Factores asociados a anemia ferropénica en lactantes y preescolares / Factors associated with iron deficiency anemia in infants and preschoolers

Introducción: La anemia se define como una afección en la cual el número de glóbulos rojos o la concentración de hemoglobina dentro de estos se encuentran por debajo del límite inferior, 11 gr/dl para menores entre 6 a 59 meses. La OMS calcula que a nivel mundial la anemia presenta una prevalencia del 42% en los niños menores de 5 años. Objetivos: Realizar una revisión panorámica de diversas publicaciones científicas acerca de los factores asociados a la anemia ferropénica en preescolares. Materiales y métodos: La revisión se realizó a través de la búsqueda electrónica de diversos artículos científicos relacionados con el tema. Se utilizó la pregunta PEO: ¿Cuáles son los factores asociados a anemia ferropénica en lactantes y preescolares? Se seleccionaron los artículos publicados desde el 2017 hasta el 2022. Resultados: De los 48 artículos encontrados en la revisión, 33 fueron descartados por no cumplir con nuestros criterios de selección, quedando 15 artículos para esta revisión. Basado en 12 artículos revisados, se halló que los factores que se asocian a anemia en menores de 5 años eran por problemas socioeconómicos, déficit de micronutrientes altos en hierro en dieta, madre con antecedente de anemia, la edad materna, falta de educación, entre otros. Conclusión: Los factores predisponentes para la presencia de anemia ferropénica en los menores de 5 años más importantes fueron los relacionados con la edad materna, el nivel socioeconómico y educativo de la madre que conllevan el déficit de hierro del menor.

Introduction: Anemia is defined as a condition in which the number of red blood cells or the hemoglobin concentration within red blood cells is below the lower limit, 11 g/dL for children aged 6-59 months. The WHO estimates that worldwide anemia has a prevalence of 42% in children under 5 years of age. Objectives: To perform an overview review of various scientific publications on the factors associated with iron deficiency anemia in preschoolers. Materials and methods: The review was carried out through an electronic search of various scientific articles related to the subject. The PEO question was used: What are the factors associated with iron deficiency anemia in infants and preschoolers? Articles published from 2017 to 2022 were selected. Results: Of the 48 articles found in the review, 33 were discarded for not meeting our selection criteria, leaving 15 articles for this review. Based on 12 articles reviewed, it was found that the factors associated with anemia in children under 5 years of age were socioeconomic problems, deficiency of micronutrients high in iron in the diet, mothers with a history of anemia, maternal age, lack of education, among others. Conclusion: The most important predisposing factors for the presence of iron deficiency anemia in children under 5 years of age were those related to maternal age, socioeconomic and educational level of the mother that lead to iron deficiency in the child.

Riesgos y beneficios de la profilaxis con sulfato ferroso en lactantes nacidos a término con niveles de hemoglobina y ferremia desconocidos / Risks and benefits of iron supplementation in full-term infants with unknown hemoglobin and ferritin levels

La seguridad y eficacia de los programas de suplementación con hierro a lactantes, está actualmente en discusión. El objetivo de esta revisión fue identificar estudios sobre riesgos y beneficios de la suplementación con hierro profiláctico en lactantes menores de un año, nacidos a término, con niveles de hemoglobina (Hb) y ferremia desconocidos. Se realizó una búsqueda en Pubmed y Cochrane, identificando 3 revisiones sistemáticas y metaanálisis. Estos estudios arrojaron resultados que indican mejoras en los niveles séricos de hierro y hemoglobina como resultado de la suplementación con hierro. Sin embargo, no se observó un beneficio significativo en el desarrollo cognitivo de los lactantes. Los efectos adversos más reportados son los gastrointestinales, efectos en el crecimiento (menor ganancia de talla y peso) y menor absorción de zinc. En resumen, la evidencia en cuanto a la profilaxis con hierro en lactantes es limitada, lo que nos lleva a recomendar un seguimiento cercano de los lactantes que reciben suplementos de hierro, con el objetivo de detectar posibles eventos adversos. Es fundamental evaluar cuidadosamente los riesgos y beneficios de esta intervención antes de su implementación (AU)

The safety and efficacy of iron supplementation programs for infants are currently under discussion. The objective of this review was to identify studies on the risks and benefits of prophylactic iron supplementation in infants under one year of age, born at term, with unknown hemoglobin (Hb) and serum iron levels. The search was conducted on Pubmed and Cochrane, identifying three systematic reviews and meta-analyses. The results indicate improvements in serum iron and hemoglobin levels as a result of iron supplementation. However, a significant benefit in infant cognitive development was not observed. The most reported adverse effects were gastrointestinal, effects on growth (reduced height and weight gain), and reduced zinc absorption. In summary, the evidence regarding iron prophylaxis in infants is limited, leading us to recommend close monitoring of infants receiving iron supplements to detect potential adverse events. It is crucial to carefully assess the risks and benefits of this intervention before implementation (AU)

Invivo and invitro evaluation of antitumor effects of iron oxide and folate core shell-iron oxide nanoparticles

Abstract Nanoparticles are considered viable options in the treatment of cancer. This study was conducted to investigate the effect of magnetite nanoparticles (MNPs) and magnetite folate core shell (MFCS) on leukemic and hepatocarcinoma cell cultures as well as their effect on the animal model of acute myelocytic leukemia (AML). Through current study nanoparticles were synthesized, characterized by various techniques, and their properties were studied to confirm their nanostructure. Invivo study, nanoparticles were evaluated to inspect their cytotoxic activity against SNU-182 (human hepatocellular carcinoma), K562 (human leukemia), and THLE2 (human normal epithelial liver) cells via MTT test. Apoptotic signaling proteins Bcl-2 and Caspase-3 expression were inspected through RT-PCR method. A cytotoxic effect of MNPs and MFCS was detected in previous cell cultures. Moreover, the apoptosis was identified through significant up-regulation of caspase-3, with Bcl-2 down-regulation. Invitro study, AML was induced in rats by N-methyl-N-nitrosourea followed by oral treatment with MNPS and MFCS. Biochemical indices such as aspartate and alanine amino transferases, and lactate dehydrogenase activities, uric acid, complete blood count, and Beta -2-microglubulin were assessed in serum. Immunophenotyping for CD34 and CD38 detection was performed. Liver, kidney, and bone marrow were microscopically examined. Bcl-2 promoter methylation, and mRNA levels were examined. Although, both MNPs and MFCS depict amelioration in biochemical parameters, MFCS alleviated them toward normal control. Anticancer activity of MNPs and MFCS was approved especially for AML. Whenever, administration of MFCS was more effective than MNPs. The present work is one of few studies used MFCS as anticancer agent.

