Diurnal difference in CAR mRNA expression

BACKGROUND: The constitutive androstane receptor (CAR, NR1I3) plays a key role in the transcriptional activation of genes that encode xenobiotic/steroid and drug metabolizing enzymes. RESULTS: The expression of CAR mRNA throughout the circadian rhythm is reported for the first time in phase with the clock gene Bmal1 and in antiphase with the clock-controlled gene Rev-erbα mRNAs, with a peak at Zeitgeber time (ZT) 20 and a trough at ZT8, and a peak/trough ratio of 2.0. The diurnal difference in CAR mRNA expression might underlie the 1.7-fold difference in the magnitude of the PB-dependent induction of CYP2B1/2 mRNA. CONCLUSION: The circadian oscillation of xenosensor gene CAR mRNA expression is partially responsible for chronopharmacokinetics and chronopharmacology in disease

Gender differences in dietary behaviors among Japanese adolescents

Unhealthy dietary behaviors in adolescence are an important public health problem. Gender differences in dietary behaviors have already appeared during adolescence. However, few studies have assessed a variety of adolescent dietary behaviors in Japan. We aimed to clarify gender differences in unhealthy dietary behaviors among Japanese adolescents. The participants consisted of 84,988 participants from seventh to 12th grades. Unhealthy dietary behaviors were defined according to the National Health and Nutrition Survey. Multivariable logistic regression was used to analyze a nationally representative sample of Japanese adolescents from the 2014 to 2015 Lifestyle Survey. The effective response rate was 51.4%. The prevalence of unhealthy dietary behaviors (skipping breakfast, snacking, eating out, skipping meals, eating alone at dinner, and subjectively poor diet quality) among boys and girls was 14.2% versus 12.4%, 19.6% versus 14.1%, 10.6% versus 7.0%, 7.9% versus 5.6%, 13.3% versus 12.1%, and 12.3% versus 15.8%, respectively. Compared with boys, girls were more negatively associated with skipping breakfast [OR = 0.76 (95% CI 0.73–0.79)], snacking [OR = 0.67 (95% CI 0.65–0.70)], eating out [OR = 0.62 (95% CI 0.59–0.66)], skipping meals [OR = 0.61 (95% CI 0.58–0.65)], and eating alone at dinner [OR = 0.79 (95% CI 0.76–0.83)]. However, girls were more positively associated with subjectively poor diet quality [OR = 1.19 (95% CI 1.14.1.24)]. The findings suggest that gender differences existed in dietary behaviors. Gender differences in dietary behaviors suggest opportunities for tailoring interventions related to dietary education in schools

Expression of Cyclooxygenase Enhances Tumor Invasion and Metastasis in Human Gastric Carcinoma

Background: Expression of COX-2 in vitro has been shown to have a number of cellular effects including increasing proliferation, reducing apoptosis promoting angiogenesis, decreasing E-cadherin expression and increasing invasive/metastatic potential. Aims: To determine the role of COX-2 in the development and metastasis potential of gastric carcinoma in human subjects. Methods: Tissue samples were obtained from surgically removed specimens of 48 patients with primary gastric adenocarcinoma who underwent gastrectomy from January 1998 to December 1999. The specimens were stained for HE while COX-2 expressions in cancer fold and antrum site were evaluated immunohistochemically. Expression of COX-2 was defined as positive when either one of cancer lesion or antrum site showed immunoreactivity. Results: Preliminary result from 12 out of 48 cases, COX-2 immunoreactivity was detected in 50% (6 of 12 specimens). Expression of COX-2 were more frequent in tumor with serosal invasion (5 of 6 specimens), lymph node metastases (3 of 3 specimens), tumor size more than 4 cm and were significant, statistically (p<0.05). The expression of COX-2 in well differential carcinoma type was similar with in poorly differentiated carcinoma type. Conclusion: COX-2 expression in gastric carcinoma tissue is correlated closely with tumor size, serosal invasion and lymph node metastases, indicating that COX-2 is involved in the growth and metastases of gastric carcinoma

Trends in sleep problems and patterns among Japanese adolescents: 2004 to 2017

Background Sleep problems in adolescence, such as insomnia and short sleep duration, are associated with physical and mental health problems. However, little is known about the recent trends in sleep problems among adolescents. Therefore, this study examined trends in sleep problems among Japanese adolescents. Methods Using data from the Lifestyle Survey of Adolescents collected in 2004 (n = 102,451), 2008 (n = 95,680), 2010 (n = 98,867), 2012 (n = 101,134), 2014 (n = 85,931), and 2017 (n = 64,417), we calculated the trends of insomnia, shorter sleep duration, late bedtimes, and poor sleep quality. Multivariable logistic regression analysis models were used to examine the association of each sleep problem and survey years. Findings We analyzed data from 545,285 Japanese adolescents. Results indicated that, since 2004, the odds ratio for insomnia have decreased (Adjusted odds ratio [AOR] 0•85, 95% CI 0•82–0•87), as have the odds ratio for poor sleep quality (AOR 0•92, 95% CI 0•88–0•95). However, the odds ratio for shorter sleep duration (AOR 1•13, 95% CI 1•10–1•17) and late bedtimes tended to increase (AOR 1•06, 95% CI 1•03–1•08) during this period. Interpretation The prevalence of insomnia symptoms and poor sleep quality among adolescents decreased from 2004 to 2017. However, there were increasing trends toward shorter sleep duration and late bedtimes. These changes are both relieving and concerning. Teachers, parents, and health professionals should consider educating adolescents regarding sleep hygiene, adjusting schedules of extracurricular activities, and enhancing time management to improve their sleep quantity

