Validity of the ESSENCE-Q neurodevelopmental screening tool in Japan.

AIM: To assess the validity of the Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations-Questionnaire (ESSENCE-Q), a simple screening tool for neurodevelopmental problems, in Japan. METHOD: Parents/caregivers completed the 11-item ESSENCE-Q for 77 612 children aged 2 years 6 months included in a national birth cohort study. Information about neurodevelopmental disorders (NDDs: autism spectrum disorder; intellectual disability and/or developmental language disorder; motor delay/motor disorder) was collected at age 3 years. Each ESSENCE-Q item was scored on a binary (0,1) scale, with a total score range of 0 to 11. Total scores and individual items were compared across children with and without NDDs. RESULTS: NDDs were recorded in 854 children (1.1%). With a total ESSENCE-Q score cut-off of ≥3, receiver operating characteristic curve analysis showed an area under the curve of 0.91, with sensitivity 84.9%, specificity 84.8%, positive predictive value 5.9%, and negative predictive value 99.8%. The proportion of parental concerns at 2 years 6 months differed significantly by NDD status for communication (89.5% vs 14.2%) and general development (80.2% vs 7.4%). ESSENCE-Q total scores were moderately negatively correlated (-0.36, p < 0.001) with Japanese Ages and Stages Questionnaire scores. INTERPRETATION: The parent/caregiver-completed ESSENCE-Q is useful as a tool for screening out children with neurotypical development at this early age. Further research into longer-term predictive validity will be possible as more NDD diagnoses are given as the children grow up.

Vitamin D deficiency associated with neurodevelopmental problems in 2-year-old Japanese boys.

AIM: While associations between vitamin D deficiency and neurodevelopmental disorders have been found, large studies on child vitamin D, neurodevelopment, and sex differences among the general population are lacking. This study aimed to investigate the association between child serum 25-hydroxyvitamin D (25(OH)D)) levels and neurodevelopmental problems (NDPs). METHODS: Serum 25(OH)D and NDPs were measured at age two among the subcohort study of the Japan Environment and Children's Study. NDPs were assessed with the Kyoto Scale of Psychological Development 2001 (Kyoto scale). Adjusted odds ratios (aORs) for the Kyoto-scale developmental quotient scores <70 were calculated, for postural-motor, cognitive-adaptive, and language-social domains and overall scores, adjusted for test month, latitude, small for gestational age, maternal age, and daycare attendance. RESULTS: Among 2363 boys and 2290 girls, boys had higher 25(OH)D levels, but scored lower in the Kyoto scale. For boys in the vitamin D deficiency (<20 ng/mL) group, aORs of scoring the Kyoto-scale DQs <70 were 2.33 (p = 0.006) for overall DQs, 1.91 (p = 0.037) for cognitive-adaptive, and 1.69 (p = 0.024) for language-social domains. For girls, results were inconclusive. CONCLUSION: Only boys showed a clear and cross-modal association between vitamin D deficiency and NDPs.

A systematic review and meta-analysis of macrolides in the management of adult patients with asthma.

BACKGROUND: The efficacy of macrolides in the management of asthma has been studied but remains controversial. We conducted a systematic review and meta-analysis of macrolides in the management of adult patients with asthma. METHODS: Randomized controlled trials of macrolides used in adult patients with asthma were searched for in MEDLINE, EMBASE, PsycINFO, Cochrane Library, CINAHL, and Igaku Chuo Zasshi databases to evaluate the efficacy and safety of macrolides. RESULTS: Seventeen reports with macrolide treatment durations ranging from 6 to 48 weeks were included. Macrolides did not reduce exacerbations requiring hospitalization, severe exacerbations, or rescue use of short-acting beta-2 agonist inhalers; improve lung function; decrease peripheral blood or sputum neutrophil counts; or decrease fractional exhaled nitric oxide compared to placebo. Macrolides statistically improved asthma control and quality of life but by less than the minimal clinically important difference. Peripheral blood eosinophil counts as well as serum and sputum eosinophilic cationic protein concentrations were significantly decreased with macrolides compared to placebo. The improvement of asthma symptoms and airway hyperresponsiveness varied by study. The safety profile of macrolides was comparable to that of placebo. CONCLUSIONS: Although macrolides have some useful clinical aspects, there is not sufficient evidence to recommend their use in the management of adult patients with asthma.

