Introduction: Sites associated with gadolinium (Gd) deposition in the brain (e.g., the globus pallidus) are known to contain high concentrations of ferric iron. There is considerable debate over the mechanism of Gd deposition in the brain. The role of iron transport mechanisms in Gd deposition has not been determined. Thus, we seek to identify if Gd deposition can be controlled by modifying iron exposure. Methods: Female Sprague-Dawley rats were given diets with controlled iron levels at 2-6 ppm, 6 ppt (20 g/kg Fe carbonyl) or 48 ppm for 3 weeks to induce iron deficiency, overload or normalcy. They were kept on those diets while receiving a cumulative 10 mmol/kg dose of gadodiamide intravenously over 2 weeks, then left to washout gadodiamide for 3 days or 3 weeks before tissues were harvested. Gd concentrations in tissues were analyzed by ICP-MS. Results: There were no significant effect of dietary iron and total Gd concentrations in the organs, but there was a significant effect of iron status on Gd distribution in the brain. For the 3-week washout cohort, there was a non-significant trend of increasing total brain deposition and decreasing dietary iron, and about 4-fold more Gd in the olfactory bulbs of the low iron group compared to the other groups. Significant brain accumulation was observed in the low iron group total brain Gd in the 3-week washout group relative to the 3-day washout group and no accumulation was observed in other tissues. There was a strong negative correlation between femur Gd concentrations and concentrations in other organs when stratifying by dietary iron. Discussion: Gd brain deposition from linear Gd-based contrast agents (GBCAs) are dependent upon iron status, likely through variable transferrin saturation. This iron dependence appears to be associated with redistribution of peripheral deposited Gd (e.g., in the bone) into the brain.

Pica is an eating disorder defined as the compulsive and repeated ingestion of substances that have no nutritional value for at least one month. This condition may be hard to diagnose without complications, as a high degree of suspicion is needed. The subject in this case was a teenager who presented with asthenia and unspecific abdominal pain. The etiological workup showed no abnormalities other than mild anemia and iron and folate deficiencies. After a thorough anamnesis, the patient\'s mother mentioned sporadic ingestion of synthetic mattress foam since childhood, which had become more frequent in the previous year. With this key information, it was possible to establish a diagnosis before serious complications occurred and thus help the patient get the necessary assistance by referring them to pediatrics, nutrition, and child and adolescent psychiatry consultations. This case report highlights the importance of a detailed anamnesis, particularly when dealing with unspecific symptoms, exploring the possibility of disorders that are rarely thought of, such as pica. It also recaps how important it is to address sensitive topics like eating disorders and create an open environment with no judgment, as these attitudes are crucial to ensuring the correct diagnosis and providing the best care for patients.

Objective. To evaluate the evidence regarding the association between iron deficiency anemia (IDA) and dental caries in children and adolescents. Methods. Searches were conducted in 4 international databases from the beginning of records until October 2023. Studies evaluating the association between IDA and dental caries in individuals aged 6 months to 18 years were included. Risk of bias was assessed using the Newcastle Ottawa Scale. Quantitative synthesis was performed using the inverse variance or Mantel-Haenzel method, depending on the type of outcome analyzed. Measures of association included odds ratios and mean differences, employing a random-effects model with a 95% confidence interval. Results. A total of 1161 studies were identified, of which 12 were selected for qualitative review and 9 for meta-analysis. A significant association was found between IDA and dental caries (odds ratio of 3.54; 95% CI: 2.54-4.94) and a higher rate of dental caries in the presence of IDA (mean difference of 1.96; 95% CI: 1.07-2.85). The certainty of evidence according to GRADE was rated as very low. Conclusions. Despite the limited certainty, the findings indicate a significant association between IDA and dental caries. It is prudent to interpret these results with caution, considering the methodological limitations of the studies. However, given the potential relevance of this association for public health, recommending oral health strategies, including preventive and corrective dental interventions, for anemia control programs underlines the importance of more rigorous future research to strengthen the certainty of the evidence and guide the implementation of these strategies.

