[The Applications of qNMR in Drug Quality Control].

NMR is well known as one of the most important methods for elucidating the structure of organic compounds. Furthermore, it has recently been recognized as a powerful tool for quantitative analysis. The quantitative NMR (qNMR) has become an official analytical method described in detail in the Japanese Pharmacopoeia. And today, it is widely applied in drug development. The qNMR method offers many new advantages over traditional and conventional quantitative analysis methods. For example, this method requires only a few milligrams of the analyte and allows absolute quantitation of the analyte without using a qualified reference standard as a control sample. Then, it can be easily applied to most chemicals without expending significant time and resources on method development. In addition, residual solvent can be determined using qNMR methods. The peak area of an NMR spectrum is directly proportional to the number of protons contributing to the resonance. Based on this principle, the residual solvent can be determined by counting the signal corresponding to the residual solvent in the sample solution. We have applied qNMR as an alternative to GC. Thus, qNMR is an innovative and promising analytical technique that is expected to make significant progress in the future. Recently, the analytical research and quality control departments have been working together to expand this technology to a wide range of areas in the pharmaceutical industry.

Quantitative 31P-NMR for the Purity Determination of the Organophosphorus Compound Brigatinib and Its Method Validation.

The spectrum of 31P-NMR is fundamentally simpler than that of 1H-NMR; consequently identifying the target signal(s) for quantitation is simpler using quantitative 31P-NMR (31P-qNMR) than using quantitative 1H-NMR (1H-qNMR), which has been already established as an absolute determination method. We have previously reported a 31P-qNMR method for the absolute determination of cyclophosphamide hydrate and sofosbuvir as water-soluble and water-insoluble organophosphorus compounds, respectively. This study introduces the purity determination of brigatinib (BR), an organophosphorus compound with limited water solubility, using 31P-qNMR at multiple laboratories. Phosphonoacetic acid (PAA) and 1,4-BTMSB-d4 were selected as the reference standards (RSs) for 31P-qNMR and 1H-qNMR, respectively. The qNMR solvents were chosen based on the solubilities of BR and the RSs for qNMR. CD3OH was selected as the solvent for 31P-qNMR measurements to prevent the influence of deuterium exchange caused by the presence of exchangeable intramolecular protons of BR and PAA on the quantitative values, while CD3OD was the solvent of choice for the 1H-qNMR measurements to prevent the influence of water signals and the exchangeable intramolecular protons of BR and PAA. The mean purity of BR determined by 31P-qNMR was 97.94 ± 0.69%, which was in agreement with that determined by 1H-qNMR (97.26 ± 0.71%), thus indicating the feasibility of purity determination of BR by 31P-qNMR. Therefore, the findings of this study may provide an effective method that is simpler than conventional 1H-qNMR for the determination of organophosphorus compounds.

Corrigendum: What kind of intervention is effective for improving subjective well-being among workers? A systematic review and meta-analysis of randomized controlled trials.

[This corrects the article DOI: 10.3389/fpsyg.2020.528656.].

Spread through air spaces is a powerful prognostic predictor in patients with completely resected pathological stage I lung adenocarcinoma.

