Infantile allergic diseases: a cohort study prenatal fish intake and mercury exposure context.

BACKGROUND: Allergic diseases (ADs) have been increasingly reported in infants and children over the last decade. Diet, especially the inclusion of fish intake, may help to lower the risk of ADs. However, fish also, can bioaccumulate environmental contaminants such as mercury. Hence, our study aims to determine what effects the type and frequency of fish intake have on ADs in six-month-old infants, independently and jointly with mercury exposure. METHODS: This study is part of the prospective birth cohort: Mothers and Children's Environmental Health (MOCEH) study in South Korea. Data was collected on prenatal fish intake, prenatal mercury concentration and ADs for infants aged six months for 590 eligible mother-infant pairs. Logistic regression analysis was conducted to evaluate the risk of prenatal fish intake and mercury concentration on ADs in infants. Finally, interaction between fish intake and mercury concentration affecting ADs in infants was evaluated. Hazard ratios of prenatal fish intake on ADs in 6 month old infants were calculated by prenatal mercury exposure. RESULTS: Logistic regression analysis showed that white fish (OR: 0.53; 95% CI 0.30-0.94; P < 0.05) intake frequency, once a week significantly decreased the risk of ADs in infants. Stratification analysis showed that consuming white fish once a week significantly reduced the hazard of ADs (HR: 0.44; 95% CI 0.21-0.92; P < 0.05) in infants in the high-mercury (≥ 50th percentile) exposure group. CONCLUSION: The result indicates that prenatal white fish intake at least once a week reduces the risk of ADs in infants, especially in the group with high prenatal mercury exposure.

Association between long-term PM2.5 exposure and risk of Kawasaki disease in children: A nationwide longitudinal cohort study.

BACKGROUND: Based on previous studies suggesting air pollution as a potential risk factor for Kawasaki Disease (KD), we examined the association of long-term exposure to childhood fine particulate matter (PM2.5) with the risk of KD. METHODS: We used National Health Insurance Service-National Sample Cohort data from 2002 to 2019, which included beneficiaries aged 0 years at enrollment and followed-up until the onset of KD or age 5 years. The onset of KD was defined as the first hospital visit record with a primary diagnostic code of M30.3, based on the 10th revision of the International Classification of Diseases, and with an intravenous immunoglobulin (IVIG) prescription. We assigned PM2.5 concentrations to 226 districts, based on mean annual predictions from a machine learning-based ensemble prediction model. We performed Cox proportional-hazards modeling with time-varying exposures and confounders. RESULTS: We identified 134,634 individuals aged five or less at enrollment and, of these, 1220 individuals who had a KD onset and an IVIG prescription during study period. The average annual concentration of PM2.5 exposed to the entire cohort was 28.2 µg/m³ (Standard Deviation 2.9). For each 5 µg/m³ increase in annual PM2.5 concentration, the hazard ratio of KD was 1.21 (95% CI 1.05-1.39). CONCLUSIONS: In this nationwide, population-based, cohort study, long-term childhood exposure to PM2.5 was associated with an increased incidence of KD in children. The study highlights plausible mechanisms for the association between PM2.5 and KD, but further studies are needed to confirm our findings.

The introduction to air pollution on pregnancy outcome (APPO) study: a multicenter cohort study.

OBJECTIVE: The air pollution on pregnancy outcome (APPO) study is a prospective hospital-based cohort study designed to investigate the maternal and fetal effects of a particulate matter with an aerodynamic below 10 µm (PM10) and PM2.5 (below 2.5 µm) exposure. This study aims to analyze a relationship between particulate matter and adverse pregnancy outcomes and to find related biomarkers and develop management guidelines. METHODS: About 1,200 pregnant women are recruited for 3 years (from January 2021 to December 2023) from seven university hospitals to investigate the effects of particulate matter on pregnancy complications and adverse pregnancy outcomes. We collect biological samples by 5 mL of maternal venous blood and 15 mL of urine in each trimester of pregnancy, and 5 mL of umbilical cord blood and 2×2×2 cm of placental tissue are collected after delivery. In addition, by applying PM10 and PM2.5 concentration values and time-activity patterns from the time weighted average model, the individual predicted exposure of air pollution for the pregnant women are obtained. RESULTS: The average exposure of PM10 and PM2.5 of the participants in the entire period of pregnancy, was exceeded the World Health Organization air quality guidelines (an annual level, PM10 >15 µg/m3, PM2.5 >5 µg/m3). Moreover, it was revealed that the PM concentration was increasing toward the 3rd trimester of pregnancy. CONCLUSION: The APPO study will be able to identify the degree of exposure to air pollution in pregnant women and use it as basic data for estimating individual exposure to particulate matter. And the results of the APPO study will facilitate in the development of health management for pregnant women against air pollution.

