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Purpose: The 2009 worldwide influenza A/H1N1 pandemic particularly affected younger people, including schoolchildren. We assessed the effects of class/school closure during the pandemic on the spread of H1N1 infection in Japan. Methods: We prospectively monitored 2,141 schoolchildren in 57 classes at two elementary schools and two junior high schools in Japan, and evaluated the effects of class/school closures on the spread of H1N1 using descriptive epidemiological methods. Results: The cumulative rate of H1N1 infection among these children was 40.9 % (876 children). There was a total of 53 closures of 40 classes, including school closures, during the pandemic. Time-course changes in the epidemic curve showed that school closure reduced the following epidemic peak more than class closure. A Poisson regression model showed that a longer duration of closure was significantly related to decreased H1N1 occurrence after the resumption of classes. Conclusions: School closure more effectively inhibits subsequent epidemic outbreaks than class closure. Longer school closures are effective in reducing the spread of infection, and school closure should be implemented as early as possible. [ABSTRACT FROM AUTHOR]

We have recovered instrumental temperature and pressure observations from Tokyo covering the periods 1825-1828, 1839-1855, and 1872-1875; from Yokohama covering the periods 1860-1871 and 1874; from Osaka covering the periods 1828-1833 and 1869-1871; and from Kobe covering the periods 1869-1871 and 1875-1888. The newly recovered records contain data before the 1870s, which is a period where, until recently, no instrumental data in Japan were believed to exist. Their addition to the previous backward extension of Japanese series, as based on the recently recovered intermittent Dejima/Nagasaki series 1819-1878, implies that the nineteenth-century extension of the Japanese instrumental record no longer contains major temporal gaps. The recovered data were used for a preliminary calculation of the west-Japan temperature (WJT) series, which is a representative temperature series for the area. The existence of a warm epoch in the 1850s over W-Japan and a downward temperature trend till the early twentieth century, as previously inferred from documentary data, is confirmed from the WJT data. The pressure data implies that the temperature differences between the nineteenth and twentieth centuries are at least partly caused by a change in atmospheric circulation. Copyright © 2006 Royal Meteorological Society. [ABSTRACT FROM AUTHOR]

Objective. To examine if iron-deficient conditions modify body burden or health effects of cadmium among women in the general population in Japan. Methods. In 2002, 1,482 women aged 20 to 74 years in six prefectures in Japan provided informed consent to participate in this study. They offered peripheral blood and spot urine samples, and answered questionnaires on their social habits and health conditions. Never-smoking, non-pregnant and non-lactating healthy women (1,190 subjects) were selected from the volunteers. Blood samples were analyzed for serum iron, ferritin and total iron-binding capacity (TIBC) in addition to red blood cell (RBC) counts and hemoglobin (Hb) concentration as markers of anemia and iron deficiency. Urine samples were analyzed for cadmium (Cd), α1-microglobulin (α1-MG), β2-microglobulin (β2-MG) as markers of Cd burden and Cd-induced tubular dysfunction; the measures were expressed after being corrected for creatinine (cr) as, e.g., Cd-Ucr. Results. The subjects were classified into anemic (37 women) and iron-deficient (388 women) groups separately from healthy controls (765 women), taking ferritin (<20 ng/ml) and Hb (<10 g/100 ml) as classification indicators. Strictly matched pairs (with regard to age and prefecture) were established for 36 anemic and 280 iron-deficient cases. Comparison between the cases and the matched controls showed that serum iron was lower and TIBC was higher in accordance with lower levels of ferritin and Hb in the anemic and iron-deficient groups, although the RBC count was only slightly reduced (the anemic group) or stayed essentially unchanged (the iron-deficient group). In contrast, no significant increase in Cd-Ucr, α1-MG, or β2-MG was observed in either the anemic group or the iron-deficient group compared with the matched controls. Cd-Ucr in one case of clinical anemia, however, tended to be higher than the levels among women of the same age range and from the same prefecture. Her α1-MG-Ucr and β2-MG-Ucr, however, remained un-elevated. Conclusions. The current level of iron deficiency among women in the general population in Japan may not induce significant increase in Cd body burden or Cd-induced tubular dysfunction. [ABSTRACT FROM AUTHOR]

Objective.. To examine whether environmental exposure to cadmium has been inducing kidney dysfunction among middle-aged women in the general population in Japan. Methods.. This study was conducted in 2000 and 2001. Morning spot urine samples were collected from 10,753 women (mostly aged 35 to 60 years) in ten prefectures all over Japan (thus about 1,000 women per site). Urine samples were analyzed for cadmium (Cd-U), calcium (Ca-U), magnesium (Mg-U), zinc (Zn-U), α1- and β2-microglobulins (α1- and β2-MG-U). The urinary analyte concentrations were corrected for creatinine (cr) concentration (i.e., Ucr). The data thus obtained were subjected to statistical evaluation by chi-square test, ANOVA, multiple comparison test, and simple regression analysis (SRA) as well as multiple regression analysis (MRA) including logistic regression analysis (LRA). Log-normal distribution was assumed for Cd-Ucr, α1-MG-Ucr and β2-MG-Ucr, whereas normal distribution was considered for age, Ca-Ucr, Mg-Ucr and Zn-Ucr. Results.. Geometric mean values (GM) of Cd-Ucr were distributed unevenly, depending on the sampling areas, with a grand GM of 1.3 µg/g cr, the highest (3.2 µg/g cr) and lowest GM values(0.8 µg/g cr) being significantly different from GMs of other areas. Correlation matrix analysis with subjects of all ages showed that log α1-MG-Ucr and log β2-MG-Ucr correlated significantly (r=0.272 and 0.202, respectively) with log Cd-Ucr, but they correlated also with age (r=0.280 and 0.213, respectively). The same analysis with the two selected age groups (41–50 and 51–60 years), however, failed to show close correlation of α1-MG-Ucr and log β2-MG-Ucr with Cd-Ucr. Both MRA and LRA indicated that age was a confounding factor in the evaluation of the effect of Cd-U on the two MG levels. Whereas the LRA with the all-age group showed a positive influence of log Cd-Ucr on log α1-MG-Ucr and log β2-MG-Ucr, such effect disappeared in parallel with the disappearance of age effects when LRA was conducted with the two selected age groups. An exceptional observation was the influence of log Cd-Ucr on log α1-MG-Ucr (but not on log β2-MG-Ucr) in LRA when a cut-off value of 5.00 mg for α1-MG-U/g cr was applied. Comparison between the low and high Cd-U groups showed that both α1-MG-Ucr and β2-MG-Ucr were higher in the high Cd-U groups, but prevalence of cases with α1-MG-Ucr and β2-MG-Ucr in excess of the cut-off values did not differ between the two groups except when a cut-off value of 5.00 mg/g cr was employed for α1-MG-U. Conclusions.. In over-all evaluation, no clear-cut evidence was obtained in the present study to show that environmental exposure to Cd has induced tubule dysfunction among middle-aged women in the general population in Japan. It might be the case, however, that an increase in α1-MG-U was associated with Cd exposure. In this sense, it is apparently desirable from public health viewpoints to make further efforts to reduce the intensity of the general population's exposure to environmental Cd. [ABSTRACT FROM AUTHOR]

Instrumental observations from Dejima (Nagasaki), Japan, taken under the responsibility of the Dutch, covering the periods 1819-28, 1845-58, and 1871-78, have been recovered. The Dejima series overlaps by six months the modern Nagasaki Observatory series, which covers 1878-present. The recovered data extend the start of the instrumental Japanese series back from 1872 to 1819, leaving major gaps during 1829-44 and 1859-71. [ABSTRACT FROM AUTHOR]

