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Aim Obstetricians sometimes administer intramyometrial oxytocin to stimulate uterine contraction during cesarean section, but its effects have not been well investigated. We performed a randomized, double-blind study to test the hypothesis that a small dose of intramyometrial oxytocin would induce acceptable uterine contractility more quickly and with fewer hemodynamic side-effects than the same dose administered intravenously. Methods Forty women with a single fetus at ≥36 weeks of gestational age scheduled for elective cesarean section under spinal anesthesia were randomized to the intravenous and intramyometrial groups to receive oxytocin at 0.07 IU/kg. The drug was administered immediately after umbilical cord clamping. Systolic blood pressure, heart rate, intraoperative blood loss, uterine tone, total amount of intraoperative oxytocin, and additional uterotonic drugs administered in the first 24 h were compared. Results Maximum uterine contractility was achieved after 2 and 10 min for the intravenous and intramyometrial groups, respectively. The mean hemodynamic parameters of the intramyometrial group were stable. In contrast, the intravenous group showed a reduction in systolic blood pressure after 2–4 min and increased heart rate after 1–2 min. Intraoperative blood loss, total oxytocin dose, and frequency of additional uterotonic drugs were comparable between the two groups. Conclusion Although intraoperative blood loss was comparable, a small dose of intramyometrial oxytocin was inappropriate to obtain a prompt and acceptable uterine contraction during cesarean section.

This study aimed to evaluate plasma 4β-hydroxycholesterol as an endogenous marker of CYP3A4/5 activity in early postpartum women and its impact on the plasma disposition of amlodipine. Twenty-seven early postpartum women treated with amlodipine for pregnancy-induced hypertension were enrolled. The plasma concentration of 4β-hydroxycholesterol and its ratio to cholesterol in postpartum and in non-perinatal women were evaluated. The predose plasma concentration of amlodipine was determined at steady state. The medians of the plasma 4β-hydroxycholesterol concentration at day 0-3 and 8-21 after delivery were 146 and 161 ng/mL, respectively. No significant difference was observed in the plasma concentration of 4β-hydroxycholesterol between the postpartum periods. The plasma concentration of 4β-hydroxycholesterol and its ratio to cholesterol in postpartum women were significantly higher than those in non-perinatal women. A large individual variability was observed in the dose-normalized plasma concentration of amlodipine in early postpartum women. A weak negative correlation was observed between the dose-normalized plasma concentration of amlodipine and the plasma concentration of 4β-hydroxycholesterol. In conclusion, early postpartum women possessed higher CYP3A activity based on plasma 4β-hydroxycholesterol and had a large pharmacokinetic variability in amlodipine. CYP3A activity during the early postpartum period had an effect on the plasma disposition of amlodipine.

The aim of the present study was to investigate the relationship between assisted reproductive technology procedures, the morphology of the basal plate of placentas, and amount of bleeding in deliveries. Fifty-five whole placentas (fresh-embryo transfer in the in vitro fertilization cycle [n = 6], frozen-thawed embryo transfer in the natural cycle [n = 13] or in the hormonal cycle [n = 10], and age-matched spontaneously conceived pregnancies [n = 26]) were retrospectively enrolled and histologically analyzed. The whole placentas were stored in our pathological division among 512 singleton pregnancies with vaginal deliveries (34-41 weeks of gestation) at Hamamatsu University Hospital. The morphology of the placental basal plate was examined using Azan staining. A total of 20 digital images (each 0.53 mm(2)) of microscopic fields were analyzed per placenta to measure the mean values of the vertical maximum thickness of Rohr and Nitabuch fibrinoid layers and % loss of decidua. The thickness of Rohr fibrinoid layer and % loss of decidua were significantly higher in the frozen-thawed embryo transfer in the hormonal cycle group than in the frozen-thawed embryo transfer in the natural cycle and spontaneously conceived pregnancy groups (each P < .01). The z scores for both the thickness of Rohr fibrinoid layer and % loss of decidua positively correlated with those for the amount of bleeding in deliveries (P < .05 each). Assisted reproductive technology procedures changed the morphology of the placental basal plate, suggesting a possible association with an increase in the amount of bleeding in deliveries.

