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Neuromuscular blocking agents play a significant role in improving the success rate for urgent intubation, although there is limited evidence about the effect on subsequent outcomes, such as the incidence of tracheostomy. In this retrospective cohort study, we aimed to examine the association between avoidance of neuromuscular blocking agents for urgent tracheal intubation and incidence of tracheostomy among patients in the intensive care unit (ICU). The setting of this study was an eight-bed ICU at a tertiary-care hospital in Okayama, Japan. We included patients who underwent urgent tracheal intubation at the emergency department or the ICU and were admitted to the ICU between April 2013 and November 2017. We extracted data on methods and medications of intubation, predictors for difficult intubation, Cormack–Lehane grade, patient demographics, primary diagnoses, reintubation. We estimated odds ratios and their 95% confidence intervals for elective tracheostomy during the ICU stay using logistic regression models. Of 411 patients, 46 patients underwent intubation without neuromuscular blocking agents and 61 patients underwent tracheostomy. After adjusting for potential confounders, patients who avoided neuromuscular blocking agents had more than double the odds of tracheostomy (odds ratio 2.59, 95% confidence interval 1.06–6.34, p value = 0.04). When stratifying the subjects by risk status for tracheostomy, the association was more pronounced in high-risk group, while we observed less significant association in the low-risk group. Avoidance of neuromuscular blocking agents for urgent intubation increases the risk of tracheostomy among emergency patients, especially those who have a higher risk for tracheostomy. Electronic supplementary material The online version of this article (10.1007/s11739-019-02214-0) contains supplementary material, which is available to authorized users.

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.

The species classification of Cambodian freshwater pufferfish is incomplete and confusing, and scientific information on their toxicity and toxin profile is limited. In the present study, to accumulate information on the phylogeny and toxin profile of freshwater pufferfish, and to contribute to food safety in Cambodia, we conducted simultaneous genetic-based phylogenetic and toxin analyses using freshwater pufferfish individuals collected from Phnom Penh and Kratie (designated PNH and KTI, respectively).Phylogenetic analysis of partial sequences of three mitochondrial genes (cytochrome b, 16S rRNA, and cytochrome c oxidase subunit I) determined for each fish revealed that PNH and KTI are different species in the genus Pao (designated Pao sp. A and Pao sp. B, respectively). A partial sequence of the nuclear tributyltin-binding protein type 2 (TBT-bp2) gene differentiated the species at the amino acid level. Instrumental analysis of the toxin profile revealed that both Pao sp. A and Pao sp. B possess saxitoxins (STXs), comprising STX as the main component. In Pao sp. A, the toxin concentration in each tissue was extremely high, far exceeding the regulatory limit for STXs set by the Codex Committee,whereas in Pao sp. B, only the skin contained high toxin concentrations. The difference in the STX accumulation ability between the two species with different TBT-bp2 sequences suggests that TBT-bp2 is involved in STX accumulation in freshwater pufferfish., Toxins, 12(11), art.no.689; 2020

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.

Objectives The effect of tongue cleaning on digestive power is mentioned in Ayurvedic information sources. However, no study has yet evaluated this. We aimed to evaluate the effects of tongue cleaning on digestive power from Ayurvedic viewpoint, and on oral health-related quality of life (OHRQoL) in healthy adults. Design Randomized cross-over. Interventions We recruited healthy adults aged 20–60 years. After randomization, the immediate intervention group started tongue cleaning with a tongue scraper every morning for 4 weeks, and then waited for 4 weeks. The delayed intervention group initially waited for 4 weeks, and then started tongue cleaning in the same way. Main outcome measures We assessed the outcomes using the questionnaire on digestive power from Ayurvedic viewpoint, and the General Oral Health Assessment Index for OHRQoL. We estimated the effects of tongue cleaning using generalized estimating equations (GEE). We also conducted a sensitivity analysis, by comparing the changes in outcomes during the first 4 weeks of both groups. Results Of 58 participants, 57 completed the study. In GEE analysis, tongue cleaning showed improvement in some components of Ayurvedic digestive power represented by fecal and body conditions. For example, the odds ratio for improvement of constipation was 2.80 (95% CI: 1.04–7.58). The General Oral Health Assessment Index score was significantly increased by 4.33 points (95% CI: 2.18–6.48) after tongue cleaning. In sensitivity analyses, the trends of the results were similar to the main GEE analyses. Conclusions Tongue cleaning may be an effective method to improve digestive power and OHRQoL.

