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OBJECTIVE To evaluate the association between regular physical activity and the risk of incident dementia in older Japanese adults. METHODS This was a retrospective cohort study performed in Okayama City, Japan. Overall, 51 477 older Japanese adults were followed from 2008 to 2014. A health checkup questionnaire was used to assess regular physical activity. The Dementia Scale of long-term care insurance was used as a measure of incident dementia. Cox proportional hazard models were used to calculate adjusted hazard ratios, with their 95% confidence intervals, for the incidence of dementia across the categories of physical activity. RESULTS During a 7-year follow-up, 13 816 subjects were considered as having incident dementia. Compared with participants who performed physical activity less than or equal to one time per week, the multivariate adjusted hazard ratio values (95% confidence intervals) for participants who performed physical activity greater than or equal to two times per week but not every day and those who performed physical activity every day were 0.79 (0.75-0.84) and 0.94 (0.89-0.98), respectively. The interaction of physical activity and sex was statistically significant (P < .01). In subgroup analysis, the multivariate-adjusted hazard ratio values (95% confidence intervals) remained low, at 0.76 (0.70-0.84) in males and 0.81 (0.76-0.87) in females who performed physical activity greater than or equal to two times per week but not every day; they were 0.82 (0.76-0.89) in males and 1.01 (0.95-1.07) in females who performed physical activity every day. CONCLUSIONS Regular physical activity could reduce the risk of incident dementia in older Japanese adults, except females who performed physical activity every day.

The prevalence of multiple births has recently increased. However, the association between gestational age and long-term morbidity among twins remains unclear.To examine the association of gestational age with child health and neurological development in early childhood among twins.Population-based longitudinal study.We included 947 children from 479 pairs of twins with information on gestational age.Hospitalization was used as an indicator of physical health, and responses to questions about age-appropriate behaviors were used as an indicator of neurobehavioral development. We conducted binomial log-linear regression analyses, controlling for both child and maternal variables in the model. We accounted for correlations within the pairs with generalized estimating equations.The early term group (i.e., 37 to 38 weeks of gestation) had a lower risk of poor child health and unfavorable neurodevelopment compared with the full term group (≥39 weeks of gestation) and preterm group (37 weeks of gestation). Compared with the early term group, the adjusted risk ratios for hospitalization for all causes during the period from 7 to 18 months of age was 2.2 (95% confidence interval: 1.3-3.8) for very preterm children (32 weeks of gestation), 1.1 (0.8-1.6) for moderately and late preterm children (32 to 36 weeks of gestation), and 1.8 (1.0-3.2) for full term children.We observed a U-shaped association of gestational age with child health and neurodevelopment. The early term group had the lowest risk of poor outcomes among twins.

Aim We examined the effects of being born small for gestational age (SGA) on the risk of being hospitalised for common diseases during childhood. Methods This Japanese nationwide, population-based longitudinal survey followed babies born before 42 weeks of gestation from 10 to 17 January and from 10 to 17 July 2001, using data from the Government's Longitudinal Survey of Babies in the 21st Century. Our study followed 41 268 children until 5.5 years of age: 39 107 full term (8.7% SGA) and 2161 preterm (15.5% SGA). We evaluated the relationship between SGA status and hospitalisation using their history of hospitalisation for common diseases and comparing full-term or preterm births. Logistic regression analysis, adjusted for potential confounders, estimated the odds ratios (ORs) and 95% confidence intervals (CIs). Results The full-term and preterm children who were born SGA were more likely to be hospitalised during infancy and early childhood than those born non SGA. The ORs for hospitalisation from six months to 18 months of age were 1.23 (95% CI: 1.10-1.37) for full-term and 1.67 (95% CI: 1.23-2.25) for preterm subjects. Higher risks of hospitalisation due to bronchitis, pneumonia, bronchial asthma and diarrhoea were also observed. Conclusion Being born SGA was associated with all-cause and cause-specific hospitalisation in early childhood, particularly for term infants.

Persistent hepatitis C virus (HCV) infection causes chronic liver diseases and is a major global health problem. Recently developed treatments with direct-acting antivirals (DAAs) have largely improved the sustained virologic response rate of patients with chronic hepatitis C. However, this approach is still hindered by its great expense and the problem of drug resistance. Using our cell-based HCV assay systems, we reported that the preclinical antimalarial drugs N-89 and N-251 exhibited potent anti-HCV activities. In this study we used our assay systems to evaluate the anti-HCV activities of six kinds of DAAs individually or in combination with N-89 or N-251. The results showed that the DAAs had potent anti-HCV activities and N-89 or N-251 contributed additive or synergistic effect. Using DAA-resistant HCV-RNA-replicating cells, which were prepared by continuous treatment with each DAA, we demonstrated that N-89 and N-251 could overcome all of the DAA-resistant HCVs. These preclinical drugs would have been potential as components of a therapeutic regimen that also included combinations of various DAAs. In addition, sequence analysis of the NS3-NS5B regions of the DAA-resistant HCV genomes newly found several amino acid (aa) substitutions that were suggested to contribute to DAA-resistance in addition to the aa substitutions already known to cause DAA-resistance. Among these new aa substitutions, we found that two substitutions in the NS3 region (D79G and S174Y) contributed to simeprevir- and/or asunaprevir-resistance.

Risk factors for intussusception have only rarely been reported. We examined the association between the risk of hospital admission for intussusception and maternal smoking, using a nationwide population-based longitudinal survey begun in Japan in 2010. Maternal smoking status was queried at 6 months of age, and responses to questions at 18 months of age about history of hospitalization for intussusception during the previous year were used as an outcome of interest. We conducted logistic regression analyses controlling for potential confounding factors. Maternal smoking increased the risk of hospitalization for intussusception (adjusted OR = 2.75, 95% CI [1.09, 6.96]) compared with not smoking, and a dose-response relationship was observed for the association. Maternal smoking is associated with an increased risk of intussusception development in children between the ages of 6 and 18 months.

Background: Although breastfeeding has been well-established as the preferred method for infant nutrition, its prophylactic effects on food allergy remain controversial. Infantile eczema has been linked to food allergy via percutaneous sensitization; however, this relationship has not been considered in previous studies. We aimed to uncover the prophylactic effects of breastfeeding on food allergy, focusing on eczema-mediated percutaneous sensitization. Methods: This retrospective cohort study was based on 46,616 children from the Longitudinal Survey of Newborns in the 21st Century in Japan, begun in 2001. We classified participants into three groups based on infant feeding practices (exclusive breastfeeding, partial breastfeeding including only colostrum, and formula feeding only) and used information from at least one outpatient visit for food allergy during two observation periods (age 6–18 months and age 6–66 months) as health outcomes. We performed log-binomial regression analysis adjusted for potential confounders and stratified analysis according to infantile eczema status. Results: Compared with formula feeding, partial breastfeeding including only colostrum reduced the risk of food allergy only in children with infantile eczema, (RR = 0.66, 95% CI: 0.46, 0.96 for age 6–66 months), whereas exclusive breastfeeding increased this risk in those without infantile eczema (RR = 2.41, 95% CI: 1.40, 4.15, age 6–66 months). The prophylactic effects of breastfeeding on food allergy in the infantile eczema group increased with shorter breastfeeding duration. Conclusions: Our results showed that breastfeeding, especially colostrum, had prophylactic effects on food allergy only among high-risk children with infantile eczema whereas prolonged breastfeeding increased the risk of food allergy. Keywords: Breastfeeding, Cohort, Colostrum, Eczema, Food allergy

