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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

Objective Methods Results Conclusion The primary objective was to evaluate the prevalence of undiagnosed iron deficiency in patients with endometriosis.We performed a multi‐center, cross‐sectional study at two tertiary care hospitals. We included 251 non‐pregnant women (18–50 years old) presenting with a clinical or surgical diagnosis of symptomatic endometriosis. Patients who consented to the study underwent screening bloodwork (including complete blood count, ferritin, and transferrin saturation) and completed the study survey assessing demographics, medical and surgical history, and validated questionnaires to assess iron deficiency and endometriosis symptoms.The prevalence of iron deficiency in our endometriosis cohort was 53.4% (134/251), and the prevalence of iron deficiency anemia was 13.5% (34/251). Patients with iron deficiency were more likely to have heavy menstrual bleeding (HMB) compared with patients without iron deficiency (66/133, 49.6% vs. 40/115, 34.8%, p = 0.022). Nonetheless, 58% (142/251) of our study population did not endorse HMB. Despite absence of HMB, 47% (67/142) of these patients were iron‐deficient. Transferrin saturation was diagnostic for iron deficiency in 63 of 176 patients (35.7%) who had a normal ferritin (≥30 ng/mL). Patients with iron deficiency had a significantly lower adjusted median Functional Assessment of Chronic Illness Therapy Fatigue Subscale score compared with those without iron deficiency (26.3. vs. 29.8, p = 0.025).This study highlights the high prevalence of iron deficiency, which remains undiagnosed in over half of patients with endometriosis presenting to a gynecologist. Future research should focus on assessing the effectiveness of iron therapy in improving symptoms and overall well‐being in this population. [ABSTRACT FROM AUTHOR]

Background: Iron deficiency is a major contributor to anaemia in chronic kidney diseases. The association of anaemia and iron deficiency with health-related quality of life in Japanese patients with non-dialysis chronic kidney disease has not been examined. In this study, we evaluated anaemia and iron deficiency in patients with chronic kidney disease G3b-5 and examined their associations with health-related quality of life. Methods: This nationwide cohort study included 2,249 patients with advanced chronic kidney disease receiving nephrologist care from 31 representative facilities throughout Japan; they were randomly selected through stratification by region and facility size and aligned with the Chronic Kidney Disease Outcomes and Practice Patterns Study. Using baseline patient data, we assessed the association of anaemia and iron deficiency with health-related quality of life, employing the 36-item Kidney Disease Quality of Life Questionnaire. Results: The mean mental and physical component summary scores for all patients were 49 and 47, respectively. Patients with haemoglobin levels < 10 g/dL had worse three kidney disease subscale, mental component summary, physical component summary, and subdomain scores than those with haemoglobin levels > 12 g/dL. Patients with absolute iron deficiency (TSAT < 20% and ferritin < 100 ng/mL) had worse three kidney disease subscale and mental component summary scores than those with functional iron deficiency (TSAT < 20% and ferritin ≥ 100 ng/mL). Conclusions: Japanese patients with chronic kidney disease G3b-5 with anaemia or absolute iron deficiency had worse health-related quality of life. Our results provide clinical evidence of renal anaemia in Japan and will be useful for international comparisons. [ABSTRACT FROM AUTHOR]

