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Trehalase (Treh) hydrolyzes trehalose to generate glucose and it plays important role in many physiological processes. Acetyl-CoA, the precursor of sex pheromone biosynthesis in the pheromone gland (PG) of Helicoverpa armigera, originates from glucose during glycolysis. However, the function of Treh in sex pheromone biosynthesis remains elusive. In the present study, H. armigera was used as a model to investigate the function of two Trehs (Treh1 and Treh2) in sex pheromone biosynthesis. Results demonstrated that knockdown of HaTreh1 or HaTreh2 in female PGs led to significant decreases in Z11-16:Ald production, female ability to attract males, and successful mating proportions. Pheromone biosynthesis activating neuropeptide (PBAN) treatment triggered HaTreh1 and HaTreh2 activities in the isolated PGs and Sf9 cells. However, the activities of HaTreh1 and HaTreh2 triggered by PBAN were offset by H-89, the specific inhibitor of protein kinase A (PKA). Furthermore, the H-89 treatment significantly decreased the phosphorylation level of Trhe2, which was induced by PBAN. In addition, sugar feeding (5% sugar) increased the enzyme activities of Treh1 and Treh2. In summary, our findings confirmed that PBAN activates Treh1/2 activities by recruiting cAMP/PKA signalling, promotes glycolysis to ensure the supply of acetyl-CoA, and ultimately facilitates sex pheromone biosynthesis and mating behaviour.

The toxicity of organophosphate esters (OPEs) on embryonic development is well noted in animal experiments, but epidemiological studies are still lacking. This study evaluated the prenatal exposure of OPEs and its trimester-specific and gender-specific effects on fetal growth. The correlations between OPE exposure and fetal growth were investigated by linear mixed-effect models and multivariable linear regression analyses. Prenatal exposure to tributyl phosphate (TBP) was negatively associated with a

It is of great significance to develop a dietary intervention strategy to prevent inflammatory bowel disease (IBD). A millet-rich diet can ameliorate IBD, but the active ingredients and mechanisms remain to be studied. Our results showed that the oral administration of foxtail millet protein hydrolysates (FMPH) reduced the disease activity index (DAI) score and improved the colon symptoms of dextran sulfate sodium (DSS)-induced colitis mice. FMPH reduced the serum LPS level, increased intestinal ZO-1 and occludin expression, inhibited NF-κB phosphorylation, and reduced the levels of TNF-α and IL-6. Further, FMPH inhibited Th17 cell differentiation, and inhibited inflammasome activation and IL-1β expression through the NLRP3/ASC/caspase-1 pathway. The results on Caco-2 cells confirmed the role of FMPH on tight junction and inflammasomes activation. A total of 2620 peptides were identified in FMPH by UPLC-MS/MS, of which 22 peptides were predicted as potential biopeptides, and the key sequences were LPF, ANP, PY, YW, and IPP. This study supports the effect of a diet rich in millet on the improvement of IBD and provides a scientific basis for the use of millet protein as a functional food to improve intestinal inflammation.

Background UV filters are emerging contaminants with endocrine disrupting effects, but little is known about their health effects, especially for children. Objective To assess the association between multiple organic UV filters exposure and adiposity measures and by gender in peripubertal children. Methods This prospective follow-up study included 327 children aged 7–15 years old. Urinary organic UV filters including benzophenone derivatives (BP-2, BP-3), octyl dimethyl para-aminobenzoic acid (OD-PABA), ethylhexyl methoxycinnamate (EHMC) and its metabolite (4-MCA and 4′-MAP) were quantified. Six adiposity biometrics including height, weight, waist and hip circumferences, and triceps and subscapular skinfold thickness were measured with 1.5-year duration. The Bayesian kernel machine regression method was used to estimate the associations of UV filters mixture with adiposity measurements, and longitudinal analyses were then considered to further evaluate the associations between individual UV filters and trajectories of growth development using linear mixed models or generalized linear mixed models. Results Exposure to mixture of UV filters was negatively associated with most adiposity measurements, with a reduction of 1.399 kg/m2 (95% CI: −2.246 to −0.551 kg/m2) in BMI, 0.674 (95% CI: −1.045 to −0.304) in BMI z-score, 0.033 BF% (95% CI: −0.053 to −0.013), and 2.301 mm (95% CI: −3.823 to −0.78) in subscapular skinfold thickness at baseline, comparing the 75th percentile to the 25th level of UV filters mixture exposure. Consistent associations were found at follow-up. Both baseline and follow-up results suggested that EHMC was identified as the most important contributor to lower adiposity measurements, which was also confirmed by linear mixed models in longitudinal analyses. No significant effects were found in girls. Conclusion This study found that childhood organic UV filters exposure was negatively associated with adiposity measures in peripubertal boys, but not girls.

Background Chronic obstructive pulmonary disease (COPD) is mainly induced by the increased content of particulate matter 2.5 (PM2.5) in the atmosphere. This study aimed to evaluate the effects of betulinic acid derivative on lung inflammation in a mouse model of chronic obstructive pulmonary disease induced by particulate matter 2.5. Material/Methods The mice were given a PM2.5 (25 μl) suspension for 7 days by the intranasal route to establish a COPD model. The content of TNF-α and IL-6 in the BALF samples was measured by commercially available ELISA kits. Results The PM2.5-induced higher LDH and ACP levels were significantly alleviated in mouse lung tissues by treatment with betulinic acid derivative. Treatment with betulinic acid derivative also suppressed PM2.5-induced increase in AKP and ALB levels in mouse lung tissues. Betulinic acid derivative reversed PM2.5-mediated suppression of SOD activity and elevation of NOS level in mouse BALF. Moreover, the PM2.5-induced excessive NO and MDA levels in mouse BALF were significantly reduced (P

Assessments for groundwater quality and potential health risk are significant for better utilization and exploitation. In the present study, seventy groundwater samples were collected from domestic tube wells and public water-supply wells in the Nanchong area, southwestern China. The integration of statistical analysis, ion correlation, geomodelling analysis, entropy water quality index and health risks assessment were compiled in this study. Statistical analysis indicated the cations followed the concentration order as Ca2+ > Na+ > Mg2+ > K+, while anions' concentrations were HCO3- > SO42- > Cl- > NO3- > F- based on Box and Whisker plot. Piper triangle diagram proposed the hydrochemical type was characterized as Ca-HCO3. Correlations of ions and geomodelling revealed the concentrations of major ions were mainly determined by calcite dissolution and ion exchange process and NO3- concentrations were controlled by agriculture activities. Entropy water quality index computation demonstrated that 96% of groundwater samples possessed the EWQI values of 29-95, and thus were suitable for drinking purpose. The HITotal values for 66% groundwater samples exceeded the acceptable limit for non-carcinogenic risk (HI =1) for infants, followed by 41% for children, 37% for adult males, and 30% for adult females. The non-carcinogenic human health risk of different population groups followed the order of infants > children > adult males > adult females. In future, targeted measures for human health risks of NO3- will focus on the improvements for agricultural activities, including reducing the use of nitrogenous fertilizer, changing irrigation pattern, etc. Our study provides the vital knowledge for groundwater management in the Nanchong and development of the Cheng -Yu Economic Circle.

Although previous studies have reported the adverse effect of air pollution exposure during pregnancy on neurodevelopment in children, epidemiological evidence is limited, and the results are inconsistent. This study aimed to explore the association between prenatal ambient fine particulate matter (PM2.5) exposure and early childhood neurodevelopment in a large birth cohort study of 4009 maternal-child pairs. Prenatal daily PM2.5 exposure concentrations at 1 km spatial revolution were estimated using high-performance machine-learning models. Neurodevelopmental outcomes of children at ages 2, 6, 12, and 24 months were assessed using the Ages and Stages Questionnaire (ASQ). Distributed lag nonlinear models were used to identify critical windows of prenatal PM2.5 exposure. General linear mixed models with binomially distributed errors were used to estimate the effect of prenatal PM2.5 exposure on suspected developmental delay (SDD) in five developmental domains based on the longitudinal design. Prenatal PM2.5 exposure was significantly associated with decreased scores for all neurodevelopmental domains of children at ages 2, 6, and 24 months. Each 10-μg/m3 increase in PM2.5 exposure was significantly associated with increased risk of SDD for all subjects (RR: 1.52 95% CI: 1.19, 2.03), specifically, in problem-solving domain for girls (RR: 2.23, 95% CI: 1.22, 4.35). Prenatal PM2.5 exposure in weeks 18 to 34 was significantly associated with both ASQ scores and SDDs. Our study proposed that prenatal PM2.5 exposure affected early childhood neurodevelopment evaluated with the ASQ scale. PM2.5 exposure might increase the risk of SDD for boys and girls, specifically in the problem-solving domain for girls.

