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1.
J Healthc Qual ; 46(4): 220-227, 2024.
Article in English | MEDLINE | ID: mdl-38833574

ABSTRACT

INTRODUCTION: Studies have demonstrated the efficacy of intravenous (IV) iron when administered to patients with congestive heart failure (CHF) and iron deficiency (ID). We aimed to better understand the adherence of treatment for ID among a population with CHF, with particular interest in high-risk groups not often studied due to inadequate recruitment. METHODS: A retrospective chart review at our institution was conducted from January 1, 2012, to July 7, 2021. Analysis included hospitalized patients with CHF and ID and dividing these patients into two time periods based on changes in iron treatment patterns and treatment between sexes. RESULTS: Four thousand eight hundred thirteen patients were included in this study. During the "early era," 7.0% of patients with CHF and ID received IV iron compared with 20.9% of "late-era" patients. Female patients with ID were statistically less likely to receive IV iron when compared with male patients, both unadjusted (0.66, confidence interval [CI] 0.55-0.79, p < .0001) and adjusted (0.72, CI 0.59-0.87, p < .0001) for covariates. CONCLUSION: This study illustrates improved adherence to treatment for ID among hospitalized population with CHF and ID over time but persistent undertreatment remains. Future studies will need to identify the barriers to treating female patients with CHF and ID to reduce these disparities.


Subject(s)
Heart Failure , Humans , Heart Failure/drug therapy , Female , Male , Retrospective Studies , Aged , Middle Aged , Anemia, Iron-Deficiency/drug therapy , Hospitalization/statistics & numerical data , Aged, 80 and over , Iron/therapeutic use , Iron/administration & dosage , Iron Deficiencies , Sex Factors
2.
Mol Med ; 30(1): 90, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38886644

ABSTRACT

BACKGROUND: Aortic dissection (AD) is a macrovascular disease which is pathologically characterized by aortic media degeneration.This experiment aims to explore how iron deficiency (ID) affects the function of vascular smooth muscle cell (VSMC) and participates in the occurrence and development of AD by regulating gene expression. METHODS: The relationship between iron and AD was proved by Western-blot (WB) and immunostaining experiments in human and animals. Transcriptomic sequencing explored the transcription factors that were altered downstream. WB, flow cytometry and immunofluorescence were used to demonstrate whether ID affected HIF1 expression through oxygen transport. HIF1 signaling pathway and phenotypic transformation indexes were detected in cell experiments. The use of the specific HIF1 inhibitor PX478 further demonstrated that ID worked by regulating HIF1. RESULTS: The survival period of ID mice was significantly shortened and the pathological staining results were the worst. Transcriptomic sequencing indicated that HIF1 was closely related to ID and the experimental results indicated that ID might regulate HIF1 expression by affecting oxygen balance. HIF1 activation regulates the phenotypic transformation of VSMC and participates in the occurrence and development of AD in vivo and in vitro.PX478, the inhibition of HIF1, can improve ID-induced AD exacerbation.


Subject(s)
Aortic Dissection , Muscle, Smooth, Vascular , Myocytes, Smooth Muscle , Oxygen , Signal Transduction , Animals , Humans , Male , Mice , Aortic Dissection/metabolism , Aortic Dissection/etiology , Aortic Dissection/genetics , Aortic Dissection/pathology , Disease Models, Animal , Gene Expression Regulation , Hypoxia-Inducible Factor 1/metabolism , Hypoxia-Inducible Factor 1/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Iron Deficiencies , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , Myocytes, Smooth Muscle/metabolism , Oxygen/metabolism , Phenotype
3.
Plant Physiol Biochem ; 213: 108786, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38878387

ABSTRACT

Iron (Fe) deficiency is a general stress for many horticulture crops, causing leaf chlorosis and stunted growth. The basic-helix-loop-helix (bHLH) transcription factor (TF) was reported to function in Fe absorption; however, the regulatory mechanism of bHLH genes on iron absorption remains largely unclear in pear. In this study, we found that PbbHLH155 was significantly induced by Fe deficiency. Overexpression of PbbHLH155 in Arabidopsis thaliana and pear calli significantly increases resistance to Fe deficiency. The PbbHLH155-overexpressed Arabidopsis lines exhibited greener leaf color, higher Fe content, stronger Fe chelate reductase (FCR) and root acidification activity. The PbbHLH155 knockout pear calli showed lower Fe content and weaker FCR activity. Interestingly, PbbHLH155 inhibited the expressions of PbFRO2 and PbbHLH38, which were positive regulators in Fe-deficiency responses (FDR). Furthermore, yeast one-hybrid (Y1H) and Dual-Luciferase Reporter (DLR) assays revealed that PbbHLH155 directly binds to the promoters of PbFRO2 and PbbHLH38, thus activating their expression. Overall, our results showed that PbbHLH155 directly promote the expression of PbFRO2 and PbbHLH38 to activate FCR activity for iron absorption. This study provided valuable information for pear breeding.


