Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that may lead to progressive joint destruction. The anti-cyclic citrullinated peptide (anti-CCP) antibody is an essential marker for the diagnosis of RA and has a crucial role in the bone destruction in RA. Recent studies have shown that interleukin (IL)-29, a vital member of type III interferon (IFN) family, could enhance proinflammatory cytokine production and might be involved in the joint destruction in RA. Therefore, in this study, we aimed to examine the role of IL-29 in RA patients with anti-CCP antibodies. The result showed that the serum IL-29 levels were higher in RA patients (n = 68) compared with healthy controls (HC, n = 68, P = 0.019). Correlation analysis demonstrated a significant positive correlation among serum IL-29 level, rheumatoid factor (RF, P < 0.001) and anti-CCP antibodies (P = 0.042). However, when RA patients were divided into two groups according to anti-CCP antibodies, the serum IL-29 levels were significantly higher in anti-CCP-antibodies positive RA patients (n = 54) than those in HC (n = 68) and anti-CCP-antibodies negative RA patients (n = 14). Furthermore, the serum IL-29 levels were positively correlated with the disease activity (P < 0.05) and significantly declined after 6 months of treatment (P < 0.01) in the anti-CCP-antibodies positive RA patients, whereas no significant change was found in the anti-CCP-antibodies negative RA patients (P > 0.05). The findings indicate that IL-29 is a potential biomarker for disease activity in anti-CCP-antibodies positive RA patients.

Infants and toddlers are prone to rapidly contracting illnesses, which are usually attributed to infectious diseases. Most nurseries and schools in Japan, however, refuse to accept children even with mild illnesses. For working parents, a sick child may therefore create new problems as the situation requires new day-care arrangements. To support such families, the Japanese government subsidizes construction and management of nurseries that operate especially for sick children. However, it has not been known whether most families are able to access such nurseries. To clarify the accessibility of these services, I calculated the distance to the nurseries from each of the 211,012 “blocks” (small residential areas with a median of 0.18 km²) in Japan and determined the proportion of children aged 0-4 years who lived within 3, 5, 10, 20 or 30 km of the nearest such nursery. Overall, 82.1% of these children lived within 10 km. However, the proportion was lower in northern parts of Japan such as Hokkaido and Tohoku, which have expansive land areas and low population and pediatric department densities. The proportion of children who lived within that same distance of the nearest nursery was also much lower in small towns and villages with 10,000 or fewer residents. Nurseries for sick children were not evenly distributed, and children and their caregivers in under-populated areas had to travel further to access these facilities. As the national government subsidizes such services, children and caregivers throughout Japan should have equal access to them.

Since the 2011 Fukushima accident, rebuilding society to protect against anxiety and improve feelings of well-being has grown in importance. A questionnaire was carried out among residents of Marumori Town, Igu County, Miyagi Prefecture, to evaluate the effects of radiation-related countermeasures implemented by the town to reduce residents’ anxiety and improve their subjective well-being (response rate: 31%; valid responses: n = 174). Further, to propose effective countermeasures regarding town planning for the improvement in subjective well-being, we analyzed associations between residents’ sense of attachment to the town and subjective well-being, and then identified primary factors behind their sense of attachment. Marumori Town, located about 50 km to the northwest of the Daiichi Nuclear Power Station, is a good site for evaluating the effects of countermeasures taken by the town itself to fight anxiety, because there have been limited surveys and professional medical support, and mitigation efforts were primarily initiated by the town. The results suggested that decontamination evaluations were associated with a reduction in anxiety after the accident, which contributed to an increase in residents’ subjective well-being. On the other hand, the evaluation of items related to human interactions in the community and the natural environment was found as a primary factor of sense of attachment toward the town, which contributed to an increase of residents’ subjective well-being. This is the first study to quantitatively measure the effects of radiation-related countermeasures on reducing anxiety and to propose an effective policy approach for improving subjective well-being.

In Japan, the percentage of leanness has been increasing in young women, and the percentage of low birth weight infants (< 2,500 g) has increased. Moreover, the average age of primiparas rose 3.5 years during the last 30 years. The purpose of this study was to clarify the relationship between maternal age and the influence of maternal pre-pregnancy physique on the neonatal physique of infants. Questionnaires were issued to the participants and collected when they submitted their gestational notifications at their local ward office in Kyoto Prefecture. After delivery, we obtained information on the course of the pregnancy and the neonatal physique of the infants from the participant’s maternal passbooks. A total of 454 mothers (age 20 ≥) were analyzed: 161 young mothers (aged 20 to 29 years), 185 mothers (aged 30 to 34 years), and 108 older mothers (age ≥ 35). Overall, the mean rate of leanness (pre-pregnancy BMI < 18.5) was 23.8%. We found that birth weight was significantly lower in female infants, born to lean young mothers, compared to non-lean young mothers, whereas no significant difference was detected in other mothers (age ≥ 30), irrespective of pre-pregnancy BMI. By contrast, male infants, born to older lean mothers (age ≥ 35), showed significantly lower birth weight. Thus, maternal pre-pregnancy BMI exerts differential effects on the fetal growth (neonatal physique), depending on the maternal age and the sex of infants. We need to improve BMI in pre-pregnancy women, especially those in the twenties and 35 years old or over.

