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Objective: Micronutrient status, specifically vitamin D and iron, represent modifiable factors for optimizing military readiness. The primary purpose of this investigation was to determine associations between micronutrient deficiency (i.e., iron status and 25-hydroxy-vitamin D [25(OH)D]) and operationally relevant outcomes (i.e., skeletal health, musculoskeletal injury) at baseline and post-10 weeks of arduous military training. Methods: A total of 227 (177 men, 50 women) Marine Officer Candidates School (OCS) candidates who completed OCS training with complete data sets were included in this analysis. Vitamin D and iron status indicators were collected at two timepoints, pre (baseline) and post OCS. Musculoskeletal outcomes at the mid- and proximal tibial diaphysis were assessed via peripheral quantitative computed tomography. Results: Micronutrient status declined following OCS training in men and women and was associated with musculoskeletal outcomes including greater bone strength (strength strain index) at the mid-diaphysis site in those with optimal status (M = 38.26 mm3, SE = 15.59) versus those without (M = −8.03 mm3, SE = 17.27). In women (p =.037), endosteal circumference was greater in the deficient group (M = 53.26 mm, SE = 1.19) compared with the optimal group (M = 49.47 mm, SE = 1.31) at the proximal diaphysis. In men, greater baseline hepcidin concentrations were associated with an increased likelihood of suffering musculoskeletal injury during training. Conclusions: Vitamin D and iron status declined over the course of training, suggesting impaired micronutrient status. Differences in musculoskeletal outcomes by micronutrient group suggests optimal vitamin D and ferritin concentrations may exert beneficial effects on bone fatigability and fracture reduction during military training. [ABSTRACT FROM AUTHOR]

Various erythropoietic abnormalities are highly prevalent among patients with pulmonary arterial hypertension (PAH) and associated with worse disease severity. Given the poorly understood yet important roles of dysregulated erythropoiesis and iron metabolism in PAH, we sought to further characterize the hematologic and iron profiles in PAH and their relationship to PAH severity. We recruited 67 patients with PAH and 13 healthy controls. Hemodynamics attained within 1 year of blood sample collection were available for 36 patients. Multiple hematologic, iron, and inflammatory parameters were evaluated for their association with hemodynamics. The subset with hemodynamic data consisted of 29 females (81%). The most common etiologies were idiopathic PAH (47%) and connective tissue disease-related PAH (33%). 19 (53%) had functional class 3 or 4 symptomatology, and 12 (33%) were on triple pulmonary vasodilator therapy. Immature reticulocyte fraction (IRF) had significant positive correlations with mean pulmonary artery (PA) pressure (mPAP) (0.59, p

Animal flesh foods are rich in bioavailable iron but infrequently consumed by young children. We aimed to determine whether flesh food intake was associated with iron and anaemia status among 585 Malawian infants enroled in a 6-month egg-feeding trial. The percentage of days of small fish, large fish and meat consumption were assessed through weekly 7-day animal-source food screeners. Grams of intake were assessed through 24-h recalls conducted at 6-9, 9-12 and 12-15 months of age. Plasma ferritin, soluble transferrin receptor (sTfR) and haemoglobin concentrations were measured at 6-9 and 12-15 months of age. Iron biomarkers were adjusted for inflammation during analysis. At enrolment, each flesh food category was consumed by

It is estimated that billions of people around the world are affected by micronutrient deficiencies. Madagascar is considered to be particularly nutritionally vulnerable, with nearly half of the population stunted, and parts of the country facing emergency, near famine-like conditions (IPC4). Although Madagascar is generally considered among the most undernourished of countries, empirical data in the form of biological samples to validate these claims are extremely limited. Our research drew data from three studies conducted between 2013-2020 and provided comprehensive biomarker profile information for 4,710 individuals from 30 communities in five different ecological regions during at least one time-point. Estimated prevalences of nutrient deficiencies and inflammation across various regions of rural Madagascar were of concern for both sexes and across all ages, with 66.5% of the population estimated to be deficient in zinc, 15.6% depleted in vitamin B12 (3.6% deficient), 11.6% deficient in retinol, and lower levels of iron deficiency (as indicated by 11.7% deficient in ferritin and 2.3% deficient assessed by soluble transferrin receptors). Beyond nutrient status biomarkers, nearly one quarter of the population (24.0%) exhibited chronic inflammation based on high values of α-1-acid glycoprotein, and 12.3% exhibited acute inflammation based on high values of C-reactive protein. There is an 8-fold difference between the lowest and highest regional observed prevalence of vitamin B12 deficiency, a 10-fold difference in vitamin A deficiency (based on retinol), and a 2-fold difference in acute inflammation (CRP) and deficiencies of zinc and iron (based on ferritin), highlighting strong geographical variations in micronutrient deficiencies across Madagascar.

Anaemia among women and young children remains a major public health concern. This secondary study describes the anaemia prevalence among young hospitalised children and their mothers in northern Lao Peoples Democratic Republic and explores possible nutritional causes and risk factors for anaemia. Hospitalised children (ages 21 days to

Iron deficiency is prevalent worldwide, and iron supplementation is a promising strategy to address iron needs of the body. However, traditional oral supplements such as ferrous sulfate, ferrous succinate, and ferrous gluconate are absorbed in the form of ferrous ions, leading to lipid peroxidation and side effects due to other reasons. In recent years, saccharide-iron (III) complexes (SICs) as novel iron supplements have aroused attention for the high iron absorption rate and no gastrointestinal irritation at oral doses. In addition, research on the biological activities of SICs revealed that they also exhibited good abilities in treating anemia, eliminating free radicals, and regulating the immune response. This review focused on the preparation, structural characterization, and bioactivities of these new iron supplements, as promising candidates for the prevention and treatment of iron deficiency. [ABSTRACT FROM AUTHOR]

AbstractSickle cell disease (SCD) is a prevalent inherited blood disorder arising from a single point mutation that results in substitution of valine with glutamic acid in the Beta hemoglobin chain, making red blood cells assume a banana shape under low oxygen state. It is most prevalent in sub-Saharan Africa, affecting approximately 2% of the population in Mali. This study aimed to evaluate the iron status and associated hematological parameters in SCD patients at steady state in an environment with a high prevalence of iron deficiency. A cross-sectional study was conducted at the Center de Recherche et de Lutte contre la Drépanocytose (CRLD) in Bamako, Mali, involving 757 SCD patients aged 10 to 29 years. Iron deficiency was defined as serum ferritin < 20 ng/mL, while iron overload was associated with serum ferritin > 500 ng/mL. The study population consisted of 171 (22.6%) hemolytic phenotypes (SS and Sβ0) and 586 (77.4%) viscous phenotypes (SC and Sβ+). Iron deficiency was found in 19 SCD patients (2.5%), with a higher prevalence in the SC phenotype (68.4%). All iron-deficient subjects exhibited microcytosis (MCV < 80 fL) and hypochromia (MCH < 26 pg). Hemoglobin levels < 12 g/dL were observed only in homozygous SCD patients. Low reticulocyte counts were noted in iron-deficient subjects with SC and Sβ+ phenotypes, but not in iron-deficient SS subjects. Serum C-reactive protein (CRP) was normal (< 10 mg/L) in all iron-deficient subjects, excluding iron deficiency due to chronic inflammation. Iron deficiency was observed among 2.5% of the study population, with a predominant occurrence among those with SC phenotype. All iron deficient subjects had microcytosis and hypochromia. Hemoglobin levels below 12 g/dL were only found in homozygous SCD patients. Additionally, low reticulocyte counts were noted in iron deficient patients with SC and Sβ+ phenotypes, though not in those with the SS phenotype. These findings contribute to the understanding of iron status in SCD patients in an African context and highlights the importance of monitoring iron levels in these population to prevent complications associated with iron deficiency or overload. [ABSTRACT FROM AUTHOR]

Iron deficiency and iron deficiency anaemia are frequently under-recognised in chronic conditions with non-specific symptoms, including fatigue. This study aimed to assess the prevalence of iron deficiency with or without anaemia in chronic pain patients, and the association between iron deficiency status, fatigue and health-related quality of life. Eighty-two patients attending chronic pain outpatient appointments were recruited into this cross-sectional study. Iron studies and haemoglobin were determined from venous blood samples. Participants' health-related quality of life was assessed with the 36-item short form survey and fatigue with the functional assessment of chronic illness therapy fatigue scale. Iron deficiency was prevalent in 58.8% of patients and 2.5% met the criteria for iron deficiency anaemia. There was no significant association between iron deficiency status and the functional assessment of chronic illness therapy fatigue scale score or 36-item short form survey domain scores. There was a high prevalence of iron deficiency in this group of chronic pain patients, while the prevalence of iron deficiency anaemia was low. There was no statistically significant association found between iron deficiency status and fatigue or quality of life measures. [ABSTRACT FROM AUTHOR]