Effect of PM concentration on anemia blood indicators reduced by air purifiers.

Housewives perform daily household chores, which directly expose them to indoor particulate matter (PM). Indoor PM exposure is a potential factor that increases systemic inflammation and affects hematopoietic action. This study investigated the decrease in indoor PM concentration by air purifiers on indicators of anemia, such as hemoglobin, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). We analyzed the data of 40 housewives who were subjected to an air purifier intervention in Seoul and Ulsan, Republic of Korea. Indoor exposure levels of PM2.5 and PM10 were analyzed with sensor adjusted and gravimetric measurement. We also investigated the same anemia indicators before and after the installation of an air purifier for three months (short-term: one month, long-term: three months). Statistical analysis was performed by a multiple linear model and a linear mixed model. The indoor PM exposure levels and air purifier use were related to anemia indicators (hemoglobin and MCHC). The increase in indoor PM2.5 level was associated with a decrease in MCHC (ß: 0.034, P = 0.031) and hemoglobin (ß: 0.013, P = 0.04). The decrease in indoor PM2.5 concentration by air purifier was associated with an increase in MCHC (ß: 0.204, P = 0.087) and hemoglobin (ß: 0.190, P = 0.039). In particular, after air purifier intervention, the amounts of MCHC and hemoglobin significantly increased. Our results suggest that indoor air purifier use could decrease indoor PM level and the risk of anemia to housewives. Because the effect on anemia is subacute, it was confirmed three months after air purifier operation. In conclusion, anemia indicators can be improved by PM reduction management.

Prospective association between phthalate exposure in childhood and liver function in adolescence: the Ewha Birth and Growth Cohort Study.

BACKGROUND: Phthalate exposure is ubiquitous due to the widespread use of plastic products in daily life, and affects several health outcomes, including metabolic diseases. In this study, we evaluated the effects of phthalate exposure in childhood on liver function in adolescence.  METHODS: Among 164 Ewha Birth and Growth Cohort Study participants followed up during two exposure periods (when the children were aged 3-5 and 7-9 years), 126 were followed up at age 10-15 years. To investigate the relationship between phthalate exposure during the two periods and liver enzyme levels (ALT, AST, γ-GTP) in adolescence, differences between groups and the dose-response relationship were analyzed. In addition, we investigated differences in liver enzymes between groups based on the combined exposure levels (high or low) during the two periods. The interaction effect between phthalates and BMI on liver enzyme levels was evaluated, stratified by sex.  RESULTS: In the 3-5 year-old exposure period, ALT levels tended to increase as MECPP levels increased, while γ-GTP levels tended to increase as MiBP, MnBP, and ∑DBP levels increased. In addition, the group exposed to consistently high levels of phthalates at both time points had higher liver enzyme levels compared to the group that had lower exposure. In particular, the interaction effect between some phthalate metabolites and BMI in 3-5 year olds affected AST and γ-GTP levels in adolescence only in girls. CONCLUSIONS: Exposure to phthalates in daily life during childhood affects liver enzyme levels in adolescence. Elevated liver enzyme levels are associated with the development of metabolic syndrome, implying that attention should be paid to phthalate exposure during childhood.

BMI trajectory and inflammatory effects on metabolic syndrome in adolescents.