PURPOSE: To evaluate the frequency of spread through air spaces (STAS) in patients with early-stage primary lung cancer and to elucidate the association between STAS and various clinicopathological factors. METHODS: We retrospectively reviewed data from a total of 265 consecutive patients who underwent lobectomy and mediastinal lymph node dissection (172 patients) or sublobar resection (93 patients) for completely resected pathological stage I lung adenocarcinoma. We evaluated clinical variables, including the preoperative serum carcinoembryonic antigen (CEA) level, tumour size, consolidation tumour ratio (CTR), maximum standardized uptake value (SUVmax) on FDG-PET, histological results, presence of STAS and vascular and lymphatic invasion. RESULTS: The median follow-up time after surgery was 49 months. Eighty-seven patients (32.8 %) had STAS. The overall survival rates of patients in the STAS-positive and STAS-negative groups were 92.7 % and 97.1 % at 3 years, respectively (p = 0.1255), and the recurrence-free survival rates were 82.1 % and 95.9 % at 3 years, respectively (p = 0.0001). STAS was found in 73 patients (42.4 %) in the lobectomy group, which was a significantly higher proportion than the 14 patients (15.1 %) in the sublobar resection group. The STAS-positive group had significantly larger areas of invasion, higher CTRs, preoperative CEA and SUVmax levels, and more lymphatic and vascular invasion. STAS also correlated significantly with large consolidation sizes, larger invasive size, higher CTRs and the presence of a micropapillary pattern. Cox regression analysis after adjustment for important prognostic factors revealed that the presence of STAS was an independent predictor associated with postoperative recurrence, most of which was observed locoregionally. CONCLUSIONS: STAS was an independent factor associated with postoperative recurrence after lung resection for stage I lung adenocarcinoma. Among stage IA patients, the postoperative outcomes of STAS-positive patients were worse than those of STAS-negative patients and were similar to those of stage IB patients.

Quantitative 31P-NMR for Purity Determination of Sofosbuvir and Method Validation.

Quantitative 1H-NMR (1H-qNMR) is useful for determining the absolute purity of organic molecules; however, it is sometimes difficult to identify the target signal(s) for quantitation because of their overlap and complexity. Therefore, we focused on the 31P nucleus because of the simplicity of its signals and previously reported 31P-qNMR in D2O. Here we report 31P-qNMR of an organophosphorus compound, sofosbuvir (SOF), which is soluble in organic solvents. Phosphonoacetic acid (PAA) and 1,4-bis(trimethylsilyl)benzene-d4 (1,4-BTMSB-d4) were used as reference standards for 31P-qNMR and 1H-qNMR, respectively, in methanol-d4. The purity of SOF determined by 31P-qNMR was 100.63 ± 0.95%, whereas that determined by 1H-qNMR was 99.07 ± 0.50%. The average half bandwidths of the 31P signal of PAA and SOF were 3.38 ± 2.39 and 2.22 ± 0.19 Hz, respectively, suggesting that the T2 relaxation time of the PAA signal was shorter than that of SOF and varied among test laboratories. This difference most likely arose from the instability in the chemical shift due to the deuterium exchange of the acidic protons of PAA, which decreased the integrated intensity of the PAA signal. Next, an aprotic solvent, dimethyl sulfoxide-d6 (DMSO-d6), was used as the dissolving solvent with PAA and sodium 4,4-dimethyl-4-silapentanesulfonate-d6 (DSS-d6) as reference standards for 31P-qNMR and 1H-qNMR, respectively. SOF purities determined by 31P-qNMR and 1H-qNMR were 99.10 ± 0.30 and 99.44 ± 0.29%, respectively. SOF purities determined by 31P-qNMR agreed with the established 1H-qNMR values, suggesting that an aprotic solvent is preferable for 31P-qNMR because it is unnecessary to consider the effect of deuterium exchange.