Mature cystic teratoma (MCT) is rarely involved in the overproduction of steroid hormones in contrast to sex cord stromal tumors. A 31-year-old woman visited our hospital with hirsutism, hoarseness, and hair loss from the scalp. Serum testosterone and free-testosterone levels were 7.3 ng/ml and 2.3 pg/ml, respectively, which were markedly in excess of the age adjusted female standard levels. Basal blood levels of steroid hormones and serum levels of 17-hydroxyprogesterone at 1 h after intravenous injection of adrenocorticotropic hormone demonstrated that 21-hydroxylase deficiency was not the underlying cause of her virilization. A subsequent chromosomal test with G-banding revealed a karyotype of 46XX. Magnetic resonance imaging revealed a mass in the left ovary, which was subsequently diagnosed as MCT. Detailed pathological analysis of the tumor indicated that it was comprised of skin components, sweat glands, with hair and fat texture, glandular epithelium and fibrous connective tissue, consistent with the characteristic composition of MCT. Immunohistochemical analysis demonstrated marked immunoreactivity of 17beta-hydroxysteroid dehydrogenase (HSD17B5), an enzyme that can convert androstenedione to testosterone. Following surgical removal of the tumor, testosterone and free testosterone levels were markedly decreased (0.3 ng/ml and 0.4 pg/ml, respectively) and other symptoms abated. In conclusion, this is the first report of an ovarian MCT associated with clinical virilization caused by the ectopic production of testosterone possibly because of an overexpression of intratumoral HSD17B5.

Dental problems among athletes have been cautioned due to negative impacts not only on their oral health but also on athletic performance. Acquirement of appropriate oral health behavior mainly composed of toothbrushing in childhood can be one of the most important strategies for advancing children’s athletic possibilities. Although habits of screen viewing, including game playing, and TV viewing have direct impacts on children’s health and behavioral development, little is known about the association between these habits and toothbrushing frequency. A cross-sectional survey examining sports activities was conducted using a self-report questionnaire among school-aged athletic children belonging to the Miyagi Amateur Sports Association (n = 6,658). All statistical analyses were performed with SPSS, and P-values less than 0.05 were considered statistically significant. The association between a lower brushing frequency (< 2 times a day) and screen-viewing behavior was examined using multivariate logistic models after adjusting for sex, age, body mass index (BMI), studying time, and sleep duration. After adjustment for all covariates, longer game playing (> 2 hrs a day), but not TV viewing, significantly correlated with lower brushing frequency (P for trend < 0.001). Importantly, longer game-playing behavior was also associated with unhealthy dental behavior defined as a lower brushing frequency regardless of the awareness of dental caries (P for trend < 0.001). In conclusion, this is the first study indicating a type-specific unfavorable impact of screen viewing on oral health behavior among athletic children. Excessive game playing may adversely affect oral health literacy more strongly than TV viewing.

Sepsis is a systemic host response to infection, and patients with sepsis are frequently handled in the intensive care unit. However, mortality related to sepsis remains high throughout the world. In addition, there have been no efficient prognostic biomarkers for sepsis to be employed in clinical practice. We therefore aimed to identify prognostic biomarkers for sepsis using the chemokine/cytokine array. This study included 143 patients with sepsis, who were divided into survivor and nonsurvivor groups according to their 28-day mortality status. The cytokine array analysis was performed with plasma samples from two randomly selected patients in each sepsiofgroup. We thus identified seven cytokines with significantly and consistently different expression levels between nonsurvivors and survivors. The validity of the selected cytokines was then assessed by enzyme-linked immunosorbent assay (ELISA). We finally found monocyte chemoattractant protein 1 (MCP-1) as the most useful biomarker to distinguish the two sepsis groups; namely, non-surviving patients (n = 56) exhibited significantly higher plasma concentrations of MCP-1 compared to survivors (n = 87). MCP-1 is a CC chemokine, a potent chemoattractant that contributes to systemic inflammatory response syndrome. Areas under the receiver operating characteristic curves for prediction of 28-day mortality were 0.763 for MCP-1, 0.680 for the Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) score, 0.64 for the Sequential Organ Failure Assessment (SOFA) score, 0.621 for procalcitonin, and 0.785 for MCP-1 plus APACHE II score. In conclusion, we propose that plasma MCP-1 is a useful biomarker in predicting outcome of sepsis.