Aim To evaluate the association between the amount and frequency of alcohol consumption and incident dementia in older Japanese adults using large sample size data over a long follow-up period. Methods This was a retrospective cohort study carried out in Japan. A total of 53 311 older adults were followed from 2008 to 2014. A health checkup questionnaire was used to assess the amount and frequency of alcohol consumption. The Dementia Scale of long-term care insurance was used as a measure of incident dementia. Cox proportional hazards models were used to calculate adjusted hazard ratios, with their 95% confidence intervals, for the incidence of dementia across the categories of alcohol consumption by sex. Results During a 7-year follow-up period, 14 479 participants were regarded as having incident dementia. Compared with non-drinkers, the multivariate adjusted hazard ratios for participants with alcohol consumption ≤2 units per day, occasionally (0.88, 95% CI 0.81-0.96 in men and 0.84, 95% 0.79-0.90 in women) and daily (0.79, 95% 0.73-0.85 in men and 0.87, 95% 0.78-0.97 in women) were statistically significant, and the difference between occasional and daily consumption was only statistically significant in men; however, for participants with alcohol consumption >2 units per day, occasionally (0.91, 95% 0.71-1.16 in men and 1.09, 95% 0.72-1.67 in women) and daily (0.89, 95% 0.81-1.00 in men and 1.16, 95% 0.84-1.81 in women) were not significant. Conclusions Alcohol consumption of ≤2 units per day, occasionally or daily, could reduce the risk of incident dementia, with greater benefit for men with such daily consumption. Geriatr Gerontol Int 2019; 19: 740-746.

Aim Despite increased interest in an obesity paradox (i.e. a survival advantage of being obese), evidence remains sparse in Japanese populations. We aimed to verify this phenomenon among community-dwelling older adults in Japan. Methods Older adults aged 65–84 years randomly chosen from all 74 municipalities in Shizuoka Prefecture completed questionnaires including body mass index information. Participants were followed from 1999 to 2009. Following World Health Organization guidelines, participants were classified using an appropriate body mass index for Asian populations as follows

Objective To investigate neurological development in small for gestational age (SGA) infants, with a focus on full-term SGA infants. Methods We analyzed data from a large, Japanese, nationwide, population-based longitudinal survey started in 2001. We restricted the study to participants born before 42weeks of gestation ( n =46,563). Parents were asked questions about motor and language development when the children were 2.5years old, and about behavioral development at 5.5years. We analyzed the relationships between SGA status and development by logistic regression. Odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated for each outcome for full-term and preterm births, adjusting for potential infant- and parent-related confounding factors. We also calculated the population-attributable fractions to estimate the public impact of SGA births. Results SGA full-term children were more likely to demonstrate developmental delays at 2.5years, e.g., being unable to walk alone (OR 3.0, 95% CI: 1.7, 5.3), compose a two-phrase sentence (OR 1.5, 95% CI: 1.2, 1.8), or use a spoon to eat (OR 1.5, 95% CI: 1.1, 1.9). SGA status also had some degree of negative impacts on behavioral problems at 5.5years among term children, e.g., being unable to listen without fidgeting (OR 1.2, 95% CI: 1.1, 1.3), or remain patient (OR 1.1, 95% CI: 1.0, 1.2). The public health impacts were comparable between full-term and preterm SGA children at 2.5years. Conclusion SGA is a risk factor for developmental delay, even in full-term infants, with non-negligible public health impacts.

Kawasaki disease is the leading cause of acquired childhood heart disease in most developed countries, but the etiology of the disease is unknown. An aberrant immune response to some environmental triggers may play a role and involuntary exposure to tobacco smoke can alter immune functions. We thus prospectively examined the association between early childhood exposure to maternal smoking and the incidence of Kawasaki disease. We used a large, nationwide population-based longitudinal survey ongoing since 2010 and restricted participants to a total of 38,444 children for whom information on maternal smoking was available. Maternal smoking status was ascertained at 6months of age, and responses to questions about hospital admission for Kawasaki disease between the ages of 6 and 30months were used as outcome. We conducted binomial log-linear regression analyses adjusting for children's, parental, and residential factors with children of non-smoking mothers as our reference group. Maternal smoking increased the risk of admission, in particular for the period between 6 and 18months of age, in a dose-dependent manner. Compared with children of non-smoking mothers, the children of mothers who smoked had a risk ratio of 1.83 (95% confidence interval: 1.06, 3.35) for hospital admissions between 6 and 30months of age and a risk ratio of 2.69 (95% confidence interval: 1.56, 4.64) for hospital admissions between 6 and 18months of age. Early childhood exposure to maternal smoking may increase the risk of Kawasaki disease hospitalizations in childhood.

Objective To examine the relationship between the catch-up growth of preterm, SGA children and their behavioral development. Methods We analyzed data from a large Japanese, nationwide, population-based, longitudinal survey that started in 2001. We restricted the study participants to preterm children with information on height at 2 years of age (n = 1667). Catch-up growth for SGA infants was defined as achieving a height at 2 years of age above −2.0 standard deviations for chronological age. We then used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations of SGA/catch-up status with neurobehavioral development both at 5.5 and 8 years of age, adjusting for potential infant- and parent-related confounding factors. Results Twenty-six percent of preterm SGA infants failed to catch up. SGA children without catch-up growth were more likely to be unable to listen without fidgeting (OR 2.51, 95% CI: 1.06–5.93) and unable to focus on one task (OR 2.66, 95% CI: 1.09–6.48) compared with non-SGA children at 5.5 years of age. Furthermore, SGA children without catch-up growth were at significant risk for inattention at 8 years of age. Conclusions SGA infants with poor postnatal growth were at risk for attention problems throughout preschool-age to school-age among preterm infants. Early detection and intervention for attention problems among these infants is warranted.

The association between early daycare attendance and risk of allergic diseases remains inconclusive. Therefore, we examined the association among Japanese children on a long-term basis using a nationwide longitudinal survey data. We estimated the association between daycare attendance at age 6 or 18 months and allergy development using information on outpatient visits for atopic dermatitis (AD), food allergy (FA), and asthma and admission for asthma up to 12 years of age as a proxy for developing these diseases, with multilevel logistic regression. Early daycare attendance was associated with increased odds of AD at ages 2.5-3.5 years: the adjusted odds ratio (OR) was 1.34 [95% CI: 1.21, 1.47]. The association with FA was equivocal. The odds of asthma was increased before age 3.5 years and afterwards decreased: the adjusted ORs were 1.60 [1.44, 1.77] for ages 1.5-2.5 years and 0.77 [0.69, 0.87] for ages 5.5-7 years. The effect of early daycare attendance depends on the type of allergies.