Association between maternal cholesterol level during pregnancy and placental weight and birthweight ratio: data from the Japan Environment and Children's Study.

BACKGROUND: Placental weight to birthweight ratio (PW/BW ratio), or its inverse, is used as an indicator of placental efficiency. Past studies have shown an association between an abnormal PW/BW ratio and adverse intrauterine environment, however, no previous studies have examined the effect of abnormal lipid levels during pregnancy on PW/BW ratio. We aimed to evaluate the association between maternal cholesterol levels during pregnancy and placental weight to birthweight ratio (PW/BW ratio). METHODS: This study was a secondary analysis using the data from the Japan Environment and Children's Study (JECS). 81 781 singletons and their mothers were included in the analysis. Maternal serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels during pregnancy were obtained from participants. Associations between maternal lipid levels and placental weight and PW/BW ratio were assessed by regression analysis using restricted cubic splines. RESULTS: Dose-response relationships were observed between maternal lipid level during pregnancy and placental weight and PW/BW ratio. High TC and LDL-C levels were associated with heavy placental weight and high PW/BW ratio, i.e., inappropriately heavy placenta for birthweight. Low HDL-C level was also associated with inappropriately heavy placenta. Low TC and LDL-C levels were associated with low placental weight and low PW/BW ratio, i.e., inappropriately light placenta for birthweight. High HDL-C was not associated with PW/BW ratio. These findings were independent of pre-pregnancy body mass index and gestational weight gain. CONCLUSIONS: Abnormal lipid levels such as elevated TC and LDL-C, and low HDL-C level, during pregnancy were associated with inappropriately heavy placental weight.

Influence of chest/head circumference ratio at birth on obstetric and neonatal outcomes: The Japan environment and children's study.

OBJECTIVES: Some newborns that are not small-for-gestational-age (non-SGA, birthweight ≥10th percentile for a given gestational age) may have pathologic growth restrictions. This study examined the association of adverse obstetric and neonatal outcomes with chest/head circumference ratio at birth in non-SGA and SGA newborns. METHODS: This study was a cross-sectional evaluation of data from a nationwide prospective birth cohort study, the Japan Environment and Children's Study. We analyzed 93 690 non-anomalous singletons born at 34-41 gestational weeks. We defined low, normal, and high chest/head circumference ratio as <10th percentile, 10th-90th percentile, and >90th percentile, respectively, according to the internally constructed chest/head circumference percentile chart. Modified Poisson regression was used to estimate adjusted prevalence ratios (aPR) for the outcomes studied. RESULTS: Compared with non-SGA newborns with a normal ratio, those with a low ratio had an increased occurrence of low birthweight (1.75, 1.58-1.94 [aPR, 95% confidence interval]), cesarean delivery (1.34, 1.29-1.38), Apgar score <7 at 5 min (1.57, 1.14-2.17), respiratory complications (1.20, 1.04-1.39), and prolonged hospitalization (1.36, 1.30-1.42). In contrast, the high-ratio group had a lower rate of low birthweight (0.71, 0.59-0.86), cesarean delivery (0.82, 0.77-0.87), and prolonged hospitalization (0.83, 0.78-0.89). In SGA newborns, a low ratio was associated with increased aPRs for low birthweight, cesarean delivery, hypoglycemia, and prolonged hospitalization, whereas a high ratio showed no such association. CONCLUSIONS: Findings indicate that the chest/head circumference ratio at birth influence obstetric and neonatal outcomes regardless of the birthweight status.

Dose-response relationships between maternal urinary cotinine and placental weight and ratio of placental weight to birth weight: The Japan Environment and Children's Study.