Background: Many pregnant women are reluctant to follow the recommendation concerning oral iron prophylaxis due to concerns about gastrointestinal (GI) side effects. Objective: To assess the frequency of GI complaints during low‐dose oral iron prophylaxis and compare three iron formulas in equipotent doses: ferrous fumarate versus ferrous bisglycinate versus ferrous sulphate, in healthy women with an uncomplicated single pregnancy. Methods: Results from two randomized, double‐blind studies are reported: the Gentofte study comprising 404 women allocated into four groups taking 20, 40, 60, and 80 mg of elemental iron as ferrous fumarate/day and the Naestved study comprising 78 women allocated into two groups: 25 mg of elemental iron as ferrous bisglycinate/day and 50 mg of elemental iron as ferrous sulphate/day between meals from 15 to 19 weeks of gestation to delivery. GI complaints (nausea, vomiting, epigastric pain/pyrosis, belching, meteorism, borborygmi, intestinal colic, flatulence, loose stools, constipation, and use of laxatives), as well as black stools, were recorded by interview at the time of inclusion and at regular intervals during gestation. Results: At inclusion, the frequency of total combined GI complaints in all women (n = 482) was 21%. The Gentofte study showed that in the groups taking 20–60 mg iron/day as fumarate, there was no association between the iron dose and the frequency of GI side effects. An iron dose of 80 mg as fumarate was associated with significantly higher frequencies of constipation and the use of laxatives. Comparing the three equipotent doses of iron formulas, which can prevent iron deficiency, ferrous bisglycinate 25 mg iron had the most favourable GI side effect profile, while ferrous fumarate 40 mg iron and ferrous sulphate 50 mg iron had higher but similar GI side effect profiles. The frequency of black stools increased with the iron dose. Ferrous bisglycinate 25 mg iron had a lower frequency of black stools (8%) than ferrous fumarate 40 mg iron (22%) and ferrous sulphate 50 mg iron (31%). Conclusion: Low‐dose iron supplementation appears to have no clinically significant GI side effects, as none of the included women presented with GI complaints of such severity that it necessitated either reduction of iron dose, change to an alternative iron formula, or discontinuation of iron supplement. However, ferrous bisglycinate 25 mg iron/day is associated with significantly fewer GI complaints than ferrous fumarate 40 mg iron/day and ferrous sulphate 50 mg iron/day. Ferrous bisglycinate may be preferred for iron prophylaxis, especially in women experiencing GI side effects when taking other conventional iron formulas. [ABSTRACT FROM AUTHOR]

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]

Patients with heart failure (HF) often experience iron deficiency. Intravenous iron supplementation has been widely used in clinical practice to facilitate the treatment of HF. However, the association between dietary iron intake and HF still needs to be elucidated. This study aimed to evaluate the impact of dietary iron intake on HF in American adults. The data were extracted from the National Health and Nutrition Examination Survey (NHANES) 2009–2018. Iron dietary intake data were obtained from two 24-h dietary recall interviews. We examined baseline data and HF prevalence in different quartile groups of dietary iron intake (Q1–Q4). Two logistic regression models were established to evaluate the impact of Q4 (highest iron consumption) on the risk of HF. The study included 20,853 American adults (age ≥ 20 years). The participants with the highest iron intake (Q4) had the lowest prevalence of HF (Q1: 3.25%, Q2: 2.18%, Q3: 1.92%, Q4: 1.72%; P < 0.001). After adjusting for possible confounding factors, the highest iron intake (Q4) was significantly associated with a reduced risk of HF compared with that of Q1 (odds ratio 0.58, 95% confidence interval 0.41–0.82; P = 0.003). This association remained stable in subgroups of women, current smokers, and Hispanics other than Mexican Americans. This study revealed that the dietary intake of iron was negatively associated with HF in adults without exceeding the tolerable maximum daily intake of 45 mg/day. [ABSTRACT FROM AUTHOR]

Background and Aims Intravenous iron therapies contain iron–carbohydrate complexes, designed to ensure iron becomes bioavailable via the intermediary of spleen and liver reticuloendothelial macrophages. How other tissues obtain and handle this iron remains unknown. This study addresses this question in the context of the heart. Methods A prospective observational study was conducted in 12 patients receiving ferric carboxymaltose (FCM) for iron deficiency. Myocardial, spleen, and liver magnetic resonance relaxation times and plasma iron markers were collected longitudinally. To examine the handling of iron taken up by the myocardium, intracellular labile iron pool (LIP) was imaged in FCM-treated mice and cells. Results In patients, myocardial relaxation time T1 dropped maximally 3 h post-FCM, remaining low 42 days later, while splenic T1 dropped maximally at 14 days, recovering by 42 days. In plasma, non-transferrin-bound iron (NTBI) peaked at 3 h, while ferritin peaked at 14 days. Changes in liver T1 diverged among patients. In mice, myocardial LIP rose 1 h and remained elevated 42 days after FCM. In cardiomyocytes, FCM exposure raised LIP rapidly. This was prevented by inhibitors of NTBI transporters T-type and L-type calcium channels and divalent metal transporter 1. Conclusions Intravenous iron therapy with FCM delivers iron to the myocardium rapidly through NTBI transporters, independently of reticuloendothelial macrophages. This iron remains labile for weeks, reflecting the myocardium's limited iron storage capacity. These findings challenge current notions of how the heart obtains iron from these therapies and highlight the potential for long-term dosing to cause cumulative iron build-up in the heart. [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]