Subject(s)
Arabidopsis , Basic Helix-Loop-Helix Transcription Factors , Gene Expression Regulation, Plant , Iron Deficiencies , Plant Proteins , Pyrus , Pyrus/genetics , Pyrus/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Arabidopsis/genetics , Arabidopsis/metabolism , Basic Helix-Loop-Helix Transcription Factors/metabolism , Basic Helix-Loop-Helix Transcription Factors/genetics , Plants, Genetically Modified , Iron/metabolism , FMN Reductase/metabolism , FMN Reductase/genetics
4.
Nutrients ; 16(12)2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38931165

ABSTRACT

Iron deficiency is the number one nutritional problem worldwide. Iron uptake is regulated at the intestine and is highly influenced by the gut microbiome. Blood from the intestines drains directly into the liver, informing iron status and gut microbiota status. Changes in either iron or the microbiome are tightly correlated with the development of metabolic dysfunction-associated steatotic liver disease (MASLD). To investigate the underlying mechanisms of the development of MASLD that connect altered iron metabolism and gut microbiota, we compared specific pathogen free (SPF) or germ-free (GF) mice, fed a normal or low-iron diet. SPF mice on a low-iron diet showed reduced serum triglycerides and MASLD. In contrast, GF low-iron diet-fed mice showed increased serum triglycerides and did not develop hepatic steatosis. SPF mice showed significant changes in liver lipid metabolism and increased insulin resistance that was dependent upon the presence of the gut microbiota. We report that total body loss of mitochondrial iron importer Mitoferrin2 (Mfrn2-/-) exacerbated the development of MASLD on a low-iron diet with significant lipid metabolism alterations. Our study demonstrates a clear contribution of the gut microbiome, dietary iron, and Mfrn2 in the development of MASLD and metabolic syndrome.


Subject(s)
Gastrointestinal Microbiome , Liver , Animals , Female , Male , Mice , Fatty Liver/etiology , Insulin Resistance , Iron/metabolism , Iron Deficiencies , Iron, Dietary/administration & dosage , Lipid Metabolism , Liver/metabolism , Mice, Inbred C57BL , Mice, Knockout , Mitochondria/metabolism , Mitochondrial Proteins/metabolism , Triglycerides/blood
7.
Nutrients ; 16(11)2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38892681

ABSTRACT

In pregnant women with multiple infections, nutrient deficiencies, and inflammation (MINDI), the study of anemia and iron status is limited. For this cross-sectional study (n = 213 Panamanian indigenous women), we investigated if hemoglobin, anemia (Hb < 110 g/L), ferritin, serum iron, serum transferrin receptor, and hepcidin were associated with (1) maternal nutritional status and supplementation practices, (2) biomarkers of inflammation, and (3) presence/absence of infections. Hierarchical generalized linear and logistic regression models and dominance analyses identified the relative importance of these predictors. Anemia (38%), which was likely underestimated due to low plasma volume (95%), was associated with lower ferritin, vitamin A, and weight-for-height, suggesting anemia of undernutrition. Inflammation was not associated with Hb or anemia; nevertheless, higher CRP was associated with increased odds of low serum iron and higher ferritin and hepcidin, indicating iron restriction due to inflammation. The length of iron supplementation did not enter models for anemia or iron indicators, but a multiple nutrient supplement was associated with higher ferritin and hepcidin. Moreover, iron supplementation was associated with higher odds of vaginal trichomoniasis but lower odds of caries and bacterial vaginosis. The complex pathogenesis of anemia and iron deficiency in MINDI settings may require other interventions beyond iron supplementation.