The impact of workplace psychosocial factors on menstrual disorders and infertility: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Workplace environment, especially psychosocial factors at work such as job strain, workplace social support, and shift work, may affect the menstrual abnormalities and fertility of female workers. However, the association between psychosocial factors at work and menstrual abnormalities or fertility is not well understood. To address this relationship, we will conduct a systematic review and a meta-analysis of the literature that has utilized a longitudinal or prospective cohort design. METHODS AND ANALYSIS: The inclusion criteria for this systematic review and meta-analysis are defined as follows: (P) adult female workers (over 18 years old), (E) the presence of adverse psychosocial factors at work, (C) the absence of adverse psychosocial factors at work, and (O) any menstrual cycle disorders, menstrual-related symptoms, or fertility. The MEDLINE, Embase, PsycINFO, PsycArticles, and Japan Medical Abstracts Society electronic databases will be used to search for published studies. The statistical synthesis of the studies included in the meta-analysis will be conducted to estimate pooled coefficients and 95% CIs. For the main analysis, we will synthesize measures of association between psychosocial factors at work and menstrual-related disorders/symptoms. At least three eligible studies will have to be gathered to conduct a meta-analysis; otherwise (i.e., if only one or two studies will be eligible and included), the results will be presented in a narrative table. We will use the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) to determine the quality of selected studies. To assess meta-bias, Egger's test, along with a funnel plot, will be used to check for publication bias. Lastly, we will examine heterogeneity using the χ2 test with Cochran's Q statistic and I2. ETHICS AND DISSEMINATION: The results and findings will be submitted and published in a scientific peer-reviewed journal and will be disseminated broadly to researchers and policymakers interested in the translatability of scientific evidence into good practices. SYSTEMATIC REVIEW REGISTRATION: The study protocol was registered at the UMIN registry (registration number: UMIN000039488). The registration date is on 14 Feb 2020. URL: https://upload.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000044704.

STRENGTH AND LIMITATIONS OF THIS STUDY: • This systematic review and a meta-analysis will investigate the associations between psychosocial factors at work and menstrual abnormalities or fertility. • This review will include only the literature that has utilized a longitudinal design. • Various outcomes related to reproductive health in female workers will be examined (e.g., fertility, premenstrual symptoms, cycle disorders, menopausal symptoms).

Associations between work-related stressors and QALY in a general working population in Japan: a cross-sectional study.

OBJECTIVE: To investigate an association between quality-adjusted life years (QALY) and work-related stressors (job strain, effort/reward imbalance, and poor support from supervisor and coworkers), and estimate loss in QALY caused by these stressors. METHODS: A cross-sectional study investigated data from a third-wave survey (in December 2017) of a 2-year prospective cohort study of Japanese workers. At baseline (first-wave survey), 5000 participants were recruited from workers who registered with an internet survey company. A total of 2530 participants responded to the second-wave survey 1 year later. Participants were then further recruited to the third-wave survey. An online questionnaire collected information regarding health-related quality of life (measured by EQ-5D-5L), job strain, supervisor and coworker support (Brief Job Stress Questionnaire), effort/reward imbalance (Effort/reward Imbalance Questionnaire), and demographic variables (age, sex, education, occupation, work contract, smoking, and alcohol drinking). Multiple linear regression analysis of the QALY score calculated from responses to EQ-5D-5L was employed on standardized scores of the work-related stressors and adjusted for demographic variables (SPSS version 26). RESULTS: Data of 1986 participants were analyzed. Job strain (unstandardized coefficient, b = - 0.013, p < 0.01) and effort/reward imbalance (b = - 0.011, p < 0.01) and coworker support (b = 0017, p < 0.01) were significantly associated with QALY score in the fully adjusted model. CONCLUSION: Job strain, effort/reward imbalance, and poor coworker support may be associated with a reduced QALY score among workers. A substantial impairment in QALY associated with the work-related stressors indicates that workplace interventions targeting work-related stressors may be cost-effective.

Purity Determination of Cyclophosphamide Hydrate by Quantitative 31P-NMR and Method Validation.