Resumo Nanopartículas são consideradas opções viáveis no tratamento do câncer. Este estudo foi conduzido para investigar o efeito de nanopartículas de magnetita (MNPs) e núcleo de folato de magnetita (MFCS) em culturas de células leucêmicas e de hepatocarcinoma, bem como seu efeito no modelo animal de leucemia mielocítica aguda (LMA). Através do atual estudo, nanopartículas foram sintetizadas, caracterizadas por várias técnicas, e suas propriedades foram estudadas para confirmar sua nanoestrutura. No estudo in vivo, as nanopartículas foram avaliadas para inspecionar sua atividade citotóxica contra células SNU-182 (carcinoma hepatocelular humano), K562 (leucemia humana) e THLE2 (fígado epitelial humano normal) por meio do teste MTT. A expressão das proteínas sinalizadoras apoptóticas Bcl-2 e Caspase-3 foram inspecionadas através do método RT-PCR. Um efeito citotóxico de MNPs e MFCS foi detectado em culturas de células anteriores. Além disso, a apoptose foi identificada por meio de regulação positiva significativa da Caspase-3, com regulação negativa de Bcl-2. No estudo in vitro, a AML foi induzida em ratos por N-metil-N-nitrosoureia seguida por tratamento oral com MNPS e MFCS. Índices bioquímicos como aspartato e alanina aminotransferases e atividades de lactato desidrogenase, ácido úrico, hemograma completo e Beta-2-microglubulina foram avaliados no soro. A imunofenotipagem para detecção de CD34 e CD38 foi realizada. Fígado, rim e medula óssea foram examinados microscopicamente. A metilação do promotor Bcl-2 e os níveis de mRNA foram examinados. Embora tanto os MNPs quanto os MFCS representem uma melhora nos parâmetros bioquímicos, o MFCS os aliviou em direção ao controle normal. A atividade anticâncer de MNPs e MFCS foi aprovada especialmente para AML. Sempre, a administração de MFCS foi mais eficaz do que MNPs. O presente trabalho é um dos poucos estudos que utilizou o MFCS como agente anticâncer.

Invivo and invitro evaluation of antitumor effects of iron oxide and folate core shell-iron oxide nanoparticles / Avaliação in vivo e in vitro dos efeitos antitumorais de nanopartículas de óxido de ferro e óxido de ferro com núcleo de folato

Abstract Nanoparticles are considered viable options in the treatment of cancer. This study was conducted to investigate the effect of magnetite nanoparticles (MNPs) and magnetite folate core shell (MFCS) on leukemic and hepatocarcinoma cell cultures as well as their effect on the animal model of acute myelocytic leukemia (AML). Through current study nanoparticles were synthesized, characterized by various techniques, and their properties were studied to confirm their nanostructure. Invivo study, nanoparticles were evaluated to inspect their cytotoxic activity against SNU-182 (human hepatocellular carcinoma), K562 (human leukemia), and THLE2 (human normal epithelial liver) cells via MTT test. Apoptotic signaling proteins Bcl-2 and Caspase-3 expression were inspected through RT-PCR method. A cytotoxic effect of MNPs and MFCS was detected in previous cell cultures. Moreover, the apoptosis was identified through significant up-regulation of caspase-3, with Bcl-2 down-regulation. Invitro study, AML was induced in rats by N-methyl-N-nitrosourea followed by oral treatment with MNPS and MFCS. Biochemical indices such as aspartate and alanine amino transferases, and lactate dehydrogenase activities, uric acid, complete blood count, and Beta -2-microglubulin were assessed in serum. Immunophenotyping for CD34 and CD38 detection was performed. Liver, kidney, and bone marrow were microscopically examined. Bcl-2 promoter methylation, and mRNA levels were examined. Although, both MNPs and MFCS depict amelioration in biochemical parameters, MFCS alleviated them toward normal control. Anticancer activity of MNPs and MFCS was approved especially for AML. Whenever, administration of MFCS was more effective than MNPs. The present work is one of few studies used MFCS as anticancer agent.

Resumo Nanopartículas são consideradas opções viáveis ​​no tratamento do câncer. Este estudo foi conduzido para investigar o efeito de nanopartículas de magnetita (MNPs) e núcleo de folato de magnetita (MFCS) em culturas de células leucêmicas e de hepatocarcinoma, bem como seu efeito no modelo animal de leucemia mielocítica aguda (LMA). Através do atual estudo, nanopartículas foram sintetizadas, caracterizadas por várias técnicas, e suas propriedades foram estudadas para confirmar sua nanoestrutura. No estudo in vivo, as nanopartículas foram avaliadas para inspecionar sua atividade citotóxica contra células SNU-182 (carcinoma hepatocelular humano), K562 (leucemia humana) e THLE2 (fígado epitelial humano normal) por meio do teste MTT. A expressão das proteínas sinalizadoras apoptóticas Bcl-2 e Caspase-3 foram inspecionadas através do método RT-PCR. Um efeito citotóxico de MNPs e MFCS foi detectado em culturas de células anteriores. Além disso, a apoptose foi identificada por meio de regulação positiva significativa da Caspase-3, com regulação negativa de Bcl-2. No estudo in vitro, a AML foi induzida em ratos por N-metil-N-nitrosoureia seguida por tratamento oral com MNPS e MFCS. Índices bioquímicos como aspartato e alanina aminotransferases e atividades de lactato desidrogenase, ácido úrico, hemograma completo e Beta-2-microglubulina foram avaliados no soro. A imunofenotipagem para detecção de CD34 e CD38 foi realizada. Fígado, rim e medula óssea foram examinados microscopicamente. A metilação do promotor Bcl-2 e os níveis de mRNA foram examinados. Embora tanto os MNPs quanto os MFCS representem uma melhora nos parâmetros bioquímicos, o MFCS os aliviou em direção ao controle normal. A atividade anticâncer de MNPs e MFCS foi aprovada especialmente para AML. Sempre, a administração de MFCS foi mais eficaz do que MNPs. O presente trabalho é um dos poucos estudos que utilizou o MFCS como agente anticâncer.