Perinatal care in Japan has progressed rapidly in recent decades, remarkably reducing maternal, perinatal and neonatal mortality rates. This is attributable not only to the sustained efforts and dedication of past obstetricians and midwives, but also to the collective results achieved by the Japan Society of Obstetrics and Gynecology and healthcare administration, including research on advanced medical care, education, medical care improvements and establishing perinatal care centers. Although the maternal mortality rate was in steady decline until 2007 (3.1/100 000 births), it repeatedly fluctuated thereafter, plateauing at 3.4 per 100 000 births in 2013 and 2.7 per 100 000 births in 2014. Thus, the Perinatology Committee has analyzed the current situation of maternal deaths and has proposed countermeasures to reduce such death. The items deliberated upon by related subcommittees in 2015 are presented herein. The addition of indications for ‘fibrinogen concentrate’, ‘eptacog alfa’ and approval of the PGE2 vaginal tablet for cervical ripening were discussed in the subcommittee for unapproved drug review. Thus, a request for approval for health insurance coverage was submitted to the ‘Evaluation committee on unapproved or off-label drugs with high medical needs’ of the Ministry of Health, Labour and Welfare. Maternal and late-maternal deaths from suicide during the 10 years from 2005 to 2014 in Tokyo's 23 wards were jointly examined with the Tokyo Medical Examiner's Office. The suicide rate in the 23 wards is very high, at 8.7 per 100 000 births. Thus, the subcommittee for the reduction of maternal death discussed countermeasures for the eradication of maternal death and maternal suicide and the revision of death certificates.

Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Its prevalence is currently increasing not only in developed obese countries but also in developing countries. Recent findings from human cohorts and animal studies suggest that a nutritional imbalance in the early critical period is causatively associated with the incidence of NAFLD in later life. Based on the current theory of the developmental origins of health and disease (DOHaD), undernourishment and overnourishment in utero are both hypothesized to prime the predisposition for hepatic fat storage. Current knowledge on the developmental origins of NAFLD is introduced in this chapter.

WAP-8294A2 (lotilibcin, 1) is a potent antibiotic with superior in vivo efficacy to vancomycin against methicillin-resistant Staphylococcus aureus (MRSA). Despite the great medical importance, its molecular mode of action remains unknown. Here we report the total synthesis of complex macrocyclic peptide 1 comprised of 12 amino acids with a β-hydroxy fatty-acid chain, and its deoxy analogue 2. A full solid-phase synthesis of 1 and 2 enabled their rapid assembly and the first detailed investigation of their functions. Compounds 1 and 2 were equipotent against various strains of Gram-positive bacteria including MRSA. We present evidence that the antimicrobial activities of 1 and 2 are due to lysis of the bacterial membrane, and their membrane-disrupting effects depend on the presence of menaquinone, an essential factor for the bacterial respiratory chain. The established synthetic routes and the menaquinone-targeting mechanisms provide valuable information for designing and developing new antibiotics based on their structures.

We recently reported that a treatment with tauroursodeoxycholic acid (TUDCA), a secondary bile acid, improved developmentally-deteriorated hepatic steatosis in an undernourishment (UN, 40% caloric restriction) in utero mouse model after a postnatal high-fat diet (HFD). We performed a microarray analysis and focused on two genes (Cidea and Cidec) because they are enhancers of lipid droplet (LD) sizes in hepatocytes and showed the greatest up-regulation in expression by UN that were completely recovered by TUDCA, concomitant with parallel changes in LD sizes. TUDCA remodeled developmentally-induced histone modifications (dimethylation of H3K4, H3K27, or H3K36), but not DNA methylation, around the Cidea and Cidec genes in UN pups only. Changes in these histone modifications may contribute to the markedly down-regulated expression of Cidea and Cidec genes in UN pups, which was observed in the alleviation of hepatic fat deposition, even under HFD. These results provide an insight into the future of precision medicine for developmentally-programmed hepatic steatosis by targeting histone modifications.

Aim To measure cerebral tissue hemoglobin in uncomplicated and complicated pregnant women during the peripartum period. Methods Time-resolved spectroscopy (TRS-20) can measure absolute concentration of oxygenated, deoxygenated, and total tissue hemoglobin based on the transit time of individual photons. Therefore, we used TRS-20 to measured tissue hemoglobin in the hemi-prefrontal lobes of normotensive pregnant women with (n = 51) or without (n = 19) epidural anesthesia, hypertensive pregnant women with pre-eclampsia (n = 10), a pregnant woman with acute onset of hypertension soon after delivery, and a hypertensive woman after hemorrhagic stroke in delivery. Results Cyclic labor concomitant with intra-abdominal pressure caused synergistic elevation in cerebral tissue hemoglobin. In contrast, epidural anesthesia reduced the amplitude of the cyclic increase of cerebral tissue hemoglobin in normotensive pregnant women. Hypertension in labor due to pre-eclampsia increased the amplitude of synergistic elevation of cerebral tissue hemoglobin caused by cyclic labor and intra-abdominal pressure. A prolonged high basal level of cerebral tissue hemoglobin was observed in a case of acute onset of hypertension soon after delivery. A decrease in cerebral tissue hemoglobin in the hemi-prefrontal lobe was observed in a woman 2 h after the onset of hemorrhagic stroke in labor. Conclusions TRS-20 can detect specific changes in maternal cerebral tissue hemoglobin level in response to physiological and pathophysiological changes in delivery. Thus, it represents a promising new conventional tool for maternal cerebral monitoring in the peripartum period.

