Quantitative determination of plasma cholesteryl ester levels in Japanese preadolescents from the Hokkaido study using liquid chromatography/tandem mass spectrometry.
Divyavani Gowda, Siddabasave Gowda B Gowda, Atsuko Ikeda, Rahel Mesfin Ketema, Yu Ait Bamai, Reiko Kishi, Hitoshi Chiba, Shu-Ping Hui
Steroids, 211, 109498, 109498, 2024年11月, ［国際誌］
英語, 研究論文（学術雑誌）, Cholesteryl esters (CE) are sterols comprising various fatty acyl chains attached to a cholesterol hydroxyl moiety. CEs are often considered plasma biomarkers of liver function; however, their absolute concentrations in the plasma of Japanese preadolescents have not been well explored. This study aimed to determine the plasma CE levels in Japanese preadolescents of different sexes, ages, and body weights living in Hokkaido, Japan using targeted liquid chromatography/tandem mass spectrometry. The analysis was performed on the non-fasting plasma of preadolescents aged 9-12 years (n = 339 healthy volunteers; 178 boys and 161 girls) from Sapporo, Hokkaido, Japan. The analysis results showed that the total CE levels in boys and girls were 871 ± 153 and 862 ± 96 pmol/μL, respectively. CE 18:2 (41 ± 2.9 %) was found to be the most abundant species followed by CE 18:1 (16 ± 1.5 %) and CE 16:0 (13 ± 1.1 %). The ω-3 fatty acid-containing CEs such as CE 18:3 and CE 20:5 were significantly lower in girls than in boys. Despite the different ages, CEs were tightly regulated in the plasma of children's, and the total CEs ranged between 844 and 906 pmol/μL in boys and 824 and 875 pmol/μL in girls. The participants were further classified into three groups based on their body mass index underweight (n = 237), normal weight (n = 94), and overweight (n = 8). Most of the quantified CEs were accumulated in the overweight group. Interestingly, CE 18:3 was significantly upregulated in the overweight group compared to that in the normal range, and the area under the receiver operating characteristic curve was 0.73, suggesting that it could be a possible marker for obesity. This study marks the initial investigation of absolute CE levels in the plasma of children and can help elucidate the relationship between CEs and childhood obesity.

Alterations in plasma short-chain fatty acids in preadolescence children: The Hokkaido study
Yonghan Li, Siddabasave Gowda B. Gowda, Divyavani Gowda, Atsuko Ikeda, Yu Ait Bamai, Rahel Mesfin Ketema, Reiko Kishi, Hitoshi Chiba, Shu-Ping Hui
Journal of Chromatography B, 1242, 124191, 124191, Elsevier BV, 2024年07月
研究論文（学術雑誌）

The association between flooring materials and childhood asthma: A prospective birth cohort in the Japan Environment and Children's Study.
Hiroyoshi Iwata, Atsuko Ikeda, Mariko Itoh, Sachiko Itoh, Rahel Mesfin Ketema, Naomi Tamura, Chihiro Miyashita, Takeshi Yamaguchi, Keiko Yamazaki, Rieko Yamamoto, Maki Tojo, Yasuaki Saijo, Yoshiya Ito, Reiko Kishi
PloS one, 19, 7, e0305957, 2024年, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Childhood asthma is known to be affected by a range of factors, including conditions in the indoor environment. While flooring material influences indoor air conditions, the potential association between flooring materials and childhood asthma remains poorly understood in Japan. OBJECTIVE: The present study aims to assess the association between childhood asthma incidence and the primary flooring material with the ongoing prospective nationwide birth cohort data of the Japan Environment and Children's Study (JECS). METHODS: The JECS gathered data on mothers and children through 15 Regional Centres across Japan. The present study assessed flooring materials used in the home and asthma incidence at age four among children born between 2011 and 2014. We implemented logistic regressions, setting asthma incidence among the children as the outcome and home floor type as the exposure. Additional analyses were conducted, stratifying the home's age as a proxy for tatami age, to assess whether the potential effect of tatami flooring on asthma risk is influenced by its age. RESULTS: The present study included total of 75,629 infants. For tatami flooring, the main multivariable regression and additional sub-group regression for homes over ten years old produced odds ratios of 1.09; 95% Confidence Interval (CI) [1.01-1.17] and 1.10; 95% CI [1.00-1.21] compared with flooring, respectively. CONCLUSION: These results imply that exposure to tatami flooring, particularly in older homes, may be associated with childhood asthma incidence. Moreover, our study highlights the importance of evaluating the relationship between regional and cultural differences between asthma and flooring materials.