Background: Although recent in vitro experimental results have raised the question of whether maternal exposure to per- and polyfluoroalkyl substances (PFAS) may be a potential environmental risk factor for chromosomal abnormalities, epidemiological studies investigating these associations are lacking., Objectives: This study examined whether prenatal PFAS exposure is associated with a higher prevalence of chromosomal abnormalities among offspring., Methods: We used data from the Japan Environment and Children's Study, a nationwide birth cohort study, and employed logistic regression models to examine the associations between maternal plasma PFAS concentrations in the first trimester and the diagnosis of chromosomal abnormalities in all births (artificial abortions, miscarriages, stillbirths, and live births) up to 2 years of age. In addition, we examined associations with mixtures of PFAS using multipollutant models., Results: The final sample consisted of 24,724 births with singleton pregnancies, of which 44 confirmed cases of chromosomal abnormalities were identified (prevalence: 17.8/10,000 births). When examined individually, exposure to perfluorononanoic acid (PFNA) and perfluorooctane sulfonic acid (PFOS) showed positive associations with any chromosomal abnormalities with age-adjusted odds ratios of 1.81 (95% CI: 1.26, 2.61) and 2.08 (95% CI: 1.41, 3.07) per doubling in concentration, respectively. These associations remained significant after Bonferroni correction, although they did not reach the adjusted significance threshold in certain sensitivity analyses. Furthermore, the doubling in all PFAS included as a mixture was associated with chromosomal abnormalities, indicating an age-adjusted odds ratio of 2.25 (95% CI: 1.34, 3.80), with PFOS as the predominant contributor, followed by PFNA, perfluoroundecanoic acid (PFUnA), and perfluorooctanoic acid (PFOA)., Discussion: The study findings suggested a potential association between maternal exposure to PFAS, particularly PFOS, and chromosomal abnormalities in offspring. However, the results should be interpreted cautiously, because selection bias arising from the recruitment of women in early pregnancy may explain the associations. https://doi.org/10.1289/EHP13617.

Background: Intrauterine exposure to hypertensive disorders of pregnancy (HDP) may increase the risk of neuropsychiatric disorders. This investigation examined for associations between maternal HDP and febrile seizures (FS) in offspring by the age of three years., Methods: The present cohort study analyzed data from the Japan Environment and Children's Study, a large national birth cohort. We included mother-child pairs recruited between January 2011 and March 2014. Information regarding maternal HDP, the presence of FS in offspring up to 3 years of age, and potential confounding factors were assessed using written questionnaires administered to mothers., Results: A total of 77,699 mother-child dyads were analyzed. The prevalence of FS was 8.4% in children without HDP exposure, 10.6% in those exposed to mild HDP, and 10.4% in those with severe HDP exposure. Among children with full-term birth, logistic regression analysis indicated that exposure to mild or severe HDP was significantly associated with a higher incidence of FS (adjusted odds ratio [95% confidence interval]: 1.27 [1.05-1.53] and 1.27 [0.90-1.78], respectively, P for trend = 0.008), compared with children without HDP exposure., Conclusion: In children with full-term birth, intrauterine exposure to HDP was significantly associated with FS by the age of three years., Impact: This study revealed a significant association between intrauterine exposure to hypertensive disorders of pregnancy (HDP) and the subsequent development of febrile seizures (FS) in offspring by three years. This increased incidence of FS by HDP was independent of preterm birth status. This is the first large nationwide birth cohort study showing the impact of intrauterine exposure to HDP on FS in early childhood., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objectives: Whether the known positive association between blood lead (PbB) levels and urinary δ-aminolevulinic acid (ALAU) also exists at relatively low PbB levels (<40 μg/dL) remains unclear. We aimed to investigate this association at lower PbB levels., Methods: We analyzed data from biannual medical examinations of workers at a Japanese factory from August 2013 to August 2023. We excluded records from female workers and those with missing data, resulting in a dataset consisting of 1396 records from 155 male workers. We employed mixed-effect linear regression models with a random intercept for workers and additional adjustments for age and smoking status., Results: The median PbB level across all the analyzed records was 8 μg/dL (range: 1-31 μg/dL). Significant positive associations were observed between PbB and ALAU, with a 1-unit increase in natural logarithm-transformed PbB corresponding to a 10.0% increase in ALAU (95% CI, 2.7%-17.9%). Categorized PbB analyses showed a 23.8% increase in ALAU (95% CI, 2.7%-49.2%) for PbB levels at 20-24 μg/dL and an 83.1% increase (95% CI, 30.1%-157.7%) for PbB levels ≥25 μg/dL, compared with those <5 μg/dL. The exposure-response curve analysis indicated a plateau followed by an increasing trend., Conclusions: A positive and nonlinear association between PbB and ALAU levels was observed at relatively low PbB levels., (© The Author(s) [2024]. Published by Oxford University Press on behalf of Journal of Occupational Health.)

The effects of early-life exposure to per- and polyfluoroalkyl substances (PFAS) on the onset of asthma in children have been unclear. We examined the association between prenatal PFAS exposure and wheezing and asthma symptoms among 4-year-old children in a total of 17,856 mother-child pairs from the Japan Environment and Children's Study. Maternal first-trimester serum concentrations of six PFAS were used for the exposure assessment. We defined "wheeze ever," "current wheeze," "current symptoms of severe asthma," and "asthma ever" at the age of 4 years by the responses to the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, and "doctor-diagnosed asthma" by the response to a corresponding question. Multivariate logistic regression models were used to examine exposure-outcome associations. Our findings revealed that doubling of the PFOA concentration was associated with a reduced occurrence of "wheeze ever," yielding an adjusted odds ratio of 0.94 (95% CI: 0.90-0.98). Also, doubling in the concentrations of PFOA and PFHxS was associated with a decreased prevalence of "asthma ever," with adjusted odds ratios of 0.94 (95% CI: 0.88-1.00) and 0.95 (95% CI: 0.90-0.99), respectively. However, these associations were not significant after applying the Bonferroni correction. The estimated exposure-response curves were nearly linear with a subtle or flat slope. When stratified by the child's sex or the mother's history of asthma, most of the estimated confidence intervals were overlapped between each pair of strata. Regional stratification analysis indicated low-to-moderate heterogeneity in 12 exposure-outcome pairs and moderate-to-high heterogeneity in 9 out of the 30 examined pairs. This study found no clear associations between prenatal PFAS exposure and the prevalence of wheezing and asthma among children at the age of 4 years., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: This investigation assessed the impact of dog and/or cat ownership during infancy on the presence of functional constipation (FC) at 3 years of age., Methods: The fixed data of 73,936 singleton births from a large national birth cohort study commencing in 2011 were used to identify FC as estimated by Rome III at 3 years of age. Multiple logistic regression analysis was employed to search for correlations between FC development and dog and/or cat ownership in early childhood., Results: A total of 8,459 toddlers (11.6%) met the Rome III criteria for FC at 3 years of age. Overall, 57,264 (77.5%) participants had never owned a dog or cat. We identified 7,715 (10.4%) infant-period owners, 1,295 (1.8%) current owners, and 7,762 (10.5%) long-term owners. Multivariate analysis showed that infant-period ownership remained significantly associated with the risk of developing FC at 3 years of age after adjusting for covariates (adjusted OR [95% CI] 1.09 [1.01-1.19] based on non-ownership)., Conclusions: This Japanese large nationwide survey uncovered a possible adverse effect of infant-period dog and/or cat ownership prior to 6 months of age on FC status at 3 years of age., (© 2023. The Author(s).)

