Comprehensive Analysis of the Expression and Functions of Pattern Recognition Receptors in Differentiated Cytotrophoblasts Derived from Term Human Placentas.

Pregnant women are exposed to various microbes, some of which can harm the mother and/or fetus and can lead to life-long morbidity and even death. The syncytiotrophoblast (STB) covers the placental villi and comes into direct contact with pathogens contained in the maternal blood and plays a key role in placental host defense. However, the precise mechanisms whereby the STB recognizes and responds to pathogenic microbes remain unclear. In this study, we comprehensively analyzed the expression of functional pattern recognition receptors, which are responsible for tissue defense against pathogens, in a primary STB model differentiated from highly purified human term cytotrophoblasts (CTBs). Screening for mRNA expression and multiplex cytokine/chemokine production demonstrated that differentiated CTBs (dCTBs) predominantly expressed dsRNA receptors, including TLR3, MDA5, and RIG-I. We confirmed that term human placentas also expressed TLR3. Transcriptome analysis revealed common and unique responses of dCTBs to a synthetic dsRNA (polyinosinic-polycytidylic acid) compared with human peripheral mononuclear cells. Moreover, polyinosinic-polycytidylic acid induced the release of type I and type III IFNs (IFN-ß, IFN-λ1, IFN-λ2, IFN-λ3), as well as mRNA expression of IFN-stimulated genes (IFIT1, MX1, and OAS1). dCTBs underwent apoptosis via the mitochondrial pathway in response to dsRNA stimulation. These results suggest that dsRNA receptors expressed on the STB are key players in antiviral defense in the placenta. Elucidation of the underpinnings of these defense processes can help us better understand the pathophysiology of viral infections during pregnancy.

Brain carbon monoxide can suppress the rat micturition reflex through brain γ-aminobutyric acid receptors.

OBJECTIVES: To investigate roles of brain carbon monoxide (CO), an endogenous gasotransmitter, in regulation of the rat micturition reflex. METHODS: In urethane-anesthetized (0.8 g/kg, ip) male rats, evaluation of urodynamic parameters was started 1 h before intracerebroventricular administration of CORM-3 (CO donor) or ZnPP (non-selective inhibitor of heme oxygenase, a CO producing enzyme) and continued for 2 h after the administration. We also investigated effects of centrally pretreated SR95531 (GABAA receptor antagonist) or SCH50911 (GABAB receptor antagonist) on the CORM-3-induced response. RESULTS: CORM-3 significantly prolonged intercontraction intervals (ICIs) without changing maximal voiding pressure (MVP), while ZnPP significantly shortened ICI and reduced single-voided volume and bladder capacity without affecting MVP, post-voided residual volume, or voiding efficiency. The ZnPP-induced ICI shortening was reversed by CORM-3. The CORM-3-induced ICI prolongation was significantly attenuated by centrally pretreated SR95531 or SCH50911, respectively. CONCLUSIONS: Brain CO can suppress the rat micturition reflex through brain γ-aminobutyric acid (GABA) receptors.

Association between maternal cholesterol level during pregnancy and placental weight and birthweight ratio: data from the Japan Environment and Children's Study.

BACKGROUND: Placental weight to birthweight ratio (PW/BW ratio), or its inverse, is used as an indicator of placental efficiency. Past studies have shown an association between an abnormal PW/BW ratio and adverse intrauterine environment, however, no previous studies have examined the effect of abnormal lipid levels during pregnancy on PW/BW ratio. We aimed to evaluate the association between maternal cholesterol levels during pregnancy and placental weight to birthweight ratio (PW/BW ratio). METHODS: This study was a secondary analysis using the data from the Japan Environment and Children's Study (JECS). 81 781 singletons and their mothers were included in the analysis. Maternal serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels during pregnancy were obtained from participants. Associations between maternal lipid levels and placental weight and PW/BW ratio were assessed by regression analysis using restricted cubic splines. RESULTS: Dose-response relationships were observed between maternal lipid level during pregnancy and placental weight and PW/BW ratio. High TC and LDL-C levels were associated with heavy placental weight and high PW/BW ratio, i.e., inappropriately heavy placenta for birthweight. Low HDL-C level was also associated with inappropriately heavy placenta. Low TC and LDL-C levels were associated with low placental weight and low PW/BW ratio, i.e., inappropriately light placenta for birthweight. High HDL-C was not associated with PW/BW ratio. These findings were independent of pre-pregnancy body mass index and gestational weight gain. CONCLUSIONS: Abnormal lipid levels such as elevated TC and LDL-C, and low HDL-C level, during pregnancy were associated with inappropriately heavy placental weight.

