Vitamin D status and its dietary and lifestyle factors in children during the first 5 years of life: A cross-sectional multicentre Jiangsu bone study.

BACKGROUND: To explore the vitamin D status with its demographic and lifestyle factors including dietary, supplementation, and physical activity in 0-5 years old children. METHODS: This was a large population-based cross-sectional multicentre study in which the children were recruited from 12 Children's Health Care Centers by a stratified cluster random-sampling method in 10 cities in Jiangsu Province, China. RESULTS: A total number of 5289 children were investigated. The prevalence of vitamin D deficiency was 30.1%. The concentration of 25 hydroxyvitamin D was 64.0 (46.3-83.0) nmol mL-1 after adjustment for covariates. Children with higher risk of vitamin D deficiency were more likely to be at older age, girls, survey conducted in spring, location in southern Jiangsu province, residence in urban, outdoor activity < 2 h day-1 (all p < 0.05). Moreover, those with lower risk were more likely to be the number of parity ≥ 2 times, vitamin D supplementation from birth to 6 months, the initial time of vitamin D supplementation after birth ≤ 1 months, vitamin D and calcium supplementation in the last 3 months, and dose of vitamin D supplementation > 400 IU day-1 (all p < 0.05). Children with preferences for sweets, meat consumption > 150.0 g day-1 , milk consumption < 250 mL day-1 , time of sleeping < 10 h day-1 had higher risks of vitamin D deficiency. However, these relationships were affected by demographics. CONCLUSIONS: Vitamin D status during the first five years of life was suboptimal and was associated with demographic and lifestyle determinants including milk, meat, sweets, vitamin D and calcium supplementation, sleeping and outdoor activity.

Development and validation of a fetal genotyping assay with potential for noninvasive prenatal diagnosis of hereditary hearing loss.

OBJECTIVE: Inherited non-syndromic hearing loss (NSHL) is a common sensory disorder that afflicts otherwise healthy individuals. The aim of the study was to evaluate the performance of circulating single molecule amplification and re-sequencing technology (cSMART) for non-invasive prenatal testing (NIPT) of NSHL. METHOD: Neonatal inheritance of NSHL mutations was determined from bloodspots using SNaPshot genotyping. NIPT of cell-free DNA for fetal NSHL mutations in the GJB2, GJB3 and SLC26A4 genes was performed by a multiplex cSMART assay. The percentage of mutant alleles was used to deduce fetal DNA fractions and assign fetal genotypes. RESULTS: A total of 25 plasma samples selected with different fetal NSHL genotypes were coded and retrospectively analyzed by NIPT. Three normal fetuses, 18 carrier fetuses comprising seven GJB2 109G>A, four GBJ2 235delC, three GJB2 299-300delAT and four SLC26A4 IVS7-2A>G heterozygotes and four affected fetuses comprising two GJB2 109G>A homozygotes, one GBJ2 235delC homozygote and one compound GJB2 235delC/299-300delAT heterozygote were identified. All 25 fetal genotypes determined by the cSMART assay were concordant with neonatal genotypes. CONCLUSION: The cSMART assay applied to cell-free DNA isolated from maternal plasma of pregnant women is highly accurate for calling correct fetal NSHL genotypes. © 2016 John Wiley & Sons, Ltd.

Is vitamin D deficiency influenced by obesity during the first 5 years of life? A cross-sectional multicenter study.

Evidence on the association of 25-hydroxyvitamin D (25[OH]D) and obesity during the first 5 years of life is limited in China. The objective of this study was to examine the associations between weight, weight for age z score (ZWAZ), weight for length/height z score (ZWHZ), and body mass index for age z score (ZBMI) and 25(OH)D. This was a large population-based cross-sectional multicenter study in which the children aged 0-5 years were recruited from 12 children's healthcare centers by a stratified cluster random-sampling method in 10 cities of the Jiangsu province, China. The 25(OH)D concentration was determined by ELISA. A total of 5289 children were investigated. For 0-71 months children with obesity and nonobesity, the prevalence of vitamin D deficiency was 36.0% and 29.8%, and the 25(OH)D level was 59.8 and 64.0 nmol/L, respectively, and there were all significant difference. Compared with children with nonobesity, children with obesity had higher risk of vitamin D deficiency (OR [95% CI]: 1.33 [1.02, 1.72], p < .05), and had lower 25(OH)D level (ß = -3.84, 95% CI = -7.58, -0.09, p < .05). The results for children aged 24-71 months were similar to those for children aged 0-71 months. However, no significant difference was observed in children aged 0-23 months. Vitamin D deficiency was observed in children with greater adiposity during the first 5 years of life. However, the results mainly came from those in the age group of 2 to 5 years instead of the first 2 years in their lives.

