Detection, isolation, and characterization of a novel impurity from several folic acid products / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Folic acid belongs to the group of water-soluble B vitamins and naturally exists in multiple forms in a wide variety of foods such as legumes, vegetables, liver, and milk (Iyer and Tomar, 2009; Lyon et al., 2020). It is involved in many biochemical reactions critical for cell division, such as purine and pyrimidine biosynthesis, DNA/RNA biosynthesis, and amino acid metabolism (Iyer and Tomar, 2009). Mammals cannot synthesize folic acid and thus they must acquire it from food. Although folic acid is ubiquitous in foods, folic acid deficiency still often occurs due to various causes such as unhealthy diet (Hildebrand et al., 2021; Iimura et al., 2022), disease-related malabsorption (Arcot and Shrestha, 2005), medication-related depletion (Arcot and Shrestha, 2005), or vitamin B12 deficiency (Fishman et al., 2000). Folic acid deficiency has been associated with several health problems, such as anemia (Carmel, 2005; Bailey and Caudill, 2012), cancer (Duthie, 1999), cardiovascular diseases (Wald et al., 2002), neural tube defects in newborns (van der Put et al., 2001), neuropsychiatric dysfunction (Shea et al., 2002), depression (Falade et al., 2021), inflammatory diseases (Suzuki and Kunisawa, 2015; Jones et al., 2019), and eye diseases (Sijilmassi, 2019). To prevent folic acid deficiency, its daily intake (400 μg/d) has been recommended for adults in the European Union, and its increased intake (600 μg/d) is advised for women before and during pregnancy (FAO/WHO, 2002; IOM, 2004). The New Zealand government mandated the fortification of non-organic wheat flour with folic acid in July 2021, and the UK government mandated the fortification of non-wholemeal wheat flour with folic acid in September 2021 (Haggarty, 2021).

Assessment of folate status among women of childbearing age from 2000 to 2020 / 中华预防医学杂志

Objective: To analyze the folate status among women of childbearing age worldwide from 2000 to 2020, and explore the impact of socioeconomic factors on folate status, so as to provide support for the formulation of relevant supplementary policies in China in the future. Methods: The "folate" "folic acid" "deficiency" "status" "women" "childbearing" and "reproductive" were used as Chinese and English keywords to systematically search CNKI and PubMed database. Global Health Data Exchange database (GDHx), Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia datasets (BRINDA) and Ground Work publications were systematically searched with "micronutrients" and "nutrition" as keywords. The retrieval time was from January 1, 2000 to August 31, 2020, and the language was restricted to English and Chinese. After title, abstract and full-text screening, a total of 45 literatures were included. The folate status of women of childbearing age in the eligible literature was analyzed, and the income and folate status were tested by Kruskal Wallis H test and Nemenyi test. Results: The M (Q1, Q3) of serum folate deficiency rate and erythrocyte folate insufficiency rate in women of childbearing age were 15.0% (3.5%, 37.0%) and 49.0% (22.0%, 83.0%). There were great differences in serum folate status and serum folate deficiency rate among women of childbearing age in different income countries. The serum folate deficiency rate of women of childbearing age in low-income countries was significantly higher than that in middle and high-income countries. Conclusion: The folate status of women of childbearing age in most countries has not reached the ideal state from 2000 to 2020. More studies on folate supplementation programs should be carried out.

Effect of / 生物医学与环境科学（英文）

Objective@#This study aimed to investigate the effects of @*Methods@#In this study, 0.1% DMG was supplemented in 20% casein diets that were either folate-sufficient (20C) or folate-deficient (20CFD). Blood and liver of rats were subjected to assays of Hcy and its metabolites. Hcy and its related metabolite concentrations were determined using a liquid chromatographic system.@*Results@#Folate deprivation significantly increased pHcy concentration in rats fed 20C diet (from 14.19 ± 0.39 μmol/L to 28.49 ± 0.50 μmol/L; @*Conclusion@#DMG supplementation exhibited hypohomocysteinemic effects under folate-sufficient conditions. By contrast, the combination of folate deficiency and DMG supplementation has deleterious effect on pHcy concentration.

Validación de un cuestionario sobre factores de riesgo para defectos congénitos / Validation of a questionnaire about risk factors for congenital defects

Introducción: Los defectos congénitos constituyen la primera causa de muerte infantil en los países desarrollados y la segunda en muchos países en vías de desarrollo. Objetivo: Validar un cuestionario sobre factores de riesgo para defectos congénitos relacionados con la deficiencia de ácido fólico. Métodos: El proceso de validación se basó en un proceso dinámico de retroalimentación y toma de decisiones cambiante, de acuerdo al criterio de expertos, para lo que se utilizó el método Delphi, el cual constó de tres etapas: selección de los expertos, análisis y validación de cada uno de los ítems por parte de los expertos y su posterior reevaluación y, por último, la realización de un estudio piloto. En el proceso de validación del cuestionario se calculó el coeficiente de concordancia de Kendall y Friedman con el objetivo de determinar concordancia o similitudes de las respuestas de los evaluadores respectivamente. Resultados: Se seleccionaron 18 expertos con altos niveles de competencia de acuerdo al cálculo de los coeficientes de conocimiento y argumentación. En la segunda versión del cuestionario existió similitud en las respuestas de los expertos a favor de la categoría superior de muy bien, así como concordancia en el nivel de respuesta de los expertos. Conclusiones: El cuestionario diseñado dispone de niveles óptimos de validez de contenido y factibilidad para identificar los factores de riesgo para defectos congénitos sensibles a la deficiencia de ácido fólico(AU)