Postnatal iron deficiency, especially from ages 6 to 24 months, has long-term consequences lasting into adolescence and adulthood. We aimed to characterize iron deficiency anemia among infants from one central Israeli district by demographic and laboratory parameters. A retrospective chart review was performed on all infants from a single district who had undergone a complete blood count as part of a routine survey for iron deficiency anemia during 2010–2021. Data retrieved included hemoglobin levels, mean corpuscular volume, and demographic features: sex, sector (non-ultraorthodox Jew, ultraorthodox Jew, and Arab), socioeconomic status, and type of residence. The study group comprised 101,650 infants, aged 9 to 18 months. Iron deficiency anemia, defined as a hemoglobin level <11 g/dL and mean corpuscular volume <70 fl was observed in 4296 (4.2%) of the study infants. Iron deficiency anemia was more prevalent among Arab and ultraorthodox Jewish infants, than non-ultraorthodox Jewish infants (6.6% vs. 6% vs. 3%, respectively). It was also more prevalent among infants of low socioeconomic status, and relatively common among infants of rural residence. We identified two specific sub-populations at risk of developing iron deficiency anemia: Arab and ultraorthodox Jewish infants. We recommend enhancing the nationwide intervention program for both clinicians and parents, thereby treating iron deficiency anemia promptly to avoid short- and long-term deleterious health consequences. [ABSTRACT FROM AUTHOR]

Iron deficiency is a widespread global health concern with varying prevalence rates across different regions. In developing countries, scarcity of food and chronic infections contribute to iron deficiency, while in industrialized nations, reduced food intake and dietary preferences affect iron status. Other causes that can lead to iron deficiency are conditions and diseases that result in reduced intestinal iron absorption and blood loss. In addition, iron absorption and its bioavailability are influenced by the composition of the diet. Individuals with increased iron needs, including infants, adolescents, and athletes, are particularly vulnerable to deficiency. Severe iron deficiency can lead to anemia with performance intolerance or shortness of breath. In addition, even without anemia, iron deficiency leads to mental and physical fatigue, which points to the fundamental biological importance of iron, especially in mitochondrial function and the respiratory chain. Standard oral iron supplementation often results in gastrointestinal side effects and poor compliance. Low-dose iron therapy seems to be a valid and reasonable therapeutic option due to reduced hepatic hepcidin formation, facilitating efficient iron resorption, replenishment of iron storage, and causing significantly fewer side effects. Elevated iron levels influence gut microbiota composition, favoring pathogenic bacteria and potentially disrupting metabolic and immune functions. Protective bacteria, such as bifidobacteria and lactobacilli, are particularly susceptible to increased iron levels. Dysbiosis resulting from iron supplementation may contribute to gastrointestinal disorders, inflammatory bowel disease, and metabolic disturbances. Furthermore, gut microbiota alterations have been linked to mental health issues. Future iron therapy should consider low-dose supplementation to mitigate adverse effects and the impact on the gut microbiome. A comprehensive understanding of the interplay between iron intake, gut microbiota, and human health is crucial for optimizing therapeutic approaches and minimizing potential risks associated with iron supplementation. [ABSTRACT FROM AUTHOR]

Background: Pre‐operative iron deficiency anaemia (IDA) is common in patients undergoing elective major abdominal surgery and is associated with increased risk of perioperative complications. However, widespread implementation of pre‐operative anaemia management is lacking. Guidelines recommend investigation of anaemia preferably 4–6 weeks before surgery to allow time for correction. However, this is not always feasible in abdominal cancer surgery with short time to surgery and may be influenced by concomitant chemotherapy. The objective of this study was to assess the efficacy of implementing a pre‐operative screening and treatment programme for IDA in elective abdominal cancer surgery patients, with short duration to surgery and concomitant use of chemotherapy. Methods: All patients scheduled for elective abdominal cancer surgery with IDA were included. Anaemia was defined according to the World Health Organization‐criteria and iron deficiency as a transferrin saturation <0.20. The primary outcome was change in haemoglobin (Hb) between iron infusion and surgery in patients receiving pre‐operative intravenous iron infusion. Results: Of 178 diagnosed IDA patients 134 (75%) received intravenous iron, 103 pre‐operatively (58%) at median day 17 (interquartile range: 9–27) before surgery while 31 (17%) received post‐operative intravenous iron treatment. The pre‐operative Hb increased 0.89 g/dL (95% CI: 0.64–1.13, p <.001) compared to a decrease of 0.4 g/dL (95% CI: 0.19–0.58, p <.001) in 75 patients not treated pre‐operatively. Patients diagnosed with severe anaemia had the largest pre‐operative Hb increase. Iron infusion >2 weeks pre‐operatively resulted in a greater Hb increment of 1.13 g/dL (95% CI: 0.81–1.45) compared to iron infusion ≤2 weeks before surgery 0.48 g/dL (95% CI: 0.16–0.81). Hb increased by 0.64 g/dL (95% CI 0.19–1.21) in patients receiving chemotherapy ≤31 days prior to surgery. Conclusion: In patients scheduled for abdominal cancer surgery, including in patients with concomitant chemotherapy, pre‐operative IDA management is feasible and results in a significant pre‐operative Hb increase compared to patients not treated. On the day of surgery 25% patients treated pre‐operatively were no longer anaemic. [ABSTRACT FROM AUTHOR]

There is limited randomized controlled trial evidence to support the association between vitamin D deficiency and anemia risk, highlighting the necessity for further investigations into the role of vitamin D in influencing iron status. The aim of this study was to determine the effect of vitamin D3–fortified fruit drink consumption (4,000 IU) on vitamin D and iron status biomarkers among iron-deficient women (serum ferritin of <20 μg/L [to convert μg/L ferritin to ng/mL, multiply by 1]). An 8-week double-blind randomized controlled trial was conducted. A total of 45 healthy, nonpregnant, nonlactating subjects aged 18 through 40 years (mean [SD] 25.3 [4.6] years) were included in the study, excluding those who donated blood 6 months prior, regularly consumed nutritional supplements, or had gastrointestinal or iron metabolic disorders. Subjects were randomly assigned to receive either vitamin D3–fortified fruit drink or a placebo. Measurements of 25-hydroxyvitamin D (25[OH]D), serum ferritin, high-sensitivity C-reactive protein, and full blood count concentrations were obtained at baseline, interim, and post intervention. A mixed model, repeated measures analysis of variance was used to analyze the intervention effect. Attrition rate for the study was 13%, with 6 dropouts, and 39 subjects completed the study. Daily consumption of vitamin D3–fortified fruit drink in the intervention group resulted in significant increases in 25(OH)D and serum ferritin concentrations compared with the placebo group. The intervention group showed significantly higher mean (SD) changes (Δ) in both 25(OH)D (Δ 76.4 [30.2] nmol/L [to convert nmol/L 25(OH)D to ng/mL, multiply by.4] vs Δ –1.3 [10.7] nmol/L; P =.001) and serum ferritin concentrations (Δ 2.2 [4.2] μg/L vs Δ –0.3 [3.4] μg/L; P =.048) between baseline and post intervention. The other iron status biomarkers were not affected by the intervention. Our study found that daily vitamin D3–fortified fruit drink supplementation for 8 weeks effectively improved 25(OH)D and iron stores, indicated by increased serum ferritin concentrations, in iron-deficient women. Further research is needed to evaluate its safety, efficacy, feasibility, and optimal food fortification in diverse populations. [ABSTRACT FROM AUTHOR]

Iron deficiency (ID) without anemia is common in children with newly diagnosed celiac disease (CD). We aimed to assess the effect of iron supplementation versus no treatment on ferritin levels in newly diagnosed CD patients with ID adhering to a gluten-free diet (GFD). A retrospective review of children < 18 years, with low ferritin (≤ 10 ng/mL) and normal hemoglobin levels diagnosed between 12.2018 and 12.2021. We compared hemoglobin and ferritin levels between patients who received supplemental iron to those who did not. Data, including demographics, laboratory tests, and anthropometrics, were collected at baseline, and at 6 and 12 months following the initiation of the GFD. Adherence to GFD was assessed at each visit. Among 304 children diagnosed during the study period, 43 (14.1%) had iron deficiency anemia and 60 (19.7%) ID without anemia. Among children with ID, 29 (48%) were female, mean age 7.3 ± 3.9 years. Twenty-nine (48%) children received iron supplementation, and 31 (52%) did not. At the 12-month follow-up visit, tissue transglutaminase levels decreased significantly (p < 0.001), from a mean baseline level of 226.6 ± 47.8 to 34.5 ± 46 U/mL in children that received iron supplementation and from 234.2 ± 52.4 to 74.5 ± 88.7 U/mL in non-treated children, with no significant difference between the groups p = 0.22. Ferritin levels increased significantly (p < 0.001), from 9.0 ± 4.7 to 25.2 ± 20.8 ng/mL in patients who received supplementation and from 8.9 ± 3.8 to18.6 ± 9.5 ng/mL in patients who did not, with no significant difference between the groups (p = 0.46). Conclusion: Most children with newly diagnosed celiac disease and iron deficiency, who adhere to GFD, will normalize ferritin levels within 12 months without the need of iron supplementation. What is Known: • Iron deficiency and iron deficiency anemia are common in newly diagnosed celiac disease. • Improved iron absorption may follow mucosal healing process in patients adhering to a strict gluten-free diet. What is New: • This single-center, retrospective cohort study evaluated the effect of iron supplementation versus no treatment on ferritin levels in children with newly diagnosed celiac disease with iron deficiency adhering to a gluten-free diet. • Most children with newly diagnosed celiac disease and iron deficiency, who adhere to gluten-free diet, will normalize ferritin levels within 12 months without the need of iron supplementation. [ABSTRACT FROM AUTHOR]