Objectives: To investigate the association between the number of teeth and the new onset of pre-diabetes., Design: Retrospective cohort study., Setting: The National Database of Health Insurance Claims and Specific Health Checkups of Japan, which holds information from both the yearly health check-up programme known as the 'Specific Health Checkup' and health insurance claims data., Participants: 1 098 371 normoglycaemic subjects who participated in the Specific Health Checkup programme every year from fiscal year (FY) 2015 to FY 2018 and had dental insurance claims data with a diagnosis of periodontal disease during FY 2016., Outcome Measures: Incidence of pre-diabetes or diabetes observed at the Specific Health Checkup during FY 2018., Results: Among the participants, 1 77 908 subjects developed pre-diabetes, and 579 developed diabetes at the check-up during the subsequent follow-up year. Compared with the subjects with 26-28 teeth, those with 20-25, 15-19 or 1-14 teeth were associated with an increased likelihood of developing pre-diabetes or diabetes onset with adjusted ORs of 1.03 (95% CI: 1.02 to 1.05), 1.06 (1.03 to 1.09) and 1.07 (1.04 to 1.11), respectively. No clear modifications were observed for age, sex, body mass index or current smoking., Conclusions: Having fewer teeth was associated with a higher incidence of pre-diabetes. Due to the limitations of this study, however, causality remains undetermined., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is a lack of large, nationwide, birth cohort studies in Japan that examine the relationships of initial feeding habits and breastfeeding period duration with offspring functional constipation at 3 years of age. This study assessed the impact of breastfeeding during infancy on early childhood functional constipation., Methods: The fixed data of 70,078 singleton births from the ongoing Japan Environment and Children's Study cohort study that commenced in 2011 were used to identify functional constipation as estimated by Rome III at 3 years of age. The exposure variables were breastfeeding period duration until 12 months of age (never, up to 6 months, or ≥ 7 months) as well as breastfeeding status at 1 month and 6 months of age (breastfeeding exclusively, partial breastfeeding, or infant formula feeding only). Multiple logistic regression analysis was employed to search for correlations for functional constipation development with breastfeeding period duration until 12 months of age and breastfeeding status during infancy., Results: We identified 8,118 toddlers (11.6%) who met the Rome III criteria at 3 years of age. After controlling for potential covariates, a breastfeeding period duration of 7 months or more was inversely related to functional constipation development (≥ 7 months: adjusted odds ratio [OR] [95% confidence interval (CI)] 0.76 [0.65, 0.88] versus never breastfed, P for trend < 0.001). Other initial feeding methods were significantly related to an increased risk of functional constipation as compared with breastfeeding exclusively at 1 month of age (partial breastfeeding: adjusted OR [95% CI] 1.17 [1.11, 1.23], formula feeding only: 1.23 [1.07, 1.40]) and 6 months of age (partial breastfeeding: adjusted OR [95% CI] 1.18 [1.12, 1.24], formula feeding only: adjusted OR [95% CI] 1.42 [1.20, 1.68])., Conclusion: This large nationwide survey revealed a possible protective effect of a prolonged breastfeeding period duration and early exclusive breastfeeding in infancy on functional constipation at 3 years., (© 2023. The Author(s).)

The Tsushima leopard cat (Prionailurus bengalensis euptilurus) is a subspecies of the mainland leopard cat that lives on the small island of Tsushima, Japan. Captive breeding has been attempted in zoos in Japan because only approximately 100 animals remain in the wild and the Tsushima leopard cat is an endangered species. There are very few reports on diseases, including tumours, of this species. We analysed the deaths of 58 Tsushima leopard cats and confirmed that nine had neoplastic disease. The average age at death of the animals with neoplasia was 14 years and tumours were the primary cause of death in all animals. Eight of the nine cases involved primary tumours of the pancreas, liver, gallbladder, tongue and salivary glands, suggesting that Tsushima leopard cats may have a predilection for digestive system tumours. This is the first report of neoplastic disease in the Tsushima leopard cat., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

There have been few studies in non-western countries on the relationship between low levels of daily fine particulate matter (PM 2.5 ) exposure and morbidity or mortality, and the impact of PM 2.5 concentrations below 15 μg/m 3 , which is the latest World Health Organization Air Quality Guideline (WHO AQG) value for the 24-h mean, is not yet clear. We assessed the associations between low-level PM 2.5 exposure and cardiorespiratory admissions in Japan. We collected the daily hospital admission count data, air pollutant data, and meteorological condition data recorded from April 2016 to March 2019 in 139 Japanese cities. City-specific estimates were obtained from conditional logistic regression models in a time-stratified case-crossover design and pooled by random-effect models. We estimated that every 10-μg/m 3 increase in the concurrent-day PM 2.5 concentration was related to a 0.52% increase in cardiovascular admissions (95% CI: 0.13-0.92%) and a 1.74% increase in respiratory admissions (95% CI: 1.41-2.07%). These values were nearly the same when the datasets were filtered to contain only daily PM 2.5 concentrations <15 μg/m 3 . The exposure-response curves showed approximately sublinear-to-linear curves with no indication of thresholds. These associations with cardiovascular diseases weakened after adjusting for nitrogen dioxide or sulfur dioxide, but associations with respiratory diseases were almost unchanged when additionally adjusted for other pollutants. This study demonstrated that associations between daily PM 2.5 and daily cardiorespiratory hospitalizations might persist at low concentrations, including those below the latest WHO AQG value. Our findings suggest that the updated guideline value may still be insufficient from the perspective of public health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The effectiveness of the long-term care service in Japan has been unclear, and most of the relevant studies of this service have been limited to a single region and relatively small samples, necessitating large-scale studies. We examined the associations between long-term care service use and the service/care-need level progression at the national scale in Japan., Methods: We conducted a nationwide retrospective cohort study using data from the Japanese Long-Term Care Insurance Claims database. Individuals aged ≥ 65 years and newly certified as being at the support-need level 1 or 2 or the care-need level 1 between April 2012 and March 2013 were included. We first conducted 1:1 propensity score matching and then examined the associations between service use and the progression in support-need or care-need levels by using Kaplan-Meier survival curves and log-rank tests., Results: The final sample consisted of 332,766 individuals. We observed that service use was associated with a faster decline in the support/care-need level, although the differences in the subjects' survival rate diminished; the log-rank test showed significance (p < 0.001). When stratified for urban-rural classifications or regions of Japan, the results were similar to the primary analysis in all of the stratified groups, and no clear regional variations were observed., Conclusion: We did not observe a clear beneficial effect of receiving long-term care in Japan. Our results suggest that Japan's current long-term care service may not be effective for the recipients of these services. Considering that the system is becoming a financial burden, a re-examination of the service to provide more cost-effective care may be advisable., (© 2023. The Author(s).)