Background: UV filters, widely used in personal care and industrial products, are being found in the environment and, in humans where with limited understanding on their potential health effects, especially during puberty. Objectives: To examine the association between UV filter exposure and pubertal development in a prospective follow-up study. Methods: This study included 521 elementary and high school students from a suburban area of Shanghai. The initial study was done in October to November 2011; the follow-up study in April to May 2013. Twelve urinary organic UV filters were quantified, and the pubertal development was assessed at each study period by trained physicians using Tanner staging. We used (ordered) logistic regression model and multilevel mixed-effect (ordered) logistic regression model to assess cross-sectional and longitudinal effects between urinary concentration of five major UV filters and pubertal development of stages, onset and pace. Results: Ethylhexyl methoxycinnamate (EHMC) and its metabolite 4′-methoxyacetophenone (4′-MAP), two benzophenone derivatives (BP-2, BP-3) and Ethylhexyl dimethyl PABA (OD-PABA) were the most extensively detected UV filters in urine with geometric means (95% CI) in 2010 and 2012 as 1.77 (1.599, 1.956) and 2.28 (1.985, 2.622) ng/mL for EHMC; 4.55 (4.219, 4.907) and 5.26 (4.783, 5.775) ng/mL for 4′-MAP; 4.38 (4.011, 4.774) and 5.74 (5.023, 6.562) ng/mL for BP-2; 0.83 (0.760, 0.903) and 1.09 (0.967, 1.220) ng/mL for BP-3; 5.37 (4.949, 5.820) and 5.80 (5.193, 6.486) pg/mL for OD-PABA. Significant trend P-values (P

Objective: Metabolomics may unravel global metabolic changes in response to environmental exposures and identify important biological pathways involved in the pathophysiology of childhood obesity. Phthalate has been considered an obesogen and contributing to overweight and obesity in children. The purpose of this study is to evaluate changes in urine metabolites in response to the environmental phthalate exposure among overweight or obese children, and to investigate the metabolic mechanisms involved in the obesogenic effect of phthalate on children at puberty. Methods: Within the national Puberty Timing and Health Effects in Chinese Children (PTHEC) study, 69 overweight/obese children and 80 normal weight children were selected into the current study according to their puberty timing and WGOC (The Working Group for obesity in China) references. Urinary concentrations of six phthalate monoesters (MMP, MEP, MnBP, MEHP, MEOHP and MEHHP) were measured using API 2000 electrospray triple quadrupole mass spectrometer (ESIMS/MS). Metabolomic profiling of spot urine was performed using gas chromatography-mass spectrometry. Differentially expressed urinary metabolites associated with phthalate monoesters exposure were examined using orthogonal partial least square-discriminant analysis and multiple linear regression models. In addition, the candidate metabolites were regressed to obesity indices with multiple linear regression models and logistic regression models in all subjects. Results: Compared with normal weight children, higher levels of MnBP were detected in urinary samples of children with overweight and obesity. After adjusting for confounders including chronological age, gender, puberty onset, daily energy intake and physical activity and socio-economic level, positive association remained between urinary MnBP concentration and childhood overweight/obesity [OR = 1.586, 95% CI:1.043,2.412]. We observed elevated MnBP concentration was significantly correlated with increased levels of monostearin, 1-monopalmitin, stearic acid, itaconic acid, glycerol 3-phosphate, 5-methoxytryptamine, kyotorphin, 1-methylhydantoin, d-alanyl-d-alanine, pyrrole-2-carboxylic acid, 3,4-Dihydroxyphenylglycol, and butyraldehyde. Meanwhile, increased MnBP concentration was also significantly correlated with decreased levels of lactate, glucose 6-phosphate, d-fructose 6-phosphate, palmitic acid, 4-acetamidobutyric acid, l-glutamic acid, n-acetyl-l-phenylalanine, iminodiacetic acid, hydroxyproline, pipecolinic acid, l-ornithine, n-acetyl-l-glutamic acid, guanosine, cytosin, and (s)-mandelic acid in the normal weight subjects. The observations indicated that MnBP exposure was related to global urine metabolic abnormalities characterized by disrupting arginine and proline metabolism and increasing oxidative stress and fatty acid reesterification. Among the metabolic markers related to MnBP exposure, 1-methylhydantoin, pyrrole-2-carboxylic acid and monostearin were found to be positively correlated with obesity indices, while hydroxyproline, l-ornithine, and lactate were negatively associated with overweight/obesity in children. Conclusions: Our results suggested that the disrupted arginine and proline metabolism associated with phthalate exposure might contribute to the development of overweight and obesity in school-age children, providing insights into the pathophysiological changes and molecular mechanisms involved in childhood obesity. Keywords: Phthalate, Childhood overweight/obesity, Metabolic profiles, Arginine and proline metabolism

Outbreaks of avian influenza virus continue to pose threats to human health. Animal models such as the mouse, ferret, and macaque are used to understand the pathogenesis of avian influenza virus infection in humans. We previously reported that the tree shrew (Tupaia belangeri, family Tupaiidae), which is regarded as a “low-level primate”, has α2,3- and α2,6-linked sialic acid receptor distributions similar to those of humans and is potentially a useful mammalian model for studying mild human influenza (H1N1) virus infection. In this study, we used the tree shrew experimental model to investigate the pathogenesis of avian influenza A (H9N2) virus infection and the effect of the E627K mutation in the PB2 gene, an adaptation to mammalian hosts. Evidence of disease, virus titers in the upper and lower respiratory tract, histopathology and induction of proinflammatory cytokines are described. We also established ex vivo culture models of tree shrew respiratory tissues to study the tropism and replication of the H9N2 virus. Our results demonstrated that the tree shrew is a viable new in vivo experimental model for avian influenza research that provides results comparable to those observed in ferrets. The disease spectrum and pathogenesis in tree shrews correlate well with what is observed in humans.

Triptolide (TP), a primary bioactive ingredient isolated from the traditional Chinese herbal medicine Tripterygium wilfordii Hook. F. (TWHF), has attracted great interest for its therapeutic biological activities in inflammation and autoimmune disease. However, its clinical use is limited by severe testicular toxicity, and the underlying mechanism has not been elucidated. Our preliminary evidence demonstrated that TP disrupted glucose metabolism and caused testicular toxicity. During spermatogenesis, Sertoli cells (SCs) provide lactate as an energy source to germ cells by glycolysis. The transcription factors GATA-binding protein 4 (GATA4) and specificity protein 1 (Sp1) can regulate glycolysis. Based on this evidence, we speculate that TP causes abnormal glycolysis in SCs by influencing the expression of the transcription factors GATA4 and Sp1. The mechanism of TP-induced testicular toxicity was investigated in vitro and in vivo. The data indicated that TP decreased glucose consumption, lactate production, and the mRNA levels of glycolysis-related transporters and enzymes. TP also downregulated the protein expression of the transcription factors GATA4 and Sp1, as well as the glycolytic enzyme phosphofructokinase platelet (PFKP). Phosphorylated GATA4 and nuclear GATA4 protein levels were reduced in a dose- and time-dependent manner after TP incubation. Similar effects were observed in shGata4-treated TM4 cells and BALB/c mice administered 0.4 mg/kg TP for 28 days, and glycolysis was also inhibited. Gata4 knockdown downregulated Sp1 and PFKP expression. Furthermore, the Sp1 inhibitor plicamycin inhibited PFKP protein levels in TM4 cells. In conclusion, TP inhibited GATA4-mediated glycolysis by suppressing Sp1-dependent PFKP expression in SCs and caused testicular toxicity.

