISE study do not differ from those identified by sTfR (serum ferritin < 25.5 µg/L) and hemoglobin (serum ferritin < 26.6 µg/L) in a previous study of 5442 women, 20 to 49 years, in the US National Health and Nutrition Examination Survey 2003 to 2018 (P = .98 and 0.83, respectively). Although international comparisons are needed, these results with US data provide additional evidence for the potential usefulness of a physiologically based method to identify serum ferritin thresholds for iron deficiency.

Methane formation driven by reactive oxygen species across all living organisms.

Methane (CH4), the most abundant hydrocarbon in the atmosphere, originates largely from biogenic sources1 linked to an increasing number of organisms occurring in oxic and anoxic environments. Traditionally, biogenic CH4 has been regarded as the final product of anoxic decomposition of organic matter by methanogenic archaea. However, plants2,3, fungi4, algae5 and cyanobacteria6 can produce CH4 in the presence of oxygen. Although methanogens are known to produce CH4 enzymatically during anaerobic energy metabolism7, the requirements and pathways for CH4 production by non-methanogenic cells are poorly understood. Here, we demonstrate that CH4 formation by Bacillus subtilis and Escherichia coli is triggered by free iron and reactive oxygen species (ROS), which are generated by metabolic activity and enhanced by oxidative stress. ROS-induced methyl radicals, which are derived from organic compounds containing sulfur- or nitrogen-bonded methyl groups, are key intermediates that ultimately lead to CH4 production. We further show CH4 production by many other model organisms from the Bacteria, Archaea and Eukarya domains, including in several human cell lines. All these organisms respond to inducers of oxidative stress by enhanced CH4 formation. Our results imply that all living cells probably possess a common mechanism of CH4 formation that is based on interactions among ROS, iron and methyl donors, opening new perspectives for understanding biochemical CH4 formation and cycling.

Ferritin-guided iron supplementation in whole blood donors: optimal dosage, donor response, return and efficacy (FORTE)—a randomised controlled trial protocol

BackgroundFrequent whole blood donors have an increased risk of developing iron deficiency. Iron deficiency can have detrimental health effects when left untreated. Donation intervals are commonly too short to replenish...

Monitoring iron stores in Icelandic blood donors from 1997 through 2019.

To estimate the frequency of iron deficiency (ID) and anaemia in blood donors in Iceland and the impact of serum ferritin (SF) testing policy change. Blood donations contribute to ID and/or anaemia in whole blood donors (WBD). SF may be used to monitor blood donor iron stores. The study included WBD and new donors (ND) in the Icelandic Blood Bank in 1997-2019. SF was measured for ND and intermittently for WBD until October 2017, but thereafter for all WBD and ND at every visit. In January 2018, the SF threshold increased from 14 to 16 μg/L for ND and from 8 to 10μg/L for WBD. The study included 85 370 SF results from 243 369 visits of 32 910 donors. Median SF was higher for males than females, both for ND (88.0 vs. 31.2 μg/L, p < 0.001) and WBD (before 2018: 43.0 vs. 22.0 μg/L, p < 0.001). After the policy change in 2018, median SF increased for both male WBD (to 45.2μg/L, p < 0.001) and female WBD (to 25.7μg/L, p < 0.001). ID (SF <15 μg/L) was present in 10.6% of female ND and 0.5% of male ND. After policy change, the proportion of WB donations associated with ID decreased for males (from 6.4% to 4.0%) and females (from 18.9% to 14.1%). ID anaemia was present at some time in 3.7% of female WBD and 1.2% of male WBD. This nationwide study showed that ID in WB donors is common, especially among females, but monitoring SF may improve donor management.