Prevention of Neural Tube Defects: A Cross-Sectional Study of the Uptake of Folic Acid Supplementation in Nearly Half a Million Women

BACKGROUND: Taking folic acid supplements before pregnancy to reduce the risk of a neural tube defect (NTD) is especially important in countries without universal folic acid fortification. The extent of folic acid supplementation among women who had antenatal screening for Down's syndrome and NTDs at the Wolfson Institute of Preventive Medicine, London between 1999 and 2012 was assessed. METHODS AND FINDINGS: 466,860 women screened provided details on folic acid supplementation. The proportion of women who took folic acid supplements before pregnancy was determined according to year and characteristics of the women. The proportion of women taking folic acid supplements before pregnancy declined from 35% (95% CI 34%-35%) in 1999-2001 to 31% (30%-31%) in 2011-2012. 6% (5%-6%) of women aged under 20 took folic acid supplements before pregnancy compared with 40% of women aged between 35 and 39. Non-Caucasian women were less likely to take folic acid supplements before pregnancy than Caucasian women; Afro-Caribbean 17% (16%-17%), Oriental 25% (24%-25%) and South Asian 20% (20%-21%) compared with 35% (35%-35%) for Caucasian women. 51% (48%-55%) of women who previously had an NTD pregnancy took folic acid supplements before the current pregnancy. CONCLUSIONS: The policy of folic acid supplementation is failing and has led to health inequalities. This study demonstrates the need to fortify flour and other cereal grain with folic acid in all countries of the world

MFGE8 does not influence chorio-retinal homeostasis or choroidal neovascularization in vivo

Purpose: Milk fat globule-epidermal growth factor-factor VIII (MFGE8) is necessary for diurnal outer segment phagocytosis and promotes VEGF-dependent neovascularization. The prevalence of two single nucleotide polymorphisms (SNP) in MFGE8 was studied in two exsudative or “wet” Age-related Macular Degeneration (AMD) groups and two corresponding control groups. We studied the effect of MFGE8 deficiency on retinal homeostasis with age and on choroidal neovascularization (CNV) in mice. Methods: The distribution of the SNP (rs4945 and rs1878326) of MFGE8 was analyzed in two groups of patients with “wet” AMD and their age-matched controls from Germany and France. MFGE8-expressing cells were identified in Mfge8+/− mice expressing ß-galactosidase. Aged Mfge8+/− and Mfge8−/− mice were studied by funduscopy, histology, electron microscopy, scanning electron microscopy of vascular corrosion casts of the choroid, and after laser-induced CNV. Results: rs1878326 was associated with AMD in the French and German group. The Mfge8 promoter is highly active in photoreceptors but not in retinal pigment epithelium cells. Mfge8−/− mice did not differ from controls in terms of fundus appearance, photoreceptor cell layers, choroidal architecture or laser-induced CNV. In contrast, the Bruch's membrane (BM) was slightly but significantly thicker in Mfge8−/− mice as compared to controls. Conclusions: Despite a reproducible minor increase of rs1878326 in AMD patients and a very modest increase in BM in Mfge8−/− mice, our data suggests that MFGE8 dysfunction does not play a critical role in the pathogenesis of AMD

Periconceptional bread intakes indicate New Zealand's proposed mandatory folic acid fortification program may be outdated: results from a postpartum survey