The short-term association between ambient air pollution and hospital admissions for ischemic stroke is not fully understood. We examined the association between four regularly measured major ambient air pollutants, i.e., sulfur dioxide (SO 2 ), nitrogen dioxide (NO 2 ), photochemical oxidants (O x ), and particulate matter with aerodynamic diameters ≤ 2.5 μm (PM 2.5 ), and hospital admissions for ischemic stroke by analyzing 3 years of nationwide claims data from 97 cities in Japan. We first estimated city-specific results by using generalized additive models with a quasi-Poisson regression, and we obtained the national average by combining city-specific results with the use of random-effect models. We identified a total of 335,248 hospital admissions for ischemic stroke during the 3-year period. Our analysis results demonstrated that interquartile range increases in the following four ambient air pollutants were significantly associated with hospital admissions for ischemic stroke on the same day: SO 2 (1.05 ppb), 1.05% (95% CI: 0.59-1.50%); NO 2 (6.40 ppb), 1.10% (95% CI: 0.61-1.59%); O x (18.32 ppb), 1.43% (95% CI: 0.81-2.06%); and PM 2.5 (7.86 μg/m 3 ), 0.90% (95% CI: 0.35-1.45%). When the data were stratified by the hospital admittees' medication use, we observed stronger associations with SO 2 , NO 2 , and PM 2.5 among the patients who were taking antihypertensive drugs and weaker associations with SO 2 , NO 2 , and O x among those taking antiplatelet drugs. Short-term exposure to ambient air pollution was associated with increased hospital admissions for ischemic stroke, and medication use and season may modify the association., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Various genetic and environmental influences have been studied for developmental disorders; however, the precise cause remains unknown. This study assessed the impact of maternal serum total cholesterol (TC) level in early pregnancy on early childhood neurodevelopment., Methods: The fixed data of 31,797 singleton births from a large national birth cohort study that commenced in 2011 were used to identify developmental disorders as estimated by Ages and Stages Questionnaire, third edition (ASQ-3) scores of less than -2 standard deviations at 12 months of age. Multiple logistic regression analysis was employed to search for correlations between possibility of developmental disorders and maternal TC levels in early pregnancy classified into 4 groups based on quartile (Q1-Q4) values., Results: After controlling for potential confounding factors in 27,836 participants who ultimately underwent multivariate analysis, we observed that elevated TC levels were significantly associated with a higher risk of screen positive status for communication (Q4: adjusted odds ratio [aOR] 1.20, 95% confidence interval [CI] 1.05-1.37) and gross motor (aOR 1.13, 95% CI 1.03-1.25) ASQ-3 domain scores., Conclusion: This large nationwide survey revealed a possible deleterious effect of hypercholesterolemia in early pregnancy on infant neurodevelopment and age-appropriate skill acquisition at 12 months age., (Copyright © 2022 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Rationale: Epidemiological evidence indicates that ambient exposure to particulate matter ⩽2.5 μm in aerodynamic diameter (PM 2.5 ) has adverse effects on lung function growth in children, but it is not actually clear whether exposure to low-level PM 2.5 results in long-term decrements in lung function growth in pre- to early-adolescent schoolchildren. Objectives: To examine long-term effects of PM 2.5 within the 4-year average concentration range of 10-19 μg/m 3 on lung function growth with repeated measurements of lung function tests. Methods: Longitudinal analysis of 6,233 lung function measurements in 1,466 participants aged 8-12 years from 16 school communities in 10 cities around Japan, covering a broad area of the country to represent concentration ranges of PM 2.5 , was done with a multilevel linear regression model. Forced expiratory volume in 1 second, forced vital capacity (FVC), and maximal expiratory flow at 50% of FVC were used as lung function indicators to examine the effects of 10-μg/m 3 increases in the PM 2.5 concentration on relative growth per each 10-cm increase in height. Results: The overall annual mean PM 2.5 level was 13.5 μg/m 3 (range, 10.4-19.0 μg/m 3 ). We found no association between any of the lung function growth indicators and increases in PM 2.5 levels in children of either sex, even after controlling for potential confounders. Analysis with two-pollutant models with O 3 or NO 2 did not change the null results. Conclusions: This nationwide longitudinal study suggests that concurrent, long-term exposure to PM 2.5 at concentrations ranging from 10.4 to 19.0 μg/m 3 has little effect on lung function growth in preadolescent boys or pre- to early-adolescent girls.

Abnormal maternal gestational weight gain (GWG) increases the risk of obstetric-related complications. This investigation examined the impact of GWG on infant neurodevelopmental abnormalities at 12 months of age using the data of a nationwide Japanese cohort study. Questionnaire data were obtained from the ongoing Japan Environment and Children's Study cohort study. Maternal GWG was subdivided as below, within, or above the reference values of the Institution of Medicine pregnancy weight guidelines. The Ages and Stages Questionnaire, third edition (ASQ-3) is a parent-reported developmental screening instrument for children across five domains: communication, gross motor, fine motor, problem-solving, and personal-social. Multiple logistic regression analysis was employed to identify correlations between GWG and developmental delay defined as ASQ-3 scores of less than two standard deviations below the mean. A total of 30,694 mothers with singleton live births and partners who completed the questionnaire were analyzed. The prevalence of mothers below, within, and above the GWG guidelines was 60.4% (18,527), 32.1% (9850), and 7.5% (2317), respectively. We recorded 10,943 infants (35.7%) who were outliers in at least one ASQ-3 domain. After controlling for covariates, GWG below established guidelines was associated with a significantly higher risk of developmental delay for the communication (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.09-1.34), gross motor (OR 1.14, 95% CI 1.05-1.24), fine motor (OR 1.13, 95% CI 1.04-1.24), problem-solving (OR 1.09, 95% CI 1.01-1.18), and personal-social (OR 1.15, 95% CI 1.07-1.24) domains.Conclusion: This large survey revealed a possible deleterious effect of insufficient maternal GWG on infant neurodevelopment.Trial registration: The Japan Environment and Children's Study (JECS) was registered in the UMIN Clinical Trials Registry on January 15, 2018 (number UMIN000030786). What is Known: • Inappropriate maternal gestational weight gain may cause obstetric complications and adverse birth outcomes. • Excess maternal weight gain may result in gestational diabetes, hypertension, eclampsia, caesarean delivery, and macrosomia, while insufficient maternal weight gain has been associated with pre-term birth and small for gestational age. What is New: • This study provides important information on a possible adverse effect of insufficient maternal gestational weight gain on offspring neurodevelopment at 12 months of age. • Our findings indicate a need to reconsider the optimal body mass index and gestational weight gain for women desiring pregnancy., (© 2021. The Author(s).)

Background: The association between fetal exposure to alcohol and congenital structural disorders remains inconclusive. The present study searched for relationships between maternal alcohol consumption during pregnancy and the risk of congenital malformations., Methods: We evaluated the fixed dataset of a large national birth cohort study including 73,595 mothers with a singleton live birth. Information regarding the alcohol consumption of mothers was obtained from self-reported questionnaires. Physicians assessed for 6 major congenital malformations (congenital heart defects [CHDs], male genital abnormalities, limb defects, cleft lip and/or cleft palate [orofacial clefts (OFC)], severe brain abnormalities, and gastrointestinal obstructions) up to 1 month after birth. Multiple logistic regression analysis was performed to identify associations between maternal alcohol consumption during pregnancy and each malformation., Results: The prevalence of maternal drinking in early pregnancy and until the second/third trimester was 46.6% and 2.8%, respectively. The onset of CHD was inversely associated with mothers who quit drinking during early pregnancy (OR 0.85, 95% CI 0.74-0.98). There was no remarkable impact of maternal drinking habit status on the other congenital malformations after adjustment for covariates., Conclusions: Maternal alcohol consumption during pregnancy, even in early pregnancy, displayed no significant adverse impact on congenital malformations of interest., Impact: This large-scale Japanese cohort study revealed that no teratogenic associations were found between maternal retrospective reports of periconceptional alcohol consumption and congenital malformations after adjustment for covariates. This is the first nationwide birth cohort study in Japan to assess the effect of maternal alcohol consumption during pregnancy on major congenital malformations. Our finding indicated that maternal low-to-moderate alcohol consumption during pregnancy, even in early pregnancy, displayed no significant adverse impact on congenital heart defects, male genital abnormalities, limb defects, orofacial clefts, severe brain abnormalities, or gastrointestinal obstructions., (© 2020. The Author(s).)