Recently, quantitative NMR (qNMR), especially 1H-qNMR, has been widely used to determine the absolute quantitative value of organic molecules. We previously reported an optimal and reproducible sample preparation method for 1H-qNMR. In the present study, we focused on a 31P-qNMR absolute determination method. An organophosphorus compound, cyclophosphamide hydrate (CP), listed in the Japanese Pharmacopeia 17th edition was selected as the target compound, and the 31P-qNMR and 1H-qNMR results were compared under three conditions with potassium dihydrogen phosphate (KH2PO4) or O-phosphorylethanolamine (PEA) as the reference standard for 31P-qNMR and sodium 4,4-dimethyl-4-silapentanesulfonate-d6 (DSS-d6) as the standard for 1H-qNMR. Condition 1: separate sample containing CP and KH2PO4 for 31P-qNMR or CP and DSS-d6 for 1H-qNMR. Condition 2: mixed sample containing CP, DSS-d6, and KH2PO4. Condition 3: mixed sample containing CP, DSS-d6, and PEA. As conditions 1 and 3 provided good results, validation studies at multiple laboratories were further conducted. The purities of CP determined under condition 1 by 1H-qNMR at 11 laboratories and 31P-qNMR at 10 laboratories were 99.76 ± 0.43 and 99.75 ± 0.53%, respectively, and those determined under condition 3 at five laboratories were 99.66 ± 0.08 and 99.61 ± 0.53%, respectively. These data suggested that the CP purities determined by 31P-qNMR are in good agreement with those determined by the established 1H-qNMR method. Since the 31P-qNMR signals are less complicated than the 1H-qNMR signals, 31P-qNMR would be useful for the absolute quantification of compounds that do not have a simple and separate 1H-qNMR signal, such as a singlet or doublet, although further investigation with other compounds is needed.

[Expected research in the workplace among Japanese female workers: A cross-sectional online survey based on the framework of patient and public involvement].

OBJECTIVES: This study aimed to investigate the work-related health and social problems among Japanese female workers and the expected research in the workplace. METHOD: A cross-sectional study using an Internet survey was conducted on female workers in Japan. Using an original questionnaire, we obtained data on "a system that can be used by female workers," "female workers' problems (physical symptoms, mental symptoms, menstrual problems, pregnancy/childbirth problems, work-life balance, etc.)," and "expected research in the workplace." The last two were compared using the chi-square test and considering demographic characteristics (age, marital status, having children, having preschool children, employment status, occupation). We conducted the chi-square test to examine the relationship between the presence of symptoms and four expected studies. The survey was carried out in July 2019 by using a patient and public involvement (PPI) framework in medical research. RESULTS: We obtained 416 responses that highlighted that those who have work-related problems also have physical symptoms (89%), menstrual problems (65%), psychiatric symptoms (49%), and work-life balance problems (39%), followed by career as well as pregnancy and childbirth concerns (38%). Regarding the system, the respondents' usage rate was an infertility treatment communication card (0%), flextime and telework (1 to 3%), menstrual leave (4%), and short-time work system (8%). Expected workplace studies included "Research to ease stiff shoulders and back pain" (45%), "Research to improve women's mental health" (41%), "Research on menstruation and work performance" (35%), and "Research to improve work-life balance" (34%). Expectations for research on "mental health" and "menstruation" were high among subjects in their 20s and 30s, with no spouse or children, and working full-time. Among those who lived with preschoolers, expectations for research on "mental support after childbirth," "physical support after childbirth," and "prevention of postpartum depression" were significantly higher, but research related to work-life balance was not remarkably different. There was a significant association between having menstrual problems, work-life balance challenges, and study expectations. However, the percentage of those experiencing certain symptoms who expected workplace studies was about 48%. CONCLUSIONS: Menstruation-related symptoms are frequently observed to make work difficult and it is expected that health issues, such as mental and physical conditions related to gynecology, will be the subject of future research regarding female workers. However, discrepancies between having difficulties and whether or not they wish to accept research in the workplace should be carefully considered in each context.

Absolute Purity Determination of a Hygroscopic Substance, Indocyanine Green, Using Quantitative NMR (qNMR).

