Changes in the Non-targeted Metabolomic Profile of Three-year-old Toddlers with Elevated Exposure to Polycyclic Aromatic Hydrocarbons.

Objective: To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons (PAHs) during critical brain development and explore their potential link with the intestinal microbiota. Methods: Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs (OH-PAHs) in 36-month-old children. Subsequently, 37 children were categorized into low- and high-exposure groups based on the sum of the ten OH-PAHs. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples. Furthermore, fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq. Results: The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group (variable importance for projection > 1, P < 0.05). Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene, fluorine, and phenanthrene ( r = 0.336-0.531). The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states, including amino acid, lipid, and nucleotide metabolism. Additionally, these distinct metabolites were significantly associated with specific intestinal flora abundances ( r = 0.34-0.55), which were mainly involved in neurodevelopment. Conclusion: Higher PAH exposure in young children affected metabolic homeostasis, particularly that of certain gut microbiota-derived metabolites. Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.

[Association of exposure to polycyclic aromatic hydrocarbons during pregnancy with autism spectrum disorder-related behaviors in toddlers: a birth cohort study].

OBJECTIVE: To study the association of exposure to polycyclic aromatic hydrocarbons (PAH) during pregnancy and autism spectrum disorder (ASD)-related behaviors in toddlers. METHODS: A total of 348 toddlers who had accepted the measurement of PAH-DNA adduct in umbilical cord blood and evaluation of behavior problems at the age of 36 months were enrolled in this birth cohort study. Child Behavior Checklist (CBCL) and Autism Behavior Checklist (ABC) were used to evaluate behavior problems at the age of 36 months. The correlation of the concentration of PAH-DNA adduct in umbilical cord blood with CBCL and ABC scores at the age of 36 months were analyzed. RESULTS: The detection rate of PAH-DNA adduct in umbilical cord blood was 52.3%, and the median concentration was 0.68 ng/mL. The median total scores of CBCL and ABC scales were 23 and 8 respectively. In children aged 36 months, the concentration of PAH-DNA adduct was positively correlated with the score of social withdrawal in the CBCL scale (rs=0.205, P<0.05), the total score of the ABC scale (rs=0.412, P<0.05), and the self-care score of the ABC scale (rs=0.355, P<0.05). The concentration of PAH-DNA adduct was closely associated with the total score of the ABC scale in children aged 36 months (ß=0.122, P<0.05). CONCLUSIONS: PAH exposure during pregnancy may be a risk factor for ASD-related behaviors in toddlers. Effective reduction of PAH exposure during pregnancy and detection of PAH-DNA adduct in neonatal umbilical cord blood are of vital importance for early prevention, screening and intervention of ASD.

The Ability of Baseline Triglycerides and Total Cholesterol Concentrations to Predict Incidence of Type 2 Diabetes Mellitus in Chinese Men and Women: A Longitudinal Study in Qingdao, China.

OBJECTIVE: The purpose of this study was to assess the association between triglycerides (TG), total cholesterol (TC) at baseline, and type 2 diabetes mellitus (T2DM) incidence in a general Chinese population. Further, it aimed to evaluate the ability of TG and TC to predict T2DM incidence. METHODS: Qingdao Diabetes Prevention Program participants recruited between 2006 and 2009 were followed up in 2012-2015. TG, TC, and T2DM status were measured. Cox proportional hazards models were used to estimate the association between TG, TC, and T2DM incidence. The receiver operating characteristic (ROC) curve was used to evaluate the ability of TG and TC to identify T2DM participants. RESULTS: The incidence of T2DM significantly increased with TG in women and TC in both men and women (Ptrend < 0.05). Univariate Cox regression indicated that higher TG {borderline high TG [hazards ratio (HR): 2.05; 95% confidence interval (CI): 1.40, 3.00] and hypertriglyceridemia [HR: 2.64; 95% CI: 1.68, 4.15]} and TC [hypercholesterolemia (HR: 2.05; 95% CI: 1.43, 2.95)] were significantly associated with increased risk of T2DM incidence in women but not in men. Multivariate Cox regression showed that hypertriglyceridemia in women (HR: 1.78, 95% CI: 1.07, 2.97), borderline high TC in men (HR: 1.61, 95% CI: 1.04, 2.48), and hypercholesterolemia in women (HR: 1.68, 95% CI: 1.81, 2.61) had a higher significant risk of T2DM incidence. The optimal cutoff values of TG were > 1.15 and > 1.23 mmol/L in men and women, respectively. For TC, they were > 5.17 and > 5.77 mmol/L in men and women, respectively. The area under the ROCs of TG and TC were 0.54 (0.51-0.57) and 0.55 (0.52-0.58), respectively, in men, and 0.60 (0.58-0.62) and 0.59 (0.56-0.61), respectively, in women. CONCLUSION: Elevated TG and TC were risk factors for T2DM incidence. However, no predictive capacity was found for both factors to identify T2DM incidence in Chinese men and women. Hence, TG and TC levels in both Chinese men and women might be used for decreasing the incidence of T2DM but no clinical predictive capacity for T2DM.