The association between prenatal per-and polyfluoroalkyl substance levels and Kawasaki disease among children of up to 4 years of age: A prospective birth cohort of the Japan Environment and Children’s study
Hiroyoshi Iwata, Sumitaka Kobayashi, Mariko Itoh, Sachiko Itoh, Rahel Mesfin Ketema, Naomi Tamura, Chihiro Miyashita, Takeshi Yamaguchi, Keiko Yamazaki, Hideyuki Masuda, Yu Ait Bamai, Yasuaki Saijo, Yoshiya Ito, Shoji F Nakayama, Michihiro Kamijima, Reiko Kishi
Environment International, 183, 108321, 108321, Elsevier BV, 2024年01月
研究論文（学術雑誌）

Exposure to organophosphate flame retardants and plasticizers is positively associated with wheeze and FeNO and eosinophil levels among school-aged children: The Hokkaido study
Yi Zeng, Houman Goudarzi, Yu Ait Bamai, Rahel Mesfin Ketema, Maarten Roggeman, Fatima den Ouden, Celine Gys, Chihiro Miyashita, Sachiko Ito, Satoshi Konno, Adrian Covaci, Reiko Kishi, Atsuko Ikeda-Araki
Environment International, 181, 108278, 108278, Elsevier BV, 2023年11月
研究論文（学術雑誌）

Exposure Trends to the Non-phthalate Plasticizers DEHTP, DINCH, and DEHA in Children from 2012 to 2017: The Hokkaido Study.
Rahel Mesfin Ketema, Monika Kasper-Sonnenberg, Yu Ait Bamai, Chihiro Miyashita, Holger M Koch, Claudia Pälmke, Reiko Kishi, Atsuko Ikeda
Environmental science & technology, 57, 32, 11926, 11936, 2023年08月15日, ［国際誌］
英語, 研究論文（学術雑誌）, Phthalates owing to their endocrine-disrupting effects are regulated in certain products, leading to their replacement with substitutions such as di-2-ethylhexyl terephthalate (DEHTP), 1,2-cyclohexane dicarboxylic acid di(isononyl) ester (DINCH), and di(2-ethylhexyl) adipate (DEHA). However, information on human exposure to these substitutes, especially in susceptible subpopulations such as children, is limited. Thus, we examined the levels and exposure trends of DEHTP, DINCH, and DEHA metabolites in 7 year-old Japanese school children. In total, 180 urine samples collected from 2012 to 2017 were used to quantify 10 DEHTP, DINCH, and DEHA metabolites via isotope dilution liquid chromatography with tandem mass spectrometry. DEHTP and DINCH metabolites were detected in 95.6 and 92.2% of the children, respectively, and DEHA was not detected. This study, annually conducted between 2012 and 2017, revealed a significant (p < 0.05) 5-fold increase in DEHTP metabolites and a 2-fold increase in DINCH metabolites. However, the maximum estimated internal exposures were still below the health-based guidance and toxicological reference values. Exposure levels to DEHTP and DINCH have increased considerably in Japanese school children. DEHA is less relevant. Future studies are warranted to closely monitor the increasing trend in different aged and larger populations and identify the potential health effects and sources contributing to increasing exposure and intervene if necessary.