Quantitative NMR (qNMR) is applied to determine the absolute quantitative value of analytical standards for HPLC-based quantification. We have previously reported the optimal and reproducible sample preparation method for qNMR of hygroscopic reagents, such as saikosaponin a, which is used as an analytical standard in the assay of crude drug section of Japanese Pharmacopoeia (JP). In this study, we examined the absolute purity determination of a hygroscopic substance, indocyanine green (ICG), listed in the Japanese Pharmaceutical Codex 2002, using qNMR for standardization by focusing on the adaptation of ICG to JP. The purity of ICG, as an official non-Pharmacopoeial reference standard (non-PRS), had high variation (86.12 ± 2.70%) when preparing qNMR samples under non-controlled humidity (a conventional method). Additionally, residual ethanol (0.26 ± 0.11%) was observed in the non-PRS ICG. Next, the purity of non-PRS ICG was determined via qNMR when preparing samples under controlled humidity using a saturated sodium bromide solution. The purity was 84.19 ± 0.47% with a lower variation than that under non-controlled humidity. Moreover, ethanol signal almost disappeared. We estimated that residual ethanol in non-PRS ICG was replaced with water under controlled humidity. Subsequently, qNMR analysis was performed when preparing samples under controlled humidity in a constant temperature and humidity box. It showed excellent results with the lowest variation (82.26 ± 0.19%). As the use of a constant temperature and humidity box resulted in the lowest variability, it is recommended to use the control box if the reference ICG standard is needed for JP assays.

What Kind of Intervention Is Effective for Improving Subjective Well-Being Among Workers? A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objectives: This study aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to improve subjective well-being (SWB), including evaluative, hedonic, and eudemonic well-being, and the mental component of quality of life (QOL) of working population. Methods: A literature search was conducted, using PubMed, Embase, PsycINFO, and PsycARTICLES. Eligible studies included those that were RCTs of any intervention, conducted among healthy workers, measured SWB as a primary outcome, and original articles in English. Study characteristics, intervention, outcomes, and results on SWB outcomes were extracted by the investigators independently. After a brief narrative summarizing and classifying the contents of the interventions, the included outcomes were categorized into each aspect of SWB (evaluative, hedonic, and eudemonic well-being, and the mental component of QOL). Finally, the characteristics of the effective interventions for increasing each aspect were summarized, and the pooled effect of interventions on SWB was investigated by a meta-analysis. Publication bias was investigated by drawing a funnel plot and conducting Egger's test. Results: From the 5,450 articles found, 39 met the inclusion criteria for the systematic review. The interventions included in this review were classified into six categories (physical activity, ergonomics, psychological, environmental, multicomponent intervention, and others). The meta-analysis from 31 studies showed that the pooled effect of included interventions on SWB was significantly positive (standardized mean difference (SMD) = 0.51; standard error (SE) = 0.10). A funnel plot showed there were extremely large or small SMDs, and Egger's test was significant. Thus, we conducted sensitivity analysis, excluding these extreme SMDs, and confirmed that the estimated pooled effect was also significantly positive. Subgroup analyses for separate types of interventions showed the effects of psychological interventions (e.g., mindfulness, cognitive behavioral based approach, and other psychological interventions) were also significantly positive. Conclusion: The current study revealed the effectiveness of interventions for increasing SWB. Specifically, psychological interventions (e.g., mindfulness, cognitive behavioral based approach, and other psychological interventions) may be useful for improving SWB.

Association between psychosocial factors at work and health outcomes after retirement: a protocol for a systematic review and meta-analysis.

INTRODUCTION: The world's population is rapidly ageing, and health among older people is thus an important issue. Several previous studies have reported an association between adverse psychosocial factors at work before retirement and postretirement health. The objective of this systematic review and meta-analysis is to examine the association between psychosocial factors at work and health outcomes after retirement, based on a synthesis of well-designed prospective studies. METHODS AND ANALYSIS: The participants, exposures, comparisons and outcomes of the studies in this systematic review and meta-analysis are defined as follows: (P) people who have retired from their job, (E) presence of adverse psychosocial factors at work before retirement, (C) absence of adverse psychosocial factors at work before retirement and (O) any physical and mental health outcomes after retirement. Published studies were searched using the following electronic databases: MEDLINE, EMBASE, PsycINFO, PsycARTICLES and Japan Medical Abstracts Society. The included studies will be statistically synthesised in a meta-analysis to estimate pooled coefficients and 95% CIs. The quality of each included study will be assessed using the Risk Of Bias In Non-randomised Studies-of Interventions. For the assessment of meta-bias, publication bias will be assessed by using Egger's test, as well as visually on a funnel plot. Heterogeneity will be assessed using the χ² test with Cochran's Q statistic and I2. ETHICS AND DISSEMINATION: Results and findings will be submitted and published in a scientific peer-reviewed journal and will be disseminated broadly to researchers and policy-makers interested in the translatability of scientific evidence into good practices. PROSPERO REGISTRATION NUMBER: CRD42018099043.