Influence of chest/head circumference ratio at birth on obstetric and neonatal outcomes: The Japan environment and children's study.

OBJECTIVES: Some newborns that are not small-for-gestational-age (non-SGA, birthweight ≥10th percentile for a given gestational age) may have pathologic growth restrictions. This study examined the association of adverse obstetric and neonatal outcomes with chest/head circumference ratio at birth in non-SGA and SGA newborns. METHODS: This study was a cross-sectional evaluation of data from a nationwide prospective birth cohort study, the Japan Environment and Children's Study. We analyzed 93 690 non-anomalous singletons born at 34-41 gestational weeks. We defined low, normal, and high chest/head circumference ratio as <10th percentile, 10th-90th percentile, and >90th percentile, respectively, according to the internally constructed chest/head circumference percentile chart. Modified Poisson regression was used to estimate adjusted prevalence ratios (aPR) for the outcomes studied. RESULTS: Compared with non-SGA newborns with a normal ratio, those with a low ratio had an increased occurrence of low birthweight (1.75, 1.58-1.94 [aPR, 95% confidence interval]), cesarean delivery (1.34, 1.29-1.38), Apgar score <7 at 5 min (1.57, 1.14-2.17), respiratory complications (1.20, 1.04-1.39), and prolonged hospitalization (1.36, 1.30-1.42). In contrast, the high-ratio group had a lower rate of low birthweight (0.71, 0.59-0.86), cesarean delivery (0.82, 0.77-0.87), and prolonged hospitalization (0.83, 0.78-0.89). In SGA newborns, a low ratio was associated with increased aPRs for low birthweight, cesarean delivery, hypoglycemia, and prolonged hospitalization, whereas a high ratio showed no such association. CONCLUSIONS: Findings indicate that the chest/head circumference ratio at birth influence obstetric and neonatal outcomes regardless of the birthweight status.

Epidemiology conduction of paediatric rheumatic diseases based on the registry database of the Pediatric Rheumatology Association of Japan.

OBJECTIVES: Although epidemiological surveys of paediatric rheumatic diseases in Japan have been conducted, they were single surveys with no continuity. This is the first report of the Pediatric Rheumatology Association of Japan registry database, which was established to continuously collect data for paediatric rheumatic diseases. METHODS: Pediatric Rheumatology International Collaborate Unit Registry version 2 (PRICUREv2) is a registry database established by the Pediatric Rheumatology Association of Japan. The registry data were analysed for the age of onset, time to diagnosis, sex differences, seasonality, and other factors. RESULTS: Our data showed the same trend regarding rates of paediatric rheumatic diseases reported in Japan and other countries. The age of onset was lower in juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis and higher in systemic lupus erythematosus and Sjögren's syndrome. The time to diagnosis was relatively short in JIA and systemic lupus erythematosus but longer in juvenile dermatomyositis and Sjögren's syndrome. Rheumatoid factor-positive polyarticular JIA showed a seasonality cluster with regard to onset. CONCLUSION: PRICUREv2 aided the retrieval and evaluation of current epidemiological information on patients with paediatric rheumatic diseases. It is expected that the data collection will be continued and will be useful for expanding research in Japan.

Dose-response relationships between maternal urinary cotinine and placental weight and ratio of placental weight to birth weight: The Japan Environment and Children's Study.