Phthalates mixture on allergies and oxidative stress biomarkers among children: The Hokkaido study.
Rahel Mesfin Ketema, Yu Ait Bamai, Chihiro Miyashita, Takeshi Saito, Reiko Kishi, Atsuko Ikeda-Araki
Environment international, 160, 107083, 107083, 2022年02月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Exposure to individual phthalates and the mediation effect of oxidative stress in association with asthma and allergic symptoms have been studied previously. Little is known about the mixture effect of phthalates on health outcomes. Thus, we investigated the effect of a mixture of ten phthalate metabolites in association with wheeze, rhino-conjunctivitis, and eczema. The mediating effect of three oxidative stress biomarkers was also assessed. METHODS: Levels of 10 phthalate metabolites and 3 oxidative stress biomarkers were measured in 386 urine samples from 7-year-old children. Parents reported demographic and allergic symptoms using ISAAC questionnaires. Logistic regression for individual metabolites and mixture analysis weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) were fitted to examine the association between phthalate metabolite exposure and health outcomes. Baron and Kenny's regression approach was used for mediation analysis. RESULTS: In logistic regression model showed mono (2-ethyl-5-carboxypentyl) phthalate (MECPP) (OR = 1.41, 95% CI 1.02-1.97) and mono carboxy-isononyl phthalate (cx-MINP) (OR = 1.40, 95% CI 1.07-1.86) were associated with wheeze. The WQS index had a significant association (OR = 1.46, 95% CI 1.09-1.96) with wheeze and (OR = 1.40, 95% CI 1.07-1.82) with eczema. Mono-isononyl phthalate (MINP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) were the most highly weighted metabolites. In the BKMR model, diisononyl phthalate (DINP) metabolites showed the highest group posterior inclusion probability (PIP). Among DINP metabolites, MINP in wheeze, cx-MINP in rhino-conjunctivitis and OH-MINP in eczema showed the highest conditional PIPs. The overall metabolites mixture effect was associated with eczema. We did not find any mediation of oxidative stress in the association between phthalates and symptoms. No significant association between phthalate metabolites and oxidative stress was observed in this study. CONCLUSION: Mixture of phthalate metabolites were associated with wheeze and eczema. The main contributors to the association were DEHP and DINP metabolites. No mediation of oxidative stress was observed.

Hokkaido birth cohort study on environment and children’s health: cohort profile 2021
Reiko Kishi, Atsuko Ikeda-Araki, Chihiro Miyashita, Sachiko Itoh, Sumitaka Kobayashi, Yu Ait Bamai, Keiko Yamazaki, Naomi Tamura, Machiko Minatoya, Rahel Mesfin Ketema, Kritika Poudel, Ryu Miura, Hideyuki Masuda, Mariko Itoh, Takeshi Yamaguchi, Hisanori Fukunaga, Kumiko Ito, Houman Goudarzi
Environmental Health and Preventive Medicine, 26, 1, Springer Science and Business Media {LLC}, 2021年12月
英語, 研究論文（学術雑誌）, Abstract
Background
The Hokkaido Study on Environment and Children’s Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary objectives are to (1) examine the effects that low-level environmental chemical exposures have on birth outcomes, including birth defects and growth retardation; (2) follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders, as well as perform a longitudinal observation of child development; (3) identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) identify the additive effects of various chemicals, including tobacco.

Methods
The purpose of this report is to provide an update on the progress of the Hokkaido Study, summarize recent results, and suggest future directions. In particular, this report provides the latest details from questionnaire surveys, face-to-face examinations, and a collection of biological specimens from children and measurements of their chemical exposures.

Results
The latest findings indicate different risk factors of parental characteristics on birth outcomes and the mediating effect between socioeconomic status and children that are small for the gestational age. Maternal serum folate was not associated with birth defects. Prenatal chemical exposure and smoking were associated with birth size and growth, as well as cord blood biomarkers, such as adiponectin, leptin, thyroid, and reproductive hormones. We also found significant associations between the chemical levels and neuro development, asthma, and allergies.

Conclusions
Chemical exposure to children can occur both before and after birth. Longer follow-up for children is crucial in birth cohort studies to reinforce the Developmental Origins of Health and Disease hypothesis. In contrast, considering shifts in the exposure levels due to regulation is also essential, which may also change the association to health outcomes. This study found that individual susceptibility to adverse health effects depends on the genotype. Epigenome modification of DNA methylation was also discovered, indicating the necessity of examining molecular biology perspectives. International collaborations can add a new dimension to the current knowledge and provide novel discoveries in the future.