Four workers at a seed supply warehouse in Chiba Prefecture, Japan, complained of ocular irritation on the job. Pesticide-coated seeds were stored in the warehouse but no significant amount of pesticide was detected in the air inside the warehouse. To identify the cause of the ocular irritation and to determine an appropriate solution to the problem, the authors used thermal desorption gas chromatography-mass spectrometry to analyze the profiles of volatile organic compounds (VOCs) in the air of the two warehouses at the site-warehouse A, where the four workers experienced ocular irritation, and warehouse B, where no workers experienced ocular irritation. Comparing the profiles of VOCs in these warehouses indicated that n-butyl isocyanate, a hydrolyzed product of the fungicide benomyl, was the cause of the workers' ocular irritation. n-Butyl isocyanate is known to be a contact irritant and if the benomyl-coated seeds were not properly dried before storage in the warehouse n-butyl isocyanate would have been produced. The results of the study suggest that more attention should be paid both to the pesticide itself and to the products of pesticide degradation. In this study, n-butyl isocyanate was identified as a product of pesticide degradation and a causative chemical affecting occupational health.

Key Clinical Message We present the successful application of C1 esterase inhibitor (C1INH) concentrate to a patient with clinical amniotic fluid embolism (AFE).

We demonstrate that the cytotoxicity of dansylated polytheonamide mimic ( 2 ) is controlled by chemical modification of its N-terminal structure. Dansylated polytheonamide mimic ( 2 ) is an ion channel peptide which displays potent cytotoxicity against P388 mouse leukemia cells (IC 50 = 12 nM). To modulate its cytotoxicity, three analogues of 2 , possessing distinct N-terminal structures with different hydrophobicities, were synthesized and their cytotoxicities were evaluated. This focused structure–activity relationship study unveiled that the cytotoxicity of 2 is enhanced 10-fold by simply changing its N-terminal 5,5-dimethyl-2-oxohexanamide to the more hydrophobic palmitamide. The data obtained here provide new understanding for the functional control of the artificial ion channel peptide 2 .

Cadmium, an environmental pollutant, may act like an estrogen and be a potential risk factor for estrogen-dependent diseases such as breast cancer. We examined the hypothesis that higher dietary cadmium intake is associated with risk of overall and hormone receptor-defined breast cancer in Japanese women, a population with a relatively high cadmium intake. The study was conducted under a case-control design in 405 eligible matched pairs from May 2001 to September 2005 at four hospitals in Nagano Prefecture, Japan. Dietary cadmium intake was estimated using a food frequency questionnaire. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer and its hormone-receptor-defined subtypes were calculated by tertile of dietary cadmium intake. We found no significant association between dietary cadmium and risk of total breast cancer in either crude or multivariable-adjusted analysis. Adjusted ORs for tertiles of cadmium intake were 1.00, 1.19, and 1.23 (95% CI, 0.76-2.00; P for trend=0.39) for whole breast cancer. Further, no significant associations were seen across strata of menopausal status, smoking, and diabetes in multivariable-adjusted models except for adjusted OR for continuous cadmium intake in postmenopausal women. A statistically significant association was found for estrogen receptor-positive (ER+) tumors among postmenopausal women (adjusted OR=1.00, 1.16, and 1.94 [95% CI, 1.04-3.63; P for trend=0.032]). Although the present study found no overall association between dietary cadmium intake and breast cancer risk, higher cadmium intake was associated with increased risk of ER+ breast cancer in postmenopausal women, at least at regular intake levels in Japanese women in the general population. Further studies are needed to confirm this association.

Aim The local expression of two isoenzymes of 11β-hydroxysteroid dehydrogenase, type 1 (11βHSD-1) and type 2 (11βHSD-2), regulates the access of glucocorticoid hormones to their target cells. Reports on the association between the placental expression of 11βHSD and infantile growth are limited. The aim of the present study was to investigate if the placental gene expression of 11βHSD affects infantile growth at 10 months of age. Methods Placentas and umbilical venous cord blood were obtained from 42 singleton cases of cesarean deliveries between 31 and 40 weeks of gestation at Hamamatsu University Hospital between March 2009 and June 2010. The gene expression of both 11βHSD-1 and 11βHSD-2 was measured by quantitative reverse transcription polymerase chain reaction. Adiponectin and leptin levels in umbilical cord blood were measured using enzyme-linked immunoassay. Results 11βHSD-1 and 11βHSD-2 gene expression in human placentas did not correlate with bodyweight or the ponderal index (PI) at 10 months of age, whereas the gene expression of 11βHSD-1, but not 11βHSD-2, correlated with birthweight as well as PI at birth. Adiponectin levels in umbilical cord blood significantly correlated with the placental gene expression of 11βHSD-1 as well as bodyweight and PI at 10 months of age, although no direct correlation was observed between them. Conclusion No direct correlation was observed between the placental gene expression of 11βHSD and infantile growth at 10 months of age. However, the placental gene expression of 11βHSD-1 may be indirectly connected with infantile growth via adiponectin-associated metabolic regulation represented by adiponectin levels in umbilical cord blood.