A novel integrated quasi-zero stiffness vibration isolator for coupled translational and rotational vibrations.

Quasi-zero stiffness (QZS) vibration isolators can provide better isolation performance in the low frequency range than linear vibration isolators. Currently, most of the designed QZS isolators perform vibration isolation only in one direction and few papers are focused on simultaneously isolating the vibrations in two directions. In this paper, an integrated translational-rotational QZS vibration isolator is designed by using the cam-roller mechanism. The proposed QZS system is able to provide the high-static-low-dynamic stiffness in two directions simultaneously. The excitations in both translational and rotational directions are considered independent but with mutual interaction to their induced vibration response. The workable ranges of the QZS system and its limitations are first numerically identified. Then the static characteristics and typical nonlinear dynamic response with jump phenomena are theoretically investigated. The jump-down frequencies for small amplitude oscillations are determined from their amplitude-frequency relationships. Furthermore, the force transmissibility and moment transmissibility of the proposed QZS system are compared with those of the corresponding linear system without the cam-roller mechanism, which clearly demonstrate better isolation performance in both translational and rotational directions.

Reduced Effectiveness and Comparable Safety in Biweekly vs. Weekly PEGylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency: A Phase IV Non-Inferiority Threshold Targeted Trial.

Context: Long-acting recombinant human growth hormone (rhGH) has transformed growth hormone deficiency (GHD) treatment. However, the possibility and rationality for flexible time regimen are pending. Objective: We studied the efficacy of biweekly versus weekly PEGylated rhGH (PEG-rhGH) therapy in GHD children. Design Setting and Patients: This multicenter, phase IV trial with a non-inferiority threshold ≥20% enrolled 585 Tanner stage I GHD children. Intervention: Subjects randomly received 0.20 mg/kg once-weekly or biweekly PEG-rhGH, or 0.25 mg/kg.w rhGH once daily for 26 weeks. Main Outcome Measure: The primary outcome was height SD scores for chronological age (HtSDSCA) at week 26 and safety measurements including adverse events (AEs), IGF-2, and IGFBP-2 changes. Results: At week 26, the median HtSDSCA changed from -2.75, -2.82, and -2.78 to -2.31, -2.43, and -2.28 with weekly and biweekly PEG-rhGH, and daily rhGH, respectively. The difference in HtSDSCA was 0.17 ± 0.28 between weekly and biweekly PEG-rhGH, and 0.17 ± 0.27 between daily rhGH and biweekly PEG-rhGH, failing the non-inferiority threshold. Nevertheless, the height velocity of children receiving biweekly PEG-rhGH reached 76.42%-90.34% and 76.08%-90.60% that of children receiving weekly PEG-rhGH and daily rhGH, respectively. The rate of AEs was comparable among the groups. No statistical difference was observed in IGF-2 and IGFBP-2 levels among the groups. IGFBP-2 levels decreased over time in all groups, with no notable difference in IGF-2 and IGFBP-2 changes among the three treatment groups. Conclusions: Although notably promoted height velocity, biweekly PEG-rhGH failed the non-inferiority threshold as compared with either weekly PEG-rhGH or daily rhGH. Compared with short-term rhGH, long-acting PEG-rhGH did not significantly increase tumor-associated IGF-2 and IGFBP-2 expressions. Clinical Trial Registration: clinicaltrials.gov, identifier NCT02976675.