Exposure to air pollution is linked with an increased risk of preterm births. To provide further evidence on this relationship, we evaluated the association between proximity to major roads--as an index for air pollution exposure--and various obstetrical complications. Data were extracted from a database maintained by the perinatal hospital in Shizuoka, Japan. We restricted the analysis to mothers with singleton pregnancies of more than 22 weeks of gestation from 1997 to 2012 (n=19,077). Using the geocoded residential information, each mother was assigned proximity to major roads. We then estimated multivariate adjusted odds ratios and their 95% confidence intervals (CIs) for the effects of proximity to major roads on various obstetrical complications (preeclampsia, gestational diabetes mellitus, placenta abruption, placenta previa, preterm premature rupture of membrane (pPROM), preterm labor, and preterm births). We found positive associations of proximity to major roads with preeclampsia and pPROM. Living within 200 m increased the odds of preeclampsia by 1.3 times (95% CI, 1.0-1.8) and pPROM by 1.6 times (95% CI, 1.1-2.2). Furthermore, living within 200 m increased the odds of preterm births by 1.4 fold (95% CI, 1.2-1.7). Exposure to traffic-related air pollution increased the risk of preeclampsia and pPROM in this study. We propose a mechanism responsible for the association between air pollution and preterm births.

Introduction: Evidence has accumulated on the association between ambient air pollution and adverse birth outcomes. However, most of the previous studies were conducted in geographically distinct areas and suffer from lack of important potential covariates. We examined the effect of ambient air pollution on term low birth weight (LBW) using data from a nationwide population-based longitudinal survey in Japan that began in 2001. Methods: We restricted participants to term singletons (n = 44,109). Air pollution concentrations during the 9 months before birth were obtained at the municipality level and were assigned to the participants who were born in the corresponding municipality. We conducted multilevel logistic regression analyses adjusting for individual and municipality-level variables. Results: We found that air pollution exposure during pregnancy was positively associated with the risk of term LBW. In the fully adjusted models, odds ratios following one interquartile range increase in each pollutant were 1.09 (95% confidence interval: 1.00, 1.19) for suspended particulate matter (SPM), 1.11 (0.99, 1.26) for nitrogen dioxide (NO2), and 1.71 (1.18, 2.46) for sulfur dioxide (SO2). Specifically, effect estimates for SPM and NO2 exposure at the first trimester were higher than those at other trimesters, while SO2 was associated with the risk at all trimesters. Nonsmoking mothers were more susceptible to SPM and NO2 exposure compared with smoking mothers. Conclusions: Ambient air pollution increases the risk of term LBW in a nationally representative sample in Japan. Keywords: Air pollution, Low birth weight, Nitrogen dioxide, Particulate matter, Pregnancy outcomes, Sulfur dioxide

SummaryBackground Environmental factors seem to be related to the incidence of allergic disease. Children with a later birth order are often exposed to environments, where pathogens and endotoxins can be found, and thus have a higher risk of developing infectious diseases. Therefore, birth order is regarded as an indicator that reflects post-natal environment. However, longitudinal studies are limited on this subject. This study sought to elucidate the relationships between birth order and allergic disease. Methods From a nationwide longitudinal study that followed children born in 2001 (n = 47 015), we selected doctors’ visits for 3 types of allergic disease—bronchial asthma, food allergy and atopic dermatitis—from infancy to 12 years of age and conducted binomial log-linear regression analysis to evaluate the associations between birth order and these diseases. We adjusted for the child and parental factors and estimated risk ratio (RR) and 95% confidence interval (CI) for each outcome. Results The associations between birth order and bronchial asthma were diverse; later birth order increased the risk in early childhood, but decreased the risks during school age. For example, the adjusted RR comparing third-born or higher and first-born children was 1.19 (95% CI, 1.05-1.35) between 30 and 42 months of age, but was 0.76 (95% CI, 0.65-0.89) between 10 and 11 years. Later birth order was generally protective for food allergy but increased the risk of atopic dermatitis. Conclusion The influence of birth order depended on the type of allergic disease and the childhood period. Childhood is unique in terms of physical and immunological development, and the immune response to the post-natal environment in childhood appears to be heterogeneous.

Objective To examine the relationship between catch-up growth of full-term, small for gestational age (SGA) children and their neurobehavioral development. Study design Data were obtained from a population-based nationwide Japanese longitudinal survey that started in 2001. Study participants were full-term children with information on height at 2 years of age (n = 32 533). Catch-up growth for SGA infants was defined as achieving a height at 2 years of age of more than -2.0 standard deviations for chronological age. Logistic regression analyses were used to estimate ORs and 95% CIs for the associations of SGA and catch-up growth status with neurobehavioral development at 2.5 and 8 years of age, adjusting for potential infant- and parent-related confounding factors. Results Fifteen percent of term SGA infants failed to catch up in height. At 2.5 years of age, SGA children without catch-up growth were more likely to be unable to climb stairs (OR, 10.42; 95% CI, 5.55-19.56) and unable to compose a 2-word sentence (OR, 3.58; 95% CI, 1.81-7.08) compared with children with normal growth at birth. Furthermore, SGA children without catch-up growth were at increased risk for aggressive behaviors (OR, 3.85; 95% CI, 1.19-12.47) at 8 years of age. Conclusions Continuous follow-up for full-term SGA infants with failure of catch-up growth or poor postnatal growth may be beneficial for early detection and intervention for behavioral problems.

Supplemental Digital Content is available in the text., Background: A number of studies have linked long-term exposure to particulate matter with aerodynamic diameter

A lower bodyweight may be associated with adverse birth outcomes, such as low birth weight and being small for a given gestational age. In Japan, the rate of low birth weight has been increasing over the last two decades, such that both low pre-pregnancy weight and inadequate weight gain during pregnancy are viewed as critical issues in terms of the reproductive health of Japanese women. The aim of our study was to evaluate the relationship between socioeconomic status (SES) and inadequate weight gain during pregnancy. A cross-sectional, hospital-based study using data from a large hospital in Hamamatsu city, Japan, from 1997 to 2010 was conducted. Among a total of 21,855 deliveries, 15,020 participants were analyzed. Odds ratios and confidence intervals were estimated using a logistic regression model. We defined maternal occupational status as follows: home-maker married to a salaried-spouse, home-maker married to a self-employed spouse, home-maker married to a professional, all other home-makers, office worker, professional, and all other occupations. In the high SES groups (home-makers married to self-employed spouse and professional spouse, as well as office workers and professional workers), we found an association with inadequate weight gain during pregnancy, especially among underweight women. There was no association between SES and inadequate weight gain among normal-weight and overweight women. Japanese women from higher socioeconomic backgrounds appear to be at greater risk for inadequate weight gain. This result may contribute to enhancing prenatal education on pregnancy-related weight gain in Japan.

Background The adverse effects of maternal and paternal smoking on child health have been studied. However, few studies demonstrate the interaction effects of maternal/paternal smoking, and birth outcomes other than birth weight have not been evaluated. The present study examined individual effects of maternal/paternal smoking and their interactions on birth outcomes. Methods A follow-up hospital-based study from pregnancy to delivery was conducted from 1997 to 2010 with parents and newborn infants who delivered at a large hospital in Hamamatsu, Japan. The relationships between smoking and growth were evaluated with logistic regression. Results The individual effects of maternal smoking are related to low birth weight (LBW), short birth length and small head circumference. The individual effects of paternal smoking are related to short birth length and small head circumference. In the adjusted model, both parents' smoking showed clear associations with LBW (odds ratio [OR] = 1.64, 95% confidence interval [CI] 1.18-2.27) and short birth length (-1 standard deviation [SD] OR = 1.38, 95% CI 1.07-1.79; -2 SD OR = 2.75, 95% CI 1.84-4.10). Conclusions Maternal smoking was significantly associated with birth weight and length, but paternal smoking was not. However, if both parents smoked, the risk of shorter birth length increased.