The present study evaluated differences in the tetrodotoxin (TTX)/saxitoxins (STXs) selectivity between marine and freshwater pufferfish by performing in vivo and in vitro experiments. In the in vivo experiment, artificially reared nontoxic euryhaline freshwater pufferfish Dichotomyctere fluviatilis were intrarectally administered a mixture of TTX (24 nmol/fish) and STX (20 nmol/fish). The amount of toxin in the intestine, liver, muscle, gonads, and skin was quantified at 24, 48, and 72 h. STX was detected in the intestine over a long period of time, with some (2.7–6.1% of the given dose) being absorbed into the body and temporarily located in the liver. Very little TTX was retained in the body. In the in vitro experiments, slices of intestine, liver, and skin tissue prepared from artificially reared nontoxic D. fluviatilis and the marine pufferfish Takifugu rubripes were incubated in buffer containing TTX and STXs (20 nmol/mL each) for up to 24 or 72 h, and the amount of toxin taken up in the tissue was quantified over time. In contrast to T. rubripes, the intestine, liver, and skin tissues of D. fluviatilis selectively took up only STXs. These findings indicate that the TTX/STXs selectivity differs between freshwater and marine pufferfish., Toxins, 13(10), art. no. 731; 2021

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.

Background Although dosing and sizing of resuscitation drugs and equipment are mostly weight based, time is usually insufficient to weigh critically ill children. Many age-based weight estimation formulae for emergency use have been developed worldwide, but there is no specific formula for Japanese children. The aim of this study was therefore to develop and validate age-based formulae for estimating the bodyweight of children living in Japan. Methods A total of 370 980 measurements of bodyweight were obtained from 39 547 participants aged 12–155 months. They participated in a national survey, called the Longitudinal Survey of Babies in the 21st Century, which started in 2001. We created the new original weight estimation formulae for children living in Japan, called the Japanese Pediatric Assessment of Normal weight (JAPAN) formulae, using 75% of measurements that were randomly selected from the total measurements. To check the validity of the formulae, we applied the JAPAN formulae, the Park et al. formula for Korean children, and the commonly used Nelson formula for the remaining 25% of measurements. The mean absolute error and the root mean square error (RMSE) were calculated for each scale. Results The JAPAN formulae performed better than the two other formulae among Japanese children, with a mean absolute error and RMSE of 0.83 and 1.08 (kg), respectively. The performance of the Park et al. formulae for Korean children was poor for children living in Japan. Conclusions The newly developed JAPAN formulae for age-based weight estimation are appropriate for children living in Japan.

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.

We examined the effects of maternal smoking location at home on hospitalization for respiratory tract infections among young children in Japan. We used the large nationwide population-based longitudinal survey and restricted study participants to children born after 37 gestational weeks and singleton births (n = 43,851). We evaluated the associations among children between the ages of 6 and 18 months and between the ages of 18 and 30 months, respectively. After adjusting for potential confounders, both maternal outdoor and indoor smoking were associated with the elevated risk. The adjusted odds ratios (95% confidence intervals) of maternal outdoor and indoor smoking (vs nonsmoking mothers) were 1.21 (1.01–1.44) and 1.18 (1.04–1.33), respectively, in children between the ages of 6 and 18 months. We thus encourage a smoke-free home policy to protect children from second- and third-hand smoke exposure.

