BACKGROUND: Mitochondria, which harbor their own genome (mtDNA), have attracted attention due to the potential of mtDNA copy number (mtDNA-CN) as an indicator of mitochondrial dysfunction. Although mtDNA-CN has been proposed as a simple and accessible biomarker for metabolic disorders such as metabolic dysfunction-associated steatotic liver disease, the underlying mechanisms and the causal relationship remain insufficiently elucidated. In this investigation, we combined longitudinal epidemiological data, animal studies, and in vitro assays to elucidate the potential causal relationship between reduced mtDNA-CN and the development of steatotic liver disease (SLD). METHODS: We conducted a longitudinal study using data from a health examination cohort initiated in 1981 in Yakumo, Hokkaido, Japan. Data from examinations performed in 2015 and 2022 were analyzed, focusing on 76 subjects without SLD at baseline (2015) to assess the association between baseline mtDNA-CN and subsequent risk of SLD development. In addition, 28-day-old SD rats were fed ad libitum on a 45% high-fat diet and dissected at 2 and 8 weeks of age. Blood and liver mtDNA-CN were measured and compared at each feeding period. Additionally, in vitro experiments were performed using HepG2 cells treated with mitochondrial function inhibitors to induce mtDNA-CN depletion and to examine its impact on intracellular lipid accumulation. RESULTS: Epidemiological analysis showed that the subjects with low mtDNA-CN had a significantly higher odds ratio for developing SLD compared to high (odds ratio [95% confidence interval]: 4.93 [1.08-22.50]). Analysis of the animal model showed that 8 weeks of high-fat diet led to the development of fatty liver and a significant decrease in mtDNA-CN. A further 2 weeks of high-fat diet consumption resulted in a significant decrease in hepatic mtDNA-CN, despite the absence of fatty liver development, and a similar trend was observed for blood. Complementary in vitro experiments revealed that pharmacologically induced mitochondrial dysfunction led to a significant reduction in mtDNA-CN and was associated with increases in intracellular lipid accumulation in HepG2 cells. CONCLUSIONS Our findings suggest that reduced mtDNA-CN may contribute causally to SLD development and could serve as a convenient, noninvasive biomarker for early detection and risk assessment.
Animals ; DNA, Mitochondrial/genetics* ; Humans ; Male ; DNA Copy Number Variations ; Female ; Fatty Liver/blood* ; Rats ; Middle Aged ; Longitudinal Studies ; Rats, Sprague-Dawley ; Adult ; Japan/epidemiology* ; Aged ; Biomarkers/blood* ; Hep G2 Cells ; Diet, High-Fat/adverse effects*

BACKGROUND: Long screen time hours may be associated with behavioral problems in children. To better understand the relationship between children's behavioral problems and screen time, it the associated risk factors must be subdivided based on the purpose underlying screen use. This study examined the relationship between screen time based on intended usage and behavioral problems in Japan. METHODS: This study included 3,332 children aged between 7-17 years from the Hokkaido Study on Environment and Children's Health. From October 2020 to October 2021, the children and their parents answered questionnaires on the children's screen use duration (never used, <30 min, ≥30 min & <1 hour, ≥1 h & <2 h, ≥2 h) based on seven intended usage categories: watching television/video, video gaming, reading books/comics, sending/receiving e-mail/messages, browsing/posting on social networking services, studying for classes/homework, drawing/editing pictures/photos/videos, along with the Strengths and Difficulties Questionnaire (SDQ). Logistic regression was used to analyze the association between screen time, purpose of children's screen use, and behavioral problems across the 13 SDQ total scores. RESULTS: The mean ± standard deviation age of the participants was 12.4 ± 2.4-years-old, 487 (14.6%) children were determined to have behavioral problems, and the duration of screen time increased with their age. The children's primary purposes for screen use were watching television/video, video gaming, sending/receiving e-mail/messages, and browsing/posting on social networking services. Children who reported playing video games for ≥2 hours on weekdays had higher odds of problematic total difficulties scores than never user (Odds Ratio: 2.10, 95% confidence interval: 1.45-3.06). CONCLUSION Long video gaming screen time is associated with behavioral issues, hyperactivity/inattention, and prosocial behaviors in children. Conversely, watching television and videos for 30 min-1 h per day, using e-mail or messaging, and using social networking services were significantly association with reduced odds ratio for peer relationship problems as compared to children who never engaged in these activities. Longitudinal follow-up is needed to further examine screen time and problem behaviors.
Humans ; Screen Time ; Child ; Japan/epidemiology* ; Male ; Female ; Adolescent ; Problem Behavior/psychology* ; Surveys and Questionnaires ; Child Behavior ; Television/statistics & numerical data* ; Video Games/statistics & numerical data*

