Maternal and Neonatal Vitamin D Binding Protein Polymorphisms and 25-Hydroxyvitamin D Cutoffs as Determinants of Neonatal Birth Anthropometry

BACKGROUND: Vitamin D-binding protein (VDBP) is a vital regulator of optimal vitamin D homeostasis and bioavailability. Apart from its well-documented role as a key component in vitamin D dynamic transfer and circulation, it has a myriad of immunoregulatory functions related to innate immunity, which becomes particularly critical in states of increased immunological tolerance including pregnancy. In this regard, VDBP dyshomeostasis is considered to contribute to the development of several fetal, maternal, and neonatal adverse outcomes. However, precise physiological pathways, including the contribution of specific VDBP polymorphisms behind such phenomena, are yet to be fully deciphered. Our aim was to assess the combined effect of maternal and neonatal VDBP polymorphism heterogeneity in conjunction with different maternal and neonatal 25(OH)D cutoffs on the neonatal anthropometric profile at birth. METHODS: The study included data and samples from a cohort of 66 mother-child pairs at birth. The inclusion criterion was full-term pregnancy (gestational weeks 37-42). Neonatal and maternal 25(OH)D cutoffs were included according to vitamin D status at birth and delivery. Concentrations of 25(OH)D2 and 25(OH)D3 were measured using liquid chromatography-tandem mass spectrometry. RESULTS: The upper arm length of neonates with 25(OH)D ≤ 25 nmol/L was higher in neonate CC carriers for rs2298850. The upper thigh neonatal circumference was also higher in the ones with either 25(OH)D ≤ 50 or ≤75 nmol/L in rs2298850 CG + GG or rs4588 GT + TT carriers. We did not observe any significant effect for maternal VDBP polymorphisms nor for birth maternal 25(OH)D concentrations, on birth neonatal anthropometry. CONCLUSIONS: Our findings emphasize a potential role for neonatal VDBP genotypes rs2298850 and rs4588, in conjunction with specific neonatal 25(OH)D cutoffs, in the range of sufficiency on neonatal growth and development

Investigating the role of functional polymorphism of maternal and neonatal vitamin D binding protein in the context of 25‐hydroxyvitamin D cutoffs as determinants of maternal‐neonatal vitamin D status profiles in a sunny mediterranean region

Recent results indicate that dysregulation of vitamin D‐binding protein (VDBP) could be involved in the development of hypovitaminosis D, and it comprises a risk factor for adverse fetal, maternal and neonatal outcomes. Until recently, there was a paucity of results regarding the effect of maternal and neonatal VDBP polymorphisms on vitamin D status during pregnancy in the Mediterranean region, with a high prevalence of hypovitaminosis D. We aimed to evaluate the combined effect of maternal and neonatal VDBP polymorphisms and different maternal and neonatal 25‐hy-droxyvitamin D (25(OH)D) cut‐offs on maternal and neonatal vitamin D profile. Blood samples were obtained from a cohort of 66 mother–child pairs at birth. Our results revealed that: (i) Maternal VDBP polymorphisms do not affect neonatal vitamin D status at birth, in any given internationally adopted maternal or neonatal cut‐off for 25(OH)D concentrations; (ii) neonatal VDBP polymor-phisms are not implicated in the regulation of neonatal vitamin D status at birth; (iii) comparing the distributions of maternal VDBP polymorphisms and maternal 25(OH)D concentrations, with cutoffs at birth, revealed that mothers with a CC genotype for rs2298850 and a CC genotype for rs4588 tended to demonstrate higher 25(OH)D (≥75 nmol/L) during delivery (p = 0.05 and p = 0.04, respec-tively), after adjustments for biofactors that affect vitamin D equilibrium, including UVB, BMI and weeks of gestation. In conclusion, this study from Southern Europe indicates that maternal and neonatal VDBP polymorphisms do not affect neonatal vitamin D status at birth, whereas mothers with CC genotype for rs2298850 and CC genotype for rs4588 demonstrate higher 25(OH)D concen-trations. Future larger studies are required to establish a causative effect of these specific polymor-phisms in the attainment of an adequate (≥75 nmol/L) maternal vitamin D status during pregnancy

\u27Vitamin D and cognition in older adults\u27: updated international recommendations.