Background: Maternal exposure to pesticides during pregnancy may cause oxidative hemolysis leading to neonatal hyperbilirubinemia. This investigation examined for associations between maternal use of pesticides or repellents during pregnancy and neonatal hyperbilirubinemia requiring phototherapy., Methods: We used the dataset from the Japan Environment and Children's Study, a large national birth cohort study registered from January 31, 2011 to March 31, 2014. The fixed data of 61,751 live births were used to evaluate the presence of neonatal hyperbilirubinemia and potential confounding factors. We employed multiple logistic regression analysis to identify correlations between the frequency of maternal pesticide or repellent use during pregnancy and clinically relevant neonatal hyperbilirubinemia., Results: After controlling for confounding factors, there were significant associations between neonatal hyperbilirubinemia necessitating phototherapy and the frequent use of indoor insecticide spray (OR 1.21, 95% CI 1.05-1.38). For spray- or lotion-type insect repellents, an opposite relationship was observed (more than a few times a week: OR 0.70, 95% CI 0.61-0.81, up to a few times a month: OR 0.84, 95% CI 0.78-0.91)., Conclusion: The frequent use of indoor insecticide spray during pregnancy showed an increased risk of neonatal hyperbilirubinemia requiring phototherapy, which was absent for spray- or lotion-type insect repellents., Impact: The frequent use of indoor insecticide spray during pregnancy showed an increased risk of neonatal hyperbilirubinemia requiring phototherapy, which was absent for spray- or lotion-type insect repellents. This is the first study examining the effects of maternal exposure to pesticides or repellents on clinically relevant neonatal hyperbilirubinemia using a dataset from a nationwide birth cohort study. This large-scale Japanese cohort study revealed that the frequent use of indoor insecticide spray during pregnancy may increase the risk of neonatal hyperbilirubinemia requiring treatment.

The short-term association between ambient particulate matter ≤2.5 microns in diameter (PM 2.5 ) and hospital admissions is not fully understood. Studies of this association with hospital admission costs are also scarce, especially in entire hospitalized populations. We examined the association between ambient PM 2.5 and all-cause hospital admissions, the corresponding total charges, and the total charges per patient by analyzing the hospital admission data of 2 years from 628 hospitals in 12 cities in Japan. We used generalized additive models with quasi-Poisson regression for hospital admissions and generalized additive models with log-linear regression for total charges and total charges per patient. We first estimated city-specific results and the combined results by random-effect models. A total of 2,017,750 hospital admissions were identified. A 10 µg/m 3 increase in the 2 day moving average was associated with a 0.56% (95% CI: 0.14-0.99%) increase in all-cause hospital admissions and a 1.17% (95% CI: 0.44-1.90%) increase in total charges, and a 10 µg/m 3 increase in the prior 2 days was associated with a 0.75% (95% CI: 0.34-1.16%) increase in total charges per patient. Short-term exposure to ambient PM 2.5 was associated with increased all-cause hospital admissions, total charges, and total charges per patient.

The European-Japanese Cerebrovascular Congress originally started as a Swiss-Japanese joint conference on cerebral aneurysm. The Congress was held in Zürich, Switzerland, from 5-7 May 2001 with Prof. Y. Yonekawa of Zürich and Prof. Y. Sakurai of Sendai as the presidents.Three years later, in July of 2004, the second meeting was held at Zürich again with wide-ranging conference topics on cerebral stroke surgery.The third meeting at Zürich in 2006 was the key congress for future development. The conference was expanded to the European-Japanese Joint Conference for Stroke Surgery.As the year of 2006 was the 70th Anniversary of the Department of Neurosurgery, University Hospital Zürich, Prof. Krayenbühl, Prof. Yasargil, and Prof. Yonekawa introduced the impressive history of the Department of Neurosurgery at the conference.At the fourth European-Japanese Joint Conference on Stroke Surgery we moved from Zürich to the Nordic city of Helsinki, with Prof. Juha Hernesniemi as the conference president.The fifth joint conference was held at Düsseldolf am Rein with Prof. Hans-Jakob Steiger as the Conference president.The sixth conference, named "The European-Japanese Stroke Surgery Conference" (EJSSC), was held in Utrecht, The Netherlands. Professor Luca Regli and Prof. Gabriel Rinkel were the conference presidents.The seventh European-Japanese Stroke Surgery Conference (EJSSC) was held in Verona, Italy with the presidents Prof. Alberto Pasqualin and Prof. Giampietro Pinna.The eighth European-Japanese Cerebrovascular Congress (EJCVC) came back to Zürich in the year 2016 with Prof. Luca Regli as the president.The ninth European-Japanese Cerebrovascular Congress (EJCVC) was held in the historical room of Grande Ospedale Metropolitano Niguarda Milan, Italy, with Prof. Marco Cenzato as the president.The tenth European-Japanese Cerebrovascular Congress (EJCVC) will be held in Kyoto. It will be the first meeting of the EJCVC in Japan.Publication of the proceeding books of the conference as supplements of ACTA Neurochirurgica is one of the main reasons that we have been able to continue this conference for almost 20 years. We sincerely thank Prof. Steiger for his continuous and generous cooperation as the series Editor of ACTA Neurochirurgica.

This study investigated the preventive effects of lactoferrin (LF) on subjective acute gastrointestinal symptoms during the winter in a randomized, double-blinded, placebo-controlled parallel-group comparative trial. The eligible subjects were healthy adults working at kindergartens and nursery schools. We randomized the subjects to the Placebo group (0 mg/day), the Low LF group (200 mg/day), and the High LF group (600 mg/day) for 12 weeks. The prevalence of acute gastrointestinal symptoms was significantly lower in the High LF (13/112 vs. 26/116; p = 0.030) and the Low LF (13/107 vs. 26/116; p = 0.040) groups than in the Placebo group. The adjusted odds ratio for the prevalence of acute gastrointestinal symptoms was 2.78 (95% CI: 1.19-6.47) in the Placebo group compared with the High LF group. LF is useful to prevent acute gastrointestinal symptoms among childcare workers, who mainly consist of women.

Mount Ontake in Nagano Prefecture, Japan erupted on 27 September 2014. Many police officers were called in for duty as a disaster-support task force. We investigated the association between the peritraumatic situation and posttraumatic stress disorder (PTSD) symptoms in these police officers. In January 2015, a health survey (OHS) on disaster stress related to the Mt. Ontake eruption disaster support work was distributed to all of the police officers and staff involved in the disaster support. We analyzed the 213 participants who had PTSD symptoms following the eruption and no missing OHS data. Logistic regression analyses were conducted to clarify the relationship between the participants' symptom severity and their peritraumatic situation (i.e., stressors and daily support prior to the eruption, disaster-support work duties, and postdisaster stress relief). The symptom severity was associated with 'more than seven cumulative days at work' (odds ratio [OR] = 2.47, 1.21-5.06), 'selecting drinking and/or smoking as stress relief after disaster-support work' (OR = 2.35, 1.09-5.04), and 'female' (OR = 3.58, 1.19-10.77). As disaster-support work, 'supporting the victims' families' (OR = 1.99, 0.95-4.21) tended to be associated with symptom severity. The number of days of disaster-support work, stress-relief behavior, and gender were associated with the severity of PTSD symptoms., Competing Interests: The authors declare no conflict of interest.

