Heat wave exposure and increased heat-related hospitalizations in young children in South Korea: A time-series study.

BACKGROUND: Numerous studies have investigated the association between heat wave exposure increased heat-related hospitalizations in the general population. However, little is known about heat-related morbidity in young children who are more vulnerable than the general population. Therefore, we aimed to evaluate the association between hospitalization for heat-related illness in children and heat wave exposure in South Korea. METHODS: We used the National Health Insurance Service (NHIS) database, which provides medical records from 2015 to 2019 in South Korea. We defined daily hospitalizations for heat-related illness of children younger than five years during the summer period (June to August). We considered the definition of heat waves considering the absolute temperature and percentile. A total of 12 different heat waves were used. A time-series analysis was used to investigate the association between heat wave exposure and heat-related hospitalization among children younger than five years. We used a two-stage design involving a meta-analysis after modeling by each region. RESULTS: We included 16,879 daily heat-related hospitalizations among children younger than five years. Overall, heat wave exposure within two days was most related for heat-related hospitalizations in young children. The relative risk (RR) due to heat wave exposure within two days (lag2) (12 definitions: 70th to 90th percentile of maximum temperature) ranged from 1.038 (95% confidence interval (CI): 0.971, 1.110) to 1.083 (95% CI: 1.036, 1.133). We found that boys were more vulnerable to heat exposure than girls. In addition, we found that urban areas were more vulnerable to heat exposure than rural areas. CONCLUSIONS: In our study, heat wave exposure during summer was found to be associated with an increased risk of hospitalization for heat-related illness among children younger than five years. Our findings suggest the need for summer heat wave management and prevention for children.

Long-term exposure to air pollution and precocious puberty in South Korea.

BACKGROUND AND AIM: The increasing prevalence of precocious puberty (PP) has emerged as a significant medical and social problem worldwide. However, research on the relationship between long-term air pollution exposure and PP has been relatively limited. We thus investigated the association between long-term air pollution exposure and the onset of PP in South Korea. METHODS: We investigated a retrospective cohort using the Korea National Health Insurance Database. Six-year-old children born from 2007 to 2009 were examined (2013-2015). We included boys ≤10 years and girls aged ≤9 years who visited hospitals for early pubertal development, were diagnosed with PP per the ICD-10 (E228, E301, and E309), and received gonadotropin-releasing hormone agonist treatment. We analyzed data for boys up until 10 years old (60-month follow-up) and for girls up to 9 years old (48-month follow-up). We assessed the association between long-term air pollution exposure and the onset of PP using a Cox proportional hazard model. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) per 1 µg/m3 increase in fine particulate matter (PM2.5) and particulate matter (PM10) and per 1 ppb increase in sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3). RESULTS: This study included 1,205,784 children aged six years old between 2013 and 2015. A positive association was found between the 48-month moving average PM2.5 (HR: 1.019; 95% CI: 1.012, 1.027), PM10 (HR: 1.009; 95% CI: 1.006, 1.013), SO2 (HR: 1.037; 95% CI: 1.018, 1.055), and O3 (HR: 1.006; 95% CI: 1.001, 1.010) exposure and PP in girls but not boys. CONCLUSIONS: This study provides valuable insights into the harmful effects of air pollution during childhood and adolescence, emphasizing that air pollution is a risk factor that should be managed and reduced.

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.

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.

Comparison of Immune Responses to Two Quadrivalent Meningococcal Conjugate Vaccines (CRM197 and Diphtheria Toxoid) in Healthy Adults.

BACKGROUND: After the introduction of the meningococcal ACWY-CRM197 conjugate vaccine (MenACWY-CRM) in 2012 and the meningococcal ACWY-diphtheria toxoid conjugate vaccine (MenACWY-DT) in 2014, immunization was recommended for certain high-risk groups including new military recruits in Korea. However, comparative immunogenicity studies for these vaccines have not been performed in Korea. Here, we compared the immunogenicity of these two vaccines in healthy adults. METHODS: A total of 64 adults, 20-49 years of age, were randomly divided into two groups (1:1) to receive either of the two vaccines. The sera were obtained before and 1 month after vaccination and tested for serogroup-specific serum bactericidal activity using baby rabbit complement. RESULTS: There were no significant differences post-vaccination in the geometric mean indices and the seropositive rate to all serogroups between the vaccines. The proportion of seropositive subjects after vaccination ranged from 88% to 100%. CONCLUSION: Both meningococcal conjugate vaccines showed good immunogenicity in healthy Korean adults without statistically significant differences. Further investigations for serotype distribution of circulating meningococci and the immune interference between other diphtheria toxin-containing vaccines concomitantly used for military recruits are needed to optimize immunization policies. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0002460.