INTRODUCTION: Studies on the relationship between maternal self-reported smoking status and placental weight report inconsistent results. This study examined the relationships between maternal urinary cotinine concentration and placental weight and the ratio of placental weight to birth weight (PW/BW ratio). The study also examined the relationship between maternal smoking status, as determined by cotinine concentration, with placental weight and with PW/BW ratio, stratified by sex of offspring. METHODS: Our analysis used information of 91,049 mother-child pairs enrolled in the Japan Environment and Children's Study. Maternal urinary cotinine concentration was quantified (during the second or third trimester) with high-performance liquid chromatography-tandem mass spectrometry. Using restricted cubic splines, placental weight and PW/BW ratio were plotted against natural log-transformed cotinine concentration. Taking cotinine levels of <0.17 ng/mL, 0.17 to <21.5 ng/mL (natural log-transformed values, -1.77 to 3.07), and ≥21.5 ng/mL as indicative of non-smokers, passive smokers, and active smokers, respectively, the relationships between maternal smoking status and placental weight and PW/BW ratio were examined, adjusting for confounders. RESULTS: Placental weight and PW/BW ratio increased with increasing cotinine concentration. After cotinine reached a certain concentration, the placental weight decreased in male offspring whereas it plateaued in female offspring. Compared with not smoking, active smoking during pregnancy significantly increased placental weight and PW/BW ratio. CONCLUSION: Placental weight responded as an inverted U-shape whereas the PW/BW ratio followed a J-shape with increasing maternal urinary cotinine concentration measured during pregnancy, suggesting exposure to tobacco smoke induces a disproportionate reduction in fetal growth. The effect of tobacco smoke on placental growth varied by sex of offspring.

Gestational weight gain mediates the effects of energy intake on birth weight among singleton pregnancies in the Japan Environment and Children's Study.

BACKGROUND: Extra energy intake is commonly recommended for pregnant women to support fetal growth. However, relevant data regarding variations in energy intake and expenditure, body mass index and gestational weight gain (GWG) are frequently not considered. This study aimed to investigate how energy intake during pregnancy and gestational weight gain (GWG) are associated with birth weight. METHODS: Early pregnant women were recruited into a Japanese nationwide prospective birth cohort study between 2011 and 2014. We analysed data of 89,817 mother-child pairs of live-born non-anomalous singletons after excluding births before 28 weeks or after 42 weeks. Energy intake during pregnancy was estimated from self-administered food frequency questionnaires (FFQ) and was stratified into low, medium, and high. Participants completed the FFQ in mid-pregnancy (mean 27.9 weeks) by recalling food consumption at the beginning of pregnancy. Effects of energy intake on birth weight and mediation by GWG were estimated using the Karlson-Holm-Breen method; the method separates the impact of confounding in the comparison of conditional and unconditional parameter estimates in nonlinear probability models. Relative risks and risk differences for abnormal birth size were calculated. RESULTS: Mean daily energy intake, GWG, and birth weight were 1682.1 (533.6) kcal, 10.3 (4.0) kg, and 3032.3 (401.4) g, respectively. 6767 and 9010 women had small-for-gestational-age and large-for-gestational-age infants, respectively. Relative to low energy intake, moderate and high intakes increased adjusted birth weights by 13 g and 24 g, respectively: 58 and 69% of these effects, respectively, were mediated by GWG. Compared with the moderate energy intake group, the low energy intake group had seven more women per 1000 women with a small-for-gestational-age birth, whereas the high energy intake group had eight more women per 1000 women with a large-for-gestational-age birth. CONCLUSION: GWG mediates the effect of energy intake on birth weight. All pregnant women should be given adequate nutritional guidance for optimal GWG and fetal growth.

Development of a parent-reported screening tool for avoidant/restrictive food intake disorder (ARFID): Initial validation and prevalence in 4-7-year-old Japanese children.

The prevalence of avoidant/restrictive food intake disorder (ARFID) in the general child population is still largely unknown and validated screening instruments are lacking. The aims of this study were (1) to investigate the prevalence of children screening positive for ARFID in a Japanese birth cohort using a newly developed parent-reported screening tool, (2) to estimate the prevalence of children with ARFID experiencing physical versus psychosocial consequences of their eating pattern, and (3) to provide preliminary evidence for the validity of the new screening tool. Data were collected from 3728 4-7-year-old children born between 2011 and 2014 in Kochi prefecture, Japan (response rate was 56.5%); a sub-sample of the Japan Environment and Children's Study (JECS). Parents completed a questionnaire including the ARFID screener and several other measures to assess convergent validity. The point prevalence of children screening positive for ARFID was 1.3%; half of them met criteria for ARFID based on psychosocial impairment alone, while the other half met diagnostic criteria relating to physical impairment (and additional psychosocial impairment in many cases). Sensory sensitivity to food characteristics (63%) and/or lack of interest in eating (51%) were the most prevalent drivers of food avoidance. Children screening positive for ARFID were lighter in weight and shorter in height, they showed more problem behaviors related to mealtimes and nutritional intake, and they were more often selective eaters and more responsive to satiety, which together provides preliminary support for the validity of the new screening tool. This is the largest screening study to date of ARFID in children up to 7 years. Future studies should examine the diagnostic validity of the new ARFID screener using clinically ascertained cases. Further research on ARFID prevalence in the general population is needed.

