Study Profile of the Tsuruoka Metabolomics Cohort Study (TMCS).

The Tsuruoka Metabolomics Cohort Study (TMCS) is an ongoing population-based cohort study being conducted in the rural area of Yamagata Prefecture, Japan. This study aimed to enhance the precision prevention of multi-factorial, complex diseases, including non-communicable and aging-associated diseases, by improving risk stratification and prediction measures. At baseline, 11,002 participants aged 35-74 years were recruited in Tsuruoka City, Yamagata Prefecture, Japan, between 2012 and 2015, with an ongoing follow-up survey. Participants underwent various measurements, examinations, tests, and questionnaires on their health, lifestyle, and social factors. This study used an integrative approach with deep molecular profiling to identify potential biomarkers linked to phenotypes that underpin disease pathophysiology and provide better mechanistic insights into social health determinants. The TMCS incorporates multi-omics data, including genetic and metabolomic analyses of 10,933 participants and comprehensive data collection ranging from physical, psychological, behavioral, and social to biological data. The metabolome is used as a phenotypic probe because it is sensitive to changes in physiological and external conditions. The TMCS focuses on collecting outcomes for cardiovascular disease, cancer incidence and mortality, disability, functional decline due to aging and disease sequelae, and the variation in health status within the body represented by omics analysis that lies between exposure and disease. It contains several sub-studies on aging, heated tobacco products, and women's health. This study is notable for its robust design, high participation rate (89%), and long-term repeated surveys. Moreover, it contributes to precision prevention in Japan and East Asia as a well-established multi-omics platform.

Patterns of alcohol and alcohol-flavoured non-alcoholic beverage advertisements over Japanese free-to-air television networks.

BACKGROUND: Alcohol use is a serious public health challenge worldwide. Japan has no government regulations or legal penalties against advertising alcoholic beverages on television (TV). Instead, advertisements depend on the Japanese alcohol industry's self-regulation on airtime (no advertisements from 5 am to 6 pm) and the content of alcoholic beverages, which must not tempt minors. However, many adolescents (10 to 19 years old) watch TV from 6 pm to 11 pm. The aim of this study was to describe the pattern in the advertising of alcoholic beverages and alcohol-flavoured non-alcoholic beverages (AFNAB) in Japan during the popular TV viewing time for adolescents. METHODS: A secondary analysis of advertising airtime data from five free-to-air Japanese TV networks in the Greater Tokyo area that aired between 12 August and 3 November 2019, was performed. RESULTS: During the study period, 5215 advertisements for alcoholic beverages and AFNABs aired (1451.75 min). In total, 2303 advertisements (44.2%) were beer, low-malt beer, or beer-taste beverages, 277 (5.3%) were whisky, 2334 (44.8%) were local alcoholic beverages (shochu and seishu), and 301 (5.8%) were AFNAB. On average, more advertisements aired on weekends (67.6 advertisements) than on weekdays (59.3 advertisements) per day. Approximately 30% of advertisements for AFNABs were aired during the time restricted for alcohol advertising, although AFNABs are considered alcohol according to industry guidelines. During the popular television viewing time for young adolescents, about two to three times more advertisements were aired per hour than during the rest of the day, on both weekdays and weekends (p < 0.001). CONCLUSION: The number of alcohol advertisements aired at times when adolescents often watch TV is 2 to 3.2 times higher than that at other times of the day. Furthermore, despite the industry's self-imposed regulations, some alcoholic beverages are still advertised. Therefore, other methods to protect children and adolescents from exposure to advertisements for alcoholic beverages should be investigated and implemented.

Relationship of living arrangement with the decline in functional capacity in elderly people by gender: a longitudinal observational study.