BACKGROUND: Various life course factors can affect susceptibility to diseases during adolescence and adulthood, and those relationships are complex. However, few studies have assessed the potential mediating factors. Therefore, we assessed the mediating effects of factors related to growth and inflammation between perinatal factors and metabolic syndrome risk during adolescence. METHODS: The study was conducted on adolescents who participated in the follow-up in the Ewha Birth and Growth Cohort. We considered the ponderal index (PI) as a perinatal factor and the continuous metabolic syndrome score (cMetS) as the outcome and confirmed the mediating effects of body mass index (BMI) trajectory pattern in childhood and inflammation levels by using the PROCESS macro for SAS. RESULTS: Although the direct effect of BMI trajectory on the relationship between PI and cMetS was not significant (0.545), the indirect effect was significant (1.044). In addition, the indirect effect was statistically significant in the pathways mediating the BMI trajectory pattern and inflammation (ß = 1.456). CONCLUSIONS: The direct and indirect effects on the relationship between PI and cMetS suggest that childhood factors related to growth may be involved in disease susceptibility. Therefore, appropriate interventions for the management of obesity during the growth phase are necessary. IMPACT: Unlike other existing studies, this study assessed multiple mediating effects by considering the BMI trajectory pattern and inflammatory indexes as mediating factors between the ponderal index and the continuous metabolic syndrome score during adolescence. We found significant indirect effects of the BMI trajectory between PI and cMetS, and also significant indirect effects in the pathways mediating the BMI trajectory and hs-CRP. The significant indirect mediating effects support that childhood factors related to growth may be involved in disease susceptibility.

Association of paternal cadmium and other heavy metal exposure to birth outcomes using propensity score matching.

BACKGROUND: Human exposure to cadmium has various effects on health, especially on male reproductive organs. Although it is widely known that prenatal maternal cadmium exposure can affect birth outcomes, the effect of paternal exposure to cadmium remains unclear. OBJECTIVES: This study aimed to evaluate the effect of paternal cadmium exposure on fetal growth by considering maternal cadmium exposure and exposure to other heavy metals, namely mercury and lead. METHODS: The Mothers and Children's Environmental Health (MOCEH) study is a prospective birth cohort study in Korea. Overall, 1313 families (father-mother-child triple) without child abnormalities and who completed paternal whole blood cadmium assessments were included in this study. Families were divided into two subgroups based on the blood sampling periods, namely early and late pregnancy. Subjects were selected as follows: one family triple with a high level of paternal cadmium and two triples with low levels of paternal cadmium, using the method of propensity score matching. And linear regression analyses were performed. RESULTS: The group with high paternal cadmium exposure (80% or more; 1.93 µg/L) had lower birth weight infants compared to the group with low cadmium concentrations (ß(se) = -0.21(0.10); p-value = 0.0283). After stratification by infant sex, prenatal paternal cadmium exposure significantly reduced the birth weight of females in subgroups of different sampling times, namely early pregnancy (ß(se) = -0.52 (0.22); p-value = 0.0170) and late pregnancy (ß(se) = -0.43 (0.18); p-value = 0.0160). Finally, after performing propensity score matching in the early pregnancy measurement group, it was found that the prenatal exposure of father to cadmium significantly reduced birth weight in females (ß(se) = -0.72(0.25); p-value = 0.0047). CONCLUSION: This study assessed the effect of paternal cadmium exposure on birth outcomes in family units consisting of a father, mother, and child. Prenatal paternal cadmium exposure negatively affected birth weight, especially that of female, considering covariates and other heavy metals exposure, namely mercury and lead.

A COVID-19 mortality prediction model for Korean patients using nationwide Korean disease control and prevention agency database.

The experience of the early nationwide COVID-19 pandemic in South Korea led to an early shortage of medical resources. For efficient resource allocation, accurate prediction of the prognosis or mortality of confirmed patients is essential. Therefore, the aim of this study was to develop an accurate model for predicting COVID-19 mortality using epidemiolocal and clinical variables and for identifying a high-risk group of confirmed patients. Clinical and epidemiolocal variables of 4049 patients with confirmed COVID-19 between January 20, 2020 and April 30, 2020 collected by the Korean Disease Control and Prevention Agency were used. Among the 4049 total confirmed patients, 223 patients died, while 3826 patients were released from isolation. Patients who had the following risk factors showed significantly higher risk scores: age over 60 years, male sex, difficulty breathing, diabetes, cancer, dementia, change of consciousness, and hospitalization in the intensive care unit. High accuracy was shown for both the development set (n = 2467) and the validation set (n = 1582), with AUCs of 0.96 and 0.97, respectively. The prediction model developed in this study based on clinical features and epidemiological factors could be used for screening high-risk groups of patients and for evidence-based allocation of medical resources.