Objectives: Delays in the evaluation and treatment of iron deficiency can lead to increased disease‐related morbidity and mortality. Electronic consultation (e‐consult) is a referral modality that allows providers quicker access to recommendations from a specialist based on electronic chart review. While the use of e‐consult is expanding in classical hematology, gaps exist in the understanding of patient outcomes related to its use for iron deficiency. Methods: We randomly selected 200 e‐consults and 200 traditional referrals from 3,336 hematology referrals for iron deficiency at a single center. The primary outcomes of the retrospective analysis were: time to completion of the referral, and time to treatment with intravenous iron. Secondary outcomes included recurrence of iron deficiency, need for repeat e‐consult, conversion to in‐person evaluation, and assessment of whether the etiology of iron deficiency was addressed. Results: E‐consults significantly reduced the time from referral to intravenous iron repletion (e‐consult, 33 days; traditional referral, 68 days; p <.05). Assessment of the underlying etiology occurred in 70.7% of the e‐consult encounters compared to 92.5% of traditional referrals (p <.05). Conclusions: These findings highlight advantages of e‐consults in improving care delivery in iron deficiency, and identifying gaps that can be improved through practice standardization to ensure equitable, high‐value care. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusions Concerns exist that intravenous (IV) iron might increase the risk of infections. The IRONMAN trial provided an opportunity to investigate whether giving IV ferric derisomaltose (FDI) to patients with heart failure and iron deficiency alters the rate of hospitalization or death due to infections.IRONMAN was a randomized trial of IV FDI versus usual care in patients with symptomatic heart failure, left ventricular ejection fraction (LVEF) ≤45%, and transferrin saturation (TSAT) <20% or ferritin <100 μg/L. Infection was a pre‐specified, blindly‐adjudicated, safety endpoint. The primary analysis of interest was infection as the main reason for hospitalization or death, using first and recurrent events analyses. The composite primary event of interest tended to be lower in those randomized to FDI when analysed as first (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.62–1.01, p = 0.055) or recurrent event (rate ratio 0.85, 95% CI 0.64–1.13, p = 0.089). The composite results were driven by fewer hospitalizations for infection (HR 0.76, 95% CI 0.49–0.98, p = 0.032), with 5% fewer patients (absolute reduction) experiencing such an event if assigned to FDI. Similar trends were observed for recurrent events (HR 0.82, 95% CI 0.62–1.10). Further analyses suggested that the reduction in hospitalizations due to infection with FDI was restricted to patients with TSAT <20%.In patients with heart failure and a reduced LVEF, correction of iron deficiency is not associated with an increased risk of hospitalization or death from infection, and may reduce such events, especially when TSAT is <20%.Clinical Trial Registration: ClinicalTrials.gov, NCT02642562. [ABSTRACT FROM AUTHOR]

Importance: Neonatal anemia has a long-term effect on children's growth and development. Anemia during pregnancy is also the most widespread nutritional deficiency among pregnant women in the world; If it leads to anemia in newborns, it will affect a wide range of people and be a public health problem worthy of attention. Objective: To study the relationship between maternal anemia during pregnancy and neonatal hemoglobin levels. Data sources: PubMed, Web of science, Scopus, MEDLINE, Embase, ProQuest, Dissertations & Theses Global, The Cochrane Library, China Biology Medicine Database, Chinese CNKI Database, and Chinese Wanfang Database were systematically searched from inception to August 31, 2022. Study selection: The meta-analysis included all original studies which pertain to cohort studies, case-control studies or cross-sectional studies that investigated the relationship between maternal anemia during pregnancy and neonatal hemoglobin levels. Data extraction and synthesis: Hemoglobin level of both anemic and non-anemic pregnant mothers and their paired newborns were pooled from the selected studies. The random-effects model was used to assess the risk of getting a lower neonatal hemoglobin level between mothers with and without pregnant anemia. Data analyses were performed from September 5, 2022, to March 10, 2023. Main outcomes and measures: Maternal anemia during pregnancy is a risk factor of lower neonatal hemoglobin levels. Results: The initial search yielded 4267 records of which 116 articles underwent full-text evaluation, which identified 18 articles and a total of 1873 patients that were included. The findings of the meta-analysis showed a significant difference between the two groups(MD=-1.38; 95%CI:[-1.96,-0.80]. p<0.01), while the co-effect showed that the neonatal hemoglobin value of anemic mothers was 1.38g/dL lower than that of non-anemic mothers(-1.96,-0.80), suggesting a correlation between maternal anemia lower neonatal hemoglobin levels. Conclusions and relevance: This systematic review and meta-analysis demonstrated that maternal anemia during pregnancy were associated with a lower level of newborn hemoglobin levels. This may enable a better understanding of neonatal anemia and provide guidance towards future development of nutritional supplementation during pregnancy and the prediction of postpartum outcomes. Trial registration: PROSPERO Identifier: CRD42022352759. [ABSTRACT FROM AUTHOR]

Anaemia in pregnancy is a global problem of significance in all settings. The most common cause is iron deficiency. Large numbers of women are affected, ranging up to 25–30% antenatally and 20–40% postnatally. It is associated with serious adverse outcomes for both the mother and her baby. The risk of low birth weight, preterm birth, postpartum haemorrhage, stillbirth, and neonatal death are all increased in the presence of anaemia. For the infants of affected pregnancies, complications may include neurocognitive impairment. Making an accurate diagnosis during pregnancy has its challenges, which include the choice of thresholds of haemoglobin below which a diagnosis of anaemia in each trimester of pregnancy can be made and, aligned with this question, which are the most appropriate biomarkers to use to define iron deficiency. Treatment with oral iron supplements increases the haemoglobin concentration and corrects iron deficiency. But high numbers of women fail to respond, probably due to poor adherence to medication, resulting from side effects. This has resulted in an increased use of more expensive intravenous iron. Doubts remain about the optimal regimen to of oral iron for use (daily, alternate days, or some other frequency) and the cost-effectiveness of intravenous iron. There is interest in strategies for prevention but these have yet to be proven clinically safe and effective. [ABSTRACT FROM AUTHOR]

SUMMARY E2 ubiquitin‐conjugating enzymes play a crucial role in the ubiquitination process by catalyzing ubiquitin transfer. Although the function of ubiquitin‐protein ligases (E3s) in plants response to diverse abiotic stress by targeting specific substrates has been well studied, the involvement of E2s in environmental responses and their downstream targets are not well understood. In this study, we demonstrated that the E2 ubiquitin‐conjugating enzyme 18 (UBC18) influences the stability of FREE1 to modulate iron deficiency stress. UBC18 affects the ubiquitination of FREE1 and promotes its degradation, and overexpression of UBC18 decreases plants’ sensitivity to iron deficiency by reducing FREE1 level, whereas the ubc18 mutant exhibits sensitivity due to elevated FREE1 accumulation. This study also identified that lysine residues K227, K295, K315, and K540 are required for FREE1 ubiquitination and stability regulation. Mutating these lysine residues in FREE1 resulted in plants’ sensitivity to iron starvation. Taken together, our findings shed light on the mechanism of UBC18 in responding to iron deficiency stress by modulating the abundance of FREE1, and further elucidate the role of ubiquitination sites in FREE1 stability regulation and the plant iron deficiency response. [ABSTRACT FROM AUTHOR]

Summary Background Methods Results Conclusions Iron deficiency is present in up to 75% of patients presenting for colorectal cancer surgery. It is unclear whether iron deficiency without anaemia is associated with worse postoperative outcomes. We hypothesised that, in adults without anaemia undergoing surgery for colorectal cancer, iron deficiency would be associated with worse postoperative outcomes relative to an iron‐replete state.We performed a prospective, observational study, recruiting adults (aged ≥ 18 y) without anaemia who were undergoing surgery for colorectal cancer in 16 hospitals across Australia and Aotearoa/New Zealand. Anaemia was defined as a haemoglobin concentration < 130 g.l‐1 for men and < 120 g.l‐1 for women. Iron deficiency was defined primarily as transferrin saturation < 20%. The primary endpoint was days alive and at home on postoperative day 90. The primary endpoint analysis was adjusted for surgical risk based on recruiting institution; sex; Charlson comorbidity index; CR‐POSSUM score; surgical approach; and requirement for neoadjuvant therapy.Of 420 patients, 170 were iron deficient and 250 were iron replete. The median (IQR [range]) days alive and at home in the iron‐deficient group was 84.0 (80.7–85.9 [0–88.2]) days and in the iron‐replete group was 83.1 (78.7–85.1 [0–88.9]) days. The unadjusted difference in medians between groups was 0.9 (95%CI 0–1.8, p = 0.047) days and the adjusted difference was 0.9 (95%CI 0–1.80, p = 0.042) days, favouring the iron‐deficient group.In adult patients without anaemia undergoing surgery for colorectal cancer, iron deficiency defined by transferrin saturation < 20% was not associated with worse patient outcomes and appeared to be associated with more days alive and at home on postoperative day 90. [ABSTRACT FROM AUTHOR]

