Examination of the relationship between iron status and cognitive function among healthy young women with and without a recent history of blood donation.

BACKGROUND: With growing awareness of the prevalence of nonanemic iron deficiency among blood donors, there is a need to explore the extent of potential negative consequences. This study examined the relationship between various measures of iron status, blood donation history, and neuropsychological and psychosocial functioning in healthy young women. STUDY DESIGN AND METHODS: Using a cross-sectional design, 160 female undergraduates completed neuropsychology tests and measures of sleep, fatigue, quality of life, and depression before providing a blood sample. Correlational analyses examined the relationship between iron status (ferritin, iron, hemoglobin, and zinc protoporphyrin) and cognitive and psychosocial functioning. Performance on these measures was also examined as a function of recent blood donation history (zero, one, more than one donation in the past year). RESULTS: Iron status (low ferritin, iron, or hemoglobin or high zinc protoporphyrin) was not associated with poorer performance on the cognitive tasks. Further, participants who reported donating once in the previous year performed better, rather than worse, than those with no recent donation history on several measures of executive function, even when controlling for ferritin levels. Although there was some evidence of greater fatigue among those who had donated more than once in the past year, this effect was not accounted for by ferritin levels. CONCLUSION: The present findings are consistent with prior evidence that nonanemic iron deficiency is not associated with cognitive impairment or psychosocial dysfunction in healthy young females. Because these results are based on cross-sectional evidence, further study using longitudinal research is needed to confirm these findings.

Qualitative evaluation of ferritin in serum samples by Raman spectroscopy and principal component analysis.

Iron molecule is of great importance in the synthesis of hemoglobin which is essential for oxygen transport. Iron levels are quantified by accurately high sensitivity tests, such as serum ferritin (SF). However, common studies to quantify SF are long and strenuous (~ 5 h), for example enzyme-linked immunosorbent assay (ELISA). In this paper, blood serum samples were analyzed by Raman spectroscopy (RS), and a computational analysis of spectra is proposed to detect differences in SF as an alternative procedure. Serum samples were obtained from 22 patients, 9 who were clinically diagnosed with anemia and 13 controls. Patients with anemia had low levels of SF (< 30 ng/ml), and a control group had levels between 30 and 500 ng/ml. The spectra obtained were conditioned with a baseline correction and smoothing, then evaluated by principal component analysis (PCA), and a predictive model was estimated by lineal discrimination analysis (LDA). The results showed a clear differentiation of the study groups by PCA, also 99.69% sensitivity and 100% specificity by LDA. This study suggest that Raman spectroscopy is a fast (~ 5 min) and a powerful tool capable to qualitative differentiate ferritin concentrations.

A RhABF2/Ferritin module affects rose (Rosa hybrida) petal dehydration tolerance and senescence by modulating iron levels.

Plants often develop the capacity to tolerate moderate and reversible environmental stresses, such as drought, and to re-establish normal development once the stress has been removed. An example of this phenomenon is provided by cut rose (Rosa hybrida) flowers, which experience typical reversible dehydration stresses during post-harvest handling after harvesting at the bud stages. The molecular mechanisms involved in rose flower dehydration tolerance are not known, however. Here, we characterized a dehydration- and abscisic acid (ABA)-induced ferritin gene (RhFer1). Dehydration-induced free ferrous iron (Fe2+ ) is preferentially sequestered by RhFer1 and not transported outside of the petal cells, to restrict oxidative stresses during dehydration. Free Fe2+ accumulation resulted in more serious oxidative stresses and the induction of genes encoding antioxidant enzyme in RhFer1-silenced petals, and poorer dehydration tolerance was observed compared with tobacco rattle virus (TRV) controls. We also determined that RhABF2, an AREB/ABF transcription factor involved in the ABA signaling pathway, can activate RhFer1 expression by directly binding to its promoter. The silencing of RhABF2 decreased dehydration tolerance and disrupted Fe homeostasis in rose petals during dehydration, as did the silencing of RhFer1. Although both RhFer1 and Fe transporter genes are induced during flower natural senescence in plants, the silencing of RhABF2 or RhFer1 accelerates the petal senescence processes. These results suggest that the regulatory module RhABF2/RhFer1 contributes to the maintenance of Fe levels and enhances dehydration tolerance through the action of RhFer1 locally sequestering free Fe2+ under dehydration conditions, and plays synergistic roles with transporter genes during flower senescence.