Subject(s)
Anemia, Iron-Deficiency , Ferritins , Hepcidins , Inflammation , Iron , Nutritional Status , Humans , Female , Pregnancy , Inflammation/blood , Adult , Cross-Sectional Studies , Iron/blood , Anemia, Iron-Deficiency/epidemiology , Anemia, Iron-Deficiency/blood , Ferritins/blood , Hepcidins/blood , Dietary Supplements , Biomarkers/blood , Young Adult , Iron Deficiencies , Hemoglobins/analysis , Hemoglobins/metabolism , Cohort Studies , Anemia/epidemiology , Anemia/blood , Anemia/etiology , Receptors, Transferrin/blood , Maternal Nutritional Physiological Phenomena
8.
Int J Mol Sci ; 25(11)2024 May 24.
Article in English | MEDLINE | ID: mdl-38891917

ABSTRACT

The European "Green Deal" policies are shifting toward more sustainable and environmentally conscious agricultural practices, reducing the use of chemical fertilizer and pesticides. This implies exploring alternative strategies. One promising alternative to improve plant nutrition and reinforce plant defenses is the use of beneficial microorganisms in the rhizosphere, such as "Plant-growth-promoting rhizobacteria and fungi". Despite the great abundance of iron (Fe) in the Earth's crust, its poor solubility in calcareous soil makes Fe deficiency a major agricultural issue worldwide. Among plant promoting microorganisms, the yeast Debaryomyces hansenii has been very recently incorporated, for its ability to induce morphological and physiological key responses to Fe deficiency in plants, under hydroponic culture conditions. The present work takes it a step further and explores the potential of D. hansenii to improve plant nutrition and stimulate growth in cucumber plants grown in calcareous soil, where ferric chlorosis is common. Additionally, the study examines D. hansenii's ability to induce systemic resistance (ISR) through a comparative relative expression study by qRT-PCR of ethylene (ET) biosynthesis (ACO1), or ET signaling (EIN2 and EIN3), and salicylic acid (SA) biosynthesis (PAL)-related genes. The results mark a significant milestone since D. hansenii not only enhances nutrient uptake and stimulates plant growth and flower development but could also amplify induced systemic resistance (ISR). Although there is still much work ahead, these findings make D. hansenii a promising candidate to be used for sustainable and environmentally friendly integrated crop management.


Subject(s)
Crop Production , Fertilizers , Crop Production/methods , Iron/metabolism , Cucumis sativus/microbiology , Cucumis sativus/growth & development , Cucumis sativus/metabolism , Crops, Agricultural/microbiology , Crops, Agricultural/growth & development , Crops, Agricultural/metabolism , Iron Deficiencies , Gene Expression Regulation, Plant , Debaryomyces/metabolism , Rhizosphere , Ethylenes/metabolism , Soil Microbiology , Salicylic Acid/metabolism
9.
Open Heart ; 11(1)2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38839367

ABSTRACT

BACKGROUND: Iron deficiency (ID) has been reported in patients with congenital heart disease. There is, however, a scarcity of data on its prevalence in patients with a Fontan circulation. The aim of this study is to investigate the prevalence of ID in Fontan patients and to investigate the association between ID and exercise capacity in this population. METHODS AND RESULTS: Blood count and haematological parameters were determined in plasma of 61 Fontan patients (51% female, mean age 29±9 years). ID was defined as transferrin saturation (TSAT) ≤19.8%. The prevalence of ID was 36% (22/61 patients). Especially among women, the diagnosis of ID was highly prevalent (52%) despite normal haemoglobin levels (153.7±18.4 g/L). Mean ferritin levels were 98±80 µg/L and mean TSAT levels were 22%±12%. Cardiopulmonary exercise testing was performed in 46 patients (75%). Patients with ID had a lower peak oxygen uptake (V̇O2peak) (1397±477 vs 1692±530 mL/min; p=0.039), although this relationship was confounded by sex. The presence of ID increased the likelihood of not achieving a respiratory exchange ratio (RER) ≥1.1 by 5-fold (p=0.035). CONCLUSION: ID is highly prevalent among patients with a Fontan circulation. V̇O2peak is lower in patients with ID. Fontan patients with ID are less likely to achieve an RER≥1.1 during cardiopulmonary exercise testing.