Targeting ferroptosis for treatment of Alzheimer' s disease / 中国药理学通报

Alzheimer' s disease (AD) is a progressive neurodegenerative disorder histologically characterized by the presence of senile plaques and neurofibrillary tangles (NFTs) found in and around pyramidal neurons in cortical tissue. Mounting evidence suggests regional increased iron load and dyshomeostasis have been associated with oxidative stress, oxidation of proteins and lipids, and cell death, and appears to be a risk factor for more rapid cognitive decline, thereby involved in multiple aspects of the pathophysiology of AD. Ferroptosis is a newly identified iron-dependent lipid peroxidation-driven cell death and emerging evidences have demonstrated the involvement of ferroptosis in the pathological process of AD. Notably, some novel compounds targeting ferroptosis can relieve AD-related pathological symptoms in AD cells and animal model and exhibit potential clinical benefits in AD patients. This review systematically summarizes the growing molecular and clinical evidence implicating ferroptosis in the pathogenesis of AD, and then reviews the application of ferroptosis inhibitors in mouse/cell models to provide valuable information for future treatment and prevention of AD.

Research progress in ferroptosis pathways and ubiquitination modification of ferroptosis-related molecules / 中国药理学通报

Ferroptosis is an iron-dependent cell death caused by phospholipid peroxidation damage of polyunsaturated fatty acids on cell membranes and involves several pathways, including the iron homeostasis regulatory pathway, the cystine glutamate reverse transporter (system Xc) pathway and the voltage-dependent anion channel (VDAC) pathway. Ferroptosis is involved in the development of several diseases (e. g. myocardial infarction, stroke, cancer and degenerative diseases). The ubiquitination is an important post-translational modification of various protein molecules in the organism. Studies have shown that regulating the ubiquitination of ferroptosis pathway-related molecules can control cellular ferroptosis. Targeting the ubiquitination of ferroptosis pathway-related molecules can effectively promote or inhibit ferroptosis, which is expected to be a new strategy for the treatment of cancer or cardiovascular diseases. In this paper we review the progress of the ferroptosis pathways and the ubiquitination modification of ferroptosis-related molecules.

Active Ingredients of Chinese Medicines Induce Ferroptosis in Tumor Cells： A Review / 中国实验方剂学杂志

Ferroptosis， a new form of programmed cell death different from apoptosis， necrosis， and autophagy， is closely associated with a variety of physiological and pathological processes. Iron-mediated accumulation of reactive oxygen species is the main inducement of ferroptosis， the mechanism of which is related to intracellular lipid metabolism， iron metabolism， and antioxidant defense pathways. Multiple signaling axes and regulators jointly regulate the occurrence and disruption of ferroptosis. Studies have demonstrated that ferroptosis regulates the growth and proliferation of tumor cells. Inducing ferroptosis in tumor cells can control the growth， metastasis， and multi-drug resistance of tumors. Therefore， the effect and mechanism of ferroptosis on tumor cells have become a hot topic in anti-cancer research. As the research advances， a variety of ferroptosis inducers has been used in the clinical chemotherapy for cancers and demonstrate significant efficacy. Accordingly， the development of ferroptosis-inducing anticancer drugs has become a new research direction for tumor treatment. Some active ingredients such as lycorine， oleanolic acid， dihydroartemisinin， pseudolaric acid B， and ophiopogonin B of Chinese medicines can induce ferroptosis in tumor cells via lipid metabolism， iron metabolism， system Xc-， and GPX4/GSH to regulate the development of tumors， demonstrating a promising prospect in clinical treatment. Based on the theory of the mechanism of ferroptosis， this paper reviews the research progress in ferroptosis induced by active ingredients of Chinese medicines in tumor cells and describes the metabolic regulatory network of ferroptosis from signaling pathways and regulatory factors， providing new strategies for applying active ingredients of Chinese medicines in the treatment of tumors.

Research status of ocular changes in beta-thalassemia major / 国际眼科杂志(Guoji Yanke Zazhi)

Beta-thalassemia major(β-TM)is an inherited disease caused by a defect in the synthesis of globin. The disease requires long-term blood transfusion and iron chelator treatment, which can cause various secondary changes in the body and eye tissues. Compared with normal peers, β-TM patients will show changes in the eye such as steeper corneal curvature, shallower anterior chamber, increased lens thickness, shorter axial length, and reduced tear secretion. At the same time, nutritional deficiencies and the use of iron chelator drugs will increase the risk of complicated cataract and retinal degeneration, thus affecting the quality of life of β-TM patients.This article combines relevant domestic and foreign literatures to explore and review the changes in the eye of β-TM patients, with a view to providing valuable insights for clinical practice.