Protease-digested egg-white products induce oral tolerance in mice but elicit little IgE production upon epicutaneous exposure.

BACKGROUND: Early food introduction induces tolerance, but epicutaneous exposure, especially via eczema lesions, promotes IgE sensitization. Aiming for safe and effective primary prevention of egg allergy, we examined several protease-digested egg-white (EW) products for three properties: 1) induction of oral tolerance that prevents IgE sensitization, 2) weak IgE binding that can prevent allergic reactions even in IgE-sensitized mice, and 3) minimal epicutaneous IgE sensitization even when in contact with inflamed skin. METHODS: Heated EW was digested with several proteases under optimal conditions. First, three-week-old BALB/c female mice were intragastrically administered EW or each protease-digested EW product, followed by intraperitoneal ovalbumin (OVA) or ovomucoid (OVM) injection with alum. Serum OVA- and OVM-specific IgE titers were measured. Second, six-week-old mice were sensitized with OVA/OVM, and the rectal temperature was measured after intraperitoneal administration of EW or each protease-digested EW. Third, EW or each protease-digested EW product was applied to the tape-stripped skin for 3 days/week for 3 weeks. Serum OVA- and OVM-specific IgE titers were measured. RESULTS: Orally administered pepsin-digested EW product (PDEW) and Thermoase PC10F-digested EW product (TDEW) significantly suppressed OVA-/OVM-specific IgE production. Neither product elicited a body temperature decline (anaphylaxis) in OVA-/OVM-sensitized mice. Serum OVA-/OVM-specific IgE levels were significantly lower in mice epicutaneously exposed to PDEW or TDEW than in EW-exposed mice. CONCLUSIONS: Two protease-digested EWs showed potential as optimal EW products for early introduction for primary prevention of egg allergy.

Helicobacter pylori protein that binds to and activates platelet specifically reacts with sera of H. pylori-associated chronic immune thrombocytopenia.

Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by antiplatelet antibodies and/or CD8 + T cells, resulting in the destruction of platelets and decreased platelet counts. Helicobacter pylori that persistently colonizes the stomach causes various disorders, including extragastric diseases such as chronic ITP (cITP). Several studies have reported increased platelet counts in H. pylori-infected cITP patients with eradication treatment and also the pathophysiological pathways involving cross-reaction of antibodies against H. pylori with platelets, the modulation of Fcrγ receptors balance and others. We previously reported an immunocomplex pathway comprising H. pylori low-molecular-weight (LMW) antigens, their antibodies, and platelets, involved in the development of H. pylori-associated cITP; however, the LMW antigens were not identified. In the present study, we demonstrated that the H. pylori LMW antigen of the immunocomplex was identified as Lpp20 of outer membrane proteins. Lpp20 could bind to platelets and specifically react with sera of H. pylori-associated cITP patients.

Lack of concern about body image and health during pregnancy linked to excessive gestational weight gain and small-for-gestational-age deliveries: the Japan Environment and Children's Study.