Infants with Down Syndrome (DS) are at risk of developing a transient abnormal myelopoiesis (TAM). TAM is characterised by increased circulating blast cells but usually self-limiting. DS patients with TAM sometimes show fetal hydrops and effusion in body cavities, but the mechanism remains unclear. We report here a case of infant with DS who had pericardial effusion, TAM, and eosinophilia. In her pericardial effusion, white blood cell count was 6.0 × 10³/µL, 41% of which were eosinophils. After administration of prednisolone, pericardial effusion gradually decreased, and TAM and eosinophilia improved. In order to elucidate the immunological mechanism, we measured the levels of 17 cytokines in her pericardial effusion fluid and serum. In her pericardial fluid, there were high levels of 12 cytokines, and they were higher than those in her serum. In particular, IL-6 (44,573 pg/mL), IL-8 (4,865 pg/mL), and IL-13 (579.41 pg/mL) were at extremely high levels in her pericardial fluid. After administration of prednisolone, the levels of 8 of the 12 elevated cytokines in her pericardial fluid decreased and all of the elevated cytokines decreased in her serum. Corticosteroids can be effective to reduce cytokine levels and the amount of effusion in patients with DS. It is presumed that effusion seen in DS with TAM could be related to an abnormal production of cytokines at the effusion site.

DNA methylation is a fundamental epigenetic modification to regulate gene expression. N-Myc downstream-regulated gene (NDRG) 2 is a cytoplasmic protein and participates in the pathogenesis of liver fibrosis. In this study, the mRNA expression and methylation status of NDRG2 was evaluated in patients with chronic hepatitis B (CHB). The study included 143 CHB patients and 65 normal controls (NC). The mRNA expression of NDRG2 in peripheral blood mononuclear cells (PBMCs) was detected by quantitative real-time polymerase chain reaction. The methylation status of the NDRG2 promoter in PBMCs was detected by methylation-specific polymerase chain reaction. The NDRG2 mRNA level was lower in the CHB group than in the NC group (p < 0.001). Methylation frequency of the NDRG2 promoter was significantly higher in CHB patients than in the NC group (52.44% vs. 26.15%, p < 0.001). Importantly, the relative expression levels of NDRG2 mRNA were significantly lower in the methylated group than in the unmethylated group in both CHB patients and NC (p < 0.001). Furthermore, a lower mRNA level and hypermethylation of NDRG2 were associated with liver fibrosis and inflammation grade in CHB. The aspartate aminotransferase-to-platelet ratio index (APRI) score is widely used to predict liver fibrosis. The mRNA expression levels and methylation status of NDRG2 showed a better score compared to APRI for discriminating the severity of liver fibrosis. In conclusion, hypermethylation of NDRG2 in PBMCs was correlated with decreased mRNA expression and with liver fibrosis. The methylation status of the NDRG2 promoter in PBMCs is a potential noninvasive biomarker to predict the severity of liver fibrosis.

Ovarian serous carcinoma (OSC) is the most common epithelial ovarian cancer. Inorganic pyrophosphatase (PPA1) catalyzes the hydrolysis of pyrophosphate to inorganic phosphate, thereby providing extra energy for metabolism. The significance of PPA1 in the prognosis of OSC has not been investigated. Our study aimed to explore the expression and predictive role of PPA1 in OSC progression. We screened the expression of PPA1 protein in OSC tissues from 139 patients by immunohistochemistry, and evaluated its correlation with clinicopathological characteristics. PPA1 was categorized as high expression in 58 OSC cases (41.7%), which was correlated with poor differentiation, positive lymph node (LN) metastasis and advanced FIGO (The International Federation of Gynecology and Obstetrics) stages. Univariate and multivariate analyses identified PPA1 as a novel independent prognostic biomarker in OSC patients; meanwhile, conventional factors such as LN status and FIGO stages also showed statistical significance. Moreover, the expression levels of PPA1 protein were higher in A2780 and OVCAR3 human ovarian cancer cell lines than those in normal ovarian surface epithelial cells. Using these ovarian cancer cell lines, we showed that PPA1 overexpression caused the decrease in the expression level of p53, the tumor suppressor, with the increase in β-catenin level, as determined by Western blot analysis. Conversely, knockdown of PPAI expression was associated with the increase of p53 level and the decreased of β-catenin level. Consistently, the proliferation and invasion capacities of ovarian cancer cells were enhanced upon PPA1 overexpression. In conclusion, PPA1 serves as a potential prognostic biomarker for patients with OSC.