Introduction: Congenital defects are the leading cause of child mortality in developed countries and the second in many developing countries. Objective: Validate a questionnaire about risk factors for congenital defects related to folic acid deficiency. Methods: Validation was based on a dynamic process of feedback and changing decision-making geared by expert criteria for which use was made of the Delphi method in three stages: selection of experts, analysis and validation of each item by the experts and further re-evaluation, and conduct of a pilot study. Kendall and Friedman's coefficient of concordance was estimated to determine the agreement or similarities between the answers provided by the evaluators. Results: Eighteen highly-qualified experts were selected based on the knowledge and argumentation coefficients estimated. In the second version of the questionnaire the answers provided by experts coincided in awarding the higher category of 'very good', and there was concordance in the experts' response level. Conclusions: The questionnaire designed is characterized by optimal levels of content validity and feasibility to identify risk factors for congenital defects related to folic acid deficiency(AU)

Estomatitis aftosa recurrente y deficiencias nutricionales: Reporte de tres casos y revisión de literatura / Recurrent Aphthous Stomatitis and Nutritional Deficiencies: Report of Three Cases with Literature Review

RESUMEN Introducción: La estomatitis aftosa recurrente (EAR) es la enfermedad ulcerativa más común que afecta la mucosa oral no queratinizada. La etiología aún se desconoce, pero se han propuesto varios factores locales y sistémicos como agentes causales. Descripción del caso: se informa tres pacientes con presencia de EAR asociada a deficiencias nutricionales, debidas a dietas de restricción alimentaria. El primer caso, una mujer de 19 años con deficiencia de hierro, refirió tomar té verde a diario y consumir poca cantidad de carbohidratos, grasas y carne. El segundo caso, un hombre de 32 años con deficiencia de hierro y vitamina B12 asociada a dieta tipo vegana, aunque a veces si consumía carne. El tercer caso, hombre de 50 años, vegano y exfumador desde hace un año, presentó deficiencia de hierro, vitamina B12 y ácido fólico. En los tres casos un detallado interrogatorio, examen clínico y análisis sanguíneo completo, permitió establecer un adecuado diagnóstico, manejo odontológico y derivación con un nutricionista, con el fin de tratar la patología de base y no sólo brindarles un tratamiento sintomático de las lesiones. Discusión: Ante un cuadro de EAR es recomendable realizar un análisis que incluya hemograma, ácido fólico, hierro y vitamina B12, para descartar posibles causas sistémicas y eventualmente tratarlas. El manejo clínico tiene como objetivo mejorar la función del paciente y la calidad de vida mediante terapias tópicas y sistémicas; sin embargo, es fundamental identificar y controlar los factores causales que contribuyen; así como, la exclusión o tratamiento de la enfermedad sistémica subyacente.

ABSTRACT Introduction: Recurrent aphthous stomatitis (RAS) is the most common ulcerative disease that affects the non-keratinized oral mucosa. The etiology is still unknown, but several local and systemic factors have been proposed as causal agents. Case description: three patients are reported with RAS associated with nutritional deficiencies, due to dietary restriction diets. The first case, a 19-year- old woman with iron deficiency, reported taking green tea daily and consuming a small amount of carbohydrates, fats and meat. The second case, a 32-year-old man with iron deficiency and vitamin B12 associated with vegan diet, although sometimes if he consumed meat. The third case, man of 50 years, vegan and ex-smoker for a year, presented deficiency of iron, vitamin B12 and folic acid. In all three cases a detailed questioning, clinical examination and complete blood analysis allowed to establish an adequate diagnosis, dental management and referral with a nutritionist, in order to treat the underlying pathology and not only provide a symptomatic treatment of the injuries. Discussion: In the setting of RAS, it is advisable to perform an analysis that includes a blood count, folic acid, iron and vitamin B12, to rule out possible systemic causes and eventually treat them. Clinical management aims to improve patient function and quality of life through topical and systemic therapies; however, it is essential to identify and control the causal factors that contribute; as well as, the exclusion or treatment of the underlying systemic disease.

Seleção e aplicação de bactérias láticas produtoras de folato para obtenção de um leite fermentado bioenriquecido e avaliação de biodisponibilidade do folato produzido / Screening and application of folate-producing lactic acid bacteria for production of bioenriched fermented milk and evaluation of the bioavaliability of the produced folate

