Corrigendum: Safe and effective delivery of supplemental iron to healthy adults: a two-phase, randomized, double-blind trial - the safe iron study.

[This corrects the article DOI: 10.3389/fnut.2023.1230061.].

Safe and effective delivery of supplemental iron to healthy adults: a two-phase, randomized, double-blind trial - the safe iron study.

Introduction: The safety of novel forms of iron in healthy, iron-replete adults as might occur if used in population-based iron supplementation programs was examined. We tested the hypotheses that supplementation with nanoparticulate iron hydroxide adipate tartrate (IHAT), an iron-enriched Aspergillus oryzae product (ASP), or ferrous sulphate heptahydrate (FS) are safe as indicated by erythrocyte susceptibility to malarial infection, bacterial proliferation, and gut inflammation. Responses to FS administered daily or weekly, and with or without other micronutrients were compared. Methods: Two phases of randomized, double-blinded trials were conducted in Boston, MA. Phase I randomized 160 volunteers to six treatments: placebo, IHAT, ASP, FS, and FS plus a micronutrient powder (MNP) administrated daily at 60 mg Fe/day; and FS administered as a single weekly dose of 420 mg Fe. Phase II randomized 86 volunteers to IHAT, ASP, or FS administered at 120 mg Fe/day. Completing these phases were 151 and 77 participants, respectively. The study was powered to detect effects on primary endpoints: susceptibility of participant erythrocytes to infection by Plasmodium falciparum, the proliferation potential of selected pathogenic bacteria in sera, and markers of gut inflammation. Secondary endpoints for which the study was not powered included indicators of iron status and gastrointestinal symptoms. Results: Supplementation with any form of iron did not affect any primary endpoint. In Phase I, the frequency of gastrointestinal symptoms associated with FS was unaffected by dosing with MNP or weekly administration; but participants taking IHAT more frequently reported abdominal pain (27%, p < 0.008) and nausea (4%, p = 0.009) than those taking FS, while those taking ASP more frequently reported nausea (8%, p = 0.009). Surprisingly, only 9% of participants taking IHAT at 120 mg Fe/day (Phase II) reported abdominal pain and no other group reported that symptom. Discussion: With respect to the primary endpoints, few differences were found when comparing these forms of iron, indicating that 28 days of 60 or 120 mg/day of IHAT, ASP, or FS may be safe for healthy, iron-replete adults. With respect to other endpoints, subjects receiving IHAT more frequently reported abdominal pain and nausea, suggesting the need for further study. Clinical Trial Registration: ClinicalTrials.gov, NCT03212677; registered: 11 July 2017.

Genomic analysis of oceanic cyanobacterial myoviruses compared with T4-like myoviruses from diverse hosts and environments.

T4-like myoviruses are ubiquitous, and their genes are among the most abundant documented in ocean systems. Here we compare 26 T4-like genomes, including 10 from non-cyanobacterial myoviruses, and 16 from marine cyanobacterial myoviruses (cyanophages) isolated on diverse Prochlorococcus or Synechococcus hosts. A core genome of 38 virion construction and DNA replication genes was observed in all 26 genomes, with 32 and 25 additional genes shared among the non-cyanophage and cyanophage subsets, respectively. These hierarchical cores are highly syntenic across the genomes, and sampled to saturation. The 25 cyanophage core genes include six previously described genes with putative functions (psbA, mazG, phoH, hsp20, hli03, cobS), a hypothetical protein with a potential phytanoyl-CoA dioxygenase domain, two virion structural genes, and 16 hypothetical genes. Beyond previously described cyanophage-encoded photosynthesis and phosphate stress genes, we observed core genes that may play a role in nitrogen metabolism during infection through modulation of 2-oxoglutarate. Patterns among non-core genes that may drive niche diversification revealed that phosphorus-related gene content reflects source waters rather than host strain used for isolation, and that carbon metabolism genes appear associated with putative mobile elements. As well, phages isolated on Synechococcus had higher genome-wide %G+C and often contained different gene subsets (e.g. petE, zwf, gnd, prnA, cpeT) than those isolated on Prochlorococcus. However, no clear diagnostic genes emerged to distinguish these phage groups, suggesting blurred boundaries possibly due to cross-infection. Finally, genome-wide comparisons of both diverse and closely related, co-isolated genomes provide a locus-to-locus variability metric that will prove valuable for interpreting metagenomic data sets.

Quantifying gastric Helicobacter pylori infection: a comparison of quantitative culture, urease breath testing, and histology.

Although there are several methods to detect Helicobacter pylori infection, there is no simple validated test to quantify the density of infection, which is believed to play a major role in the pathogenesis of H. pylori-associated gastritis and peptic ulceration. The aim of this study was to evaluate and compare noninvasive and invasive tests for assessing the level of H. pylori infection so as to facilitate the development and clinical testing of new antibiotic treatments. Healthy volunteers (n=323) were screened for H. pylori infection by serology and, if positive (n=86), invited to undergo (13)C urea breath testing (UBT) (n=55). An increase of >2.4 parts per thousand (13)CO(2) at 15 min compared to baseline was considered a positive test. Total cumulative urease activity (mumol) at 60 min was also calculated. UBT-positive subjects underwent endoscopy and nine biopsies were obtained from defined sites for quantitative culture and histological grading using the modified Sydney System. A total of 19 subjects were studied, 4 of whom underwent repeat testing. All subjects were positive for H. pylori by serology, UBT, culture, and histology. The increase in (13)CO(2) at 30 min correlated with the total cumulative urease activity at 60 min (r (2)=0.92, P< 0.0001). Bacterial counts (log cfu/biopsy; mean+/-SD) were 3.9+/-0.5, 3.9+/-0.4, and 3.9+/-0.6 at the lesser curve antrum, greater curve antrum, and corpus, respectively. There was no significant correlation between UBT results and bacterial counts at any biopsy site. Nor was there any significant correlation between the histology grading and either the UBT or the bacterial counts at any site. This study indicates that there is little correlation among the three methods used to measure bacterial burden in H. pylori infection. Thus, decrements in bacterial numbers during single-agent therapy cannot be measured reliably by UBT and therefore cannot be used to evaluate the potential efficacy of novel agents to treat gastric H. pylori infection.