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.
Biomarkers/blood* ; Child ; Child Health ; Child, Preschool ; Cohort Studies ; Environmental Exposure/adverse effects* ; Environmental Health ; Environmental Pollutants/adverse effects* ; Female ; Fetal Blood/chemistry* ; Follow-Up Studies ; Growth/drug effects* ; Humans ; Hypersensitivity/etiology* ; Infant ; Japan/epidemiology* ; Male ; Neurodevelopmental Disorders/etiology* ; Pregnancy ; Prenatal Exposure Delayed Effects/etiology* ; Prevalence ; Smoking/adverse effects*

BACKGROUND: There have been inconsistent findings reported on maternal passive smoking during pregnancy and child risk of ADHD. In this study, ADHD symptoms at pre-school age children in association with prenatal passive and active tobacco smoke exposure determined by maternal plasma cotinine levels in the third trimester were investigated. METHODS: This was a follow-up study of the birth cohort: the Hokkaido Study on Environment and Children's Health. Children whose parents answered Strengths and Difficulties Questionnaire (SDQ) to identify child ADHD symptoms (hyperactivity/inattention and conduct problems) and total difficulties at age 5 years with available maternal plasma cotinine level at the third trimester were included (n = 3216). Cotinine levels were categorized into 4 groups; ≦ 0.21 ng/ml (non-smoker), 0.22-0.51 ng/ml (low-passive smoker), 0.52-11.48 ng/ml (high-passive smoker), and ≧ 11.49 ng/ml (active smoker). RESULTS: Maternal cotinine levels of active smokers were significantly associated with an increased risk of total difficulties (OR = 1.67) and maternal low- and high-passive smoking also increased the risk (OR = 1.11, 1.25, respectively) without statistical significance. Similarly, maternal cotinine levels of active smokers were associated with an increased risk of hyperactivity/inattention (OR = 1.49). Maternal low- and high-passive smoking and active smoking increased the risk of hyperactivity/inattention (OR = 1.45, 1.43, and OR = 1.59, respectively) only in boys. CONCLUSION Our findings suggested that maternal active smoking during pregnancy may contribute to the increased risk of child total difficulties and hyperactivity/inattention at pre-school age. Pregnant women should be encouraged to quit smoking and avoid exposure to tobacco smoke.
Adult ; Attention Deficit Disorder with Hyperactivity ; epidemiology ; etiology ; physiopathology ; psychology ; Child, Preschool ; Cotinine ; blood ; Female ; Follow-Up Studies ; Humans ; Japan ; epidemiology ; Male ; Maternal Exposure ; adverse effects ; Mothers ; Pregnancy ; Pregnancy Trimester, Third ; Prenatal Exposure Delayed Effects ; epidemiology ; etiology ; Risk ; Sex Factors ; Tobacco Smoking ; adverse effects ; epidemiology

BACKGROUND: Age-related musculoskeletal diseases are becoming increasingly burdensome in terms of both individual quality of life and medical cost. We intended to establish a large population-based cohort study to determine environmental, lifestyle, and genetic risk factors of musculoskeletal and other age-related diseases, and to clarify the association between vitamin D status and such diseases. METHODS: We targeted 34,802 residents aged 40-74 years living in areas of northern Niigata Prefecture, including Sekikawa Village, Awashimaura Village, and Murakami City (Murakami region). The baseline questionnaire survey, conducted between 2011 and 2013, queried respondents on their lifestyle and environmental factors (predictors), and self-reported outcomes. Plasma 25-hydroxyvitamin D (25[OH]D) concentration, an indicator of vitamin D status, was determined with the Liaison® 25OH Vitamin D Total Assay. The primary outcome of this study was osteoporotic fracture; other outcomes included age-related diseases including knee osteoarthritis, perception of chronic pain, dementia, and long-term care insurance use. Mean ages of men and women were 59.2 (SD = 9.3, N = 6907) and 59.0 (SD = 9.3, N = 7457) years, respectively. From the blood samples provided by 3710 men and 4787 women, mean 25(OH)D concentrations were 56.5 (SD = 18.4) nmol/L (22.6 ng/mL) and 45.4 (SD = 16.5) nmol/L (18.2 ng/mL), respectively. DISCUSSION Follow-up surveys are planned every 5 years for 15 years, and incident cases of our targeted diseases will be followed at hospitals and clinics in and nearby the cohort area. We anticipate that we will be able to clarify the association between vitamin D status and multiple disease outcomes in a Japanese population.
Aged ; Aging ; Cohort Studies ; Epidemiologic Research Design ; Female ; Humans ; Incidence ; Japan ; epidemiology ; Male ; Middle Aged ; Musculoskeletal Diseases ; epidemiology ; prevention & control ; Predictive Value of Tests ; Quality of Life ; Risk Factors ; Vitamin D ; analogs & derivatives ; blood