ABSTRACT: Introduction: Intravenous iron sucrose (IVIS) is a rapidly acting, safe, and effective treatment for moderate anemia among pregnant women. The effectiveness of IVIS at 6 months post IVIS infusion was unknown. We, therefore, assessed the mean increase in hemoglobin concentration and body iron replenishment status at 6 months after the last dose of IVIS infusion. Methods: The study was conducted in 28 villages served by two primary health centers in district Faridabad, Haryana. The participants (n = 129), when originally recruited in 2020, were all moderately anemic (hemoglobin level 7.0 to 9.9 g/dL) pregnant women in either the second or third trimester of pregnancy. Their iron deficiency was calculated by Ganzoni's formula with additional allowance of 500 mg of depot iron. The calculated deficit was rounded off to the nearest 100 mg. The dose of IVIS was 300 mg of iron diluted in 300 ml of normal saline administered intravenously every third day till the full calculated dose was administered. In this study, we collected the follow-up blood specimen 6 months after the last dose of IVIS and measured the hemoglobin concentration, C-Reactive protein (CRP), and serum ferritin level. Hemoglobin concentration was measured using an automated hematology analyzer (Sysmex XS-1000i). Serum ferritin and CRP were measured by enhanced chemiluminescence immunoassay and the enzymatic heterogeneous, sandwich immunoassay method, respectively (VITROS ECiQ, Ortho Clinical Diagnostics, New Jersey, USA). Results: The mean [standard deviation (SD)] duration of time elapsed since the administration of the last dose of IVIS infusion was 6.4 (0.9) months. The mean (SD) hemoglobin level at the time of original recruitment (baseline) was 8.7 ± 0.8 g/dL. The mean (SD) increase in the hemoglobin concentration at 6 months follow-up was 3.2 [95% confidence interval (CI): 3.0–3.4)] g/dL. The median [interquartile range (IQR)] serum ferritin level (ng/mL) at follow-up was 28.1 (12.7, 61.5). A total of 10.2% of the participants had a raised (>10 mg/L) CRP level. Adjusting for CRP level and based on serum ferritin level, the proportion of participants who were iron-deficient was 35.3%. The proportion of participants who had any degree of anemia was 70.5%. Conclusion: Administration of IVIS infusion was effective in raising the mean hemoglobin concentration and in replenishing the body iron reserve at 6 months post infusion. [ABSTRACT FROM AUTHOR]

ABSTRACT: Purpose: Undernutrition in children is a critical worldwide concern that hampers both their physical and cognitive growth. The nutritional status of school-going children and adolescents remains insufficiently addressed with no comprehensive data. This is the first study from the Himalayan foothills that aims to assess the clinical and laboratory aspects of anemia with micronutrient status in undernourished children above the age of five along with association of clinical features with anemia severity. Materials and Methods: A cross-sectional study was conducted involving children aged 5-18 years with undernutrition in a tertiary hospital in North India over eighteen months. We observed the prevalence of anemia, its morphological type, micronutrient status, clinical features, and demographic parameters of these children. The association of various clinical features and anthropometric parameters with the severity of anemia was determined. Results: Of the 200 children who were enrolled in the study, 77% were found anemic, with the proportion of mild, moderate, and severe anemia being 18.2%, 46.8%, and 35%, respectively. Iron (67%) was the most common micronutrient deficient in these children with a significant number suffering from vitamin B12 (53.9%) deficiency. Folic acid deficiency was relatively low (10.4%). Body mass index (P = 0.009), fatigability (P = 0.001), pallor (P ≤ 0.001), poor academic performance (P = 0.023), and knuckle hyperpigmentation (P = 0.018) were significantly associated with the severity of anemia. Conclusion: Despite the significant tread in various aspects of human development, undernutrition and anemia remain a formidable challenge, especially in developing countries. A high proportion of anemia in undernutrition indicates the gravity of the issue, yet not received the deserved attention. [ABSTRACT FROM AUTHOR]