Mortality Risk within 14 Days after Coronavirus Disease 2019 Diagnosis in Dementia Patients: A Nationwide Analysis.

INTRODUCTION: The study evaluated the increased mortality risk within 14 days of coronavirus disease 2019 (COVID-19) diagnosis in dementia patients. METHODS: This retrospective study was conducted from February to April 2020 using the COVID-19 patients' database from the Korea Disease Control and Prevention Agency. The risk factors for early death within 14 days were determined using generalized logistic regression performed in a stepwise manner. Dementia patients diagnosed with COVID-19 were used for the study. The propensity score-matched cohort was included as controls. The differences in mortality within 14 days after COVID-19 diagnosis between the dementia patients and controls were evaluated. RESULTS: We enrolled 5,349 COVID-19 patients from the database; 224 had dementia as comorbidity. The mortality rate within 14 days after COVID-19 diagnosis in dementia patients and the controls was 23.7% versus 1.7%, respectively, before propensity score matching (PSM) (p < 0.001), and 23.7% versus 9.2% after PSM (p < 0.001). The hazard ratio (HR) for mortality within 14 days in COVID-19 patients with dementia was significant even after PSM (HR 5.104, 95% confidence interval 2.889-5.673, p < 0.001). The survival curve of dementia patients was steeply inclined within 14 days after COVID-19 diagnosis, resulting in 70.7% of all deaths in dementia patients. CONCLUSIONS: COVID-19 patients with dementia had a higher risk of early death within 14 days. Thus, prompt intervention is necessary for dementia patients after COVID-19 diagnosis.

Cohort profile: the Ewha Birth and Growth Study.

With the introduction of life-course epidemiology, researchers realized the importance of identifying risk factors in early life to prevent chronic diseases. This led to the establishment of the Ewha Birth and Growth Study in 2001; the study is a prospective birth cohort designed to provide evidence of early life risk factors for a child's growth and health. Participants were recruited from those who visited Ewha Womans University Mokdong Hospital (a tertiary hospital in southwest Seoul, Korea) for prenatal care at 24-28 weeks of gestation. In total, 891 mothers enrolled in this study between 2001 and 2006 and their offspring (n=940) were followed-up. Regular check-up examinations of offspring were conducted at 3 years, 5 years, and 7 years of age and every year thereafter. To consider age-related health issues, extensive data were collected using questionnaires and measurements. In 2021, the study subjects will reach 19 years of age, and we are planning a check-up examination for early adulthood. About 20 years have passed since the cohort data were collected, and we have published results on childhood health outcomes associated with prenatal and birth characteristics, genetic and epigenetic characteristics related to childhood metabolism, the effects of exposure to endocrine disruptors, and dietary patterns in childhood. Recently, we started reporting on topics related to adolescent health. The findings will facilitate identification of early life risk factors for chronic diseases and the development of interventions for diseases later in life.

The Association of Ovarian Reserve with Exposure to Bisphenol A and Phthalate in Reproductive-aged Women.

BACKGROUND: Exposure to endocrine disrupting chemicals (EDCs) that influence the hormonal and homeostatic systems is known to be associated with gynecologic health risks in many countries. In this study, we evaluated exposure to EDCs associated with diminished ovarian reserve (DOR) and gynecologic health risks. METHODS: This cross-sectional study was performed from September 2014 to November 2014 and included 307 Korean reproductive-aged women. Anthropometric measurements, laboratory tests with urine and blood sampling and pelvic ultrasound examinations were performed. RESULTS: Urinary bisphenol A (BLA) level was significantly higher in the DOR group with anti-Müllerian hormone lower than 25 percentile (1.89 ± 2.17 ug/g and 1.58 ± 1.08 ug/g, P < 0.05). Urinary mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate and mono-N-butyl phthalate, and substrates of phthalate were evaluated and no significant difference was observed between the DOR group and non-DOR group. Logistic regression analysis suggested an increase in infertility in high BPA exposure group and the odds ratio (OR, 4.248) was statistically significant after adjustment for age, birth control pills, and the age of menarche, parity, and waist circumference. High phthalate exposure was associated with endometrial polyp after adjustment (OR, 2.742). CONCLUSION: BPA exposure might be associated with DOR and infertility. Meanwhile, endometrial polyp is increased in women with high phthalate exposure. Therefore, the risk of exposures to EDCs for reproduction should be a matter of concern in reproductive-aged women.