BACKGROUND: The living arrangement has been suggested as an important factor affecting health. Recent studies have also suggested that there was a risk among elderly persons who were not alone. This study examined whether the detailed living arrangement was associated with a future decline in functional capacity in the elderly, by gender, in a Japanese suburban city. METHODS: A 3-year longitudinal questionnaire survey (baseline: 2011; follow-up: 2014) for aged 65 years or older was conducted in Kurihara city, Japan. Of the respondents in the baseline survey, we analyzed those who scored 13 points (a perfect score which indicates the highest functional capacity; n = 2627) on the Tokyo Metropolitan Institute of Gerontology Index of Competence at the baseline. The exposure was living arrangement at baseline, divided into five categories: "with spouse only," "living alone," "with child and his/her spouse," "with child without his/her spouse," and "with other family/person." The outcome was the decline in functional capacity at the follow-up survey (score decreased to 10 points or less from 13 points). RESULTS: Of the 2627 analyzed population, 1199 (45.6%) were men. The incidence of the decline was 5.8% in men and 5.9% in women. Multivariable logistic regression analyses adjusted for age, educational attainment, and health behavior and condition revealed that in women, the odds ratio of the decline was higher in living with child and his/her spouse (2.41, 95% confidence interval; 1.10-5.28) referring to living with spouse only. When adjusting activities inside and outside the home such as housework additionally, the association was attenuated to marginal significance (2.25, 0.98-5.18). No statistical significance was observed in men. CONCLUSIONS: These results suggested that living with child and spouse of a child was associated with the future decline in women's functional capacity.

Correction to: Relationship of living arrangement with the decline in functional capacity in elderly people by gender: a longitudinal observational study.

An amendment to this paper has been published and can be accessed via the original article.

The effects of community-wide dissemination of information on perceptions of palliative care, knowledge about opioids, and sense of security among cancer patients, their families, and the general public.

PURPOSE: Prejudices against palliative care are a potential barrier to quality end-of-life care. There have been few large-scale community-wide interventions to distribute appropriate information about palliative care, and no studies have investigated their impact on cancer patients, their families, and the general public. Thus, we conducted a 3-year community intervention and evaluated the effects of distributing such information at the community level, and explored associations among levels of exposure, perceptions, knowledge, and the sense of security achieved. METHODS: Over a period of 3 years, we provided flyers, booklets, posters, and public lectures about palliative care in four regions of Japan, and carried out pre- and post-intervention surveys with repeated cross-sectional samplings of cancer patients (pre 859, post 857), bereaved family members (1110, 1137), and the general public (3984, 1435). The levels of exposure to the provided information were measured by a multiple-choice questionnaire after intervention. Multiple logistic regression analyses were used to estimate multivariable-adjusted odds ratios (ORs) for perceptions of palliative care, knowledge about opioids, and sense of security among the exposure groups. RESULTS: Overall perceptions of palliative care, opioids, and receiving care at home improved significantly among the general public and families, but not among the patients at the community level. However, multiple regression revealed that patients of extensive exposure category had significantly more positive perceptions of palliative care to those of non-exposure category (p = 0.02). The sense of security regarding cancer care of all patients, family members, and the general public improved. Among others, the respondents who reported extensive exposure in the general public and family members scored significantly higher sense of security. CONCLUSION: Our findings indicate that providing palliative care information via small media and lectures in the community is effective in improving perceptions of palliative care and knowledge about opioids among the community dwellers, especially for caregivers of the patients. The acquisition of adequate knowledge about palliative care from various information sources may improve people's sense of security regarding cancer.

Metabolomic profiling reveals novel biomarkers of alcohol intake and alcohol-induced liver injury in community-dwelling men.

OBJECTIVE: Metabolomics is a promising approach to the identification of biomarkers in plasma. Here, we performed a population-based, cross-sectional study to identify potential biomarkers of alcohol intake and alcohol-induced liver injury by metabolomic profiling using capillary electrophoresis-mass spectrometry (CE-MS). METHODS: Fasting plasma samples were collected from 896 Japanese men who participated in the baseline survey of the Tsuruoka Metabolomics Cohort Study, and 115 polar metabolites were identified and absolutely quantified by CE-MS. Information on daily ethanol intake was collected through a standardized, self-administered questionnaire. The associations between ethanol intake and plasma concentration of metabolites were examined. Relationships between metabolite concentrations or their ratios and serum liver enzyme levels in the highest ethanol intake group (>46.0 g/day) were then examined by linear regression analysis. Replication analysis was conducted in 193 samples collected from independent population of this cohort. RESULTS: Nineteen metabolites were identified to have an association with daily alcohol consumption both in the original and replication population. Three of these metabolites (threonine, glutamine, and guanidinosuccinate) were found to associate well with elevated levels of serum liver enzymes in the highest ethanol intake group, but not in the non-drinker group. We also found that the glutamate/glutamine ratio had a much stronger relation to serum γ-glutamyltransferase, aspartate transaminase, and alanine transaminase than glutamate or glutamine alone (standardized beta = 0.678, 0.558, 0.498, respectively). CONCLUSIONS: We found 19 metabolites associated with alcohol intake, and three biomarker candidates (threonine, guanidinosuccinate and glutamine) of alcohol-induced liver injury. Glutamate/glutamine ratio might also be good biomarker.