Background and Objectives: In Japan, apheresis donation of plasma is allowed to a maximum of 24 times a year, and plateletpheresis are counted as two plasmapheresis donations. Diversion of the initial blood flow is conducted for all donations, and additionally, blood remaining in apheresis machine circuit is lost. Here, we aimed to investigate on the health impact of frequent apheresis donations, as measured by the serum ferritin (sFer). Materials and Methods: A total of 538 male apheresis donors and 538 age‐matched whole blood (WB) donors, who gave informed consent to join the study, were enrolled. sFer were compared, according to age. Another group of 19 apheresis donors were followed during four consecutive donations. Results: About half (48%) of repeat male apheresis donors had iron deficiency (sFer < 26 ng/mL), compared with lower rates (13.9%) among male WB donors. It was evident in all age groups, except for teenagers, possibly because of the lower number of donations. Follow‐up of the 19 donors for 4 months revealed a progressive decrease in sFer. Conclusion: Blood remaining in the apheresis machine circuit and diversion of the initial blood flow have been implicated in iron deficiency for many years. Taking the present results, the manufacturer of apheresis equipment was requested to improve it to allow rinseback of the remaining blood, which was achieved only for plateletpheresis. Until further improvement, plasmapheresis frequency was reduced to 12 times a year. Additional measures, such as oral supplementation of iron, need to be considered. [ABSTRACT FROM AUTHOR]

Introduction: Children are more vulnerable to anaemia due to their rapid growth, which requires an expanding erythroid mass and a high tissue iron demand. Anaemia can negatively impact psychomotor and cognitive development and can lead to a decline in immunity. Reticulocytes are precursors to erythrocytes and make up about 1% (ranging from 0.5% to 2.5%) of circulating erythrocytes. The reticulocyte content serves as a measurement of haemoglobin within the reticulocyte and correlates directly with the functional availability of iron in the bone marrow. Consequently, it is considered one of the strongest predictors of Iron Deficiency (ID). The Reticulocyte Haemoglobin Content (RET-Hb) level is useful for diagnosing anaemia before it clinically manifests in a patient. Aim: To assess the effectiveness of RET-Hb content as a predictor for early response to oral iron therapy in comparison to haemoglobin levels. Materials and Methods: This prospective interventional study was conducted in the Department of Paediatrics at a tertiary care Hospital in Thrissur, Central Kerala, India, over a period of 18 months, from December 2019 to June 2021. A total of 44 samples were included in the study, and socio-demographic details were collected using a semistructured proforma from patients with haemoglobin levels below the mean reference value. Baseline haemogram parameters {Mean Corpuscular Volume (MCV), Mean Corpuscular Haemoglobin (MCH), Mean Corpuscular Haemoglobin Concentration (MCHC), Red Cell Distribution Width (RDW), Haemtocrit (HCT)}, reticulocyte indices, and ferritin levels were measured before administering oral iron therapy (T0). These parameters were reassessed after seven days (T1) and 30 days (T2) following the initiation of therapy. The Chi-square test was used to assess the association between various factors, and Pearson's correlation coefficient was utilised to find the correlation. Results: The mean age of the participants was 3.46±2.2 years, with 24 males and 20 females included in the study. The mean RET-Hb was 21.15±1.71 pg before the initiation of treatment, which significantly increased to 23.37±1.95 pg and 25.77±1.56 pg at days 7 and 30, respectively. The haemoglobin level increased from 8.37±1.25 g/L to 8.55±1.19 g/L and 9.72±0.98 g/L at T1 and T2, respectively, which was statistically significant. The Absolute Reticulocyte Count (RET#) also showed a significant early increase after initiating treatment. Conclusion: These findings indicate that RET-Hb and RET# are reliable early predictors of response to iron therapy, alongside haemoglobin levels, and can be used as effective alternatives. [ABSTRACT FROM AUTHOR]

Genes involved in iron deficiency responses have been well characterized in Arabidopsis thaliana, but their roles in crop species have not been well explored. Reliance on model species may fail to identify novel iron stress mechanisms present within crop species, likely selected by hundreds of years of selection. Fiskeby III (PI 438471) is a soybean line from Sweden that demonstrates high levels of resilience to numerous stresses. Earlier Fiskeby III studies have identified a suite of genes responding to iron deficiency stress in Fiskeby III that are also associated with Arabidopsis iron deficiency responses. We were interested in determining how canonical iron genes function in Fiskeby III under normal and iron stress conditions. To investigate this, we used virus-induced gene silencing to knock down gene expression of three iron deficiency response genes (FER-like iron deficiency induced transcription factor (FIT), elongated hypocotyl 5 (HY5) and popeye (PYE)) in Fiskeby III. Analyses of RNAseq data generated from silenced plants in iron-sufficient and -deficient conditions found silencing FIT and HY5 altered general stress responses but did not impact iron deficiency tolerance, confirming Fiskeby III utilizes novel mechanisms to tolerate iron deficiency stress. [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]