The aim of the study was to determine whether applying an assistance force to the pelvis and legs during treadmill training can improve walking function in children with cerebral palsy.Twenty-three children with cerebral palsy were randomly assigned to the robotic or treadmill only group. For participants who were assigned to the robotic group, a controlled force was applied to the pelvis and legs during treadmill walking. For participants who were assigned to the treadmill only group, manual assistance was provided as needed. Each participant trained 3 times/wk for 6 wks. Outcome measures included walking speed, 6-min walking distance, and clinical assessment of motor function, which were evaluated before, after training, and 8 wks after the end of training, and were compared between two groups.Significant increases in walking speed and 6-min walking distance were observed after robotic training (P = 0.03), but no significant change was observed after treadmill training only. A greater increase in 6-min walking distance was observed after robotic training than that after treadmill only training (P = 0.01).Applying a controlled force to the pelvis and legs, for facilitating weight-shift and leg swing, respectively, during treadmill training may improve walking speed and endurance in children with cerebral palsy.Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) discuss the importance of physical activity at the participation level (sports programs) for children with cerebral palsy; (2) contrast the changes in walking ability and endurance for children in GMFCS level I, II and III following sports programs; and (3) identify the impact of higher frequency of sports program attendance over time on walking ability.Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

The early postnatal period is the most dynamic and vulnerable stage in the assembly of intestinal microbiota. Antibiotics are commonly prescribed to newborn preterm babies and are frequently used for a prolonged duration in China. We hypothesized that the prolonged antibiotic therapy would affect the early development of intestinal microbiota and their metabolites. To test this hypothesis, we analyzed the stool microbiota and metabolites in 36 preterm babies with or without antibiotic treatment. These babies were divided into three groups, including two groups treated with the combination of penicillin and moxalactam or piperacillin-tazobactam for 7 days, and the other group was free of antibiotics. Compared to the antibiotic-free group, both antibiotic-treated groups had distinct gut microbial communities and metabolites, including a reduction of bacterial diversity and an enrichment of harmful bacteria such as Streptococcus and Pseudomonas. In addition, there was a significant difference in the composition of gut microbiota and their metabolites between the two antibiotic-treated groups, where the piperacillin-tazobactam treatment group showed an overgrowth of Enterococcus. These findings suggest that prolonged antibiotic therapy affects the early development of gut microbiota in preterm infants, which should be considered when prescribing antibiotics for this population.

Background Currently, Staphylococcus aureus is one of the most important pathogens worldwide, especially for methicillin-resistant S. aureus (MRSA) infection. However, few reports referred to patients’ MRSA infections in Yunnan province, southwest China. Methods In this study, we selected representative MRSA strains from patients’ systemic surveillance in Yunnan province of China, performed the genomic sequencing and compared their features, together with some food derived strains. Results Among sixty selective isolates, forty strains were isolated from patients, and twenty isolated from food. Among the patients’ strains, sixteen were recognized as community-acquired (CA), compared with 24 for hospital-acquired (HA). ST6-t701, ST59-t437 and ST239-t030 were the three major genotype profiles. ST6-t701 was predominated in food strains, while ST59-t437 and ST239-t030 were the primary clones in patients. The clinical features between CA and HA-MRSA of patients were statistical different. Compared the antibiotic resistant results between patients and food indicated that higher antibiotic resistant rates were found in patients’ strains. Totally, the average genome sizes of 60 isolates were 2.79 ± 0.05 Mbp, with GC content 33% and 84.50 ± 0.20% of coding rate. The core genomes of these isolates were 1593 genes. Phylogenetic analysis based on pan-genome and SNP of strains showed that five clustering groups were generated. Clustering ST239-t030 contained all the HA-MRSA cases in this study; clustering ST6-t701 referred to food and CA-MRSA infections in community; clustering ST59-t437 showed the heterogeneity for provoking different clinical diseases in both community and hospital. Phylogenetic tree, incorporating 24 isolates from different regions, indicated ST239-t030 strains in this study were more closely related to T0131 isolate from Tianjin, China, belonged to ‘Turkish clade’ from Eastern Europe; two groups of ST59-t437 clones of MRSA in Yunnan province were generated, belonged to the ‘Asian-Pacific’ clone (AP) and ‘Taiwan’ clone (TW) respectively. Conclusions ST239-t030, ST59-t437 and ST6-t701 were the three major MRSA clones in Yunnan province of China. ST239-t030 clonal Yunnan isolates demonstrated the local endemic of clone establishment for a number of years, whereas ST59-t437 strains revealed the multi-origins of this clone. In general, genomic study on epidemic clones of MRSA in southwest China provided the features and evolution of this pathogen.

Background: Polybrominated diphenyl ethers (PBDEs) are environmental chemicals with harmful effects on pregnancy, but their effects on adverse developmental outcomes are not fully understood. The placental DNA methylation is strongly influenced by prenatal environmental factors and has been linked to fetal growth. Objective: To evaluate the association between in utero PBDEs exposure, placental DNA methylation changes (growth regulatory genes), and pathophysiology of fetal growth (birth outcomes, fetal growth retardation) in a population-based pregnancy cohort study. Methods: This was a nested case-control study within the prospective Wenzhou Birth Cohort including 130 fetal growth retardation (FGR) cases and 130 healthy controls and their mothers recruited from June 2016 to June 2017. FGR was diagnosed based on the comprehensive evaluation of ultrasound results at 24, 28, and 32 weeks of gestation. Neonatal birth measurements were obtained from medical records. Gestational exposure to 19 PBDEs, including 13 lower BDE congeners (BDE-17–190) and 6 higher brominated BDE congeners (BDE-196–209), were determined by gas chromatography tandem mass spectrometry in the umbilical cord blood. Placental DNA methylation changes of one repetitive element (LINE1) and two candidate genes (HSD11B2, IGF2) were characterized by quantitative polymerase chain reaction-pyrosequencing. Multiple linear regression and logistic regression models were used to examine the associations among PBDEs exposure, fetal growth indicators, and DMR (differential methylation region) methylation fractions. Sobel tests were conducted to assess DNA methylation as a mediator in multivariate models. Results: After excluding women who withdrew from the study or were lost to follow-up or failed to provide placenta or umbilical cord blood, 249 mother-newborn pairs (124 FGR cases, 125 controls) were included in the final analysis. Elevated BDE-206 (OR: 1.569, 95% CIs: 1.053–2.338), BDE-17–190 (OR: 2.860, 95% CIs: 1.233–6.634), BDE-196–209 (OR: 1.688, 95% CIs: 1.024–2.783) and ∑19PBDEs (OR: 2.387, 95% CIs: 1.220–4.668) concentrations were associated with increased risk of FGR in newborns. FGR birth was also associated with increased DNA methylation of HSD11B2 (OR: 1.145, 95% CIs: 1.032–1.270) and decreased DNA methylation of IGF2 (OR: 0.892, 95% CIs: 0.845–0.941). In addition, BDE-17–190 showed significant associations with DNA methylation of HSD11B2 and IGF2 (β: 1.127, 95% CIs: 0.069–2.186; β: −3.452, 95% CIs: −5.512–1.392), indicating placental DNA methylation changes of HSD11B2 and IGF2 were related to both lower BDE congeners exposure and fetal growth. Further mediation analyses showed that IGF2 methylation mediated about 40% of the effects of BDE-17–190 in umbilical cord blood on neonatal FGR. Conclusion: We report an inverse association between in utero exposures to PBDEs and fetal growth and provide evidence supporting epigenetic gene plasticity in these associations. Changes in placental DNA methylation might be part of the underlying biological pathway between prenatal PBDEs exposure and adverse fetal growth. Keywords: PBDEs, DNA methylation, Fetal growth, Fetal growth restriction, Placenta

Knowledge of the origins of polycyclic aromatic hydrocarbon (PAH) in vegetables is essential to reduce human health risks induced by dietary exposure. The current study developed a vegetation-advanced multimedia model, SESAMe-Veg, to identify the major uptake pathway of 15 priority PAHs in vegetables and assess the PAHs in edible parts of cabbages and carrots in Jinzhong City, Shanxi Province, China. The model was well evaluated against site- and plant-specific measurements. Edible parts exhibited lower PAH concentrations than the other parts for both vegetables. The estimated concentrations of ΣPAH15 were 79 ng/g in cabbage shoots and 83 ng/g in carrot roots. Higher concentrations were estimated in shoots of the leafy vegetable than in roots of the root vegetable for most PAHs. Although air-shoot is the major transport pathway, 98% was deposition of particles, which was attached outside and could be removed relatively easily by washing. Soils might be the origin of PAHs inside vegetables, especially for lighter PAHs. PYR was more likely to be stored in roots than other congeners. The translocation of PAHs inside vegetables was negligible. Adulthood dietary exposure to local vegetables probably caused a high health risk; however, contributions from consuming cabbages and especially carrots were low. Females generally exhibited slightly higher risks than males of exposure to PAHs in local vegetables. Considering the dominant role of particle deposition, carefully vegetable washing before ingestion could reduce this risk. This study has provided a functional tool to evaluate vegetable contamination by PAHs. Capsule A vegetation-advanced multimedia model of PAHs in different parts of vegetables and other environmental media was developed to evaluate the potential health risk to local populations of different sexes and ages via vegetable ingestion.

To determine whether repeat exposure to force perturbations during treadmill training can induce long-term retention of improved step length and overall improvements in locomotor function in persons with spinal cord injury.Fourteen patients with spinal cord injury were recruited and randomly assigned to swing resistance or swing assistance training groups. A controlled swing resistance or assistance force, for resistance or assistance training groups, respectively, was applied to both legs through a cable-driven robotic system during treadmill training. Each participant trained 3 times per week for 6 weeks. Step length, walking speed, 6-minute walking distance, and other clinical assessments were evaluated before and after 6 weeks of training and 8 weeks after the end of training.A significant increase in step length was observed after 6 weeks of resistance training (P = 0.04). Step length tended to increase after assistance treadmill training, but the change was not significant (P = 0.18). The changes in step length and functional gains had no significant difference between 2 groups.Repeat exposure to swing resistance during treadmill training may induce a prolonged retention of increased step length, although it remains unclear whether swing resistance versus assistance is more effective in inducing increased step length.