BACKGROUND: Pregnant women in Japan express various reasons for limiting gestational weight gain (GWG). We aimed to identify and characterise groups where the women share common reasons to limit GWG and to examine how these groups are associated with inappropriate GWG and abnormal foetal size. METHODS: We prospectively studied information from the Japan Environment and Children's Study (JECS) on 92,539 women who gave birth to live singletons from 2011 through 2014. Pregnant women were recruited during early pregnancy. Their reasons for limiting GWG and other information were collected through self-reported questionnaires and medical records. We applied latent class analysis to group the women based on their reported reasons. We used multinomial logistic regression to compare the risks of inappropriate (inadequate and excessive) GWG and abnormal foetal size (determined by new-born weight for gestational age) between the identified groups. RESULTS: We identified three groups: Group 1 (76.7%), concerned about delivery and new-born health (health-conscious women); Group 2 (14.5%), concerned about body shape, delivery, and new-born health (body-shape- and health-conscious women); and Group 3 (8.8%), women without strong reasons to limit GWG (women lacking body-shape and health consciousness). Compared with Group 1 members, Group 2 members tended to be younger, have lower pre-pregnancy weight, be unmarried, be nulliparous, have practiced weight loss before pregnancy, and not have chronic medical conditions. Group 3 members tended to be less educated, unmarried, multiparous, smokers, and have a higher prevalence of pre-pregnancy underweight and previous caesarean delivery. Relative to Group 1, Group 2 had a lower unadjusted risk for inadequate GWG (relative risk ratio [RRR] = 0.86, 95% CI: 0.81-0.90) and large-for-gestational-age birth (RRR = 0.91, 95% CI 0.86-0.97), whereas Group 3 had a higher unadjusted risk for excessive GWG (RRR = 1.36, 95% CI: 1.29-1.43) and small-for-gestational-age (SGA) births (RRR = 1.15, 95% CI: 1.05-1.25). CONCLUSIONS: In this Japanese nationwide birth cohort study, pregnant women who were less conscious about body shape and health had complex risks for excessive GWG and SGA birth. Health care providers should consider a woman's perception of GWG when addressing factors affecting GWG and foetal growth.

Brain hydrogen sulfide suppresses the micturition reflex via brain GABA receptors in rats.

We recently reported that hydrogen sulfide (H2S) is a possible relaxation factor in the rat bladder. However, there is no available information about the roles of central H2S in the micturition reflex, so we investigated the effects of centrally administered GYY4137 (H2S donor) and AOAA (H2S synthesis inhibitor) on the micturition reflex in urethane-anesthetized (0.8 g/kg, ip) male Wistar rats. Cystometry was performed before and after the administration of GYY4137 (3 or 10 nmol/rat, icv) or AOAA (30 or 100 µg/rat, icv). In some rats, SR95531 (GABAA receptor antagonist, 0.1 nmol/rat, icv) or SCH50911 (GABAB receptor antagonist, 0.1 nmol/rat, icv) was administered 30 min before GYY4137 administration (10 nmol/rat, icv). Centrally administered GYY4137 dose-dependently prolonged the intercontraction intervals (ICI) without altering maximum voiding pressure (MVP). On the other hand, centrally administered AOAA dose-dependently shortened ICI without altering MVP. The AOAA (30 µg/rat, icv)-induced ICI shortening was reversed in the central presence of GYY4137 (10 nmol/rat, icv). Centrally pretreated SR95531 or SCH50911 significantly attenuated the GYY4137 (10 nmol/rat, icv)-induced prolongation of ICI, respectively. These findings suggest that endogenous brain H2S can inhibit the rat micturition reflex via both GABAA and GABAB receptors in the brain.

Effects of silodosin and tadalafil on bladder dysfunction in spontaneously hypertensive rats: Possible role of bladder blood flow.

OBJECTIVES: To investigate the effects of an alpha1-adrenoceptor antagonist, silodosin, or a phosphodiesterase type 5 inhibitor, tadalafil, on bladder overactivity in spontaneously hypertensive rats. METHODS: Twelve-week-old male spontaneously hypertensive rats were perorally administered silodosin (100 µg/kg), tadalafil (2 or 10 mg/kg) or vehicle once daily for 6 weeks. Wistar rats were used as normotensive controls and were treated with the vehicle. At 18-weeks-old, the effects of silodosin or tadalafil on blood pressure, bladder blood flow, urodynamic parameters (i.e. micturition frequency, urine output, inter-contraction interval, maximum voiding pressure, single voided volume and post-voiding residual urine volume), and bladder tissue levels of malondialdehyde, interleukin-6 and tumor necrosis factor-alpha were measured. RESULTS: A significant increase in blood pressure, micturition frequency and bladder tissue levels of malondialdehyde, interleukin-6 and tumor necrosis factor-alpha was noted in spontaneously hypertensive rats. The single voided volume, bladder capacity and bladder blood flow were significantly lower in the spontaneously hypertensive rats than in the Wistar rats. Treatment with silodosin and the higher dose of tadalafil improved the urodynamic parameters, bladder blood flow and bladder tissue levels of malondialdehyde in the spontaneously hypertensive rats without affecting the blood pressure and bladder tissue levels of interleukin-6 and tumor necrosis factor-alpha. CONCLUSIONS: Treatment with silodosin or tadalafil might improve hypertension-related bladder overactivity, as shown in spontaneously hypertensive rats through an improvement in the bladder blood flow and bladder tissue levels of oxidative stress.

