Relationship between Birth Order and Postnatal Growth until 4 Years of Age: The Japan Environment and Children's Study.

Later-borns tend to be shorter than first-borns in childhood and adulthood. However, large-scale prospective studies examining growth during infancy according to birth order are limited. We aimed to investigate the relationship between birth order and growth during the first 4 years of life in a Japanese prospective birth cohort study. A total of 26,249 full-term singleton births were targeted. General linear and multivariable logistic regression models were performed and adjusted for birth weight, parents' heights, maternal age at delivery, gestational weight gain, maternal smoking and alcohol drinking status during pregnancy, household income, breastfeeding status, and Study Areas. The multivariate adjusted mean length Z-scores in "first-borns having no sibling", "first-borns having siblings", "second-borns", and "third-borns or more" were -0.026, -0.013, 0.136, and 0.120 at birth and -0.324, -0.330, -0.466, and -0.569 at 10 months, respectively. Results similar to those at 10 months were observed at 1.5, 3, and 4 years. The adjusted odds ratios (95% confidence intervals) of short stature at 4 years in "first-borns having siblings", "second-borns", and "third-borns or more" were 1.08 (0.84-1.39), 1.36 (1.13-1.62), and 1.50 (1.20-1.88), respectively, versus "first-borns having no sibling". Birth order was significantly associated with postnatal growth and may be a factor predisposing to short stature in early childhood.

Adverse pregnancy outcomes of cancer survivors and infectious disease in their infants: The Japan Environment and Children's Study.

Birth cohort studies examining pregnancy and infant outcomes among adolescent and young adult (AYA) cancer survivors have been limited. The present study examined whether AYA cancer affects pregnancy outcomes of survivors and infectious diseases in their infants up to 1 year of age. Pregnant women were recruited for the Japan Environment and Children's Study, a nationwide, large-scale, prospective cohort study. The present study included 103,060 pregnant women and collected questionnaire-based data during the first and second/third trimester, and at 1 month, 6 months and 1 year after delivery. Adverse pregnancy outcomes and infectious diseases in infants up to 1 year of age were compared between AYA cancer survivors and pregnant women without a history of cancer using binominal logistic regression analyses and a multiple imputation method. Of 99,816 participants (3,244 were missing), 1,102 (1.1%) had a cancer history, including 812 participants (0.8%) with a history of cervical cancer. Among cervical cancer survivors, the adjusted (a)ORs were as follows: 3.25 (95% CI, 2.31-4.57; q=0.00) for a preterm birth <34 weeks' gestation; 2.82 (95% CI, 2.31-3.44; q=0.00) for a preterm birth <37 weeks' gestation; and 1.67 (95% CI, 1.36-2.06; q=0.00) for premature rupture of the membrane. Among the other cancer survivors, the aOR for caesarean section was 1.43 (95% CI, 1.10-1.87; q=0.0). Furthermore, lower respiratory tract inflammation in 1-year-old infants born by vaginal delivery increased significantly in cases with a history of cervical cancer (aOR, 1.77; 95% CI, 1.33-2.36; q=0.00). The present study identified the risk of lower respiratory tract inflammation in 1-year-old infants born by vaginal delivery in cervical cancer survivors for the first time. In addition, the frequency of caesarean section increased in all cancer survivors. No risk of congenital anomalies or other infections were found in the total group of cancer survivors.

Relationship Between Fasting Blood Glucose Levels in Middle Age and Cognitive Function in Later Life: The Aichi Workers' Cohort Study.