Effect of Baihe Yuzi Prescription on CFTR， AQP， and ZIP Ion Channels and Oxidative Stress in Epididymis of Oligoasthenozoospermia Rats / 中国实验方剂学杂志

ObjectiveTo observe the effects of Baihe Yuzi prescription （BYP） on the cystic fibrosis transmembrane conductance regulator （CFTR）， aquaporin （AQP）， zinc/iron-regulated transporter-like protein （ZIP） and local oxidative stress in epididymis of oligoasthenozoospermia （OAS） rats， and to explore the mechanism of its intervention in OAS. MethodAfter 35 rats were acclimatized for 1 week， 7 rats were randomly selected as the normal group， and the remaining 28 rats were given tripterygium glycosides （TG） 30 mg·kg-1. After 4 weeks of modeling， they were randomly divided into 4 groups： model group， BYP low-dose group （LBYP）， BYP high-dose group （HBYP） and levocarnitine group， with 7 rats in each group. The rats in the normal group and model group were given normal saline at the same dosage. The levocarnitine group rats were given L-carnitine oral liquid （100 mg·kg-1） by gavage. The LBYP group rats were given BYP 6.3 g·kg-1， and the HBYP group rats were given BYP 12.6 g·kg-1 by gavage once a day for consecutive 4 weeks. After the end of the intervention， sperm count and motility of all rats were detected， the histopathological structure of epididymis was observed by hematoxylin-eosin （HE） staining， and the expressions of CFTR， AQP9， AQP3， ZIP8， ZIP12 and other proteins were detected by Western blot. The contents of α-glycosidase （α-GC）， sialic acid （SA）， carnitine， superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px） and malondialdehyde （MDA） were detected by enzyme-linked immunosorbent assay （ELISA）. Total zinc content was measured using an inductively coupled plasma mass spectrometer. Free zinc ion content was detected by zinc ion probes. ResultCompared with those in the normal group， the sperm count and motility of rats were decreased and the epididymal structure was disordered in the model group. The contents of α-GC and carnitine were decreased in epididymis （P<0.05）. MDA levels were increased， while SOD， GSH-Px and zinc levels were decreased （P<0.05）. The expressions of CFTR and ZIP12 in the head and cauda of the epididymis were down-regulated， and AQP3 expression was up-regulated. The expression of ZIP8 in the cauda epididymis was up-regulated （P<0.05）. Compared with the model group， BYP can significantly improve the sperm count and motility， the epididymal structure of OAS rats and the levels of α-GC and carnitine （P<0.05）. The expressions of CFTR and ZIP12 in the head and cauda of the epididymis were up-regulated， while the expressions of ZIP8 in the cauda epididymis and AQP3 in the head of the epididymis were decreased （P<0.05）. The SOD and GSH-Px levels and total zinc content in epididymis were increased， and the MDA levels were decreased （P<0.05）. ConclusionBYP may improve the sperm quality and repair epididymal tissue structure and function of OAS rats， by regulating the expressions of CFTR， AQP3， and ZIP12 ion channels and local antioxidant mechanism.

Intermittent Theta Burst Stimulation Attenuates Cognitive Deficits and Alzheimer's Disease-Type Pathologies via ISCA1-Mediated Mitochondrial Modulation in APP/PS1 Mice / 神经科学通报·英文版

Intermittent theta burst stimulation (iTBS), a time-saving and cost-effective repetitive transcranial magnetic stimulation regime, has been shown to improve cognition in patients with Alzheimer's disease (AD). However, the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown. Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation. Here, we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1 (ISCA1, an essential regulatory factor for mitochondrial respiration) in the brain of APP/PS1 mice. In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function, which is required for ISCA1. Moreover, iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice. The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD. We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.

Targeting ferroptosis and ferritinophagy: new targets for cardiovascular diseases / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Cardiovascular diseases (CVDs) are a leading factor driving mortality worldwide. Iron, an essential trace mineral, is important in numerous biological processes, and its role in CVDs has raised broad discussion for decades. Iron-mediated cell death, namely ferroptosis, has attracted much attention due to its critical role in cardiomyocyte damage and CVDs. Furthermore, ferritinophagy is the upstream mechanism that induces ferroptosis, and is closely related to CVDs. This review aims to delineate the processes and mechanisms of ferroptosis and ferritinophagy, and the regulatory pathways and molecular targets involved in ferritinophagy, and to determine their roles in CVDs. Furthermore, we discuss the possibility of targeting ferritinophagy-induced ferroptosis modulators for treating CVDs. Collectively, this review offers some new insights into the pathology of CVDs and identifies possible therapeutic targets.

The role of iron-uptake factor PiuB in pathogenicity of soybean pathogen Xanthomonas axonopodis pv. glycines / 生物工程学报

Iron is an essential element for living organisms that plays critical roles in the process of bacterial growth and metabolism. However, it remains to be elucidated whether piuB encoding iron-uptake factor is involved in iron uptake and pathogenicity of Xanthomonas axonopodis pv. glycines (Xag). To investigate the function of piuB, we firstly generated a piuB deletion mutant (ΔpiuB) by homologous recombination. Compared with the wild-type, the piuB mutant exhibited significantly reduced growth and virulence in host soybean. The mutant displayed markedly increased siderophore secretory volume, and its sensitivity to Fe3+, Cu2+, Zn2+ and Mn2+ was significantly enhanced. Additionally, the H2O2 resistance, exopolysaccharide yield, biofilm formation, and cell mobility of ΔpiuB were significantly diminished compared to that of the wild-type. The addition of exogenous Fe3+ cannot effectively restore the above characteristics of ΔpiuB. However, expressing piuB in trans rescued the properties lost by ΔpiuB to the levels in the wild-type. Taken together, our results demonstrated that PiuB is a potential factor for Xag to assimilate Fe3+, and is necessary for Xag to be pathogenic in host soybean.