Abstract Background In September 2009, a folic acid fortification mandate (135 μg/100 g bread) was to be implemented in New Zealand. However, due to political and manufacturer objection, fortification was deferred until May 2012. Based on estimates of bread consumption derived from a 1997 nationally representative survey, this program was intended to deliver a mean additional intake of 140 μg folic acid/d to women of childbearing age. Little is known about current bread consumption patterns in this target group. The aim of this study was to assess bread consumption among women prior to and during pregnancy with the intent to estimate periconceptional folic acid intakes that would be derived from bread if mandatory fortification were implemented as currently proposed. Methods A retrospective survey of 723 postpartum women in hospitals and birthing centres across New Zealand was conducted using a self-administered questionnaire on bread intake prior to and during pregnancy and maternal socio-demographic and obstetric characteristics. Results Median bread intake before conception (2 slices/d) was below that of previous data upon which the current fortification proposal was modeled (3-4 slices/d). If mandatory fortification is implemented as proposed, only 31% (95% CI = 24%-37%) of childbearing-age women would attain an additional folic acid intake of ≥ 140 μg/d, with a mean of 119 μg/d (95% CI = 107 μg/d-130 μg/d). Based on these data, a fortification level of 160 μg/100 g bread is required to achieve the targeted mean of 140 μg folic acid/d. Nonetheless, under the current proposal additional folic acid intakes would be greatest among the least advantaged segments of the target population: Pacific and indigenous Māori ethnic groups; those with increased parity, lower income and education; younger and single mothers; and women with unplanned pregnancies. Subgroups predicted to derive less than adequate folic acid intakes from the proposed policy were women of Asian descent and those with a postgraduate education. Conclusions This study provides insight on the ability of a fortification policy to benefit the groups at highest risk of poor folate intakes in a population. However, bread consumption among the target group of childbearing women appears to have declined since the data used in previous dietary modeling were collected. Thus, it seems prudent to re-model dietary folic acid intakes based on more recent national survey data prior to the implementation of a mandatory folic acid fortification policy.</p

1H-NMR-Based Metabolic Profiling of Maternal and Umbilical Cord Blood Indicates Altered Materno-Foetal Nutrient Exchange in Preterm Infants

Background: Adequate foetal growth is primarily determined by nutrient availability, which is dependent on placental nutrient transport and foetal metabolism. We have used 1H nuclear magnetic resonance (NMR) spectroscopy to probe the metabolic adaptations associated with premature birth. Methodology: The metabolic profile in 1H NMR spectra of plasma taken immediately after birth from umbilical vein, umbilical artery and maternal blood were recorded for mothers delivering very-low-birth-weight (VLBW) or normo-ponderal full-term (FT) neonates. Principal Findings: Clear distinctions between maternal and cord plasma of all samples were observed by principal component analysis (PCA). Levels of amino acids, glucose, and albumin-lysyl in cord plasma exceeded those in maternal plasma, whereas lipoproteins (notably low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) and lipid levels were lower in cord plasma from both VLBW and FT neonates. The metabolic signature of mothers delivering VLBW infants included decreased levels of acetate and increased levels of lipids, pyruvate, glutamine, valine and threonine. Decreased levels of lipoproteins glucose, pyruvate and albumin-lysyl and increased levels of glutamine were characteristic of cord blood (both arterial and venous) from VLBW infants, along with a decrease in levels of several amino acids in arterial cord blood. Conclusion: These results show that, because of its characteristics and simple non-invasive mode of collection, cord plasma is particularly suited for metabolomic analysis even in VLBW infants and provides new insights into the materno-foetal nutrient exchange in preterm infants