A deficiência de folato é um problema de saúde pública que vem sendo combatido através da fortificação obrigatória de ácido fólico. Entretanto, a ingestão excessiva pode causar efeitos colaterais indesejados. A forma natural da vitamina produzida por algumas cepas de bactérias láticas pode ser uma alternativa segura para aumentar a ingestão de folato pela população. Este trabalho visou selecionar as melhores cepas de BAL produtoras de folato, identificar as melhores condições para a produção da vitamina e avaliar a biodisponibilidade do folato produzido pelas cepas no leite fermentado, empregando-se testes em modelos animais. O estudo foi desenvolvido com cinco cepas de Streptococcus thermophilus (34v, 170v, 268v, 361v e 341 pc) e um cepa de Lactobacillus plantarum (16cv), todas boas produtoras de folato. As condições de produção e a combinação de cepas que resultaram na melhor produção folato foram utilizadas para produzir um leite biofermentado (BFM), avaliando-se a biodisponibilidade da vitamina produzida empregando-se um modelo animal de depleção/repleção, com camundongos Balb/c submetidos a 14 dias de depleção, seguido de 21 dias de repleção da vitamina. Após os 35 dias, os animais foram sacrificados, retirando-se sangue, rins, fígado, baço e intestino para quantificação de folato e avaliação histológica da mucosa intestinal. Todas as quantificações de folato foram feitas pelo método microbiológico. A melhor combinação de cepas (St. Thermophilus 34v + Lb. Plantarum 16cv) resultou na produção de 300 ng/mL de folato, sendo a temperatura de 42ºC melhor que 37ºC para a produção da vitamina. A produção de folato no leite na fermentação em pH controlado 6,0 foi 35% superior à observada no leite fermentado em pH livre. As concentrações de folato no baço e glóbulos vermelhos foram mais altas nos camundongos que ingeriram leite fermentado bioenriquecido (BFM) em relação aos demais grupos de animais. A relação vilosidade/cripta nos camundongos dos grupos BFM foi igual à observada nos animais que receberam leite suplementado com ácido fólico. Houve aumento da hemoglobina, hematócrito e hemácias nos camundongos que ingeriram BFM, evidenciando a bioeficácia do folato produzido. Esses resultados indicam que a produção de folato por bactérias láticas selecionadas em produtos fermentados pode ser uma boa alternativa para aumentar a ingestão de vitamina B9 pela população

A deficiência de folato é um problema de saúde pública que vem sendo combatido através da fortificação obrigatória de ácido fólico. Entretanto, a ingestão excessiva pode causar efeitos colaterais indesejados. A forma natural da vitamina produzida por algumas cepas de bactérias láticas pode ser uma alternativa segura para aumentar a ingestão de folato pela população. Este trabalho visou selecionar as melhores cepas de BAL produtoras de folato, identificar as melhores condições para a produção da vitamina e avaliar a biodisponibilidade do folato produzido pelas cepas no leite fermentado, empregando-se testes em modelos animais. O estudo foi desenvolvido com cinco cepas de Streptococcus thermophilus (34v, 170v, 268v, 361v e 341 pc) e um cepa de Lactobacillus plantarum (16cv), todas boas produtoras de folato. As condições de produção e a combinação de cepas que resultaram na melhor produção folato foram utilizadas para produzir um leite biofermentado (BFM), avaliando-se a biodisponibilidade da vitamina produzida empregando-se um modelo animal de depleção/repleção, com camundongos Balb/c submetidos a 14 dias de depleção, seguido de 21 dias de repleção da vitamina. Após os 35 dias, os animais foram sacrificados, retirando-se sangue, rins, fígado, baço e intestino para quantificação de folato e avaliação histológica da mucosa intestinal. Todas as quantificações de folato foram feitas pelo método microbiológico. A melhor combinação de cepas (St. Thermophilus 34v + Lb. Plantarum 16cv) resultou na produção de 300 ng/mL de folato, sendo a temperatura de 42ºC melhor que 37ºC para a produção da vitamina. A produção de folato no leite na fermentação em pH controlado 6,0 foi 35% superior à observada no leite fermentado em pH livre. As concentrações de folato no baço e glóbulos vermelhos foram mais altas nos camundongos que ingeriram leite fermentado bioenriquecido (BFM) em relação aos demais grupos de animais. A relação vilosidade/cripta nos camundongos dos grupos BFM foi igual à observada nos animais que receberam leite suplementado com ácido fólico. Houve aumento da hemoglobina, hematócrito e hemácias nos camundongos que ingeriram BFM, evidenciando a bioeficácia do folato produzido. Esses resultados indicam que a produção de folato por bactérias láticas selecionadas em produtos fermentados pode ser uma boa alternativa para aumentar a ingestão de vitamina B9 pela população

Prevalence of low folate deficiency after wheat flour supplementation - should we still measure serum folate?

ABSTRACT Objectives: To determine the frequency of folic acid deficiency in consecutive serum folate determinations and to determine whether there was a significant decrease in serum folate deficiency after folate was added to wheat flour. Methods: A retrospective descriptive observational study was performed of consecutive folate measurements at the Hospital Privado Universitario, Cordoba, Argentina. Results: Two cohorts were analyzed: 1197 folate measurements between 2001 and 2008 (before supplementation) and 3335 folate measurements from 2009 to 2014 (after supplementation). Folate deficiency was found in 84/1197 (7%) subjects in the pre-supplementation group and in 58/3335 (1.73%) after supplementation. The prevalence of folate deficiency was 12% between 2001 and 2003 when folate was not added to flour compared to 4% in 2004-2007 (p-value < 0.0001) when folate was added to the flour but no widespread use was documented. Conclusions: In the studied population, the prevalence of serum folic acid deficiency after folate supplementation was low at 1.73%. There was a significant decrease in folate deficiency after folate was added to wheat flour. Given the low prevalence of folic acid deficiency observed in this and similar studies, and the observed change with supplementation, we conclude that routine measurement of serum folate is of limited clinical use.