Role of Ferroptosis in Bone Homeostasis and Traditional Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

Osteoporosis （OP） is a systemic metabolic bone disease characterized by bone microstructure degeneration and bone mass loss， which has a high prevalence and disability rate. Effective prevention and treatment of OP is a major difficulty in the medical community. The nature of OP is that multiple pathological factors lead to the imbalance of human bone homeostasis maintained by osteoblasts and osteoclasts. Ferroptosis is a non-apoptotic cell death pathway， and its fundamental cause is cell damage caused by iron accumulation and lipid peroxidation. Studies have shown that ferroptosis is involved in and affects the occurrence and development of OP， which leads to OP by mediating the imbalance of bone homeostasis. Ferroptosis is an adjustable form of programmed cell death. The intervention of ferroptosis can regulate the damage degree and death process of osteoblasts and osteoclasts， which is beneficial to maintain bone homeostasis， slow down the development process of OP， improve the clinical symptoms of patients， reduce the risk of disability， and improve their quality of life. However， there are few studies on ferroptosis in OP. Traditional Chinese medicine （TCM） is a medical treasure with unique characteristics and great application value in China. It has been widely used in China and has a long history. It has the multi-target and multi-pathway advantages in the treatment of OP， with high safety， few toxic and side effects， and low treatment cost， and has a significant effect in clinical application. The intervention of TCM in ferroptosis to regulate bone homeostasis may be a new direction for the prevention and treatment of OP in the future. This article summarized the regulatory mechanisms related to ferroptosis， discussed the role of ferroptosis in bone homeostasis， and reviewed the current status and progress of active ingredients in TCM compounds and monomers in the regulation of OP through ferroptosis， so as to provide a theoretical basis for the participation of TCM in the prevention and treatment of OP in the future.

Anemia y el desarrollo de la psicomotricidad en la primera infancia / Anemia and the development of psychomotor skills in early childhood / Anemia e desenvolvimento psicomotor na primeira infância

Los bajos niveles de hemoglobina se definen como una concentración baja de hemoglobina en la sangre. La activad metabólica cerebral está vinculada con el desarrollo psicomotor. El desarrollo psicomotor durante la infancia se desarrolla a partir de los reflejos innatos, se organizan en esquemas de conducta, se internalizan durante el segundo año de vida como modelos de pensamiento. En Perú, se contabilizan el 50.99% de los niños con bajos niveles de concentración de hemoglobina en menores de 3 años. Objetivo. Identificar la relación entre la anemia y el desarrollo de la psicomotricidad en la primera infancia. Materiales y Métodos. Para evaluar los niveles de hemoglobina se empleó el método de la azidametahemoglobina, con un hemoglobinómetro, y para evaluar el desarrollo psicomotor se empleó la escala del desarrollo psicomotor. En el estudio participaron 32 niños de 6 a 24 meses de edad. Resultados. El 40,6% presenta niveles de hemoglobina entre 14,2 - 17.2 g/dl, el 31,3% presenta niveles de hemoglobina entre 13.2 -14.1 g/dl seguido del 25,0% que presenta niveles de hemoglobina entre 10,2 -13.1 g/dl y el 3.1% presenta niveles de hemoglobina <10.2 g/dl; respecto al desarrollo psicomotor expresados en coeficiente de desarrollo se evidencia que el 59.4% de niños muestran un desarrollo normal seguido del 31.3% de niños que presenta un desarrollo en riesgo y 9.4% en retraso. Conclusiones. El coeficiente de desarrollo del niño(a) se encontró que la mayoría tiene un desarrollo psicomotor normal seguido de riesgo y de retraso, a pesar que mayoría tiene un coeficiente de desarrollo normal

Low hemoglobin levels are defined as a low hemoglobin concentration in the blood. Brain metabolic activity is linked to psychomotor development. Psychomotor development during infancy develops from innate reflexes, which are organized in behavioral schemes and internalized during the second year of life as thought models. In Peru, 50.99% of children under 3 years of age have low hemoglobin concentration levels. Objective. To identify the relationship between anemia and psychomotor development in early childhood. Materials and Methods. To evaluate hemoglobin levels, the azidametahemoglobin method was used, with a hemoglobinmeter, and to evaluate psychomotor development the psychomotor development scale was used. Thirty-two children aged 6 to 24 months participated in the study. Results. 40.6% presented hemoglobin levels between 14.2 - 17.2 g/dl, 31.3% presented hemoglobin levels between 13.2 -14.1 g/dl followed by 25.0% presenting hemoglobin levels between 10.2 -13.1 g/dl and 3.1% presented hemoglobin levels <10. 2 g/dl; with respect to psychomotor development expressed in development coefficient, 59.4% of children show normal development followed by 31.3% of children with development at risk and 9.4% with delayed development. Conclusions. The development coefficient of the child showed that most of the children have a normal psychomotor development followed by at risk and retardation, although most of them have a normal development coefficient.

Níveis baixos de hemoglobina são definidos como uma baixa concentração de hemoglobina no sangue. A atividade metabólica do cérebro está ligada ao desenvolvimento psicomotor. O desenvolvimento psicomotor durante a infância se desenvolve a partir de reflexos inatos, que são organizados em padrões de comportamento e internalizados durante o segundo ano de vida como padrões de pensamento. No Peru, 50,99% das crianças com menos de 3 anos de idade têm baixas concentrações de hemoglobina. Objetivo. Identificar a relação entre a anemia e o desenvolvimento psicomotor na primeira infância. Materiais e métodos. Para avaliar os níveis de hemoglobina, foi usado o método da azidameta-hemoglobina, com um hemoglobinômetro portátil HemoCue® Hb 201+ e, para avaliar o desenvolvimento psicomotor, foi usada a escala de desenvolvimento psicomotor. Trinta e duas crianças com idade entre 6 e 24 meses participaram do estudo. Resultados. 40,6% tinham níveis de hemoglobina entre 14,2 - 17,2 g/dl, 31,3% tinham níveis de hemoglobina entre 13,2 -14,1 g/dl, seguidos por 25,0% com níveis de hemoglobina entre 10,2 -13,1 g/dl e 3,1% com níveis de hemoglobina <10. 2 g/dl; com relação ao desenvolvimento psicomotor expresso em coeficiente de desenvolvimento, é evidente que 59,4% das crianças apresentam um desenvolvimento normal, seguido por 31,3% de crianças que apresentam um desenvolvimento em risco e 9,4% em atraso. Conclusões. O coeficiente de desenvolvimento infantil mostrou que a maioria das crianças tem um desenvolvimento psicomotor normal, seguido por risco e atraso, embora a maioria delas tenha um coeficiente de desenvolvimento normal.