Secular trends of urinary phthalate metabolites in 7-year old children and association with building characteristics: Hokkaido study on environment and children's health
Rahel Mesfin Ketema, Yu Ait Bamai, Atsuko Ikeda-Araki, Takeshi Saito, Reiko Kishi
International Journal of Hygiene and Environmental Health, 234, 113724, 113724, Elsevier {BV}, 2021年05月
英語, 研究論文（学術雑誌）

Lifestyle behaviors and home and school environment in association with sick building syndrome among elementary school children: a cross-sectional study
Rahel Mesfin Ketema, Atsuko Araki, Yu Ait Bamai, Takeshi Saito, Reiko Kishi
Environmental Health and Preventive Medicine, 25, 1, Springer Science and Business Media {LLC}, 2020年12月
英語, 研究論文（学術雑誌）, Abstract
Background
Sick building syndrome (SBS) refers to the combination of symptoms experienced by occupants of specific building characteristics. This study investigated the associations of children’s lifestyle behaviors, allergies, home, and school environment with SBS symptoms.

Methods
A total of 4408 elementary school children living in Sapporo City, Japan participated in this study. SBS was determined on parental answers to MM080 standardized school questionnaires on symptoms that were weekly experienced by these children, and if the symptom is attributed to their home or school environment. The Japanese version of the International Study of Asthma and Allergies in Childhood questionnaire was used to assess wheeze, rhino-conjunctivitis, and eczema. A logistic regression analysis was conducted to evaluate the associations between SBS symptoms and variables by controlling the potential confounders (gender, grade, school, and parental history of allergies). A stepwise backward elimination was conducted to assess independent variables related to SBS.

Results
Participants revealed mucosal (6.9%), skin (2.0%), and general (0.8%) symptoms. The presence of one or more allergy was associated with increased mucosal and skin symptoms. Children who skipped breakfast, displayed faddiness (like/dislike of food), had constipation, have insufficient sleep, did not feel refreshed after sleep, and lacked deep sleep showed significantly high odds ratios with SBS symptoms. The stepwise analysis showed faddiness for mucosal symptoms and not feeling refreshed after sleep for mucosal and skin symptoms, whereas constipation and lacking deep sleep for general symptoms were independent variables in increasing the symptoms. We found no significant relationship between SBS in children and schools. Considering children’s home, old building, no ventilation, wall-to-wall carpet, and heavy nearby traffic were associated with elevated mucosal symptom, while living in a multifamily home increased general symptoms. Home dampness was an independent variable in increasing all SBS symptoms.

Conclusions
Allergies and lifestyle behaviors were associated with increased SBS in children, including skipping breakfast, displaying faddiness, constipation, insufficient sleep, not feeling refreshed after sleep, and the lack of deep sleep. Further, dampness at home was associated with increase in all SBS symptoms. Lifestyle (e.g., eating and sleeping habits) and home (i.e., dampness) improvements might alleviate SBS symptoms in children.

Long-term effects of maternal resveratrol intake during lactation on cholesterol metabolism in male rat offspring
Shojiro Yamasaki, Tomomi Tomihara, Goh Kimura, Yukako Ueno, Rahel Mesfin Ketema, Shin Sato, Yuuka Mukai, Tajuddin Sikder, Masaaki Kurasaki, Toshiyuki Hosokawa, Takeshi Saito
International Journal of Food Sciences and Nutrition, 71, 2, 226, 234, Informa {UK} Limited, 2020年02月17日
英語, 研究論文（学術雑誌）

Polyphenol-enriched azuki bean (Vina angularis) extract reduces the oxidative stress and prevents DNA oxidation in the hearts of streptozotocin-induced early diabetic rats
Tomomi Kita-Tomihara, Shin Sato, Shojiro Yamasaki, Yukako Ueno, Goh Kimura, Rahel M. Ketema, Tae Kawahara, Masaaki Kurasaki, Takeshi Saito
International Journal of Food Sciences and Nutrition, 70, 7, 845, 855, Informa {UK} Limited, 2019年10月03日
英語, 研究論文（学術雑誌）