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

To clarify the differences in toxin selectivity between marine and freshwater pufferfish, we conducted experiments in artificially reared nontoxic specimens of Takifugu pardalis (marine) and Pao suvattii (freshwater) using tetrodotoxin (TTX) and paralytic shellfish poison (PSP, decarbamoylsaxitoxin (dcSTX) or saxitoxin (STX)). T. pardalis specimens were administered feed homogenate containing TTX or dcSTX (dose of toxin, 55.2 nmol/fish) and P. suvattii specimens were administered feed homogenate containing TTX + STX (dose of each toxin, 19.2 nmol/fish) by oral gavage. The toxin content in the intestine, muscle, skin, liver, and gonads was quantified after 24 and 48 or 72 h. In T. pardalis, TTX administered into the intestine was absorbed into the body and transferred and retained mainly in the skin and liver, while dcSTX was hardly retained in the body, although it partly remained in the intestine. In strong contrast, in P. suvattii, little TTX remained in the body, whereas STX was absorbed into the body and was transferred and retained in the ovary and skin. The findings revealed that TTX/PSP selectivity differs between the marine species T. pardalis and the freshwater species P. suvattii. T. pardalis, which naturally harbors TTX, selectively accumulates TTX, and P. suvattii, which naturally harbors PSP, selectively accumulates PSP.

BackgroundBody mass index (BMI) is a significant predictor of functional disability in older adults. However, when evaluated, the association between BMI and incident functional disability, considering behaviors only as covariates or not, may not be appropriate. The primary purpose of the study was to investigate the combined effects of BMI and unhealthy behaviors on the risk of incident functional disability.MethodsThis was a retrospective cohort study that took place in Okayama City, Japan. Data on BMI and unhealthy behaviors were obtained using the health check-up questionnaire. The certification of Long-Term Care Insurance was used to measure functional disability. Cox proportional hazard models were used; adjusted hazard ratios (HRs) with 95% confidence interval (CI) were calculated for incidence of functional disability across categories of BMI and number of unhealthy behaviors.ResultsThe relationship between BMI and incident functional disability was U-shaped (HR = 1.18, 95% CI [1.11–1.25], among the underweight range; and 1.26 [1.19–1.34] among the obesity range), and its risk was significantly higher within the normal-to-overweight range of BMI values with co-occurring unhealthy behaviors (with normal weight range and one, 1.17 [1.01–1.21]; two, 1.29 [1.18–1.41]; and three or four unhealthy behaviors 1.38 [1.24–1.54]; as well as among overweight range and one, 1.16 [1.05–1.27]; two, 1.26 [1.15–1.38]; and three or four unhealthy behaviors, 1.47 [1.31–1.64]). In each BMI category, the risk of incident functional disability increased with increasing number of unhealthy behaviors (p< 0.05 for linear tread), with the highest risk (1.87 [1.58–2.20]) occurring in combination with at least three unhealthy behaviors with BMI ≥ 27.5, for both sexes (2.20 [1.64–2.92] in men and 1.66 [1.35–2.04] in women).ConclusionIt is necessary to consider the combined effects of BMI and behaviors on incident functional disability. Furthermore, interventions targeting multiple behaviors should be considered as such interventions may offer greater benefits than simple interventions.

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.

Background Evidence linking air pollution with adverse health outcomes is accumulating. However, few studies have adopted a quasi-experimental design to evaluate whether decline in air pollution from regulatory action improves public health. We evaluated the effect of a diesel emission control ordinance introduced in 2003 on mortality rates in 23 wards of the Tokyo metropolitan area, Japan, from October 2000 to September 2012, taking into account change in mortality rates in a reference population (Osaka) with a introduction of such a regulation in 2009. Methods We obtained daily counts of all-cause and cause-specific mortality and concentrations of nitrogen dioxide (NO2) and particulate matter less than 2.5 μm in diameter (PM2.5) during the study period. We employed interrupted time-series analysis to analyze the data. Results Decline in NO2 during the study period was similar in the two areas, while decline in PM2.5 and the improvement in age-standardized mortality rates were greater in Tokyo's 23 wards compared with Osaka. Even after adjusting for age-standardized mortality rates in Osaka, percent changes in mortality between the first 3-year interval (October 2000 to September 2003) and the last 3-year interval (October 2009 to September 2012) were -6.0% for all causes, -11% for cardiovascular disease, -10% for ischemic heart disease, -6.2% for cerebrovascular disease, -22% for pulmonary disease, and -4.9% for lung cancer. We did not observe a decline in mortality from other causes. Conclusions This quasi-experimental study in Tokyo suggests that emission control was associated with improvements in both air quality and health outcomes.