Aim To examine the relationship between preterm birth and socioeconomic factors, past history, cervical length, cervical interleukin-8, bacterial vaginosis, underlying diseases, use of medication, employment status, sex of the fetus and multiple pregnancy. Methods In a multicenter, prospective, observational study, 1810 Japanese women registering their future delivery were enrolled at 8+0 to 12+6 weeks of gestation. Data on cervical length and delivery were obtained from 1365 pregnant women. Multivariate logistic regression analysis was performed. Results Short cervical length, steroid use, multiple pregnancy and male fetus were risk factors for preterm birth before 34 weeks of gestation. Multiple pregnancy, low educational level, short cervical length and part-timer were risk factors for preterm birth before 37 weeks of gestation. Conclusion Multiple pregnancy and cervical shortening at 20–24 weeks of gestation was a stronger risk factor for preterm birth. Any pregnant woman being part-time employee or low educational level, having a male fetus and requiring steroid treatment should be watched for the development of preterm birth.

Aim The associations among changes in dietary intake, maternal bodyweight, and fetal growth during the course of pregnancy were investigated in a prospective cohort study carried out on 135 Japanese women. Material and Methods Dietary intake was analyzed using digital photos of meals taken over 3 consecutive days, in the first, second and third trimester, and was compared with maternal bodyweight, estimated fetal bodyweight by ultrasound examination, and birthweight. Results Surprisingly, the mean total calorie intake remained below 1600 kcal/day during pregnancy, much lower than the value recommended in the 2010 edition of ‘Dietary Reference Intakes for Japanese’. Dietary intake was similar throughout despite the recommendation of extra intake in late pregnancy. Maternal dietary intake did not correlate with fetal growth, although maternal bodyweight in the second trimester positively correlated with estimated fetal bodyweight in the third trimester. Maternal bodyweight before pregnancy positively correlated with birthweight. Conclusions Maternal bodyweight as well as eating habits established before pregnancy may have a considerable effect on fetal growth. There is an urgent need to improve the diet of Japanese women of child-bearing age, especially during pregnancy.

Rapid growth in infancy considerably increases the risk of obesity and metabolic disorders in adulthood especially among neonates born small. To investigate the mechanism involved, we developed an animal model of undernourishment in utero by maternal caloric restriction, in which the Z scores of body weight at weaning (19.5 days) positively correlated with parameters of obesity, metabolic disorders, and remodeling of subcutaneous adipose tissue, such as numbers of macrophages in adipose tissue, the ratio of inflammatory M1 to anti-inflammatory M2 macrophages, estimated by gene expression of specific antigens, and the relative ratio of small adipocytes less than 30 μm in diameter, on a high-fat diet at 17 weeks of age. To our knowledge, this is the first report of a possible connection between infantile body weight and adipose tissue remodeling in obesity after undernourishment in utero.

Few clinical studies have determined the quantitative transfer of vaginal chloramphenicol to circulating blood in pregnant women. This study aimed to evaluate the plasma concentration of chloramphenicol in pregnant women treated with trans-vaginal tablets and its relationship with maternal background and neonatal health. Thirty-seven pregnant women treated with 100 mg of trans-vaginal chloramphenicol once daily for bacterial vaginosis and its suspected case were enrolled. The plasma concentration of chloramphenicol was determined using liquid chromatography coupled to tandem mass spectrometry at day 2 or later after starting the medication. The correlations between the maternal plasma concentration of chloramphenicol and the background and neonatal health at birth were investigated. Chloramphenicol was detected from all maternal plasma specimens and its concentration ranged from 0.043 to 73.1 ng/mL. The plasma concentration of chloramphenicol declined significantly with the administration period. The plasma concentration of chloramphenicol was lower at the second than the first blood sampling. No correlations were observed between the maternal plasma concentration of chloramphenicol and background such as number of previous births, gestational age at dosing, and clinical laboratory data. Neonatal infant health parameters such as birth-weight, Apgar score at birth, and gestational age at the time of childbearing were not related to the maternal plasma concentration of chloramphenicol. Vaginal chloramphenicol transfers to circulating blood in pregnant women. The maternal plasma concentration of chloramphenicol varied markedly and was associated with the administration day, but not with maternal background or her neonatal health.