This study was designed to assess the effect of lactational polybrominated diphenyl ether (PBDE) exposure on early physical development of both healthy and fetal growth restriction (FGR) infants. Z scores of head circumference-for-age (ZHC), length-for-age (ZLEN), weight-for-age (ZWEI) and weight-for-length (ZWFL) were calculated according to the WHO Child Growth Standards. FGR infants had a higher PBDE exposure level and faster growth speed from 42 days to 6 months compared with healthy infants. Exposure of lower brominated BDEs (BDE28∼154) and the sum of 18 BDE congeners (BDE28∼209) negatively associated with ZHC [mean difference estimate (95 % CI): -0.71 (-1.22, -0.22) and -0.81 (-1.31, -0.33)] in FGR boys. Both BDE153 and BDE196 exposure had a significant correlation with ZLEN of boys in FGR group [mean difference estimate (95 % CI): -0.28 (-0.48, -0.07) and -0.52 (-0.91, -0.14)]. Each 10 ng/g lipid increase in the concentrations of BDE154 were respectively associated with 0.16 increase in ZWEI among boys in healthy group. No significant association was found in girls. Lactational PBDE exposure had effects on the early growth of both FGR and healthy infants. The encouragement of breastfeeding should therefore be considered in conjunction with PBDE contamination levels.

The synthesis, evaluation, and structure-activity relationships of a class of acyl guanidines which inhibit the BACE-1 enzyme are presented. The prolinyl acyl guanidine chemotype (7c), unlike compounds of the parent isothiazole chemotype (1), yielded compounds with good agreement between their enzymatic and cellular potency as well as a reduced susceptibility to P-gp efflux. Further improvements in potency and P-gp ratio were realized via a macrocyclization strategy. The in vivo profile in wild-type mice and P-gp effects for the macrocyclic analog 21c is presented.

It remains unknown how fine particulate matter (PM2.5) constituents affect differently the fractional concentration of exhaled nitric oxide (FeNO, a biomarker of airway inflammation) and the DNA methylation of its encoding gene (NOS2A). We aimed to investigate the short-term effects of PM2.5 constituents on NOS2A methylation and FeNO. We designed a longitudinal study among chronic obstructive pulmonary disease (COPD) patients with six repeated health measurements in Shanghai, China. We applied linear mixed-effect models to evaluate the associations. We observed that the inverse association between PM2.5 and methylation at position 1 was limited within 24 h, and the positive association between PM2.5 and FeNO was the strongest at lag 1 day. Organic carbon, element carbon, NO3(-) and NH4(+) were robustly and significantly associated with decreased methylation and elevated FeNO. An interquartile range increase in total PM2.5 and the four constituents was associated with decreases of 1.19, 1.63, 1.62, 1.17, and 1.14 in percent methylation of NOS2A, respectively, and increases of 13.30%,16.93%, 8.97%, 18.26%, and 11.42% in FeNO, respectively. Our results indicated that organic carbon, element carbon, NO3(-) and NH4(+) might be mainly responsible for the effects of PM2.5 on the decreased NOS2A DNA methylation and elevated FeNO in COPD patients.

Background: Phthalates are synthetic chemicals and ubiquitous environmental contaminants, with hormonal activity that may alter the course of pubertal development in children. Objectives: To determine whether exposure to phthalate metabolites is associated with timing of pubertal development in a cross-sectional study of a school-based clustered sample of 503 children from a suburban district in Shanghai, China, who were 7–14 years of age at enrollment (2010 October to November). Methods: We analyzed six phthalate metabolites in urine samples by isotope-dilution liquid chromatography tandem mass spectrometry. The associations of exposures to phthalates with pubertal timing of testes, breast, and pubic hair development (represented as Tanner stages) were evaluated using an ordered logistic regression model adjusted for chronological age, body fat proportion (BF%), and parental education. Results: In boys, urinary mono-n-butyl phthalate (MBP) levels were negatively associated with testicular volume, and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) levels were negatively associated with pubic hair stages. The odds of being in an advanced stage were decreased by 43%–51%. In girls, mono (2-ethylhexyl) phthalate (MEHP), MEHHP, and MEOHP levels, as well as the sum of these levels, were positively associated with breast stages, and the association was much stronger in girls with high BF%; the odds of being in an advanced stage were increase by 29% to 50%. Conclusions: Phthalate metabolites investigated in this study show significant associations with pubertal timing both in boys and in girls, especially among girls with high BF%.

Background A large body of evidence has shown that phthalate exposure can lower birth weight in animals and human beings. However, there are only limited data on whether phthalates could affect birth weight directly or indirectly through gestational age and pregnancy syndrome. Objectives To evaluate the effects of prenatal exposure to phthalates on birth weight in neonates and the mediation effects of gestational age and pregnancy syndrome on the association between phthalate exposure and birth weight. Methods In this study, 181 mother-newborn pairs were recruited from Wenzhou city. Maternal urine samples were collected during the third trimester and measured for phthalate metabolites by ESI-MS/MS. Structural equation models (SEMs) were used to evaluate effects of phthalate on birth weight controlling for maternal education, monthly income, nutritional supplements, infant gender, and maternal weight gain per week. The potential mediated effects of phthalate exposure through gestational age and pregnancy syndrome on birth weight were also calculated by structural equation modeling. Results After adjusting for potential confounders, urinary mono-phthalate levels (including MMP, MBP, MEHP, MEOHP, and MEHHP) were negatively associated with birth weight. A ten-fold increase in the concentration of MEOHP and MEHHP would be directly associated with lower birth weights (reduced to 124 g and 107 g, respectively). However, MBP had mediated effects on birth weight through gestational age, which was associated with an 85-g reduction in birth weight for every ten-fold increase in exposure. Both direct and mediated effects on birth weight were found in MMP and MEHP. The indirect effects of MMP and MEHP were mediated through gestational age and pregnancy syndrome. Thus, prenatal MMP and MEHP exposures were associated with decrease in birth weight. Conclusions A negative association exists between prenatal phthalate exposure and birth weight in Chinese neonates. In addition to direct pathway, phthalate exposures could affect birth weight through the mediated effects of gestational age and pregnancy syndrome.

Maternal exposure to particulate matter with aerodynamic diameter

The determination of Prostaglandin (PG) E1 in plasma is challenged by its low concentration (pg/mL) and endogenous interference. An LC-MS/MS method for the determination of PGE1 in dog plasma has been developed and validated. Plasma being sampled at 4°C and treated with indomethacin effectively inhibited interferents synthesized post-sampling. Samples were subjected to one-step extraction and separated by reversed phase HPLC with a short cycle time of 3min. An LLOQ of 10pg/mL was achieved with 500μl plasma. The method was applied to a pharmacokinetic study in beagle dogs involving an intravenous infusion of 3.2μg/kg PGE1. The half-life was recovered at 7min. The simple, sensitive and rapid method was suitable to be applied to pharmacokinetic studies of PGE1 at clinically relevant doses.

Falls and their consequences are among the major health care problems affecting functional mobility and quality of life among older people. Even for people living independently in the community, falls are common occurrences (1,2). Although the causes of falls are varied and complex, a critical requirement needed for fall prevention is the ability to respond effectively to loss of balance. Protective stepping, an automatic reaction to instability, is a common strategy for maintaining balance in the everyday environment (3). Stepping is not a strategy of last resort but is often initiated well before the body approaches the limits of stability provided by the base of support (4) especially for older people (5,6). To effectively sustain standing balance, steps must be appropriately directed, timed, and executed to arrest the motion of the body center of mass by altering the base of support. Mounting evidence indicates that age-associated impairments in protective stepping contribute importantly to loss of balance and falls (3,6–8). An impaired ability to maintain lateral balance stability is especially relevant to falls among older people. For example, measures of mediolateral stability are associated with future falls (9) and past falls (10), and impaired control of lateral balance through stepping is particularly apparent for older adults (6,11,12). Furthermore, age-related falls often involve lateral body motion and associated hip fractures (13,14). Therefore, these observations underscore the specific challenges to maintaining balance and preventing falls that are linked with deficits in controlling lateral balance stability. Although there is accumulating support for the existence of a directional vulnerability to lateral instability and falls with aging, comprehensive and systematic investigations of this postulation are currently lacking. The aims of this study were (i) to determine the protective stepping response patterns evoked by different directions of externally applied waist-pull perturbations of standing balance and (ii) to identify the changes in stepping characteristics attributable to aging and in relation to the risk of falling. We hypothesized that the laterally oriented disturbances to balance would exacerbate the changes with age in protective stepping responses due to the increased demands for controlling lateral stability, and that these changes would be greater for those individuals who subsequently experienced falls.