Introduction: Heart failure (HF) is a global health challenge that requires a multidisciplinary approach. Despite recent advances in pharmacological and interventional therapy, morbidity and mortality in these patients remain high. For this reason, and because of its interplay with other cardiovascular and non-cardiovascular diseases, HF represents a major area of research, with new trials being published every year and international guidelines constantly updated. Areas covered: The authors review the current status and possible future developments in HF pharmacotherapy. Expert opinion: The treatment of HF has made significant advances in recent years, and the current recommendations are based on large outcome trials. This has led to significant reductions in both mortality and morbidity, but the death rate remains unacceptably high. In this context, a patient-centered approach that considers comorbidities and specific clinical scenarios when dosing HF medication is essential. Prevention of hospital admissions for cardiac decompensation is of utmost importance in patients with HF as is the enablement of activities of daily living, an endpoint which has only recently been incorporated into major HF trials. [ABSTRACT FROM AUTHOR]

Background: Iron Deficiency (ID) affects two billion people worldwide, predominantly adolescent girls, and may be associated with increased psychopathology. The associations between ID and symptoms of depression and anxiety in adolescents were examined using data from the National Health and Nutrition Examination Survey (NHANES), a cross-sectional survey of a nationally representative sample of non-institutionalized Americans. Methods: The current analysis included survey cycles where both iron-related markers and mental health-related outcomes were collected in adolescents 12 to 17 years old. Acute and serious medical conditions, acute inflammation, and abnormal birth weight led to exclusion. Linear multivariable regression analyses examined the association between ID status (defined based on the total body iron model) and (1) total Patient Health Questionnaire (PHQ-9) score, (2) one item examining anxiety severity, and (3) one item examining overall mental well-being. Covariates included age, sex, race and ethnicity, body mass index, household income, head-of-household marital status, and psychotropic medication use. Sensitivity analyses examined the robustness of the findings when ID was defined based on the ferritin model. Results: In 1990 adolescents (age [mean ± SD]: 14.5 ± 1.7 years; 85.7% females), ID with and without anemia was significantly associated with a higher PHQ-9 score in multiracial adolescents (Cohen's d = 1.09, p = 0.0005 for ID without anemia; d = 0.92, p = 0.0395 for ID with anemia). Moreover, ID with anemia was associated with more severe anxiety (d = 3.00, p = 0.0130) and worse mental well-being (d = 2.75, p = 0.0059) in multiracial adolescents. The findings remained significant after adjusting for psychotropic use and in the sensitivity analyses. Conclusions: Iron deficiency is associated with poorer mental health in adolescents of multiracial background. Future studies should confirm these findings prospectively and examine the underlying mechanism. [ABSTRACT FROM AUTHOR]

Background/Objectives. Iron deficiency is one of the most common nutritional deficiencies worldwide and is the leading cause of anemia in the pediatric population (microcytic, hypochromic anemia due to iron deficiency). Moreover, untreated iron deficiency can lead to various systemic consequences and can disrupt the child's development. Methods/Results. Therefore, a team of experts from the Polish Pediatric Society, the Polish Society of Pediatric Oncology and Hematology, the Polish Neonatology Society, and the Polish Society of Family Medicine, based on a review of the current literature, their own clinical experience, and critical discussion, has developed updated guidelines for the diagnosis, prevention, and treatment of iron deficiency in children from birth to 18 years of age. These recommendations apply to the general population and do not take into account the specifics of individual conditions and diseases. [ABSTRACT FROM AUTHOR]