Regional medical professionals' confidence in providing palliative care, associated difficulties and availability of specialized palliative care services in Japan.

BACKGROUND: Although confidence in providing palliative care services is an essential component of providing such care, factors relating to this have not been investigated in Japan. OBJECTIVE: This study aimed to explore confidence in the ability to provide palliative care and associated difficulties and to explore correlations between these variables. Design A cross-sectional mail survey of medical doctors and registered nurses in Japan was performed as part of a regional intervention trial: the Outreach Palliative Care Trial of Integrated Regional Model study. Subjects Questionnaires were sent to 7905 medical professionals, and 409 hospital doctors, 235 general practitioners, 2160 hospital nurses and 115 home visiting nurses completed them. RESULTS: Confidence in providing palliative care was low and difficulties frequent for all types of medical professionals assessed. In particular, only 8-24% of them, depending on category, agreed to 'having adequate knowledge and skills regarding cancer pain management'. In particular, 55-80% of medical professionals acknowledged difficulty with 'alleviation of cancer pain'. Multiple regression analysis revealed that confidence was positively correlated with the amount of relevant experience and, for medical doctors, with 'prescriptions of opioids (per year)'. Moreover, difficulties were negatively correlated with the amount of relevant clinical experience. CONCLUSIONS: Effective strategies for developing regional palliative care programs include basic education of medical professionals on management of cancer-related pain (especially regarding opioids) and other symptoms.

Effects of a programme of interventions on regional comprehensive palliative care for patients with cancer: a mixed-methods study.

BACKGROUND: Improvement of palliative care is an important public health issue, but knowledge about how to deliver palliative care throughout a region remains inadequate. We used surveys and in-depth interviews to assess changes in the quality of palliative care after regional interventions and to gain insights for improvement of palliative care at a regional level. METHODS: In this mixed-methods study, a comprehensive programme of interventions for regional palliative care for patients with cancer was implemented from April 1, 2008, to March 31, 2011 in Tsuruoka, Kashiwa, Hamamatsu, and Nagasaki in Japan. Interventions included education, specialist support, and networking. We surveyed patients, bereaved family members, physicians, and nurses before and after the interventions were introduced. We also did qualitative interviews with health-care professionals after the interventions were introduced. Primary endpoints were numbers of home deaths, coverage of specialist services, and patient-reported and family-reported qualities of care. This trial is registered with UMIN Clinical Trial Registry, Japan (UMIN000001274). FINDINGS: 859 patients, 1110 bereaved family members, 911 physicians, and 2378 nurses provided analysable preintervention surveys; 857 patients, 1137 bereaved family members, 706 physicians, and 2236 nurses provided analysable postintervention surveys. Proportions of home deaths increased significantly, from 348 of 5147 (6.76%) before the intervention programme to 581 of 5546 (10.48%) after the intervention programme (p<0.0001). Furthermore, 194 of 221 (87.78%) family members of patients who died at home answered that these patients had wanted to die at home. The ratio of patients who received palliative care services to all patients who died of cancer increased significantly (from 0.31 to 0.50; p<0.0001). The patient-reported (effect size 0.14; adjusted p=0.0027) and family-reported (0.23; p<0.0001) qualities of care were significantly better after interventions than before interventions. Physician-reported and nurse-reported difficulties decreased significantly after the introduction of the interventions. Qualitative interviews showed improved communication and cooperation between health-care professionals because of greater opportunities for interactions at various levels. INTERPRETATION: A regional programme of interventions could improve the quality of palliative care. Improvement of communication between health-care professionals is key to improvement of services. FUNDING: Third Term Comprehensive Control Research for Cancer Health and Labor Sciences Research Grants of the Ministry of Health, Labour and Welfare of Japan.