Corrigendum: Reduced Effectiveness and Comparable Safety in Biweekly vs. Weekly PEGylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency: A Phase IV Non-Inferiority Threshold Targeted Trial.

[This corrects the article DOI: 10.3389/fendo.2021.779365.].

Human SMAD4 is phosphorylated at Thr9 and Ser138 by interacting with NLK.

Smads are important intracellular effectors in signaling pathways of the transforming growth factor-beta (TGF-beta). Receptor-activated Smads combine with a common Smad4 to translocate into the nucleus where they cooperate with other transcription factors to activate or repress transcription. SMAD4 is an important tumor suppressor gene. Smad4 has been shown to be constitutively phosphorylated, but the kinase that performs this phosphorylation is unknown. In this study, Smad4 was identified to interact with Nemo-like kinase (NLK) by a yeast two-hybrid system, and this interaction was confirmed in vitro and in vivo. Furthermore, the linker sequence of Smad4 is sufficient for this specific interaction. NLK is a conserved Ser/Thr kinase. Using in vitro kinase assays, we identified that threonine 9 (Thr9) and Serine 138 (Ser138) within the N-terminal Mad homology1 (MH1) domain of Smad4 could be phosphorylated by NLK. Our research suggests that NLK may play a novel role in the regulatory of Smad4 through phosphorylation.

Adiposity is not beneficial to bone mineral density in 0-5 year old Chinese children: The Jiangsu bone health study.

OBJECTIVE: Data on obesity in relation to bone mineral density(BMD) in infants and preschool children were sparse in China. The objective of this study was to examine the associations between body mass index (BMI) and BMD. SUBJECTS AND METHODS: This was a large population-based multicenter study in which the representative children aged 0-5 years were recruited from 13 Children's Health Care Centers by a stratified cluster random-sampling method in Jiangsu Province, China. BMD was measured by using quantitative ultrasound. The association of BMD with BMI and obesity were evaluated using multiple linear regression and logistic regression analysis taking into account the effects of confounders. The relations between age, weight, height, BMI and BMD were analyzed by using Pearson's correlation and further tested using partial correlation in the additive model. RESULTS: A total of 5,289 children (2786 boys and 2503 girls) were recruited. The BMD was positively linear relation with age, length/height, and was inversely linear relation with BMI (r=0.711, P<0.001; r=0.727, P<0.001; r=-0.318, P<0.001, respectively). The BMD gradually increased when the weight was in the range within 21.2kg, but started to gain slowlyand even decreased when the weight was over 21.2kg. After adjusting for confounders, compared with control group, children with obesityhad higher odds of low BMD (OR 95%CI: 2.73 (1.57, 4.76), P<0.001), the speed of sound (SOS)value in children with obesity was lower 47.45 (ß=-47.45, 95%CI=-85.07, -9.83, P=0.013). CONCLUSIONS: Adiposity was not advantageous for bone mineral density in 0-5-year-old Chinese children.

The reliability and validity of Bayley-III cognitive scale in China's male and female children.

BACKGROUND: Since publication in 2006, the Bayley-III scale has been used widely in pediatric populations worldwide; however, there have been very few studies which examined the usefulness and the potential sex differences in a Chinese context. AIMS: To assess the reliability and validity of the Bayley-III cognitive scale, and detect possible sex differences in term children so as to provide evidence for clinical and research use in China. STUDY DESIGN: Cross-sectional study PARTICIPANTS AND OUTCOME MEASURES: Of the 1589 children from 3 healthcare institutions that were initially recruited, a total of 1444 children were included in the final analysis. We randomly selected 5-10% children from the total sample to evaluate the test-retest, inter-rater and criteria-related reliability in order to meet the psychometric criteria of Bayley-III scale. Inter-item consistency, test-retest and inter-rater reliability of the scale were estimated using Split-half method and Intra-class Correlation Coefficient (ICC). The content validity was evaluated by the Item-level Content Validity Index (I-CVI). The Mann-Kendall trend test was performed to assess trends of cognitive development, and post-hos Least Significant Difference test was used to detect age-appropriateness of items. RESULTS: Six developmental pediatricians were trained to administer the Bayley-III cognitive scale. Inter-item consistency (n = 1444) with Guttman split-half coefficient was above 0.8, while test-retest (n = 144) and inter-rater reliability (n = 74) had good to excellent ICCs of over 0.9. The criteria-related validity (n = 74) of Bayley-III was acceptable, and associations with Gesell Developmental Schedules (GDS) were mainly above 0.8. The raw score of Bayley-III scale in total subjects (n = 1444) showed an increased trend across all months of age (p < 0.05), and only the score in age group of 35M16D to 36M15D declined in females (p < 0.05, n = 722). Female children presented a higher score than male children in all subjects and in the 18-23 months age group (p < 0.05). CONCLUSIONS: Our findings provide important evidence that the Bayley-III cognitive scale is a valid measurement which could be used in Chinese population, as well as the consideration of sex differences when used in a Chinese context.

