Obesity is associated with biliary tract cancer mortality and incidence: A pooled analysis of 21 cohort studies in the Asia Cohort Consortium

Body fatness is considered a probable risk factor for biliary tract cancer (BTC), whereas cholelithiasis is an established factor. Nevertheless, although obesity is an established risk factor for cholelithiasis, previous studies of the association of body mass index (BMI) and BTC did not take the effect of cholelithiasis fully into account. To better understand the effect of BMI on BTC, we conducted a pooled analysis using population-based cohort studies in Asians. In total, 905 530 subjects from 21 cohort studies participating in the Asia Cohort Consortium were included. BMI was categorized into four groups: underweight (<18.5 kg/m²); normal (18.5-22.9 kg/m²); overweight (23-24.9 kg/m²); and obese (25+ kg/m²). The association between BMI and BTC incidence and mortality was assessed using hazard ratios (HR) and 95% confidence intervals (CIs) by Cox regression models with shared frailty. Mediation analysis was used to decompose the association into a direct and an indirect (mediated) effect. Compared to normal BMI, high BMI was associated with BTC mortality (HR 1.19 [CI 1.02-1.38] for males, HR 1.30 [1.14-1.49] for females). Cholelithiasis had significant interaction with BMI on BTC risk. BMI was associated with BTC risk directly and through cholelithiasis in females, whereas the association was unclear in males. When cholelithiasis was present, BMI was not associated with BTC death in either males or females. BMI was associated with BTC death among females without cholelithiasis. This study suggests BMI is associated with BTC mortality in Asians. Cholelithiasis appears to contribute to the association; and moreover, obesity appears to increase BTC risk without cholelithiasis.     

Developing a questionnaire on the quality of working life for female medical and healthcare professionals

This study aimed to develop a questionnaire on the quality of working life among female medical and healthcare professionals and examine its validity and reliability. The questionnaire was developed from an item pool drawing on the literature. The four trait scales included 40 items, covering female-specific stress in continuing a career, stress of lifestyle in maintaining personal values, job satisfaction and social support network. The questionnaire’s validity and reliability were assessed using data from 1,784 female doctors, dentists, and nurses. Validity was examined using exploratory factor analysis on each trait for construct validity, and multitrait scaling analysis for convergent and discriminant validity. Reliability was tested using Cronbach’s alpha for trait subscales and scales. Exploratory factor analysis on each trait was convergent. One trait derived three subscales, and another two. The remaining two traits were convergent for one factor. Multitrait scaling analysis showed that all scales and subscales were independent. The questionnaire was therefore internally consistent and had construct validity. Cronbach’s alpha was 0.85 for the total and between 0.72 and 0.83 for the subscales. These results validate the four-trait combination questionnaire and suggest that it would be suitable for use in future research, perhaps in combination with other existing scales.     

Unique Habitual Food Intakes in the Gut Microbiota Cluster Associated with Type 2 Diabetes Mellitus

This cross-sectional study aimed to clarify the characteristic gut microbiota of Japanese patients with type 2 diabetes (T2DM) using t-distributed stochastic neighbor embedding analysis and the k-means method and to clarify the relationship with background data, including dietary habits. The gut microbiota data of 383 patients with T2DM and 114 individuals without T2DM were classified into red, blue, green, and yellow groups. The proportions of patients with T2DM in the red, blue, green, and yellow groups was 86.8% (112/129), 69.8% (81/116), 76.3% (90/118), and 74.6% (100/134), respectively; the red group had the highest prevalence of T2DM. There were no intergroup differences in sex, age, or body mass index. The red group had higher percentages of the Bifidobacterium and Lactobacillus genera and lower percentages of the Blautia and Phascolarctobacterium genera. Higher proportions of patients with T2DM in the red group used α-glucosidase inhibitors and glinide medications and had a low intake of fermented soybean foods, including miso soup, than those in the other groups. The gut microbiota pattern of the red group may indicate characteristic changes in the gut microbiota associated with T2DM in Japan. These results also suggest that certain diabetes drugs and fermented foods may be involved in this change. Further studies are needed to confirm the relationships among traditional dietary habits, the gut microbiota, and T2DM in Japan.     

Generation of Budding-Like Intestinal Organoids from Human Induced Pluripotent Stem Cells

Human induced pluripotent stem (iPS) cell-derived intestinal organoids have low invasiveness; however, the current differentiation method does not reflect the crypt-villus-like structure due to structural immaturity. Here, we generated budding-like organoids that formed epithelial tissue-like structures and had the characteristics of the mature small intestine from human iPS cells. They showed a high expression of drug transporters and induced the expression of cytochrome P450 3A4 and P-glycoprotein. When treated with tumor necrosis factor-α and/or transforming growth factor-β, the budding-like organoids replicated the pathogenesis of mucosal damage or intestinal fibrosis. Upon dissociation and seeding on cell culture inserts, the organoids retained intestinal characteristics, forming polarized intestinal folds with approximately 400 Ω × cm² transepithelial electrical resistance. This novel method has great potential for disease modeling and drug screening applications.     

A possible mechanism for decrease in serum thyroxine level by polychlorinated biphenyls in Wistar and Gunn rats.