Factores de riesgo prenatales y su asociación a malformaciones congénitas en un Hospital Universitario de Referencia / Congenital Malformations: New Challenges For Public Health

Introducción: Las malformaciones congénitas constituyen la segunda causa de mortalidad infantil en América del Sur, según datos de la OMS. Objetivo: Determinar la asociación entre los factores de riesgo prenatales y las malformaciones congénitas de pacientes internados en un hospital de referencia. Material y Método: Estudio retrospectivo, analítico de caso-control, corte transversal en pacientes internados desde Octubre 2014 a Octubre 2015 que cumplieron con criterios de inclusión y exclusión como caso; además en pacientes ambulatorios que cumplieron criterios de inclusión y exclusión como control. Con pareo 1:1 por edad y sexo. Instrumento: encuesta estructurada. Tamaño de muestra con variable cualitativa, valor de Z: 1,9, P: 4% (Porcentaje en población general 2 a 5%) de la variable principal, valor de D: 95% y el valor de p de 0,05, resultando N: 60 por grupo. Resultados: Se consideraron 66 casos y 66 controles pareados por edad y sexo; edades comprendidas de 1 mes a 15 años, media de 2 años (DE: +2,63), masculino 61%. Los Casos provenían 41% (27) del Interior del País y los Controles 11% (7). Las malformaciones más frecuentes fueron las del sistema nervioso central 29% (19/66) seguidas de las cardíacas 23% (15/66). El diagnóstico prenatal por ecografía obstétrica se observó en 33% de los casos (21/66). Al realizar regresión logística multivariada se encontró asociación entre malformaciones congénitas y antecedentes de malformaciones en la familia (OR 20,8, 95% CI 2,66- 162,2), antecedente de un hijo previo con síndrome genético (OR 8,84, 95% CI 1,35- 73,86) y falta de suplementación con ácido fólico antes o durante el embarazo (OR 3,44, 95% CI 1,49- 8,33) distancia de la vivienda de campos fumigados menor a 1 km (OR 3,75, 95% CI 0,98- 14,31) y exposición materna directa a plaguicidas(OR 4,51, 95% CI 1,77- 11,46). Conclusión: La falta de suplemento de ácido fólico, el antecedente de malformación congénita en la familia y la exposición materna a agroquímicos tuvieron asociación estadística significativa. Se plantea probable sesgo de la falta de pareo por Procedencia.

¿Existe tendencia estacional en las anomalías del tubo neural en Guatemala? / Exist a stational trends in neural tube defects in Guatemala?

Antecedentes: Las anomalías del tubo neural son frecuentes en Guatemala. Una mayor frecuencia se observa en el antiplano guatemalteco, con mayor concentración de población indígena y con mayor depauperación económica. Observaciones de especialistas indican que en el primer semestre del año son mucho más frecuentes que en el segundo. Estas observaciones señalan que algo existe en el ambiente, probablemente en el ambiente alimentario, relacionado con el consumo de maíz, base dietética del guatemalteco. En el grano de este cereal, existe, fumomisinas (micotoxinas producidas por hongos) en gran cantidad, que tienen un efecto inhibidor de la captación celular de ácido fólico, micronutriente íntimamente relacionado con el cierre temprano del tubo neural. Objetivo: Demostrar si es cierto que existe mayor frecuencia de anomalías del tubo neural en Guatemala en el primer semestre del año que en el segundo, principalmente en los denominados meses de verano. Sugerir hipótesis futuras que expliquen este comportamiento epidemiológico. Metodología: Estudio descriptivo-analítico retrospectivo en la Unidad de Espina Bífida del Hospital General San Juan de Dios y en las 8 áreas geoeconómicas de Guatemala, analizando una sola variable: La fecha de nacimiento de niños y niñas que presentaron anomalías del tubo neural de diferente tipo. Resultados: Se demuestra que en efecto las anomalías del tubo neural son más frecuentes en el primer semestre del año que en el segundo. Principalmente en los meses de marzo-abril. Y que ocurren con menos frecuencia en el segundo semestre. Estos datos se podrían vincular con el consumo dietético de maíz, grano que también tiene diferencias estacionales en cuanto a su producción, almacenamiento, preparación y consumo (AU)

Pruebas bioquímicas para el diagnóstico de anemia megaloblástica / Biochemical tests for diagnosis of megaloblastic anemias / Testes bioquímicos para o diagnóstico de anemia megaloblástica

Es intención de este trabajo hacer un breve repaso sobre el metabolismo de la Vitamina B12 y del Folato o Vitamina B9. Estas dos vitaminas hidrosolubles juegan un papel importante en el metabolismo celular. Son cofactores de reacciones metabólicas de transferencia de grupos monocarbonados, esenciales para el mantenimiento de la vida. Además se describen las nuevas determinaciones de laboratorio, se evalúan cuáles son los estudios necesarios para arribar a un correcto diagnóstico del paciente con Anemia Macrocítica (AM), su etiología y cómo muchas drogas de uso frecuente en medicina producen AM. Se realiza también la evaluación del conjunto de metodologías que se pueden efectuar como rutina en el laboratorio especializado en hematología y se propone un algoritmo para el diagnóstico del paciente con AM.