Ammonia (NH3), which is an intermediate of nitrogen metabolism, has been found to be a gasotransmitter in plants. It has a dual physiological effect in a concentration-dependent manner, namely as a signaling molecule at low concentrations and a cytotoxin at high concentrations. In plants, NH3, as a gasotransmitter, can maintain homeostasis by multiple pathways, which are involving in biosynthesis, assimilation, and transport. Gasotransmitter NH3 can regulate plant growth, development, and response to multiple environmental stresses by crosstalk with other signaling molecules. However, a few reviews have summarized NH3 homeostasis and its signaling role in plant growth and stress response. Hence, in this review, based on the progress in NH3, whose toxicity, metabolism, and membrane transport were summarized. Also, the signaling role of NH3 in cell division, seed germination, and root system architecture was discussed. Furthermore, NH3-induced stress resistance, including drought, heat, salt, iron deficiency, elevated CO2, and pathogen infection tolerance, was summed up. This review is to further understanding the gasotransmitter role of NH3, and lays the foundation for designing and developing climate-resilient crops for food safety and sustainable agriculture. [ABSTRACT FROM AUTHOR]

Introduction: Nitrogen (N) and iron (Fe) are involved in several biochemical processes in living organisms, and their limited bioavailability is a strong constraint for plant growth and yield. This work investigated the interplay between Fe and N nutritional pathways in tomato plants kept under N and Fe deficiency and then resupplied with Fe and N (as nitrate, ammonium, or urea) through a physiological, metabolomics and gene expression study. Results: After 24 hours of Fe resupply, the Fe concentration in Fe-deficient roots was dependent on the applied N form (following the pattern: nitrate > urea > ammonium > Fe-deficient control), and whereas in leaves of urea treated plants the Fe concentration was lower in comparison to the other N forms. Untargeted metabolomics pointed out distinctive modulations of plant metabolism in a treatment-dependent manner. Overall, N-containing metabolites were affected by the treatments in both leaves and roots, while N form significantly shaped the phytohormone profile. Moreover, the simultaneous application of Fe with N to Fe-deficient plants elicited secondary metabolites’ accumulation, such as phenylpropanoids, depending on the applied N form (mainly by urea, followed by nitrate and ammonium). After 4 hours of treatment, ammonium- and urea-treated roots showed a reduction of enzymatic activity of Fe(III)-chelate reductase (FCR), compared to nitrate or N-depleted plants (maintained in Fe deficiency, where FCR was maintained at high levels). The response of nitrate-treated plants leads to the improvement of Fe concentration in tomato roots and the increase of Fe(II) transporter (IRT1) gene expression in tomato roots. Conclusions: Our results strengthen and improve the understanding about the interaction between N and Fe nutritional pathways, thinning the current knowledge gap. [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]

Introduction: The factors contributing to blood loss during hemodialysis (HD) procedures remain underexplored. This study aimed to quantify blood loss during HD and identify the potential factors associated with it. Methods: The study included 70 ESRD patients undergoing HD. After dialysis, the extracorporeal blood circuits were rinsed with 1,000 mL of 0.05% NH3 solution in distilled water, and hemoglobin levels were measured. Univariate regression was used to assess the linear relationship between residual red blood cell (RBC) volume and various parameters, including HD mode, dialyzer surface area, ultrafiltration goal, hypotension during HD, blood flow rate, activated partial thromboplastin time, and C-reactive protein. Multivariate regression was also conducted to explore the relationships among these parameters. Results: The mean RBC volume remaining in the extracorporeal blood circuit after HD was 1.6 ± 0.9 mL (mode: 1.0, range: 0.3–6.5 mL). When converted to whole blood volume per patient, the mean blood volume was 5.3 ± 3.0 mL (median: 4.1 mL, mode: 4.0 mL, range: 1.0–19.0 mL). Multivariate analysis identified the dialyzer surface area as the only significant determinant of residual RBC volume. Conclusion: After HD, the remaining RBC volume in the extracorporeal blood circuit varies from 1.6 to 6.5 mL. When the RBC volume was converted to whole blood volume for each case, the blood loss ranged from 1.0 to 19.0 mL. Dialyzer surface area was the only significant determinant of residual RBC volume. [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]

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]

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]

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]

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]