There have been no large, nationwide, birth cohort studies in Japan examining the effects of house renovation during pregnancy on congenital abnormality. This study examined the impact of (1) prenatal exposure to house renovation and (2) maternal occupational exposure to organic solvents and/or formaldehyde on the incidence of congenital abnormality. The fixed data of 67,503 singleton births from a large national birth cohort study that commenced in 2011 were used to evaluate the presence of congenital abnormalities and potential confounding factors. We employed multiple logistic regression analysis to search for correlations between maternal exposure to house renovation or organic solvents and/or formaldehyde during pregnancy and such congenital abnormalities as congenital heart disease, cleft lip and/or palate, male genital abnormality, limb defect, and gastrointestinal obstruction. After controlling for potential confounding factors, we observed that house renovation was significantly associated with male genital abnormality (OR 1.81, 95% CI 1.03-3.17, P = 0.04) when stratified by congenital abnormality, with no other remarkable relations to house renovation or occupational use of organic solvents and/or formaldehyde during pregnancy. There were also significant correlations for maternal BMI before pregnancy, history of ovulation induction through medication, maternal diabetes mellitus/gestational diabetes mellitus, and hypertensive disorder of pregnancy with an increased risk of congenital abnormality. In conclusion, this large nationwide survey provides important information on a possible association of house renovation during pregnancy with congenital male genital abnormality which needs confirmation in future studies.

There have been no large nationwide birth cohort studies examining for the effects of maternal alcohol use during pregnancy on placental abnormality. This study searched for associations between alcohol consumption and the placental abnormalities of placenta previa, placental abruption, and placenta accreta using the fixed dataset of a large national birth cohort study commencing in 2011 that included 80,020 mothers with a singleton pregnancy. The presence of placental abnormalities and potential confounding factors were recorded, and multiple logistic regression analysis was employed to search for correlations between maternal alcohol consumption during pregnancy and placental abnormalities. The overall rate of prenatal drinking until the second/third trimester was 2.7% (2,112). The prevalence of placenta previa, placental abruption, and placenta accreta was 0.58% (467), 0.43% (342), and 0.20% (160), respectively. After controlling for potential confounding factors, maternal alcohol use during pregnancy was significantly associated with the development of placenta accreta (OR 3.10, 95%CI 1.69-5.44). In conclusion, this large nationwide survey revealed an association between maternal drinking during pregnancy and placenta accreta, which may lead to excessive bleeding during delivery.

Currently, amrubicin is permitted for relapsed small-cell lung carcinoma (SCLC) only in Japan. The efficacy and adverse effects of amrubicin as reported by previous studies varied greatly. The inclusion criterion was a prospective study that was able to provide data for efficacy and safety by the AMR single agent regimen as second-line chemotherapy for a patient with SCLC. Binary data were meta-analyzed with the random-model generic inverse variance method. We included nine articles consisted of 803 patients. The pooled three-, six-, and nine-month progression-free survival were 63% (95% CI 57-69%, I(2) = 53%), 28% (95% CI 21-35%, I(2) = 71%), and 10% (95% CI 6-14%, I(2) = 41%), respectively. The pooled six-, 12-, and 18-month overall survival were 69% (95% CI 61-78%, I(2) = 83%), 36% (95% CI 28-44%, I(2) = 80%), and 15% (95% CI 8-21%, I(2) = 81%), respectively. Amrubicin seemed much more beneficial for Japanese patients. However, compared to the efficacy of topotecan presented in a previous meta-analysis, amrubicin may be a better treatment option than topotecan for both Japanese and Euro-American. Adverse effects by amrubicin were almost exclusively observed to be hematological. Notably, grade III/IV neutropenia incidence was 70% and febrile neutropenia incidence was 12%.

The pandemic influenza A/H1N1 2009 virus is commonly known to affect younger individuals. Several epidemiological studies have clarified the epidemic features of university students in Japan. In this study, we reviewed these studies in Japan in comparison with reports from other countries. The average cumulative incidence rate among university students was 9.6 %, with the major symptoms being cough, sore throat, and rhinorrhea. These epidemiological features were similar between Japan and other countries. Attitudes and behaviors toward pandemic influenza control measures were different before and improved during and after the epidemic. These features were also similar to those in other countries. On the other hand, the epidemic spread through club activities or social events, and transmission was attenuated after temporary closure of such groups in Japan. This transmission pattern was inconsistent among countries, which may have been due to differences in lifestyle and cultural habits. Based on these results, infection control measures of pandemic influenza for university organizations in Japan should be considered.

Although the natural history of H1N1 has been found to vary among patients, little is known about the factors that affect these variations. Infected patients with an extended infection history may shed virus longer and spread infection. To further clarify these variations, we evaluated the natural history of H1N1 infection in 324 university students using a descriptive epidemiological method and analyzed factors affecting the natural history of infection. The median times from infection to fever development and from fever development to cure were 2 days (range 0-8 days) and 5 days (range 1-12 days), respectively, and the median time not attending classes was 5 days (range, 1-13 days). Variations in H1N1 natural history were associated with both environmental and individual factors, including route of infection, grade, gender, epidemic period, respiratory and gastrointestinal symptoms and headache. Steps affecting these factors may help control variations in H1N1 natural history and may enhance infection control measures.

Background: Knowledge concerning palliative care and the associated skills, including effective pain control, is essential for surgeons who treat cancer patients in daily practice. This study focuses on a palliative care training course that has been mandatorily conducted for all surgical residents of our hospital since 2009., Methods: We evaluated the effectiveness of our mandatory palliative care training course by conducting a retrospective study of the patients' medical records and participants' questionnaire results and discussed the importance of palliative care education for surgical residents., Results: All 12 surgical residents who participated in the course in 2009 had graduated 4-9 years back. They were assigned to look after a total of 92 cases (average, 7.66 cases per resident) during the course. The purpose of care in most cases (92.3%) was to mitigate pain. Introducing analgesic adjuvants such as gabapentin or amitriptyline accounted for the largest part of initial interventions (23.9%) aimed at controlling cancer pain, followed by changes in route of administration or doses of prior opioid analgesics (21.7%). Interventions with opioid analgesics were conducted most frequently (47.7%). The overall pain improvement rate was 89.1%. We used a questionnaire after the course to evaluate its effectiveness., Conclusions: The surgical residents stated that it was a meaningful course through which they gained practical knowledge on palliative care and that the experience would change their approach to home care.

Objective: To investigate the association of workplace occupational mental health (OMH) and related activities with psychological distress of workers in Japan., Methods: A total of 121 workplaces and their 3540 workers were surveyed using questionnaires assessing selected workplace OMH activities, demographic characteristics, psychological distress, and psychosocial work environment of the workers. A multilevel analysis was conducted., Results: Promotion of communication correlated significantly and negatively with psychological distress among workers after adjusting for the covariates (P < 0.01). Occupational mental health activities correlated marginally significantly and negatively with psychological distress (P = 0.06). Their moderating effect for the worker-level association between psychosocial work environment and psychological distress was not significant., Conclusions: The findings suggest that promotion of communication in the workplace is associated with reduced psychological distress among workers. In addition, OMH activities may also be useful in reducing psychological distress.

