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Background We aimed to develop a chemoimmunotherapy regimen consisting of a novel Wilms’ tumor 1 (WT1) peptide-pulsed dendritic cell (WT1-DC) vaccine and multiagent chemotherapy and to investigate the safety, clinical outcomes, and WT1-specific immune responses of patients with unresectable advanced pancreatic ductal adenocarcinoma (UR-PDAC) who received this treatment.Methods Patients with UR-PDAC with stage III disease (locally advanced (LA-PDAC; n=6)), stage IV disease (metastatic (M-PDAC; n=3)), or recurrent disease after surgery (n=1) were enrolled in this phase I study. The patients received one cycle of nab-paclitaxel plus gemcitabine alone followed by 15 doses of the WT1-DC vaccine independent of chemotherapy. The novel WT1 peptide cocktail was composed of a multifunctional helper peptide specific for major histocompatibility complex class II, human leukocyte antigen (HLA)-A*02:01, or HLA-A*02:06 and a killer peptide specific for HLA-A*24:02.Results The chemoimmunotherapy regimen was well tolerated. In the nine patients for whom a prognostic analysis was feasible, the clinical outcomes of long-term WT1 peptide-specific delayed-type hypersensitivity (WT1-DTH)-positive patients (n=4) were significantly superior to those of short-term WT1-DTH-positive patients (n=5). During chemoimmunotherapy, eight patients were deemed eligible for conversion surgery and underwent R0 resection (four patients with LA-PDAC, one patient with M-PDAC, and one recurrence) or R1 resection (one patient with M-PDAC), and one patient with LA-PDAC was determined to be unresectable. Long-term WT1-DTH positivity was observed in three of the four patients with R0-resected LA-PDAC. These three patients exhibited notable infiltration of T cells and programmed cell death protein-1+ cells within the pancreatic tumor microenvironment (TME). All patients with long-term WT1-DTH positivity were alive for at least 4.5 years after starting therapy. In patients with long-term WT1-DTH positivity, the percentage of WT1-specific circulating CD4+ or CD8+ T cells that produced IFN-γ or TNF-α was significantly greater than that in patients with short-term WT1-DTH positivity after two vaccinations. Moreover, after 12 vaccinations, the percentages of both circulating regulatory T cells and myeloid-derived suppressor cells were significantly lower in patients with long-term WT1-DTH-positive PDAC than in short-term WT1-DTH-positive patients.Conclusions Potent activation of WT1-specific immune responses through a combination chemoimmunotherapy regimen including the WT1-DC vaccine in patients with UR-PDAC may modulate the TME and enable conversion surgery, resulting in clinical benefits (Online supplemental file 1).Trial registration number jRCTc030190195.

Abstract Objective Inflammatory bowel disease (IBD) is closely related to stress and fatigue. Human herpesvirus 6B (HHV‐6B) is reactivated by stress and fatigue and is associated with IBD. This study aimed to clarify the relationship between IBD and HHV‐6B. Methods Antibody titers to SITH‐1, a protein specific to HHV‐6B latent infection, were measured in 163 patients with IBD (107 with ulcerative colitis [UC] and 56 with Crohn's disease [CD]); clinical and endoscopic scores and depression scores of UC and CD were analyzed to examine the relationship between SITH‐1 and IBD. The SITH‐1 cut‐off value was set as 1.96, according to known reports. Results In patients with UC, C‐reactive protein (CRP) level was significantly higher (1.5 vs 0.6 mg/L, P = 0.006) and disease exacerbation within 6 months after entry was significantly more common in the SITH‐1 (+) group (20% vs 0%, P

Summary: The heritability of major depressive disorder (MDD) is reportedly 30–50%. However, the genetic basis of its heritability remains unknown. Within SITH-1, a risk factor for MDD in human herpesvirus 6B (HHV-6B), we discovered a gene polymorphism with a large odds ratio for an association with MDD. It was a sequence whose number of repeats was inversely correlated with SITH-1 expression. This number was significantly lower in MDD patients. Rates for 17 or fewer repeats of the sequence were 67.9% for MDD and 28.6% for normal controls, with an odds ratio of 5.28. For patients with 17 or less repeats, the rate for presence of another MDD patient in their families was 47.4%, whereas there were no MDD patients in the families of patients with more than 17 repeats. Since HHV-6B is transmitted primarily mother to child and within families and persists for life, this gene polymorphism could potentially influence heritability of MDD.