Subject(s)
Exercise Test , Exercise Tolerance , Fontan Procedure , Heart Defects, Congenital , Humans , Female , Male , Fontan Procedure/adverse effects , Heart Defects, Congenital/surgery , Heart Defects, Congenital/blood , Heart Defects, Congenital/physiopathology , Heart Defects, Congenital/epidemiology , Exercise Tolerance/physiology , Adult , Prevalence , Young Adult , Biomarkers/blood , Anemia, Iron-Deficiency/blood , Anemia, Iron-Deficiency/epidemiology , Anemia, Iron-Deficiency/diagnosis , Anemia, Iron-Deficiency/physiopathology , Oxygen Consumption/physiology , Iron/blood , Iron Deficiencies , Adolescent , Ferritins/blood
10.
BMC Plant Biol ; 24(1): 495, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38831411

ABSTRACT

BACKGROUND: Phosphorus (P) and iron (Fe) deficiencies are relevant plants nutritional disorders, prompting responses such as increased root exudation to aid nutrient uptake, albeit at an energy cost. Reacquiring and reusing exudates could represent an efficient energy and nitrogen saving strategy. Hence, we investigated the impact of plant development, Fe and P deficiencies on this process. Tomato seedlings were grown hydroponically for 3 weeks in Control, -Fe, and -P conditions and sampled twice a week. We used Isotope Ratio Mass-Spectrometry to measure δ13C in roots and shoots after a 2-h exposure to 13C-labeled glycine (0, 50, or 500 µmol L-1). Plant physiology was assessed with an InfraRed Gas Analyzer and ionome with an Inductively Coupled Plasma Mass-Spectrometry. RESULTS: Glycine uptake varied with concentration, suggesting an involvement of root transporters with different substrate affinities. The uptake decreased over time, with -Fe and -P showing significantly higher values as compared to the Control. This highlights its importance during germination and in nutrient-deficient plants. Translocation to shoots declined over time in -P and Control but increased in -Fe plants, suggesting a role of Gly in the Fe xylem transport. CONCLUSIONS: Root exudates, i.e. glycine, acquisition and their subsequent shoot translocation depend on Fe and P deficiency. The present findings highlight the importance of this adaptation to nutrient deficiencies, that can potentially enhance plants fitness. A thorough comprehension of this trait holds potential significance for selecting cultivars that can better withstand abiotic stresses.


Subject(s)
Glycine , Phosphorus , Plant Roots , Solanum lycopersicum , Solanum lycopersicum/metabolism , Solanum lycopersicum/growth & development , Glycine/metabolism , Plant Roots/metabolism , Plant Roots/growth & development , Phosphorus/metabolism , Phosphorus/deficiency , Iron Deficiencies , Iron/metabolism , Biological Transport , Seedlings/metabolism , Seedlings/growth & development , Plant Shoots/metabolism , Plant Shoots/growth & development
11.
JAMA Netw Open ; 7(6): e2413967, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38848068

ABSTRACT

Importance: The prevalence of iron deficiency varies widely according to how it is defined. Objective: To compare the prevalence of iron deficiency among women using 3 different definitions. Design, Setting, and Participants: The cross-sectional Hemochromatosis and Iron Overload Screening Study (HEIRS; 2000-2006) evaluated the prevalence, determinants, and outcomes of hemochromatosis and other iron-related disorders. Multiethnic, primary care-based screening (2001-2003) was performed at 5 field centers (4 in the US and 1 in Canada). Volunteer women aged 25 years and older were recruited at primary care venues associated with the field centers. Data were analyzed from June to December 2023. Main Outcomes and Measures: Measures included transferrin saturation, serum ferritin level, and self-reported age, pregnancy, and race and ethnicity. Three iron deficiency definitions were studied: (1) combined transferrin saturation less than 10% and serum ferritin less than 15 ng/mL (HEIRS), (2) serum ferritin less than 15 ng/mL (World Health Organization [WHO]), and (3) serum ferritin less than 25 ng/mL (a threshold for iron-deficient erythropoiesis [IDE]). Results: Among 62 685 women (mean [SD] age, 49.58 [14.27] years), 1957 women (3.12%) had iron deficiency according to the HEIRS definition, 4659 women (7.43%) had iron deficiency according to the WHO definition, and 9611 women (15.33%) had iron deficiency according to the IDE definition. Among 40 381 women aged 25 to 54 years, 1801 women (4.46%) had iron deficiency according to HEIRS, 4267 women (10.57%) had iron deficiency according to WHO, and 8573 women (21.23%) had iron deficiency according to IDE. Prevalence rates of iron deficiency among 2039 women aged 25 to 44 years who reported pregnancy were 5.44% (111 women) according to HEIRS, 18.05% (368 women) according to WHO, and 36.10% (736 women) according to IDE. Iron deficiency prevalence by the 3 respective definitions increased significantly in each racial and ethnic group and was significantly higher among Black and Hispanic participants than Asian and White participants. The relative iron deficiency prevalence among the 62 685 women increased 2.4-fold (95% CI, 2.3-2.5; P < .001) using the WHO definition and increased 4.9-fold (95% CI, 4.7-5.2; P < .001) using the IDE definition. Conclusions and Relevance: Three definitions of iron deficiency were associated with significantly different prevalence of iron deficiency in women, regardless of self-reported age, pregnancy, or race and ethnicity. Using higher serum ferritin thresholds to define iron deficiency could lead to diagnosis and treatment of more women with iron deficiency and greater reduction of related morbidity.