Effectiveness of Screening and Brief Alcohol Intervention at the Workplace: A Study Protocol for a Randomized Controlled Trial at Five Japan-Based Companies

Background: Despite evidence regarding the effectiveness of screening and brief interventions for excessive alcohol use in primary care, these tools are not a part of routine practice. It has been suggested that using these tools at the workplace may be critical to alcohol-associated harm; however, evidence for this claim is unclear. The aim of this article is to develop a study protocol which evaluates the effect of brief alcohol intervention at the workplace to reduce harmful alcohol drinking. Methods: A randomized controlled trial involving employees (aged 20–74 years) of five Japan-based companies who were screened “positive” by Alcohol Use Disorder Identification Test (AUDIT) is on-going. Participants were randomized into “Patient Information Leaflet” (control group), “Brief Advice and Counselling,” and “Five-minute Brief Advice” groups. A self-administered questionnaire was used to assess alcohol consumption, lifestyle behavior, health status, work performance, and consequences of alcohol use. Data of laboratory markers were collected from routine health checkups.Results: A total of 351 participants were randomized into Patient Information Leaflet (n = 111), Brief Advice and Counselling (n = 128), and Five-minute Brief Advice (n = 112) groups. Participants were mostly men with a median age of 49 years. Median AUDIT score and weekly alcohol consumption were 11 points and 238 g/week, respectively. Two-thirds of the participants were manufacturing workers. Conclusion: This study protocol developed the first trial in Japan to investigate the effect of brief alcohol intervention combined with a recommended screening tool at the workplace. Our findings can provide evidence on the effectiveness and relevance of these tools to occupational health

Heat-not-burn tobacco, electronic cigarettes, and combustible cigarette use among Japanese adolescents: a nationwide population survey 2017

Background: From among the global public health concerns, smoking remains one of the most crucial challenges. Especially for adolescents, the increase in the use of electronic cigarettes is controversial, as its use may lead to established smoking. In Japan, where a unique tobacco regulation system exists, the heat-not-burn tobacco market has been growing. However, the prevalence and association of combustible cigarettes and new tobacco-related products have not yet been closely investigated among Japanese adolescents. This study aimed to clarify the prevalence of smoking among adolescents, including new types of tobacco-related products, and to compare the characteristics of their users. Methods: The 2017 Lifestyle Survey of Adolescents is a nationally-representative survey collected in Japan. From the national school directory, 98 junior high schools and 86 high schools were randomly sampled throughout Japan. The students completed an anonymous questionnaire at school. We calculated the prevalence of use for each type of tobacco product. Then, the use of a combination of products and the characteristics of different types of products were examined. Results: In total, 64,152 students from 48 junior high schools and 55 high schools were included the analysis (school response rate = 56%, Mage = 15.7 years, 53.9% boys). The age-adjusted rate of ever (current) use of electronic cigarettes was 2.1% (0.7%) in junior high school and 3.5% (1.0%) in high school; that of combustible cigarettes was 2.6% (0.6%) in junior high school and 5.1% (1.5%) in high school. The rate of heat-not-burn tobacco use was lower relative to other products: 1.1% (0.5%) in junior high school and 2.2% (0.9%) in high school. An examination of the combined use of the three products identified a high number of dual users. Comparisons between different types of users indicated different backgrounds for combustible cigarette users and new product users. Conclusions: The prevalence of new tobacco-alternative products is growing in popularity among Japanese adolescents. Dual use is common, and many adolescents use new products only. Moreover, e-cigarettes might attract a broader range of groups to smoking. Continuous monitoring and research are needed to investigate their influence as a possible gateway to tobacco smoking

Pancreatic Cancer Research beyond DNA Mutations

Pancreatic ductal adenocarcinoma (PDAC) is caused by genetic mutations in four genes: KRAS proto-oncogene and GTPase (KRAS), tumor protein P53 (TP53), cyclin-dependent kinase inhibitor 2A (CDKN2A), and mothers against decapentaplegic homolog 4 (SMAD4), also called the big 4. The changes in tumors are very complex, making their characterization in the early stages challenging. Therefore, the development of innovative therapeutic approaches is desirable. The key to overcoming PDAC is diagnosing it in the early stages. Therefore, recent studies have investigated the multifaced characteristics of PDAC, which includes cancer cell metabolism, mesenchymal cells including cancer-associated fibroblasts and immune cells, and metagenomics, which extend to characterize various biomolecules including RNAs and volatile organic compounds. Various alterations in the KRAS-dependent as well as KRAS-independent pathways are involved in the refractoriness of PDAC. The optimal combination of these new technologies is expected to help treat intractable pancreatic cancer