Identification and expression profiles of twenty-six glutathione S-transferase genes from rice weevil, Sitophilus oryzae (Coleoptera: Curculionidae).

The rice weevil, Sitophilus oryzae, is one of the most destructive pests in stored cereals products. In this study, 26 cDNAs encoding glutathione S-transferases (GSTs) were sequenced and characterized in S. oryzae. Phylogenetic analysis displayed the categorization of 26 GSTs into six different cytosolic classes, including two in the delta, twelve in epsilon, three in omega, six in sigma, two in theta, and one in zeta class. RT-qPCR assay illustrated that the relative expression of ten GST genes was significantly higher in adult stages than in larval and pupal developmental stages. Tissue-specific expression analysis revealed that the SoGSTe5, SoGSTe7, SoGSTe12, and SoGSTz1 were up-regulated in the midgut, SoGSTe2, SoGSTe6, and SoGSTs2 were up-regulated in the fat body, and three GSTs (SoGSTd1, SoGSTd2 and SoGSTe4) were up-regulated in Malpighian tubules. RT-qPCR indicated that five GST genes were over expressed after exposure to phosphine at various times and concentrations. The increase in GST gene expressions after phosphine exposure in S. oryzae may lead to an improved tolerance for fumigations and xenobiotics.

Increased Cortisol and Cortisone Levels in Overweight Children.

BACKGROUND It has been unclear whether relatively high cortisol and cortisone levels are related to overweight in childhood, parental body mass index (BMI), and family dietary habits. The aim of this study was to compare cortisol and cortisone levels in urine and saliva from overweight and normal children, as well as correlations between children's BMI, parental BMI and family dietary behavior questionnaire score (QS). MATERIAL AND METHODS We analyzed the data from 52 overweight children and 53 age- and sex-matched normal-weight children aged 4-5 years. The concentrations of salivary cortisol (SF), salivary cortisone (SE), urinary cortisol (UF) and urinary cortisone (UE) were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The family dietary behavior QS was answered by the parent mainly responsible for the family diet. RESULTS Average cortisol and cortisone levels were significantly higher in overweight children. There was no significant difference in the ratio of cortisol to cortisone (Rcc) and the marker of 11b-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) activities. The results displayed correlations among cortisol, cortisone, and Rcc. Positive correlations were weak-to-moderate between BMI and SF, SE, UF, and UE. There were correlations between BMI and maternal BMI (mBMI), and BMI was significantly associated with QS. CONCLUSIONS Our results suggest that cortisol and cortisone levels are associated with overweight in children, but the 11ß-HSD2 activities showed no significant differences. Unhealthy family diet was associated with higher BMI, UF, and UE, and families with maternal overweight or obesity had a higher prevalence of children's overweight or obesity.

[Application of the pin-hole marker measurement of the irregular silicone impression accuracy].