Subject(s)
Anemia, Iron-Deficiency , Ferritins , Humans , Female , Prevalence , Canada/epidemiology , Adult , Cross-Sectional Studies , Middle Aged , United States/epidemiology , Anemia, Iron-Deficiency/epidemiology , Anemia, Iron-Deficiency/blood , Anemia, Iron-Deficiency/diagnosis , Ferritins/blood , Transferrin/analysis , Transferrin/metabolism , Pregnancy , Iron Deficiencies , Aged
13.
J Am Coll Cardiol ; 83(25): 2674-2689, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38897678

ABSTRACT

Iron deficiency and heart failure frequently co-occur, sparking clinical research into the role of iron repletion in this condition over the last 20 years. Although early nonrandomized studies and subsequent moderate-sized randomized controlled trials showed an improvement in symptoms and functional metrics with the use of intravenous iron, 3 recent larger trials powered to detect a difference in hard cardiovascular outcomes failed to meet their primary endpoints. Additionally, there are potential concerns related to side effects from intravenous iron, both in the short and long term. This review discusses the basics of iron biology and regulation, the diagnostic criteria for iron deficiency and the clinical evidence for intravenous iron in heart failure, safety concerns, and alternative therapies. We also make practical suggestions for the management of patients with iron deficiency and heart failure and outline key areas in need of future research.


Subject(s)
Anemia, Iron-Deficiency , Heart Failure , Iron , Humans , Heart Failure/drug therapy , Anemia, Iron-Deficiency/drug therapy , Iron/administration & dosage , Administration, Intravenous , Iron Deficiencies
14.
Adv Nutr ; 15(6): 100238, 2024 06.
Article in English | MEDLINE | ID: mdl-38729263

ABSTRACT

Vaccines can prevent infectious diseases, but their efficacy varies, and factors impacting vaccine effectiveness remain unclear. Iron deficiency is the most common nutrient deficiency, affecting >2 billion individuals. It is particularly common in areas with high infectious disease burden and in groups that are routinely vaccinated, such as infants, pregnant women, and the elderly. Recent evidence suggests that iron deficiency and low serum iron (hypoferremia) not only cause anemia but also may impair adaptive immunity and vaccine efficacy. A report of human immunodeficiency caused by defective iron transport underscored the necessity of iron for adaptive immune responses and spurred research in this area. Sufficient iron is essential for optimal production of plasmablasts and IgG responses by human B-cells in vitro and in vivo. The increased metabolism of activated lymphocytes depends on the high-iron acquisition, and hypoferremia, especially when occurring during lymphocyte expansion, adversely affects multiple facets of adaptive immunity, and may lead to prolonged inhibition of T-cell memory. In mice, hypoferremia suppresses the adaptive immune response to influenza infection, resulting in more severe pulmonary disease. In African infants, anemia and/or iron deficiency at the time of vaccination predict decreased response to diphtheria, pertussis, and pneumococcal vaccines, and response to measles vaccine may be increased by iron supplementation. In this review, we examine the emerging evidence that iron deficiency may limit adaptive immunity and vaccine responses. We discuss the molecular mechanisms and evidence from animal and human studies, highlight important unknowns, and propose a framework of key research questions to better understand iron-vaccine interactions.