BACKGROUND: Hypovitaminosis D, a condition that is highly prevalent in older adults aged 65 years and above, is associated with brain changes and dementia. Given the rapidly accumulating and complex contribution of the literature in the field of vitamin D and cognition, clear guidance is needed for researchers and clinicians. METHODS: International experts met at an invitational summit on \u27Vitamin D and Cognition in Older Adults\u27. Based on previous reports and expert opinion, the task force focused on key questions relating to the role of vitamin D in Alzheimer\u27s disease and related disorders. Each question was discussed and voted using a Delphi-like approach. RESULTS: The experts reached an agreement that hypovitaminosis D increases the risk of cognitive decline and dementia in older adults and may alter the clinical presentation as a consequence of related comorbidities; however, at present, vitamin D level should not be used as a diagnostic or prognostic biomarker of Alzheimer\u27s disease due to lack of specificity and insufficient evidence. This population should be screened for hypovitaminosis D because of its high prevalence and should receive supplementation, if necessary; but this advice was not specific to cognition. During the debate, the possibility of \u27critical periods\u27 during which vitamin D may have its greatest impact on the brain was addressed; whether hypovitaminosis D influences cognition actively through deleterious effects and/or passively by loss of neuroprotection was also considered. CONCLUSIONS: The international task force agreed on five overarching principles related to vitamin D and cognition in older adults. Several areas of uncertainty remain, and it will be necessary to revise the proposed recommendations as new findings become available

The Effects of Vitamin D Receptor Silencing on the Expression of LVSCC-A1C and LVSCC-A1D and the Release of NGF in Cortical Neurons

Recent studies have suggested that vitamin D can act on cells in the nervous system. Associations between polymorphisms in the vitamin D receptor (VDR), age-dependent cognitive decline, and insufficient serum 25 hydroxyvitamin D(3) levels in Alzheimer's patients and elderly people with cognitive decline have been reported. We have previously shown that amyloid β (Aβ) treatment eliminates VDR protein in cortical neurons. These results suggest a potential role for vitamin D and vitamin D-mediated mechanisms in Alzheimer's disease (AD) and neurodegeneration. Vitamin D has been shown to down-regulate the L-type voltage-sensitive calcium channels, LVSCC-A1C and LVSCC-A1D, and up-regulate nerve growth factor (NGF). However, expression of these proteins when VDR is repressed is unknown. The aim of this study is to investigate LVSCC-A1C, LVSCC-A1D expression levels and NGF release in VDR-silenced primary cortical neurons prepared from Sprague-Dawley rat embryos.qRT-PCR and western blots were performed to determine VDR, LVSCC-A1C and -A1D expression levels. NGF and cytotoxicity levels were determined by ELISA. Apoptosis was determined by TUNEL. Our findings illustrate that LVSCC-A1C mRNA and protein levels increased rapidly in cortical neurons when VDR is down-regulated, whereas, LVSCC-A1D mRNA and protein levels did not change and NGF release decreased in response to VDR down-regulation. Although vitamin D regulates LVSCC-A1C through VDR, it may not regulate LVSCC-A1D through VDR.Our results indicate that suppression of VDR disrupts LVSCC-A1C and NGF production. In addition, when VDR is suppressed, neurons could be vulnerable to aging and neurodegeneration, and when combined with Aβ toxicity, it is possible to explain some of the events that occur during neurodegeneration

Adiponectin and vitamin D-binding protein are independently associated at birth in both mothers and neonates

CONTEXT: Adult body fat is associated with birth anthropometry, suggesting a role for metabolic regulators including vitamin D and the adipokines-adiponectin and irisin-which have been reported to interact but, as yet, data remain controversial. OBJECTIVE: To study (i) the relationship between vitamin D, its binding protein (VDBP) and the adipokines, adiponectin, and irisin in mothers and neonates at birth and (ii) their effects on neonate anthropometric outcomes. DESIGN: Cross-sectional study for healthy mothers with full-term and uncomplicated births. SETTING: Primary care. SUBJECTS: Seventy pairs of newly delivered neonates and their mothers. MAIN OUTCOMES FEATURES: Biochemical markers from maternal and cord: VDBP, adiponectin, irisin, calcium, albumin, parathyroid hormone, 25OHD, 1,25(OH)D. Maternal demographic and social characteristics and neonate anthropometric parameters were recorded. RESULTS: Maternal VDBP levels (364.1 ± 11.9 μg/ml) demonstrated a strong positive correlation with maternal adiponectin (4.4 ± 0.4 μg/ml) and irisin (308.8 ± 50.8 ng/ml) concentrations, which remained significant (p < 0.001 and p < 0.041, respectively) after adjustment with multiple parameters, including weeks of gestation, maternal age, and BMI. The finding of a strong association of VDBP (355.3 ± 29.2 μg/ml) and adiponectin (11.9 ± 2.0 μg/ml) but not irisin (174.4 ± 26.0 ng/ml) was also evident in neonates (p = 0.03 and p = 0.94, respectively). No association was observed in both maternal and neonatal vitamin D, adiponectin, and irisin. CONCLUSIONS: The main findings of this study are (i) the perspective of a potential independent interaction of VDBP and adiponectin in both mothers and neonates and (ii) the lack of a causative model effect of both maternal/neonatal vitamin D status and adipokine profile on neonatal anthropometry at birth, as a surrogate marker of future metabolic health of the offspring