BACKGROUND: There is limited evidence regarding the relationship between Diabetes mellitus (DM) in middle age and mild cognitive impairment after a follow-up. Therefore, we investigated the relationship between fasting blood glucose (FBG) levels in middle age and cognitive function assessed using the Japanese version of the Montreal Cognitive Assessment (MoCA-J) in later life, following over 15 years of follow-up in the Aichi Workers' Cohort Study in Japan. METHODS: Participants were 253 former local government employees aged 60-79 years in 2018 who participated in a baseline survey conducted in 2002. Using baseline FBG levels and self-reported history, participants were classified into the normal, impaired fasting glucose (IFG) and, and DM groups. Total MoCA-J score ranges from 0 to 30, and cognitive impairment was defined as MoCA-J score ≤25 in this study. A general linear model was used to estimate the mean MoCA-J scores in the FBG groups, adjusted for age, sex, educational year, smoking status, alcohol consumption, physical activity, body mass index, systolic blood pressure, total cholesterol, and estimated glomerular filtration rate. RESULTS: The mean MoCA-J score in the total population was 25.0, and the prevalence of MoCA-J score ≤25 was 49.0%. Multivariable-adjusted total MoCA-J scores were 25.2, 24.8, and 23.4 in the normal, IFG, and DM groups, respectively. The odds ratio of MoCA-J score ≤25 in the DM group was 3.29. CONCLUSION: FBG level in middle age was negatively associated with total MoCA-J scores assessed later in life, independent of confounding variables.

Quantitative Measurement of Phthalate Exposure Biomarker Levels in Diaper-Extracted Urine of Japanese Toddlers and Cumulative Risk Assessment: An Adjunct Study of JECS Birth Cohort.

Phthalate exposure monitoring and risk assessment in non-toilet-trained children are rarely reported. This adjunct study of the Japan Environment and Children's Study assessed cumulative health risks in 1.5-year-old toddlers in the Aichi regional subcohort by biomonitoring 16 urinary metabolites of eight phthalate plasticizers. Overnight urine was extracted from toddlers' diapers (n = 1077), and metabolites were quantified using ultraperformance liquid chromatography coupled with tandem mass spectrometry. The analyses' quality was assured by running quality control samples. The highest geometric mean concentration was found for mono-(2-ethyl-5-carboxypentyl) phthalate, followed by mono-isobutyl phthalate (23 and 21 µg/L, respectively). Di-2-ethylhexyl phthalate (DEHP) and di-butyl phthalate exhibited higher risks [hazard quotient (HQ) > 1] than the cutoff level in a small proportion of toddlers; 8 and 14% of toddlers were at cumulative risk of multiple phthalates beyond the cutoff level [hazard index, (HI) > 1], based on the tolerable daily intake of the European Food Safety Authority and the United States Environmental Protection Agency Reference Dose. HI > 1 for antiandrogenicity in creatinine-unadjusted and -adjusted estimations were exhibited by 36 and 23% of the children, respectively. Thus, identifying exposure sources and mitigating exposure are necessary for risk management. Additionally, continuous exposure assessment and evaluation of health outcomes, especially antiandrogenic effects, are warranted.

Epidemiological Studies of Children's Gut Microbiota: Validation of Sample Collection and Storage Methods and Microbiota Analysis of Toddlers' Feces Collected from Diapers.

The composition of human gut microbiota influences human health and disease over the long term. Since the flora in specimens can easily change at ambient temperature outside the body, epidemiological studies need feasible methods of stool specimen collection and storage to be established. We aimed to validate two methods: feces frozen-stored in tubes containing guanidine thiocyanate solution for two months after collection (Method B), and feces excreted in diapers and frozen-stored (Method C). Validation was by comparison with a gold standard Method A. Bacterial flora of five adults were sampled and stored by all three methods. Bacterial composition was examined by amplicon sequencing analysis. Bland-Altman analyses showed that Methods B and C might change relative abundances of certain bacterial flora. Thereafter, we analyzed the bacterial flora of 76 toddlers (two age groups) in stools sampled and processed by Method C. The diversity indices of toddlers' flora were less than those of adults. The relative abundance of some bacteria differed significantly between children aged 1.5 and 3 years. The specimen collection and storage methods validated in this study are worth adopting in large-scale epidemiological studies, especially for small children, provided the limited accuracy for some specific bacteria is understood.

High Maternal Total Cholesterol Is Associated With No-Catch-up Growth in Full-Term SGA Infants: The Japan Environment and Children's Study.