Background Small for gestational age (SGA) birth is linked with neurological deficits among children at pre-school age, but the evidence is still limited on whether such deficits are still observable at school age. We investigated the association between SGA birth and behavioral development at school age among full-term infants. Methods We analyzed data from a large, Japanese, nationwide, population-based longitudinal survey that started in 2001. We restricted the study participants to children born at 37–41weeks of gestation with information on birth weight and behavioral outcomes at 8years of age ( n =33,795). Behavioral outcomes including three attentional problems and four aggressive behaviors queried at 8years of age by survey questions were used as outcome indicators. We then used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the associations between SGA birth and each outcome, adjusting for potential infant- and parent-related confounding factors. Results Among full-term children, SGA children were more likely to interrupt people (OR 1.10, 95% CI 1.01, 1.20), unable to wait his/her turn (OR 1.17, 95% CI 1.00, 1.38), and destroy toys and/or books (OR 1.15, 95% CI 1.00, 1.31). Conclusions This is the largest study ever conducted on this issue. SGA birth is negatively associated with some attentional problems and aggressive behavior at school age among full-term children. Appropriate long-term developmental follow-up and support may be needed for full-term SGA infants.

There has been a growing concern that maternal employment could have adverse or beneficial effects on children's health. Although recent studies demonstrated that maternal employment was associated with a higher risk of childhood overweight, the evidence remains sparse in Asian countries. We sought to examine the relationship between maternal working hours and early childhood overweight in a rural town in Okayama Prefecture.In February 2008, questionnaires were sent to parents of all preschool children aged ≥3 yr in the town to assess maternal working status (working hours and form of employment), children's body mass index, and potential confounders. Childhood overweight was defined following the age and sex-specific criteria of the International Obesity Task Force. Odds ratios (ORs) and 95% confidence intervals (CIs) for childhood overweight were estimated in a logistic regression. We used generalized estimating equations with an exchangeable correlation matrix, considering the correlation between siblings.We analyzed 364 preschool children. Adjusting for each child's characteristics (age, sex), mother's characteristics (age, obesity, educational attainment, smoking status, and social participation), and family's characteristics (number of siblings), children whose mothers work8 h/day had a substantially lower risk for being overweight (OR: 0.28, 95% CI: 0.09, 0.93) compared with children of non-working mothers, whereas the relationship was less pronounced among children whose mothers work ≥8 h/day (OR: 0.71, 95% CI: 0.19, 2.68). We observed similar patterns in a stratified analysis by the form of maternal employment.Short maternal working hours are associated with a lower odds of early childhood overweight.

S-1 is an oral anticancer fluoropyrimidine agent designed to elevate anticancer activity with a decrease in gastrointestinal toxicity. We conducted a phase II study to evaluate the efficacy and safety of combination chemotherapy with S-1 plus cisplatin in patients with advanced non-small cell lung cancer (NSCLC). Chemotherapy-naïve patients were treated with S-1 administered orally at 40 mg/m(2) twice a day for 21 consecutive days, and cisplatin (60 mg/m(2)) infused intravenously on day 8, repeated every 5 weeks. Of the 44 patients enrolled in the study, 40 were assessable for efficacy and safety. The median number of cycles administered was 3 (range 1-9 cycles). Among the 40 assessable patients, 7 partial responses were observed, with an overall response rate (RR) of 17.5% [95% confidence interval (CI), 5.2-29.8]. Patients with squamous cell carcinoma showed a significantly higher RR (55.5%) than those with adenocarcinoma (9.1%) or other types of NSCLC (0%). The median progression-free survival was 4.3 months (95% CI, 3.4-4.9), the median survival time was 17.9 months (95% CI, 15.0-20.8), and the 1- and 2-year survival rates were 63.3 and 27.3%, respectively. Major grade 3-4 hematologic toxicities were leukocytopenia (7.5%), neutropenia (5.0%), anemia (15.0%) and thrombocytopenia (2.5%). No grade 4 non-hematologic toxicity or treatment-related death occurred. These results suggest that combination chemotherapy with S-1 plus cisplatin is a promising therapeutic candidate for patients with advanced NSCLC, particularly squamous cell carcinoma.

Objectives To examine the effects of prenatal and postnatal exposure to particulate matter on Kawasaki disease (KD) occurrence, using data from a nationwide population-based longitudinal survey in Japan that began in 2010. Study design Prenatal and postnatal suspended particulate matter concentrations were obtained at municipality level and assigned to participants based on their municipality of birth. We analyzed data from 30 367 participants with data on either exposure period. We used hospital admission for KD from 6 to 30 months of age as the main outcome of interest. We conducted a multilevel logistic regression analysis, adjusting for individual and municipality-level variables. Results Children who were exposed to higher levels of suspended particulate matter, in particular during pregnancy, were more likely to be hospitalized for KD. The ORs for ≥25 µg/m3 exposure compared with Conclusions Early life exposure to particulate air pollution, in particular during pregnancy, is associated with an increased risk of KD hospital admission in early childhood in a nationally representative sample in Japan.

Purpose To investigate the association between green tea consumption and mortality from all causes, cancer, and cardiovascular disease (CVD) among elderly people. Methods In a population-based, prospective cohort study, a total of 14,001 elderly residents (aged 65–84 years), randomly chosen from all 74 municipalities in Shizuoka, Japan, completed questionnaires that included items about frequency of green tea consumption. They were followed for up to 6 years, from December 1999 to March 2006. Consequently, 12,251 subjects were analyzed to estimate the hazard ratios (HRs) for all-cause mortality, cancer, and CVD. Results Among 64,002 person-years, 1,224 deaths were identified (follow-up rate, 71.6%). The multivariate HRs and 95% confidence intervals (CIs) for CVD mortality compared those who consumed seven or more cups per day with those who consumed less than one cup per day, were 0.24 (0.14–0.40), 0.30 (0.15–0.61), and 0.18 (0.08–0.40) for total participants, men, and women, respectively. Although green tea consumption was not inversely associated with cancer mortality, green tea consumption and colorectal cancer mortality were inversely associated with a moderate dose-response relationship. Conclusions Green tea consumption is associated with reduced mortality from all causes and CVD. This study also suggests that green tea could have protective effects against colorectal cancer.

Objectives The number of studies investigating the health effects of long-term exposure to air pollution is increasing, however, most studies have been conducted in Western countries. The health status of Asian populations may be different to that of Western populations and may, therefore, respond differently to air pollution exposure. Therefore, we evaluated the health effects of long-term exposure to traffic-related air pollution in Shizuoka, Japan. Methods Individual data were extracted from participants of an ongoing cohort study. A total of 14 001 older residents, who were randomly chosen from all 74 municipalities of Shizuoka, completed questionnaires and were followed from December 1999 to March 2006. Individual nitrogen dioxide exposure data, as an index for traffic-related exposure, were modelled using a land use regression model. We assigned participants an estimated concentration of nitrogen dioxide exposure during 2000–2006. We then estimated the adjusted HR and their CI for a 10 μg/m3 increase in exposure to nitrogen dioxide for all-cause or cause-specific mortality. Results The adjusted HR for all-cause mortality was 1.02 (95% CI 0.96 to 1.08). Regarding cause-specific mortality, the adjusted HR for cardiopulmonary mortality was 1.16 (95% CI 1.06 to 1.26); in particular the adjusted HR for ischaemic heart disease mortality was 1.27 (95% CI 1.02 to 1.58) and for pulmonary disease mortality it was 1.19 (95% CI 1.02 to 1.38). Furthermore, among non-smokers, a 10 μg/m3 increase in nitrogen dioxide was associated with a higher risk for lung cancer mortality (HR 1.30, 95% CI 0.85 to 1.93). Conclusion Long-term exposure to traffic-related air pollution, indexed by nitrogen dioxide concentration, increases the risk of cardiopulmonary mortality, even in a population with a relatively low body mass index and increases the risk of lung cancer mortality in non-smokers.