Background: Iron deficiency (ID) is common in patients with pulmonary arterial hypertension and has been associated with increased morbidity and mortality. We aimed to evaluate the therapeutic effects of iron supplementation in iron deficient patients with group 1 to 4 pulmonary hypertension (PH). Methods: A total of 85 PH patients (mean age 69.8 ± 12.0 years, 56.5% female) were included in this prospective trial. Patients were screened for ID at baseline. PH patients with ID received intravenous iron supplementation (500-1000 mg ferric carboxymaltose). PH patients without ID served as control group. At baseline and 16-week follow up, six-minute walk test (6MWT), laboratory testing and echocardiography were performed. Additionally, World Health Organization (WHO) functional class, fatigue score and quality of life (QoL) by the SF-36 questionnaire were assessed. Results: Overall, ID was present in 26.7% (n=8/30), 37.5% (n=9/24), 45.5% (n=10/22) and 44.4% (n=4/9) of patients in PH groups 1-4, respectively. In the total study population, iron restoration led to a significant mitigation of fatigue (p=0.01). However, 6MWT, WHO function class, NT-proBNP levels, QoL and right ventricular function did not change significantly. With regard to the underlying PH group, only PH group 3 patients experienced significant improvements in 6MWT distance (p=0.019), WHO functional class (p=0.017), fatigue (p=0.009) and some QoL domains, as compared to controls. Conclusions: ID was common in PH groups 1 to 4. Though intravenous iron supplementation adequately restored iron status and improved fatigue throughout all patients, in the underlying PH groups treatment was accompanied by improvements in exercise capacity, WHO function class and fatigue only in group 3 PH.

Iron is an important cofactor for many proteins and is used to create Fe-S clusters and heme prosthetic groups that enzymes use to catalyze enzymatic reactions. Proteins involved in the import, export, and sequestration of iron are regulated by Iron Regulatory Proteins (IRPs). Recently, a patient with bi-allelic loss of function mutations in IREB2 leading to the absence of IRP2 protein was discovered. The patient failed to achieve developmental milestones and was diagnosed with dystonic cerebral palsy, epilepsy, microcytic hypochromic anemia, and frontal lobe atrophy. Several more IREB2 deficient patients subsequently identified manifested similar neurological problems. To better understand the manifestations of this novel neurological disease, we subjected an Irp2-null mouse model to extensive behavioral testing. Irp2-null mice had a significant motor deficit demonstrated by reduced performance on rotarod and hanging wire tests. Somatosensory function was also compromised in hot and cold plate assays. Their spatial search strategy was impaired in the Barnes maze and they exhibited a difficulty in flexibly adapting their response in the operant touchscreen reversal learning task. The latter is a cognitive behavior known to require an intact prefrontal cortex. These results suggest that loss of Irp2 in mice causes motor and behavioral deficits that faithfully reflect the IREB2 patient\'s neurodegenerative disorder.

BACKGROUND: Overweight/obesity and iron deficiency are highly prevalent in women of reproductive age (WRA), impacting on women\'s health. Obesity is a risk factor for nutritional deficiencies but its association with iron deficiency is unclear.
OBJECTIVE: To determine the association between adiposity and markers of iron status and iron deficiency prevalence in WRA.
METHODS: This cross-sectional study analyzed the National Diet and Nutrition Survey (NDNS, 2008-2019) data, focusing on women aged 18-49y with BMI ≥18.5 kg/m2. Prevalence of anemia, Iron Deficiency Anemia (IDA), and Iron Deficiency (ID) were analyzed. Ferritin was adjusted for C-reactive protein. Iron status was assessed across high and low BMI, waist circumference (WC), waist-to-height (WHtR), and waist-to-hip ratio (WHR). Chi2, linear and logistic regression were performed adjusting for covariates.
RESULTS: Among 1,098 WRA, 496 normal weight and 602 overweight/obesity, prevalence rates were: anemia 9.2% and IDA 6.8%. Anemia was more prevalent in those with higher WHtR and WHR (11.9% vs 5.9% and 16.7% vs 6.5%, both p<0.001). WRA with increased WC, WHtR, and WHR had higher IDA prevalence than those with lower adiposity. (8.5% vs 4.3%, p=0.005; 9.4% vs 3.3%, p<0.001; 12.1% vs 4.9%, p<0.001). ID prevalence was 49.7% (ferritin cut-off 30 μg/L) and 19.6% (ferritin cut-off 15 μg/L), showing similar rates across adiposity groups. ID prevalence defined by soluble transferrin receptor (sTfR) was higher in women with increased WHR (p=0.001). Higher WHR predicted ID categorized by sTfR (aOR 2.104, p=0.004), and WHtR and WHR predicted anemia and IDA (anemia: WHtR aOR 2.006 p=0.036; WHR aOR 4.489 p<0.001; IDA: WHtR: aOR 2.942, p=0.012; WHR aOR 4.142, p<0.001).
CONCLUSIONS: At least one in five WRA in the UK are iron deficient, highlighting the need to revise current policies. Greater central adiposity was strongly associated with impaired iron status and the development of anemia, IDA, and ID.