Iron deficiency and child psychomotor development in a rural region of Chota, Peru, 2022 / Deficiencia de hierro y desarrollo psicomotor infantil en una zona rural de Chota, Perú 2022 / Deficiência de ferro e desenvolvimento psicomotor infantil em uma área rural de Chota, Peru 2022

Introduction: Iron deficiency and psychomotor developmental delay are two public health problems that cause high childhood morbidity and mortality worldwide, which can be related to social, economic, cultural and health factors that affect the environment where children and their family live. Objective: To determine the relationship between iron deficiency anemia and psychomotor development in children aged 2 to 4 years treated at the Cuyumalca Clinic, Chota. Materials and methods: Relational, cross-sectional study conducted on 48 children, who underwent hemoglobin testing through a portable hemoglobinometer and were subjected to the Psychomotor Development Test. Results: 31.2% of the children displayed some type of anemia, with the most common being moderate anemia (17.7%). On average, 10.9% showed some type of psychomotor developmental delay, including coordination (6.3%), language (8.4%), motor skills (16.7%), and overall development (12.5%). 4.2% of the children who had minor to moderate anemia showed developmental delay risks in the three assessed areas as well as in their overall development. Conclusion: There is no statistically significant relationship between iron deficiency anemia and several domains of psychomotor development, including coordination, language, motor skills as well as overall development.

Introducción: La deficiencia de hierro y las alteraciones en el desarrollo psicomotor son dos problemas de salud pública que causan una alta morbimortalidad infantil alrededor del mundo. Los estudios apuntan a que esto se relaciona con los factores sociales, económicos, culturales y sanitarios en los que el niño y su familia vive. Objetivo: Determinar la relación entre anemia ferropénica y desarrollo psicomotor en niños de 2 a 4 años atendidos en el Puesto de Salud de Cuyumalca, Chota. Materiales y métodos: Estudio relacional, transversal, desarrollado con 48 niños a quienes se les realizó un dosaje de hemoglobina con hemoglobinómetro portátil y se les aplicó el Test de Desarrollo Psicomotor. Resultados: El 31,2% de niños presentaron algún tipo de anemia, siendo la anemia moderada la más frecuente (16,7%); en promedio 10,9% evidenciaron alguna alteración en el desarrollo psicomotor en coordinación (6,3%), lenguaje (8,4%), motricidad (16,7%) y desarrollo global (12,5%). El 4,2% de niños con riesgo para el desarrollo presentaron anemia leve o moderada en las tres áreas evaluadas, al igual que en el desarrollo global. Conclusión: No existe relación estadística significativa entre anemia ferropénica y desarrollo psicomotor para las áreas de coordinación, lenguaje y motricidad; además del desarrollo global.

Introdução: A deficiência de ferro e as alterações no desenvolvimento psicomotor são dois problemas de saúde pública que causam elevada morbidade e mortalidade infantil em todo o mundo. Estudos sugerem que isso está relacionado aos fatores sociais, econômicos, culturais e de saúde em que vivem a criança e sua família. Objetivo: Determinar a relação entre anemia ferropriva e desenvolvimento psicomotor em crianças de 2 a 4 anos atendidas no Posto de Saúde Cuyumalca, Chota. Materiais e métodos: Estudo relacional, transversal, desenvolvido com 48 crianças que realizaram dosagem de hemoglobina com hemoglobinômetro portátil e foi aplicado o Teste de Desenvolvimento Psicomotor. Resultados: 31,2% das crianças apresentaram algum tipo de anemia, sendo a anemia moderada a mais frequente (16,7%); em média, 10,9% apresentaram alguma alteração no desenvolvimento psicomotor na coordenação (6,3%), linguagem (8,4%), motricidade (16,7%) e desenvolvimento global (12,5%). 4,2% das crianças em risco de desenvolvimento apresentaram anemia leve ou moderada nas três áreas avaliadas, bem como no desenvolvimento global. Conclusão: Não há relação estatística significativa entre anemia ferropriva e desenvolvimento psicomotor para as áreas de coordenação, linguagem e motricidade; bem como o desenvolvimento global.

Experiencia de uso de hierro intravenoso para el tratamiento de la anemia en niños y adolescentes. Respuesta terapéutica y evolución / Experience in using intravenous iron for the treatment of anemia in children and adolescents. Therapeutic response and evolution

Introducción: El hierro de administración intravenosa (iv) está indicado en los casos en que el tratamiento oral no es posible. El objetivo de este trabajo fue describir el perfil de uso, respuesta terapéutica y seguridad de la administración de hierro iv en el tratamiento de la anemia ferropénica en niños, niñas y adolescentes (NNA) asistidos en un centro de referencia de Uruguay entre 2018 y 2023. Método: Estudio retrospectivo mediante revisión de historias. Incluyó todos los NNA que recibieron hierro iv. Se registraron variables sociodemográficas, comorbilidades, clínica y severidad de la anemia. Se evaluó: motivos de la indicación y tipo de hierro iv, dosis, tiempo de infusión, respuesta terapéutica y efectos adversos. Resultados: Se incluyeron 35 pacientes, mediana de edad 4 años; 51,4% de sexo masculino, con comorbilidades 37,1%. Todos los menores de 3 años presentaban factores de riesgo para anemia ferropénica, la falta de adherencia al hierro oral se asoció con mayor severidad de la anemia (p<0,05). El motivo principal de indicación de hierro iv fue la severidad de la anemia e inadecuada respuesta al hierro oral concomitante en 37,1%. Todos recibieron hierro sacarato; mediana de dosis: 2 mg/kg y de tiempo de infusión: 1 hora. Se registró un caso de edema y exantema de cara vinculado a la rápida infusión. La evolución fue satisfactoria. Conclusiones: La administración de hierro iv fue segura. Es necesario establecer consensos respecto a la posología y monitorización. Se requieren nuevos estudios para continuar evaluando la eficacia y seguridad del hierro iv en sus diversas formulaciones.