Iron deficiency anemia is a significant global health concern, diagnosed by measuring hemoglobin concentrations in combination with plasma ferritin concentration. This study investigated the variability in ferritin reference intervals among laboratories in the Netherlands and examined how this affects the identification of iron-related disorders.Ferritin reference intervals from 52 Dutch ISO15189-certified medical laboratories were collected. Ferritin, hemoglobin and mean corpuscular volume data of non-anemic apparently healthy primary care patients, measured by four laboratory platforms (Beckman, Abbott, Siemens, and Roche), were collected (n=397,548). Median ferritin levels were determined per platform, stratified by sex and age. The proportion of ferritin measurements outside of the reference interval was calculated using the reference intervals from the 52 laboratories (using a total of n=1,093,442 ferritin measurements). Lastly, ferritin data from 3,699 patients as captured in general practitioner (GP) data from the PHARMO Data Network were used to assess the variation of abnormal ferritin measurements per GP.Median plasma ferritin concentrations were approximately four times higher in men and twice as high in postmenopausal women compared to premenopausal women. Moreover, there are substantial differences in the median plasma ferritin concentration between the four platforms. However, even among laboratories using the same platform, ferritin reference intervals differ widely. This leads to significant differences in the percentages of measurements classified as abnormal, with the percentage of ferritin measurements below the reference limit in premenopausal women ranging from 11 to 53 %, in postmenopausal women from 3 to 37 %, and in men from 2 to 19 %. The percentage of ferritin measurements above the reference limit in premenopausal women ranged from 0.2 to 11 %, in postmenopausal women from 3 to 36 % and in men from 7 to 32 %.The lack of harmonization in ferritin measurement and the disagreement in plasma ferritin reference intervals significantly impact the interpretation of the iron status of patients and thereby the number of iron disorder diagnoses made. Standardization or harmonization of the ferritin assays and establishing uniform reference intervals and medical decision limits are essential to reduce the substantial variability in clinical interpretations of ferritin results. [ABSTRACT FROM AUTHOR]

Iron deficiency anemia (IDA) is prevalent in exclusively breastfed (EBF) Thai infants. However, in Thailand, iron supplementation guidelines for EBF infants are not available. This prospective open-label study aimed to estimate the prevalence of IDA in 9-month-old EBF infants after receiving iron supplementation from 4 months of age until they consumed adequate iron-rich food. Forty-seven healthy, 4-month-old EBF infants were prescribed 1 mg/kg/day ferrous sulfate. Their complementary food records from 6 to 9 months were calculated for daily iron intake. Complete blood count and iron study were performed at 9 months of age. The results showed that the prevalence of IDA at 9 months was 6.4%. An employed caregiver and the male sex of the baby were significantly associated with iron deficiency. The food record revealed that the median daily iron intake was less than the Thai dietary reference intake recommendation. In summary, the prevalence of IDA in infants with 9 months of exclusive breastfeeding who received iron supplementation was lower than the background rate (25.7%) when iron was not prescribed. Most infants did not have adequate iron in complementary foods. Iron supplementation should be prescribed routinely during 4–9 months of age in healthy Thai EBF infants. [ABSTRACT FROM AUTHOR]

Background and Objectives Study Design and Methods Results Conclusion Reproductive‐aged women are at an increased risk of developing iron deficiency (ID). We aimed to develop a non‐invasive screening tool to identify ID in women and assess the acceptability of screening.We screened women (age 18–49 years) in the community of Western Australia. Primary outcome: acceptability of screening, assessed by the feasibility of recruiting the required sample size (n = 323). Secondary outcomes: Hand grip strength, finger prick haemoglobin concentration (Hb), prevalence of heavy menstrual bleeding (HMB), diet, pregnancy history, blood donation, symptoms of ID and history of ID or anaemia (Hb < 120 g/L). Those with Hb <130 g/L and no history of iron therapy in the past 2 years were given referrals for venous full blood count and ferritin sampling.Across 5 days, we recruited 640 eligible women. Of which, 178 (28%) had HMB and 79 (12%) were anaemic. Mean age was 33.5 ± 9.2 years, and mean Hb was 132.4 ± 11.9 g/L. In the past 2 years: 335 (52%) were diagnosed with ID or anaemia; 322 (50%) had taken oral iron; and 210 (33%) had an intravenous iron infusion. Vegetarian diets were followed by 89 (14%); 40 (6%) were regular blood donors; 290 (45%) had a previous pregnancy.HMB increased the risk of symptoms of ID and having prior ID/anaemia diagnosis (67% vs. 47%) or treatment (p < 0.022). Hand grip strength showed a positive relationship with both Hb (adjusted R2 = 0.012, p = 0.004) and ferritin (adjusted R2 = 0.135, p = 0.005).ID screening was well accepted by women in the community, with high recruitment rates over a short period. Future screening tool development may consider incorporating hand grip strength and HMB assessment. [ABSTRACT FROM AUTHOR]

Background/Objectives: Women of reproductive age are reported to be the largest population that practises geophagia. The short-term and long-term health related conditions originating from the practise of geophagia are often not understood by geophagic women of reproductive age. This study has explored the health-related experiences of geophagia among women of reproductive age of Tshwane District, Gauteng Province. Methods: This was a qualitative study design following inductive thematic content analysis. In-depth interviews and focus group discussions were used to collect data using an interview guide and audio record. Data collection took place in 2023. Results: Mental health disorders, pregnancy complications, appendicitis, cancers, breathing complications, fatigue, premature deaths, worms, piles, and nutrients deficiencies were reported as some of the health-related challenges and diseases experienced by women of reproductive age of Tshwane District, Gauteng Province resulting from the practise of geophagia. Conclusions: The practise of geophagia was associated with various negative health outcomes. The reproductive health statuses of women of reproductive age were negatively impacted by the practise of geophagia affecting maternal and childhood mortalities and morbidities. [ABSTRACT FROM AUTHOR]

Background: Iron deficiency (ID) remains the leading cause of anemia, affects a vast number of persons globally, and continues to be a significant global health burden. Comprehending the patterns of ID burden is essential for developing targeted public health policies. Methods: Using data from the Global Burden of Disease (GBD) 2021 study for the years 1990–2021, the XGBoost model was constructed to predict prevalence and disability-adjusted life years (DALYs) for the period 2022–2050, based on key demographic variables. Shapley Additive exPlanations (SHAP) values were applied to interpret the contributions of each variable to the model's predictions. Additionally, the Age–Period–Cohort (APC) model was used to evaluate the effects of age, period, and birth cohort on both prevalence and DALYs. The relationship between the Socio-Demographic Index (SDI) and ID's age-standardized prevalence rate (ASPR) as well as the age-standardized DALYs rate (ASDR) was also analyzed to assess the influence of socioeconomic development on disease burden. Results: The global prevalent cases of ID grew from 984.61 million in 1990 to 1270.64 million in 2021 and are projected to reach 1439.99 million by 2050. Similarly, global DALYs from ID increased from 28.41 million in 1990 to 32.32 million in 2021, with a projected rise to 36.13 million by 2050. The ASPR declined from 18,204/100,000 in 1990 to 16,433/100,000 in 2021, with an estimated annual percentage change (EAPC) of −0.36% over this period. It is expected to decrease further to 15,922 by 2050, with an EAPC of −0.09% between 2021 and 2050. The ASDR was 518/100,000 in 1990 and 424/100,000 in 2021, with an EAPC of −0.68% from 1990 to 2021. It is expected to remain relatively stable at 419/100,000 by 2050, with an EAPC of −0.02% between 2021 and 2050. In 2021, the highest ASPRs were recorded in Senegal (34,421/100,000), Mali (34,233/100,000), and Pakistan (33,942/100,000). By 2050, Mali (35,070/100,000), Senegal (34,132/100,000), and Zambia (33,149/100,000) are projected to lead. For ASDR, Yemen (1405/100,000), Mozambique (1149/100,000), and Mali (1093/100,000) had the highest rates in 2021. By 2050, Yemen (1388/100,000), Mali (1181/100,000), and Mozambique (1177/100,000) are expected to remain the highest. SHAP values demonstrated that gender was the leading predictor of ID, with age and year showing negative contributions. Females aged 10 to 60 consistently showed higher prevalence and DALYs rates compared to males, with the under-5 age group having the highest rates for both. Additionally, men aged 80 and above exhibited a rapid increase in prevalence. Furthermore, the ASPR and ASDR were significantly higher in regions with a lower SDI, highlighting the greater burden of ID in less developed regions. Conclusions: ID remains a significant global health concern, with its burden projected to persist through 2050, particularly in lower-SDI regions. Despite declines in ASPR and ASDR, total cases and DALYs are expected to rise. SHAP analysis revealed that gender had the greatest influence on the model's predictions, while both age and year showed overall negative contributions to ID risk. Children under 5, women under 60, and elderly men aged 80+ were the most vulnerable groups. These findings underscore the need for targeted interventions, such as improved nutrition, early screening, and addressing socioeconomic drivers through iron supplementation programs in low-SDI regions. [ABSTRACT FROM AUTHOR]