INTRODUCTION: Studies on the relationship between maternal self-reported smoking status and placental weight report inconsistent results. This study examined the relationships between maternal urinary cotinine concentration and placental weight and the ratio of placental weight to birth weight (PW/BW ratio). The study also examined the relationship between maternal smoking status, as determined by cotinine concentration, with placental weight and with PW/BW ratio, stratified by sex of offspring. METHODS: Our analysis used information of 91,049 mother-child pairs enrolled in the Japan Environment and Children's Study. Maternal urinary cotinine concentration was quantified (during the second or third trimester) with high-performance liquid chromatography-tandem mass spectrometry. Using restricted cubic splines, placental weight and PW/BW ratio were plotted against natural log-transformed cotinine concentration. Taking cotinine levels of <0.17 ng/mL, 0.17 to <21.5 ng/mL (natural log-transformed values, -1.77 to 3.07), and ≥21.5 ng/mL as indicative of non-smokers, passive smokers, and active smokers, respectively, the relationships between maternal smoking status and placental weight and PW/BW ratio were examined, adjusting for confounders. RESULTS: Placental weight and PW/BW ratio increased with increasing cotinine concentration. After cotinine reached a certain concentration, the placental weight decreased in male offspring whereas it plateaued in female offspring. Compared with not smoking, active smoking during pregnancy significantly increased placental weight and PW/BW ratio. CONCLUSION: Placental weight responded as an inverted U-shape whereas the PW/BW ratio followed a J-shape with increasing maternal urinary cotinine concentration measured during pregnancy, suggesting exposure to tobacco smoke induces a disproportionate reduction in fetal growth. The effect of tobacco smoke on placental growth varied by sex of offspring.

Gestational weight gain mediates the effects of energy intake on birth weight among singleton pregnancies in the Japan Environment and Children's Study.

BACKGROUND: Extra energy intake is commonly recommended for pregnant women to support fetal growth. However, relevant data regarding variations in energy intake and expenditure, body mass index and gestational weight gain (GWG) are frequently not considered. This study aimed to investigate how energy intake during pregnancy and gestational weight gain (GWG) are associated with birth weight. METHODS: Early pregnant women were recruited into a Japanese nationwide prospective birth cohort study between 2011 and 2014. We analysed data of 89,817 mother-child pairs of live-born non-anomalous singletons after excluding births before 28 weeks or after 42 weeks. Energy intake during pregnancy was estimated from self-administered food frequency questionnaires (FFQ) and was stratified into low, medium, and high. Participants completed the FFQ in mid-pregnancy (mean 27.9 weeks) by recalling food consumption at the beginning of pregnancy. Effects of energy intake on birth weight and mediation by GWG were estimated using the Karlson-Holm-Breen method; the method separates the impact of confounding in the comparison of conditional and unconditional parameter estimates in nonlinear probability models. Relative risks and risk differences for abnormal birth size were calculated. RESULTS: Mean daily energy intake, GWG, and birth weight were 1682.1 (533.6) kcal, 10.3 (4.0) kg, and 3032.3 (401.4) g, respectively. 6767 and 9010 women had small-for-gestational-age and large-for-gestational-age infants, respectively. Relative to low energy intake, moderate and high intakes increased adjusted birth weights by 13 g and 24 g, respectively: 58 and 69% of these effects, respectively, were mediated by GWG. Compared with the moderate energy intake group, the low energy intake group had seven more women per 1000 women with a small-for-gestational-age birth, whereas the high energy intake group had eight more women per 1000 women with a large-for-gestational-age birth. CONCLUSION: GWG mediates the effect of energy intake on birth weight. All pregnant women should be given adequate nutritional guidance for optimal GWG and fetal growth.

Development of a parent-reported screening tool for avoidant/restrictive food intake disorder (ARFID): Initial validation and prevalence in 4-7-year-old Japanese children.

The prevalence of avoidant/restrictive food intake disorder (ARFID) in the general child population is still largely unknown and validated screening instruments are lacking. The aims of this study were (1) to investigate the prevalence of children screening positive for ARFID in a Japanese birth cohort using a newly developed parent-reported screening tool, (2) to estimate the prevalence of children with ARFID experiencing physical versus psychosocial consequences of their eating pattern, and (3) to provide preliminary evidence for the validity of the new screening tool. Data were collected from 3728 4-7-year-old children born between 2011 and 2014 in Kochi prefecture, Japan (response rate was 56.5%); a sub-sample of the Japan Environment and Children's Study (JECS). Parents completed a questionnaire including the ARFID screener and several other measures to assess convergent validity. The point prevalence of children screening positive for ARFID was 1.3%; half of them met criteria for ARFID based on psychosocial impairment alone, while the other half met diagnostic criteria relating to physical impairment (and additional psychosocial impairment in many cases). Sensory sensitivity to food characteristics (63%) and/or lack of interest in eating (51%) were the most prevalent drivers of food avoidance. Children screening positive for ARFID were lighter in weight and shorter in height, they showed more problem behaviors related to mealtimes and nutritional intake, and they were more often selective eaters and more responsive to satiety, which together provides preliminary support for the validity of the new screening tool. This is the largest screening study to date of ARFID in children up to 7 years. Future studies should examine the diagnostic validity of the new ARFID screener using clinically ascertained cases. Further research on ARFID prevalence in the general population is needed.