Exploring the perceived changes and the reasons why expected outcomes were not obtained in individual levels in a successful regional palliative care intervention trial: an analysis for interpretations.

CONTEXT: The Japan Outreach Palliative Care Trial of Integrated Model (OPTIM) study, a mixed-methods study to evaluate the effects of a comprehensive regional palliative care program, revealed that the program provided broad positive outcomes at the regional level: increased home death, palliative care use, patient- and family-reported qualities of care, and health care professionals' difficulties. Not all participants however obtained positive outcomes and thus exploring the reasons why expected outcomes were observed in individual levels could be of value. AIMS: The primary aims were to explore why expected outcomes were not obtained in individual participants, and the perceived changes in daily practices of physicians and nurses were explored. SUBJECTS AND METHODS: Postintervention questionnaire survey on 857 patients, 1,137 bereaved family members, 706 physicians, and 2,236 nurses were analyzed. RESULTS: The reasons for not achieving home deaths included unexpected rapid deterioration, caregivers unavailable, concerns about adequate responses to sudden changes, and physical symptoms uncontrolled, while lack of physician availability at home and lack of information from physicians were less frequently reported. The reasons for not receiving specialized palliative care services were the lack of recommendations from physicians and no information about palliative care services. The reason for evaluating the quality of palliative care as not high was that clinicians tried to relieve symptoms, but there were limited effects and insufficient time. Many physicians and nurses reported that they became more aware of palliative care, that the availability of palliative care specialists and knowledge about palliative care improved, and that they cooperated with other regional health care providers more easily. CONCLUSION: The OPTIM study seemed to succeed in optimizing physician availability at home, improves physician information about home care, achieved maximum efforts to relieve patient distress by clinicians, and increased communication among regional health care professionals. To achieve further better outcomes, multiple interventions to the health care system to be performed on the basis of a comprehensive regional palliative care program are proposed.

Effect of digital messages from health professionals on COVID-19-related outcomes: A systematic review of randomized controlled trials.

Effectiveness of health professionals' messages via digital tools on COVID-19-related outcomes remains unknown. In this systematic review, we examined this issue by searching randomized controlled trials in six databases until August, 2022 (PROSPERO, CRD 42022350788). Risk of bias was assessed using revised Cochrane risk-of-bias tool. Primary outcomes were COVID-19 infections, preventive behaviors, and factors that support behavioral change. Seven trials with 16 reports (some reported two or more outcomes) were included. One trial showed that physician videos distributed by Facebook ads significantly reduced COVID-19 infections. Five of 6 reports showed that interventions can promote non-pharmaceutical preventive behaviors, vaccination, or information-seeking behaviors and half of the results were significant. Interventions improved the factors that support behavioral change. 14 reports had some concerns of bias risk and 2 had high risk of bias. Our findings suggest that digital messages by health professionals may help reduce COVID-19 infections through promoting behavioral change.

Screening practices of cancer survivors and individuals whose family or friends had a cancer diagnoses-a nationally representative cross-sectional survey in Japan (INFORM Study 2020).