There is increasing evidence that cadmium (Cd) exposure can cause male subfertility and even complete infertility in mammals. Long noncoding (lnc) RNAs are critical for spermatogenesis, and their dysregulation might lead to male infertility. However, whether they are involved in Cd-induced subfertility is unknown. Here we found that intraperitoneal exposure to Cd in mice led to male subfertility indicated by reductions in testicular sperm production and motility, and by abnormal morphology. Testicular and sperm RNAs were used to investigate lncRNA expression profiles by strand-specific RNA sequencing at the transcriptome level to help determine any RNA-related mechanisms in Cd-induced subfertility. The Cd-treated testes and spermatozoa exhibited aberrant expression profiles for lncRNAs and mRNAs. Of the lncRNAs, there were 139 with upregulated expression and 174 with downregulated expression in testes; in contrast, 685 were upregulated and 375 were downregulated in spermatozoa. For mRNA expression, 214 were upregulated and 226 were downregulated in testes; 272 were upregulated and 111 were downregulated in spermatozoa. Gene ontology and pathway analyses showed that the functions of differentially expressed lncRNA targets and mRNAs were closely linked with many processes involved in spermatogenesis. Additionally, many newly identified lncRNAs showed inducible expression, suggesting that they might be good candidate markers for Cd-induced male reproductive toxicity. This study provides a preliminary database for further exploring lncRNA-related mechnisms in male infertility induced by Cd.

di(2-ethylhexyl) phthalate (DEHP) is one of the most commonly-used plasticizers and can exert estrogen-like effects and anti-androgen-like effects after entering the body. The critical windows for DEHP exposure are in utero and during lactation. There's substantial evidence that hormonally active environmental estrogen perturbations in early life are associated with prostate carcinogenesis susceptibility later in life. In order to explore the effects of in utero and lactational exposure to DEHP on the male offspring's susceptibility to prostate carcinogenesis, we established a rat model of developmental estrogenization: pregnant rats in three treatment groups were treated with DEHP at 0.01, 0.1 and 1mg/kg BW/day from GD7 to PND21, and the male pups in positive group were treated with EB at 25ug/pup on PND 1, 3, 5. In order to induce the prostate carcinogenesis, half of the male offspring were given implants packed with estradiol and testosterone, and the other half were given empty tubes on PND90. The prostate weight, concentration of PSA in serum and histopathological changes were measured in male offspring on PND196. Data was analyzed by one-way analysis of variance (ANOVA) and x2 using SPSS Statistics software. Results showed that in utero treatment of DEHP decreased the prostate weight, prostate/body weight ratio and increased PSA concentrations of male pups in a dose-dependent manner. Compared with non-T+E treatment groups, T+E treatment increased the prostate weight and ratio of prostate/body weight, as well as the concentration of PSA. The results of prostate carcinogenesis parameters including PIN scores/frequency and Gleason scores/frequency were consistent with PSA, which meant that in utero and lactational exposure of DEHP was a risk factor of prostate carcinogenesis, and the increased estrogen/testosterone (E/T) ratio in adult might exert synergistic effects in the process of prostate carcinogenesis formation.

Background: In utero polybrominated diphenyl ethers (PBDEs) exposure has been associated with adverse fetal growth. Alterations in placental DNA methylation might mediate those adverse effects. Objectives: To examine the associations between in utero PBDEs exposure and DNA methylation in human placenta. Methods: Eighty apparently healthy mother-newborn pairs delivering at the Second Affiliated Hospital of Wenzhou Medical College were enrolled in this study. Placental DNA methylation of LINE1, NR3C1 and IGF2 was measured by quantitative polymerase chain reaction-pyrosequencing. In utero PBDEs exposure was assessed by measuring umbilical cord blood PBDEs concentrations. Results: For LINE-1, higher levels of BDE-66 exposure were associated with decreased DNA methylation (β = −0.9, 95% CI, −1.8 to −0.1); For NR3C1, BDE-153 concentrations was significantly inversely associated with DNA methylation (β = −2.0, 95% CI, −3.7 to −0.2); For IGF2, elevated concentrations of both BDE-153 (β = −1.7; 95% CI, −3.0 to −0.4) and BDE-209 (β = −1.0; 95% CI, −1. 9 to −0.1) were significantly associated with decreased DNA methylation. Conclusions: We found that placental DNA methylation is associated with in utero PBDEs exposure. Changes in placental DNA methylation might be part of the underlying biological pathway between in utero PBDEs exposure and adverse fetal growth. Keywords: PBDEs, DNA methylation, Fetal growth, Placenta

International audience; During the initiation of stepping, anticipatory postural adjustments (APAs) for lateral weight transfer and propulsion normally precede the onset of locomotion. In Parkinson's disease (PD), impaired step initiation typically involves altered APA ground force production with delayed step onset and deficits in stepping performance. If, as in stance and gait, sensory information about lower limb load is important for the control of stepping, then perturbations influencing loading conditions could affect the step initiation process. This study investigated the influence of changes in lower limb loading during step initiation in patients with PD and healthy control subjects. Participants performed rapid self-triggered step initiation with the impending single stance limb positioned over a pneumatically actuated platform. In perturbation trials, the stance limb ground support surface was either moved vertically downward (DROP) or upward (ELEVATE) by 1.5 cm shortly after the onset of the APA phase. Overall, PD patients demonstrated a longer APA duration, longer time to first step onset, and slower step speed than controls. In both groups, the DROP perturbation reinforced the intended APA kinetic changes for lateral weight transfer and resulted in a significant reduction in APA duration, increase in peak amplitude, and earlier time to first step onset compared with other conditions. During ELEVATE trials that opposed the intended weight transfer forces both groups rapidly adapted their stepping to preserve standing stability by decreasing step length and duration, and increasing step height and foot placement laterally. The findings suggested that sensory information associated with limb load and/or foot pressure modulates the spatial and temporal parameters of posture and locomotion components of step initiation in interaction with a centrally generated feedforward mode of neural control. Moreover, impaired step initiation in PD may at least acutely be enhanced by augmenting the coupling between posture and locomotion.

This paper reports the development and validation of an assay for quantitation of bergenin in human plasma using liquid chromatography/tandem mass spectrometry (LC-MS/MS). Bergenin and the internal standard (I.S.), 5-bromo-2,4(1H,3H)-pyrimidinedione (5-BrU), were separated by reversed phase HPLC and quantitated by MS/MS using electrospray ionization (ESI) and multiple reaction monitoring (MRM) in the negative ion mode. The most intense [M-H](-) MRM transition of bergenin at m/z 326.9--312.3 was used for quantitation and the transition at m/z 188.9--42.2 was used to monitor 5-BrU. Stability issues with bergenin required the addition of ascorbic acid to plasma samples prior to storage and analysis within 10 days storage at -80 degrees C. The method was linear in the range 3-1000 ng/mL with intra- and inter-day precision of 3.94-5.96 and 1.62-8.31%, respectively, and accuracy2.33%. The assay was successfully applied to a pharmacokinetic study in healthy volunteers after administration of a single 250 mg oral dose.

Hilliard MJ, Martinez KM, Janssen I, Edwards B, Mille M-L, Zhang Y, Rogers MW. Lateral balance factors predict future falls in community-living older adults. Objective To prospectively determine the capacity of measures of mediolateral (ML) protective stepping performance, maximum hip abduction torque, and trunk mobility, in order to predict the risk of falls among community-living older people. Design Cross-sectional study. Setting A balance and falls research laboratory. Participants Medically screened and functionally independent community-living older adult volunteers (N=51). Interventions Not applicable. Main Outcome Measures Measures included: (1) protective stepping responses: percentage of trials with multiple balance recovery steps and sidestep/crossover step recovery patterns, and first step length following motor-driven waist-pull perturbations of ML standing balance; (2) hip abduction strength and axial mobility: (3) peak isokinetic hip abduction joint torque and trunk functional axial rotation (FAR) range of motion; and (4) fall incidence: monthly mail-in reporting of fall occurrences with follow-up contact for 1 year post-testing. One- and 2-variable logistic regression analysis models determined which single and combined measures optimally predicted fall status. Results The single variable model with the strongest predictive value for falls was the use of multiple steps in all trials (100% multiple steps) (odds ratio, 6.2; P =.005). Two-variable models, including 100% multiple steps and either hip abduction torque or FAR variables, significantly improved fall prediction over 100% multiple steps alone. The hip abduction and FAR logistic regression optimally predicted fall status. Conclusions The findings identify new predictor variables for risk of falling that underscore the importance of dynamic balance recovery performance through ML stepping in relation to neuromusculoskeletal factors contributing to lateral balance stability. The results also highlight focused risk factors for falling that are amenable to clinical interventions for enhancing lateral balance function and preventing falls.