ObjectiveTo analyse the effect of different preterm birth categories on behavioural outcomes.DesignProspective cohort design.SettingsThe Japanese Longitudinal Survey of Babies in the 21st Century was used for the study.SubjectsNeonates born in 2001 in Japan (n=34 163) and followed up at the age of 8 years. Post-term births were excluded and the sample was divided into four groups according to gestational age: Outcome measuresSeven behavioural outcomes were examined: three attention problems and four delinquent/aggressive behaviours.ResultsLogistic regression was used to estimate adjusted ORs and 95% CIs for each outcome. Positive associations were found between preterm birth (ConclusionsChildren who are born

Objectives We investigated the association between breastfeeding duration during the first half year of life and the risk of early childhood caries from the age of 30 to 66 months in Japan. Design Observational study of a longitudinal survey. Setting A secondary data analysis of the Japanese Longitudinal Survey of Babies in the 21st Century. Participants 43 383 infants at the age of 6 months. Outcome measures Early childhood caries—defined as a child9s visit to a dentist for treatment of dental caries during the past 12 months—was ascertained from the caregiver from the age of 30 months in the survey. We estimated the risk of dental caries each year according to duration of breast feeding using logistic regression analyses. We controlled for a set of biological factors (birth weight, sex, parity and maternal age at delivery) and socioeconomic factors (maternal educational attainment and smoking status, marital status at delivery, family income and region of birth and residence). Results We found that infants who had been breast fed for at least 6 or 7 months, both exclusively and partially, were at elevated risk of dental caries at the age of 30 months compared with those who had been exclusively formula fed. Adjusted ORs were 1.78 (95% CI, (1.45 to 2.17)) for the exclusively breastfed group and 1.39 (1.14 to 1.70) for the partially breastfed group. However, the associations became attenuated through the follow-up period and were no longer statistically significant beyond the age of 42 months for the partially breastfed group and beyond the age of 54 months for the exclusively breastfed group. Conclusions We found an association between breast feeding for at least 6 or 7 months and elevated risk of dental caries at age 30 months. However, the association became attenuated as children grew older.

Recent studies suggest potential adverse effects of methylmercury exposure on myocardial infarction and hypertension, although the evidence is still limited. We thus evaluated this association using age-standardized mortality ratios (ASMRs) in Minamata, where severe methylmercury poisoning had occurred. We obtained mortality data from annual vital statistics and demographic statistics from census. We then compared mortality of atherosclerotic heart disease including degenerative heart disease and hypertension in Minamata-city with those in Kumamoto Prefecture, which includes Minamata city, as a control. We estimated ASMRs and 95% confidence intervals (CIs) during the period from 1953 to 1970. ASMRs of atherosclerotic heart disease were continuously decreased during the period from 1953 to 1967. In contrast, the ASMR of hypertension was significantly elevated during the period from 1963 to 1967 (SMR=1.38, CI; 1.06-1.80); but they decreased later. Although dilution is present in this ecological study, our study supports the notion that methylmercury exposure induces hypertension.

Average maternal age at birth has been rising steadily in Western and some Asian countries. Older maternal age has been associated with adverse pregnancy and birth outcomes; however, studies on the relationship between maternal age and young children’s health remain scarce. Therefore, we sought to investigate the association of maternal age with child health outcomes in the Japanese population. We analyzed data from two birth cohorts of the nationwide Japanese Longitudinal Survey of Babies in 21st Century (n2001 = 47,715 and n2010 = 38,554). We estimated risks of unintentional injuries and hospital admissions at 18 and 66 months according to maternal age, controlling for the following potential confounders: parental education; maternal parity, smoking status, and employment status; household income; paternal age, and sex of the child. We also included the following as potential mediators: preterm births and birthweight. We observed a decreasing trend in the risks of children’s unintentional injuries and hospital admissions at 18 months according to maternal age in both cohorts. In the 2001 cohort, compared to mothers 40.0 years, respectively, controlling for confounders. Our findings were in line with previous findings from population-based studies conducted in the United Kingdom and Canada suggesting that older maternal age may be beneficial for early child health.

ObjectiveWhether or not breast-feeding is protective against asthma among children is still controversial. Therefore, we examined the effects of breast-feeding on hospitalization for asthma in early childhood.DesignSecondary data analyses of a nationwide longitudinal survey of children in Japan ongoing since 2001, with results collected from 2001 to 2004. We used logistic regression models to evaluate the associations of breast-feeding with hospitalization for asthma in children between the ages of 6 and 42 months, adjusting for children’s factors (sex, day-care attendance and presence of older siblings) and maternal factors (educational attainment and smoking habit).SettingAll over Japan.SubjectsTerm singleton children with information on feeding practices during infancy (n 43367).ResultsAfter adjusting for maternal factors and children’s factors, exclusive breast-feeding at 6–7 months of age was associated with decreased risk of hospitalization for asthma in children. The adjusted odds ratio was 0·77 (95 % CI 0·56, 1·06). One-month longer duration of breast-feeding was associated with a 4 % decreased risk of hospitalization for asthma (OR=0·96; 95 % CI 0·92, 0·99).ConclusionsThe protective effects of breast-feeding on hospitalization for asthma were observed in children between the ages of 6 and 42 months.

症例は, 70歳男性.健診で右下肺野の異常影を指摘され近医で約10ヵ月間経過観察されていたが, 徐々に陰影の増強を認めた.胸部単純X線およびCTでは, 小嚢胞状の含気の混在する肺炎様浸潤影が主体であった.経気管支肺生検 (TBLB) にて特発性間質性肺炎と診断し治療を開始したが, 陰影の改善を認めなかった.再び施行したTBLBでは, 悪性腫瘍が強く疑われたため, 審査開胸し診断的右下葉切除術を行った.下葉は750gで, 外観は肝状であり, 含気に乏しく牽糸性の粘液が充満していた.病理所見は, 立方状から円柱状の腫瘍細胞が, 既存の肺胞上皮を置換して散在性に下葉全体に増殖していた。腫瘍は, 粘液形成が著明で, 細気管支肺胞型腺癌と診断された.本例は, 一葉限局型の細気管支肺胞型腺癌で, pT2N0M0であり, 治癒切除を行い得たと考えられるが, 術前診断の困難さから健診発見から手術まで約1年を要しており, 経気道播種の可能性を考えて注意深い経過観察が必要と考える.