Associations between allergic symptoms and phosphate flame retardants in dust and their urinary metabolites among school children
Atsuko Araki, Michiel Bastiaensen, Yu Ait Bamai, Nele Van den Eede, Toshio Kawai, Tazuru Tsuboi, Rahel Mesfin Ketema, Adrian Covaci, Reiko Kishi
Environment International, 119, 438, 446, Elsevier {BV}, 2018年10月
英語, 研究論文（学術雑誌）

Indoor environmental pollutants and their association with sick house syndrome among adults and children in elementary school
Reiko Kishi, Rahel Mesfin Ketema, Yu Ait Bamai, Atsuko Araki, Toshio Kawai, Tazuru Tsuboi, Ikue Saito, Eiji Yoshioka, Takeshi Saito
Building and Environment, 136, 293, 301, Elsevier {BV}, 2018年05月
英語, 研究論文（学術雑誌）

House Dust and Its Adverse Health Effects
Atsuko ARAKI, Yu AIT BAMAI, Rahel Mesfin KETEMA, Reiko KISHI
Nippon Eiseigaku Zasshi (Japanese Journal of Hygiene), 73, 2, 130, 137, Japanese Society for Hygiene, 2018年
英語, 研究論文（学術雑誌）

The Hokkaido birth cohort study on environment and children's health: Cohort profile-updated 2017
Reiko Kishi, Atsuko Araki, Machiko Minatoya, Tomoyuki Hanaoka, Chihiro Miyashita, Sachiko Itoh, Sumitaka Kobayashi, Yu Ait Bamai, Keiko Yamazaki, Ryu Miura, Naomi Tamura, Kumiko Ito, Houman Goudarzi, S. Sasaki, T. Ikeno, E. Okada, S. Nishihara, R. M. Ketema, T. Kita, I. Kashino, T. Baba, T. S. Braimoh, S. Minakami, K. Cho, N. Shinohara, K. Moriya, T. Mitsui, T. Saito, S. Suyama, T. Nomura, S. Konno, H. Matsuura, M. Ishizuka, T. Endo, T. Baba, F. Sata, K. Sengoku, Y. Saijo, E. Yoshioka, T. Miyamoto, M. Yuasa, J. Kajiwara, T. Hori, Y. Chisaki, T. Matsumura, F. Mizutani, J. Yamamoto, Y. Onoda, T. Kawai, T. Tsuboi
Environmental Health and Preventive Medicine, 22, 1, 2017年
研究論文（学術雑誌）, The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary study goals are (1) to examine the effects of low-level environmental chemical exposures on birth outcomes, including birth defects and growth retardation; (2) to follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders and perform a longitudinal observation of child development; (3) to identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) to identify the additive effects of various chemicals, including tobacco smoking. The purpose of this report is to update the progress of the Hokkaido Study, to summarize the recent results, and to suggest future directions. In particular, this report provides the basic characteristics of the cohort populations, discusses the population remaining in the cohorts and those who were lost to follow-up at birth, and introduces the newly added follow-up studies and case-cohort study design. In the Sapporo cohort of 514 enrolled pregnant women, various specimens, including maternal and cord blood, maternal hair, and breast milk, were collected for the assessment of exposures to dioxins, polychlorinated biphenyls, organochlorine pesticides, perfluoroalkyl substances, phthalates, bisphenol A, and methylmercury. As follow-ups, face-to-face neurobehavioral developmental tests were conducted at several different ages. In the Hokkaido cohort of 20,926 enrolled pregnant women, the prevalence of complicated pregnancies and birth outcomes, such as miscarriage, stillbirth, low birth weight, preterm birth, and small for gestational age were examined. The levels of exposure to environmental chemicals were relatively low in these study populations compared to those reported previously. We also studied environmental chemical exposure in association with health outcomes, including birth size, neonatal hormone levels, neurobehavioral development, asthma, allergies, and infectious diseases. In addition, genetic and epigenetic analyses were conducted. The results of this study demonstrate the effects of environmental chemical exposures on genetically susceptible populations and on DNA methylation. Further study and continuous follow-up are necessary to elucidate the combined effects of chemical exposure on health outcomes.

Indoor environmental quality and health risk toward healthier environment for all
Kishi, Reiko, Norbäck, Dan, Araki, Atsuko
Springer, 2020年, 9789813291812, viii, 333 p., 英語