Psychosocial factors at work and inflammatory markers: protocol for a systematic review and meta-analysis.

INTRODUCTION: Chronic inflammation may be a mediator for the development of cardiovascular disease (CVD), metabolic diseases and psychotic and neurodegenerative disorders. Meta-analytic associations between work-related psychosocial factors and inflammatory markers have shown that work-related psychosocial factors could affect the flexibility and balance of the immune system. However, few systematic reviews or meta-analyses have investigated the association between work-related psychosocial factors and inflammatory markers. Based on prospective studies, the present investigation will conduct a comprehensive systematic review and meta-analysis of the association between work-related psychosocial factors and inflammatory markers. METHODS AND ANALYSIS: The systematic review and meta-analysis will include published studies identified from electronic databases (PubMed, EMBASE, PsycINFO, PsycARTICLES, Web of Science and Japan Medical Abstracts Society) according to recommendations of the Meta-analysis of Observational Studies in Epidemiology guideline. Inclusion criteria are studies that: examined associations between work-related psychosocial factors and increased inflammatory markers; used longitudinal or prospective cohort designs; were conducted among workers; provided sufficient data for calculating ORs or relative risk with 95% CIs; were published as original articles in English or Japanese; and were published up to the end of 2017. Study selection, data extraction, quality assessment and statistical syntheses will be conducted by 14 investigators. Any inconsistencies or disagreements will be resolved through discussion. The quality of studies will be evaluated using the Risk of Bias Assessment Tool for Non-randomized Studies. ETHICS AND DISSEMINATION: The investigation study will be based on published studies, so ethics approval is not required. The results of this study will be submitted for publication in a scientific peer-reviewed journal. The findings may be useful for assessing risk factors for increased inflammatory markers in the workplace and determining future approaches for preventing CVD, metabolic diseases and psychotic and neurodegenerative disorders. PROSPERO REGISTRATION NUMBER: CRD42018081553.

Effect of the National Stress Check Program on mental health among workers in Japan: A 1-year retrospective cohort study.

OBJECTIVES: This retrospective cohort study evaluated the impact of the Stress Check Program, a recently introduced national policy and program aimed at reducing psychological distress among Japanese workers. METHODS: A baseline survey was conducted from November 2015 to February 2016, the period when Japan began enforcing the Stress Check Program. A one-year follow-up survey was conducted in December 2016. In the follow-up survey, two exposure variables were collected: having taken the annual stress survey, and experiencing an improvement in the psychosocial work environment. Psychological distress was assessed using the Brief Job Stress Questionnaire (BJSQ) at baseline and 1-year follow-up. The two exposure variables were used to define four groups: "Neither", "Stress survey (SS) only", "Psychosocial work environment improvement (WI) only", and "Both". BJSQ results were analyzed using repeated measures general linear modeling (GLM). RESULTS: The study included 2,492 participants: 1,342 in the "Neither" group, 1,009 in the "SS only" group, 76 in the "WI only" group, and 65 in the "Both" group. Overall time-group interaction effects were not significant. The "Both" group showed significantly greater improvements in psychological distress than the "Neither" group (p = 0.02) at the 1-year follow-up, although the effect size was small (d = -0.14). CONCLUSIONS: Combination of the annual stress survey and improvement in psychosocial work environment may have been effective in reducing psychological distress in workers, although the effect size was small.