BACKGROUND: Studies reported adverse behavioral development including internalizing and externalizing problems in association with prenatal exposure to bisphenol A (BPA) and phthalates; however, findings were not sufficient due to using different assessment tools and child ages among studies. This study aimed to examine associations between maternal serum levels of BPA and phthalate metabolites and behavioral problems at preschool age. METHODS: The Strengths and Difficulties Questionnaire (SDQ) was used to assess behavioral problems at 5 years of age. BPA and phthalate metabolite levels in the first trimester maternal serum was determined by LC-MS/MS for 458 children. Variables used for adjustment were parental ages, maternal cotinine levels, family income during pregnancy, child sex, birth order, and age at SDQ completed. RESULTS: The median concentrations of BPA, MnBP, MiBP, MEHP, and MECPP, primary and secondary metabolites of phthalates, were 0.062, 26.0, 7.0, 1.40, and 0.20 ng/ml, respectively. MECPP level was associated with increase conduct problem risk (OR = 2.78, 95% CI 1.36-5.68) overall and the association remained after child sex stratification, and odds ratios were increased with wider confidence interval (OR = 2.85, 95% CI 1.07-7.57 for boys, OR = 4.04, 95% CI 1.31-12.5 for girls, respectively). BPA, ∑DBP (MnBP + MiBP), and ∑DEHP (MEHP+MECPP) levels were not associated with any of the child behavioral problems. CONCLUSIONS Our analyses found no significant association between BPA or summation of phthalate metabolite levels and any of the behavioral problems at 5 years of age but suggested possible association between MECPP levels and increased risk of conduct problems.
Adult ; Age Factors ; Benzhydryl Compounds ; blood ; Child, Preschool ; Environmental Exposure ; analysis ; Female ; Humans ; Male ; Phenols ; blood ; Phthalic Acids ; blood ; Pregnancy ; Prenatal Exposure Delayed Effects ; epidemiology ; Problem Behavior ; Smoking ; epidemiology ; Socioeconomic Factors

Background: To obtain suggestions regarding the methods of cooperative learning in basic nursing education, the nursing students' perceptions of cooperative learning and the relationship between such perceptions and their influencing factors were elucidated.Methods: Anonymous, self-administered questionnaires were conducted among 131 nursing students at University A in the Chubu region of Japan.Results: Binomial logistic regression confirmed that cooperative learning experiences in high school, learning satisfaction at University A, social support, styles of handling interpersonal conflicts, and undervaluing others in regard to assumed competence were significant influencing factors on the cooperative work recognition scale.Discussion: Factors, including professional identity, communication ability and students' past negative experiences, may have an effect on the recognition of cooperative work. This suggests the need for the continued investigation of the aspects of cooperative learning that take these factors into account.

We investigated the relationship between daily physical activity level and response inhibition control aspect of cognitive function in older adults using event-related potentials. Twenty-eight Japanese older adults (70.6 ± 3.8 years) participated in the present study. Daily physical activity (PA) was measured using an accelerometer, including step count and the intensity of PA. Participants were divided on the basis of their step count into “Higher PA group” (more than 10,000 steps/day, n = 14) and “Lower PA group”(less than 10,000 steps/day, n = 14). Cognitive function was evaluated by performance, NoGo-N2, and NoGo-P3 while they performed a Go/NoGo task. The results indicated that the Higher PA group exhibited shorter reaction time on Go trials, relative to the Lower PA group. NoGo-P3 amplitude was larger in the Higher PA group compared to the Lower PA group, but NoGo-P3 latency did not differ between groups. PA was positively correlated with NoGo-P3 amplitude. NoGo-N2 component was not related to PA. Thus, PA was more sensitive to monitoring of the outcome of response inhibition rather than pre-motor inhibition in Go/NoGo task. These findings suggest that daily PA is associated with preservation of age-related declines in response inhibition control.