The aim of this article is to make a little review on Vitamin B12 and Folate or Vitamin B9 metabolism. These hydrosoluble vitamins have a very important role in cell metabolism. They are cofactors in metabolic reactions of methyl group transfer, essential for life maintaining. Furthermore, new laboratory tests are described, and it is evaluated which the necessary studies are to arrive at a correct diagnosis for macrocytic anemia (MA) patients, their etiology, and how many drugs frequently used in medicine originate MA. Also, the set of methodologies that can be carried out routinely in the laboratory specialized in hematology is evaluated. Finally, a diagnosis algorithm to detect MA in patients is proposed.

Este trabalho visa a realizar uma breve revisão sobre o metabolismo da Vitamina B12 e do Folato ou Vitamina B9. Estas duas vitaminas hidrossolúveis têm um papel importante no metabolismo celular. São cofatores de reações metabólicas de transferência de grupos monocarbonados, essenciais para manter a vida. Também são descritas novas determinações de laboratório, avaliam-se quais são os estudos necessários para chegar a um diagnóstico correto do paciente com Anemia Macrocítica (AM), sua etiologia e de qué maneira muitas drogas de uso frequente em medicina produzem AM. Realiza-se também a avaliação do conjunto de metodologias que podem realizar-se como rotina no laboratório especializado em hematologia e se propõe um algoritmo para o diagnóstico do paciente com AM.

Effects of maternal folate deficiency on the methylation of insulin-like growth factor system in the offspring rats / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effects of maternal folate deficiency on fetal growth and development and the methylation profiles of insulin-like growth factor system in the offspring rats.</p><p><b>METHODS</b>Twenty-two Sprague-Dawley female rats were randomly assigned to two groups: a folate deficient group (n=12) and a control group (n=10). They were fed with folate deficient and normal diet respectively. Dams were mated after 2 weeks of feeding. Eight female rats from each group were pregnant. On the 20th day of gestation, the fetuses were delivered by caesarean section. Thirty-two fetal rats from each group were randomly selected and the body length and weight were measured. Eight fetal rats from each group were randomly selected and ELISA was used to measure the level of folate content, IGF-1 and IGFBP-3 in the fetal brain and liver. Three fetal rats from each group were randomly selected and methylated DNA immunoprecipitation sequencing (MeDIP-Seq) was used to detect the methylation level of insulin-like growth factor system in the fetal brain and liver. ELISA was used to measure the level of IGF-1 and IGFBP-3 in the maternal serum from both groups.</p><p><b>RESULTS</b>The mean fetal length and weight were lower in the folate deficient group than in the control group (P<0.05). The levels of IGF-1 and IGFBP-3 in the maternal serum, as well as folate content and IGFBP-3 in the fetal brain and liver were significantly lower in the folate deficient group than in the control group (P<0.05). The methylation levels of IGF-1R, IGF-2R, IGFBP-2, IGFBP-5, IGFBP-6 and IGFBP-7 in the fetal brain were higher in the folate deficient group than in the control group (P<0.05). The methylation levels of IGF-1R, IGF-2R, IGFBP-3 and IGFBP-5 in the fetal liver were higher in the folate deficient group than in the control group. The methylation of IGF-2 gene showed a significant reduction in the folate deficient group (P<0.05).</p><p><b>CONCLUSIONS</b>Maternal folate deficiency may cause retardation of growth and development of the offspring, which is possibly associated with the changes of methylation profiles of insulin-like growth factors.</p>

Folic acid and diseases - supplement it or not? / Ácido fólico e doenças - suplementá-lo ou não?

SUMMARY Introduction: folic acid is a water soluble vitamin, which is synthetically-produced and found in fortified foods and supplements. Folate is found naturally in plants, such as the dark green leafy vegetables. Folate is not synthesizedde novo by humans, therefore the daily requirements are met from the dietary intake of folic acid supplements or food rich in this vitamin. Folate deficiency could lead to numerous common health problems. Hyperhomocysteinemia and the possibility of malignancy developments are the long term consequences of this deficit albeit contradictory findings on these claims. Methods: the articles included in this review focused on recent updated evidence-based reports and meta-analyses on the associations of the serum folate/folic acid and the various diseases found globally. Results: the benefit of folic acid supplementation in the pre-conception period for the prevention of neural tube defects (NTDs) was well established and it was suggested that counseling sessions should be given to women with previous pregnancies affected by NTDs. However, supplementation of folic acid and its medicinal effects in the treatment of other diseases were contradictory and unclear. Conclusion: more detailed investigations into the health benefits of folic acid are needed before it could be recommended for supplementation, treatment or prevention of some of the diseases discussed in this review.

RESUMO Introdução: ácido fólico é uma vitamina solúvel em água produzida sinteticamente e encontrada em alimentos e suplementos enriquecidos. O folato é encontrado naturalmente em plantas, como vegetais folhosos verde-escuros. O folato não é sintetizado de novo por seres humanos; portanto, as necessidades diárias são satisfeitas a partir da ingestão de suplementos de ácido fólico ou alimentos ricos nessa vitamina. A deficiência de folato pode levar a inúmeros problemas de saúde comuns. Hiper-homocisteinemia e a possibilidade de desenvolver malignidades são as consequências a longo prazo desse déficit, ainda que os resultados sejam contraditórios sobre essas afirmações. Métodos: os artigos incluídos nesta revisão tratam de relatórios recentes atualizados com base em provas e metanálises sobre a associação entre o folato/ácido fólico e várias doenças encontradas globalmente. Resultados: o benefício da suplementação de ácido fólico no período de pré-concepção para a prevenção de defeitos do tubo neural (DTN) foi bem estabelecido e foi sugerido que sessões de aconselhamento devem ser providas às mulheres com gravidezes anteriores afetadas por DTN. No entanto, os benefícios da suplementação de ácido fólico e os efeitos medicinais no tratamento de outras doenças são contraditórios e pouco claros. Conclusão: investigações mais detalhadas sobre os benefícios do ácido fólico são necessárias antes que a suplementação seja recomendada para tratamento ou prevenção de algumas das doenças discutidas nesta revisão.