Severity of Nausea and Vomiting in Singleton and Twin Pregnancies in Relation to Fetal Sex: The Japan Environment and Children's Study (JECS).

BACKGROUND: Some studies have indicated that female birth and multiple births were risk factors for nausea and vomiting during pregnancy (NVP). The results, however, were conflicting. Our study was conducted to evaluate the association of maternal NVP with fetal sex in singleton and twin pregnancies. METHODS: We used the data set from a birth cohort study, the Japan Environment and Children's Study (JECS). In the self-administered questionnaire, participants were asked whether they experienced NVP prior to 12 gestational weeks. Main outcome measures were the presence of NVP and severity of NVP. We estimated the association of fetal sex and birth plurality with NVP using logistic regression analysis, followed by interaction analysis. RESULTS: Of 91,666 women, 75,828 (82.7%) experienced at least some symptoms of NVP and 10,159 (11.1%) experienced severe NVP. Women with female pregnancies and twin pregnancies had higher odds for the presence of NVP and severe NVP compared to women with male pregnancies and singleton pregnancies, respectively. Moreover, of mothers with twin pregnancies, higher odds for the presence of NVP and severe NVP were reported when one or both infants were female, compared to those in which both infants were male. There was no significant interaction between fetal sex and birth plurality. CONCLUSIONS: Female sex birth and multiple births are risk factors for the presence of NVP, and especially for severe NVP without interaction. These findings suggest that a factor abundant in the female fetus associates with the severity of NVP.

Magnetocardiographic recognition of abnormal depolarization and repolarization in patients with coronary artery lesions caused by Kawasaki disease.

Myocardial ischemia changes the electrophysiological properties of the myocardium, but it is difficult to detect the abnormalities of depolarization and repolarization noninvasively in patients with coronary artery disease. Depolarization and repolarization abnormalities were retrospectively investigated in 61 patients (48 males and 13 females) with coronary artery lesions (CALs) caused by Kawasaki disease (KD) from 2007 to 2014 using magnetocardiography (MCG). CAL had been diagnosed by selective coronary angiography. Current arrow maps (CAMs) were constructed during depolarization and repolarization [corrected]. The MCG findings were compared between the stenotic lesions group (SL group) and the non-stenotic lesions group (non-SL group). The incidence of MCG abnormalities was significantly higher in the SL group than in the non-SL group (p < 0.0001). The incidence of abnormal repolarization was significantly higher than that of abnormal depolarization (p < 0.0001). The number of coronary artery occlusions significantly affected the severity of abnormal repolarization (p = 0.02). Six (75%) of the patients with abnormal depolarization had a previous anteroseptal myocardial infarction. The transmural myocardial infarction affects on abnormalities of depolarization, and the non-transmural myocardial infarction might relate on abnormalities of repolarization. The myocardial electrical properties were preserved in patients except very severe coronary stenosis. MCG is possible to detect electrical myocardial abnormalities noninvasively in patients with CALs caused by KD.

Correction to: Magnetocardiographic recognition of abnormal depolarization and repolarization in patients with coronary artery lesions caused by Kawasaki disease.

In the original publication of the article, the sentence "The integral value was computed for each channel, and isointegral maps were constructed during depolarization and repolarization." was published incorrectly under the abstract section.

Common carotid arteritis and polymyalgia with Mycoplasma pneumoniae infection.