A meta-analysis of association between serum iron levels and lung cancer risk.

Many studies conducted on the relationship between serum iron levels and lung cancer risk had produced inconsistent results. We therefore conducted a meta-analysis to determine whether serum iron levels were lower in lung cancer patients compared to those in controls.A literature survey was conducted by searching the PubMed, WanFang, CNKI, and SinoMed databases for articles published as of Mar 1, 2018. Standard mean differences (SMD) with the corresponding 95% confidence intervals (CI) were executed by Stata 12.0 software. A total of 13 publications involving 1118 lung cancer patients and 832 controls were included in our study. The combined results showed that serum iron levels in lung cancer cases had no significantly lower when compared to those in controls [summary SMD = -0.125, 95%CI= -0.439, 0.189, Z = 0.78, p for Z test= 0.435], with high heterogeneity (I2= 89.9%, P< 0.001) found. In the stratified analysis by geographic locations, consistent results were found for serum iron levels between lung cancer patients and controls both in Asian populations [summary SMD = -0.113, 95%CI= -0.471, 0.245] and European populations [summary SMD = -0.215, 95%CI= -0.835, 0.404]. Publication bias was not found when evaluated by Begg's funnel plot and Egger's regression asymmetry test.In summary, the current study showed that serum iron levels had no significant association on lung cancer risk.

The Phosphoinositide 3-Kinase Regulates Retrograde Trafficking of the Iron Permease CgFtr1 and Iron Homeostasis in Candida glabrata.

The phosphoinositide 3-kinase (PI3K), which phosphorylates phosphatidylinositol and produces PI3P, has been implicated in protein trafficking, intracellular survival, and virulence in the pathogenic yeast Candida glabrata Here, we demonstrate PI3-kinase (CgVps34) to be essential for maintenance of cellular iron homeostasis. We examine how CgVps34 regulates the fundamental process of iron acquisition, and underscore its function in vesicular trafficking as a central determinant. RNA sequencing analysis revealed iron homeostasis genes to be differentially expressed upon CgVps34 disruption. Consistently, the Cgvps34Δ mutant displayed growth attenuation in low- and high-iron media, increased intracellular iron content, elevated mitochondrial aconitase activity, impaired biofilm formation, and extenuated mouse organ colonization potential. Furthermore, we demonstrate for the first time that C. glabrata cells respond to iron limitation by expressing the iron permease CgFtr1 primarily on the cell membrane, and to iron excess via internalization of the plasma membrane-localized CgFtr1 to the vacuole. Our data show that CgVps34 is essential for the latter process. We also report that macrophage-internalized C. glabrata cells express CgFtr1 on the cell membrane indicative of an iron-restricted macrophage internal milieu, and Cgvps34Δ cells display better survival in iron-enriched medium-cultured macrophages. Overall, our data reveal the centrality of PI3K signaling in iron metabolism and host colonization.

Increased iron levels and lipid peroxidation in a Mediterranean population of Spain.

BACKGROUND: Many chronic diseases are adversely affected by elevated iron levels. It has been speculated that this relationship is mediated by increased oxidative stress, due to the ability of iron to generate reactive oxygen species. The aim of this study was to assess the relationship between elevated iron levels and lipid peroxidation in Caucasian adults residing in the north-eastern Mediterranean region of Spain. MATERIALS AND METHODS: This cross-sectional case-control study included 300 subjects: 150 adults displaying elevated iron levels (cases) selected from a representative sample of our general population and 150 age- and sex-matched adults exhibiting normal iron levels (controls). Dietary assessment (3-day food records), iron biomarkers (serum iron, ferritin and transferrin saturation) and lipid profile were determined. Elevated iron levels were defined by high serum ferritin (SF>110 µg/L in women and>200 µg/L in men) and/or transferrin saturation (TS)>45%. Oxidized low-density lipoprotein (oxLDL) plasma levels were measured, and oxLDL/LDL-cholesterol ratio was calculated to estimate lipid peroxidation. Multiple linear regression (MLR) models were applied. RESULTS: Individuals with elevated serum iron levels showed increased oxLDL/LDL ratio, but not oxLDL levels, compared to control subjects (20·92 ± 4·89 U/mmol vs. 19·72 ± 3·573 U/mmol, P = 0·028). These results were further confirmed by the regression models adjusted for demographic characteristics, diet, lipid profile and inflammation. Importantly, higher serum levels of triglycerides, LDL-cholesterol and lower intake of Vitamin E increased lipid peroxidation. CONCLUSIONS: In our general population, we have observed that higher circulating levels of iron, measured by serum ferritin and/or TS, increased lipid peroxidation (measured by oxLDL/LDL ratio).