Subject(s)
Adaptive Immunity , Iron Deficiencies , Iron , Vaccine Efficacy , Humans , Animals , Anemia, Iron-Deficiency/prevention & control , Anemia, Iron-Deficiency/immunology , Female , Nutritional Status , Mice , Pregnancy , Vaccination , Vaccines/immunology , Infant
15.
Eur J Heart Fail ; 26(6): 1298-1312, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38727791

ABSTRACT

According to current guidelines, iron deficiency is defined by a serum ferritin level <100 ng/ml or a transferrin saturation (TSAT) <20% if the serum ferritin level is 100-299 µg/L. These criteria were developed to encourage the use of intravenous iron as an adjunct to erythropoiesis-stimulating agents in the treatment of renal anaemia. However, in patients with heart failure, these criteria are not supported by any pathophysiological or clinical evidence that they identify an absolute or functional iron deficiency state. A low baseline TSAT-but not serum ferritin level-appears to be a reliable indicator of the effect of intravenous iron to reduce major heart failure events. In randomized controlled trials, intravenous iron decreased the risk of cardiovascular death or total heart failure hospitalization in patients with a TSAT <20% (risk ratio 0.67 [0.49-0.92]) but not in patients with a TSAT ≥20% (risk ratio 0.99 [0.74-1.30]), with the magnitude of the risk reduction being proportional to the severity of hypoferraemia. Patients who were enrolled in clinical trials solely because they had a serum ferritin level <100 µg/L showed no significant benefit on heart failure outcomes, and it is noteworthy that serum ferritin levels of 20-300 µg/L lie entirely within the range of normal values for healthy adults. Current guidelines reflect the eligibility criteria of clinical trials, which inadvertently adopted unvalidated criteria to define iron deficiency. Reliance on these guidelines would lead to the treatment of many patients who are not iron deficient (serum ferritin level <100 µg/L but normal TSAT) and ignores the possibility of iron deficiency in patients with a low TSAT but with serum ferritin level of >300 µg/L. Importantly, analyses of benefit based on trial eligibility-driven guidelines substantially underestimate the magnitude of heart-failure-event risk reduction with intravenous iron in patients who are truly iron deficient. Based on all available data, we recommend a new mechanism-based and trial-tested approach that reflects the totality of evidence more faithfully than the historical process adopted by clinical investigators and by the guidelines. Until additional evidence is forthcoming, an iron deficiency state in patients with heart failure should be defined by a TSAT <20% (as long as the serum ferritin level is <400 µg/L), and furthermore, the use of a serum ferritin level <100 µg/L alone as a diagnostic criterion should be discarded.


Subject(s)
Anemia, Iron-Deficiency , Ferritins , Heart Failure , Iron , Humans , Heart Failure/blood , Heart Failure/drug therapy , Heart Failure/complications , Anemia, Iron-Deficiency/drug therapy , Anemia, Iron-Deficiency/blood , Anemia, Iron-Deficiency/diagnosis , Iron/blood , Iron/administration & dosage , Ferritins/blood , Iron Deficiencies , Transferrin/metabolism , Transferrin/analysis , Chronic Disease
16.
Am J Clin Nutr ; 120(1): 211-216, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38710446

ABSTRACT

BACKGROUND: The iron intake requirement distribution for premenopausal females is not symmetric, which invalidates the EAR cut-point approach for assessing the prevalence of iron inadequacy. Therefore, Beaton's Full Probability Approach (PA) must be used. Although the PA requires information on the entire iron intake requirement distribution, the European Food Safety Authority (EFSA) only provided the EAR (50th percentile), 90th, 95th (population reference intake), and 97.5th percentiles. OBJECTIVES: This study aimed to reliably estimate the prevalence of iron inadequacy in premenopausal females using the PA, based on the intake requirements established by EFSA, and compare the results with those obtained from the EAR cut-point method. METHODS: Habitual iron intakes were calculated using the statistical program to assess dietary exposure with data from 484 females (20-45 y) from the Dutch National Food Consumption Survey 2012-2016. Iron requirements of EFSA (including additionally obtained information) were applied. Results from the PA were compared to results obtained with the EAR cut-point method. Sensitivity analyses examined the impact of lower iron intake distributions on differences in estimated inadequate intakes between PA and EAR cut-point methods. RESULTS: A 2-fold higher prevalence of iron inadequacy among Dutch premenopausal females was observed when employing the PA compared to the EAR cut-point method, using EFSA's reference values. Sensitivity analysis showed that the EAR cut-point method could also result in large overestimations for populations with lower intake distributions. CONCLUSIONS: This study provided an example of using the PA method by using additionally derived information on the full requirement distribution underlying EFSA's reference values. Results showed once more the unsuitability of the EAR cut-point method to calculate the prevalence of iron inadequacy in premenopausal females. Hence, we recommend that institutions deriving dietary reference values provide all the information needed to use the correct method to determine inadequate intakes in the population.