Monoallelic, antisense and total RNA transcription in an in vitro neural differentiation system based on F1 hybrid mice.

We developed an in vitro system to differentiate embryonic stem cells (ESCs) derived from reciprocally crossed F1 hybrid mice into neurons, and used it to investigate poly(A)+ and total RNA transcription at different stages of cell differentiation. By comparing expression profiles of transcripts assembled from 20 RNA sequencing datasets [2 alleles×(2 cell lines×4 time-points+2 mouse brains)], the relative influence of strain, cell and parent specificities to overall expression could be assessed. Divergent expression profiles of ESCs converged tightly at neural progenitor stage. Patterns of temporal variation of monoallelically expressed transcripts and antisense transcripts were quantified. Comparison of sense and antisense transcript pairs within the poly(A)+ sample, within the total RNA sample, and across poly(A)+ and total RNA samples revealed distinct rates of pairs showing anti-correlated expression variation. Unique patterns of sharing of poly(A)+ and poly(A)- transcription were identified in distinct RNA species. Regulation and functionality of monoallelic expression, antisense transcripts and poly(A)- transcription remain elusive. We demonstrated the effectiveness of our approach to capture these transcriptional activities, and provided new resources to elucidate the mammalian developmental transcriptome.

Lack of concern about body image and health during pregnancy linked to excessive gestational weight gain and small-for-gestational-age deliveries: the Japan Environment and Children's Study.

BACKGROUND: Pregnant women in Japan express various reasons for limiting gestational weight gain (GWG). We aimed to identify and characterise groups where the women share common reasons to limit GWG and to examine how these groups are associated with inappropriate GWG and abnormal foetal size. METHODS: We prospectively studied information from the Japan Environment and Children's Study (JECS) on 92,539 women who gave birth to live singletons from 2011 through 2014. Pregnant women were recruited during early pregnancy. Their reasons for limiting GWG and other information were collected through self-reported questionnaires and medical records. We applied latent class analysis to group the women based on their reported reasons. We used multinomial logistic regression to compare the risks of inappropriate (inadequate and excessive) GWG and abnormal foetal size (determined by new-born weight for gestational age) between the identified groups. RESULTS: We identified three groups: Group 1 (76.7%), concerned about delivery and new-born health (health-conscious women); Group 2 (14.5%), concerned about body shape, delivery, and new-born health (body-shape- and health-conscious women); and Group 3 (8.8%), women without strong reasons to limit GWG (women lacking body-shape and health consciousness). Compared with Group 1 members, Group 2 members tended to be younger, have lower pre-pregnancy weight, be unmarried, be nulliparous, have practiced weight loss before pregnancy, and not have chronic medical conditions. Group 3 members tended to be less educated, unmarried, multiparous, smokers, and have a higher prevalence of pre-pregnancy underweight and previous caesarean delivery. Relative to Group 1, Group 2 had a lower unadjusted risk for inadequate GWG (relative risk ratio [RRR] = 0.86, 95% CI: 0.81-0.90) and large-for-gestational-age birth (RRR = 0.91, 95% CI 0.86-0.97), whereas Group 3 had a higher unadjusted risk for excessive GWG (RRR = 1.36, 95% CI: 1.29-1.43) and small-for-gestational-age (SGA) births (RRR = 1.15, 95% CI: 1.05-1.25). CONCLUSIONS: In this Japanese nationwide birth cohort study, pregnant women who were less conscious about body shape and health had complex risks for excessive GWG and SGA birth. Health care providers should consider a woman's perception of GWG when addressing factors affecting GWG and foetal growth.

Characterization and selection of Japanese electronic health record databases used as data sources for non-interventional observational studies.