Association between serum iron levels and atherosclerotic cardiovascular diseases among American older adults: a cross-sectional study based on the National Health and Nutrition Examination Survey, 2009-2018.

Background: There is controversy regarding the relationship between serum iron levels and atherosclerotic cardiovascular disease (ASCVD). Objective: To investigate the relationship between serum iron levels and ASCVD among older adults using data from the 2009-2018 National Health and Nutrition Examination Survey (NHANES). Methods: We performed a cross-sectional analysis involving 8,682 participants aged 60 years and older, with complete data on serum iron levels and confirmed ASCVD status, sourced from the 2009-2018 National Health and Nutrition Examination Survey (NHANES). Multivariable logistic regression models were used to examine the association between serum iron levels and ASCVD. To assess the consistency of this association across different demographic groups, subgroup analyses, and interaction tests were performed. Results: The group with the highest serum iron levels (fourth quartile, 100-369 µg/dL) exhibited several distinct characteristics: they were the youngest on average (69.57 ± 6.91 years), had the highest proportion of males (61.42%), and the highest hemoglobin levels (14.43 ± 1.33 g/dL). This group also showed the lowest iron supplement usage (19.71 ± 12.85 mg/30 days), white blood cell counts (6.73 ± 2.41 1,000 cells/µL), and serum creatinine levels (0.98 ± 0.45 mg/dL). Moreover, they had higher levels of education and income, a higher likelihood of being married, and a lower body mass index (BMI). Additionally, they had significantly lower rates of diabetes, hypertension, stroke, and heart attacks (all p < 0.05). After adjusting for potential confounders, a linear relationship between serum iron levels and ASCVD was initially observed (OR = 0.97; 95% CI, 0.95-0.99, p < 0.05). However, further analysis using a two-part logistic regression model with an inflection point at 131 µg/dL revealed more nuanced results. For serum iron levels below 131 µg/dL, each 10 µg/dL increase was associated with a 4% decrease in the odds of ASCVD (OR = 0.96; 95% CI, 0.93-0.98, p < 0.001). Conversely, for serum iron levels above 131 µg/dL, each 10 µg/dL increase corresponded to a 1% increase in the odds of ASCVD, though this finding was not statistically significant (OR = 1.01; 95% CI, 0.98-1.08, p > 0.05). Conclusion: In the US elderly population, serum iron levels are negatively associated with ASCVD, particularly when serum iron levels are below 131 µg/dL.

Comparative analysis of quantitative susceptibility mapping in preclinical dementia detection.

PURPOSE: This review aims to explore the role of Quantitative Susceptibility Mapping (QSM) in the early detection of neurodegenerative diseases, particularly Alzheimer's disease (AD) and Lewy body dementia (LBD). By examining QSM's ability to map brain iron deposition, we seek to highlight its potential as a diagnostic tool for preclinical dementia. METHODOLOGY: QSM techniques involve the advanced processing of MRI phase images to reconstruct tissue susceptibility, employing methods such as spherical mean value filtering and Tikhonov regularization for accurate background field removal. This review discusses how these methodologies enable the precise quantification of iron and other elements within the brain. RESULTS: QSM has demonstrated effectiveness in identifying early pathological changes in key brain regions, including the hippocampus, basal ganglia, and substantia nigra. These regions are significantly impacted in the early stages of AD and LBD. Studies reviewed indicate that QSM can detect subtle neurodegenerative changes, providing valuable insights into disease progression. However, challenges remain in standardizing QSM processing algorithms to ensure consistent results across different studies. CONCLUSION: QSM emerges as a promising tool for early dementia detection, offering precise measurements of brain iron deposition and other critical biomarkers. The review underscores the importance of refining QSM methodologies and integrating them with other imaging modalities to improve early diagnosis and management of neurodegenerative diseases. Future research should focus on standardizing QSM techniques and exploring their synergistic use with other neuroimaging methods to enhance its clinical utility.