Abstract Aims/Introduction We aimed to study the relationships among the copper (Cu)/zinc (Zn) ratio, inflammatory biomarkers, and the prevalence of diabetic kidney disease (DKD) in patients with type 2 diabetes. Materials and Methods A cross‐sectional study was performed on 651 patients with type 2 diabetes. DKD was defined as a urinary albumin‐to‐creatinine ratio of ≥30 mg/g creatinine and/or an estimated glomerular filtration rate using cystatin C of

Background: Students and workers have been subjected to increased levels of psychological distress due to the quarantine policy and containment measures during the COVID-19 pandemic. This scoping review aimed to present an overview of published evidence regarding formal and informal help-seeking intentions/behaviors for non-mental health-related issues as well as mental health-related issues among students and workers during the pandemic. Methods: In June 2022, we searched MEDLINE, APA PsycNet, and CINAHL for articles reporting the state of help-seeking intentions/behaviors among students and workers during the pandemic. Peer-reviewed original articles published in English were selected. Results: In total, 150 articles were identified, and 12 articles were selected for final analysis after removing articles that met the exclusion criteria. Three studies targeted university students, and nine targeted healthcare workers. Study settings were restricted to Western countries and China. Of the 12 studies, 11 were observational and predominantly cross-sectional studies. Two longitudinal studies using student samples suggested that university students became more reluctant to seek help from both formal and informal sources during the COVID-19 pandemic compared to before, despite the increased need for support during the pandemic. Among healthcare workers, the proportions of those who sought help from formal sources in person were low (7–26%), even among those with mental health issues, despite the increase in the need for mental health services. One randomized controlled study reported that a brief video-based intervention increased treatment-seeking intentions among healthcare workers in the intervention group compared with the non-intervention group. Conclusions: The present review revealed that, although most studies included in the final analysis were cross-sectional, intentions/behaviors to seek help from both formal and informal sources decreased among university students, even those with mental health issues. Among healthcare workers, while the frequency of help-seeking from formal sources in person was low, a brief online intervention was suggested to be useful for promoting help-seeking from formal sources. During public health crises such as the COVID-19 pandemic, system and infrastructure development of online help-seeking services could potentially promote formal and informal help-seeking intentions/behaviors for diverse issues, including non-mental health-related issues, among university students and healthcare workers/providers.

Abstract Background Both activated tumor-infiltrating lymphocytes (TILs) and immune-suppressive cells, such as regulatory T cells (Tregs), in the tumor microenvironment (TME) play an important role in the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). Methods The densities of TILs, programmed death receptor 1 (PD-1) + T cells, and forkhead box P3 (Foxp3) + T cells were analyzed by immunohistochemical staining. The associations of the immunological status of the PDAC microenvironment with overall survival (OS) time and disease-free survival (DFS) time were evaluated. Results PDAC patients with a high density of TILs in the TME or PD-1-positive T cells in tertiary lymphoid aggregates (TLAs) demonstrated a significantly better prognosis than those with a low density of TILs or PD-1-negativity, respectively. Moreover, PDAC patients with high levels of Foxp3-expressing T cells showed a worse prognosis than those with low levels of Foxp3-expressing T cells. Importantly, even with a high density of the TILs in TME or PD-1-positive T cells in TLAs, PDAC patients with high levels of Foxp3-expressing T cells showed a worse prognosis than patients with low levels of Foxp3-expressing T cells. A PDAC TME with a high density of TILs/high PD-1 positivity/low Foxp3 expression was an independent predictive marker associated with superior prognosis. Conclusion Combined assessment of TILs, PD-1+ cells, and Foxp3+ T cells in the TME may predict the prognosis of PDAC patients following surgical resection.