Effect of heat waves and fine particulate matter on preterm births in Korea from 2010 to 2016.

BACKGROUND: Previous studies have reported that fine particulate matter (PM2.5) affects the incidence of premature births. In addition, recent studies have suggested that heat waves have a negative impact on birth outcomes. However, the combined effect of PM2.5 and heat waves on the incidence of premature birth is controversial. This study investigated the independent and combined effects of PM2.5 and heat wave exposures during the 1st and 2nd trimesters on premature birth. METHODS: The National Statistical Office of Korea provided birth data from 2010 to 2016. Preterm birth was defined as birth between 22 and 36 weeks. To assess the exposure to PM2.5 and heat waves, we used PM2.5 data estimated by the Community Multiscale Air Quality Modeling System (CMAQ) and heat wave warning data provided by the Korea Meteorological Administration. A multivariate logistic regression was used to investigate the risk of preterm birth according to the exposure to PM2.5 and heat waves during the 1st and 2nd trimesters, and it was adjusted for residential area, year of birth, season of birth, parity, education level of the mother, age of the mother, and sex of the baby. RESULTS: In the 2nd trimester, compared with the 0 h of heat wave exposure (≤67 percentile), 62.50-314.00 h (79-88 percentile) and>315.00 h of heat wave exposure (>88 percentile) were both significantly associated with preterm birth (OR for 79-88 percentile, 1.037, 95% CI, 1.003-1.073; OR for > 88 percentile, 1.174, 95% CI, 1.134-1.215). However, PM2.5 exposure was not significantly associated with preterm birth. On the other hand, in the analysis to evaluate the combined effect of PM2.5 and heat wave exposures of the 2nd trimester, compared with 0 h of heat wave exposure (≤67 percentile) and<11.64 µg/m3 (≤25 percentile) of PM2.5, 11.64-22.74 µg/m3 (≤25 percentile), 22.74-27.58 µg/m3 (26-50 percentile), and 27.57-32.39 µg/m3 (51-75 percentile) of PM2.5 exposure combined with>315.00 h of heat wave exposure (>88 percentile) were all significantly associated with preterm birth. In addition, the effect size was increased with an increase of PM2.5 exposure (OR for ≤ 25 percentile, 1.148, 95% CI, 1.095-1.203; OR for 26-50 percentile, 1.248, 95% CI, 1.178-1.323; OR for 51-75 percentile, 1.370, 95% CI, 1.245-1.507). CONCLUSION: Our findings suggest that the combined effect of heat wave and PM2.5 exposure during the 2nd trimester on the risk of preterm birth was greater than that of each exposure alone. In other words, exposure to PM2.5 increases the impact of heat waves on the risk of preterm birth. These results indicate that control of prenatal exposure to fine particular matter and extreme temperatures is important for the prevention of preterm birth.

Dietary factors associated with inflammatory laryngeal disease in South Korea.

Laryngeal inflammation causes not only benign diseases of the larynx, such as laryngitis and granuloma, but also malignancy. Dietary factors are known to control or modulate the inflammatory reaction in the body. To date, the association between laryngeal inflammation and dietary factors has not been reported using nationwide population-based data. The aim of this study was to analyze the association between several dietary factors and inflammatory laryngeal disease in the Korean population. This study analyzed the data from Korean National Health and Nutrition Examination Surveys which is cross-sectional nationwide-population-based study. Association between the dietary nutrient intake and the prevalence of inflammatory laryngeal diseases was analyzed in 21,116 participants who underwent a laryngoscopy and filled in the dietary intake questionnaires. Of the 21,116 participants included in the analysis, 758 (3.59%) were diagnosed with inflammatory laryngeal disease. Prevalence of inflammatory laryngeal disease was higher in men (4.58%) than in women (2.84%). The mean age of patients was 53.77 years. When analyzing the risk using propensity score matching, ILD group tend to consume more coffee and to intake less fiber and iron than normal group. On Logistic regression analysis, an increased intake of carbohydrate, fiber, and iron was associated with lowered risk of having ILD in female. The association between inflammatory laryngeal disease and dietary factors was prominent in the group aged ≥50 years and female. Increased intake of fiber, iron, and vitamin A were associated with lower risk in the group aged ≥50 years. In female, increased intake of fiber, iron were associated with lower risk of having ILD. In the group aged ≤50 years, only an increased consumption of makgeolli, Korean traditional rice wine, was associated with a higher risk of ILD.