Berberine ameliorates iron levels and ferroptosis in the brain of 3 × Tg-AD mice.

BACKGROUND: Berberine (BBR) is a natural alkaloid extracted from the herb Coptis chinensis. This compound has the ability to penetrate the blood-brain barrier (BBB) and exhibit neuroprotective value in the treatment of Alzheimer's disease (AD). AD is a neurodegenerative disease characterized by ß-amyloid (Aß) deposition, hyperphosphorylated tau and other characters. Iron accumulation and ferroptosis were also detected in AD brain, which can result in neuronal damage. However, it is still unclear whether BBR can suppress ferroptosis in AD and alleviate its underlying pathology. PURPOSE: This study investigated whether BBR may affect ferroptosis and related signaling pathways in triple transgenic AD (3 × Tg-AD) mice. METHODS: Four-month-old 3 × Tg-AD mice received oral administration of BBR at a dose of 50 mg/kg for 7.5 months. Cognitive function and anxiety levels in mice were assessed using the morris water maze test, open field test, and novel object recognition test. Western blot, immunohistochemistry, and ICP-MS were employed to assess the pathology of AD, brain iron metabolism, and ferroptosis signaling pathways. Transmission electron microscopy was used to detect mitochondrial changes. The synergistic effects of BBR combined with Nrf2 were investigated using molecular docking programs and surface plasmon resonance technology. Co-inmunoprecipitation assay was used to examine the effect of BBR on the binding ability of Nrf2 and Keap1. RESULTS: The results indicated that chronic treatment of BBR mitigated cognitive disorders in 3 × Tg-AD model mice. Reductions in Aß plaque, hyperphosphorylated tau protein, neuronal loss, and ferroptosis in the brains of 3 × Tg-AD mice suggested that BBR could alleviate brain injury. In addition, BBR treatment attenuated ferroptosis, as evidenced by decreased levels of iron, MDA, and ROS, while enhancing SOD, GSH, GPX4, and SLC7A11. Consistent with the in vivo assay, BBR inhibited RSL3-induced ferroptosis in N2a-sw cells. BBR increased the expression levels of GPX4, FPN1 and SLC7A11 by regulating Nrf2 transcription levels, thereby inhibiting ferroptosis. Molecular docking programs and surface plasmon resonance technology demonstrated the direct combination of BBR with Nrf2. Co-inmunoprecipitation analysis showed that BBR inhibited the interaction between Keap1 and Nrf2. CONCLUSION: For the first time, these results showed that BBR could inhibit iron levels and ferroptosis in the brains of 3 × Tg-AD model mice and partially protect against RSL3-induced ferroptosis via the activation of Nrf2 signaling.

Iron Levels and Markers of Inflammation in a Population of Adults with Severe Obesity, a Cross-Sectional Study.

Low-grade chronic inflammation linked to obesity can lead to alterations in biomarkers of iron status. The aim of this study was to investigate the primary determinant of serum iron levels among anthropometric measurements, body fat, and serum biomarkers of low-grade chronic inflammation in a group of adult individuals with severe obesity. We enrolled 114 individuals (84 females; 30 males) aged 40.96 ± 12.54 years. Weight and body mass index (BMI) were 121.20 ± 22.33 kg and 44.94 ± 7.29 kg/m2, respectively. Some 30% of individuals had class-II obesity (BMI ≥ 35 ≤ 39.9 kg/m2) and 70% had class-III obesity (BMI ≥ 40 kg/m2). A weak, albeit significant, inverse correlation was found between serum iron levels and c-reactive protein (CRP) (r = -0.259, p = 0.008), fibrinogen (r = -0.261, p = 0.006), BMI (r = -0.186, p = 0.04), waist circumference (WC) (r = -0.265, p = 0.004), and fat mass % (r = -0.285, p = 0.003). With multiple linear regression analysis including CRP, fibrinogen, BMI, WC, and fat mass % as independent variables and serum iron levels as dependent variable, WC was entered in the first step (p = 0.001), which was followed by fat mass % (p = 0.047) and CRP (p = 0.047). Grouping the individuals according to the interquartile range of BMI, WC, and fat mass % (Q1-Q4), the lowest serum iron levels were found in Q4 groups of WC and fat mass % (p = 0.02), while no significant differences were found between groups in BMI quartiles. In conclusion, in our study, population serum iron levels were inversely associated with BMI, visceral obesity, fat mass %, CRP, and fibrinogen, but WC was the major negative predictor of serum iron level. These results supported the fact that visceral distribution of body fat, more than obesity per se, was associated with low serum iron levels in adult individuals with severe obesity.