Subject(s)
Iron, Dietary , Premenopause , Humans , Female , Adult , Cross-Sectional Studies , Reference Values , Prevalence , Young Adult , Iron, Dietary/administration & dosage , Middle Aged , Netherlands/epidemiology , Food Safety , Iron Deficiencies , Diet , Nutritional Requirements , Iron/administration & dosage
17.
Cell Death Dis ; 15(5): 361, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38796462

ABSTRACT

Disease models of neurodegeneration with brain iron accumulation (NBIA) offer the possibility to explore the relationship between iron dyshomeostasis and neurodegeneration. We analyzed hiPS-derived astrocytes from PANK2-associated neurodegeneration (PKAN), an NBIA disease characterized by progressive neurodegeneration and high iron accumulation in the globus pallidus. Previous data indicated that PKAN astrocytes exhibit alterations in iron metabolism, general impairment of constitutive endosomal trafficking, mitochondrial dysfunction and acquired neurotoxic features. Here, we performed a more in-depth analysis of the interactions between endocytic vesicles and mitochondria via superresolution microscopy experiments. A significantly lower number of transferrin-enriched vesicles were in contact with mitochondria in PKAN cells than in control cells, confirming the impaired intracellular fate of cargo endosomes. The investigation of cytosolic and mitochondrial iron parameters indicated that mitochondrial iron availability was substantially lower in PKAN cells compared to that in the controls. In addition, PKAN astrocytes exhibited defects in tubulin acetylation/phosphorylation, which might be responsible for unregulated vesicular dynamics and inappropriate iron delivery to mitochondria. Thus, the impairment of iron incorporation into these organelles seems to be the cause of cell iron delocalization, resulting in cytosolic iron overload and mitochondrial iron deficiency, triggering mitochondrial dysfunction. Overall, the data elucidate the mechanism of iron accumulation in CoA deficiency, highlighting the importance of mitochondrial iron deficiency in the pathogenesis of disease.


Subject(s)
Astrocytes , Cytosol , Iron Overload , Iron , Mitochondria , Astrocytes/metabolism , Astrocytes/pathology , Humans , Mitochondria/metabolism , Cytosol/metabolism , Iron/metabolism , Iron Overload/metabolism , Iron Overload/pathology , Tubulin/metabolism , Phosphorylation , Iron Deficiencies , Acetylation
18.
J Sci Med Sport ; 27(7): 437-450, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38749874

ABSTRACT

OBJECTIVES: Iron deficiency, anaemia, and menorrhagia - or heavy menstrual bleeding - are interrelated conditions that are highly prevalent and commonly underrecognised in exercising females of reproductive age. This study utilised a screening tool to identify risk factors and symptoms associated with heavy menstrual bleeding, iron deficiency, and anaemia in this population. DESIGN: An observational, cross sectional survey study was employed. METHODS: 1042 active females (aged 18-65) completed a comprehensive screening questionnaire and 887 (85 % compliance) provided a fingerprick blood sample for haemoglobin (Hb) concentration measurement. Women that presented as anaemic (defined as a [Hb] < 120 g/L) or deemed to be at risk of iron deficiency (120 < [Hb] < 130 g/L) were asked to complete follow-up blood tests to screen for iron studies. RESULTS: Average [Hb] was 134.2 ±â€¯12.1 g/L, with 94 individuals considered anaemic (10.6 %). Of the sample, 104 underwent follow-up blood tests; 51 (~49 %) presented with iron deficiency (defined as ferritin <30 µg/L). Based on survey responses, 274 (30.9 %) participants were determined to have heavy menstrual bleeding. Those presenting with heavy menstrual bleeding were younger, exercised fewer hours per week, and were more likely to have a history of iron deficiency or anaemia (all p < 0.05). Participants reporting a history of anaemia or iron deficiency were more likely to have heavy menstrual bleeding (anaemia: 39.7 %; iron deficiency; 36.9 %; both p < 0.05). CONCLUSIONS: In this cohort of exercising females of reproductive age, the prevalence of anaemia was 10.6 %. There is a strong association between heavy menstrual bleeding and a self-reported history of iron deficiency and anaemia. Greater awareness of heavy menstrual bleeding and its relationship with iron deficiency and anaemia is needed in this population. Non-invasive screening should be conducted to raise awareness and further understand the associated risk factors and symptomatology.