Background: A worldwide outbreak of influenza A/H1N1 occurred in 2009. Little information is available regarding how the epidemic spread among young people, who composed the majority of individuals infected with this virus. We assessed the route of transmission of H1N1 among university students at Shinshu University, Japan., Methods: A total of 11,424 students were monitored between August 2009 and March 2010, and those who were diagnosed with confirmed, probable, or suspected H1N1 at a hospital or clinic were registered based on self-report to the university. Data including date of onset and suspected infection route were collected from the affected patients., Results: Of the 11,424 students, 1,016 (8.9%) were infected with H1N1. In most infected students, the suspected transmission route was associated with club activity, followed by close contact with friends and through lectures or laboratory work. After suspension of activity by clubs with more than 2 infected members, the number of infected individuals decreased., Conclusion: H1N1 influenza spread in the university through specific routes, including club activity, close contact with friends, and lectures or laboratory work. During future outbreaks of influenza, interventions to reduce transmission through these routes may be effective infection control strategies in university students., (Copyright © 2012 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

We examined the effect of ambient temperature, air pressure and air pollutants on daily emergency admissions by identifying the cause of admission for each type of stroke and cardiovascular disease using generalized linear Poisson regression models allowing for overdispersion, and controlling for seasonal and inter-annual variations, days of the week and public holidays, levels of influenza and respiratory syncytial viruses. Every 1°C decrease in mean temperature was associated with an increase in the daily number of emergency admissions by 7.83% (95% CI 2.06-13.25) for acute coronary syndrome (ACS) and heart failure, by 35.57% (95% CI 15.59-59.02) for intracerebral haemorrhage (ICH) and by 11.71% (95% CI 4.1-19.89) for cerebral infarction. An increase of emergency admissions due to ICH (3.25% (95% CI 0.94-5.51)), heart failure (3.56% (95% CI 1.09-5.96)) was observed at every 1 hPa decrease in air pressure from the previous days. We found stronger detrimental effect of cold on stroke than cardiovascular disease.

Background: A worldwide outbreak of swine flu H1N1 pandemic influenza occurred in April 2009. To determine the mechanism underlying the spread of infection, we prospectively evaluated a survey implemented at a local university., Methods: Between August 2009 and March 2010, we surveyed 3 groups of subjects: 2318 children in six schools attached to the Faculty of Education, 11424 university students, and 3344 staff members. Subjects with influenza-like symptoms who were diagnosed with swine flu at hospitals or clinics were defined as swine flu patients and asked to make a report using a standardized form., Results: After the start of the pandemic, a total of 2002 patients (11.7%) were registered in the survey. These patients included 928 schoolchildren (40.0%), 1016 university students (8.9%), and 58 staff members (1.7%). The incidence in schoolchildren was significantly higher than in the other 2 groups (P < 0.0001) but there were no within group differences in incidence rate between males and females. During the period of the survey, three peaks of patient numbers were observed, in November 2009, December 2009, and January 2010. The first peak consisted mainly of schoolchildren, whereas the second and third peaks included many university students. Staff members did not contribute to peak formation. Among the university students, the most common suspected route of transmission was club activity. Interventions, such as closing classes, schools, and clubs, are likely to affect the epidemic curves., Conclusion: Schoolchildren and university students are vulnerable to swine flu, suggesting that avoidance of close contact, especially among these young people, may be effective way in controlling future severe influenza pandemics, especially at educational institutions.

To investigate the transition in concentration of porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) and antibody for these viruses in serum, serum samples were collected from 29 pigs on weaning day and at 7, 14, 21, 28, 53, 84, and 120 days after weaning. The concentration of circulated PRRSV and PCV2 in serum was measured by real-time RT-PCR and real-time PCR, respectively. The specific antibody for PRRSV and PCV2 was measured using ELISA. PRRSV was not detected on 0 days post-weaning (dpw). The specific antibody for PRRSV began to increase as the concentration of PRRSV in serum increased, and the level of PRRSV then tended to decrease. PCV2 was detected in 12 of 28 pigs on 0 dpw. The concentration of PCV2 and the specific antibody for PCV2 showed a similar tendency to those of PRRSV. The correlation analysis suggests that a decline in the daily weight gain coincided with an increase in the PRRSV concentration. Pigs with a higher antibody titer against PRRSV or PCV2 on 0 dpw showed the lower level of PRRSV or PCV2, respectively.

We retrospectively studied clinical characteristics of 368 patients with cerebral artery dissections who were diagnosed in 172 Japanese hospitals. Of these patients, 130 (35%) presented with subarachnoid hemorrhage, 217 (59%) with cerebral infarctions, and 21 (6%) with transient ischemic attacks. We analyzed 109 (84%) subarachnoid hemorrhage cases caused by vertebrobasilar artery dissection to evaluate conservative and surgical treatment from the viewpoint of postoperative rerupture and infarction.Subsequent ruptures were observed in 14% of the 21 cases with nonsurgical treatment. For the preventive purpose of rerupture, 88 patients received surgical interventions: 68 trappings, 13 proximal occlusions, 6 aneurysmal sac occlusions and 1 stenting. Rerupture was experienced in 33% of the aneurysmal sac occlusion patients while not occurring in the other three surgical interventions. In the group without vascular anastomosis, postoperative cerebral infarction was observed in 25% of the trapping, none of the proximal occlusion and 33% of the aneurysmal sac occlusion cases.In this study, aneurysmal sac occlusion treatments were more frequently complicated by rerupture or cerebral infarction postoperatively than the other treatment methods. It was difficult to determine which surgical treatment can achieve better surgical outcome among the proximal occlusion and trapping with or without vascular anastomosis.

Spontaneous cervicocephalic arterial dissection (SCAD) has been recognized as an uncommon cause of cerebral stroke. Although it has been viewed as an important cause of stroke, especially in juvenile cases, its natural course and pathophysiology have yet to be fully clarified, and no treatment criteria have been established. Recent studies have suggested that clinical features of SCAD in Japan are different from those in European countries. Herein, we reviewed the current status of the management of SCAD in Japan, and clarified its clinical characteristics to establish an appropriate treatment.

Diarrhea in pigs has the potential to have a serious economic impact on the swine industry. Previously, we suggested that the likely cause of the presence of non-infectious diarrhea in pigs characterized by lactate accumulation was dyspepsia. In this experiment, the prevalence of enteropathogens and hyper-lactate accumulation in feces of piglets in 4 distinct growth stages was examined. The feces were collected when veterinarian experts recognized abnormalities in sporadic outbreaks. Prevalence of enteropathogens in diarrheal feces was 100% in fattening pigs (FP), 75% in weaning pigs (WP), 50% in suckling pigs (SP), and 42% in growing pigs (GP). Prevalence of enteropathogens in loose feces was 53% in WP, 50% in SP, 40% in FP, and 28% in GP. Prevalence of hyper-lactate accumulation in diarrheal feces was 33% in GP, 33% in SP, 25% in WP, and 25% in FP. Prevalence of hyper-lactate accumulation in loose feces was 40% in GP, 0% in SP, 7% in WP, and 5% in FP. Accordingly, non-infectious dyspepsia is frequent in growing pigs. In this period, pigs are potentially exposed to needless antimicrobial therapeutic treatments in sporadic cases.