BACKGROUND: Interventional studies are the fundamental method for obtaining answers to clinical questions. However, these studies are sometimes difficult to conduct because of insufficient financial or human resources or the rarity of the disease in question. One means of addressing these issues is to conduct a non-interventional observational study using electronic health record (EHR) databases as the data source, although how best to evaluate the suitability of an EHR database when planning a study remains to be clarified. The aim of the present study is to identify and characterize the data sources that have been used for conducting non-interventional observational studies in Japan and propose a flow diagram to help researchers determine the most appropriate EHR database for their study goals. METHODS: We compiled a list of published articles reporting observational studies conducted in Japan by searching PubMed for relevant articles published in the last 3 years and by searching database providers' publication lists related to studies using their databases. For each article, we reviewed the abstract and/or full text to obtain information about data source, target disease or therapeutic area, number of patients, and study design (prospective or retrospective). We then characterized the identified EHR databases. RESULTS: In Japan, non-interventional observational studies have been mostly conducted using data stored locally at individual medical institutions (663/1511) or collected from several collaborating medical institutions (315/1511). Whereas the studies conducted with large-scale integrated databases (330/1511) were mostly retrospective (73.6%), 27.5% of the single-center studies, 47.6% of the multi-center studies, and 73.7% of the post-marketing surveillance studies, identified in the present study, were conducted prospectively. We used our findings to develop an assessment flow diagram to assist researchers in evaluating and choosing the most suitable EHR database for their study goals. CONCLUSIONS: Our analysis revealed that the non-interventional observational studies were conducted using data stored local at individual medical institutions or collected from collaborating medical institutions in Japan. Disease registries, disease databases, and large-scale databases would enable researchers to conduct studies with large sample sizes to provide robust data from which strong inferences could be drawn.

Acute effect of the COVID-19 pandemic on emergency transportation due to acute alcoholic intoxication: a retrospective observational study.

BACKGROUND: The COVID-19 pandemic has caused changes in people's drinking habits and the emergency management system for various diseases. However, no studies have investigated the pandemic's impact on emergency transportation for acute alcoholic intoxication. This study examines the effect of the pandemic on emergency transportation due to acute alcoholic intoxication in Kochi Prefecture, Japan, a region with high alcohol consumption. METHODS: A retrospective observational study was conducted using data of 180,747 patients from the Kochi-Iryo-Net database, Kochi Prefecture's emergency medical and wide-area disaster information system. Chi-squared tests and multiple logistic regression analyses were performed. The association between emergency transportation and alcoholic intoxication was examined. The differences between the number of transportations during the voluntary isolation period in Japan (March and April 2020) and the same period for 2016-2019 were measured. RESULTS: In 2020, emergency transportations due to acute alcoholic intoxication declined by 0.2%, compared with previous years. Emergency transportation due to acute alcoholic intoxication decreased significantly between March and April 2020, compared with the same period in 2016-2019, even after adjusting for confounding factors (adjusted odds ratio 0.67; 95% confidence interval 0.47-0.96). CONCLUSIONS: This study showed that lifestyle changes due to the COVID-19 pandemic affected the number of emergency transportations; in particular, those due to acute alcoholic intoxication decreased significantly.

SOD2 mRNA as a potential biomarker for exercise: interventional and cross-sectional research in healthy subjects.

The health-promoting effects of exercise are explained by the biological adaptation to oxidative stress via maintenance of mitochondrial function especially in muscles. Although the induction of antioxidant enzymes in muscle is a useful indicator of exercise, it is not widely used due to the invasiveness of muscle biopsies. To explore more suitable biomarkers for exercise, we examined mRNA levels of antioxidant enzymes in peripheral blood mono-nuclear cells of 14 volunteers in an exercise intervention study. These results were validated in a cross-sectional study of 392 healthy individuals, and we investigated the association between exercise habits, smoking, alcohol consumption, mitochondrial DNA, malondialdehyde, and various clinical features. The 2-week exercise increased superoxide dismutase 1 at the end of exercise and superoxide dismutase 2 from week 4 onwards. In the cross-sectional study, superoxide dismutase 2 correlated positively with exercise habits and number of mitochondrial DNA, and negatively with malondialdehyde levels. Multivariate binominal regression analysis showed that superoxide dismutase 2 was positively associated with exercise habits in nonsmoking individuals. These results suggest that mRNA levels of superoxide dismutase 2 in blood might be a potentially useful biomarker for exercise in healthy individuals. This study was registered with University Hospital Medical Information Network (No: 000038034).

Biological functions of mesenchymal stem cells and clinical implications.