Background Whether physical activity reduces the risk of sleep-disordered breathing (SDB) for non-obese people remains unclear. The present cross-sectional study examined the association between physical activity and SDB among non-obese male Japanese workers. Methods All 200 workers in a company in Tokyo, Japan, who drove a motor vehicle as part of their job, were invited to be screened for SDB to prevent traffic accidents. Of these, 195 agreed to participate in this study. The number of apnea and hypopnea episodes occurring during one night was measured using a single-channel airflow monitor to obtain an individual respiratory disturbance index (RDI). SDB was defined as RDI ≥15 apneas/hypopneas/h. Non-obese males (body mass index

Noncommunicable diseases (NCDs) are chronic, noninfectious, and non-transmissible diseases. The World Health Organization (WHO) estimated that 63% of global deaths, approximately 36 million, were attributed to NCDs. The concept of the developmental origins of health and disease (DOHaD) revealed that undernourishment and overnourishment in utero are both causatively associated with the risk of NCDs in later life; a “U-shaped curve” was proposed for the relationship between nutritional conditions in utero and the risk of developing adult NCDs. The DOHaD concept of the “U-shaped curve” is assumed to explain, at least partly, why NCDs are becoming increasingly prevalent in both developing and developed countries because the former is expected to be related to undernourishment in utero and the latter overnourishment in utero. In this chapter, a possibility was discussed that supports the promising future contribution of perinatal and neonatal care to the establishment of “preemptive medicine” against the rapid spread of adult NCDs.

Little is reported regarding economic burden of work-related low back pain except for the United States. In the present study, annual medical cost of work-related low back pain in Japan was calculated based on the treatment fee per day, a total of days of treatment received for low-back pain of all causes, employment rates, and an estimated number of work-related low-back cases. The analysis indicated that, in 2011, the total annual medical cost for work-related low back pain was 82.14 billion yen, consisting of 26.48 and 55.66 billion yen for inpatients and outpatients, respectively. As well as for 2011, the costs were also estimated for 2008, 2005, and 2002. Whereas the total medical costs of work-related low back pain monotonically increased during 2002–2011, the costs for spine disorder (including spondylosis) have also increased in recent years. Work-related low back pain entails a considerable economic burden to Japanese society.

Background Workers in Japan are not sufficiently active; however, it remains unclear how their leisure-time physical activity habits may be developed. This cross-sectional study investigated the relationship of age- and intensity-specific leisure-time physical activity in youth to adulthood leisure-time physical activity habits among Japanese workers. Methods In 2012, 968 workers (333 males and 635 females) from three companies and six hospitals in the Tokai region of Japan agreed to complete and submit a self-administered questionnaire. Intensity-specific leisure-time physical activity at ages 12 and 20 years was assessed retrospectively, and workers’ current participation in regular leisure-time physical activity was assessed as an outcome measure. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis. Results Mean ages for males and females were 40 and 37 years, respectively. Strenuous leisure-time physical activity at age 12 years was significantly positively associated with adulthood participation in leisure-time physical activity among male workers [adjusted OR (95% CI) = 2.29 (1.02, 5.14)]. Additionally, both strenuous and moderate physical activity at age 20 years was significantly positively associated with participation in regular leisure-time physical activity in adulthood among males and females. Conclusions Our results suggest that some leisure-time physical activity in youth may predict adult workers’ participation in regular leisure-time physical activity in Japan. Encouragement of leisure-time physical activity in youth could therefore be an effective measure to develop adult leisure-time physical activity habits among workers.

Liver dysfunction with decreased antithrombin (AT) activity and/or thrombocytopenia is life threatening in pregnant women. Whether AT is clinically useful for prediction of liver dysfunction remains unclear.A total of 541 women were registered prospectively at gestational week 34.7 (20.0-41.4) with available data on antenatal AT and platelet count (PLC).Liver dysfunction defined as serum aspartate aminotransferase 45 IU/L concomitant with lactate dehydrogenase 400 IU/L occurred in five women antenatally (≤ 2 weeks before delivery) and in 17 women post-partum (within 1 week post-partum). Median (5th-95th) antenatal value was 85 (62-110)% for AT and 202 (118-315) × 10Reduced AT not accompanied by thrombocytopenia can precede liver dysfunction. Clinical introduction of AT may enhance the safety of pregnant women.

Assisted reproductive technology (ART) has become widespread, accounting for ∼2% of all births worldwide, with a similar proportion in Japan. Our goal was to determine whether ART is associated with an increased risk of congenital heart defect (CHD). The study subjects were 2716 pregnant women (2317 in a spontaneous conception [SC] group and 399 in an assisted conception [AC] group). Of patients in the AC group, 142 were treated with ovulation-inducing agents (OIAs), 56 with artificial insemination by the husband (AIH), 159 with in vitro fertilization (IVF), and 42 with intracytoplasmic sperm injection (ICSI). CHD screening on the fetus or newborn was performed using two-dimensional echocardiography. Severe CHD was defined as requiring surgical treatment, or leading to death within one year. There were 2746 births (one of 31 twins was a still birth), 410 resulted from AC and within this group, 111 cases of CHD were found (AC group, 17 [4.1%]; SC group, 94 [4.0%]). Five cases of severe CHD were found in the AC group and 19 in the SC group, with no significant difference between the groups (p = 0.892). In conclusion, there was no evidence of increased CHD risk associated with ART treatment.

Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. The prevalence of NAFLD in Japan has nearly doubled in the last 10-15 years. Increasing evidence supports undernourishment in utero being causatively connected with the risk of NAFLD in later life. Low body mass index (BMI) has been common among Japanese women of childbearing age for several decades due to their strong desire to be thin. It is plausible that insufficient maternal energy intake by pregnant Japanese women may underlie the rapid increase in the prevalence of NAFLD in Japan. In order to clarify the mechanisms by which undernourishment in utero primes adult hepatic steatosis, we developed a mouse model of fetal undernourishment with a hepatic fat deposit-prone phenotype on an obesogenic high fat diet in later life. We found that endoplasmic reticulum (ER) stress response parameters were activated concomitantly with the deterioration of hepatic steatosis and also that the alleviation of ER stress with the chemical chaperone, tauroursodeoxycholic acid (TUDCA), significantly improved hepatic steatosis. Therefore, undernourishment in utero may program the future integration of ER stress in the liver on an obesogenic diet in later life and also induce the deterioration of hepatic steatosis. These results also provide an insight into interventions for the potential high-risk population of NAFLD, such as those born small or exposed to maternal undernourishment during the fetal period, with the alleviation of ER stress by dietary supplements and/or specific food including chaperones.

Oxygen saturation during the term of delivery to the first cry, when fetal circulation dynamically changes, has not yet been examined. The aim of this study was therefore to determine whether the continuous measurement of regional tissue oxygen saturation (rSOOxygen saturation levels in fetal cranial tissue between the second stage of delivery to crowning and up to 5 min after delivery were measured using fetal tissue oximetry with a sensor attached to the examiner's finger. Thirty-five deliveries were examined, and oxygen saturation was measured in seven infants from delivery of the head until 5 min after birth. Umbilical cord blood gas was measured in all cases. This clinical test was performed under the permission of the Ethics Committee of Hamamatsu University School of Medicine.Average tissue oxygen saturation in the second stage of delivery and at 5 min after delivery were 50.3 ± 16.3% and 56.8 ± 8.46%, respectively. In cases of continuous measurement, average rSOWe herein successfully measured oxygen saturation levels in fetal cranial tissue during crowning, delivery of the head, the first cry, and 5 min after delivery using fetal tissue oximetry with a sensor attached to the examiner's finger.

We investigated the potential relationship between maternal depressive symptoms during the postpartum period and non-verbal communication skills of infants at 14 months of age in a birth cohort study of 951 infants and assessed what factors may influence this association. Maternal depressive symptoms were measured using the Edinburgh Postnatal Depression Scale, and non-verbal communication skills were measured using the MacArthur-Bates Communicative Development Inventories, which include Early Gestures and Later Gestures domains. Infants whose mothers had a high level of depressive symptoms (13+ points) during both the first month postpartum and at 10 weeks were approximately 0.5 standard deviations below normal in Early Gestures scores and 0.5-0.7 standard deviations below normal in Later Gestures scores. These associations were independent of potential explanations, such as maternal depression/anxiety prior to birth, breastfeeding practices, and recent depressive symptoms among mothers. These findings indicate that infants whose mothers have postpartum depressive symptoms may be at increased risk of experiencing delay in non-verbal development.

Yaku'amide B is a highly unsaturated linear tridecapeptide and an extremely potent cytotoxin. Herein, we describe the synthesis of fourteen new stereoisomers of yaku'amide B using a unified assembly strategy. The hydrophobicities and cytotoxicities of these analogues were analyzed, along with those of four previously prepared isomers. Although all of the analogues share a common planar structure, their log D values varied significantly (3.39–5.32), presumably reflecting their distinct three-dimensional shapes. Subnanomolar-level cytotoxicity was observed for the natural yaku'amide B and its epimer of the N-terminal acyl group, whereas the other sixteen isomers exhibited 13- to 1200-fold weaker activities than that of the natural isomer. These data indicated the importance of the overall stereostructure of the 13-mer sequence of yaku'amide B for exerting its potent toxicity.

To elucidate the socioeconomic factors influencing lead exposure in elementary school children by gender, 108 children (56 male, 52 female), aged 6–7 years, were randomly selected from 39 elementary state schools in Serpong, Banten, Indonesia. Their parents were interviewed to obtain information on sociodemographic characteristics. Their blood lead (BPb) levels were measured by atomic absorption spectrophotometry. BPb concentrations were significantly higher in males than in females, i.e., 6.8 ± 2.0 (2.9–12.5) µg/dL and 5.9 ± 1.9 (3.1–11.7) µg/dL, respectively (p < 0.05). Lower socioeconomic status and well water use were associated with increased BPb concentrations, especially in females. The proportion of well water use was related to lower socioeconomic status. Lower socioeconomic status linked with well water drinking seemed to be associated with increased lead exposure in children in Serpong. Their exposure levels possibly varied according to gender differences in behavior. An intervention should be instituted among children in Serpong with BPb concentrations of 10 µg/dL or above.