Pokémon GO and psychological distress, physical complaints, and work performance among adult workers: a retrospective cohort study.

The effects of Pokémon GO, a new mobile game application which utilizes augmented reality, on risky behavior and health have already been discussed in anecdotal evidence. However, there have been no studies about its effects on mental health. This study investigated the relationships between Pokémon GO and psychological distress from an existing workers' cohort in Japan. Online surveys were conducted to 3,915 full-time workers, at baseline (Nov 26, 2015-Feb 18, 2016) and at follow-up (Dec 1-4, 2016), using a self-report questionnaire. Pokémon GO players were defined as participants who had played Pokémon GO for one month or longer. Psychological distress was measured using validated scales. Of the completers, 246 (9.7%) had continued to play Pokémon GO. They were significantly younger than non-players. From the results of the general linear modeling, improvement in psychological distress was significantly greater among Pokémon GO players than among non-players (p = 0.025). Cohen's d for the difference in psychological distress was -0.20 (95% CI, -0.33, -0.07). Pokémon GO may be effective for improving psychological distress among workers. Although its effect size is small, the game could have positive effects on the mental health of the adult working population.

Association of Job Stressors With Panic Attack and Panic Disorder in a Working Population in Japan: A Cross-Sectional Study.

OBJECTIVE: This study aimed to investigate associations of job stressors with panic attack (PA) and panic disorder (PD) among Japanese workers. METHODS: A cross-sectional online questionnaire survey was conducted of 2060 workers. Job strain, effort/reward imbalance, and workplace social support were measured by the job content questionnaire and effort/reward imbalance questionnaire. These variables were classified into tertiles. PA/PD were measured by self-report based on the mini international neuropsychiatric interview (MINI). Multiple logistic regression was conducted, adjusting for demographic, lifestyle, and health-related covariates. RESULTS: Data from 1965 participants were analyzed. Adjusted odds ratio (OR) of PA/PD was significantly greater for the group with high effort/reward imbalance compared with the group with low effort/reward imbalance (ORs, 2.64 and 2.94, respectively, both P < 0.05). CONCLUSION: This study found effort/reward imbalance was associated with having PA/PD among Japanese workers.

Work-related psychosocial factors and onset of metabolic syndrome among workers: a systematic review and meta-analysis protocol.

INTRODUCTION: Metabolic syndrome is an important public health target because of its high prevalence worldwide. Work-related psychosocial factors have been identified as determinants of metabolic syndrome components. However, there have been no systematic reviews or meta-analyses conducted to evaluate the relationship between work-related psychosocial factors and metabolic syndrome as an aggregated cluster. The aim of this study is to examine this association from published prospective studies. METHODS AND ANALYSIS: The systematic review and meta-analysis will be conducted using published studies that will be identified from electronic databases (ie, PubMed, EMBASE, PsycINFO, PsycARTICLES and Japan Medical Abstracts Society). Studies that (1) examined the association between work-related psychosocial factors and the onset of metabolic syndrome, (2) had a longitudinal or prospective cohort design, (3) were conducted among workers, (4) provided sufficient data for calculating ORs or relative risk with a 95% CI, (5) were published as original articles written in English or Japanese, and (6) having been published until the end of 2016 will be included. Study selection, data collection, quality assessment and statistical syntheses will be conducted based on discussions among investigators. ETHICS AND DISSEMINATION: Ethics approval was not required for this study because it was based on published studies. The results and findings of this study will be submitted and published in a scientific peer-reviewed journal. The findings from this study could be useful for assessing metabolic syndrome risk factors in the workplace, and determining approaches for prevention of metabolic syndrome in the future. TRIAL REGISTRATION NUMBER: PROSPERO CRD42016039096 (http://www.crd.york.ac.uk/PROSPERO_REBRANDING/display_record.asp?ID=CRD42016039096).