Levels of polychlorinated biphenyls in settled house dust from urban dwellings in China and their neurodevelopmental effects on preschool-aged children.

We investigated the levels of polychlorinated biphenyls (PCBs) in settled house dust (SHD) from urban dwellings with resident preschool-aged children in Nanjing, China. The possible neurodevelopmental effects of house-dust PCBs were also explored. SHD was collected from 114 urban houses. The levels of 39 PCB congeners were measured by gas chromatography-tandem mass spectrometry. The Child Behavior Checklist and the Gesell Development Inventory were used to evaluate the child's development. All 39 target congeners measured were detected. The mass percentage of di-PCBs was the highest at 47.8%, followed by tetra- and tri-PCBs at 16.8% and 13.0%, respectively. Spearman's rho correlation showed that di-, tri-, hexa-, hepta-, nona- and total PCBs were positively associated with somatic, thought problem and total problem scores (0.24

Levels of polybrominated diphenyl ethers in settled house dust from urban dwellings with resident preschool-aged children in Nanjing, China.

We investigated the levels and possible determinants of polybrominated diphenyl ethers (PBDEs) in the settled house-dust (SHD) of urban dwellings with resident preschool-aged children in Nanjing, China. The possible neurodevelopmental effects of house-dust PBDEs were also explored. SHD was collected from 216 urban houses. Levels of 8 PBDEs were measured by gas chromatography-negative chemical ionization mass spectrometry. The Child Behavior Checklist and the Gesell Development Inventory were used to evaluate the child's development. BDE47, BDE99, BDE153, BDE18, and BDE209 were detected in the SHD of >90 % of houses, of which BDE209 predominated. Most PBDEs were found at significantly greater levels in indoor than in outdoor dust (P < 0.05). Levels of BDE28 and BDE154 in houses with solid-wood floors were significantly greater than those in houses with plywood floors (P < 0.05). BDE154 levels in houses with wallpaper were significantly greater than those without wallpaper (P < 0.05). Greater BDE47 concentrations were found in houses with less natural ventilation time (linear trend P < 0.05). After dichotomization at the geometric mean concentration, BDE209 and total BDEs showed significant risks for depressed behavior problems and lower personal social developmental quotients (DQs); BDE99 and BDE153 indicated a risk for lower personal social DQs. In conclusion, PBDEs (especially BDE209) are ubiquitous in urban SHD in Nanjing residences. Natural ventilation and floor materials potentially influence PBDE levels in SHD. The potential adverse effect of postnatal exposure to PBDEs on the behavior and neurodevelopment of preschool-age children requires follow-up in larger studies.

Association between maternal allergic rhinitis and asthma on the prevalence of atopic disease in offspring.

BACKGROUND: Asthma is a common co-morbidity of allergic rhinitis (AR). The prevalence of these two allergic diseases has increased in China and has been shown to cluster in families independently. This study evaluated the association between maternal AR (presenting with or without asthma) and the allergic conditions in offspring. METHODS: Women (n = 592) diagnosed with AR were recruited for this study; 379 patients presented with AR and 213 presented with both AR and asthma. Total serum IgE levels and nasal eosinophil counts were analyzed and correlated with disease presentation. RESULTS: The prevalence of allergic conditions in offspring of mothers diagnosed with AR and asthma was significantly higher than the prevalence observed in children born to mothers presenting with AR only. Maternal total serum IgE and eosinophil counts were predictive of atopy in offspring. Children born to mothers presenting with persistent moderate-to-severe AR had the highest risk of developing atopic conditions (OR 6.26, 95% CI 3.26-12.02). Maternal age of 25-30 years at delivery was also associated with a higher risk for the allergic disease in offspring compared to maternal age of 36-40 (OR 2.13, 95% CI 1.31-3.47). CONCLUSIONS: The severity of maternal AR, asthma co-morbidity, elevated serum IgE levels and nasal eosinophilia were all associated with an increased risk of offspring developing allergic conditions. Children born to older mothers were protected against developing atopic disease.

Prevalence of and risk factors for subjective symptoms in urban preschool children without a cause identified by the guardian.