Subject(s)
Anemia, Iron-Deficiency , Menorrhagia , Humans , Female , Menorrhagia/blood , Menorrhagia/epidemiology , Adult , Cross-Sectional Studies , Middle Aged , Young Adult , Adolescent , Anemia, Iron-Deficiency/epidemiology , Anemia, Iron-Deficiency/blood , Anemia, Iron-Deficiency/diagnosis , Hemoglobins/analysis , Risk Factors , Iron Deficiencies , Exercise , Aged , Surveys and Questionnaires , Prevalence , Ferritins/blood , Anemia/epidemiology , Anemia/blood , Anemia/diagnosis
19.
Clin Transplant ; 38(6): e15367, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38809215

ABSTRACT

INTRODUCTION: The prevalence of iron deficiency and anemia in the setting of modern-day maintenance immunosuppression in pediatric heart transplant (HTx) recipients is unclear. The primary aim was to determine the prevalence of iron deficiency (serum ferritin < 30 ng/mL ± transferrin saturation < 20%) and anemia per World Health Organization diagnostic criteria and associated risk factors. METHODS: Single-center, cross-sectional analysis of 200 consecutive pediatric HTx recipients (<21 years old) from 2005 to 2021. Data were collected at 1-year post-HTx at the time of annual protocol biopsy. RESULTS: Median age at transplant was 3 years (IQR .5-12.2). The median ferritin level was 32 ng/mL with 46% having ferritin < 30 ng/mL. Median transferrin saturation (TSAT) was 22% with 47% having TSAT < 20%. Median hemoglobin was 11 g/dL with 54% having anemia. Multivariable analysis revealed lower absolute lymphocyte count, TSAT < 20%, and estimated glomerular filtration rate <75 mL/min/1.73 m2 were independently associated with anemia. Ferritin < 30 ng/mL in isolation was not associated with anemia. Ferritin < 30 ng/mL may aid in detecting absolute iron deficiency while TSAT < 20% may be useful in identifying patients with functional iron deficiency ± anemia in pediatric HTx recipients. CONCLUSION: Iron deficiency and anemia are highly prevalent in pediatric HTx recipients. Future studies are needed to assess the impact of iron deficiency, whether with or without anemia, on clinical outcomes in pediatric HTx recipients.


Subject(s)
Anemia, Iron-Deficiency , Heart Transplantation , Humans , Heart Transplantation/adverse effects , Male , Female , Cross-Sectional Studies , Child , Prevalence , Child, Preschool , Follow-Up Studies , Risk Factors , Prognosis , Anemia, Iron-Deficiency/epidemiology , Anemia, Iron-Deficiency/diagnosis , Anemia, Iron-Deficiency/etiology , Postoperative Complications/epidemiology , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Postoperative Complications/blood , Iron Deficiencies , Infant , Adolescent , Anemia/epidemiology , Anemia/etiology , Anemia/diagnosis , Transplant Recipients/statistics & numerical data , Graft Rejection/etiology , Graft Rejection/epidemiology , Graft Rejection/blood , Graft Rejection/diagnosis
20.
J Infus Nurs ; 47(3): 163-174, 2024.
Article in English | MEDLINE | ID: mdl-38744241

ABSTRACT

There is a direct correlation between being overweight and iron deficiency. Physiological changes occur in obese adipose cells that contribute to the development of iron deficiency (ID) and iron deficiency anemia (IDA). These changes disrupt the normal iron metabolic checks and balances. Furthermore, bariatric surgery can lead to long-term ID and IDA. Oral iron supplementation may not be effective for many of these patients. Intravenous iron infusions can significantly increase the quality of life for individuals experiencing this condition but are also associated with potentially serious complications. Adequate knowledge about intravenous (IV) iron administration can greatly increase the safety of this beneficial therapy. This review article explains the relationship between obesity, ID/IDA, bariatric surgery and the safe administration of IV iron.


Subject(s)
Anemia, Iron-Deficiency , Bariatric Surgery , Iron , Obesity , Humans , Obesity/complications , Anemia, Iron-Deficiency/drug therapy , Iron/administration & dosage , Infusions, Intravenous , Iron Deficiencies , Quality of Life
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