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.

Few studies have evaluated the effect of short-term exposure to particulate matter (PM) less than 2.5μm in diameter (PM2.5) or to coarse particles on infant mortality. We evaluated the association between short-term exposure to PM and infant mortality in Japan and assessed whether adverse health effects were observable at PM concentrations below Japanese air quality guidelines. We used a time-stratified, case-crossover design. The participants included 2086 infants who died in the 23 urbanized wards of the Tokyo Metropolitan Government between January 2002 and December 2013. We obtained measures of PM2.5 and suspended particulate matter (SPM; PM

Gonadotropin-inhibitory hormone (GnIH) plays as a multifunctional neurohormone that controls reproduction in birds and mammals. LPXRFamide (LPXRFa) peptide, the fish ortholog of GnIH, has been shown to regulate the secretion of not only gonadotropin (GTH) but also growth hormone (GH) and prolactin (PRL), which are potentially important for gonadal function. To investigate the role of LPXRFa peptide on reproduction of the grass puffer, which spawns in semilunar cycles, we examined changes in the levels of gh and prl expression over the several months during the reproductive cycle, and the effects of goldfish LPXRFa peptide-1 (gfLPXRFa-1) on their expression were examined using primary pituitary cultures. The expression levels of both gh and prl showed significant changes during the reproductive cycle in both sexes with one peak in the spawning and pre-spawning periods for gh and prl, respectively. Particularly, gh showed substantial increase in expression in the spawning and post-spawning periods, indicative of its essentiality in the advanced stage of reproduction. gfLPXRFa-1 stimulated the expression of both gh and prl but there was a marked difference in response between them: gfLPXRFa-1 stimulated gh expression at a relatively low dose but little effect was observed on prl. Combined with the previous results of daily and circadian oscillations of lpxrfa expression, the present results suggest that LPXRFa peptide is important in the control of the cyclic reproduction by serving as a multifunctional hypophysiotropic factor that regulates the expression of gh and prl as well as GTH subunit genes.

Recent studies suggest that prenatal exposure to outdoor air pollution is associated with unfavorable neurodevelopment in children. We examined associations between prenatal exposure to traffic-related air pollution and child behavioral development milestone delays, using data from a nationwide population-based longitudinal survey in Japan, where the participants were recruited in 2001 and followed.Particulate matter, nitrogen dioxide, and sulfur dioxide concentrations during the 9 months before birth were obtained at the municipality level and assigned to the participants who were born in the corresponding municipality. We analyzed data from singleton births with linked pollution data available (N = 33,911 at the maximum). We used responses to survey questions about age-appropriate behaviors at ages 2.5 and 5.5 years as indicators of behavioral development. We conducted multilevel logistic regression analysis, adjusting for individual and municipality-level variables.Air pollution exposure during gestation was positively associated with the risk of some developmental milestone delays at both ages. Specifically, air pollution was associated with verbal and fine motor development at age 2.5 years, and with behaviors related to inhibition and impulsivity at 5.5 years. In the fully-adjusted models, odds ratios following one-interquartile-range increase in nitrogen dioxide and suspended particulate matter were 1.24 (95% confidence interval: 1.07, 1.43) for inability to compose a two-phrase sentence at ages 2.5 and 1.10 (1.05, 1.16) for inability to express emotions at age 5.5 years, respectively.Prenatal exposure to traffic-related air pollution was associated with behavioral development milestone delays of children in a nationally representative sample in Japan.