Association of myocardial iron deficiency based on T2* CMR with the risk of mild left ventricular dysfunction in HIV-1-infected patients.

Objectives: This study sought to noninvasively determine myocardial iron levels in HIV-1-infected patients using CMR and explore the association between T2* values and mild left ventricular systolic dysfunction (LVSD). Methods: This prospective study was conducted from June 2019 to July 2021. HIV-1-infected adults and healthy controls were consecutively enrolled for CMR exam. CMR exam included the assessment of myocardium iron content (T2*), cardiac function (cine), inflammation (T2), and fibrosis (through extracellular volume fraction [ECV] and late gadolinium enhancement [LGE]) measurements. Mild LVSD is defined as a left ventricular ejection fraction (LVEF) between 40% and 49%. Results: Of 47 HIV-1-infected patients enrolled, 12 were diagnosed with mild LVSD (HIV-1+/LEVF+) and 35 were diagnosed with preserved LV function (HIV-1+/LEVF-). Compared with healthy controls, HIV-1-infected patients displayed higher T2*, T1, T2, ECV values and lower global circumferential strain (GCS) and global radial strain (GRS) (all P < 0.05). However, between patients with and without mild LVSD, only the T2* values and ECV (all P <0.05) were different. The association between increased T2* values (>26 ms) and mild LVSD remained significant after adjusting for the established univariate predictors (ECV >32.9%, T1 values >1336 ms) of mild LVSD (odds ratio [OR], 10.153; 95% confidence interval [CI] 1.565-65.878, P = 0.015). Conclusions: Myocardial T2* values were elevated in HIV-1-infected patients, supporting the notion that ID was associated with mild LVSD. Our findings highlight the potential for ID in HIV-1-infected patients as an auxiliary biomarker to monitor the course of LVSD.

Correlation of iron levels with glycemia and microvascular complications among type II diabetes mellitus patients in Najran university hospital.

Background: Diabetes is influenced by changes in the body's iron levels. Because iron deficiency anemia is common in diabetes, this study examines the link between iron, glycemic control, and complication in patients with type 2 diabetes mellitus (T2DM). Methods: The study is a cross-sectional study conducted from October 2019 to June 2020 at Najran university hospital in the Najran area, Saudi Arabia. All T2DM patients (N = 201) during the study were recruited by simple random sampling. A checklist was completed to extract the study variables from each patient's medical record. Results: There is a positive poor correlation between hemoglobin (Hb) and diabetic foot (r = 0.186, P < 0.05), but not with other diabetic microvascular complications (i.e., retinopathy, nephropathy, and peripheral neuropathy) or glycemic indicators fasting blood sugar, random blood sugar and hemoglobin A1C (i.e., FBS, RBS, and HbA1C). No link is found between ferritin and glycemic indicators or diabetic microvascular complications. Conclusion: The study suggests that particular attention be paid to regular monitoring of iron levels before modifying the treatment plans for type 2 diabetes mellitus (T2DM) patients. It raises critical inquiry about the reality of iron role in diabetes mellitus either in pathogenesis or treatment. It recommends accurately assessing body iron status with careful interpretation for better clinical judgment, encouraging large-scale and long-term epidemiological as well as interventional trials examining the effect of lowering iron in controlling glycemia.

The association of vascular endothelial growth factor related SNPs and circulating iron levels might depend on body mass index.

BACKGROUND AND OBJECTIVES: Vascular Endothelial Growth Factor (VEGF) is an essential regulator of vascular biology. In addition to the well-established role in angiogenesis, circulating VEGF levels were found elevated in severely anemic patients, pointing out that anemia might affect the progression of angiogenesis in malignant and benign diseases through the alteration of VEGF levels. Ten single nucleotide polymorphisms (SNPs) in VEGFA and other loci were shown to explain more than 50% of its circulating levels. This study investigated the association of those ten VEGF-related SNPs with serum iron levels in a general Lebanese population free of chronic diseases (N = 460). RESULT: We found that the rs10738760 and the body mass index (BMI) were associated with decreased Iron levels (p = 0.002, and p < 0.001, respectively). When taken together, both variables, rs10738760 and BMI, interacted to reduce iron levels (p < 0.001). According to obesity status, the stratification revealed that the effect of rs10738760 was more pronounced in obese than non-obese individuals (p = 0.025). Conclusion: The intergenic SNP rs10738760 is associated with circulating iron levels, and this association depends on BMI status. Although of interest, these results need replication in larger populations from different ancestries.