Objectives: Infants born small for gestational age (SGA) with no catch-up growth (No-CU) are at high risk of intellectual and developmental disabilities. However, factors leading to No-CU among SGA infants are unclear. This study aimed to examine the association between maternal total cholesterol (TC) in mid-pregnancy and No-CU at 3 years among full-term SGA infants. Study Design: The Japan Environment and Children's Study (JECS) is a nationwide prospective birth cohort study. We extracted a total of 2,222 mothers and full-term SGA infants (length and/or weight <-2 standard deviation [SD]) without congenital abnormalities from the original JECS cohort comprising a total of 104,062 fetal records. According to the distribution of maternal TC in the entire cohort, participants were classified into nine groups per each fifth percentile with the 20th-79th percentiles (204-260 mg/dl) as the reference group. No-CU was defined by a Z-score of height at 3 years <-2 SD according to the growth standard charts for Japanese children. Multivariable-adjusted logistic regression models were carried out using multiple imputations. Additionally, a multiple-adjusted restricted cubic spline model was performed in the complete dataset. Results: A total of 362 (16.3%) children were No-CU at 3 years. After adjusting for the Z-score of birth weight, age of mother, smoking status, weight gain during pregnancy, breastfeeding and meal frequency at 2 years, and parents' heights, the odds ratio (95% confidence intervals) of No-CU was 2.95 (1.28-6.80) for children whose maternal TC levels were in the highest category (≥294 mg/dl), compared to the reference group. A multiple-adjusted restricted cubic spline model showed a non-linear trend of the significant association between high maternal TC and No-CU (p for linear trend = 0.05, p for quadratic trend <0.05). Conclusion: High maternal TC at mid-pregnancy was associated with No-CU among SGA infants. Such infants should be carefully followed up to introduce appropriate growth hormonal treatment. The findings may support previous animal experimental studies which indicated that maternal high-fat diet exposure induces impairment of growth and skeletal muscle development in the offspring. Future studies are required to elucidate the detailed mechanism.

Depression symptoms during pregnancy and postpartum in patients with recurrent pregnancy loss and infertility: The Japan environment and children's study.

There are a limited number of studies in which the depression status was followed up throughout pregnancy and postpartum to 1 year after delivery though 8.6-33% of women with recurrent pregnancy loss (RPL) and 10-25% of women who undergo in vitro fertilization and embryo transfer (IVF-ET) suffer from depression. We examined whether RPL and IVF-ET affect depressive symptoms during pregnancy and postpartum. A nationwide large-scale birth cohort study known as the "Japan Environment and Children's Study (JECS)" was conducted. The subjects consisted of 99,202 pregnant women recruited between January 2011 and March 2014. The Kessler Psychological Distress Scale was used for the 1st trimester, 2nd/3rd trimester and 1 year postpartum. The Edinburgh Postnatal Depression Scale was used for the first and the sixth month postpartum. The screening instruments were used to quantify depressive symptoms. Women with no live births had a significantly higher prevalence of elevated depressive symptoms throughout pregnancy and postpartum. The prevalence of elevated depressive symptoms was significantly higher in the second/third trimester among women with three or more pregnancy losses with no live births. IVF-ET was associated with reduced risk of developing depressive symptoms during all pregnancies and at 1 and 6 months after delivery in women with no live births. RPL and IVF-ET did not affect postpartum depressive symptoms, and IVF-ET rather reduced the risk of depression throughout pregnancy and postpartum. Psychological support for RPL women would be necessary.

Simultaneous quantification of pyrethroid metabolites in urine of non-toilet-trained children in Japan.

BACKGROUND: Pyrethroid (PYR) insecticides are widely used for controlling various pests. There are two types that differ in terms of usage: agricultural-purpose PYR (agriculture-PYR) and hygiene purpose PYR (hygiene-PYRs). Few studies exist on the exposure to these chemicals in small children. In this study, we conducted biomonitoring of urinary pyrethroid metabolites in 1.5-year-old children throughout the year. METHODS: Study subjects were 1075 children participating in an Aichi regional sub-cohort of the Japan Environment and Children's Study as of 18-month health check-up. The concentrations of four specific hygiene-PYR metabolites including 2,3,5,6-tetrafluoro-1,4-benzenedimethanol (HOCH2-FB-Al), and five common metabolites of hygiene- and agriculture-PYRs including 3-phenoxybenzoic acid (3PBA) and cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (DCCA), were measured in urine samples extracted from soiled diapers using a triple quadrupole gas chromatograph-mass spectrometer. RESULTS: The highest detection frequencies were for 3PBA, followed by DCCA, 1R-trans-chrysanthemum dicarboxylic acid, and HOCH2-FB-Al. Among the six metabolites, urinary concentrations were seasonally varied. However, this variation was not observed in the most studied PYR metabolite, 3PBA. Spearman's correlation analysis demonstrated a significant positive correlation between FB-Al and DCCA (r = 0.56) and HOCH2-FB-Al and 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol (r = 0.60). CONCLUSIONS: This biomonitoring survey found widespread and seasonally specific exposure to multiple hygiene- and agriculture-PYRs in 1.5-year-old Japanese children.