Adverse effects of prenatal mercury exposure on neurodevelopment during the first 3 years of life modified by early growth velocity and prenatal maternal folate level.

BACKGROUND AND AIMS: Previous studies have suggested that mercury exposure and folate levels during pregnancy may influence early childhood neurodevelopment. Rapid catch-up growth in children is associated with an increased risk of pathological nervous system development. We evaluated whether the association between prenatal folate and mercury-related neuropsychological dysfunction was modified by growth velocity during childhood. METHODS: The Mothers and Children's Environmental Health (MOCEH) birth cohort study began in 2006 and by 2010, 1751 women had been enrolled before the second trimester of their pregnancy along with their partners. Participants visited the research center at birth and 6, 12, 24, and 36 months. We measured mercury levels in maternal and cord blood and folate in maternal serum. Questionnaires to evaluate the environment and health of their child were administered and anthropometric factors including body weight and height were measured. Certified investigators used the Bayley test to measure neurobehavioral outcomes. We calculated postnatal growth change as the change in infant weight for-age z-score between birth and 3 years. Multiple linear regression and mixed models were used to examine the association between mercury exposure and children's neurodevelopment as well as the modifying effects of folate and growth velocity. RESULTS: A total of 30.6% of children experienced rapid growth during the first 3 years of life. Median values of mercury in the low folate group were significantly higher in rapid growers (3.41 µg/L in maternal blood and 5.63 µg/L in cord blood) than in average/slow growers (3.05 µg/L in maternal blood and 5.19 µg/L in cord blood). Rapid growers were also significantly associated with decreased psychomotor development scores during the first 3 years of life and with having mothers who had low prenatal folate levels, even after adjusting for potential confounders. CONCLUSION: Prenatal mercury exposure adversely affects infant neurodevelopment and is associated with rapid growth during the first 3 years of life. This effect was limited to children whose mothers had low prenatal folate levels, suggesting a protective effect of folate against developmental neurotoxicity due to mercury exposure and rapid catch-up growth.

Association between prenatal exposure to PM2.5 and the increased risk of specified infant mortality in South Korea.

BACKGROUND: Findings from previous studies on the association between exposure to fine particulate matter (PM2.5) and the risk of infant mortality were inconsistent. Thus, two main objectives of our study were to examine the association between exposure to PM2.5 and specified infant mortality and to identify critical trimesters. METHODS: We retrospectively created a birth cohort of singleton full-term infants born in South Korea between 2010 and 2015 using national birth and infant mortality data. The specified causes of infant mortality were circulatory and respiratory diseases, perinatal conditions, congenital anomalies, and sudden infant death syndrome. We performed 1:10 propensity score matching for various exposure windows: each trimester, prenatal, and postnatal (up to age 1). Conditional logistic regression was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs), while accounting for gestational age, birth weight, maternal education level, season of birth, and regions (metropolitan areas/provinces). We also conducted sex-stratified analyses and used different matching ratios for sensitivity analyses. RESULTS: A total of 2,501,836 births and 761 deaths (0.03%) were identified in the birth cohort. We found an increased risk of infant mortality per 10 µg/m3 increase in PM2.5 exposure during the prenatal period (OR: 1.29, 95% CI: 1.07-1.55). Exposure in the 1st and 2nd trimesters was linked to an elevated risk (OR: 1.19, 95% CI: 1.02-1.37; OR: 1.21, 95% CI: 1.04-1.40). However, no association was shown in the third trimester. PM2.5 exposure in the 1st and 2nd trimesters was associated with elevated male infant mortality, but did not reach statistical significance in female infants. The use of different matching ratios did not significantly affect the results. CONCLUSION: The study findings suggest that exposure to PM2.5 could affect infant mortality differently by the timing of exposure and sex, which suggests a relation to fetal development. However, further investigations are warranted.