A few pediatric cases with brain vasculitis most frequently affecting the middle cerebral artery have been reported in association with Mycoplasma pneumoniae infection, but involvement of the common carotid artery (CCA) before the bifurcation has not been reported to date. We report herein a case of 10-year-old boy with common carotid arteritis and polymyalgia associated with Mycoplasma pneumoniae infection. His fever and cough began 2 weeks before, and his right upper and lower extremity pains began 2 days before admission. He had initially been treated with clarithromycin followed by tosufloxacin, but his symptoms persisted. His M. pneumonia-specific antibody titer was high on admission (1:10240 by particle agglutination method) and the gene of M. pneumoniae was detected in a throat swab specimen by the loop-mediated isothermal amplification method with initial high levels of serum interleukin-8, tumor necrosis factor-α, and interleukin-18 along with elevated blood levels of complements. On the 5th day of hospitalization, vascular echograms of the extremities and neck showed increasing intima-media thickness of bilateral CCAs without stenosis and/or thrombosis and T2-weighted with lipid suppression magnetic resonance imaging of the neck showed high signal intensity of bilateral CCA walls. Coagulation studies were unremarkable and no autoantibodies were detected as far as tested. He was successfully treated by intravenous administration of prednisolone and was stable without any neurological sequelae 17 months after the onset without medication. His particle agglutination titer decreased to 1:5120, and serum interleukin-8, tumor necrosis factor-α, interleukin-18, and complement levels returned to normal.

Nausea and vomiting during pregnancy associated with lower incidence of preterm births: the Japan Environment and Children's Study (JECS).

BACKGROUND: Nausea and vomiting during pregnancy (NVP) is considered to be associated with favorable fetal outcomes, such as a decreased risk for spontaneous abortion. However, the relationship between NVP and preterm births remains unknown. This study was conducted to evaluate the association between NVP and the risk of preterm births. METHODS: The dataset of a birth cohort study, the Japan Environment and Children's Study (JECS), was retrospectively reviewed. Participants' experience of NVP prior to 12 gestational weeks were evaluated by a questionnaire administered from 22 weeks of pregnancy to 1 month before delivery. NVP responses were elicited against four choices based on which the study population was divided into four subcohorts. Preterm birth was the main study outcome. Logistic regression analysis was used to quantify an association between NVP and risk of preterm birth. RESULTS: Of 96,056 women, 79,460 (82.7%) experienced some symptoms of NVP and 10,518 (10.9%) experienced severe NVP. Compared to those who did not experience NVP, women with severe NVP had lower odds for preterm birth [adjusted odds ratio (aOR) 0.84, 95% confidence interval (95% CI) 0.74-0.95]. An even lower OR was found among very preterm birth and extremely preterm birth (aOR 0.44, 95% CI 0.29-0.65). CONCLUSION: An inverse association exists between NVP and preterm births, especially, very preterm births and extremely preterm births.

The true distribution volume and bioavailability of mizoribine in children with chronic kidney disease.

BACKGROUND: Mizoribine (MZR) is used kidney transplant and various kidney diseases. However, few studies reported the association between pharmacokinetics and pharmacodynamics. The Pharmacokinetics Study Group for Pediatric Kidney Disease (PSPKD) used population pharmacokinetics (PPK) analysis and Bayesian analysis to investigate the usefulness of MZR. In this study, the fact that almost all MZR are excreted unchanged in urine was used to calculate its bioavailability (F) and true distribution volume (V d), and analyzed these correlation with age. METHODS: Ishida et al. reported a PPK analysis by the PSPKD. In the present study, 71 samples extracted from their study population of 105 pediatric chronic kidney disease patients aged between 1 and 20 years were investigated. The bioavailability was calculated by measuring total excreted MZR in 24 h urine samples, and this was compared to the oral dosage. The apparent distribution volume (V d/F) obtained from Bayesian analysis was then used to calculate true distribution volume (V d), and the correlation of each parameter with age was investigated. RESULTS: The median dose of MZR per weight was 5.17 mg/kg/day. Median bioavailability was 32.02%. Median V d per weight was 0.46 L/kg. There was a significant, weakly positive correlation between bioavailability and age (p = 0.026). There was also a significant, weakly negative correlation between V d per weight and age (p = 0.003). CONCLUSION: Bioavailability and V d per weight tended to decrease depending on age. The younger patient required larger dose required to obtain the maximum effect from MZR, and this is important for immunosuppressive therapy.