Repeated maternal non-responsiveness to baby's crying during postpartum and infant neuropsychological development: The Japan Environment and Children's Study.

BACKGROUND: Longitudinal adverse effects of neglect-related behaviors during postpartum, especially repeated maternal non-responsiveness to the crying baby on their neuropsychological developmental trajectory, have not been fully clarified. OBJECTIVE: This study aimed to examine the association between postpartum maternal neglect-related behaviors and infant neuropsychological outcomes using the Japan Environment and Children's Study (JECS). PARTICIPANTS AND SETTING: JECS data on 100,286 mother-child pairs were analyzed. Explanatory variables were "frequency of leaving the baby alone at home" (i.e., leaving the baby alone at home) and "frequency of ignoring the baby when he or she cries" (i.e., ignoring the crying baby) at one month postpartum. The outcomes were measured using the Japanese version of the Ages & Stages Questionnaires-Third Edition (J-ASQ-3). METHODS: After multiple imputations, logistic regression analysis was performed to evaluate the association between neglect-related behaviors and the J-ASQ-3 domains at each age. RESULTS: The "sometimes or more" group of "ignoring the crying baby" from six months to three years reported relatively consistent significant associations with developmental delay in communication (maximum adjusted odds ratio [aOR]: 1.456, 95% confidence interval [CI]: 1.261-1.682), gross motor (maximum aOR: 1.279, 95% CI: 1.159-1.411), fine motor (maximum aOR: 1.274, 95% CI: 1.113-1.457), problem-solving (maximum aOR: 1.178, 95% CI: 1.104-1.256), and personal-social domains (maximum aOR: 1.326, 95% CI: 1.255-1.402). The adverse effects of "leaving the baby alone at home" disappeared in many domains by the age of one. CONCLUSIONS: Repeated maternal non-responsiveness to baby's crying during postpartum may suppress multiple neuropsychological development during early childhood.

Association of Maternal Total Cholesterol With SGA or LGA Birth at Term: the Japan Environment and Children's Study.

CONTEXT: Maternal cholesterol is important for fetal development. Whether maternal serum total cholesterol (maternal TC) levels in midpregnancy are associated with small (SGA) or large (LGA) for gestational age independent of prepregnancy body mass index (BMI) and weight gain during pregnancy is inconclusive. OBJECTIVE: This work aimed to prospectively investigate the association between maternal TC in midpregnancy and SGA or LGA. METHODS: The Japan Environment and Children's Study is a nationwide prospective birth cohort study in Japan. Participants in this study included 37 449 nondiabetic, nonhypertensive mothers with singleton birth at term without congenital abnormalities. Birth weight for gestational age less than the 10th percentile and greater than or equal to the 90th percentile were respectively defined as SGA and LGA by the Japanese neonatal anthropometric charts. RESULTS: The mean gestational age at blood sampling was 22.7 ±â€…4.0 weeks. After adjustment for maternal age, sex of child, parity, weight gain during pregnancy, prepregnancy BMI, smoking, alcohol drinking, blood glucose levels, household income, and study areas, 1-SD decrement of maternal TC was linearly associated with SGA (odds ratio [OR]: 1.20; 95% CI, 1.15-1.25). In contrast, 1-SD increment of maternal TC was linearly associated with LGA (OR: 1.13; 95% CI, 1.09-1.16). Associations did not differ according to prepregnancy BMI and gestational weight gain (P for interaction > .20). CONCLUSION: Maternal TC levels in midpregnancy were associated with SGA or LGA in a Japanese cohort. It may help to predict SGA and LGA. Favorable maternal lipid profiles for fetal development must be explored.