Approximately half of pregnant women in India are anemic, representing over 7.5 million women. Few studies have assessed the relationship between multiple micronutrient deficiencies and anemia during pregnancy or the trajectory of hemoglobin (Hb) during pregnancy in low‐resource settings. We enrolled 200 pregnant women from the Maternal and Newborn Health (MNH) registry, a population‐based pregnancy and birth registry in Eastern Maharashtra, India to address these gaps. The women provided capillary (finger‐prick) and venous blood specimens at enrollment (<15 weeks), and a second capillary specimen in the 3rd trimester (>27 weeks). Capillary specimens were analyzed at the time of collection with a HemoCue Hb 201+; venous specimens were shipped on dry ice to a laboratory for cyanmethemoglobin assessment. In the 1st trimester, mean Hb concentration and anemia (Hb<11.0 g/dL) prevalence using capillary specimens were 10.9 ± 1.5 g/dL and 51.1%; mean Hb concentration using venous blood specimens was estimated to be 11.3 ± 1.3 g/dL and anemia prevalence was 37.5%. The prevalence of iron, vitamin B12 and folate deficiencies were 40%, 30% and 0%, respectively. Among women with anemia in the 1st trimester (venous blood), 56% had concurrent iron deficiency (inflammation‐adjusted serum ferritin <15 µg/L) indicating that their anemia may be amenable to iron supplementation. In total, 21% of women had ID and anemia, 19% ID in the absence of anemia, 16.5% anemia in the absence of ID and 43.5% had neither. By the 3rd trimester, mean Hb from capillary specimens had declined to 10.1 ± 1.35 g/dL and anemia prevalence increased to 70.7%, despite 99.4% mothers reporting receipt of iron‐folic acid (IFA) supplements during her current pregnancy, and 83.9% reporting IFA consumption the previous day. Significant predictors of anemia in the 1st trimester (both venous and capillary) included the number of weeks gestation at the time of Hb assessment and inflammation‐adjusted serum ferritin. For 3rd trimester anemia, significant predictors included 1st trimester height, BMI and IFA consumption during the 3rd trimester (but not 1st trimester micronutrient biomarkers), indicating that IFA supplementation over the course of pregnancy may have influenced micronutrient status and anemia risk. Our findings highlight the severity of the burden of anemia and micronutrient deficiencies in Eastern Maharashtra, but also highlight that in many cases, ID and anemia affect different individuals. Preventing and managing anemia in pregnancy in India will require strengthening both clinical and community‐based strategies targeting iron deficiency, as well as other causes of anemia. Key messages: Anemia, iron deficiency and vitamin B12 deficiency were all highly prevalent in pregnant women in Eastern Maharashtra, India. The prevalence of anemia increased over the course of pregnancy despite high reported rates of receipt (99.4%) and consumption of iron folic acid supplements (83.9% in the previous day).Measuring hemoglobin concentration from single‐drop capillary blood specimens (from finger pricks) with a point‐of‐care analyzer (i.e. HemoCue Hb 201+) resulted in lower concentration estimates (10.9 g/dL vs. 11.3 g/dL) and higher anemia prevalence (51.1% vs. 37.5%) in the 1st trimester of pregnancy than venous blood tested in a laboratory with the cyanmethemoglobin method.Addressing anemia during pregnancy in India, and other Low‐ and Middle‐income country settings, will require strengthening clinical and community‐based strategies addressing iron deficiency, but also other nutritional and non‐nutritional causes of anemia. When possible, hemoglobin assessment should be conducted on venous blood specimens. [ABSTRACT FROM AUTHOR]

The purpose of this quasi-experimental research was to study the outcomes of a behavior modification program aimed at preventing iron deficiency anemia among primary school students in schools under the jurisdiction of Yasothon Municipality. The sample group consisted of two groups of 50 participants each, comprising an experimental group that received the program and a comparison group that underwent the standard program. Data were collected from both groups twice, before and after the intervention, between October 1, 2023, and February 29, 2024. The data were analyzed using statistical software, with a significance level set at 0.05. The independent t-test was employed to compare mean values between the two independent groups, and the paired t-test was utilized to assess mean differences within the groups. The results indicated that the hemoglobin concentration, knowledge of anemia, attitude towards anemia prevention, participation in anemia prevention, social support for anemia prevention, and iron-deficiency anemia prevention behavior of elementary school students in the intervention group were significantly higher than those in the comparison group at the 0.05 significance level. Therefore, the intervention program on iron-deficiency anemia prevention behavior in elementary school students was deemed effective according to the objectives set. [ABSTRACT FROM AUTHOR]