Treadmill training has been used for improving locomotor function in children with cerebral palsy (CP), but the functional gains are relatively small, suggesting a need to improve current paradigms. The understanding of the kinematic and EMG responses to forces applied to the body of subjects during treadmill walking is crucial for improving current paradigms. The objective of this study was to determine the kinematics and EMG responses to the pelvis and/or leg assistance force. Ten children with spastic CP were recruited to participate in this study. A controlled assistance force was applied to the pelvis and/or legs during stance and swing phase of gait through a custom designed robotic system during walking. Muscle activities and spatial-temporal gait parameters were measured at different loading conditions during walking. In addition, the spatial-temporal gait parameters during overground walking before and after treadmill training were also collected. Applying pelvis assistance improved step height and applying leg assistance improved step length during walking, but applying leg assistance also reduced muscle activation of ankle flexor during the swing phase of gait. In addition, step length and self-selected walking speed significantly improved after one session of treadmill training with combined pelvis and leg assistance.

A sensitive and selective method for the determination of long-acting released octreotide in human plasma has been developed based on liquid chromatography/tandem mass spectrometry (LC/MS/MS). Octreotide and the internal standard, triptorelin, were precipitated from the matrix, washed with dichloromethane and subsequently separated by reversed-phase high-performance liquid chromatography (HPLC) employing a 1% formic acid/methanol gradient system. Detection was by electrospray ionization mass spectrometry in the positive ion mode using multiple-reaction monitoring. The assay was linear in the concentration range 0.0500–50.0 ng/mL with intra- and inter-day precision (as relative standard deviation) of

Aim: To examine the associations between fetal growth restriction (FGR) and DNA methylation of six growth-related genes in human placenta. Materials & methods: A total of 181 mother-newborn pairs (80 FGR cases and 101 controls) were enrolled in this case–control study. Placental DNA methylation was measured by bisulfite pyrosequencing. Results: DNA methylation levels of IGF2 and AHRR were positively associated with newborn birth weight and Quetelet's index, while DNA methylation levels of HSD11B2 and WNT2 were negatively associated with those fetal growth indicators. In addition, significantly elevated odds of FGR birth were associated with increasing DNA methylation of HSD11B2 and WNT2, and decreasing DNA methylation of IGF2. Conclusion: Our findings demonstrated that placental DNA methylation levels of IGF2, AHRR, HSD11B2 and WNT2 were associated with measures of fetal growth.

Short-term exposure to outdoor air pollution has been linked to adverse health effects, including increased mortality, increased rates of hospital admissions and emergency department visits, exacerbation of chronic respiratory conditions (e.g., asthma), and decreased lung function (American Thoracic Society 1996; Dockery and Pope 1994). Most of these studies were conducted in the developed countries, and only a small number of studies have been conducted in Asia (Health Effects Institute 2004). In mainland China, the largest developing country, the relation between outdoor air pollution and daily mortality has been investigated in several large cities, including Beijing (Xu et al. 1994), Shenyang (Xu et al. 2000), Chongqin (Venners et al. 2003), and Shanghai (Kan and Chen 2003a, 2003b). These studies basically followed the commonly used time-series and case-crossover approaches, and their results were in accordance with those reported from Western Europe and the United States, where most epidemiologic studies were conducted. However, there are still some key scientific issues to be addressed regarding the health effects of outdoor air pollution in China. For example, although ozone is recognized as an air pollutant that could increase death risk (Bates 2005; Bell et al. 2004, 2005; Gryparis et al. 2004; Ito et al. 2005; Levy et al. 2005; Schwartz 2005), no study has been conducted in mainland China to assess the acute effect of O3. Moreover, the previous findings of the effects of O3 on death risk have been inconsistent (Anderson et al. 2001; Borja-Aburto et al. 1997; Goldberg et al. 2001; Hoek et al. 1997; Hong et al. 1999, 2002; Ito and Thurston 1996; Loomis et al. 1999; Prescott et al. 1998); therefore, in recent regulatory impact analyses of air pollution control measures [U.S. Environmental Protection Agency (EPA) 1999a, 1999b, 2003], the U.S. EPA excluded the O3–mortality relationship from primary benefits estimates, stating that the epidemiologic literature was too uncertain to infer causality and provide reasonable quantitative estimates. Also, much is unknown about the synergistic effects of O3 and the complex mix of pollutants found in the ambient air. China has one of the world’s worst levels of ambient air pollution. Coal has been the major source of energy in the country, constituting about 75% of all energy sources. Consequently, air pollution in China predominantly consists of coal smoke, with suspended particulate matter (PM) and sulfur dioxide as the principal air pollutants. However, with the rapid increase in the number of motor vehicles in recent years, air pollution in China’s large cities has gradually changed from the conventional coal combustion type to mixed coal combustion/motor vehicle emissions (Chen et al. 2004). Given the relatively high levels of copollutants (PM, SO2, and nitrogen dioxide) and change of air pollution type in China’s cities, it is worthwhile to investigate the independent effect of O3 on mortality outcomes in the country. Moreover, in setting air pollution control policy from a public health viewpoint, it is important to identify the health effects of air pollution from local data. In the present study, we conducted a time-series analysis to evaluate the association between mortality outcomes (both total and cause specific) and O3 exposure in metropolitan Shanghai using 4 years of daily data (2001–2004).

To study the association between phthalate esters (PAEs) metabolites in maternal urine and 11beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2 ) enzyme activity, explore the possible mechanism of PAEs effect on fetal development.All of 33 cases of intrauterine growth retardation (IUGR) newborn were selected by random sampling in 2012. And 33 cases of normal control newborn were enrolled, use high performance liquid chromatography-tandem mass spectrometry method was used to detect 4 kinds of phthalate esters (PAEs) metabolites in maternal urine: mono-n-butyl phthalate ester (MBP), mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) and three kinds of cortisol corticosterone metabolites, tetrahydrocortisol (THF), allo-tetrahydrocortisol (allo-THF), tetrahydrocortisone (THE), and analyze the association between phthalate esters (PAEs) metabolites in maternal urine and 11β-HSD2 enzyme activity.MBP, MEHP, MEHHP, MEOHP metabolites can be detected in 98% (65 cases) , 89% (59 cases), 91% (60 cases), 91% (60 cases) of all 66 maternal urine samples, respectively. The median concentrations of test material in case group were 31.20 ng/ml for MBP, 24.61 ng/ml for MEHHP, 11.72 ng/ml for MEOHP and 48.67 ng/ml for SumDEHP which were significantly higher than those of the control group (were 17.32, 12.03, 5.68 and 28.64 ng/ml); 11β-HSD2 activity in case group ((THF+allo-THF)/THE = (0.79 ± 0.09) ng/ml) was significantly lower than that of the control group((THF+allo-THF)/THE = (0.58 ± 0.04) ng/ml); PAEs metabolites MBP (β' = 1.12), MEHHP(β' = 1.14), MEOHP(β' = 1.10), SumDEHP(β' = 1.08) in baby boy mother's urine was reversely correlated to 11β-HSD2 activity.PAEs could affect fetal development by inhibit 11β-HSD2 activity.

Background Phthalates have been proven to be antiandrogenic, which may interfere with the timing of puberty. Children with Constitutional Delay of Growth and Puberty (CDGP) typically display short stature and pubertal delay. This study investigated whether phthalate's exposure was associated with CDGP, and evaluated the potential mediator role of testosterone. Methods In this case-control study, a total of 167 boys, including 57 boys with CDGP (cases) and 110 controls were enrolled. We measured six major phthalate metabolites in urine samples using high-performance liquid chromatography and tandem mass spectrometry (LC–MS/MS). The serum testosterone level was determined by radioimmunoassay. Results Children in the CDGP group were determined to have significantly elevated urinary phthalates concentration compared with control subjects (total phthalates median: case, 107.00 ng/ml; control, 62.22 ng/ml, p = 0.001). After adjustment for BMI and other confounding factors: mono-n-butyl phthalate (MBP), monoethyl phthalate (MEP) and total phthalate concentrations were significantly negatively associated with serum testosterone level (MBP: β = −45.7, p = 0.017; MEP: β = −31.6, p = 0.022; total phthalates: β = −24.6, p = 0.011); MBP, MEP, mono (2-ethylhexyl) phthalate (MEHP) and total phthalates were significantly associated with CDGP (odds ratio: MBP: 8.30, p = 0.002; MEP: 5.43, p = 0.002; MEHP: 3.83, p = 0.017; total phthalates: 9.09, p = 0.001). Serum testosterone level acted as a mediator of the association between phthalates' exposure and CDGP (p = 0.002) (proportion mediated: 34.4%). Conclusions In this case–control study, elevated phthalates' level was detected in children with CDGP in Shanghai, China and phthalate level was associated with CDGP, which appeared to be mediated by circulating testosterone level.