Seroprevalence of Opsonophagocytic Antibodies against Serotype Ia, Ib, II, III, and V Group B Streptococcus among Korean Population.

BACKGROUND: Invasive Streptococcus agalactiae (group B streptococcus, GBS) infection most commonly occurs in infants; however, cases of GBS infection in adults, particularly in the elderly with significant underlying diseases, are being increasingly reported. We analyzed the serotype specific opsonophagocytic antibodies (the major mechanism of protection against GBS) in infants, adults, and the elderly. METHODS: The opsonization indices (OIs) of antibodies against serotype Ia, Ib, II, III, and V GBS were studied in 89 infants, 35 adults (age, 30-50 years), and 62 elderly individuals (age, 65-85 years) according to the University of Alabama at Birmingham GBS opsonophagocytic killing assay protocol (www.vaccine.uab.edu). RESULTS: In infants, adults, and elderly groups respectively, geometric mean of OI against GBS serotype Ia were 3, 7, and 32; against GBS serotype Ib were 7, 242, and 252; against serotype II were 93, 363, and 676; against serotype III were 8, 212, and 609; and against serotype V were 4, 639, and 610. The seropositive rate (% of subjects with OI ≥ 4) increased significantly in older age group for all five serotypes. CONCLUSION: During infancy, only a limited proportion of infants have functional immunity against serotype Ia, Ib, II, III, and V GBS. Furthermore, a lack of opsonic activities against GBS observed in some adults and the elderly might predispose such individuals to the risk of invasive GBS infection. Epidemiological monitoring and development of suitable vaccine for these populations are needed.

Validation of a Multiplexed Opsonophagocytic Assay for 11 Additional Pneumococcal Serotypes and Its Application to Functional Antibody Evaluation Induced by Pneumococcal Polysaccharide Vaccine.

BACKGROUND: Various pneumococcal vaccines have been evaluated for immunogenicity by opsonophagocytic assay (OPA). A multiplexed OPA (MOPA) for 13 pneumococcal serotypes was developed by Nahm and Burton, and expanded to 26 serotypes in 2012. The development of new conjugate vaccines with increased valence has necessitated expanded MOPAs to include these additional serotypes. In this study, we validated this expanded MOPA platform and applied to measure antibodies against 11 additional serotypes (2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20B, 22F, and 33F) in human sera. METHODS: All materials, including serum, complement, bacterial master stocks, and HL-60 cells, were evaluated for assay optimization. Following optimization, the assay was validated for accuracy, specificity, and intra- and inter-assay precision with sera from adult donors following standard protocols. The assay was applied to evaluate functional antibodies of 42 sera immunized with 23-valent pneumococcal polysaccharide vaccine (PPV23). RESULTS: The expanded MOPA platform was specific for all serotypes, with the exception of serotype 20. The assay results were highly correlated with those obtained from single-serotype OPA, indicating acceptable accuracy. The coefficients of variation were 7%-24% and 13%-39% in tests of intra- and inter-assay precision, respectively, using three quality-control samples. A MOPA that included 11 additional serotypes in the PPV23 was established and validated with respect to accuracy, specificity, and precision. The opsonic indices of immune sera were obtained using this validated assay. CONCLUSION: The expanded MOPA will be useful for evaluation of the immunogenicity of PPV23 and future conjugate vaccine formulations.

Opsonophagocytic Antibodies to Serotype Ia, Ib, and III Group B Streptococcus among Korean Infants and in Intravenous Immunoglobulin Products.

Group B streptococcus (GBS) infection is a leading cause of sepsis and meningitis among infants, and is associated with high rates of morbidity and mortality in many countries. Protection against GBS typically involves antibody-mediated opsonization by phagocytes and complement components. The present study evaluated serotype-specific functional antibodies to GBS among Korean infants and in intravenous immunoglobulin (IVIG) products. An opsonophagocytic killing assay (OPA) was used to calculate the opsonization indices (OIs) of functional antibodies to serotypes Ia, Ib, and III in 19 IVIG products from 5 international manufacturers and among 98 Korean infants (age: 0-11 months). The GBS Ia, Ib, and III serotypes were selected because they are included in a trivalent GBS vaccine formulation that is being developed. The OI values for the IVIG products were 635-5,706 (serotype Ia), 488-1,421 (serotype Ib), and 962-3,315 (serotype III), and none of the IVIG lots exhibited undetectable OI values (< 4). The geometric mean OI values were similar for all 3 serotypes when we compared the Korean manufacturers. The seropositive rate among infants was significantly lower for serotype Ia (18.4%), compared to serotype Ib and serotype III (both, 38.8%). Infant age of ≥ 3 months was positively correlated with the seropositive rates for each serotype. Therefore, only a limited proportion of infants exhibited protective immunity against serotype Ia, Ib, and III GBS infections. IVIG products that exhibit high antibody titers may be a useful therapeutic or preventive measure for infants. Further studies are needed to evaluate additional serotypes and age groups.