Resección de la superficie articular por abordaje dorsal mínimamente invasivo para artrodesis de la articulación interfalángica distal / Joint surface resection with a minimally invasive dorsal approach for arthrodesis of the distal interphalangeal joint

La enfermedad articular degenerativa de la articulación interfalángica distal de los dedos de la mano precede en aparición a todas las demás regiones del cuerpo y genera discapacidad importante. Presentamos el desarrollo de una técnica de artrodesis interfalángica distal asociado con cirugía mínima invasiva. La etiología de los casos fue diversa y nuestro seguimiento promedio fue de 10 meses, todos los casos consolidaron y la recuperación funcional inició desde las dos semanas del postoperatorio. Consideramos que esta técnica puede ser reproducible con resultados satisfactorios en el corto y mediano plazo.

Degenerative joint disease of the distal interphalangeal joint of the fingers precedes its occurrence in all the remaining regions of the body and produces major disability. We describe a distal interphalangeal arthrodesis technique performed with minimally invasive surgery. Case etiology was varied and mean follow-up was 10 months. All cases healed and functional recovery started at postoperative week two. This is a reproducible technique that produces satisfactory results in the short and medium term.

Nutritional status of iron, vitamin B12, folate, retinol and anemia in children 1 to 11 years old: Results of the Ensanut 2012 / Estado nutricional de hierro, vitamina B12, folato, retinol y anemia en niños de 1 a 11 años: Resultados de la Ensanut 2012

Objective. To describe the frequency of anemia, iron, vitamin B12, folate, retinol and predictors of anemia among Mexican children from Ensanut 2012. Materials and methods. Hemoglobin, ferritin, CRP, vitamin B12, retinol and folate concentrations were measured in 2 678 children aged 1-4 y and 4 275 children aged 5-11 y. Adjusted logistic regression models were constructed to assess the risk for anemia and micronutrient deficiencies. Results. In preschoolers and scholars, the overall prevalence of anemia was 20.4 and 9.7%, iron deficiency 14 and 9.3%, low vitamin B12 (LB12S) 1.9 and 2.6%; Folate 0.30 and 0%, and retinol depletion (VADp) 15.7 and 2.3%, respectively. ID and VADp were negatively associated with Hb (coefficient: -0.38 and -0.45, p<0.05); a higher log-CRP was associated with higher risk for anemia and VADp (OR=1.13 and OR=2.1, p<0.05, respectively). Conclusions. Iron deficiency, anemia and VADp are some of the main nutritional problems among Mexican infants.

Objetivo. Describir la frecuencia de anemia, deficiencia de hierro, vitamina B12, folato, retinol y predictores de la anemia en niños mexicanos de la Ensanut 2012. Material y métodos. Se midieron las concentraciones de hemoglobina, ferritina, PCR, vitamina B12, retinol y folato en 2 678 niños de 1-4 años y 4 275 niños de 5-11 años. Se construyeron modelos de regresión logística para evaluar el riesgo de anemia y deficiencias de micronutrientes. Resultados. La prevalencia de anemia en preescolares y escolares fue 20.4 y 9.7%; deficiencia de hierro (DH) 14 y 9.3%; baja concentración de vitamina B12 (BCB12) 1.9 y 2.6%; folato 0.30 y 0%, y depleción de vitamina A (DpVA), 15.7 y 2.3%, respectivamente. La DH y DpVA se asociaron negativamente con la Hb (coeficiente: -0.38 y -0.45, p<0.05); a mayor log-PCR, mayor riesgo de anemia y DpVA (OR=1.13 y OR=2.1, p<0.05, respectivamente). Conclusiones. DH, anemia y DpVA son algunos de los principales problemas de nutrición en niños mexicanos.

Prevalence of iron, folate, and vitamin B12 deficiencies in 20 to 49 years old women: Ensanut 2012 / Prevalencia de deficiencias de hierro, folato y vitamina B12 en mujeres de 20 a 49 años: Ensanut 2012

Objective. To describe the prevalence of iron, folate, and B12 deficiencies in Mexican women of reproductive age from the National Health and Nutrition Survey (Ensanut) 2012. Materials and methods. Data came from a national probabilistic survey, representative from rural and urban areas, and different age groups. Blood samples were obtained from 4 263, 20 to 49 years old women for serum ferritin, vitamin B12 and serum folate concentrations. The prevalence of deficiencies, was assessed using adjusted logistic regression models. Results. The deficiency of folate was 1.9% (95%CI 1.3-2.8), B12 deficiency was 8.5% (95%CI 6.7-10.1) and iron deficiency was 29.4% (95%CI 26.5-32.2). No differences were found when compared with 2006, 24.8% (95%CI 22.3-27.2). Conclusions. The vitamin B12 deficiency is still a problem for women of reproductive age and their offspring in Mexico, while folate deficiency disappeared as a problem. Iron deficiency needs prevention and fortification strategies.