Risk and population attributable fraction of metabolic syndrome and impaired fasting glucose for the incidence of type 2 diabetes mellitus among middle-aged Japanese individuals: Aichi Worker's Cohort Study.

AIMS/INTRODUCTION: The Japanese government started a nationwide screening program for metabolic syndrome (MetS) to prevent cardiovascular diseases and diabetes in 2008. Although impaired fasting glucose (IFG) is a strong predictor for type 2 diabetes mellitus, the program does not follow up IFG in non-MetS individuals. This study aimed to examine the risk and the population attributable fraction (PAF) of MetS and IFG for incidence of type 2 diabetes mellitus. MATERIALS AND METHODS: Japanese workers (3,417 men and 714 women) aged 40-64 years without a history of diabetes were prospectively followed. MetS was defined as either abdominal obesity plus two or more metabolic risk factors, or being overweight in the case of normal waist circumference plus three or more metabolic risk factors. IFG was defined as fasting blood glucose 100-125 mg/dL. RESULTS: During a mean 6.3 years, 240 type 2 diabetes mellitus cases were identified. Compared with those without MetS and IFG, the multivariable-adjusted hazard ratios (95% confidence interval) of non-MetS individuals with IFG, MetS individuals without IFG and MetS individuals with IFG for type 2 diabetes mellitus were 4.9 (3.4-7.1), 2.4 (1.6-3.5) and 8.3 (5.9-11.5), respectively. The corresponding PAFs for type 2 diabetes mellitus incidence were 15.6, 9.1 and 29.7%, respectively. CONCLUSIONS: IFG represented a higher risk and PAF than MetS for type 2 diabetes mellitus incidence in middle-aged Japanese individuals. The coexistence of MetS and IFG showed the highest risk and PAF for type 2 diabetes mellitus incidence. The current Japanese MetS screening program should be reconsidered to follow up non-MetS individuals with IFG.

Association of gamma-glutamyl transferase and alanine aminotransferase with type 2 diabetes mellitus incidence in middle-aged Japanese men: 12-year follow up.

AIMS/INTRODUCTION: To prospectively investigate whether simultaneous elevation of gamma-glutamyl transferase (GGT) and alanine aminotransferase (ALT) is associated with the increase of type 2 diabetes mellitus incidence independent of alcohol drinking, body mass index and triglycerides. METHODS: A total of 2,775 Japanese male workers who had no history of type 2 diabetes mellitus were followed. High GGT and ALT were defined as the top tertiles (GGT cutpoint: 49 IU/L, ALT cutpoint: 28 IU/L). Three groups were created using these dichotomized GGT and ALT cutpoints: both low, either high or both high. Multivariable Cox proportional hazards models were carried out adjusted for potential confounding factors. RESULTS: A total of 276 type 2 diabetes mellitus cases were identified during 12 years (27,040 person-years) of follow up. Participants with simultaneously elevated GGT and ALT had a significantly higher incidence of type 2 diabetes mellitus, even after adjustment for fasting insulin and fasting blood glucose compared with the group without GGT or ALT elevation. Similar associations were observed in non- or light-to-moderate alcohol drinkers, as well as in participants with normal weight. However, the association was weaker in participants with triglycerides <150 mg/dL. We then evaluated whether the addition of GGT and ALT would improve the prediction of type 2 diabetes mellitus incidence, and found that their inclusion significantly increased the C-statistic, net reclassification improvement and integrated discrimination improvement. CONCLUSIONS: Simultaneous elevation of GGT and ALT was significantly associated with type 2 diabetes mellitus incidence, independent of potential confounding factors, including alcohol drinking and obesity, although the association might require concomitant elevation of triglycerides. Inclusion of GGT and ALT improved type 2 diabetes mellitus risk prediction.

Scavenging of reactive oxygen species by astaxanthin inhibits epithelial-mesenchymal transition in high glucose-stimulated mesothelial cells.