Background Exposure to air pollution has been demonstrated to increase the risk of preterm birth and low birth weight (LBW). Although evidence has accumulated on characteristics associated with increased risk of air pollution-related health effects, most studies have been conducted in the adult population and evidence on reproductive outcomes is limited. We examined whether socio-economic position (SEP) and parental characteristics (parental behavior and co-morbidity) modified the relationship between air pollution and adverse birth outcomes. Methods Data were extracted from a perinatal hospital database based in Shizuoka, Japan. We restricted the analysis to mothers who delivered live-born single births from January 1997 to December 2010 (n = 16,615). Each birth was assigned proximity to major roads. Multivariate adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated for the outcomes of preterm birth and term LBW. We stratified subjects by individual/area-level SEP and parental characteristics. We then measured interactions on the additive scale between the respective factors and exposure. Results Lower SEP at both individual and area levels was associated with the increased occurrence of adverse birth outcomes. Living within 200 m from a major road increased the risk of preterm birth by 1.5 times (95% CI: 1.3-1.9) and LBW by 1.2 times (95% CI: 0.9-1.6). Mothers with lower individual SEP defined by household occupation experienced higher ORs for term LBW (OR = 3.1, 95% CI: 1.2-8.2) compared with those with higher individual SEP. In contrast, mothers who lived in the highest area-level SEP region (i.e., affluent areas) showed slightly higher point estimates compared with those who lived in middle or poor areas. In addition, maternal diabetic and hypertensive status modified the association between proximity and preterm birth, while maternal smoking status modified the association between proximity and term LBW. Conclusions The present study demonstrated that air pollution is an independent risk factor for adverse birth outcomes. Mothers with lower individual SEP and mothers living in higher SEP region may be susceptible to the adverse effect of air pollution. Maternal diabetic, hypertensive, and smoking status may also increase susceptibility to this air pollution-related health effect.

Background The proportions of preterm birth (PTB, ie., delivered before 37 gestational weeks) and low birth weight (LBW, ie., birth weight less than 2500 g at delivery) have been rising in developed countries. We sought to examine the factors contributing to the rise in Japan, with particular focus on the effects of obstetric interventions. Methods We used a database maintained by one large regional hospital in Shizuoka, Japan. We restricted the analysis to mothers who delivered live singleton births from 1997 to 2010 (n = 19,221). We assessed the temporal trends in PTB and LBW, then divided the study period into four intervals and compared the proportions of PTB and LBW. We also compared the newborns’ outcomes between the intervals. Results PTB, in particular medically indicated PTB, increased considerably. The increase was largely explained by changes in caesarean sections. The neonatal outcomes did not worsen, and instead the Apgar scores and proportions requiring neonatal intensive care unit (NICU) admission improved. In particular, the risks of NICU admission in the interval from 2007 to 2010 were decreased among all births [odds ratio (OR): 0.84; 95% confidence interval (CI): 0.75, 0.95] and medically indicated births (OR: 0.44; 95% CI: 0.29, 0.68) compared with the interval from 1997 to 2000. Conclusions Despite the increases in PTB as well as LBW, the present study suggests benefits of obstetric interventions. Rather than simple categorization of PTB or LBW, indicators such as perinatal mortality or other outcomes may be more appropriate for evaluation of perinatal health in developed countries.

Few epidemiological studies have examined the potential protective effects of physical activity on insomnia. The authors thus evaluated the association between physical activity and insomnia in a large population-based study in Shizuoka, Japan. Individual data were obtained from participants in an ongoing cohort study. A total of 14,001 older residents who completed questionnaires were followed for 3 yr. Of these, 10,211 and 3,697 participants were eligible for the cross-sectional and longitudinal analyses, respectively. The authors obtained information about the frequency of physical activity and insomnia. Then, the adjusted odds ratios and 95% confidence intervals between physical activity and insomnia were estimated. Habitual physical activity was related to lower prevalence of insomnia. Frequent physical activity also reduced the incidence of insomnia, especially difficulty maintaining sleep. For elderly people with sufficient mobility and no preexisting disease, high-frequency physical activity (e.g., 5 or more days/wk) may help reduce insomnia.

Background The link between long working hours and health has been extensively studied for decades. Despite global concern regarding metabolic syndrome, however, no studies to date have solely evaluated the relationship between long working hours and that syndrome. We therefore examined the association between long working hours and metabolic syndrome in a cross-sectional study. Methods Between May and October 2009, we collected data from annual health checkups and questionnaires from employees at a manufacturing company in Shizuoka, Japan. Questionnaires were returned by 1,601 workers (response rate: 96.2%; 1,314 men, 287 women). After exclusions, including women because of a lack of overtime work, the analysis was performed for 933 men. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for metabolic syndrome. Further, we conducted a stratified analysis by age-group ( Results Metabolic syndrome was identified in 110 workers (11.8%). We observed a positive association between working hours and metabolic syndrome after adjusting for age, occupation, shift work, smoking status, frequency of alcohol consumption, and cohabiting status. Compared with subjects who worked 7–8 h/day, multivariate ORs for metabolic syndrome were 1.66 (95% CI, 0.91–3.01), 1.48 (95% CI, 0.75–2.90), and 2.32 (95% CI, 1.04–5.16) for those working 8–9 h/day, 9–10 h/day, and >10 h/day, respectively. Similar patterns were obtained when we excluded shift workers from the analysis. In age-stratified analysis, the corresponding ORs among workers aged ≥40 years were 2.02 (95% CI, 1.04–3.90), 1.21 (95% CI, 0.53–2.77), and 3.14 (95% CI, 1.24–7.95). In contrast, no clear association was found among workers aged Conclusions The present study suggests that 10 h/day may be a trigger level of working hours for increased risk of metabolic syndrome among Japanese male workers.

A number of studies have linked exposure to long-term outdoor air pollution with cardiopulmonary disease; however, the evidence for stroke is limited. Furthermore, evidence with the risk for lung cancer (LC) is still inconsistent. We, therefore, evaluated the association between long-term exposure to traffic-related air pollution and cause-specific mortality. Individual data were extracted from participants of an ongoing cohort study in Shizuoka, Japan. A total of 14,001 elderly residents completed questionnaires and were followed from December 1999 to January 2009. Annual individual nitrogen dioxide (NO(2)) exposure data, as an index for traffic-related exposure, were modeled using a Land Use Regression model and assigned to the participants. We then estimated the adjusted hazard ratios (HRs) and their confidence intervals (CIs) associated with a 10 μg/m(3) elevation in NO(2) for all-cause or cause-specific mortality using time-varying Cox proportional hazards models. We found positive associations of NO(2) levels with all-cause (HR=1.12, 95% CI: 1.07-1.18), cardiopulmonary disease (HR=1.22, 95% CI: 1.15-1.30), and LC mortality (HR=1.20, 95% CI: 1.03-1.40). Among cardiopulmonary disease mortality, not only the risk for ischemic heart disease (HR=1.27, 95% CI: 1.11-1.47) but also the risks for stroke were elevated: intracerebral hemorrhage (HR=1.28, 95% CI: 1.05-1.57) and ischemic stroke (HR=1.20, 95% CI: 1.04-1.39). The present study supports the existing evidence that long-term exposure to traffic-related air pollution increases the risk of cardiopulmonary as well as LC mortality, and provides additional evidence for adverse effects on intracerebral hemorrhage as well as ischemic stroke.