PURPOSE: We examined cancer screening practices and related beliefs in cancer survivors and individuals with family or close friends with a cancer diagnosis compared to individuals without the above cancer history for 5 population-based (gastric, colorectal, lung, breast, cervical) and 1 opportunistic (prostate) cancer screenings using nationally representative cross-sectional survey in Japan. METHODS: We analyzed 3269 data from 3605 respondents (response rate, 37.1%) and compared the screening beliefs and practices of cancer survivors (n = 391), individuals with family members (n = 1674), and close friends with a cancer diagnosis (n = 685) to those without any cancer history (n = 519). RESULTS: Being a cancer survivor was associated with screening for gastric (OR, 1.75; 95% CI, 1.04-2.95), colorectal (OR, 1.56; 95% CI, 1.03-2.36), and lung cancer (OR, 1.71; 95% CI, 1.10-2.66) but not breast, cervical cancer or PSA test. Having a family cancer diagnosis was associated with colorectal and lung cancer screening. Having friends with a cancer diagnosis was associated with PSA test. Cancer survivors and family members perceived themselves as being more susceptible and worried about getting cancer than individuals without any cancer history. Cancer survivors strongly believed screening can detect cancer and were more likely to undergo screening. Subgroup analysis indicated an interrelation between gastric and colorectal cancer screening among survivors. CONCLUSIONS: A cancer diagnosis in oneself or family or friend influences an individual's health-related belief and risk perception, which can increase the likelihood of cancer screening. IMPLICATIONS FOR CANCER SURVIVORS: Targeted and tailored communication strategies can increase awareness of cancer screening.

Preferred place of care and place of death of the general public and cancer patients in Japan.

Dying at a favorite place is one of the important determinants for terminally ill cancer patients. The primary aim was to clarify (1) differences in preferred place of care and place of death among the general public across four areas across Japan and (2) preferred place of care and place of death among community-representative cancer patients. A cross-sectional mail survey was conducted on 8,000 randomly selected general population. We examined preferred place of care and place of death using two vignettes and obtained a total of 3,984 (50%) responses. For the pain scenario, approximately 50% of the general public throughout four areas chose home as their preferred place of care; and for the dependent-without-pain scenario, about 40% chose home as preferred place of care. In cancer patients, for both scenarios, approximately 40% chose home as the preferred place of care, and they were significantly less likely to choose home. The most preferred combination of place of care and place of death was home hospice for both groups. Although there were statistically significant differences in preferred place of care and place of death among the four regions, the absolute difference was less than 8%. Independent determinants of choosing home as place of care included concern about family burden and being unable to adequately respond to sudden changes out of working hours. In conclusion, establishing more accessible home and hospice service is strongly required through arranging regional resources to reduce family burden, alleviating patient-perceived burdens, and improving 24-h support at home.

Knowledge, beliefs, and concerns about opioids, palliative care, and homecare of advanced cancer patients: a nationwide survey in Japan.

PURPOSE: Patients' knowledge, beliefs, or concerns about opioids, palliative care, and homecare can be potential barriers to providing quality palliative care. The primary aim of this study was to clarify knowledge about opioids, beliefs about palliative care, and concerns about homecare in advanced cancer patients. METHODS: An anonymous questionnaire was sent to 1,619 outpatients with advanced cancer at 25 hospitals in four different regions of Japan. The respondents were asked to report their knowledge about opioids, beliefs about palliative care, and concerns about homecare, in addition to the levels of their sense of security regarding receiving cancer care in the region. RESULTS: A total of 925 responses were received. In total, 28% believed that opioids are addictive and/or shorten life; 52% believed that palliative care is only for terminally ill patients; 75% agreed that being taken care of at home puts a heavy burden on the family; and 61% agreed that home-visit services cannot respond to sudden changes in a patient's condition. Levels of patients' sense of security were significantly higher in those who agreed that "opioids can relieve most pain caused by cancer" "palliative care relieves pain and distress", "palliative care is provided along with chemotherapy and/or radiation therapy", and "pain can be alleviated as effectively through home-visit services as it can at the hospital", and those who disagreed with the statements that "home-visit services cannot respond to sudden changes in a patient's condition" and "being taken care of at home puts a burden on the family". CONCLUSIONS: Advanced cancer patients frequently had incorrect knowledge about opioids, a belief that palliative care is only for terminally ill patients, and concerns about homecare, especially the family burden and responses to sudden changes. Providing appropriate information about the safety of opioids, the availability of palliative care during the entire course of the disease, and realistic information about homecare is of marked importance to promote patients' sense of security.

A region-based palliative care intervention trial using the mixed-method approach: Japan OPTIM study.

