Cord blood vitamin D and neurocognitive development are nonlinearly related in toddlers

Background Little is known about the relation between vitamin D status in early life and neurodevelopment outcomes. Objective This study was designed to examine the association of cord blood 25-hydroxyvitamin D [25(OH)D] at birth with neurocognitive development in toddlers. Methods As part of the China-Anhui Birth Cohort Study, 363 mother-infant pairs with completed data were selected. Concentrations of 25(OH)D in cord blood were measured by radioimmunoassay. Mental development index (MDI) and psychomotor development index (PDI) in toddlers were assessed at age 16–18 mo by using the Bayley Scales of Infant Development. The data on maternal sociodemographic characteristics and other confounding factors were also prospectively collected. Results Toddlers in the lowest quintile of cord blood 25(OH)D exhibited a deficit of 7.60 (95% CI: −12.4, −2.82; P = 0.002) and 8.04 (95% CI: −12.9, −3.11; P = 0.001) points in the MDI and PDI scores, respectively, compared with the reference category. Unexpectedly, toddlers in the highest quintile of cord blood 25(OH)D also had a significant deficit of 12.3 (95% CI: −17.9, −6.67; P < 0.001) points in PDI scores compared with the reference category. Conclusions This prospective study suggested that there was an inverted-U–shaped relation between neonatal vitamin D status and neurocognitive development in toddlers. Additional studies on the optimal 25(OH)D concentrations in early life are needed.

Crystal structures and hydrogen bonding in the anhydrous tryptaminium salts of the isomeric (2,4-dichlorophenoxy)acetic and (3,5-dichlorophenoxy)acetic acids

The anhydrous salts of 1H-indole-3-ethanamine (tryptamine) with isomeric (2,4-dichlorophenoxy)acetic acid (2,4-D) and (3,5-dichlorophenoxy)acetic (3,5-D), C10H13N2+ (C8H5Cl2O3)-, [(I) and (II), respectively] have been determined and their one-dimensional hydrogen-bonded polymeric structures are described. In the crystal of (I),the aminium H-atoms are involved in three separate inter-species N-H...O hydrogen-bonding interactions, two with carboxyl O-atom acceptors and the third in an asymmetric three-centre bidentate carboxyl O,O' chelate [graph set R2/1(4)]. The indole H-atom forms an N-H...O~carboxyl~ hydrogen bond, extending the chain structure along the b axial direction. In (II), two of the three aminium H-atoms are also involved in N-H...O(carboxyl) hydrogen bonds similar to (I) but with the third, a three-centre asymmetric interaction with carboxyl and phenoxy O-atoms is found [graph set R2/1(5)]. The chain polymeric extension is also along b. There are no pi--pi ring interactions in either of the structures. The aminium side chain conformations differ significantly between the two structures, reflecting the conformational ambivalence of the tryptaminium cation, as found also in the benzoate salts.

Antioxidant responses to an acute ultra-endurance exercise: Impact on DNA stability and indications for an increased need for nutritive antioxidants in the early recovery phase

Antioxidant requirements have neither been defined for endurance nor been defined for ultra-endurance athletes. To verify whether an acute bout of ultra-endurance exercise modifies the need for nutritive antioxidants, we aimed (1) to investigate the changes of endogenous and exogenous antioxidants in response to an Ironman triathlon; (2) to particularise the relevance of antioxidant responses to the indices of oxidatively damaged blood lipids, blood cell compounds and lymphocyte DNA and (3) to examine whether potential time-points of increased susceptibility to oxidative damage are associated with alterations in the antioxidant status. Blood that was collected from forty-two well-trained male athletes 2 d pre-race, immediately post-race, and 1, 5 and 19 d later was sampled. The key findings of the present study are as follows: (1) Immediately post-race, vitamin C, alpha-tocopherol, and levels of the Trolox equivalent antioxidant capacity, the ferric reducing ability of plasma and the oxygen radical absorbance capacity (ORAC) assays increased significantly. Exercise-induced changes in the plasma antioxidant capacity were associated with changes in uric acid, bilirubin and vitamin C. (2) Significant inverse correlations between ORAC levels and indices of oxidatively damaged DNA immediately and 1 d post-race suggest a protective role of the acute antioxidant responses in DNA stability. (3) Significant decreases in carotenoids and gamma-tocopherol 1 d post-race indicate that the antioxidant intake during the first 24 h of recovery following an acute ultra-endurance exercise requires specific attention. Furthermore, the present study illustrates the importance of a diversified and well-balanced diet to maintain a physiological antioxidant status in ultra-endurance athletes in reference to recommendations.

Genome-wide association study identifies eight loci associated with blood pressure

Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N 71,225 European ancestry, N 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10 24), CYP1A2 (P = 1 × 10 23), FGF5 (P = 1 × 10 21), SH2B3 (P = 3 × 10 18), MTHFR (P = 2 × 10 13), c10orf107 (P = 1 × 10 9), ZNF652 (P = 5 × 10 9) and PLCD3 (P = 1 × 10 8) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

Diet-induced hypercholesterolemia promotes androgen-independent prostate cancer metastasis via IQGAP1 and caveolin-1

Obesity and metabolic syndrome are associated with several cancers, however, the molecular mechanisms remain to be fully elucidated. Recent studies suggest that hypercholesterolemia increases intratumoral androgen signaling in prostate cancer, but it is unclear whether androgenindependent mechanisms also exist. Since hypercholesterolemia is associated with advanced, castrate-resistant prostate cancer, in this study, we aimed to determine whether and how hypercholesterolemia affects prostate cancer progression in the absence of androgen signaling. We demonstrate that diet-induced hypercholesterolemia promotes orthotopic xenograft PC-3 cell metastasis, concomitant with elevated expression of caveolin-1 and IQGAP1 in xenograft tumor tissues. In vitro cholesterol treatment of PC-3 cells stimulated migration and increased IQGAP1 and caveolin-1 protein level and localization to a detergent-resistant fraction. Down-regulation of caveolin-1 or IQGAP1 in PC-3 cells reduced migration and invasion in vitro, and hypercholesterolemia-induced metastasis in vivo. Double knock-down of caveolin-1 and IQGAP1 showed no additive effect, suggesting that caveolin-1 and IQGAP1 act via the same pathway. Taken together, our data show that hypercholesterolemia promotes prostate cancer metastasis independent of the androgen pathway, in part by increasing IQGAP1 and caveolin-1. These results have broader implications for managing metastasis of cancers in general as IQGAP1 and hypercholesterolemia are implicated in the progression of several cancers.