Background Phthalates were reported to be associated with increased risk of LBW in newborns, but the mechanism and potential influencing factor was still unclear. The objectives of this study were to investigate whether paraoxonase-2 (PON2) Ala148Gly (A148G) polymorphisms have impacts on fetal growth, and evaluate potential modifying effect on the association between phthalate exposures and LBW and short birth length. Methods In the current case-control study, 185 mother–newborn pairs including 74 low birth weight (LBW) cases and 111 controls were enrolled. Newborns' meconium specimens were collected and detected for mono-n-butyl phthalate (MBP) and mono-2-ethyhexyl phthalate (MEHP) by the method of high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Umbilical vein blood samples were used to identify PON2 A148G polymorphisms by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results Newborns prenatally exposed to higher level of phthalates had lower birth weight (β=−0.92. p=0.045 for MBP, β=−0.62, p=0.013 for MEHP) and short birth length (SBL) (β=−0.024. p=0.049 for MBP, β=−0.023, p=0.007 for MEHP). Comparing with low-phthalate-exposed subjects with PON2 148AA genotype, newborns with PON2 148AG/GG genotype exposed to high concentrations of MBP and MEHP had higher risks of LBW and short birth length (LBW: OR: 5.0, p=0.017 for MEHP; OR: 2.6, p=0.023 for MBP; SBL: OR: 6.6, p=0.005 for MEHP; OR: 6.4, p=0.017 for MBP). Effects of MBP and MEHP on LBW were significantly modified by PON2 A148G (p=0.044 and 0.034, respectively), while the modifying effect of PON2 A148G polymorphisms on the association of two phthalate metabolites with SBL was not significant. Conclusion Prenatal exposure to phthalates affected birth weight and length in newborns. PON2 A148G polymorphisms modified the effects of prenatal phthalates' exposure on fetal development. Newborns with PON2 148AG/GG genotype and exposed to high concentrations of MBP and MEHP had higher risks of LBW and SBL.

Purpose: Phthalates may interfere with the timing of pubertal development in adolescence and existing studies have shown inconsistent results. This study aims to assess the associations of pubertal onset and progression with urinary concentrations of phthalate metabolites in school-aged boys and girls. Methods: Using isotope-dilution liquid chromatography tandem mass spectrometry, we analyzed 6 phthalate metabolites in urine samples of 430 children (222 boys and 208 girls) aged 9.7 ± 2.2 years (age range 6.1 to 13.8 years) at baseline and 18 months of follow-up. The associations of exposures to phthalates with pubertal development such as the testis, breast and pubic hair were evaluated using ordered logistic regression models, adjusting for baseline development stage, current chronological age, current body fat composition, and parental education. Results: Urinary mono-n-butyl phthalate (MnBP) was associated with a 39% increase in the odds of presenting lower pubic hair development stages in boys, and mono (2-ethylhexyl) phthalate (MEHP) (p

Locomotor training using treadmill has been shown to elicit significant improvements in locomotor ability for some children with cerebral palsy (CP), the functional gains are relatively small and it requires greater involvement from a physical therapist. Current robotic gait training systems are effective in reducing the strenuous work of a physical therapist during locomotor training, but are less effective in improving locomotor function in some children with CP due to the limitations of the systems. Thus, a 3D cable-driven robotic gait training system was developed and tested in five children with CP through a 6 week of long-term gait training. Results indicated that both overground walking speed and 6 minute walking distance improved after robot assisted treadmill training through the cable-driven robotic system, and partially retained at 8 weeks after the end of training. Results from this pilot study indicated that it seems feasible to conduct locomotor training in children with CP through the 3D cable-driven robotic system.

ObjectiveTo examine the age and sex-specific associations of urine levels of six mono-phthalates with body size and fat distribution in Chinese children at puberty.Materials and methodsFour hundred and ninety-three school-aged children (247 boys, 246 girls) were recruited. Obesity related anthropometric indices were measured and body fat proportion (BF%) was calculated. Spot urine samples were collected and phthalate monoesters were detected by an API 2000 electrospray triple quadrupole mass spectrometer (ESI-MS/MS). Associations between phthalate exposure and overweight/obesity measures and their trends were examined by multiple linear regression and Logistic regression analyses, respectively.ResultsDi-2-ethylhexyl phthalate (DEHP) metabolites and monobutyl phthalate (MBP) were found to be the most detectable chemicals. In 8-10 years (yrs) group, concentrations of MEHP and MBP were significantly higher in girls than those in boys. However, concentrations of all phthalate monoesters, except for MEP and MEHP, in 11-13 yrs boys were significantly higher than those in girls. After adjusting for confounders including puberty onset, urinary concentrations of MBP and sum of low molecular-weight phthalate metabolites (∑LMP) were positively associated with boys' obesity in a concentration-effect manner, while concentrations of MEHP, MEHHP and sum of DEHP metabolites (∑MEHP) were negatively associated with girls' obesity. Associations between phthalate exposure levels and BMI z-score changes were age- and sex-specific in school-age children.ConclusionThere are age and sex-specific concentration-effect associations between phthalate exposure and fat distribution in Chinese children. Urinary phthalate levels in 11-13 yrs boys were about 30 percent higher than those in girls, and ∑MEHP levels in younger boys (10 yrs). Associations were positive for MBP and ∑LMP with both BMI z-score and fat distribution in boys >10 years of age, and negative for ∑MEHP with fat distribution in girls

International audience; Objectives: To examine the stepping performance during voluntary and waist-pull perturbation-induced step initiation in people with chronic stroke. Design: Repeated-measures single-case design. Setting: University-based research laboratory. Participants: Community-dwelling stroke survivors (N=10). Interventions: Not applicable. Main Outcome Measures: Ground reaction forces and kinematic data were recorded to assess anticipatory postural adjustments (APAs) and step characteristics for both voluntary and induced stepping conditions. Results: Induced stepping was performed with both the paretic (35% trials) and nonparetic legs (65% trials). Induced first steps occurred earlier and were executed faster than rapid voluntary steps. Compared with voluntary stepping, induced first step APAs were shorter in duration. Step height was higher with the nonparetic leg for both stepping conditions. Use of the paretic leg increased (52%) during the diagonal perturbations that passively unloaded the stepping limb compared with the use of the paretic leg (33%) for forward perturbations. Conclusions: The results indicated differences in executing voluntary and induced stepping, and between the paretic and nonparetic limbs in individuals with chronic stroke. The findings suggested guidelines for using stepping as a component of neurorehabilitation programs for enhancing balance and mobility. Additional larger-scale studies remain to be undertaken to further investigate these issues. Archives of Physical Medicine and Rehabilitation 2013;94:2425-32 (C) 2013 by the American Congress of Rehabilitation Medicine

Intrauterine growth restriction (IUGR) is associated with detrimental effects on neurodevelopmental progress in childhood and higher risk of degenerative diseases in adulthood. Placental 11β-hydroxysteroid dehydrogenase (HSD11B2) is a key gene involved in glucocorticoid metabolism, which in turn seems to be related to fetal growth impairment. As reduction of placental HSD11B2 gene expression has been associated with reduced human fetal growth, and methylation of HSD11B2 gene promoter has been shown to have an important role in HSD11B2 gene repression, we seek to investigate the relationship between IUGR and HSD11B2 gene promoter methylation in human placentas. We found that methylation levels of all studied CpG sites were significantly higher in IUGR newborns than those in controls. Further, methylation levels of the first and the third CpG sites were inversely associated with measures of fetal growth (birth weight and ponderal index). In addition, consistent with the above negative correlation, methylation levels of the first and the third CpG sites were inversely associated with HSD11B2 gene expression. These results together show a link between the site-specific methylation of placental HSD11B2 promoter and the development of IUGR.

Leydig cells are the primary source of generating testosterone, and the differentiation of Leydig cells in testes is a signature event of the ontogenesis of males. Many studies elucidating the molecular changes and the mechanisms involved in the progressive differentiation of stem Leydig cells into adult Leydig cells have been appeared recently. Herein, the hormonal regulation on the ontogenesis of fetal and mature Leydig cells was reviewed in this paper.