Protoporphyrins are organic compounds with cyclic structure that are synthesised by a wide variety of organisms. In humans, these compounds are detected in blood and urine, with significantly higher levels in blood. Their potential as biomarkers of anemia and other diseases is currently being investigated, as their levels change according to the biochemical processes associated with the disease. The most widely used biomarker of anemia is serum ferritin, but it is unreliable in patients with inflammatory bowel disease (IBD) because its levels can be altered by acute inflammation and/or infections. There is therefore a need to look for new markers to help diagnose anemia in IBD patients. This work develops and validates a method for the determination of three protoporphyrins in human urine: protoporphyrin IX (PPIX), protoporphyrin IX complex with Zn (ZnPPIX) and protoporphyrin IX complex with Fe (II) (FePPIX), the latter also known as heme. The aim is to evaluate their potential as biomarkers of anemic disease in patients diagnosed with IBD. The proposed analytical method is based on high performance liquid chromatography (HPLC) with dual detection based on photodiode array (PDA) and fluorescence (FD). Quantification of the analytes at very low concentrations is possible due to the efficient preconcentration provided by dispersive liquid-liquid microextraction (DLLME) and the sensitivity of the detection systems. The method was validated by evaluating linearity (25-1000 ng mL-1), matrix effect, sensitivity (limits of quantification were between 5 and 11 ng mL-1), selectivity, accuracy, carry-over, dilution integrity, stability and precision (< 12.1 %). Finally, statistical analyses applied to the sample quantification results showed these three markers, together with five clinical markers, were significantly different between anemic and non-anemic IBD patients.

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.

Restless Legs Syndrome (RLS) is a neurological disorder characterized by an irresistible urge to move the legs and is associated with decreased quality of life and sleep, and may result in cognitive changes. Physical exercise generates cognitive improvements and improves RLS symptoms. Our objective is to analyze recognition memory in the iron-deficient rodent model of RLS, and the effect of exercise. The animals (male Wistar rats) were distributed at 21 days of age into a control group (CTRL) (standard diet) or an ID group (iron-deficient diet). After performance classification (at 77 days of age), the animals were redistributed into CTRL (no exercise), CTRL EX (exercise), ID (no exercise) and ID EX (exercise), totaling 9 animals per group. The exercise groups performed treadmill exercise for four weeks. In the 14th week of the diet, the sleep recording of CTRL and ID animals was carried out to validate the RLS model. The Novel Object Recognition Memory test (NOR) was performed before the start of exercise (8th week of diet) and after the end (14th week) in all groups. The ID group demonstrated worsening sleep parameters and increased paw movements compared to the control group. The ID group demonstrated impairment of recognition memory after 14 weeks of diet compared to the CTRL group, and, the CTRL improved recognition memory in the 14th week compared to the 8th week. No differences were found for the exercise groups. Our findings indicate that the RLS animal model exhibited cognitive alterations associated with recognition memory, and long-term aerobic exercise intervention demonstrated a protective influence against these effects.

Although it has been established that patients with chronic kidney disease and iron deficiency, as indicated by a transferrin saturation of < 20%, are at increased risk of all-cause mortality and cardiovascular events, the optimal management of such patients has not yet been determined. In this post hoc subgroup analysis, we aimed to clarify the effect of ferric citrate hydrate on transferrin saturation in patients with chronic kidney disease and low transferrin saturation (< 20%) undergoing hemodialysis. To accomplish this, we extracted the relevant data on a subset of patients drawn from two previous studies: the ASTRIO study (A Study examining the contribution to Renal anemia treatment with ferric citrate hydrate, Iron-based Oral phosphate binder, UMIN000019176) and a post-marketing surveillance study. The subset of patients used for the present study were those with baseline transferrin saturation < 20%. We found that administration of ferric citrate hydrate increased transferrin saturation and maintained transferrin saturation at approximately 30%. However, because we did not have access to data on all-cause mortality or cardiovascular events, we could not ascertain whether the frequency of these outcomes was reduced in parallel with improvements in transferrin saturation. Further large studies are required.