An interesting journey of an ingested needle: a case report and review of the literature on extra-abdominal migration of ingested Foreign bodies

Swallowed foreign bodies encounter a major problem especially in children, but fortunately they mostly do not cause any related complication and are easily passed with the stool. In this paper, an interesting journey of a needle is presented. A 20-year old female admitted to our emergency service after she had swallowed a sewing machine needle, which is initially observed in the stomach in the plain abdominal radiography. During the follow-up period, the needle traveled through bowels, and surprisingly was observed in the left lung on 10th day of the follow-up. It was removed with a thoracotomy and pneumotomy under the fluoroscopic guidance. The postoperative period was uneventful and the patient was discharged from the hospital on the day 5. We also review the literature on interesting extra-abdominal migrations of swallowing foreign bodies

Vitamin D Receptor Fokl polymorphism is a determinant of both maternal and neonatal Vitamin D concentrations at birth

© 2019 Elsevier Ltd Maternal vitamin D deficiency is considered to be the key determinant of the development of neonatal vitamin D deficiency at birth and during early infancy. Specific vitamin D receptor (VDR) gene polymorphisms have been associated with adverse pregnancy and offspring outcomes. The aim of this study was to evaluate the effect of maternal and neonatal VDR polymorphisms (ApaI, TaqI, BsmI, FokI, Tru9I) on maternal and neonatal vitamin D status. VDR polymorphisms were genotyped in 70 mother-neonate pairs of Greek origin, and classified according to international thresholds for Vitamin D status. Mean neonatal and maternal 25-hydroxy-vitamin D [25(OH)D] concentrations were 35 ± 20 and 47 ± 26 nmol/l, respectively. Neonatal VDR polymorphisms were not associated with neonatal 25(OH)D concentrations. In contrast, mothers with the Fokl FF polymorphism had a 70 % lower risk of vitamin D deficiency [25(OH)D \u3c30 nmol/l] compared with ff ones, after adjustment for several confounders. They were also in 73 % and 88 % lower risk of giving birth to vitamin D deficient [25(OH)D \u3c30 nmol/l] neonates compared with Ff and ff mothers, respectively. These results suggest a protective role of maternal Fokl FF genotype against both maternal and neonatal vitamin D deficiency. Further studies are needed to clarify the complex gene-gene and gene-environment interactions that determine vitamin D status at birth

Fine-scale detection of population-specific linkage disequilibrium using haplotype entropy in the human genome

<p>Abstract</p> <p>Background</p> <p>The creation of a coherent genomic map of recent selection is one of the greatest challenges towards a better understanding of human evolution and the identification of functional genetic variants. Several methods have been proposed to detect linkage disequilibrium (LD), which is indicative of natural selection, from genome-wide profiles of common genetic variations but are designed for large regions.</p> <p>Results</p> <p>To find population-specific LD within small regions, we have devised an entropy-based method that utilizes differences in haplotype frequency between populations. The method has the advantages of incorporating multilocus association, conciliation with low allele frequencies, and independence from allele polarity, which are ideal for short haplotype analysis. The comparison of HapMap SNPs data from African and Caucasian populations with a median resolution size of ~23 kb gave us novel candidates as well as known selection targets. Enrichment analysis for the yielded genes showed associations with diverse diseases such as cardiovascular, immunological, neurological, and skeletal and muscular diseases. A possible scenario for a selective force is discussed. In addition, we have developed a web interface (ENIGMA, available at <url>http://gibk21.bse.kyutech.ac.jp/ENIGMA/index.html</url>), which allows researchers to query their regions of interest for population-specific LD.</p> <p>Conclusion</p> <p>The haplotype entropy method is powerful for detecting population-specific LD embedded in short regions and should contribute to further studies aiming to decipher the evolutionary histories of modern humans.</p

L'Auto-vélo : automobilisme, cyclisme, athlétisme, yachting, aérostation, escrime, hippisme / dir. Henri Desgranges

07 juillet 19021902/07/07 (A3,N631)