The effect of a behavioral activation program on improving mental and physical health complaints associated with radiation stress among mothers in Fukushima: a randomized controlled trial.

BACKGROUND: Mothers living with small children in Fukushima prefecture may experience radiation anxiety and related symptoms after the Fukushima Dai'ich Nuclear Power Plant Accident. A behavioral activation (BA) program was developed to improve their psychosomatic symptoms. The purpose of this randomized controlled trial was to examine the effectiveness of a BA program for improving psychological distress and physical symptoms among mothers with preschool children in Fukushima-prefecture 3 years after the Fukushima Daiichi Nuclear Power Plant accident. METHODS: Participants were recruited from mothers living with a preschool child(ren) in Fukushima city and surrounding areas though a newspaper advertisement, posters, and flyers. Participants allocated to the intervention group received a newly developed group-based BA program, which consisted of two 90- min lessons with a 1-week interval. Psychological distress and physical symptoms as a primary outcome, and radiation anxiety and positive well-being (liveliness and life satisfaction) as a secondary outcome, were measured at baseline, 1- and 3-month follow-ups. RESULTS: Participants were randomly allocated to either an intervention or a control group (18 and 19, respectively). The BA program showed a marginally significant intervention effect on psychological distress (p = 0.051) and physical symptoms (p = 0.07) at 1-month follow-up, while the effect became smaller at 3-month follow-up. The effect sizes at 1-month were medium to large (-0.72 and -0.56, respectively). There was a significant intervention effect on increasing liveliness at 3-month follow-up (p = 0.02); and there were marginally significant effects on life satisfaction at 1- and 3-month follow-ups (both p = 0.09). CONCLUSIONS: This BA program may be effective for improving psychological distress, physical symptoms, and well-being, at least for a short duration, among mothers with preschool children after the nuclear power plant accident in Fukushima, while a further large-scale study is needed. TRIAL REGISTRATION: The UMIN Clinical Trials Registry (UMIN-CTR; ID = UMIN000014081 ). Registered 27 May 2014.

Trans-3,4-dideoxyglucone-3-ene (trans-3,4-DGE), a most reactive glucose degradation product in freshly heat sterilized glucose solutions.

In our study, one or more glucose degradation products (GDPs) in freshly heat sterilized dextrose 5% in water (D5W) were found to react with a drug candidate having a ß-keto amide group (Compound A) to form several drug related compounds with the same molecular weight. However the previously identified GDPs did not react with Compound A to produce the observed adducts, indicating that unidentified GDP(s) reacted with Compound A to form these adducts. Our investigation by reaction-directed fractionation of the reactive D5W with HPLC led to the identification of the reactive GDP, trans-3,4-dideoxyglucosone-3-ene (trans-3,4-DGE), responsible for producing these reaction products. The trans-3,4-DGE was identified from its derivatives of dinitrophenylhydrazine (DNPH) and acetoacetanilide and confirmed by (1) admixing Compound A with authentic trans-3,4-DGE to produce the identical impurities as admixing with freshly heat sterilized D5W, and (2) NMR analysis of the reactive fraction of glucose solutions.

Mycoleptodiscins A and B, cytotoxic alkaloids from the endophytic fungus Mycoleptodiscus sp. F0194.

Two novel reddish-orange alkaloids, mycoleptodiscin A (1) and mycoleptodiscin B (2), were isolated from liquid cultures of the endophytic fungus Mycoleptodiscus sp. that had been isolated from Desmotes incomparabilis in Panama. Elucidation of their structures was accomplished using 1D and 2D NMR spectroscopy in combination with IR spectroscopic and MS data. These compounds are indole-terpenes with a new skeleton uncommon in nature. Mycoleptodiscin B (2) was active in inhibiting the growth of cancer cell lines with IC50 values in the range 0.60-0.78 µM.