BACKGROUND: High glucose concentrations influence the functional and structural development of the peritoneal membrane. We previously reported that the oral administration of astaxanthin (AST) suppressed peritoneal fibrosis (PF) as well as inhibited oxidative stress, inflammation, and epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) in a chlorhexidine-induced PF rat model. This suggests that oxidative stress induction of EMT is a key event during peritoneal damage. The present study evaluated the therapeutic effect of AST in suppressing EMT, in response to glucose-induced oxidative stress. METHODS: Temperature-sensitive mesothelial cells (TSMCs) were cultured in the presence or absence of AST and then treated with 140 mM glucose for 3 or 12 hours. Expression levels of TNF-α, TGF-ß, and VEGF were determined at the mRNA and protein levels, and nuclear factor kappa B (NF-κB) activity was evaluated. We measured NO2-/NO3- concentrations in cellular supernatants and determined 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in mitochondrial and nuclear DNA. The expressions of E-cadherin and alpha-smooth muscle actin (α-SMA) were evaluated by double immunofluorescence and protein levels. RESULTS: High glucose concentrations induced overproduction of reactive oxidative species (ROS), increasing 8-OHdG mitochondrial DNA and cytokine levels. The NF-κB pathway was activated in response to high glucose concentrations, whereas de novo α-SMA expression was observed with decreased E-cadherin expression. AST treatment attenuated ROS production, inflammatory cytokine production, NF-κB activation, and EMT. CONCLUSION: The findings of the present study indicate that AST may have an anti-EMT effect due to anti-oxidative and anti-inflammatory activities by scavenging glucose-induced ROS from mitochondria in PMCs. AST may be an efficacious treatment for PF.

Effectiveness of the Maternal and Child Health handbook in Burundi for increasing notification of birth at health facilities and postnatal care uptake.

BACKGROUND: In Burundi, birth certificate ownership (56.4%) and postnatal care (PNC) coverage (30%) remain low. Birth certificates prove birth registration and allow clients to receive free medical care including PNC. To obtain birth certificates, notification of birth by witnesses is indispensable. However, use of existing parallel home-based records for mother and child has prevented clients from successfully receiving notification of birth and related information. OBJECTIVE: To assess the effectiveness of the Maternal and Child Health (MCH) handbook for increasing notification of birth at health facilities and PNC uptake. METHODS: Pre- and post-introduction measurement were applied including: (i) structured interviews with two different sets of randomly selected mothers having infants aged less than six weeks at the pre- or post-studies; and (ii) secondary data from the national health management information system. RESULTS: 95.1% of mothers had an MCH handbook post-study. Significant improvement was observed in the proportion of mothers receiving notification of birth at health facilities, from 4.6% to 61.0% (95% confidence interval [CI]: 55.9%-66.2%), and the proportion of mothers receiving guidance on PNC, from 35.9% to 64.2% (95% CI: 59.2%-69.3%). The annual PNC coverage (43.9% to 54.2%; p < 0.05) in the Gitega District significantly increased from 2013 to 2014. Among MCH handbook owners, mothers giving birth at hospitals/clinics had 2.62 higher odds (95% CI: 1.63-4.22) of obtaining notification of birth than mothers giving birth at health centers. Conversely, mothers delivering at hospitals/clinics had 0.51 lower odds (95% CI: 1.63-4.22) of receiving PNC guidance than mothers delivering at health centers. CONCLUSIONS: As previous studies showed, the MCH handbook appeared to help health personnel provide guidance on PNC, thereby it may have increased PNC. Furthermore, this study suggests the handbook contributed to every birth being counted. However, to increase the effectiveness of the handbook, health personnel should be encouraged toward its proper use.