Copper, zinc and iron levels in premature infants following red blood cell transfusion.

This study aimed to investigate effect of erythrocyte suspension (ES) transfusion on Cu, Zn, and Fe levels. It was conducted on 53 premature infants who were admitted to Hacettepe Hospital and received EST for first time. Blood samples were drawn before and 96h after ES transfusion to determine Cu, Zn, and Fe levels in plasma and/or erythrocytes. The mean plasma Cu levels were 99±3µg/dl and 113±3µg/dl; Zn levels were 105±2µg/dl and 115±23µg/dl; mean plasma Fe level was 58.1±19.4 and 75.2±25.4µg/dl and mean erythrocyte Fe level was 4182±2314µg/ml and 7009±5228µg/ml, before and after ES transfusion. The differences between before and after ES transfusion in Cu, Zn and Fe levels were significant. Correlation between plasma and erythrocyte Fe levels was significant both before and after ES transfusion. Though Fe overload is a major cause of morbidity/mortality after ES transfusion, alterations in trace elements should also be considered when transfusing blood to infants and children.

Deferoxamine stimulates LDLR expression and LDL uptake in HepG2 cells.

SCOPE: Iron overload contributes to the pathogenesis of atherosclerosis and iron chelators are beneficial through their antioxidant properties. Hepatic iron loading increases cholesterol synthesis. Whether iron depletion could affect hepatic cholesterol metabolism is unknown. METHODS AND RESULTS: We examined the effect of the iron chelator deferoxamine (DFO) on mRNA expression of genes involved in cholesterol metabolism and/or cholesterol uptake. Our results revealed that DFO increases LDL receptor (LDLR) mRNA levels in human hepatocyte-derived cell lines HepG2 and Huh7 cells, and in K562 cells. In HepG2 cells, we observed that DFO increases (i) LDLR-mRNA levels in a time- and dose-dependent manner, (ii) LDLR-protein levels; (iii) cell surface LDLR; and (iv) LDL uptake. In contrast, the mRNA levels of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, sterol regulatory element-binding proteins, and the mRNA/protein levels of proprotein convertase subtilisin-kexin 9 were not modulated by DFO, suggesting that the LDLR regulation by DFO is not at the transcriptional or posttranslational levels. Since LDLR-mRNA was stabilized by DFO, a posttranscriptional mechanism is suggested for the DFO-mediated upregulation of LDLR. CONCLUSION: DFO induced an increase in LDLR expression by a posttranscriptional mechanism resulting in an enhancement of LDL uptake in HepG2 cells, suggesting increased LDLR activity as one of the underlying causes of the hypocholesterolemic effect of iron reduction.

Does Iron Increase the Risk of Malaria in Pregnancy?

Background. Pregnancy-associated malaria (PAM) remains a significant health concern in sub-Saharan Africa. Cross-sectional studies report that iron might be associated with increased malaria morbidity, raising fears that current iron supplementation policies will cause harm in the present context of increasing resistance against intermittent preventive treatment in pregnancy (IPTp). Therefore, it is necessary to assess the relation of iron levels with malaria risk during the entire pregnancy. Methods. To investigate the association of maternal iron levels on malaria risk in the context of an IPTp clinical trial, 1005 human immunodeficiency virus-negative, pregnant Beninese women were monitored throughout their pregnancy between January 2010 and May 2011. Multilevel models with random intercept at the individual levels and random slope for gestational age were used to analyze the factors associated with increased risk of a positive blood smear and increased Plasmodium falciparum density. Results. During the follow-up, 29% of the women had at least 1 episode of malaria. On average, women had 0.52 positive smears (95% confidence interval [CI], 0.44-0.60). High iron levels (measured by the log10 of ferritin corrected on inflammation) were significantly associated with increased risk of a positive blood smear (adjusted odds ratio = 1.75; 95% CI, 1.46-2.11; P < .001) and high P falciparum density (beta estimate = 0.22; 95% CI, 0.18-0.27; P < .001) during the follow-up period adjusted on pregnancy parameters, comorbidities, environmental and socioeconomic indicators, and IPTp regime. Furthermore, iron-deficient women were significantly less likely to have a positive blood smear and high P falciparum density (P < .001 in both cases). Conclusions. Iron levels were positively associated with increased PAM during pregnancy in the context of IPTp. Supplementary interventional studies are needed to determine the benefits and risks of differently dosed iron and folate supplements in malaria-endemic regions.