Recent studies have reported adverse health effects of short-term exposure to coarse particles independent of particulate matter less than 2.5 μm in diameter (PM2.5), but evidence in Asian countries is limited. We therefore evaluated associations between short-term exposure to particulate matter (PM) and mortality among older people in Tokyo, Japan. We used a time-stratified, case-crossover design. Study participants included 664,509 older people (≥65 years old) in the 23 urbanized wards of the Tokyo Metropolitan Government, who died between January 2002 and December 2013. We obtained PM2.5 and suspended particulate matter (SPM; PM

Purpose Although 1,2-intercompartmental supraretinacular artery (1,2-ICSRA)–based vascularized bone grafting (VBG) has gained popularity in the treatment of scaphoid nonunion, correcting humpback deformities with this technique remains challenging. The purpose of this retrospective study was to determine the possibility of correcting humpback deformities using a 1,2-ICSRA VBG with a dorsoradial approach. Methods We treated 25 patients with scaphoid nonunion using a 1,2-ICSRA VBG between January 2007 and December 2017. For those with a humpback deformity, we performed vascularized wedge grafting from the dorsoradial side, instead of inlay bone grafting from the dorsal or volar side of the scaphoid. After excluding patients with scaphoid nonunion without a humpback deformity and those followed up for less than 6 months, we reviewed the imaging results and union rate in the remaining 19 patients (18 men and 1 woman). The nonunion sites and patient distribution were as follows: proximal one-third, 2; waist, 16; and distal one-third, 1. Results The union rate at the last follow-up performed a minimum of 6 months after the intervention was 94.7%. The correction was adequate in 17 patients and inadequate in 2 patients. The lateral intrascaphoid, radiolunate, and scapholunate angles were improved. Conclusions Humpback and dorsal intercalated segmental instability deformities can be corrected adequately using a 1,2-ICSRA VBG with a dorsoradial approach. Type of study/level of evidence Therapeutic IV.

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.

Objective: We aimed to evaluate the annual health impacts of particulate matter (PM) less than 10 μm diameter (PM10) and less than 2.5-μm diameter (PM2.5) in 27 cities in Southeast and East Asian countries (Japan, the Philippines, the Republic of Korea, Singapore, and Vietnam) for the year 2009 (n = 50,756,699). Methods: We estimated the number of cases attributable to long-term exposure. We used a scenario that reduced the annual mean values for PM10 and PM2.5 to 20 and 10 μg/m3, respectively. Results: A reduction in long-term exposure to PM10 and PM2.5 would have postponed 8% to 9% of all-cause mortality or about 37,000 deaths. One third of them were associated with cardiopulmonary mortality and one ninth of them were associated with lung cancer mortality. Conclusions: Current air pollution levels in Southeast and East Asian countries have a nonnegligible public health impact.

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.

In teleosts, the spinal cord generally extends along the entire vertebral canal. The Tetraodontiformes, in which the spinal cord is greatly reduced in length with a distinct long filum terminale and cauda equina, have been regarded as an aberration. The aims of this study are: 1) to elucidate whether the spinal cord in all tetraodontiform fishes shorten with the filum terminale, and 2) to describe the gross anatomical and histological differences in the spinal cord among all families of the Tetraodontiformes. Representative species from all families of the Tetraodontiformes, and for comparison the carp as a common teleost, were investigated. In the Triacanthodidae, Triacanthidae, and Triodontidae, which are the more ancestral taxa of the Tetraodontiformes, the spinal cord extends through the entire vertebral canal. In the Triacanthidae and Triodontidae, the caudal half or more spinal segments of the spinal cord, however, lack gray matter and consist largely of nerve fibers. In the other tetraodontiform families, the spinal cord is shortened forming a filum terminale with the cauda equina, which is prolonged as far as the last vertebra. The shortened spinal cord is divided into three groups. In the Ostraciidae and Molidae, the spinal cord tapers abruptly at the cranium or first vertebra forming a cord-like filum terminale. In the Monacanthidae, Tetraodontidae, and Diodontidae, it abruptly flattens at the rostral vertebrae forming a flat filum terminale. The spinal cord is relatively longer in the Monacanthidae than that in the other two families. It is suggested by histological features of the flat filum terminale that shortening of the spinal cord in this group progresses in order of the Monacanthidae, Tetraodontidae, and Diodontidae. In the Balistidae and Aracanidae, the cord is relatively long and then gradually decreased in dorso-ventral thickness.