Introduction: Intravenous (IV) iron administration it is indicated in cases where oral treatment is impossible. The objective of this work was to describe the profile of use, therapeutic response, and safety of the iron IV administration in treating anemia in children and adolescents (NNA) assisted in a reference center in Uruguay between 2018 and 2023. Method: Retrospective study through review of histories. It included all children and adolescents who received IV iron. Sociodemographic variables, comorbidities, clinical symptoms, and severity of anemia they were recorded. They were evaluated: reasons for the indication and type of IV iron, dose, infusion time, therapeutic response, and adverse effects. Results: we included 35 patients, with a median age of four years; 51.4% were male, and 37.1% had comorbidities. All children under three years of age had risk factors for iron deficiency anemia; greater severity of anemia was associated with lack of adherence to oral iron (p<0.05). The main reason for the indication of IV iron was the severity of anemia and inadequate response to concomitant oral iron at 37.1%. All received iron saccharate; median dose: 2 mg/kg and infusion time: 1 hour. A case of facial edema and rash linked to rapid infusion was recorded. The evolution was satisfactory. Conclusions: The administration of IV iron was safe. It is necessary to establish a consensus regarding dosage and monitoring. New studies are required to continue evaluating the efficacy and safety of IV iron in its various formulations.

Clinico-Hematological Profile and Management of Children With Non-Transfusion Dependent Thalassemia (NTDT) at a Pediatric Center in Northern India

Objective: To study the clinico-hematological profile, complications, and management of children with non-transfusion dependent thalassemia (NTDT) in northern India. Method: We retrieved and analyzed the data of 69 children with NTDT diagnosed between January, 2006 to December, 2018, aged under 18 years from our unit’s records. Result: The participants mean (SD) age was 4.4 (3.1) years, and they presented with anemia (29%), jaundice (13%), hemolytic facies (13%), splenomegaly (87%), thromboembolism (2.9%) and pathological short stature (28.5%). The most common cause of NTDT was ?-thalassemia (45%), followed by either compound-heterozygous or homozygous for E?-thalassemia mutation. The most frequent single genotype observed was compound heterozygous for IVS1-5 (G>C) and codon 26 (G>A). The mean (SD) follow-up duration was 3.5 (2.4) years. On follow-up, 27 children (%) remained transfusion free, and 30 (%) needed occasional transfusions. 63% of patients initially presenting with pathological short stature showed improvement in growth. Amongst children older than 10 years (n=20), subclinical hypothyroidism was detected in 6 children and impaired glucose tolerance test in 1 child. Conclusion: Eß-thalassemia was the commonest cause of NTDT in this population.

Uso de carboximaltose férrica no tratamento de deficiência de ferro em pacientes com insuficiência cardíaca na perspectiva da saúde suplementar: análise de custo-efetividade e impacto orçamentário / Ferric carboxymaltose for treatment of iron deficiency in heart failure patients from the supplementary health care system perspective: cost-effectiveness and budgetary impact analysis

Objetivo: Avaliar a relação de custo-efetividade e impacto orçamentário (AIO) do tratamento de deficiência de ferro (DF), com ou sem anemia, em pacientes com insuficiência cardíaca (IC) com fração de ejeção reduzida NYHA II e III, com uso de carboximaltose férrica (CMF), comparada ao placebo (não intervenção), sob a perspectiva pagadora da saúde suplementar (SS). Métodos: No modelo econômico, foi utilizada a árvore de decisão, no horizonte temporal de 52 semanas, na perspectiva da SS, sendo mensurados os benefícios clínicos e os custos associados à intervenção. Também foram executadas análises de sensibilidade determinística e probabilística para avaliar possíveis incertezas futuras. A elaboração da AIO foi realizada considerando o horizonte temporal de cinco anos, a população a ser tratada, os diferentes cenários de market share e os custos diretos envolvidos no tratamento atual e no tratamento proposto. Resultados: A razão de custo-efetividade incremental (RCEI) foi de -R$ 20.517,07 para um ano de vida ajustado pela qualidade (QALYs). O impacto da incorporação da CMF na SS gerou uma economia em cinco anos de -R$ 43.945.225. Conclusões: A análise apresentada mostrou que o tratamento com CMF reduziu o custo de hospitalização, o número de consultas ambulatoriais e o custo de outros medicamentos relacionados à IC e proporcionou uma economia anual. Considerando um horizonte de tempo de 52 semanas, a terapia intravenosa com CMF resultou em uma estratégia de redução de custos, quando comparada ao tratamento proposto para a DF em pacientes com IC.

Objective: This study aims to evaluate the cost-effectiveness and budget impact (AIO) of iron carboxymaltose (CMF) for treatment of iron deficiency (ID), with or without anemia, in patients with heart failure (HF) and reduced ejection fraction NYHA II and III compared to placebo (non-intervention), from the perspective of paying supplementary health (SS). Methods: In the economic model, the decision tree was used, with a time horizon of 52 weeks, from the SS perspective, measuring the clinical benefits and costs associated with the intervention. Deterministic and probabilistic sensitivity analyzes were also performed to assess possible future uncertainties. The elaboration of the AIO was carried out considering a time horizon of five years, population to be treated, different market share scenarios and direct costs involved in the current treatment and in the proposed treatment. Results: The incremental cost effectiveness ratio (ICER) was -R$ 20,517.07 for 1 quality-adjusted life year (QALY). The budget impact of incorporation of the CMF in SSprovided savings in five years of -R$ 43,945,225. Conclusions: The presented analysis showed that treatment with CMF reduced the cost of hospitalization, the number of outpatient visits and the cost of other HF-related medications and provided annual savings. Considering a time horizon of 52 weeks, intravenous therapy with CMF resulted in a cost-saving strategy when compared to the proposed treatment for DF in patients with HF.