Viscoelastic and ultrastructural characteristics of whole blood and plasma in Alzheimer-type dementia, and the possible role of bacterial lipopolysaccharides (LPS).

Alzheimer-type dementia (AD) is a neurodegenerative disorder and the most common form of dementia. Patients typically present with neuro- and systemic inflammation and iron dysregulation, associated with oxidative damage that reflects in hypercoagulability. Hypercoagulability is closely associated with increased fibrinogen and in AD patients fibrinogen has been implicated in the development of neuroinflammation and memory deficits. There is still no clear reason precisely why (a) this hypercoagulable state, (b) iron dysregulation and (c) increased fibrinogen could together lead to the loss of neuronal structure and cognitive function. Here we suggest an alternative hypothesis based on previous ultrastructural evidence of the presence of a (dormant) blood microbiome in AD. Furthermore, we argue that bacterial cell wall components, such as the endotoxin lipopolysaccharide (LPS) of Gram-negative strains, might be the cause of the continuing and low-grade inflammation, characteristic of AD. Here, we follow an integrated approach, by studying the viscoelastic and ultrastructural properties of AD plasma and whole blood by using scanning electron microscopy, Thromboelastography (TEG®) and the Global Thrombosis Test (GTT®). Ultrastructural analysis confirmed the presence and close proximity of microbes to erythrocytes. TEG® analysis showed a hypercoagulable state in AD. TEG® results where LPS was added to naive blood showed the same trends as were found with the AD patients, while the GTT® results (where only platelet activity is measured), were not affected by the added LPS, suggesting that LPS does not directly impact platelet function. Our findings reinforce the importance of further investigating the role of LPS in AD.

[Clinical and socio-medical factors related to anemia in pregnant women: prevalence study in Mara Township, Venezuela, 2013]. / Factores clínicos y socio-sanitarios relacionados a la anemia en gestantes: estudio de prevalencia en Municipio Mara, Venezuela, 2013.

Anemia during pregnancy is a frequent finding and can increase morbidity and mortality in both mother and child. This paper aims to identify clinical, social and healthcare-related factors that affect the incidence of anemia in pregnant patients in a primary care prenatal clinic in Mara municipality. This is a descriptive field study that took place between November and December, 2013. Sixty-two patients were selected through non-probability sampling among four primary care clinics in the municipality of Mara. A high prevalence of anemia (76%) was found, with normal MCV (mean corpuscular volume), normal MCH (mean corpuscular hemoglobin), and normal MCHC (mean corpuscular hemoglobin concentration). In only 36% of cases serum iron levels fell below 50 ug/dl. Some clinical factors found to be related to anemia in pregnancy are multiparity (69.9%), infections before or during pregnancy (77.5%), low protein intake (91.8%), less than a year birth interval (63.3%), and gestational age (89.8%). The main socioeconomic factor related to anemia is poverty (89.8%). Prenatal checkup schedule needs to be adjusted in primary care clinics in the municipality of Mara taking into consideration clinical and socioeconomic factors in order to lower the prevalence of anemia during pregnancy in this population.

La anemia es un problema frecuente durante el embarazo y puede tener efectos adversos en la madre y el recién nacido, incrementando el riesgo de morbi-mortalidad. Por ello, el presente estudio se plantea como objetivo el identificar los factores clínicos, sociales y sanitarios relacionados a la prevalencia de anemia en mujeres gestantes que acuden a consulta prenatal en los servicios de atención ambulatoria del municipio Mara. El estudio es del tipo descriptivo y de campo, realizado durante los meses de noviembre y diciembre de 2013. Se analizaron a 62 pacientes seleccionadas por un muestreo no probabilístico, en cuatro servicios de atención ambulatoria del municipio de Mara. Entre los resultados destaca la alta prevalencia de anemia (76%), con valores normales de volumen corpuscular medio, concentración hemática media y concentración hemática corpuscular media. Sólo 36% de los casos presentó hierro sérico por debajo de 50 µg/dL. Entre los factores clínicos relacionados con la anemia destaca la multiparidad (69,9%), infecciones antes o durante el embarazo (77,5%); bajo consumo de proteínas (91,8%), periodo intergenésico menor a un año (63,3%) y edad gestacional (89,8%). Entre los factores socioeconómicos relacionados con la anemia, se encuentra la pobreza (89,8%). Es necesario adecuar los programas de control prenatal vigentes en los servicios de atención ambulatoria del municipio de Mara, considerando las variables clínicas y socioeconómicas estudiadas, para lograr disminuir la prevalencia de anemia en esta población.