Manovacuometria realizada por meio de traqueias de diferentes comprimentos

Manovacuometry is a simple, fast, and non-invasive test, with maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) obtained to assist respiratory muscle assessment. Currently, there is a wide variety of models and brands of manovacuometers with different trachea diameters and lengths. However, the interference of these models in the measurements obtained by these equipments needs to be investigated. Thus, this study mainly aimed to verify the influence of tracheal length on maximal respiratory pressures (MRP), obtained by an analog manovacuometer, in healthy individuals. Our secondary objective was to verify the correlation between measurements. Fifty individuals, aged 18 to 30, of both sexes, were evaluated by spirometry and manovacuometry. MIP and MEP were performed using tracheas with same internal diameter (0.5 cm) and 30 cm, 60 cm, and 90 cm length. Significantly lower MIP values were observed when comparing a 90 cm trachea to 30 and 60 cm tracheas (Friedman’s ANOVA test and Wilcoxon test with Bonferroni adjustment). Tracheas with 30, 60, and 90 cm length and same diameter did not affect MIP and MEP values, except the 90 cm trachea for MIP values, which may interfere in the physical therapy clinical practice. Further studies are required to analyze the need for standardizing the trachea length used in manovacuometers.La manovacuometría es una prueba sencilla, rápida y no invasiva por la cual se obtienen la presión inspiratoria máxima (PImax) y la presión espiratoria máxima (PEmax), con el objetivo de ayudar en el examen muscular respiratorio. Hoy día se encuentran una gran variedad de modelos y marcas de manovacuometros, con diferentes diámetros y longitudes de las tráqueas, pero hacen falta estudios sobre la interferencia de estos modelos en las mediciones por este instrumento. En este texto se propone examinar en sujetos sanos, en primer lugar, la influencia en la longitud de las tráqueas en las presiones respiratorias máximas, obtenidas por manovacuometros analógicos, y en segundo lugar comprobar la existencia de correlación entre las mediciones. Se evaluaron a cincuenta sujetos entre 18 y 30 años de edad, tanto varones como mujeres, empleando la espirometría y la manovacuometría. Se midió la PImax y la PEmax empleando tráqueas de mismo diámetro interno (0,5 cm) y con longitudes de 30, 60 e 90 cm. Se observaron valores significativamente menores de PImax con la tráquea de longitud de 90 cm en comparación con las PImax con las tráqueas de 30 y 60 cm (prueba de Friedman’s ANOVA, la de Wilcoxon con ajustes de Bonferroni). Las tráqueas de 30, 60 y 90 cm de longitud y mismo diámetro no influyeron en los valores de la PEmax y de la PImax, con excepción de la tráquea de 90 cm en los valores de la PImax, lo que puede interferir la práctica clínica fisioterapéutica. Se necesitan más estudios para evaluar la necesidad de estándares de la longitud de tráqueas empleadas en manovacuometros.A manovacuometria é um teste simples, rápido e não invasivo por meio do qual a pressão inspiratória máxima (PImáx) e a pressão expiratória máxima (PEmáx) são obtidas, a fim de auxiliar na avaliação muscular respiratória. Atualmente, há grande variedade de modelos e marcas de manovacuômetros, com diferentes diâmetros e comprimentos de traqueias, no entanto, a interferência desses modelos nas medidas obtidas por esses equipamentos necessita de investigação. Desta forma, o objetivo primário deste estudo foi verificar a influência do comprimento de traqueias nas pressões respiratórias máximas, obtidas por meio de manovacuômetro analógico, em indivíduos saudáveis e, secundariamente, se há correlação entre as medidas. Foram avaliados 50 indivíduos, de 18 a 30 anos, de ambos os sexos, por meio da espirometria e manovacuometria. As PImáx e PEmáx foram realizadas com uso de traqueias de mesmo diâmetro interno (0,5 cm) e comprimentos de 30, 60 e 90 cm. Foram observados valores significativamente menores de PImáx obtidos com a traqueia de comprimento de 90 cm comparados às PImáx obtidas com as traqueias de 30 e 60 cm (teste de Friedman’s ANOVA com teste de Wilcoxon com ajuste de Bonferroni). As traqueias de 30, 60 e 90 cm de comprimento e mesmo diâmetro não influenciaram os valores de PEmáx e PImáx, exceto a traqueia de 90 cm para os valores de PImáx, o que pode interferir na prática clínica fisioterapêutica. Novos estudos são necessários para analisar a necessidade de padronização do comprimento da traqueia utilizada em manovacuômetros

Toll-Like Receptor 3 (TLR3) Plays a Major Role in the Formation of Rabies Virus Negri Bodies

Human neurons express the innate immune response receptor, Toll-like receptor 3 (TLR3). TLR3 levels are increased in pathological conditions such as brain virus infection. Here, we further investigated the production, cellular localisation, and function of neuronal TLR3 during neuronotropic rabies virus (RABV) infection in human neuronal cells. Following RABV infection, TLR3 is not only present in endosomes, as observed in the absence of infection, but also in detergent-resistant perinuclear inclusion bodies. As well as TLR3, these inclusion bodies contain the viral genome and viral proteins (N and P, but not G). The size and composition of inclusion bodies and the absence of a surrounding membrane, as shown by electron microscopy, suggest they correspond to the previously described Negri Bodies (NBs). NBs are not formed in the absence of TLR3, and TLR3−/− mice—in which brain tissue was less severely infected—had a better survival rate than WT mice. These observations demonstrate that TLR3 is a major molecule involved in the spatial arrangement of RABV–induced NBs and viral replication. This study shows how viruses can exploit cellular proteins and compartmentalisation for their own benefit