PURPOSE: To investigate the feasibility of the pin-hole marker measurement of the irregular silicone dental impression accuracy. METHODS: The metal model simulating abutment preparations had triangle-formed circular needles on the surface. Two silicone impressions were made by the metal model with the corresponding pin-hole markers. The dimensional change of the markers was evaluated by stereomicroscope. The records were output by the software which could simulate the centre of a circle to measure the displacement and dimensional accuracy. RESULTS: The outline of pin-hole marker was clear and shape was stable. Values of center coordinates were repeated well. The percentage of linear dimensional change of two impression samples was 0.023% and 0.042% at 48h respectively. Between two abutment preparations, the percentage of linear dimensional change of Zhermeck silicone impression increased 0.214% (45.1µm) at 1h and decreased 0.019% (4.0µm) at 48h while 3M silicone impression increased 0.087%(18.2µm) at 1h and decreased 0.09% (18.8µm) at 48h. CONCLUSION: The pin-hole marker measurement of the irregular silicone impression accuracy was feasible.

Resveratrol attenuates radiation damage in Caenorhabditis elegans by preventing oxidative stress.

Resveratrol, a member of a class of polyphenolic compounds known as flavonols, has been extensively studied for its anticancer, antiviral, anti-inflammatory, and neuroprotective roles. Caenorhabidits elegans is a well-established animal for investigating responses to radiation. We found that resveratrol may provide protection against hazardous radiation. Pre-treatment with resveratrol extended both the maximum and mean life span of irradiated C. elegans. Resveratrol acted as a strong radical scavenger and regulated superoxide dismutase (SOD) expression. In addition, resveratrol was shown to be capable of alleviating gamma-ray radiation exposure-induced reduction in mitochondrial SOD expression. Ultimately, a correlation may exist between dietary intake of trace amounts of resveratrol and anti-aging effects. A specific response mechanism may be activated after the administration of resveratrol in irradiated animals. Our results suggest the protective effect of resveratrol is due to its strong ability to protect from oxidative stress and protective effects in mitochondria. Therefore, resveratrol is potentially an effective protecting agent against irradiative damage.

Casein kinase 2 interacts with human mitogen- and stress-activated protein kinase MSK1 and phosphorylates it at multiple sites.

Mitogen- and stress-activated protein kinase (MSK1) palys a crucial role in the regulation of transcription downstream of extracellular-signal-regulated kinase1/2 (ERK1/2) and mitogen- activated protein kinase p38. MSK1 can be phosphorylated and activated in cells by both ERK1/2 and p38alpha. In this study, Casein Kinase 2 (CK2) was identified as a binding and regulatory partner for MSK1. Using the yeast two-hybrid system, MSK1 was found to interact with the CK2beta regulatory subunit of CK2. Interactions between MSK1 and the CK2alpha catalytic subunit and CK2beta subunit were demonstrated in vitro and in vivo. We further found that CK2alpha can only interact with the C-terminal kinase domain of MSK1. Using site-directed mutagenesis assay and mass spectrometry, we identified five sites in the MSK1 C-terminus that could be phosphorylated by CK2 in vitro: Ser757, Ser758, Ser759, Ser760 and Thr793. Of these, Ser757, Ser759, Ser760 and Thr793 were previously unknown.

A novel method of protein extraction from perennial Bupleurum root for 2-DE.

The perennial Bupleurum root is thick and woody and contains high levels of interfering compounds. Common protein extraction methods have proved refractory towards the isolation of proteins suitable for 2-DE, due to the presence of interfering compounds. A novel method for extracting proteins suitable for 2-DE was established to overcome these problems. The main characteristic of this protocol is the partitioning of the proteins into the aqueous (fraction A-2), chloroform and isoamyl alcohol phases (A-3), and the interphase (A-1). The proteins are then extracted from each of these phases. From A-1, 85% (extracted protein against total proteins) proteins could be extracted and purified. For fraction A-2, a novel phenol extraction step is employed for the extraction of proteins. Based on the well-resolved 2-DE patterns, our protein preparation is free of interfering compounds. Using these methods (A-1, A-2, and A-3-3), a total of 3662 (1526 + 1128 + 1008) spots could be separated, and a protein yield of about 1.41 mg per 1.0 g fresh root material was obtained. To our knowledge, this is the first time that a protocol for protein extraction from perennial Bupleurum root has been reported that gives reproducible results. The protocol is expected to be applicable to other recalcitrant plant tissues as well.