Longitudinal association between environmental tobacco smoke exposure and behavioral problems in children from ages 5 to 9.

Few studies have assessed the cumulative effects of exposure to environmental tobacco smoke (ETS1) in relation to children's neurobehavioral problems over time. We assessed the longitudinal associations between ETS exposure at age 5 and behavioral problems at ages 5, 7, and 9 using the Ewha Birth and Growth Cohort, in Seoul, Korea. Children with available urinary cotinine levels at age 5 and one or more behavioral problem scores measured with the Korean Version of Child Behavior Checklist (CBCL2) at age 5, 7, and 9 were included in the study. Those whose mothers smoked during pregnancy were excluded, and a total of 179 children were included in the analysis. A linear mixed-model analysis using a REPEATED statement was conducted to assess whether ETS exposure was associated with the total, internalizing, and externalizing behavioral problem scores of the CBCL. The group with higher levels of cotinine showed continuously higher total and external behavioral problem scores from ages 5 to 9, which was seen after adjusting for preterm birth, father's education level, and television watching time. In addition, the difference in the total and external behavioral problem scores between the higher and lower cotinine groups at age 5 was statistically significant after a Bonferroni correction (p = 0.02 and 0.04, respectively), even though the fixed effect of cotinine level was almost but not statistically significant (p = 0.07 and 0.08, respectively). The results of this longitudinal cohort study provide evidence regarding the negative effects of ETS exposure in early childhood and their behavioral problems over time. This study supports the strengthening of anti-smoking policies used in educational interventions for parents, in order to reduce early ETS exposure in children.

Prenatal exposure to mixtures of heavy metals and neurodevelopment in infants at 6 months.

BACKGROUND: Exposure to mixture of neurotoxic metals such as lead, mercury and cadmium occurs at a specific point of time. When exposed to metal mixtures, one metal may act as an agonist or antagonist to another metal. Thus, it is important to study the effects of exposure to a combination of metals on children's development using advance statistical methods. OBJECTIVES: In this study, we explored the effects of prenatal metal exposure including lead, mercury and cadmium in early pregnancy (12-20 weeks), late pregnancy (>28 weeks), and at birth on neurodevelopment of infants at 6 months of age. METHODS: We included 523 eligible mother-child pairs from the mothers and children environmental health (MOCEH) study, a prospective birth cohort study in Korea. We used linear regression, Bayesian kernel machine regression (BKMR) and generalized additive models (GAM), to evaluate the effects of exposure to metal mixtures on neurodevelopment of infants aged 6 months. The Korean version of Bayley scale of infant and toddler development-II was used to measure the child's neurodevelopment. RESULTS: Linear regression models showed a significant negative effect of lead exposure during late pregnancy on the mental development index (MDI) [ß = -2.51 (-4.92, -0.10)] scores of infants aged 6 months following co-exposure to mercury. Further, linear regression analysis showed a significant interaction between late pregnancy lead and mercury concentrations. BKMR analysis showed similar results as those obtained in linear regression models. These results were also replicated in the GAM. Stratification analysis showed that greater than 50 percentile concentration of mercury in late pregnancy potentiated the adverse effects of lead in late pregnancy on MDI [ß = -4.33 (-7.66, -1.00)] and psychomotor development index (PDI) [ß = -5.30 (-9.13, -1.46)] at 6 months of age. Prenatal cadmium exposure did not show a significant association with MDI and PDI at 6 months in the linear regression or BKMR analysis. CONCLUSION: Based on all the statistical methods used, we demonstrated the effect of combined exposure to metals on the neurodevelopment of infants aged 6 months, with significant interaction between lead and mercury.

Association between pre-and postnatal growth and longitudinal trends in serum uric acid levels and blood pressure in children aged 3 to 7 years.