Granuloma piogénico oral de comportamiento agresivo: Reporte de un caso

El granuloma piogénico es una lesión vascular reactiva benigna del tejido blando que surge en respuesta a irritantes crónicos de bajo grado. Rara vez crece más de 2 cm de diámetro y por lo general, no provoca cambios en el hueso alveolar. Presentamos un caso inusual de granuloma piógeno en una mujer de 19 años, de extenso tamaño y comportamiento agresivo, asociado a resorción ósea severa, movilidad dentaria, hemorragia, anemia ferropénica y recurrencias.

Pyogenic granuloma is a benign reactive vascular lesion of the soft tissue that arises in response to chronic low-grade irritants. It rarely grows more than 2 cm in diameter and usually does not cause changes in the alveolar bone. We present the case of a 19-year-old woman with an unusual pyogenic granuloma of extensive size and aggressive behavior, associated with severe bone resorption, tooth mobility, hemorrhage, iron deficiency anemia and recurrences.

Programa Nacional de Suplementação de Ferro nos primeiros mil dias de vida em Salvador (BA) / National Iron Supplementation Program in the first thousand days of life in Salvador (BA) / Programa Nacional de Suplementación de Hierro en los primeros mil días de vida en Salvador, Bahía

Os primeiros mil dias de vida correspondem ao período desde a concepção até os primeiros dois anos após o nascimento. Durante essa fase, as necessidades nutricionais são elevadas devido às aceleradas alterações fisiológicas inerentes ao período, e o ferro está entre os micronutrientes mais requisitados. Considerando que a anemia, em especial por deficiência de ferro, é um problema de saúde pública, principalmente nessa fase da vida, foi instituído em 2005 o Programa Nacional de Suplementação de Ferro (PNSF). No entanto, há uma lacuna de estudos que analisam sua execução em municípios da Bahia. Por esse motivo, este estudo observacional descritivo objetivou avaliar a cobertura real do PNSF entre gestantes e crianças de 6 a 24 meses de vida, público-alvo do programa, no município de Salvador (BA), entre os anos de 2017 e 2022, a partir da análise de dados secundários disponibilizados pelo Ministério da Saúde. A cobertura real do PNSF ocorreu de forma insatisfatória no município, alcançando quantidades inferiores a 7% das gestantes e 1% das crianças, entre os anos de 2019 e 2021, e valores iguais a 0% para ambos os grupos nos anos de 2017, 2018 e 2022. Tais resultados podem ser motivados por diferentes fatores, como problemas operacionais na gestão/monitoramento do programa e/ou a baixa adesão da população. Destaca-se, assim, a necessidade da constante avaliação do desempenho do PNSF no intuito de identificar suas limitações e propor melhorias em sua execução.

The first thousand days of life correspond to the period from conception to the first two years after birth. During this phase, nutritional needs are high due to the accelerated physiological changes inherent to the period, and iron is among the most required micronutrients. Considering that anemia, especially due to iron deficiency, is a public health problem, especially at this stage of life, the National Iron Supplementation Program (PNSF) was instituted in 2005. However, there is a lack of studies that analyze its execution on municipalities in Bahia (BA). For this reason, this descriptive observational study aimed to evaluate the coverage of the PNSF among pregnant women and children between 6 and 24 months of life, the target audience of the program, in the municipality of Salvador (BA), between 2017 and 2022, based on the analysis of secondary data provided by the Ministry of Health. The actual coverage of the PNSF occurred unsatisfactorily in the municipality, reaching numbers below 7% of pregnant women and 1% of children, between the years 2019 and 2021, and values equal to 0% for both groups in the years 2017, 2018, and 2022. Such results can be due to different factors, such as operational problems in the management/monitoring of the program and/or the low adherence of the population. Thus, we highlight the need for constant evaluation of the PNSF performance to identify its limitations and propose improvements in its execution.

Los primeros mil días de vida corresponden al período que va desde la concepción hasta los primeros dos años después del nacimiento. Durante esta fase, las necesidades nutricionales son elevadas, debido a los cambios fisiológicos acelerados propios del período, y el hierro es uno de los micronutrientes más requeridos. Como la anemia, especialmente por deficiencia de hierro, es un problema de salud pública, especialmente en esta etapa de la vida, en 2005 se instituyó el Programa Nacional de Suplementación con Hierro (PNSF, por sus siglas en portugués). Sin embargo, faltan estudios que analicen su ejecución en municipios de Bahía (Brasil). Por esta razón, este estudio observacional descriptivo tuvo por objetivo evaluar la cobertura real del PNSF en mujeres embarazadas y en niños de entre 6 y 24 meses de vida, público objetivo del programa, en la ciudad de Salvador (Bahía), entre 2017 y 2022, con base en el análisis de datos secundarios proporcionados por el Ministerio de Salud. La cobertura real del PNSF se presentó de manera insatisfactoria en el municipio, alcanzando cifras inferiores al 7% de embarazadas y al 1% de niños, entre los años 2019 y 2021, con valores iguales al 0% para ambos grupos analizados en los años 2017, 2018 y 2022. Estos resultados pueden ser causados por diferentes factores, entre ellos, problemas operativos en la gestión/seguimiento del programa y/o baja adherencia de la población. Así, se destaca la necesidad de una evaluación constante del desempeño del Programa para identificar sus limitaciones y proponer mejoras en su ejecución.