OBJECTIVE: To examine the relationship between frequency of antenatal care visits as a whole and in each trimester and neonatal mortality in Indonesia. SUBJECTS: 13 055 single births from the fifth Indonesia Demographic Health Survey in 2006-07. METHODS: Estimate adjusted odds ratios (ORs) and their 95% confidence intervals (95% CIs). RESULTS: Pregnant women who had more antenatal care visits experienced a lower risk of neonatal mortality and more benefit in the last trimester: the ORs against the 0-1 visit group were 0.76 (95% CI 0.45-1.29) for 2 visits group 0.54 (95% CI 0.33-0.87) for 3 visits group and 0.31 (95% CI 0.17-0.57) for 4 visits group respectively. Individual ORs as a whole period were not significant but ORs declined markedly at 7 visits or more. CONCLUSION: The results may provide a valuable recommendation for the care of pregnant women in Indonesia.

Exposure to air pollution has been demonstrated to increase the risk of preterm birth and low birth weight. We examined whether proximity to major roads (as a marker of exposure to air pollution) is associated with increased placenta/birth weight ratio (as a biomarker of the placental transport function). Data on parental characteristics and birth outcomes were extracted from the database maintained by a major hospital in Shizuoka Prefecture, Japan. We restricted the analysis to mothers who delivered liveborn single births from 1997 to 2008 (n = 14,189). Using geocoded residential information, each birth was classified according to proximity to major roads. We examined the association between proximity to major roads and the placenta/birth weight ratio, using multiple linear regression. Proximity to major roads was associated with higher placenta/birth weight ratio. After adjusting for potential confounders, living within 200 m of a major road increased the ratio by 0.48% (95% CI = 0.15 to 0. 80). In addition, proximity to major roads was associated with lower placenta weight and birth weight. These observed associations were stronger among participants living closer to major roads. Exposure to traffic-related air pollution is associated with higher placenta/birth weight ratio. Impaired placental oxygen and nutrient transport function might be a mechanism for explaining the observed association between air pollution and low birth weight as well as preterm birth.

Evidence linking short-term exposure to outdoor air pollution with hemorrhagic stroke is inconsistent.We evaluated the associations between outdoor air pollution and specific types of stroke in Tokyo, Japan, from April 2003 to December 2008. We obtained daily counts of stroke mortality (n = 41,440) and concentrations of nitrogen dioxide as well as particles less than 2.5 μm in diameter. Time-series analysis was employed.Although same-day air pollutants were positively associated with ischemic stroke and intracerebral hemorrhage mortality, both air pollutants were more strongly associated with subarachnoid hemorrhage mortality: rate ratio was 1.041 (95% confidence interval: 1.011-1.072) for each 10 μg/m3 increase in the previous-day particles less than 2.5 μm.This study suggests that short-term exposure to outdoor air pollution increases the risks of hemorrhagic stroke mortality as well as ischemic stroke mortality.

Seventy-six patients with advanced non-small-cell lung cancer were randomly allocated to two groups and treated with cisplatin (CDDP; 80 mg/m2 on day 1) plus either vindesine (VDS; 3 mg/m2 on days 1 and 8) or mitomycin C (MMC; 8 mg/m2 on days 1 and 8) every 3-4 weeks. The objective response rates were 26% (10/38) for CDDP plus VDS and 32% (11/34) for CDDP plus MMC; the corresponding response rates in patients with adenocarcinoma were 7% (1/14) and 43% (6/14), respectively. The median survival times ofpatients treated with CDDP plus VDS and CDDP plus MMC were 33 and 30 weeks, respectively, the difference in survival times in the two groups not being significant. There was no significant difference in toxic effects in the two groups except that alopecia and leukopenia were more frequent in patients treated with CDDP plus VDS.

Preterm births cause a large public-health burden, and air pollution is considered to be a potential risk factor. We evaluated the association between proximity to major roads (as an index for air pollution) and preterm births, classified by gestational age and specific clinical manifestations.Data on parental information and birth outcomes were extracted from the database maintained by the perinatal hospital in Shizuoka, Japan. We restricted the analysis to mothers who delivered liveborn single births from 1997 to 2008 (n = 14,226). Using the geocoded residential information, each birth was classified on its proximity to major roads. We estimated the multivariate-adjusted odds ratios and their 95% confidence intervals (CIs) for the association of proximity to major roads with preterm births, using logistic regression.We found positive associations between proximity to major roads and preterm births at all gestational ages. Living within 200 m increased the risk of births before 37 weeks by 1.5 times (95% CI = 1.2-1.8), birth before 32 weeks by 1.6 times (1.1-2.4), and births before 28 weeks by 1.8 times (1.0-3.2). Proximity specifically increased the risk of preterm births with preterm premature rupture of the membranes and with pregnancy hypertension.This study demonstrates that exposure to traffic-related air pollution increases even the risk of preterm births of less than 30 weeks' gestational age and proposes a possible mechanism.

Long-term exposure to inorganic arsenic is related to increased risk of cancer in the lung, skin, bladder, and, possibly, other sites. However, little is known about the consequences of developmental exposures in regard to cancer risk. During early summer in 1955, mass arsenic poisoning of infants occurred in the western part of Japan because of contaminated milk powder. Okayama Prefecture was most severely affected. We examined whether the affected birth cohorts in this prefecture experienced increased cancer mortality.We targeted subjects who were born from September 1950 to August 1960 and died in Okayama Prefecture between January 1969 and March 2008 due to malignant neoplasm (N = 3,141). We then compared cancer mortality (total, liver, pancreatic, lung, bladder/kidney, and hematopoietic cancers) between cohorts born before the milk poisoning (exposed group) and cohorts born after the poisoning (nonexposed group). We estimated mortality ratios and 95% confidence intervals.Total and liver cancers were elevated in the cohort up to 1 year of age at time of the poisoning. In addition, pancreatic and hematopoietic cancers were elevated in the cohorts up to 5 years of age, and mortality ratios were approximately twice those of the nonexposed group. Increased risk of lung and bladder/kidney cancers was not apparent.Although dilution is present in these cohort-based data, our study highlights the notion that developmental arsenic exposure may lead to a different pattern of cancer, including increases in pancreatic and hematopoietic cancer, as compared with adult or lifetime exposures to inorganic arsenic.

An association between exposure to traffic-related air pollution and reduced birth weight has been suggested. However, previous studies have failed to adjust for maternal size, which is an indicator of individual genetic growth potential. Therefore, we evaluated the association of air pollution with birth weight, term low birth weight (term-LBW), and small for gestational age (SGA), with adjustment for maternal size. Individual data were extracted from a database that is maintained by a maternal and perinatal care center in Shizuoka, Japan. We identified liveborn singleton births (n=14,204). Using geocoded residential information, each birth was assigned a number of traffic-based exposure indicators: distance to a major road; distance-weighted traffic density; and estimated concentration of nitrogen dioxide by land use regression. The multivariate adjusted odds ratios and their 95% confidence intervals (CIs) for the associations between exposure indicators and outcomes were then estimated using logistic regression models. Overall, exposure indicators of air pollution showed no clear pattern of association. Although there are many limitations, we did not find clear associations between birth-weight-related outcomes and the three markers of traffic-related air pollution.