OBJECTIVE: The aim of this study was to explore the prevalence of and the risk factors for subjective symptoms without an identified cause by the guardian (SSWICG) in urban preschool children. METHODS: A questionnaire was used to collect information from 661 urban preschool children. The subjective symptoms were cited from the MM075NA Indoor Environment Quality Investigation Questionnaire. Information about living conditions, kindergarten and outdoor environments was collected, as well as health information from each child. RESULTS: The prevalence of SSWICG reached 31%, among which the prevalence of general symptoms in the central nervous system (CNS) reached 54.6%. Univariate analysis showed that the materials that made indoor furniture, walls and doors, indoor biological factors, outdoor pollution sources near the house and traffic pollution were associated with SSWICG and mucosal, dermal and general symptoms in the CNS subgroups. Multivariate analysis also showed that furniture materials, traffic pollution, kindergarten environment quality and allergies were associated. CONCLUSIONS: The prevalence of SSWICG was relatively high. Possible risk factors include indoor furnishing materials, allergy, traffic pollution and kindergarten environmental pollution.

Relationship between indoor chemical concentrations and subjective symptoms associated with sick building syndrome in newly built houses in Japan.

OBJECTIVES: This study explored possible associations between chemical substances and sick building syndrome (SBS)-type symptoms of residents living in new houses in Japan. METHODS: We randomly sampled 5,709 newly built conventional homes. In the end, 1,479 residents in 425 households completed a questionnaire survey and agreed to environmental monitoring for indoor aldehydes and volatile organic compounds (VOCs) to be conducted in their homes. If the residents had complained about at least one SBS-related symptom, they were classified as suffering from SBS. Multiple logistic regression analysis was used to select predictive chemical factors of SBS symptoms. RESULTS: About 14% of the subjects suffered from SBS. Many aldehydes and VOCs were associated factors of optical, nasal, and gular symptoms in univariate analysis. After adjustment for other possible risk factors, formaldehyde dose-dependently showed to be a significant risk factor for SBS. Several chemicals had tendency to be associated with SBS symptoms. CONCLUSIONS: Chemicals detected in Japanese newly built houses tend to increase the risk of subjective symptoms in residents suffering from SBS.

A longitudinal study of environmental risk factors for subjective symptoms associated with sick building syndrome in new dwellings.

This study was performed to explore possible environmental risk factors, including indoor chemicals, mold, and dust mite allergens, which could cause sick building syndrome (SBS)-type symptoms in new houses. The study was conducted in 2004 and 2005 and the final study population consisted of 86 men and 84 women residing in Okayama, Japan. The indoor concentrations of indoor aldehydes, volatile organic compounds, airborne fungi, and dust mite allergens in their living rooms were measured and the longitudinal changes in two consecutive years were calculated. A standardized questionnaire was used concomitantly to gather information on frequency of SBS-type symptoms and lifestyle habits. About 10% of the subjects suffered from SBS in the both years. Crude analyses indicated tendencies for aldehyde levels to increase frequently and markedly in the newly diseased and ongoing SBS groups. Among the chemical factors and molds examined, increases in benzene and in Aspergillus contributed to the occurrence of SBS in the logistic regression model. Indoor chemicals were the main contributors to subjective symptoms associated with SBS. A preventive strategy designed to lower exposure to indoor chemicals may be able to counter the occurrence of SBS.

Effects of mask fitness and worker education on the prevention of occupational dust exposure.

To decrease the incidence of pneumoconiosis, we examined dust protective mask performance and its relation to pulmonary function as well as the effects of worker education on the proper wearing of masks. One hundred and seventy-eight workers from 15 factories subject to dust exposure participated in this study. All participants were interviewed to obtain relevant personal information and underwent both a mask leakage and a pulmonary function test. The mask leakage was expressed as a percentage, with under 10% leakage indicating that the dust protective mask worked efficiently. In addition, 23 workers from 2 factories were educated on how to wear masks properly. The average mask leakage was 24.3%, and 58% of workers wore ineffective masks. Though pulmonary function was almost normal, the percent vital capacity (%VC) tended to be lower depending on the mask leakage. Mask education, which was very easy and took only a short time, dramatically decreased average mask leakage from 32.1% to 10.5% (p0.001). Educating workers to wear masks properly might prevent the worsening of pulmonary function in response to dust exposure. Appropriate mask fitness by education could be useful in preventing the development of pneumoconiosis.

Effect of sports activity on bone mineral density in wheelchair athletes.