In seasonally breeding animals, the circadian and photoperiodic regulation of neuroendocrine system is important for precisely-timed reproduction. Kisspeptin, encoded by the Kiss1 gene, acts as a principal positive regulator of the reproductive axis by stimulating gonadotrophin-releasing hormone (GnRH) neurone activity in vertebrates. However, the precise mechanisms underlying the cyclic regulation of the kisspeptin neuroendocrine system remain largely unknown. The grass puffer, Takifugu niphobles, exhibits a unique spawning rhythm: spawning occurs 1.5-2 h before high tide on the day of spring tide every 2 weeks, and the spawning rhythm is connected to circadian and lunar-/tide-related clock mechanisms. The grass puffer has only one kisspeptin gene (kiss2), which is expressed in a single neural population in the preoptic area (POA), and has one kisspeptin receptor gene (kiss2r), which is expressed in the POA and the nucleus dorsomedialis thalami. Both kiss2 and kiss2r show diurnal variations in expression levels, with a peak at Zeitgeber time (ZT) 6 (middle of day time) under the light/dark conditions. They also show circadian expression with a peak at circadian time 15 (beginning of subjective night-time) under constant darkness. The synchronous and diurnal oscillations of kiss2 and kiss2r expression suggest that the action of Kiss2 in the diencephalon is highly dependent on time. Moreover, midbrain GnRH2 gene (gnrh2) but not GnRH1 or GnRH3 genes show a unique semidiurnal oscillation with two peaks at ZT6 and ZT18 within a day. The cyclic expression of kiss2, kiss2r and gnrh2 may be important in the control of the precisely-timed diurnal and semilunar spawning rhythm of the grass puffer, possibly through the circadian clock and melatonin, which may transmit the photoperiodic information of daylight and moonlight to the reproductive neuroendocrine centre in the hypothalamus.

High-energy X-ray diffraction measurements were carried out at 26 °C for aqueous 1.0, 2.0 and 2.05 mol% disodium adenosine 5′-triphosphate (ATP) and 2.0 and 2.05 mol% disodium adenosine 5′-diphosphate (ADP) solutions in order to obtain direct experimental information on the intramolecular conformations of ATP and ADP molecules in aqueous solutions. Observed interference terms were analyzed in terms of the intramolecular geometry of the ATP and ADP molecules. Dihedral angles between adenine and the ribose group (t1), ribose-ring and methylene group of ribose (t2), and the methylene group of ribose and triphosphate (or diphosphate) group (t3), were determined through the least-squares fitting procedure of the observed interference term.

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

Objectives. We examined the association between social cohesion and mortality in a sample of older adults in Japan. Methods. Data were derived from a cohort study of elderly individuals (65–84 years) in Shizuoka Prefecture; 14 001 participants were enrolled at baseline (1999) and followed up in 2002, 2006, and 2009. Among the 11 092 participants for whom we had complete data, 1427 had died during follow-up. We examined the association between social cohesion (assessed at both the community and individual levels) and subsequent mortality after control for baseline and time-varying covariates. We used clustered proportional hazard regression models to estimate hazard ratios (HRs) and confidence intervals (CIs). Results. After control for individual characteristics, individual perceptions of community cohesion were associated with a reduced risk of all-cause mortality (HR = 0.78; 95% CI = 0.73, 0.84) as well as mortality from cardiovascular disease (HR = 0.75; 95% CI = 0.67, 0.84), pulmonary disease (HR = 0.66; 95% CI = 0.58, 0.75), and all other causes (HR = 0.76; 95% CI = 0.66, 0.89). However, no statistically significant relationship was found between community cohesion and mortality risk. Conclusions. Among the elderly in Japan, more positive individual perceptions of community cohesion are associated with reduced risks of all-cause and cause-specific mortality.