Mesenchymal stem cells (MSCs) are isolated from multiple biological tissues-adult bone marrow and adipose tissues and neonatal tissues such as umbilical cord and placenta. In vitro, MSCs show biological features of extensive proliferation ability and multipotency. Moreover, MSCs have trophic, homing/migration and immunosuppression functions that have been demonstrated both in vitro and in vivo. A number of clinical trials are using MSCs for therapeutic interventions in severe degenerative and/or inflammatory diseases, including Crohn's disease and graft-versus-host disease, alone or in combination with other drugs. MSCs are promising for therapeutic applications given the ease in obtaining them, their genetic stability, their poor immunogenicity and their curative properties for tissue repair and immunomodulation. The success of MSC therapy in degenerative and/or inflammatory diseases might depend on the robustness of the biological functions of MSCs, which should be linked to their therapeutic potency. Here, we outline the fundamental and advanced concepts of MSC biological features and underline the biological functions of MSCs in their basic and translational aspects in therapy for degenerative and/or inflammatory diseases.

Severity of Nausea and Vomiting in Singleton and Twin Pregnancies in Relation to Fetal Sex: The Japan Environment and Children's Study (JECS).

BACKGROUND: Some studies have indicated that female birth and multiple births were risk factors for nausea and vomiting during pregnancy (NVP). The results, however, were conflicting. Our study was conducted to evaluate the association of maternal NVP with fetal sex in singleton and twin pregnancies. METHODS: We used the data set from a birth cohort study, the Japan Environment and Children's Study (JECS). In the self-administered questionnaire, participants were asked whether they experienced NVP prior to 12 gestational weeks. Main outcome measures were the presence of NVP and severity of NVP. We estimated the association of fetal sex and birth plurality with NVP using logistic regression analysis, followed by interaction analysis. RESULTS: Of 91,666 women, 75,828 (82.7%) experienced at least some symptoms of NVP and 10,159 (11.1%) experienced severe NVP. Women with female pregnancies and twin pregnancies had higher odds for the presence of NVP and severe NVP compared to women with male pregnancies and singleton pregnancies, respectively. Moreover, of mothers with twin pregnancies, higher odds for the presence of NVP and severe NVP were reported when one or both infants were female, compared to those in which both infants were male. There was no significant interaction between fetal sex and birth plurality. CONCLUSIONS: Female sex birth and multiple births are risk factors for the presence of NVP, and especially for severe NVP without interaction. These findings suggest that a factor abundant in the female fetus associates with the severity of NVP.

Nausea and vomiting during pregnancy associated with lower incidence of preterm births: the Japan Environment and Children's Study (JECS).

BACKGROUND: Nausea and vomiting during pregnancy (NVP) is considered to be associated with favorable fetal outcomes, such as a decreased risk for spontaneous abortion. However, the relationship between NVP and preterm births remains unknown. This study was conducted to evaluate the association between NVP and the risk of preterm births. METHODS: The dataset of a birth cohort study, the Japan Environment and Children's Study (JECS), was retrospectively reviewed. Participants' experience of NVP prior to 12 gestational weeks were evaluated by a questionnaire administered from 22 weeks of pregnancy to 1 month before delivery. NVP responses were elicited against four choices based on which the study population was divided into four subcohorts. Preterm birth was the main study outcome. Logistic regression analysis was used to quantify an association between NVP and risk of preterm birth. RESULTS: Of 96,056 women, 79,460 (82.7%) experienced some symptoms of NVP and 10,518 (10.9%) experienced severe NVP. Compared to those who did not experience NVP, women with severe NVP had lower odds for preterm birth [adjusted odds ratio (aOR) 0.84, 95% confidence interval (95% CI) 0.74-0.95]. An even lower OR was found among very preterm birth and extremely preterm birth (aOR 0.44, 95% CI 0.29-0.65). CONCLUSION: An inverse association exists between NVP and preterm births, especially, very preterm births and extremely preterm births.

Occupation exposed to road-traffic emissions and respiratory health among Congolese transit workers, particularly bus conductors, in Kinshasa: a cross-sectional study.