BACKGROUND: Disseminating palliative care is a critical task throughout the world. Several outcome studies explored the effects of regional palliative care programs on a variety of end-points, and some qualitative studies investigated the process of developing community palliative care networks. These studies provide important insights into the potential benefits of regional palliative care programs, but the clinical implications are still limited, because: 1) many interventions included fundamental changes in the structure of the health care system, and, thus, the results would not be applicable for many regions where structural changes are difficult or unfeasible; 2) patient-oriented outcomes were not measured or explored only in a small number of populations, and interpretation of the results from a patient's view is difficult; and 3) no studies adopted a mixed-method approach using both quantitative and qualitative methodologies to interpret the complex phenomenon from multidimensional perspectives. METHODS/DESIGNS: This is a mixed-method regional intervention trial, consisting of a pre-post outcome study and qualitative process studies. The primary aim of the pre-post outcome study is to evaluate the change in the number of home deaths, use of specialized palliative care services, patient-reported quality of palliative care, and family-reported quality of palliative care after regional palliative care intervention. The secondary aim is to explore the changes in a variety of outcomes, including patients' quality of life, pain intensity, family care burden, and physicians' and nurses' knowledge, difficulties, and self-perceived practice. Outcome measurements used in this study include the Care Evaluation Scale, Good Death Inventory, Brief pain Inventory, Caregiving Consequence Inventory, Sense of Security Scale, Palliative Care Knowledge test, Palliative Care Difficulties Scale, and Palliative Care Self-reported Practice Scale. Study populations are a nearly representative sample of advanced cancer patients, bereaved family members, physicians, and nurses in the region.Qualitative process studies consist of 3 studies with each aim: 1) to describe the process in developing regional palliative care in each local context, 2) to understand how and why the regional palliative care program led to changes in the region and to propose a model for shaping regional palliative care, and 3) to systemically collect the barriers of palliative care at a regional level and potential resolutions. The study methodology is a case descriptive study, a grounded theory approach based on interviews, and a content analysis based on systemically collected data, respectively. DISCUSSION: This study is, to our knowledge, one of the most comprehensive evaluations of a region-based palliative care intervention program. This study has 3 unique aspects: 1) it measures a wide range of outcomes, including quality of care and quality of life measures specifically designed for palliative care populations, whether patients died where they actually preferred, the changes in physicians and nurses at a regional level; 2) adopts qualitative studies along with quantitative evaluations; and 3) the intervention is without a fundamental change in health care systems. A comprehensive understanding of the findings in this study will contribute to a deeper insight into how to develop community palliative care. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR), Japan, UMIN000001274.

Health-related quality of life among community-dwelling patients with intractable neurological diseases and their caregivers in Japan.

AIMS: The aims of this study were: (i) to clarify the general quality of life (QOL) of patients with intractable neurological disease; (ii) to clarify the general QOL of the caregivers of these patients; and (iii) to explore the association of QOL in patient-caregiver pairs. METHODS: A cross-sectional survey was conducted between November 2003 and May 2004 among community-dwelling patients diagnosed with Parkinson's disease (PD), spinocerebellar degeneration (SCD), multiple system atrophy (MSA), and amyotrophic lateral sclerosis (ALS) and their caregivers using a mailed, self-administered questionnaire. To measure QOL, we used the Medical Outcome Study 36-Item Short Form (SF-36) for patients and the short form of the health-related QOL scale SF-36 (SF-8) for caregivers. RESULTS: A total of 418 questionnaires were analyzed. For the patients, all of the general QOL domains of the SF-36 were significantly lower than the national standard value for all of the diagnoses. Physical function, role physical, and role emotional domains were also low. For caregivers, all of the QOL summary scores of the SF-8 for all diagnoses were significantly lower than the national standard value. Although there were several significant correlations of QOL between patients and caregivers, overall the correlations were low. CONCLUSIONS: Support for patients with neurological diseases and their caregivers is needed in order to maintain physical and mental QOL.

Correction: Charged metabolite biomarkers of food intake assessed via plasma metabolomics in a population-based observational study in Japan.

[This corrects the article DOI: 10.1371/journal.pone.0246456.].

Charged metabolite biomarkers of food intake assessed via plasma metabolomics in a population-based observational study in Japan.