Background: Gallstones are a common digestive disorder that threatens human health. Iron deficiency may be related to the formation of gallstones, but there is limited current epidemiological research. The objective of this study was to investigate the relationship between iron status and gallstones. Methods: The datasets from the National Health and Nutrition Examination Survey (NHANES) 2017–2020 were used in a cross-sectional investigation. Gallstones were determined by using the 2007–2010 NHANES questionnaire. Multivariate linear regression models were used to examine the association between serum iron, serum ferritin and iron intake with the risk for gallstones. Subgroup analysis based on gender, age, race, and diabetes were performed. Fitted smoothing curves were used to describe the linear relationship. Results: The research involved 7847 participants aged 20 and above, among whom 845 were identified as having gallstones. Participants with higher serum iron levels tended to have a lower gallstones prevalence. A negative relationship between serum iron and gallstones prevalence was observed (OR = 0.979, 95% CI:0.965–0.992). The group with the highest serum iron tertile had a 23.7% lower risk of gallstones compared to the lowest tertile (OR = 0.763, 95% CI:0.628‒0.929). Gallstone prevalence was inversely correlated with iron intake in model 1. The negative association between serum iron and gallstones remained stable in stratifications, including gender, age, race, and diabetes. Conclusions: Elevated serum iron was associated with a decreased prevalence of gallstones. However, to confirm the impact of long-term iron metabolism on gallstone formation, additional prospective research is necessary. [ABSTRACT FROM AUTHOR]

Introduction and Purpose: Iron deficiency, alongside anaemia, is one of the most significant global health concern with potentially long-lasting implications on child development and health outcomes. The period of infancy represents a crucial phase of central nervous system maturation, rendering infants particularly susceptible to the adverse effects of iron deficiency. It is therefore crucial to pay close attention to this issue. The aim of this review is to elucidate the neurological implications of iron deficiency in infancy and emphasize the necessity of implementing preventive strategies to safeguard child development. State of Knowledge: Iron deficiency in infancy can result in impairments of brain development. Extensive research highlights the influence of this micronutrient on various physiological processes, including the synthesis of neurotransmitters, neuronal metabolism, myelination, synaptogenesis and gene expression. Furthermore, iron deficiency during infancy is associated with adverse developmental outcomes, including cognitive, motor, and socioemotional deficits. Long-term follow-up studies have elucidated the enduring neurological consequences of iron deficiency in infancy, with effects extending into childhood and beyond. Summary: Given that the changes that occur during the infantile period are often irreversible and have long-lasting implications for future development, it is of the utmost importance to prioritize prevention strategies. [ABSTRACT FROM AUTHOR]

AbstractIron, an essential micronutrient for plant growth, is often found in insoluble forms in alkaline soils, leading to inadequate absorption, poor plant growth, and iron deficiency chlorosis. This study explores the effects of co-inoculation with the siderophore bacteria Lysinibacillus fusiformis (S5) and Arbuscular mycorrhizal fungi (AMF) on the iron uptake and growth of Cinnamomum camphora seedlings. The experiment included four treatment groups: a control with plain water, AMF only, S5 only, and a combined AMF+S5 group, over a three-month pot experiment. Compared to the control, the combined AMF+S5 treatment significantly enhanced root mycorrhizal colonization and spore density by 15.6% and 31.8%, respectively. Additionally, there were increases in stem thickness, plant height, and root length by 34.7%, 15.6%, and 80.3%, respectively. In terms of photosynthetic physiology, the combined treatment improved the net photosynthetic rate and stomatal conductance by 37.5% and 46.7%, respectively, while reducing intercellular CO2 concentration by 8.7%. Furthermore, total iron content in Cinnamomum camphora increased by 11%, and root-available iron content (FCR) by 26.6%. These results demonstrate that co-inoculation with AMF and siderophore bacteria significantly promotes growth and iron absorption in seedlings, effectively mitigating symptoms of iron deficiency chlorosis, providing a scientific basis for developing efficient microbial co-inoculation techniques. [ABSTRACT FROM AUTHOR]

Background: Despite routine iron supplementation for pregnant women in South Africa, anaemia and iron deficiency (ID) in pregnancy remain a public health concern. Objective: To determine the associations between iron status and birth outcomes of pregnant women attending antenatal clinic at a regional hospital in Bloemfontein. Methods: In this cross-sectional study of 427 pregnant women, blood was taken to analyze biomarkers of anaemia (haemoglobin), iron status (ferritin and soluble transferrin receptor) and inflammation (C-reactive protein and α-1-acid glycoprotein). A questionnaire was used to collect information about birth outcomes (birth weight and gestational age at birth), HIV exposure, sociodemographics, iron supplement intake, and maternal dietary iron intake using a validated quantified food frequency questionnaire. Results: The median (Q1, Q3) weeks of gestation of participants was 32 (26, 36) at enrolment. Anaemia, iron deficiency (ID), ID anaemia (IDA) and ID erythropoiesis (IDE) were present in 42%, 31%, 19% and 9.8% of participants, respectively. Median (Q1, Q3) dietary and supplemental iron intake during pregnancy was 16.8 (12.7, 20.5) mg/d and 65 (65, 65) mg/d, respectively. The median (max-min) total iron intake (diet and supplements) was 81 (8.8-101.8) mg/d, with 88% of participants having a daily intake above the tolerable upper intake level of 45 mg/d. No significant associations of anaemia and iron status with low birth weight and prematurity were observed. However, infants born to participants in the third hemoglobin (Hb) quartile (Hb > 11.3–12.2 g/dL) had a shorter gestation by 1 week than those in the fourth Hb quartile (Hb > 12.2 g/dL) (p = 0.009). Compared to pregnant women without HIV, women with HIV had increased odds of being anaemic (OR:2.14, 95%CI: 1.41, 3.247), having ID (OR:2.19, 95%CI: 1.42, 3.37), IDA (OR:2.23, 95%CI: 1.36, 3.67), IDE (OR:2.22, 95%CI: 1.16, 4.22) and delivering prematurely (OR:2.39, 95%CI: 1.01, 5.64). Conclusion: In conclusion, anaemia, ID, and IDA were prevalent in this sample of pregnant women, despite the reported intake of prescribed iron supplements, with HIV-infected participants more likely to be iron deficient and anaemic. Research focusing on the best formulation and dosage of iron supplementation to enhance iron absorption and status, and compliance to supplementation is recommended, especially for those living with HIV infection. Highlights: • Only 19% of the pregnant women met the daily estimated average requirement for iron through dietary intake, highlighting the need for iron supplementation. • Despite the intake of routine 65 mg of elemental iron as a single micronutrient, anaemia and iron deficiency was prevalent in 42% and 31% of pregnant women respectively. •In the total sample, anaemia, iron deficiency, iron deficiency anaemia (IDA), and iron deficiency erythropoiesis (IDE) were not associated with low birth weight and premature birth. • Women living with HIV had over two times increased odds of being anaemic, iron deficient, having IDA and IDE, and delivering prematurely compared to those without HIV. [ABSTRACT FROM AUTHOR]

Agronomic biofortification with iron (Fe) in tomatoes has emerged as a promising strategy to combat global iron deficiency. Iron is essential for human health and plays a critical role in the growth and development of crops. This study aimed to determine the optimal dose of Fe for tomato biofortification and assess its impact on its growth, yield and quality attributes, particularly the fruit’s Fe content. A greenhouse experiment was conducted using tomato hybrids Sandal and Sahel, applying Fe foliar treatments at concentrations of 0, 1, 3, 6 and 9 mM Fe per plant. The results demonstrated that foliar application of 6 mM Fe significantly enhanced the tomato’s growth, yield and quality, while markedly increasing the fruit’s Fe content to 30.07 and 34.1 mg kg−1 in Sandal and Sahel hybrids, respectively. These values were substantially higher than those of the control treatment with Fe contents of 14.77 and 15.0 mg kg−1, respectively. However, higher doses of Fe (> 6 mM Fe per plant) showed adverse effects on growth, yield, and quality. Foliar application of iron proved an effective and economical solution, readily integrated into commercial tomato production, offering farmers a practical method to produce Fe-biofortified tomatoes and combat iron deficiency-linked malnutrition. [ABSTRACT FROM AUTHOR]