OBJECTIVES: Road-traffic emissions (RTE) induce adverse health effects, notably respiratory symptoms and respiratory diseases, as a result of pollutants deposited into the respiratory tract. The aim of this study was to evaluate the association between occupation groups of Congolese transit workers exposed to RTE, particularly bus conductors and respiratory health, in Kinshasa. METHODS: A cross-sectional study was conducted from 2015 April 20th to May 14th, whose participants were bus conductors (n = 110), bus drivers (n = 107), taxi-motorcyclists (n = 102) and high school teachers (control group; n = 106). Subjects had completed the American Thoracic Society respiratory symptom questionnaire. Lung function test was performed by spirometry. Air pollutants levels of PM2.5, NO2 and SO2 were measured between 7:30 and 8:30 and 16:30-17:30 using a portable gas monitor. Multivariate analysis was performed to evaluate the association between occupation exposed to RTE and impaired pulmonary function, after adjustment by plausible confounders. RESULTS: The prevalence of mixed syndrome was 21.9% for bus conductors, 10.9% for bus drivers, 15.4% for taxi-motorcyclists and 7.1% for high school teachers with (p < 0.05). The risk of developing a mixed syndrome was seven times higher among bus conductors [OR = 7.64; 95% CI: 1.83-31.67; p < 0.05] than other groups. Additionally, the prevalence of respiratory syndromes increased with the duration of exposure. CONCLUSIONS: Occupation exposed to RTE is associated with impaired pulmonary function and the prevalence of respiratory symptoms among transit workers, especially bus conductors. Furthermore, this association increases with the duration of exposure suggesting the necessity to regulate these categories of occupations and to apply preventives measures.

Fibrotic gene expression coexists with alveolar proteinosis in early indium lung.

Occupational inhalation of indium compounds can cause the so-called "indium lung disease". Most affected individuals show pulmonary alveolar proteinosis (PAP) and fibrotic interstitial lung disease. In animal experiments, inhalation of indium tin oxide or indium oxide has been shown to cause lung damage. However, the mechanisms by which indium compounds lead to indium lung disease remain unknown. In this study, we constructed a mouse model of indium lung disease and analyzed gene expression in response to indium exposure. Indium oxide (In2O3, 10 mg/kg, primary particle size <100 nm) was administered intratracheally to C57BL/6 mice (male, 8 weeks of age) twice a week for 8 weeks. Four weeks after the final instillation, histopathological analysis exhibited periodic acid-Schiff positive material in the alveoli, characteristic of PAP. Comprehensive gene expression analysis by RNA-Seq, however, revealed expression of fibrosis-related genes, such as surfactant associated protein D, surfactant associated protein A1, mucin 1, and collagen type I and III, was significantly increased, indicating that fibrotic gene expression progresses in early phase of indium lung. These data supported the latest hypothesis that PAP occurs as an acute phase response and is replaced by fibrosis after long-term latency.

Regulation of Gene Expression by Sodium Valproate in Epithelial-to-Mesenchymal Transition.

PURPOSE: Epithelial-to-mesenchymal transition (EMT) is an important mechanism in cancer metastasis and pulmonary fibrosis. Previous studies demonstrated effect of histone H3 and H4 acetylation in cancer and pulmonary fibrosis, so we hypothesized that histone modification might play a crucial role in gene regulation during EMT. In this study, we investigated the mechanism behind EMT by analyzing comprehensive gene expression and the effect of sodium valproate (VPA), a class I histone deacetylase inhibitory drug, on histone modification. METHODS: EMT was induced in human alveolar epithelial cells (A549) using 5 ng/mL of transforming growth factor (TGF)-ß1. Various concentrations of VPA were then administered, and Western blotting was used to analyze histone acetylation or methylation. Comprehensive gene expression analysis was carried out by RNA sequencing, and chromatin immunoprecipitation was performed with an anti-acetyl histone H3 lysine 27 antibody. RESULTS: TGF-ß1 stimulation led to a decrease in histone acetylation, especially that of histone H3K27, and H3K27ac localization was decreased at particular gene loci. This decrease was recovered by VPA treatment, which also up-regulated the mRNA expression of genes down-regulated by TGF-ß1, and correlated with the localization of H3K27ac. However, genes up-regulated by TGF-ß1 stimulation were not suppressed by VPA, with the exception of COL1A1. CONCLUSIONS: Histone acetylation was down-regulated by TGF-ß1 stimulation in A549 cells. VPA partially inhibited EMT and the decrease of histone acetylation, which plays an important role in the progression of EMT.