BACKGROUND: In industrializing countries, occupational safety and health have been affected by globalization. However, a lack of reliable data prevents evaluation of this situation. Therefore, we examined industrial distributions and risks of severe occupational injuries among workers in Thailand, which is one of the few industrializing countries that compiles nationwide data. METHODS: Data on workers who made claims for occupational injuries from 2007 to 2009 were extracted from the Workmen's Compensation Fund records in Thailand. Among 501,334 claimants, we evaluated the industrial distributions of severe occupational injuries (i.e., permanent disability and death). We then examined the associations between industry and those injuries, using proportionate ratios (PRs) between each industrial category and the overall distribution of occupational injuries. RESULTS: The number of workers in manufacturing making claims for severe occupational injuries was the largest among all industrial categories (319,114/501,334 injuries), although the total number of occupational injuries recently declined. Additionally, workers in manufacturing experienced severe occupational injuries more often compared with the overall distribution of occupational injuries. The PRs (95% confidence interval) for manufacturing were 1.17 (1.14-1.20) in men and 1.33 (1.27-1.38) in women. After adjusting for individual characteristics, the results did not substantially change. CONCLUSIONS: Manufacturing seems to have the largest burden of occupational injuries in industrializing countries like Thailand. Language: en

Background Barker's fetal programming hypothesis suggests that disproportionate size at birth may have a lifelong impact on one's health. However, the literature on birth length is considerably more sparse compared with birthweight. We, therefore, examined the relationship between birth length and hospitalisation early in life among Japanese children. Methods We used the nationwide Longitudinal Survey of Babies in 21st Century and restricted the study subjects to full-term singleton babies (n = 44 057). We estimated the effects of birth length and birthweight on the risk of hospitalisation using log linear regression models. We controlled for a set of neonatal and maternal factors. Results Birth length was associated with the chance of hospitalisation due to all causes between 6 and 18 months of age. In addition, the association was stronger than that with birthweight. Adjusted risk ratios showed that the relationship between birth length and hospitalisation was U-shaped: 1.16 [95% confidence intervals, 1.08, 1.25] at 30–48 cm, 1 [Reference] at 49 cm, 1.13 [1.04, 1.22] at 50 cm, and 1.11 [1.02, 1.20] at 51–60 cm. Short babies with low or high weight, as well as long babies with low weight, seem to be at increased risk of hospitalisation. Conclusions We found a U-shaped relationship between birth length and risk of hospitalisation due to all causes during the period from 6 to 18 months.

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.

Aim Associations between markedly low activities of daily living (ADL) at the start of home visit care and patient home death were analyzed using data from a home care support clinic in Japan that has a low rate of home deaths. Methods The study was a historical cohort study. It involved patients who began to receive home visit care from a home visit care support clinic between 1 April 2006 and 31 March 2011. Using home death as a dependent variable and presence/absence of markedly low ADL and other parameters (cancer, the patient's desire for home death, etc.) as independent variables, the adjusted hazard ratio and 95% confidence interval (CI) were calculated using the Cox proportional hazards model. Results Markedly low ADL were associated with home death even after adjustment for factors that influence home death (adjusted hazard ratio 4.40; 95% CI 2.37–8.16). Cancer and the patient's desire for home death were statistically significant factors involved in home death. In a subgroup analysis according to the presence/absence of cancer, the association between markedly low ADL and home death was stronger in the cancer-free group (adjusted hazard ratio 10.78; 95% CI 2.89–40.26) than in the cancer group (adjusted hazard ratio 5.58; 95% CI2.39–13.05). Conclusion Patients' desire for home death could be fulfilled if home care support clinics provide home visit services to not only terminal-stage cancer patients, but also bedridden cancer-free patients. We must establish systems for older adults to remain at home during the terminal period of their lives. Geriatr Gerontol Int 2012; ●●: ●●–●●.