Objetivo. Describir las prevalencias de deficiencias de hierro, folato y B12 en mujeres mexicanas en edad reproductiva de la Encuesta Nacional de Salud y Nutrición (Ensanut) 2012. Material y métodos. Datos derivados de una encuesta probabilística nacional, representativa del área rural y urbana por grupos de edad. Se obtuvo una submuestra de sangre en 4 263 mujeres de 20 a 49 años de edad para medir las concentraciones séricas de ferritina, vitamina B12 y folato. Las deficiencias fueron evaluadas mediante regresiones logísticas múltiples ajustadas. Resultados. La prevalencia de deficiencias de folatos fue de 1.9% (IC95% 1.3-2.8) y vitamina B12 de 8.5% (IC95% 6.7-10.1). La deficiencia de hierro no fue diferente a la de 2006: 29.4% (IC95% 26.5-32.2) vs 24.8% (IC95% 22.3-27.2). Conclusiones. La prevalencia de deficiencias de hierro y vitamina B12 todavía representan un problema en mujeres mexicanas (20-49), mientras que la deficiencia de folato ha dejado de ser un problema de salud pública. Aún se requieren estrategias de prevención en México.

Characteristics of fetuses evaluated due to suspected anencephaly: a population-based cohort study in southern Brazil / Características de fetos avaliados por suspeita de anencefalia: um estudo de coorte de base populacional do Sul do Brasil

CONTEXT AND OBJECTIVE: Anencephaly is considered to be the most common type of neural tube defect. Our aim was to assess the clinical and gestational features of a cohort of fetuses with suspected anencephaly. DESIGN AND SETTING: Population-based retrospective cohort study in a referral hospital in southern Brazil. METHODS: The sample consisted of fetuses referred due to suspected anencephaly, to the Fetal Medicine Service of Hospital Materno Infantil Presidente Vargas, between January 2005 and September 2013. Clinical, radiological, pathological and survival data were gathered. RESULTS: Our sample was composed of 29 fetuses. The diagnosis of suspected anencephaly was made on average at 21.3 weeks of gestation. Seven fetuses had malformations that affected other organs, and these included oral clefts (n = 4) and congenital heart defects (n = 2). In 16 cases, there was termination of pregnancy (n = 12) or intrauterine death (n = 4). Regarding those who were born alive (n = 13), all of them died in the first week of life. After postnatal evaluation, the diagnosis of anencephaly was confirmed in 22 cases (75.9%). Other conditions included amniotic band disruption complex (6.9%), microhydranencephaly (6.9%), merocrania (3.4%) and holoprosencephaly (3.4%). CONCLUSIONS: Different conditions involving the cranial vault may be confused with anencephaly, as seen in our sample. However, these conditions also seem to have a poor prognosis. It seems that folic acid supplementation is not being properly performed. .

CONTEXTO E OBJETIVO: A anencefalia é considerada o tipo mais comum de defeito de fechamento do tubo neural. Nosso objetivo foi avaliar as características clínicas e gestacionais de uma coorte de fetos com suspeita de anencefalia. TIPO DE ESTUDO E LOCAL: Estudo de coorte retrospectivo de base populacional em um hospital de referência no sul do Brasil. MÉTODOS: A amostra foi composta por fetos encaminhados por suspeita de anencefalia ao Serviço de Medicina Fetal do Hospital Materno Infantil Presidente Vargas, no período de janeiro de 2005 a setembro de 2013. Foi realizada coleta de dados clínicos, radiológicos, patológicos e de sobrevida. RESULTADOS: Nossa amostra foi composta por 29 fetos. A suspeita do diagnóstico de anencefalia foi realizada em média com 21,3 semanas de gestação. Sete fetos apresentavam malformações que afetavam outros órgãos, e incluíram fendas orais (n = 4) e defeitos cardíacos congênitos (n = 2). Em 16 casos houve interrupção da gravidez (n = 12) ou morte intrauterina (n = 4). Daqueles que nasceram vivos (n = 13), todos morreram na primeira semana de vida. Após a avaliação pós-natal, o diagnóstico de anencefalia foi confirmado em 22 casos (75,9%). Outras condições incluíram o complexo disruptivo de banda amniótica (6,9%), microhidranencefalia (6,9%), merocrania (3,4%) e holoprosencefalia (3,4%). CONCLUSÕES: Diferentes condições que envolvem a calota craniana podem ser confundidas com a anencefalia, como verificado em nossa amostra. No entanto, estas também parecem ter um prognóstico pobre. A suplementação com ácido fólico parece não estar sendo realizada de forma adequada. .