Background Few studies have investigated the relationship between myocardial tissue Doppler parameters and fetal size adjusted for gestational age and its trend has been controversial. Aims To investigate fetal cardiac function before birth using tissue Doppler imaging (TDI: indicated by the prime symbol (′)) in low-risk term pregnancies by comparing the TDI parameters with gestational age-specific birth weight percentiles and z scores. Study design and measurements Interventricular septum, left and right ventricular myocardial peak early diastolic (E′), late diastolic (A′) and systolic (S′) velocities, E′/A′ ratios, myocardial performance index (MPI′) and umbilical artery pulsatility index were measured within three days before birth in 76 low-risk term pregnancies, including appropriate for gestational age (AGA, n = 50), small for gestational age (SGA, n = 10), and large for gestational age (LGA, n = 16) subjects. Results Myocardial peak velocities showed higher in the LGA and lower in the SGA compared with the AGA group, and All S′ positively correlated with birth weight (r = 0.51–0.57). All z scores of S′ demonstrated a positive correlation with birth weight z score (Spearman r = 0.45–0.53). MPI′ was significantly higher in the SGA and lower in the LGA compared with the AGA group. All MPI′ negatively correlated with birth weight (r = − 0.55 to − 0.65). All z scores of MPI′ showed a negative correlation with birth weight z score (Spearman r = − 0.40 to − 0.56). Conclusions Fetal myocardial peak velocities and MPI′ physiologically changed in proportion to body size adjusted for gestational age in low-risk term pregnancies.

Since Aristotle, people have believed that metaphors and similes express the same type of figurative meaning, despite the fact that they are expressed with different sentence patterns. In contrast, recent psycholinguistic models have suggested that metaphors and similes may promote different comprehension processes. In this study, we investigated the neural substrates involved in the comprehension of metaphor and simile using functional magnetic resonance imaging (fMRI) to evaluate whether simile comprehension differs from metaphor comprehension or not. In the metaphor and simile sentence conditions, higher activation was seen in the left inferior frontal gyrus. This result suggests that the activation in both metaphor and simile conditions indicates similar patterns in the left frontal region. The results also suggest that similes elicit higher levels of activation in the medial frontal region which might be related to inference processes, whereas metaphors elicit more right-sided prefrontal activation which might be related to figurative language comprehension.

Chemical point mutation: Polytheonamide B is a naturally occurring polypeptide containing 48 amino acids. It both displays potent cytotoxicity and acts as a monovalent cation channel in vitro. Chemoselective methods to modify the 44th, N-, and C-terminal residues of the natural product have been developed, and evaluation of the resultant derivatives suggests that the intrinsic activities of the peptide can only be altered by switching its N-terminal substitution.

Objective To develop the immunohistochemistry specific for meconium in the placenta, fetal membrane and umbilical cord. Study design We previously reported the specific presence of zinc coproporphyrin I (ZnCP-I) in human meconium and demonstrated the possible diagnostic use of an elevation in maternal plasma ZnCP-I levels in cases of amniotic fluid embolism. In this study, we developed a new specific monoclonal antibody for ZnCP-I and applied it to the immunostaining of meconium in the placenta, fetal membrane, and umbilical cord. Results Immunoreactivity of ZnCP-I clearly and specifically identified meconium in the placenta, fetal membrane, and umbilical cord. It was especially useful in cases of severe chorioamnionitis to detect meconium in the macrophages surrounded by numerous neutrophils. In more than half of the cases, meconium was detected in clear amniotic fluid at delivery, suggesting previous exposure. Conclusions Immunohistochemical detection of ZnCP-I is a highly sensitive histological diagnosis of meconium.

Although seasonal variation in high-sensitivity C-reactive protein (hsCRP) has been studied cross-sectionally and longitudinally, the results to date have been mixed. Here, to test sea- sonal variation in this compound with regard to within-subject, inter-day variation, we conducted a longitudinal follow-up study with repeated measurements in Japanese workers with low hsCRP. Blood samples were obtained from four male indoor daytime workers, who were aged 32-57 and commuted to offices in Kawasaki City, on six days within 2-wk windows in February and October, 2008. Serum hsCRP was measured using ultrasensitive latex-enhanced immunonephelometry. Among the subjects with detectable levels of hsCRP, individual median serum hsCRP levels were 38-74% higher in October than in February (p=0.03). This study identified the presence of a sea- sonal variation in the serum hsCRP level of Japanese workers with low hsCRP levels.