The present study carried out a measurement of body composition and a nutrition survey, targeting 28 male wheelchair athletes and comparing them with 25 male physically able healthy athletes as the controls. The DXA method was used to measure bone mineral density (BMD), percentage of body fat (% body fat), and lean body mass (LBM). Possible factors affecting the BMD of the wheelchair athletes with spinal injuries were analyzed including age, body part, type of sport, area of injury, length of injury, and the length of time it took before restarting sports activity after injury. BMD in the arms, body trunk, legs, and entire body was measured. There were no significant differences in the BMD of the wheelchair athletes by age group (from 20 to 29, from 30 to 39, and 40 years and older), by sports (basketball, track and field, and tennis), and by area of injury (high and low paraplegia). BMD in the legs (r = -0.549, P < 0.01), body trunk (r = -0.414, P < 0.05), and entire body (r = -0.452, P < 0.05) of the wheelchair athletes was negatively correlated with the period since injury; however, no such a relationship was observed in the arms. In addition, the multiple regression analysis for BMD of each body region showed that the earlier the wheelchair athletes restarted sports after injury, the higher values the BMD of legs (r = -0.467, P < 0.05), body trunk (r = -0.469, P < 0.05), and entire body (r = -0.488, P < 0.05), independent of age and sports. The leg BMD of the wheelchair athletes was lower than that of the physically able athletes, with a BMD 76.5% of the controls. The present study suggests that restarting sports activity in a timely manner after treatment and rehabilitation for the injury is useful in preventing loss of BMD in wheelchair athletes and ultimately improving their quality of life.

Symptom definitions for SBS (sick building syndrome) in residential dwellings.

The potential risk factors for sick building syndrome (SBS) in newly built dwellings were investigated. Two different definitions for SBS were used, a narrow definition (symptoms related to home environment and continuously occurring in the last 3 months were regarded as positive) and another relatively broad definition (symptoms related to home environment and either continuously or sporadically occurring in the last 3 months were regarded as positive). With both definitions indoor air chemicals, especially TVOC, and high stress during work were found to be significantly associated with SBS symptoms. Allergic history was more associated with narrow-sense symptoms and odor perception with broad-sense symptoms. The results indicate that the broad definition be preferred to find more potential risk factors.

Unmetabolized VOCs in urine as biomarkers of low level exposure in indoor environments.

This study aimed to test the possible use of unmetabolized volatile organic compounds (VOCs) in urine as biomarkers of low-level indoor environmental exposure. Twenty-four subjects in 13 dwellings in a prefecture of Japan participated in this study. Air samples of the breathing zone were collected in the living room and bedroom, along with spot urine samples (before bedtime and first morning voids). Toluene, ethylbenzene, xylene isomers, styrene and p-dichlorobenzene in the air and urine samples were measured by gas chromatography/mass spectrometry. For the 21 subjects without solvent exposure at work, there were significant correlations between the time-weighted average air concentrations in the bedroom and morning urinary concentrations for toluene, o-xylene, total xylene and p-dichlorobenzene (correlation coefficients of 0.54, 0.61, 0.56 and 0.84, respectively). Multiple linear regression analysis showed only air VOCs in the bedroom influenced the morning urinary VOC concentrations. We concluded that unmetabolized VOCs in the urine can provide a reliable biological indicator for air VOC exposures in non-occupational environments.

Cytotoxicity of lawsone and cytoprotective activity of antioxidants in catalase mutant Escherichia coli.

Lawsone is an active naphthoquinone derivative isolated from henna (Lawsonia inermis L.), a widely used hair dye. Previous study on the toxicity of lawsone remains unclear since the involvement of oxidative stress and the kind of ROS (reactive oxygen species) involved have not been fully resolved yet. This present study reports the cytotoxic effects of lawsone and henna. We carried out CAT assay (a zone of inhibition test of bacterial growth and colony-forming efficiency test of transformant Escherichia coli strains that express mammalian catalase gene derived from normal catalase mice (Cs(a)) and catalase-deficient mutant mice (Cs(b))), Ames mutagenicity assay and H(2)O(2) generation assay. Lawsone generated H(2)O(2) slightly in phosphate buffer system and was not mutagenic in Ames assay using TA 98, TA 100 and TA 102, both in the absence and presence of metabolic activation. Lawsone exposure inhibited the growth of both Cs(a) and Cs(b) strains in a dose-dependent manner. Mean zone diameter for Cs(a) was 9.75+/-0.96 mm and 12.75+/-1.5 mm for Cs(b). Natural henna leaves did not show toxic effects, whereas two out of four samples of marketed henna products were shown toxicity effects. Catalase abolished zone of inhibition (ZOI) of marketed henna products, eliminated ZOI of lawsone in a dose-dependent manner and low concentration of exogenous MnSOD and Cu/ZnSOD eliminated the toxicity. Histidine and DTPA, the metal chelator; BHA and low concentration of capsaicin, the inducer of NADH-quinone reductase, effectively protected Cs(a) and Cs(b) against lawsone in this study. We suggest that lawsone cytotoxicity is probably mediated, at least in part, by the release of O(2)(-), H(2)O(2) and OH(-).