Long-term outcome of encapsulating peritoneal sclerosis (EPS) patients in a single center.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is the most serious complication of peritoneal dialysis (PD) with a high mortality rate. The objective of the present study was to determine the clinical characteristics, the incidence rate, and the long-term outcome of EPS patients compared with control patients. METHODS: Two hundred and seventy patients with end-stage kidney disease were started on PD from 1987 to 2013 in the Juntendo University Hospital. EPS was diagnosed by clinical findings, radiological findings, and macroscopic inspection at the time of laparoscopy or surgical operation. Patient medical records were analyzed retrospectively, including clinical characteristics, laboratory findings, treatment modality, and outcomes. Using a Kaplan-Meier analysis, we compared the survival rate between EPS patients and control PD patients, matched for age, gender, diabetes, and duration of PD. RESULTS: Among 270 PD patients, 13 patients (4.8 %) developed EPS. The mean duration of PD was 120.5 ± 42.8 months. There were no significant difference in demographic findings between EPS and control PD patients. Among the EPS patients, seven patients died, of which four deaths were directly attributed to EPS. All four patients that had had surgical enterolysis were doing well and had no recurrences. No significant difference in the survival rate between EPS and control PD patients was observed in the Kaplan-Meier analysis. CONCLUSIONS: There was no significant difference in the survival rate between EPS patients and control PD patients. It appears that an early diagnosis by laparoscopy and accurate treatment, including surgical enterolysis, might improve mortality.

Effect of AST-120 on Endothelial Dysfunction in Adenine-Induced Uremic Rats.

Aim. Chronic kidney disease (CKD) represents endothelial dysfunction. Monocyte adhesion is recognized as the initial step of arteriosclerosis. Indoxyl sulfate (IS) is considered to be a risk factor for arteriosclerosis in CKD. Oral adsorbent AST-120 retards deterioration of renal function, reducing accumulation of IS. In the present study, we determined the monocyte adhesion in the adenine-induced uremic rats in vivo and effects of AST-120 on the adhesion molecules. Methods. Twenty-four rats were divided into control, control+AST-120, adenine, and adenine+AST-120 groups. The number of monocytes adherent to the endothelium of thoracic aorta by imaging the entire endothelial surface and the mRNA expressions of adhesion and atherosclerosis-related molecules were examined on day 49. The mRNA expressions of ICAM-1 and VCAM-1 in human umbilical vein endothelial cells were also examined. Results. Adenine increased the number of adherent monocytes, and AST-120 suppressed the increase. The monocyte adhesion was related to serum creatinine and IS in sera. Overexpression of VCAM-1 and TGF- ß 1 mRNA in the arterial walls was observed in uremic rats. IS induced increase of the ICAM-1 and VCAM-1 mRNA expressions in vitro. Conclusion. It appears that uremic condition introduces the monocyte adhesion to arterial wall and AST-120 might inhibit increasing of the monocyte adherence with CKD progression.

Comparison between the fixation of peritoneal dialysis catheters to the peritoneal wall and the conventional placement technique: clinical experience and follow-up of a new implant technique for peritoneal dialysis catheters.

Peritoneal dialysis (PD) catheters often become severely dislocated, which may lead to malfunction. With the aim of preventing this complication, we have developed a simple method of fixing the catheter downwards in the peritoneal cavity (fixation technique), a technique that does not require a laparoscope. Sixteen patients were implanted using the conventional placement technique and 25 patients were implanted using the fixation technique. The location of the catheter tip was classified from grade 1 (downward, normal) to 5 (dislocated). The frequency of dislocation (defined as the extended time and/or decrease in volume when draining the PD solution) was measured for both the fixation technique and conventional placement technique. There was a significant difference in grade between the fixation technique (2.72 ± 1.01) and conventional technique (3.92 ± 1.31). The time until first dislocation was significantly different between the fixation technique (59.3 ± 48.1 days) and conventional technique (8.8 ± 14.6 days). The time until any dislocation was significantly different between the fixation technique (69.2 ± 41.9 days) and conventional technique (12.9 ± 13.7 days). Complications were not significantly different between the fixation technique and conventional technique. The fixation technique appears to be simple, safe, and useful for preventing severe dislocation and for lengthening the time until dislocation in PD patients.

Accumulation of advanced glycation end products and beta 2-microglobulin in fibrotic thickening of the peritoneum in long-term peritoneal dialysis patients.