In daily communication, we often use indirect speech to convey our intention. However, little is known about the brain mechanisms that underlie the comprehension of indirect speech. In this study, we conducted a functional MRI experiment using a scenario reading task to compare the neural activity induced by an indirect reply (a type of indirect speech) and a literal sentence. Participants read a short scenario consisting of three sentences. The first two sentences explained the situation of the protagonists, whereas the third sentence had an indirect, literal, or unconnected meaning. The indirect reply condition primarily activated the bilateral fronto-temporal networks (Brodmann's Areas (BA) 47 and 21) and the dorso-medial prefrontal cortex (dmPFC). In the literal sentence condition, only the left fronto-temporal network (BA 45 and 21) and the dmPFC (posterior region) were activated. In addition, we found greater activation resulting from comprehension of an indirect reply than from literal sentence comprehension in the dmPFC, the left middle frontal area (BA 9), the bilateral inferior frontal area (BA 9/47), and the right middle temporal area (BA 21). Our findings indicate that the right and left fronto-temporal networks play a crucial role in detecting contextual violations, whereas the medial frontal cortex is important for generating inferences to make sense of remarks within a context.

Aim: Primary elective cesarean sections are being carried out in considerable numbers in both developed and developing countries; however, little information is available concerning differences in maternal physiological responses associated with the mode of delivery. The aim of the present study was to compare the changes in the maternal complement and contact systems between delivery by cesarean section and vaginal delivery at term. Methods: Maternal levels of complement 3 (C3), complement 4 (C4) and coagulation factor XII (FXII) were measured during primary elective cesarean (n = 70) and vaginal (n = 140) deliveries. Results: The C3, C4 and FXII levels decreased significantly during delivery by cesarean section and remained low for two hours. By contrast, C3 levels, but not C4 levels, increased temporally during normal term delivery and FXII levels decreased two hours later. Conclusions: The changes in maternal C3, C4 and FXII levels during cesarean section were very different from those during delivery at term, suggesting that the maternal complement and contact systems respond differently.

Clinical guidelines for obstetrical practice were first published by the Japan Society of Obstetrics and Gynecology (JSOG) and the Japan Association of Obstetricians and Gynecologists (JAOG) in 2008, and a revised version was published in 2011. The aims of this publication include the determination of current standard care practices for pregnant women in Japan, the widespread use of standard care practices, the enhancement of safety in obstetrical practice, the reduction in burdens associated with medico-legal and medico-economical problems, and a better understanding between pregnant women and maternity-service providers. These guidelines include a total of 87 Clinical Questions followed by several Answers (CQ&A), a Discussion, a List of References, and some Tables and Figures covering common problems and questions encountered in obstetrical practice. Each answer with a recommendation level of A, B or C has been prepared based principally on 'evidence' or a consensus among Japanese obstetricians in situations where 'evidence' is weak or lacking. Answers with a recommendation level of A or B represent current standard care practices in Japan. All 87 CQ&A are presented herein to promote a better understanding of the current standard care practices for pregnant women in Japan.

Clinical guidelines for obstetrical practice were first published by the Japan Society of Obstetrics and Gynecology (JSOG) and the Japan Association of Obstetricians and Gynecologists (JAOG) in 2008, and a revised version was published in 2011. The aims of this publication include the determination of current standard care practices for pregnant women in Japan, the widespread use of standard care practices, the enhancement of safety in obstetrical practice, the reduction in burdens associated with medico-legal and medico-economical problems, and a better understanding between pregnant women and maternity-service providers. These guidelines include a total of 87 Clinical Questions followed by several Answers (CQ&A), a Discussion, a List of References, and some Tables and Figures covering common problems and questions encountered in obstetrical practice. Each answer with a recommendation level of A, B or C has been prepared based principally on "evidence" or a consensus among Japanese obstetricians in situations where "evidence" is weak or lacking. Answers with a recommendation level of A or B represent current standard care practices in Japan. All 87 CQ&As are presented herein to promote a better understanding of the current standard care practices for pregnant women in Japan.

A 25-year-old gravida two, nulliparous pregnant woman complained of a sudden onset of severe pain in the right lateral abdominal area and went to hospital at 28 weeks and 5 days' gestation. Since cyclic uterine contractions were observed, a diagnosis of preterm labor was made and tocolysis was carried out by the continuous venous infusion of ritodorine. She was transferred to Hamamatsu University Hospital and an emergency cesarean section was carried out due to non-reassuring fetal status. A hemoperitoneum of 850 mL was observed in the peritoneal cavity and an immature male baby weighing 1140 g was born. There was bleeding from a ruptured superficial varicose vein in the right lateral portion of the uterus, which was stopped by compression and the attachment of oxidized cellulose cotton. The clinical management and differential diagnosis were discussed.