Seventy-four confirmed small cell lung cancer (SCLC) patients received alternating combination chemotherapy with CAV and PVP. The CAV comprised of cyclophosphamide 800 mg/m2 on day 1, adriamycin 50 mg/m2 on day 1 and vincristine 1.4 mg/m2 on day 1, administered every 3-4 weeks. The PVP comprised cisplatin 80 mg/m2 on day 1 and etoposide 75 mg/m2 on day 1-5 administered every 3-4 weeks. Of these 74 patients, 63 (85.1%) achieved complete or partial responses with 16 (21.6%) obtaining a complete response. The median survival time was 13.2 months: 10.4 months in patients with extensive disease (ED), 16.3 months in those with limited disease (LD). A three-year disease-free period was achieved in eight patients (11.2%: 4.8% with ED, 16.8% with LD). The median duration of response was 28.3 weeks: 20.1 weeks with ED and 44.0 weeks with LD. The most commonly encountered side effects were nausea, vomiting, alopecia and myelosuppression but all were tolerable. We consider CAV-PVP to be an effective combination regimen for treating SCLC.

To clarify the host immune response and explore a new serological marker of lung cancer, we examined serum c-Myc antigens and auto-antibodies against c-Myc in 68 lung cancer patients and 30 healthy volunteers using bacterially synthesized glutathione S-transferase c-Myc fusion proteins and immunoblotting. The detection rate of anti-c-Myc antibodies was 13.2% (9/68) in lung cancer patients and 3.3% (1/30) in healthy volunteers. These anti-c-Myc antibodies were directed toward exon 2 alone (4/68), exon 3 alone (1/68), and both exon 2 and exon 3 (4/68) of c-Myc. Circulating c-Myc antigen was not detected in any individuals with lung cancer and normal controls. Age, sex, performance status, histology, stage, smoking history, and prior treatment of the patients with and without anti-c-Myc antibodies were not significantly different. The low incidence of anti-c-Myc antibodies and c-Myc antigens in peripheral blood suggests that these examinations are not useful in the serological diagnosis of lung cancer.

Drug susceptibility test using anti-bromodeoxyuridine (Doi et al., 1988) was carried out with P. falciparum cases in coastal villages of North Sumatra, Indonesia between December 1988 and February 1989. The peripheral blood specimens were withdrawn from inhabitants with consent from vein and were put into culture in test tubes. The initial parasitemia were ranged 960-6, 400/mm3. Blood samples containing parasites were transported in test tubes to Regional Health Laboratory of Medan. Experiments were carried out with 4 h culture and 16 h culture; 4 h culture was conducted in test tube at ambient temperature during transportation time, 16 h culture was done for 4 h in test tube at ambient temperature and for 12 h in candle jar at 37°C (Trager and Jensen, 1976). Experiments were conducted with 2μM of BrdU (Sigma, USA) in the presence of 0.5μM and 1.0μM of chloroquine concentrations (Aralen, Winthrop Products, USA). After BrdU flash, the ELISA was done according to our method described previously (Doi et al., 1988). Chloroquine effect on DNA synthesis was monitored by measuring BrdU incorporation at 4 h and 16 h of incubation using ELISA.Four hours culture of P. falciparum did not show any differences of BrdU incorporation under different concentration of chloroquine in 6 cases. The ring forms of 4 h culture could not be distinguished morphologically from pre-culture ones under microscopic observation. It may be mainly due to the shortage of time for the parasite to adjust to in vitroculture.Results of 8 cases of P. falciparum demonstrated that drug susceptibility was distinguished by BrdU uptake when cultured for 16 h in this assay, which implied incorporation of BrdU into parasite nucleic acids (Fig. 1). At the chloroquine concentration of 0.5μM, BrdU uptake was inhibited in the range of 21-83%, and the mean of inhibition of BrdU uptake was 39%. P. falciparum free fresh blood was used as a negative control, and its ELISA value was 0.16 after BrdU flash. The value was the same as that of BrdU-free culture. Therefore, human leucocytes in whole blood did not incorporate BrdU in this assay.The concentration of 0.2-0.3μM of chloroquine is the same level of patients blood administered that of 10 mg/kg. It is, thus, reasonable and feasible to monitor and judge chloroquine resistance at the concentration of 0.5μM. If only slight inhibition of BrdU uptake was observed at the concentration of 0.5μM chloroquine in isolated P. falciparum, chloroquine is not an effective drug against that strain in vivo.

Importance Although it is suggested that breastfeeding is protective against obesity in children, the evidence remains inconclusive because of possible residual confounding by socioeconomic status or children’s lifestyle factors. Most of the participants in the previous studies were children in Western developed countries, so studies in a different context are awaited. Objective To examine the associations of breastfeeding with overweight and obesity among schoolchildren in Japan, with adjustment for the potential confounders. Design Secondary data analyses of a nationwide longitudinal survey ongoing since 2001, with results collected from 2001 to 2009. Setting All over Japan. Participants A total of 43 367 singleton children who were born after 37 gestational weeks and had information on their feeding during infancy. Exposures Five mutually exclusive infant feeding practice categories. Main Outcomes and Measures Underweight, normal weight (referent group), overweight, and obesity at 7 and 8 years of age defined by using international cutoff points of body mass index by sex and age. Results In multinomial logistic regression models with adjustment for children’s factors (sex, television viewing time, and computer game playing time) and maternal factors (educational attainment, smoking status, and working status), exclusive breastfeeding at 6 to 7 months of age was associated with decreased risk of overweight and obesity compared with formula feeding. The adjusted odds ratios were 0.85 (95% CI, 0.69-1.05) and 0.55 (95% CI, 0.39-0.78) for overweight and obesity, respectively, at 7 years of age. Similar results were observed at 8 years of age. Conclusions and Relevance Breastfeeding is associated with decreased risk of overweight and obesity among schoolchildren in Japan. Therefore, it would be better to encourage breastfeeding even in developed countries.

An enzyme linked immunosorbent assay for malaria was used in North Sumatra, Indonesia as an epidemiological survey tool. The seroepidemiological investigation was concentrated on junior high schools. Serum samples obtained were classified according to the villages of origin of the students. The mean of ELISA values of each village group was compared with the parasite rate in primary schools in their native villages. A good correlation was observed between them (r = 0.96). The present results indicate that a survey of malaria in junior high schools by ELISA could give useful information on malaria prevalence in several peripheral villages. Province-wide information on malaria prevalence could easily be obtained by malaria-ELISA in junior high schools in tropical rural area.

The cell profiles of bronchial and bronchoalveolar lavage fluids (BLF and BALF) of patients with idiopathic pulmonary fibrosis (IPF) were compared with those of normal volunteers (NV) and age-matched control patients (CP), to characterize the cell profiles of the bronchoalveolar region in normals and patients with IPF. In BALF of nonsmokers from both control groups (NV and CP), alveolar macrophages (AM) were predominant and the percentage of neutrophil leukocytes and that of eosinophil leukocytes below 1% of the total cells. The percentage of neutrophils and that of bronchial epithelial cells were higher in BLF than in BALF of both control groups. Of the immune and inflammatory cells in BLF, the mean percentage of neutrophils was 12% in NV group and 42% in CP group. The percentage of neutrophils and that of eosinophils in BALF were higher in IPF group than in CP group, but the percentage of neutrophils in BLF of IPF group was comparable to that of CP group. In the IPF group, the percentage of neutrophils in BALF was lower than that in BLF. These results indicated that even in healthy subjects, a considerable number of neutrophils are present in the bronchial region and that the cell profile of the lavage fluid of the bronchoalveolar tree changes depending on the method of lavage. Presumably the higher percentage of neutrophils in BALF of patients with IPF is partly due to derangements of the alveolar structure, because the amount of saline infused into this region is limited.