Hepcidin production is regulated by iron concentration, erythropoietic activity, and inflammation. There is no reference method for determining its levels, but results obtained through various methods strongly correlate and can be compared using recalibration equations. Objective: To describe recalibrated serum hepcidin values at different percentiles in schoolchildren, considering age, sex, inflammatory processes, H. pylori infection, and iron status. Methods: Secondary analysis of data incorporating information on inflammation, H. pylori infection, and iron status of 349 schoolchildren. Hepcidin analysis was performed using a competitive ELISA, and recalibrated hepcidin values were calculated using the inverse of the linear regression model equation obtained by van der Vorm et al. Results: Recalibrated hepcidin values were lower than non-calibrated values. In schoolchildren without infection/inflammation and without iron deficiency, recalibrated values at the 50th percentile (25th–75th) were 4.89 ng/mL (2.68–8.42). For schoolchildren without infection/inflammation but with iron deficiency, recalibrated values were 2.34 ng/mL (1.10–6.58), the lowest hepcidin values observed. The highest values were found in the group with infection/inflammation, regardless of iron deficiency status. Conclusions: Recalibrated hepcidin values were lower than non-calibrated values. The highest values were observed in schoolchildren with infectious or inflammatory processes, and the lowest values were observed in schoolchildren with iron deficiency but only in the absence of infectious or inflammatory processes. Using recalibrated hepcidin values allows comparison between data obtained using different analytical methods. [ABSTRACT FROM AUTHOR]

Introduction: Anemia is a risk factor for all-cause mortality in older adults. Iron deficiency may also be associated with adverse outcomes, independent of its role in causing anemia. This study tested the hypotheses that anemia, and low ferritin among non-anemic participants, were associated with all-cause and cause-specific mortality in a community-based cohort of older adults. Methods: Fasting blood was obtained from 5,070 ARIC participants (median age: 75 years) in 2011–2013. Anemia was defined by hemoglobin concentrations <12 g/dL in women and <13 g/dL in men. We classified 4,020 non-anemic participants by quartiles of plasma ferritin, measured by the SomaScan proteomics platform. Cox proportional hazards regression was used. Mortality was ascertained via phone calls with proxies as part of twice-yearly cohort follow-up, surveillance of local hospital discharge indexes, state death records, and linkage to the National Death Index. Results: Of the total participants, 21% had anemia at baseline. Over a median of 7.5 years, there were 1,147 deaths, including 357 due to cardiovascular disease (CVD), 302 to cancer, and 132 to respiratory disease. Compared to those with normal hemoglobin, participants with anemia had a higher risk of all-cause mortality (hazard ratio 1.81 [95% CI: 1.60–2.06]), and mortality due to CVD (1.77 [1.41–2.22]), cancer (1.81 [1.41–2.33]), and respiratory disease (1.72 [1.18–2.52]) in demographics-adjusted models. In fully adjusted models, associations with all-cause mortality (1.37 [1.19–1.58]) and cause-specific mortality were attenuated. In non-anemic participants, lower ferritin levels were not associated with all-cause or cause-specific mortality, though associations were observed among participants with lesser evidence of inflammation (CRP below the median level of 1.9 mg/L) and for cancer mortality in men only. Conclusion: Anemia is common among older adults and is associated with all-cause mortality, as well as mortality due to CVD, cancer, and respiratory disease. Our results do not provide evidence that iron deficiency, independent of anemia, is associated with mortality in this population. [ABSTRACT FROM AUTHOR]

Introduction: Whole blood donors are at increased risk for iron deficiency (ID). ID anemia is associated with several symptoms, such as fatigue, cognitive dysfunction, pica, and restless leg syndrome (RLS). However, it is unclear if these symptoms also occur when a donor has developed ID without anemia. This study aims to determine whether non‐anemic ID (NAID) is associated with the occurrence of ID‐related symptoms. Study Designs and Methods: We combined data from three studies in whole blood donors (i.e., Donor Insight‐III, FIND'EM, and FORTE) to create a substantial sample size (N = 12,143). The self‐reported occurrence and severity of ID‐related symptoms, such as physical and mental health, fatigue, cognitive functioning, pica, and RLS, was measured using validated questionnaires. Associations were studied using logistic regression modeling with ID‐related symptoms derived from the questionnaires as the dependent variable and ferritin level group (0–15 μg/L, 15–30 μg/L, and >30 μg/L) as explanatory variable. Results: After applying inclusion and exclusion criteria, 9829 donors were eligible for analysis. In the models corrected for age, body mass index, Hb level, and cohort, only fatigue was shown to be associated with ferritin levels in men, showing lower odds (OR 1.41, 95% CI 1.11–1.79) for fatigue with higher ferritin levels. Conclusion: In these studies, NAID was only associated with self‐reported fatigue in male donors. Although selection bias may have led to underestimated associations, ferritin measurements in donors should be primarily considered as a measure to prevent anemia, rather than to prevent or mitigate NAID‐related symptoms. [ABSTRACT FROM AUTHOR]

Iron deficiency (ID) is common during gestation and in early infancy and has been shown to adversely affect cardiac development and function, which could lead to lasting cardiovascular consequences. Ketone supplementation has been shown to confer cardioprotective effects in numerous disease models. Here, we tested the hypothesis that maternal ketone supplementation during gestation would mitigate cardiac dysfunction in ID neonates. Female Sprague-Dawley rats were fed an iron-restricted or iron-replete diet before and throughout pregnancy. Throughout gestation, iron-restricted dams were given either a daily subcutaneous injection of ketone solution (containing ß-hydroxybutyrate [ßOHB]) or saline (vehicle). Neonatal offspring cardiac function was assessed by echocardiography at postnatal days (PD)3 and 13. Hearts and livers were collected post-mortem for assessments of mitochondrial function and gene expression profiles of markers oxidative stress and inflammation. Maternal iron restriction caused neonatal anemia and asymmetric growth restriction at all time points assessed, and maternal ßOHB treatment had no effect on these outcomes. Echocardiography revealed reduced ejection fraction despite enlarged hearts (relative to body weight) in ID offspring, resulting in impaired oxygen delivery, which was attenuated by maternal ßOHB supplementation. Further, maternal ketone supplementation affected biochemical markers of mitochondrial function, oxidative stress and inflammation in hearts of neonates, implicating these pathways in the protective effects conferred by ßOHB. In summary, ßOHB supplementation confers protection against cardiac dysfunction in ID neonates and could have implications for the treatment of anemic babies. [ABSTRACT FROM AUTHOR]

Summary: Optimal targets for red blood cell exchange (RCE) are not well defined in the chronic management of sickle cell disease. We analysed transfusion requirements and iron‐related outcomes in 101 patients on chronic RCE with a post‐procedure haematocrit (Ht) targeted at 34%, which is higher than typically used. A majority were of HbSS/HbSβ0 genotype (n = 72) and enrolled for neurological complications (n = 53). Fifty patients had a positive Ht balance with RCE (>2% mean increase from pre‐procedure level), while 43 patients maintained a neutral balance. The first group required fewer red blood cell units/year (65 vs. 80, p < 0.001), but a significant proportion were iron overloaded based on R2* with liver MRI (32% vs. none performed) and prescription of iron chelation (52% vs. 0%, p < 0.001, after a median of 19 months). The second group was more likely to receive iron supplementation (6% vs. 56%, p < 0.001). Chronic automated RCE with a post‐procedure Ht targeted at 34% is not iron‐neutral, and personalized Ht goals may be more appropriate in certain settings. This higher target should be compared with a lower Ht strategy in individuals with similar baseline red cell volumes to assess iron homeostasis and blood product requirements. [ABSTRACT FROM AUTHOR]

Deferiprone (DFP) is one of the iron-chelating agents used in iron overload therapy for patients with ß-thalassemia major (ß-TM). However, the use of DFP is limited as it experiences a first-pass effect and can potentially cause iron deficiency due to uncontrolled release. Therefore, iron-responsive (NP-IR) DFP nanoparticle innovation was developed to control DFP release. A dissolving microneedle system (NP-IR-DMNs) was used to maximize DFP release. However, in support of this development, validation of analytical methods using spectrophotometry and colorimetrics was carried out. UV–Vis spectrophotometry is an approach that is easy to use, practical, and more cost-effective than others. The DFP levels were determined in normal and iron-overloaded medium solutions with 1%, 2%, and 4% concentrations. In addition, DFP levels were also measured in rat plasma using the colorimetric method with the addition of FeCl3 reagent to increase sensitivity for the detection of the analyte. The procedures used as guidelines in the validation procedure are The International Council for Harmonization (ICH). As a result, all linear correlation values of medium and plasma ≥ 0.999 were obtained. The LOQ levels obtained were 0.55 µg/mL, 0.44 µg/mL, 0.42 µg/mL, 0.52 µg/mL, and 1.01 µg/mL in plasma, 1% FeSO4, 2% FeSO4, 4% FeSO4, and normal media, respectively. The accuracy and precision were confirmed valid, as all values were within the requirements and did not change during dilution. Then, this approach was successfully applied to determine the levels of DFP in NP-IR integrated into DMNs. [ABSTRACT FROM AUTHOR]