Prevention and control measures against tuberculosis still remain a contemporary issue in Japan. In April 2005, the Tuberculosis Control Law was revised, which has newly been with particular emphasis on medical screening. However, the present law has been indicated to have issues in the fields of such as public health, human rights, and legislation. Although the Tuberculosis Control Law will be integrated into the Infectious Diseases Law on the basis of those issues, the aim of the integration of these laws are mainly for the establishment of pathogen control system to prevent biological terrorism and the accidental spread of infectious diseases and for the comprehensive control of infectious diseases based on the latest medical knowledge. In March 2006, the draft for the revised the Infectious Diseases Law was approved by the Cabinet of government. The combination of the two laws is expected to improve the program quality for the control of tuberculosis and infectious diseases but some issues remains to be resolved. This paper will review the combination of the Tuberculosis Control Law and the Infectious Diseases Law in light of what has been done, what will be intended, and what will change after the combination.

The treatment and natural course of unruptured cerebral aneurysms were analyzed in 615 patients with 712 unruptured cerebral aneurysms registered from seven Japanese national hospitals and Zurich University hospital. For 209 aneurysms in 181 cases, the natural course of the aneurysms was observed without surgical treatment. During the follow-up period of 3,862 months (321.8 years), 11 of these aneurysms ruptured giving a rupture rate of 3.42%/year. Five of these 11 aneurysms were less than 10 mm in diameter. Seventeen aneurysms of these 209 untreated aneurysms had blebs. Seven of these 17 aneurysms ruptured yielding the high rupture rate of 28.3%/year. The likelihood of unruptured cerebral aneurysms to rupture was not exceedingly low even when the aneurysms were smaller than 10 mm. Since the risk of rupture and morbidity in relation to surgical treatment cannot be predicted by size alone, the morphology, especially the presence of blebs, should be considered when treating unruptured cerebral aneurysms. In 434 patients, 503 cerebral aneurysms were treated surgically either by craniotomy in 472 aneurysms or endovascular coil embolization in 31 aneurysms. Surgical outcome was influenced by the presence of concurrent diseases, patient age, size and location of the aneurysms. Complications after surgical treatment of 128 incidentally found aneurysms were reported in four cases; three cases of hemiparesis and one case showing disturbance of higher brain function, with a morbidity rate of 3.1%. These results suggest that surgical treatment may be acceptable in cases of incidentally found cerebral aneurysms, especially when blebs are present.

We report our experience with stenting for symptomatic vertebrobasilar artery stenosis. One hundred and sixteen patients with vertebrobasilar artery stenosis (101 vertebral ostial stenosis, 15 intracranial vertebrobasilar artery stenosis) were treated with stenting. Indication criteria of treatment were 1) symptomatic lesion, 2) angiographical stenosis more than 60%. Under local anesthesia, pre-dilatation was first performed, then stents were placed to the lesion. Successful dilatation was obtained in 115 cases. The stenosis rate reduced to 2% post-stenting in ostial lesions and 16% in intracranial lesions. Transient neurological complications developed in 2 patients. Follow-up angiographies more than 6 months after stenting were performed in 94 patients with ostial lesions and all patients with intracranial lesions. Of these, 8 patients (9.5%) with ostial lesions and 4 patients (27%) with intracranial lesions developed restenosis. All patients with restenosis were treated successfully with PTA (percutaneous transluminal angioplasty). During the follow-up period, 3 patients developed recurrence of VBI (vertebro-basilar insufficiency) symptoms due to restenosis. One patient developed brain stem infarction due to in-stent occlusion 8 months after stenting. Conclusion. Stenting for vertebrobasilar artery stenoses is feasible and safe. Prevention of restenosis, especially in intracranial arteries, is the next problem to be solved.

The present study examined whether levels of cadmium, and alphal- and beta2-microglobulin in urine (Cd-U, ac-MG-U, and beta2-MG-U, respectively) were reproducible in urine samples collected from the same subjects on multiple occasions. For this purpose, two databases on background exposure to cadmium in Japan-one from study I between 2000 and 2001 and the other from study II in 2002-were revisited to find 231 apparently healthy, nonpregnant, nonlactating adult women who participated in both studies and thus had provided two urine samples. The databases contained information on Cd-U, alphal,-MG-U, and beta2-MG-U, creatinine (CR), and specific gravity (SG) as well as smoking and other lifestyle factors. Of the 231 women, 195 who had never smoked were selected for the present analysis. Cd-U as well as alpha1-MG-U were reproducible (e.g., with correlation coefficients [r] between study I and II results of 0.4 to 0.6) when measured on two occasions 9 to 10 months apart. The r values were lower for beta2-MG-U (r0.3). Exclusion of urine samples with inadequate urine density(i.e., CR <0.5 or >3.0 g/L or SG <1.010 or >1.030) resulted in substantial improvement of the agreements between the two measures (e.g., r = 0.6 to 0.7 for Cd-U and alpha1-MG-U). CR and SG correlated closely with each other, especially in low-density urine samples (r >0.9), and therefore the effects of CR and SG could not be evaluated separately. In the overall evaluation,single determination (i.e., without repeated urine sampling) of Cd-U and alpha1-MG-U should be acceptable, and it may also be acceptable for beta2-MG-U. Use of samples with adequate urine density rather than application of density correction to low-density urine samples in recommended.

Carotid endarterectomy (CEA) is a beneficial procedure for patients with high-grade carotid stenosis. However, patients with bilateral carotid stenosis have a higher surgical risk during CEA. Since the introduction of carotid stenting (CAS) may decrease some of the surgical complications of CEA, a combined treatment using CEA and CAS may be favorable for patients with bilateral carotid stenosis. We analyzed the safety and efficacy of this treatment strategy. Eighteen patients with bilateral carotid stenosis were treated from January 2000. Bilateral CEA was performed on the first two patients, CAS then CEA of contra-lateral symptomatic side in 13 patients, and bilateral CAS in three patients. There were no perioperative neurological complications or strokes during the follow-up period (mean 17 months). The combined treatment of CAS and CEA was a safe and effective strategy for bilateral carotid stenosis.

This study confirms the presence of a novel variable number of tandem repeats polymorphism, designated as HumDN1, in intron 4 of the human deoxyribonuclease I (DNase I) gene. Genotyping was performed without difficulty by PCR-amplification and separation by agarose gel electrophoresis in 423 Japanese, originating from four geographically diverse areas in Japan, and 89 Germans. The HumDN1 allele variability was due to different numbers of 56-bp repeat sequences, and five different alleles were distinguished with apparent size between 364 and 588 bp. Although there was a general uniformity for the polymorphism in the Japanese population, significant differences in genotype distribution were found between the Japanese and German populations. Furthermore, linkage disequilibrium between the HumDN1 and DNase I protein polymorphisms was revealed.

The present study was initiated to assess current level of general population exposure to lead (Pb) in terms of Pb in urine (Pb-U). For this purpose, spot urine samples were collected from 2,332 never-smoking adult women in 10 areas all-over Japan, and were subjected to analysis for Pb-U by graphite furnace atomic absorption (GFAA). Data on cadmium in urine (Cd-U) as measured by GFAA were cited from a previous publication). The grand geometric means (GM) for Pb-U as observed, as corrected for creatinine (cr) and as corrected for a specific gravity of 1.016 were 1.06 microg/l, 1.28 microg/g cr and 1.14 microg/l, respectively, with small intra- and inter-variations with geometric standard deviations of about 2 or less. Arithmetic means of the 10 GMs (one each for the 10 areas) were 1.05 microg/l, 1.19 microg/g cr and 1.18 microg/l, respectively. The levels observed appeared to be lower than levels reported for other populations in the world. Chronological comparison within Japan suggested a gradual decrease in Pb-U in past over 20 yr. No close correlation was detected between Pb-U and Cd-U.