Food intake biomarkers can be critical tools that can be used to objectively assess dietary exposure for both epidemiological and clinical nutrition studies. While an accurate estimation of food intake is essential to unravel associations between the intake and specific health conditions, random and systematic errors affect self-reported assessments. This study aimed to clarify how habitual food intake influences the circulating plasma metabolome in a free-living Japanese regional population and to identify potential food intake biomarkers. To achieve this aim, we conducted a cross-sectional analysis as part of a large cohort study. From a baseline survey of the Tsuruoka Metabolome Cohort Study, 7,012 eligible male and female participants aged 40-69 years were chosen for this study. All data on patients' health status and dietary intake were assessed via a food frequency questionnaire, and plasma samples were obtained during an annual physical examination. Ninety-four charged plasma metabolites were measured using capillary electrophoresis mass spectrometry, by a non-targeted approach. Statistical analysis was performed using partial-least-square regression. A total of 21 plasma metabolites were likely to be associated with long-term food intake of nine food groups. In particular, the influential compounds in each food group were hydroxyproline for meat, trimethylamine-N-oxide for fish, choline for eggs, galactarate for dairy, cystine and betaine for soy products, threonate and galactarate for carotenoid-rich vegetables, proline betaine for fruits, quinate and trigonelline for coffee, and pipecolate for alcohol, and these were considered as prominent food intake markers in Japanese eating habits. A set of circulating plasma metabolites was identified as potential food intake biomarkers in the Japanese community-dwelling population. These results will open the way for the application of new reliable dietary assessment tools not by self-reported measurements but through objective quantification of biofluids.

Organizational justice, psychological distress, and work engagement in Japanese workers.

PURPOSE: To investigate the cross-sectional association between organizational justice (i.e., procedural justice and interactional justice) and psychological distress or work engagement, as well as the mediating roles of other job stressors (i.e., job demands and job control, or their combination, effort-reward imbalance [ERI], and worksite support). METHODS: A total of 243 workers (185 males and 58 females) from a manufacturing factory in Japan were surveyed using a self-administered questionnaire including the Organizational Justice Questionnaire, Job Content Questionnaire, Effort-Reward Imbalance Questionnaire, K6 scale, Utrecht Work Engagement Scale, and other covariates. Multiple mediation analyses with the bootstrap technique were conducted. RESULTS: In the bivariate analysis, procedural justice and interactional justice were significantly and negatively associated with psychological distress; they were significantly and positively associated with work engagement. In the mediation analysis, reward at work (or ERI) significantly mediated between procedural justice or interactional justice and psychological distress; worksite support significantly mediated between procedural justice or interactional justice and work engagement. CONCLUSION: The effects of organizational justice on psychological distress seem to be mediated by reward at work (or ERI) while those regarding work engagement may be mediated by worksite support to a large extent, at least in Japanese workers.

Activation of an estrogen/estrogen receptor signaling by BIG3 through its inhibitory effect on nuclear transport of PHB2/REA in breast cancer.

Breast cancer is known to be a hormone-dependent disease, and estrogens through an interaction with estrogen receptor (ER) enhance the proliferative and metastatic activity of breast tumor cells. Here we show a critical role of transactivation of BIG3, brefeldin A-inhibited guanine nucleotide-exchange protein 3, in activation of the estrogen/ER signaling in breast cancer cells. Knocking-down of BIG3 expression with small-interfering RNA (siRNA) drastically suppressed the growth of breast cancer cells. Subsequent coimmunoprecipitation and immunoblotting assays revealed an interaction of BIG3 with prohibitin 2/repressor of estrogen receptor activity (PHB2/REA). When BIG3 was absent, stimulation of estradiol caused the translocation of PHB2/REA to the nucleus, enhanced the interaction of PHB2/REA and ERalpha, and resulted in suppression of the ERalpha transcriptional activity. On the other hand, when BIG3 was present, BIG3 trapped PHB2/REA in the cytoplasm and inhibited its nuclear translocation, and caused enhancement of ERalpha transcriptional activity. Our results imply that BIG3 overexpression is one of the important mechanisms causing the activation of the estrogen/ERalpha signaling pathway in the hormone-related growth of breast cancer cells.