Effects of Light and Dark Conditions on the Transcriptome of Aging Cultures of Candidatus Puniceispirillum marinum IMCC1322.

To elucidate the function of proteorhodopsin in Candidatus Puniceispirillum marinum strain IMCC1322, a cultivated representative of SAR116, we produced RNA-seq data under laboratory conditions. We examined the transcriptomes of six different cultures, including sets of expression changes under constant dark (DD), constant light (LL), and diel-cycled (LD; 14 h light: 10 h dark) conditions at the exponential and stationary/death phases. Prepared mRNA extracted from the six samples was analyzed on the Solexa Genome Analyzer with 36 cycles. Differentially expressed genes on the IMCC1322 genome were distinguished as four clusters by K-mean clustering and each CDS (n = 2546) was annotated based on the KEGG BRITE hierarchy. Cluster 0 (n = 1573) covered most constitutive genes including proteorhodopsin, retinoids, and glycolysis/TCA cycle. Cluster 1 genes (n = 754) were upregulated in stationary/death phase under constant dark conditions and included genes associated with bacterial defense, membrane transporters, nitrogen metabolism, and senescence signaling. Cluster 2 genes (n = 197) demonstrated upregulation in exponential phase cultures and included genes involved in genes for oxidative phosphorylation, translation factors, and transcription machinery. Cluster 3 (n = 22) contained light-stimulated upregulated genes expressed under stationary/phases. Stringent response genes belonged to cluster 2, but affected genes spanned various cellular processes such as amino acids, nucleotides, translation, transcription, glycolysis, fatty acids, and cell wall components. The coordinated expression of antagonistic stringent genes, including mazG, ppx/gppA, and spoT/relA may provide insight into the controlled cultural response observed between constant light and constant dark conditions in IMCC1322 cultures, regardless of cell numbers and biomass.

Causal relationship between particulate matter 2.5 and diabetes: two sample Mendelian randomization.

Backgrounds: Many studies have shown particulate matter has emerged as one of the major environmental risk factors for diabetes; however, studies on the causal relationship between particulate matter 2.5 (PM2.5) and diabetes based on genetic approaches are scarce. The study estimated the causal relationship between diabetes and PM2.5 using two sample mendelian randomization (TSMR). Methods: We collected genetic data from European ancestry publicly available genome wide association studies (GWAS) summary data through the MR-BASE repository. The IEU GWAS information output PM2.5 from the Single nucleotide polymorphisms (SNPs) GWAS pipeline using pheasant-derived variables (Consortium = MRC-IEU, sample size: 423,796). The annual relationship of PM2.5 (2010) were modeled for each address using a Land Use Regression model developed as part of the European Study of Cohorts for Air Pollution Effects. Diabetes GWAS information (Consortium = MRC-IEU, sample size: 461,578) were used, and the genetic variants were used as the instrumental variables (IVs). We performed three representative Mendelian Randomization (MR) methods: Inverse Variance Weighted regression (IVW), Egger, and weighted median for causal relationship using genetic variants. Furthermore, we used a novel method called MR Mixture to identify outlier SNPs. Results: From the IVW method, we revealed the causal relationship between PM2.5 and diabetes (Odds ratio [OR]: 1.041, 95% CI: 1.008-1.076, P = 0.016), and the finding was substantiated by the absence of any directional horizontal pleiotropy through MR-Egger regression (ß = 0.016, P = 0.687). From the IVW fixed-effect method (i.e., one of the MR machine learning mixture methods), we excluded outlier SNP (rs1537371) and showed the best predictive model (AUC = 0.72) with a causal relationship between PM2.5 and diabetes (OR: 1.028, 95% CI: 1.006-1.049, P = 0.012). Conclusion: We identified the hypothesis that there is a causal relationship between PM2.5 and diabetes in the European population, using MR methods.