Background/objectives: Iron deficiency anemia is common in patients with colorectal cancer and affects postoperative outcomes. Preoperative intravenous iron supplementation corrects anemia effectively; however, the effect on the postoperative clinical course is unclear. The aim of this study was to investigate the effects of implementing a screening program for iron deficiency anemia and correction in patients with colorectal cancer. Methods: This was a retrospective single-institutional quality-assurance study that included patients undergoing elective surgery for colorectal cancer between January 2019 and December 2021. On 1 March 2020, screening for iron deficiency was implemented. Anemia was corrected by intravenous ferricarboyxmaltose. Patients with hemoglobin <7mmol/L and ferritin <30 µg/L or ferritin 30–100 µg/L and TSAT < 0.2 were divided into iron- and non-iron groups. The primary outcome was a change in hemoglobin concentration, and secondary outcomes included blood transfusion, complications, length of stay, mortality, and implementation efficacy. Data from the patients were extracted from digital patient charts and entered into a database. Results: A total of 532 patients were included, of which 177 patients (33.3%) were anemic, 63 were in the iron group, and 114 were in the non-iron group. Adherence to the screening program was 86.3%. Hemoglobin (iron group) increased from a mean of 5.7 mmol/L (SD 0.8) to 6.9 (0.8) mmol/L, p < 0.001. Iron treatment decreased transfusion rates from 27.7% to 9.1%, p = 0.007, and increased the rate of patients without complications from 53.2% to 79.6%, p < 0.001, which held true after controlling for confounding. In addition, 90-day mortality was lower in the iron group; however, this was not significant. Conclusions: Administration of intravenous iron increased hemoglobin, leading to reduced use of blood transfusion and fewer complications. [ABSTRACT FROM AUTHOR]

A cross-sectional study was performed in healthy adults (mean age 28 y, 67% women) whose habitual diet was an omnivore, lacto-ovo vegetarian, or vegan diet. The total sample (n = 297) was divided into two groups according to the parathormone (PTH) cut-off value of 65 pg/mL of either normal-PTH (n = 228) or high-PTH (n = 69). Vitamin D status (25-hydroxycholecalciferol, 25-OHD), PTH, and bone formation (bone alkaline phosphatase, BAP) and bone resorption (N-telopeptides of type I collagen, NTx) markers were determined. Hematocrit, erythrocytes, hemoglobin, platelets, serum iron, serum transferrin, transferrin saturation, and serum ferritin were also measured. In the total sample, 25-OHD and PTH were negatively correlated, and all subjects with high PTH presented vitamin D insufficiency (25-OHD < 75 nmol/L). High bone remodeling was observed in the high-PTH group, with significantly higher NTx and marginally higher BAP compared to the normal-PTH group. Hematocrit and ferritin were significantly lower in the high-PTH compared to the normal-PTH group. However, serum iron was higher in the high-PTH group, which was only observed for the lacto-ovo vegetarian and vegan subjects. It is concluded that both low vitamin D and low iron status are associated with elevated PTH and bone resorption, more in vegetarians than omnivores, which is in line with the hypothesis that chronic iron deficiency in adulthood mainly predisposes to osteoporosis in postmenopausal women and the elderly. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Limited evidence exists on the optimal strategy to correct iron deficiency anemia after variceal bleeding (VB) in cirrhosis. This trial compared the efficacy and safety of intravenous ferric carboxymaltose (IVFCM) with those of oral iron therapy in this cohort. METHODS: In this open-label, single-center, randomized controlled trial, eligible patients with hemoglobin <10 g/dL and iron deficiency (ferritin <100 ng/mL) after VB received either IV-FCM (1,500-2,000 mg) divided into 2 doses (n 5 48) or oral carbonyl iron (100 mg elemental iron/day) (n 5 44) for 3 months. The primary outcome was change in hemoglobin at 3 months. Secondary outcomes included improvement in anemia (last hemoglobin >12 g/dL), normalization of iron stores (ferritin >100 ng/mL), liver-related adverse events, adverse drug reactions, and changes in quality of life (CLDQOL questionnaire). RESULTS: Baseline characteristics, including median Child-Turcotte-Pugh score 7 (interquartile range [IQR] 6-9), Model for End-Stage Liver Disease score 12 (IQR 10-17), blood hemoglobin (8.2561.06 g/dL), and ferritin (30.00 ng/mL [15.00-66.50]), were comparable in both arms. The median increase in hemoglobin at 3 months in the IV and oral arms was 3.65 g/dL (IQR 2.55-5.25) and 1.10 g/dL (IQR 0.05-2.90 g/dL) (P < 0.001), respectively. Iron stores normalized in 84.6% and 21% of the IV and oral arms, respectively (P < 0.001). Anemia improved in 50% and 21.9% in the IV and oral arms, respectively (P < 0.009). Patients in the IV arm showed a significant improvement in all domains of CLDQOL. Liver-related adverse events were comparable in both arms. Transient mild/moderate hypophosphatemia developed in 43% of patients receiving IV-FCM. DISCUSSION: Intravenous iron replacement is efficacious and safe to treat iron deficiency anemia after VB in patients with cirrhosis. [ABSTRACT FROM AUTHOR]

Background and Objectives: 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. Materials and Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Iron (Fe) is necessary for plant growth and development. Iron deficiency disrupts major metabolic and cellular activities such as respiration, DNA synthesis, and chlorophyll synthesis. Iron also activates various metabolic pathways and is vital to numerous enzymes. Iron is widely distributed in soil, but plants do not readily absorb it. In addition to neutral pH, Fe also forms insoluble Fe complexes under alkaline conditions. The fundamental cause of Fe chlorosis is an imbalance between the solubility of Fe in soil and the demand for Fe by plants. Various Fe fertilizers, including organic, chelated, and inorganic, are administered to the soil and leaves to treat Fe deficiency and chlorosis. Currently, used Fe fertilizers are expensive, easily adsorb on soil particles, and cause Fe to leach out of the soil with water, thereby diminishing their efficiency. They also need to be applied repeatedly, resulting in an excessive Fe fertilizer concentration in the soil that can cause harm to the plants. The usage of Fe nanofertilizers in agricultural production has expanded to address the disadvantages of existing Fe fertilizers. The advantages of nanosized Fe fertilizers include their physical and chemical characteristics, such as the high surface area to volume ratio that aids in easy absorption by plants' roots and leaves. Controlled‐release iron oxide nanofertilizers supply the regulated release of nutrients in a way that is coordinated with the nutritional needs of the crops. This improves the accumulation of nutrients in the plant, filling in the gap of nutrient deficiency and lowering environmental risks due to leaching. The possibility of iron oxide nanoparticles as Fe micronutrient fertilizers, their uptake and mechanism of action, advantages, and limitations are critically highlighted in this review article. [ABSTRACT FROM AUTHOR]

Background The prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) in children with cancer is not well studied. The detection of ID and IDA using sensitive laboratory tools may facilitate early diagnosis and treatment in this cohort. In this regard, reticulocyte hemoglobin (Ret-He) content serves as a cost-effective measurement that remains unaffected by inflammation, unlike the ferritin test. Aim The objective of this study is to analyze the role of Ret-He as a diagnostic tool to identify functional and absolute ID and IDA in children with cancer. Methods We conducted a cross-sectional study in children aged 0 to 18 years. Blood samples were collected to compare Ret-He values with iron status, reflected by hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), serum iron (SI), total iron binding capacity (TIBC), and ferritin and transferrin saturation. The overall discriminative power of Ret-He in detecting ID and IDA was assessed using receiver operating characteristic analysis. Results Of the 135 children included in the study, 58 (43.0%) had anemia. Among them, 20 (14.8%) had IDA (8 [5.9%] absolute and 12 [8.9%] functional), while 25 (18.5%) had ID (16 [11.9%] absolute and 9 [6.7%] functional). The Ret-He value was significantly related to iron status (p = 0.002). Ret-He was also shown to have a significant correlation with the abovementioned hematological parameters (p=0.000), except TIBC. Multivariate analysis revealed a significant relationship between Hb (p=0.051), MCH (p=0.000), and MCHC (p=0.001) and Ret-He. Ret-He values of 33.7, 32.7, 32.4 and 28.6 pg were established as optimal cut-off values to identify functional ID, absolute ID, functional IDA, and absolute IDA, respectively. Conclusion Ret-He is a reliable diagnostic tool for absolute and functional IDA in children with cancer. [ABSTRACT FROM AUTHOR]

Objectives: Animal studies have suggested that dietary iron deficiency (ID) negatively affects dopamine (DA) synthesis and re-uptake, which in turn negatively affects memory and cognition. This study was intended to assess whether the pattern electroretinogram (pattern ERG) could be used as an indirect measure of DA in college-age women with and without ID by determining the extent to which features of the ERG were sensitive to iron status and were related to other indirect measures of DA. Methods: The pattern ERG was measured in 21 iron deficient non-anemic (IDNA) and 21 iron sufficient (IS) women, who also performed a contrast detection and probabilistic selection task, both with concurrent electroencephalography (EEG). Both spontaneous and task-related blink rates were also measured. Results: The implicit times of the A- and B-waves were significantly longer for the IDNA than for the IS women. Both the amplitudes and implicit times of the A- and B-waves were significantly correlated with levels of serum ferritin (sFt). Only the amplitude of the A-wave was correlated with spontaneous blink rate. It was possible to accurately identify a woman's iron status solely on the basis of the implicit time of the B-wave. Finally, the implicit times of the ERG features mediated the relationship between iron levels and accuracy in the probabilistic selection task. Conclusions: Results suggest the utility of the pattern ERG in testing the hypothesis that iron deficiency affects DA levels in humans and that this may be one of the mechanisms by which iron deficiency negatively affects cognition. [ABSTRACT FROM AUTHOR]