BACKGROUND: Uric acid has been identified as an important factor in the development of hypertension. If low birth weight (LBW) combined with catch-up growth (CUG) is associated with continuously elevated serum uric acid levels (SUA) level trajectories, LBW children who experience CUG may have an increased risk of hypertension later in life. Therefore, this cohort study analyzed longitudinal trends in SUA levels and changes in blood pressure in relation to pre- and postnatal growth over an extended follow-up period. METHODS: This prospective cohort study of 364 children from the Ewha Birth and Growth Cohort assessed the effects of pre- and postnatal growth status on SUA at 3, 5, and 7 years of age using a linear mixed model and the change in blood pressure over the 7-year follow-up period using a generalized linear model (analysis of covariance). CUG was defined as a change in weight (between birth and age 3) with a z-score > 0.67 for LBW subjects. The multivariate model considered sex, gestational age, and uric acid, height, and weight at 3 years of age. RESULTS: Children with LBW and CUG had higher SUA for the first 7 years of life compared to the normal birth weight group. This trend was particularly evident when comparing LBW children at term to children with normal birth weight. Within the group with LBW at term, children with greater CUG had higher SUA than children with normal birth weight, and this difference increased with age. Changes in the systolic blood pressure between 3 and 7 years of age were higher by 7.9 mmHg in children who experienced LBW and CUG compared with those who had a normal birth weight after adjusting for sex, gestational age, and height, weight, and uric acid at 3 years of age (p-value = 0.08). CONCLUSIONS: The uric acid levels and changes in systolic blood pressure were consistently higher among LBW children who experienced CUG compared with NBW children for the first 7 years of life. LBW children who experienced greater weight gain from birth to age 3 had even higher uric acid levels compared with NBW children.

Development of novel NLRP3-XOD dual inhibitors for the treatment of gout.

Gout is a crystalline-related arthropathy caused by the deposition of monosodium urate (MSU). Acute gouty arthritis is the most common first symptom of gout. Studies have shown that NOD-like receptor protein 3 (NLRP3) inflammasome as pattern recognition receptors can be activated by uric acid crystallization, triggering immune inflammation and causing acute gouty arthritis symptoms. Currently, the treatment of gout mainly includes two basic methods: reducing uric acid and alleviating inflammation. In this paper, 22 novel benzoxazole and benzimidazole derivatives were synthesized from deoxybenzoin oxime derivatives. These compounds have good inhibitory effects on NLRP3 and XOD screened by our research group in the early stage. The inhibitory activities of XOD and NLRP3 and their derivatives were also screened. Notably, compound 9b is a multi-targeting inhibitor of NLRP3 and XOD with excellent potency in treating hyperuricemia and acute gouty arthritis.

Macrophage-derived progranulin promotes allergen-induced airway inflammation.

BACKGROUND: Progranulin (PGRN), mainly produced by immune and epithelial cells, has been known to be involved in the development of various inflammatory diseases. However, the function of PGRN in allergic airway inflammation has not been clearly elucidated, and we investigated the role of PGRN in allergic airway inflammation. METHODS: Production of PGRN and various type 2 cytokines was evaluated in mouse airways exposed to house dust mite allergen, and main cellular sources of these molecules were investigated using macrophage, airway epithelial cell, and NKT cell lines. We elucidated the role of PGRN in allergic airway inflammation in mouse models of asthma using macrophage-derived PGRN-deficient mice and NKT cell knockout mice by evaluating cytokine levels in bronchoalveolar lavage fluids and histopathology. We also supplemented recombinant PGRN in the mouse models to confirm the role of PGRN in allergic airway inflammation. RESULTS: PGRN production preceded other cytokines, mainly from macrophages, in the airway exposed to allergen. PGRN induced IL-4 and IL-13 production in NKT cells and IL-33 and TSLP in airway epithelial cells. PGRN-induced Th2 cytokine production was abolished in NKT-deficient mice. Finally, allergic inflammation was significantly attenuated in allergen-exposed PGRN-deficient mice, but inflammation was restored when recombinant PGRN was supplemented during the allergen sensitization period. CONCLUSION: The presence of macrophage-derived PGRN in airways in the early sensitization period may be critical for mounting a Th2 immune response and for following an allergic airway inflammation pathway via induction of type 2 cytokine production in NKT and airway epithelial cells.