People with Parkinson's disease (PD) frequently have difficulties with generating anticipatory postural adjustments (APAs) for forward propulsion and lateral weight transfer when initiating gait. This impairment has been attributed to deficits in motor planning and preparation. This study examined the preparation of APAs prior to an imperative cue to initiate forward stepping. A startling acoustic stimulus (SAS) was used to probe the state of preparation of the APA in eight PD (off medication) and seven matched control subjects. Subjects performed visually cued trials involving a pre-cue light instructing them to prepare to step, followed 3.5 s later by a go-cue light to rapidly initiate stepping. In random trials, a SAS (124 dB) was presented at −1,500, −1,000, −500, −250, −100, or 0 ms before the go-cue. Subjects also performed self-initiated steps. Ground reaction forces (GRFs), center of pressure (CoP) changes, and electromyographic (EMG) signals were recorded. The SAS triggered APAs in 94 ± 11% (PD) and 96 ± 8% (control) of trials at latencies 89 ± 4 ms (PD) and 97 ± 3 ms (control) earlier than Control trials. The temporal profile of APA preparation was similar between groups. However, peak EMG, GRF, and mediolateral CoP amplitudes were reduced in PD. SAS-evoked APAs at 0 ms matched Control trial APAs and were enhanced compared with self-initiated stepping. These results demonstrate that people with mild to moderate PD can plan and prepare the appropriate APA sequence prior to the expected cue to initiate gait; however, the prepared APAs are underscaled in magnitude.

Although the relation between outdoor air pollution and daily mortality has been examined in several Chinese cities, there are still a number of key scientific issues to be addressed concerning the health effects of air pollution in China. Given the changes over the past decade in concentrations and sources of air pollution (e.g., the change from one predominant source [coal combustion], which was typical of the twentieth century, to a mix of sources [coal combustion and motor-vehicle emissions]) and transition in China, it is worthwhile to investigate the acute effects of outdoor air pollution on mortality outcomes in the country. We conducted a time-series study to investigate the relation between outdoor air pollution and daily mortality in Shanghai using four years of daily data (2001-2004). This study is a part of the Public Health and Air Pollution in Asia (PAPA) program supported by the Health Effects Institute (HEI). We collected data on daily mortality, air pollution, and weather from the Shanghai Municipal Center of Disease Control and Prevention (SMCDCP), Shanghai Environmental Monitoring Center, and Shanghai Meteorologic Bureau. An independent auditing team assigned by HEI validated all the data. Our statistical analysis followed the Common Protocol of the PAPA program (found at the end of this volume). Briefly, a natural-spline model was used to analyze the mortality, air pollution, and covariate data. We first constructed the basic models for various mortality outcomes excluding variables for air pollution, and used the partial autocorrelation function of the residuals to guide the selection of degrees of freedom for time trend and lag days for the autoregression terms. Thereafter, we introduced the pollutant variables and analyzed their effects on mortality outcomes, including both mortality due to all natural (nonaccidental) causes and cause-specific mortality. We fitted single- and multipollutant models to assess the stability of the effects of the pollutants. For mortality due to all natural causes, we also examined the associations stratified by sex and age. Stratified analyses by education level, used as a measure of socioeconomic status, were conducted as well. In addition to an analysis of the entire study period, the effects of air pollution in just the warm season (from April to September) and cool season (from October to March) were analyzed. We also examined the effects of alternative model specifications--such as lag effects of pollutants and temperature, degrees of freedom for time trend and weather conditions, statistical approaches, and averaging methods for pollutant concentrations-on the estimated effects of air pollution. We found significant associations between the air pollutants--particulate matter 10 pm or less in aerodynamic diameter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3) -and daily mortality from all natural causes and from cardiopulmonary diseases. The increased mortality risks found in the data from Shanghai were generally similar in magnitude, per concentration of pollutant, to the risks found in research from other parts of the world. An increase of 10 microg/m3 in 2-day moving average concentrations of PM10, SO2, NO2, and O3 corresponded to 0.26% (95% confidence interval [CI], 0.14-0.37), 0.95% (95% CI, 0.62-1.28), 0.97% (95% CI, 0.66-1.27), and 0.31% (95% CI, 0.04-0.58) increases, respectively, in mortality due to all natural causes. Sensitivity analyses suggested that our findings were generally insensitive to alternative model specifications. We found significant effects of the gaseous pollutants SO2 and NO2 on daily mortality after adjustment for PM10. Our analysis also provided preliminary, but not conclusive, evidence that women, older people, and people with a low level of education might be more vulnerable to air pollution than men, younger people, and people with a high level of education. In addition, the associations between air pollution and daily mortality appeared to be more pronounced in the cool season than in the warm. We concluded that short-term exposure to outdoor air pollution (PM10, SO2, NO2, and O3) was associated with daily mortality in Shanghai and that gaseous pollutants might have independent health effects in the city. Overall, the results of the study appeared largely consistent with those reported in other locations worldwide. Further research will be needed to disentangle the effects of the various pollutants and to gain more conclusive insights into the influence of various sociodemographic characteristics (e.g., sex, age, and socioeconomic status) and of season on the associations between air pollution and daily mortality.

Anticipatory postural adjustments (APAs) for lateral weight transfer and stability precede and accompany gait initiation. Individuals with Parkinson's disease (PD) show altered APA characteristics with delays in initiating stepping that may reflect impaired interactions between posture and locomotion. The purpose of this study was to determine the short-term effects of a single session of repetitive robotic assistance training with the APA on rapid step initiation in individuals with PD in the medications "on" state and healthy control individuals. Ground reaction forces and step kinematics were recorded.Subjects first performed baseline trials of unassisted self-paced rapid forward stepping. Next, a training acquisition series involved 50 trials with a lateral pull applied to the pelvis by a robotic system to assist with the early phase of the APA during stepping. To assess potential retention effects of training, unassisted stepping trials were evaluated immediately after acquisition trials (immediate retention) and one week later (one-week retention).Overall, the subjects with PD had a longer APA duration (P0.03), and longer first step duration (P0.04) than the healthy control individuals. Compared with baseline, APA duration was shorter (P0.001) and step onset time became earlier (P0.001) for acquisition trials but these effects were not retained. Step duration, which became shorter (P0.001) during the late acquisition trials (P = 0.002), demonstrated immediate retention (P0.001) and one-week retention (P0.001).Posture-assisted training, affecting the interaction between posture and locomotion, may have therapeutic potential for improving movement performance in individuals with PD.

Diethylhexylphthalate (DEHP) has been classified as an antiandrogen. However, whether in utero and lactational exposures of DEHP affect Leydig cells has not been well established. In the present study, the effects of DEHP exposures on fetal Leydig cells (FLCs) and adult Leydig cells (ALCs) were assessed. Pregnant dams of Long-Evans rats were treated with 0, 10, and 750 mg/kg body weight DEHP from Gestational Day 12.5 to Postnatal Day (PND) 21.5. Fetal Leydig cell clustering and FLC-specific gene expression were examined. Anogenital distances (AGDs) of male pups were assessed at PND 2. Serum testosterone levels of male pups and mRNA levels of ALC-specific genes were measured at PNDs 21 and 49. The AGDs of male pups were significantly shorter in the group treated with 750 mg/kg DEHP (mean +/- SEM, 3.68 +/- 0.16 mm) compared with control (4.62 +/- 0.13 mm). The FLCs were aggregated after 10 and 750 mg/kg DEHP exposures. Several FLC-specific genes, including luteinizing hormone receptor (Lhcgr) and steroidogenic enzyme genes, were downregulated at both doses. Serum testosterone levels were significantly lower compared with control at PND 21 after treatment of 10 or 750 mg/kg DEHP, and continued to be lower even up to 49 days postpartum at the higher dose. The mRNA levels for Lhcgr and steroidogenic enzyme genes were significantly lower at both doses of DEHP at PND 21, whereas there were no significant differences for these genes at PND 49. In conclusion, in utero and continued lactational exposures to DEHP exert long-term disruption of steroidogenesis of ALCs.

Identification of the specific pollutants contributing most to the health hazard of the air pollution mixture may have important implications for environmental and social policies. In the current study, we conducted a time-series analysis to examine the specific effects of major air pollutants [particulate matter less than 10 microns in diameter (PM(10)), sulfur dioxide (SO(2)), and nitrogen dioxides (NO(2))] on daily mortality in Shanghai, China, using both single-pollutant and multiple-pollutant models. In the single-pollutant models, PM(10), SO(2), and NO(2) were found to be associated with mortality from both all non-accidental causes and from cardiopulmonary diseases. Unlike some prior studies in North America, we found a significant effect of gaseous pollutants (SO(2) and NO(2)) on daily mortality even after adjustment for PM(10) in the multiple-pollutant models. Our findings, combined with previous Chinese studies showing a consistent, significant effect of gaseous pollutants on mortality, suggest that the role of outdoor exposure to SO(2) and NO(2) should be investigated further in China.