Iron levels in the human brain: a post-mortem study of anatomical region differences and age-related changes.

The link between brain iron homeostasis and neurodegenerative disease has been the subject of extensive research. There is increasing evidence of iron accumulation during ageing, and altered iron levels in some specific brain regions in neurodegenerative disease patients have been reported. Using graphite furnace atomic absorption spectrometry after microwave-assisted acid digestion of the samples, iron levels were determined in 14 different areas of the human brain [frontal cortex, superior and middle temporal, caudate nucleus, putamen, globus pallidus, cingulated gyrus, hippocampus, inferior parietal lobule, visual cortex of the occipital lobe, midbrain, pons (locus coeruleus), medulla and cerebellum (dentate nucleus)] of n=42 adult individuals (71±12 years old, range: 53-101 years old) with no known history or evidence of neurodegenerative, neurological or psychiatric disorders. It was found that the iron distribution in the adult human brain is quite heterogeneous. The highest levels were found in the putamen (mean±SD, range: 855±295µg/g, 304-1628µg/g) and globus pallidus (739±390µg/g, 225-1870µg/g), and the lowest levels were observed in the pons (98±43µg/g, 11-253µg/g) and medulla (56±25µg/g, 13-115µg/g). Globally, iron levels proved to be age-related. The positive correlation between iron levels and age was most significant in the basal ganglia (caudate nucleus, putamen and globus pallidus). Compared with the age-matched control group, altered iron levels were observed in specific brain areas of one Parkinson's disease patient (the basal ganglia) and two Alzheimer's disease patients (the hippocampus).

Serum iron levels as a new biomarker in chemotherapy with leucovorin and fluorouracil plus oxaliplatin or leucovorin and fluorouracil plus irinotecan, with or without molecularly-targeted drugs.

Serum iron levels have been reported to increase following the administration of various anticancer drugs. An increase in serum iron levels during therapy with leucovorin and fluorouracil plus oxaliplatin (FOLFOX) or leucovorin and fluorouracil plus irinotecan (FOLFIRI) was also observed. The aim of this study was to investigate the correlation between serum iron levels and prognosis in advanced colorectal cancer (CRC) patients treated with FOLFOX/FOLFIRI ± molecularly-targeted drugs. Serum iron levels were measured prior to and at 48 h after treatment with FOLFOX/FOLFIRI ± molecularly-targeted drugs in 72 advanced CRC patients, all of whom succumbed to the disease between December, 2005 and February, 2012. No patients received radiotherapy. Taking the median rate of increase in serum iron levels as the cut-off value in each therapy, the patients were divided into cohort I (increase rate greater than the cut-off value in at least one therapy) or cohort II (increase rate less than the cut-off value in all therapies). The χ2 test and the t-test were used to compare patient characteristics between the two cohorts. Prognosis was evaluated between the two cohorts using the Kaplan-Meier method, the log-rank test and the Cox proportional hazards regression analysis. No significant bias in patient characteristics (including the frequency of chemotherapy or number of patients treated with molecularly-targeted drugs) was observed between the two cohorts. Serum iron levels were transiently elevated following treatment (P<0.001), returning to baseline within 2 weeks. Median survival time (MST) in cohort I (n=44) and cohort II (n=28) was 430 and 377 days, respectively. The MST was significantly higher in cohort I (P=0.0382). The multivariate analysis identified a small increase in serum iron levels as an independent risk factor for overall survival (OS). These results suggest that serum iron levels may be used as a new predictive factor in FOLFOX/FOLFIRI ± molecularly-targeted drug therapy. Serum iron levels may therefore prove to be a useful and convenient biomarker for OS in CRC patients.