Chlorosis in azaleas is characterized by an interveinal yellowing of leaves that is typically caused by a deficiency of iron. This condition is usually due to the inability of cells to properly acquire iron as a consequence of unfavorable conditions, such as an elevated pH, rather than insufficient iron levels. The causes and effects of chlorosis were found to have similarities with those pertaining to a recently presented hypothesis that describes a pathogenic process in Alzheimer disease. This hypothesis states that iron becomes sequestered (e.g., by amyloid β and tau), causing a functional deficiency of iron that disrupts biochemical processes leading to neurodegeneration. Additional mechanisms that contribute to iron becoming unavailable include iron-containing structures not undergoing proper recycling (e.g., disrupted mitophagy and altered ferritinophagy) and failure to successfully translocate iron from one compartment to another (e.g., due to impaired lysosomal acidification). Other contributors to a functional deficiency of iron in patients with Alzheimer disease include altered metabolism of heme or altered production of iron-containing proteins and their partners (e.g., subunits, upstream proteins). A review of the evidence supporting this hypothesis is presented. Also, parallels between the mechanisms underlying a functional iron-deficient state in Alzheimer disease and those occurring for chlorosis in plants are discussed. Finally, a model describing the generation of a functional iron deficiency in Alzheimer disease is put forward. [ABSTRACT FROM AUTHOR]

Background/Objectives: Homocysteine (Hcy) and iron are factors co-related with the progression of cardiovascular diseases. The vascular endothelium is an important barrier for physiological homeostasis, and its impairment initiates cardiovascular injury. However, the mechanism underlying Hcy-caused vascular endothelial cell injury and the participation of iron are not fully elucidated. This study aims to investigate the Hcy-induced vascular endothelial injury and iron metabolism dysfunction as well as the underlying molecular mechanism. Methods: Human umbilical vein endothelial cells (HUVECs) were employed as the experimental model to examine the Hcy-induced endothelial injury and its underlying mechanism via various biochemical assays. Results: Hcy suppressed the cell viability and proliferation and caused cell death in a concentration-dependent manner. Hcy induced cell cycle arrest, apoptosis, and autophagy as well as impairment of intracellular energy metabolism. Hcy disrupted the intracellular antioxidant system and mitochondrial function by increasing intracellular ROS, MDA and mitochondrial content, and decreasing the SOD activity and mitochondrial membrane potential. Hcy significantly reduced the GSH-Px activity along with the accumulation of intracellular GSH in a concentration-dependent manner. Ferroptosis inhibitors, Ferrostatin-1 (Fer-1), and Deferoxamine (DFO) significantly decreased the Hcy-caused cytotoxicity accompanied by a reduction in dysregulated mitochondria content, but only DFO ameliorated the elevation of intracellular ROS, and neither Fer-1 nor DFO affected the Hcy-caused reduction in intracellular ATP. In addition, Hcy decreased the intracellular concentration of iron, and supplementing Hcy with various concentrations of Fe3+ increased the cell viability and decreased the LDH release in a concentration-dependent manner. Hcy dramatically decreased the mRNA expression level of transferrin receptor while increasing the mRNA expression levels of transferrin, ferritin light chain, ferritin heavy chain, ferroportin, and SLC7A11. Moreover, Hcy suppressed the protein expression of phospho-Akt, phospho-mTOR, Beclin-1, LC3A/B, Nrf2, HO-1, phospho-MEK1/2, phospho-ERK1/2, and Caspase-3 in concentration- and time-dependent manners. Conclusions: Hcy-induced vascular endothelial injury is likely to be associated with apoptosis and autophagy, but not ferroptosis. The key underlying mechanisms are involved in the disruption of the intracellular antioxidant system and iron metabolism via regulation of PI3K/Akt/mTOR, MAPKs, Nrf2/HO-1, and iron metabolism. [ABSTRACT FROM AUTHOR]

Iron is an essential nutrient in living organisms with multiple vital functions. Iron deficiency (ID) can cause long term health consequences beyond iron deficiency anemia (IDA). The high prevalence of ID and its long-term effects in patients with obesity and after metabolic and bariatric surgery (MBS) is recognized. Nevertheless, there is limited knowledge of the optimal route or dose for treatment of patients with obesity and post-MBS, and an evidence-based universal guideline for prevention and treatment of ID in short- and long-term post-MBS (PMBS) is not yet available. ID in the general population is currently treated with oral or parenteral iron, where oral iron treatment is considered the preferred option with parenteral iron as a second-line treatment in case there is intolerance or lack of response to oral iron. In patients with obesity with chronic low-grade inflammation and PMBS patients with altered gut anatomy and function, there are also alterations in the bioavailability and higher risks of side effects of available oral irons. The conclusions of current studies exploring effective treatment of iron deficiency in this population have been inconsistent and further well-planned randomized and prospective studies are needed. This is a narrative review of the literature on the available treatment options and strategies for treatment of ID in PMBS patients to recognize the knowledge gaps and provides topics of future research. [ABSTRACT FROM AUTHOR]

Background/Objectives: Iron (Fe) is a co-factor for enzymes of the developing brain necessitating sufficient supply. We investigated the effects of administering ferric derisomaltose/Fe isomaltoside (FDI) subcutaneously to Fe-deficient (ID) pregnant rats on cerebral and hepatic concentrations of essential metals and the expression of iron-relevant genes. Methods: Pregnant rats subjected to ID were injected with FDI on the day of mating (E0), 14 days into pregnancy (E14), or the day of birth (postnatal (P0)). The efficacy was evaluated by determination of cerebral and hepatic Fe, copper (Cu), and zinc (Zn) and gene expression of ferroportin, hepcidin, and ferritin H + L in pups on P0 and as adults on P70. Results: Females fed an ID diet (5.2 mg/kg Fe) had offspring with significantly lower cerebral and hepatic Fe compared to female controls fed a standard diet (158 mg/kg Fe). Cerebral Cu increased irrespective of supplying a standard diet or administering FDI combined with the standard diet. Hepatic hepcidin mRNA was significantly lower following ID. Cerebral hepcidin mRNA was hardly detectable irrespective of iron status. Conclusions: In conclusion, administering FDI subcutaneously to ID pregnant rats on E0 normalizes fetal cerebral and hepatic Fe. When applied at later gestational ages, supplementation with additional Fe to the offspring is needed to normalize cerebral and hepatic Fe. [ABSTRACT FROM AUTHOR]

This document provides a comprehensive overview of iron deficiency, its diagnosis, and management. It highlights the global prevalence of iron deficiency, with a particular focus on its impact on women. The document explains the classifications and diagnosis of iron deficiency, as well as the causes and investigation of the condition. It also discusses various treatment options, including oral and intravenous iron supplementation, and emphasizes the importance of monitoring response to therapy. The document includes helpful tables outlining recommended serum ferritin levels, the likelihood of different causes of iron deficiency, and the elemental iron content of different oral iron formulations. It also provides information on intravenous iron formulations and their recommended dosages. This resource is a valuable tool for individuals researching iron deficiency and its treatment options. [Extracted from the article]

Background and Aims Evidence is lacking that correcting iron deficiency (ID) has clinically important benefits for patients with heart failure with preserved ejection fraction (HFpEF). Methods FAIR-HFpEF was a multicentre, randomized, double-blind trial designed to compare intravenous ferric carboxymaltose (FCM) with placebo (saline) in 200 patients with symptomatic HFpEF and ID (serum ferritin < 100 ng/mL or ferritin 100–299 ng/mL with transferrin saturation < 20%). The primary endpoint was change in 6-min walking test distance (6MWTD) from baseline to week 24. Secondary endpoints included changes in New York Heart Association class, patient global assessment, and health-related quality of life (QoL). Results The trial was stopped because of slow recruitment after 39 patients had been included (median age 80 years, 62% women). The change in 6MWTD from baseline to week 24 was greater for those assigned to FCM compared to placebo [least square mean difference 49 m, 95% confidence interval (CI) 5–93; P =.029]. Changes in secondary endpoints were not significantly different between groups. The total number of adverse events (76 vs. 114) and serious adverse events (5 vs. 19; rate ratio 0.27, 95% CI 0.07–0.96; P =.043) was lower with FCM than placebo. Conclusions In patients with HFpEF and markers of ID, intravenous FCM improved 6MWTD and was associated with fewer serious adverse events. However, the trial lacked sufficient power to identify or refute effects on symptoms or QoL. The potential benefits of intravenous iron in HFpEF with ID should be investigated further in a larger cohort. [ABSTRACT FROM AUTHOR]