We have previously demonstrated that in mice, the decrease in serum thyroxine (T(4)) level by polychlorinated biphenyls (PCBs) occurs without an increase in the UDP-glucuronosyltransferase (T(4)-UDP-GT) for T(4) glucuronidation, although the PCB-induced decrease in rats is generally thought to occur through induction of T(4)-UDP-GT, UGT1A1, and UGT1A6. In the present study, to further clarify the relationship between the decrease in serum T(4) level and the increase in UGT1A activity by PCB in rats, we examined the relationship using Wistar rats and Gunn rats, a mutant strain of Wistar rats deficient in UGT1A isoforms. The serum total T(4) level was markedly decreased not only in the Wistar rats but also in the Gunn rats 4 days after treatment with a PCB, Kanechlor-500 (KC500, 100 mg/kg) or 2,2',4,5,5'-pentachlorobiphenyl (PentaCB, 112 mg/kg), and there was no significant difference in magnitude of the decrease between the two rat strains. At the same time, the level and activity of T(4)-UDP-GT were significantly increased by treatment with either KC500 or PentaCB in Wistar rats but not in Gunn rats. In addition, no significant change in the level of serum total triiodothyronine (T(3)) and thyroid-stimulating hormone by the KC500 treatment was observed in either Wistar or Gunn rats. Furthermore, significant decrease in the activity of hepatic type-I deiodinase, which mediates the deiodization of T(4) and T(3), by treatment with KC500 or PentaCB was observed in both Wistar and Gunn rats. From the serum of KC500- or PentaCB-treated Wistar and Gunn rats, mono- and di-hydroxylated PCB metabolites, which would bind to T(4) binding serum protein (transthyretin), were detected. In conclusion, the present results suggest that the decrease in serum total T(4) level by either KC500 or PentaCB in Gunn rats was not dependent on the increase in hepatic T(4)-UDP-GT activity. The findings further suggest that the PCB-mediated decrease in serum T(4) level might occur, at least in part, through formation of the hydroxylated PCB metabolites. Furthermore, even in Wistar rats, the PCB-mediated decrease in serum T(4) level might occur not only through the increase in hepatic T(4)-UDP-GT but also via formation of hydroxylated PCB metabolites.     

Nonviral approaches for targeted delivery of plasmid DNA and oligonucleotide

Successful gene therapy depends on the development of efficient delivery systems. Although pDNA and ODN are novel candidates for nonviral gene therapy, their clinical applications are generally limited owing to their rapid degradation by nucleases in serum and rapid clearance. A great deal of effort had been devoted to developing gene delivery systems, including physical methods and carrier-mediated methods. Both methods could improve transfection efficacy and achieve high gene expression in vitro and in vivo. As for carrier-mediated delivery in vivo, since gene expression depends on the particle size, charge ratio, and interaction with blood components, these factors must be optimized. Furthermore, a lack of cell-selectivity limits the wide application to gene therapy; therefore, the use of ligand-modified carriers is a promising strategy to achieve well-controlled gene expression in target cells. In this review, we will focus on the in vivo targeted delivery of pDNA and ODN using nonviral carriers.     

Lifestyles and psychosomatic symptoms among elementary school students and junior high school students

Objectives  To examine the relationship between lifestyles and psychosomatic symptoms in children, we conducted a self-administered questionnaire survey of elementary school students and junior high school students in Japan. Methods  We designed an original questionnaire to investigate the lifestyles and psychosomatic symptoms of children. In 1997, responses to the questionnaires were elicited from public elementary school fourth grade students (then aged 9–10) and public junior high school seventh grade students (then aged 12–13). The survey was repeated annually for three years as the students advanced through school. Results  For both boys and girls, each cross-sectional analysis revealed a strong relationship between lifestyle behaviors and psychosomatic symptoms. Psychosomatic, symptoms scores varied according to daily hours of sleep, eating of breakfast, having strong likes and dislikes of food, bowel habits, and daily hours of television watching. Both boys and girls with “good” lifestyle, behaviors evaluated by the HPI (Health Practice Index) showed lower scores for psychosomatic symptoms. Conclusions  These findings show that the lifestyle behaviors of children are significantly associated with psychosomatic symptoms and suggest that poor lifestyle behaviors are likely to increase physical and psychological health risks.     

Risk of adverse reproductive outcomes associated with proximity to municipal solid waste incinerators with high dioxin emission levels in Japan

BACKGROUND: Great public concern about health effects of dioxins emitted from municipal solid waste incinerators has increased in Japan. This paper investigates the association of adverse reproductive outcomes with maternal residential proximity to municipal solid waste incinerators. METHODS: The association of adverse reproductive outcomes with mothers living within 10 km from 63 municipal solid waste incinerators with high dioxin emission levels (above 80 ng international toxic equivalents TEQ/m3) in Japan was examined. The numbers of observed cases were compared with the expected numbers calculated from national rates adjusted regionally. Observed/expected ratios were tested for decline in risk or peak-decline in risk with distance up to 10 km. RESULTS: In the study area within 10 km from the 63 municipal solid waste incinerators in 1997-1998, 225,215 live births, 3,387 fetal deaths, and 835 infant deaths were confirmed. None of the reproductive outcomes studied here showed statistically significant excess within 2 km from the incinerators. However, a statistically significant peak-decline in risk with distance from the incinerators up to 10 km was found for infant deaths (p=0.023) and infant deaths with all congenital malformations combined (p=0.047), where a "peak" is detected around 1-2 km. CONCLUSION: Our study shows a peak-decline in risk with distance from the municipal solid waste incinerators for infant deaths and infant deaths with all congenital malformations combined. However, due to the lack of detailed exposure information to dioxins around the incinerators, the observed trend in risk should be interpreted cautiously and there is a need for further investigation to accumulate good evidence regarding the reproductive health effects of waste incinerator exposure.     

Characterization of Full Genome of Rat Hepatitis E Virus Strain from Vietnam

We amplified the complete genome of the rat hepatitis E virus (HEV) Vietnam strain (V-105) and analyzed the nucleotide and amino acid sequences. The entire genome of V-105 shared only 76.8%–76.9% nucleotide sequence identities with rat HEV strains from Germany, which suggests that V-105 is a new genotype of rat HEV.