Interaction between folate deficiency and aberrant expression related to fragile histidine triad gene in the progression of cervical cancerization / 中华流行病学杂志

<p><b>OBJECTIVE</b>To explore the interaction between folate deficiency and aberrant expression related to fragile histidine triad (FHIT) gene in the progression of cervical cancerization.</p><p><b>METHODS</b>A total number of 80 patients with histological diagnosis of cervix inflammation (CI), 55 cervical intraepithelial neoplasm I (CIN I), 55 cervical intraepithelial neoplasm II/III (CIN II/III) and 64 cervical squamous cell carcinoma (SCC) were included in this study. Levels of serum folate were detected by microbiological assay method and the methylation status of FHIT gene CpG islands was tested by methylation-specific PCR (MSP). FHIT protein levels were measured by Western blot. In vitro, cervical cancer cell lines CaSki (HPV16-positive) was treated with different concentrations of folate. Proliferation and apoptosis of cells, methylation of FHIT gene and the levels of FHIT protein expression were measured in each group. All analyses were performed with SPSS (version 17.0) statistical software. Differences among groups were assessed by chi-square test, Kruskal-Wallis test. Spearman correlation, and the interaction effects were evaluated by additive model.</p><p><b>RESULTS</b>The levels of serum folate (H = 59.08, P < 0.001) and FHIT protein expression (H = 50.93, P < 0.001) decreased gradually along with the severity of cervix lesions, while the methylation rates of FHIT gene CpG islands increased (trend χ² = 28.34, P < 0.001). Both levels of serum folate levels and FHIT protein expression were positively correlated (r = 0.213, P = 0.001), with an additive interaction seen between them in CIN I, CIN II/III, SCC groups. In vitro, both rates related to proliferation inhibition (r = 0.98, P < 0.001) and apoptosis (r = 0.99, P < 0.001) together with the levels of FHIT protein expression (r = 0.97, P < 0.001) were all increased gradually with the increase of folate concentration while the methylation status of FHIT gene CpG islands all changed from positive to negative gradually.</p><p><b>CONCLUSION</b>Results from our study revealed that both folate deficiency and FHIT protein aberrant low expression might increase the risk of developing cervical cancer and cervix precancerous lesions, and thus play a synergistic action in the progression of cervical cancerization.</p>

Prevalencia de anemia y deficiencia de hierro, ácido fólico y vitamina b12 en una comunidad wichí del noroeste argentino / Prevalence of anemia and iron, folic acid and vitamin b12 deficiencies in a wichí community from the argentine northwest region

La anemia y la malnutrición son prevalentes en comunidades de bajo nivel socioeconómico y con higiene inadecuada, como las aborígenes wichí que habitan en el noroeste argentino, región con alta prevalencia de enfermedad de Chagas. Objetivo: determinar la prevalencia de anemia y deficiencia de hierro (Fe), ácido fólico (AF) y vitamina B12 (B12) en una comunidad wichí de Salta, y evaluar la presencia de Chagas y talasemias como etiología de anemia. Material y métodos: se realizó un estudio observacional descriptivo en mayo de 2008. Se estudiaron 35 adultos wichí (21 mujeres, 14 hombres) de la comunidad La Unión. El grupo control consistió en 36 criollos adultos (21 mujeres, 15 hombres). Se realizó hemograma, Fe, transferrina, ferritina, AF, B12, electroforesis de hemoglobina (EHb) y serología para Chagas. Resultados: la prevalencia de anemia fue 76% (16/21; Intervalo de Confianza [IC] 95%=57-95%) en las mujeres wichí; en las criollas, 29% (6/21; IC95%=10-48%); en el grupo masculino criollo, 7% (1/15; IC95%=0-20%) y en los wichís, 29% (4/14; IC95%=16-42%). En las mujeres wichí, el 75% (12/16) de los casos fue por deficiencia de Fe. B12 y EHb fueron normales. El 15% (5/33) del grupo wichí y el 31% (11/35) del criollo presentó deficiencia de AF. La prevalencia de Chagas fue 31% (11/35; IC95%=16-46%) en wichís y 28% (10/36; IC95%=13-43%) en criollos, y no estuvo asociada a anemia. Conclusiones: la alta prevalencia de anemia y deficiencia de hierro indican un problema de salud y de nutrición importante en esta comunidad.

Anemia and malnutrition are prevalent in communities of low socioeconomic status and poor hygiene, including Aboriginal Wichí inhabiting the Argentine Northwest, a region with high prevalence of Chagas disease. Objetive: to investigate the prevalence of anemia and deficiencies of iron, folic acid (FA) and vitamin B12 in community wichí of Salta, and assess the presence of Chagas and thalas semia as etiology of anemia. Material and methods: a descriptive study was performed in May 2008. 35 wichí adults (21 women, 14 men) of La Union community were studied. The control group consisted of 36 adult creoles (21 women, 15 men), who shared environmental conditions. Complete blood count, iron, transferrin, ferritin, FA, vitamin B12, hemoglobin electrophoresis (HbE) and Chagas disease serology were performed. Results: the prevalence of anemia was 76% (16/21 Confidence Interval [CI] 95%=57-95%) in wichí women; in creole women, 29% (6/21, 95% CI=10-48%); in creole male group, 7% (1/15, 95% CI=0-20%) and wichí men group, 29% (4/14, 95% CI=16-42%). In anemic wichí women, 75% (12/16) of cases were produced by iron deficiency. Vitamin B12 levels and HbE were normal. FA deficiency was presented in 15% (5/33) of wichí group and 31% (11/35) of creole people. Chagasic infection prevalence was 31% (11/35, 95% CI=16-46%) in wichís and 28% (10/36, 95% CI=13-43%) in creoles, and was not associated with anemia. Conclusions: the high prevalence of anemia and iron deficiency indicates an important health and nutrition problem in this community.