Characteristics of pathological alterations in long-term peritoneal dialysis (PD) are thickening of submesothelial compact (SMC) zone, small-vessel vasculopathy, and loss of mesothelial cells. Bioincompatible PD fluid plays crucial roles in peritoneal injury. Encapsulating peritoneal sclerosis (EPS), a rare and serious complication, occurred in patients on long-term PD or frequent peritonitis episodes, and ~50 % of EPS developed after PD cessation. We hypothesized that PD-related peritoneal injury factors induced by bioincompatible PD fluid accumulated in the peritoneum and might induce EPS. We therefore examined the accumulation of advanced glycation end products (AGE) and beta 2-microglobulin (ß2M) in peritoneum and evaluated the relationship between their accumulation, clinical parameters, and outcome after PD cessation. Forty-five parietal peritoneal specimens were obtained from 28 PD patients, 14 uremic patients, and three patients with normal kidney function. The peritoneal equilibration test was used for peritoneal function. AGE- and ß2M-expressing areas were found in vascular walls, perivascular areas, and the deep layer of the SMC in short-term PD patients and extended over the entire SMC in long-term patients. Peritonitis and prolonged PD treatment aggravated peritoneal thickening and the proportion of AGE-expressing areas. The proportion of ß2M-expressing areas was increased in long-term PD patients. Thickening of the SMC and the proportions of AGE- and ß2M-expressing areas were not related to ascites or EPS after PD withdrawal. It appears that the increased proportion of AGE and ß2M deposition induced by long-term exposure of PD fluid may be a marker of peritoneal injury.

Paracrine effects of transplanted mesothelial cells isolated from temperature-sensitive SV40 large T-antigen gene transgenic rats during peritoneal repair.

BACKGROUND: The prevention and restoration of peritoneal damage is a critical mission in peritoneal dialysis (PD). Transplantation of mesothelial cells has been suggested to suppress peritoneal injury during PD. Few studies have examined the efficacy and safety of cell transplantation. We evaluated the paracrine effects of mesothelial transplantation during peritoneal repair using immortalized temperature-sensitive mesothelial cells (TSMCs) in chlorhexidine gluconate (CG)-induced peritoneal fibrosis rats. METHODS: Continuous-infusion pumps containing 8% CG were placed into the abdominal cavity for 21 days. After the removal of the pumps, the TSMCs were injected into the peritoneal cavity at Day 22 (Tx-1 group) or 29 (Tx-2 group). Morphological findings and mRNA expressions of regeneration-related factors were examined at Days 22, 29 and 35. RESULTS: Peritoneal thickness was aggravated in the Tx-1 group. Levels of transforming growth factor (TGF)-ß, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 mRNA in the Tx-1 group at Day 35 were comparable with those at Day 22. The levels of Snail, B-Raf and ERK-1, markers of epithelial to mesenchymal transition and of the RAS/MAPK pathway in the Tx-1 group, were significantly higher than those in the Tx-2 group. TGF-ß and VEGF were produced from the transplanted mesothelial cells and the surrounding cells in the Tx-1 group. CONCLUSION: It appears that the paracrine effect of transplanted mesothelial cells during peritoneal repair is associated with its surrounding condition. It is important to determine the most appropriate time for developing peritoneal repair through mesothelial transplantation.

An in-silico genomic survey to annotate genes coding for early development-relevant signaling molecules in the pearl oyster, Pinctada fucata.

The pearl oyster Pinctada fucata has great potential as a model system for lophotrochozoan developmental biology research. Pinctada fucata is an important commercial resource, and a significant body of primary research on this species has emphasized its basic aquaculture biology such as larval biology and growth, aquaculture, pearl formation and quality improvement, shell formation, and biomineralization. Recently, a draft genome sequence of this species was published, and many experimental resources are currently being developed, such as bioinformatics tools, embryo and larva manipulation methods, gene knockdown technique, etc. In this paper, we report the results from our genomic survey pertaining to gene families that encode developmental signaling ligands (Fgf, Hedgehog, PDGF/VEGF, TGFß, and Wnt families). We found most of the representative genes of major signaling pathways involved in axial patterning, as well as copies of the signaling molecule paralogs. Phylogenetic character mapping was used to infer a possible evolutionary scenario of the signaling molecules in the protostomes, and to reconstruct possible copy numbers of signaling molecule-coding genes for the ancestral protostome. Our reconstruction suggests that P. fucata retains the ancestral protostome gene complement, providing further justifications for the use of this taxon as a model organism for developmental genomics research.