Background: For patients with neurofibromatosis type 2 (NF2), maintaining an independent state of living is important. The present study aimed to examine the loss of social independence (i.e., a status that patients can work and go to school) and its contributing factors in patients with NF2 using data from a national registry in Japan. Methods: This longitudinal study used a registry database containing information on patients with NF2 who had submitted initial claims to receive medical expense subsidies between 2004 and 2010. Patients with “employed,” “studying,” and “housekeeping” categories were classified as “socially independent.” Patients who were socially independent at baseline were followed-up for up to nine years. The primary outcome of the present study was the loss of social independence during the follow-up period, which was defined as the change in status from being socially independent to socially dependent. First, we examined longitudinal associations between demographic variables and neurological symptoms at baseline and the loss of social independence. Second, we examined whether the occurrence of neurological symptoms is associated with a loss of social independence in patients. Results: A total of 156 patients were included in the present study. During the follow-up period, 37 (23.7%) patients experienced a loss of social independence. In the first analysis, the multivariate logistic regression model showed that the loss of social independence was significantly more frequent among patients with spinal dysfunction than among patients without. In the second analysis, logistic regression analyses showed that neurological symptoms, including bilateral hearing loss, facial nerve palsy, cerebellar dysfunction, decreased facial sensation, speech dysfunction (dysphagia/dysarthria and aphasia), double vision, blindness, hemiparesis, and seizures, were significantly associated with loss of social independence. Conclusions: The occurrence of various neurological symptoms of NF2 can hinder social independence in the long term. Medical service providers need to observe patients while considering the risks, and provide appropriate support to address neurological symptoms that can restrict social independence, as this will lead to maintaining social engagement.

Abstract Aims/Introduction To identify thresholds for postprandial hyperglycemia and hypertriglyceridemia predictive of all‐cause mortality in patients with type 2 diabetes. Materials and Methods A total of 1,928 patients with type 2 diabetes visited our clinic for the first time from 1995 to 1999 and were followed up for ≥1 year. During the first year, 2‐h post‐breakfast blood glucose (2h‐BG) levels were measured in 1,122 patients (BG cohort) and postprandial serum triglyceride (ppTG) levels were measured in 1,826 patients (TG cohort). Patients were retrospectively followed until 2017 and administered questionnaires. Associations between 2h‐BG and ppTG levels and mortality risk were assessed by the multivariate Cox regression analysis. Results Over of 17,429 person‐years, 162 deaths occurred in the BG cohort, and over 28,026 person‐years, 253 deaths occurred in the TG cohort. Hazard ratios (HRs) with 95% confidence intervals for all‐cause mortality per 1‐standard deviation increases in 2h‐BG and ppTG were 1.34 (1.08–1.67) and 1.24 (1.06–1.45), respectively. HRs showed increasing trends across quintiles of 2h‐BG (P = 0.034) and ppTG (P = 0.007). The HR was significantly elevated (2.37, 1.26–4.47) in the fifth quintile of 2h‐BG (≥13.8 mmol/L) compared with the first quintile (

Abstract Background This study aimed to examine the change in health status of the general public after starting the COVID-19 pandemic and its association with changes in workload and lifestyle. Methods A web-based survey was conducted in November 2020, about 9 months after starting the COVID-19 pandemic in Japan, among 8000 Japanese men and women aged 25–64 years. Participants asked for the changes after starting the COVID-19 pandemic in health status, workload, daily life, and health behavior. Ordinal logistic regression was performed to elucidate factors associated with deterioration in general health status. Results A deterioration in general health status was reported by 17.0% of male and 19.4% of female. There has been a clear shift to sedentary life with decreasing moderate activity and increasing screen time. The multivariate analysis revealed that deteriorated work style, increased burden of housework, decreased moderate activity, increased digital media exposure, and increased body weight were significantly associated with deteriorating health status. Conclusion Both men and women have experienced significant changes in workload and lifestyle since the COVID-19 pandemic started. People should be aware of the risks associated with their recent life changes and take self-care measures to prevent serious health consequences.

Abstract Aims/Introduction We assessed the relationship between diabetic retinopathy (DR) and/or diabetic kidney disease (DKD) according to their severity and all‐cause, cancer, vascular and non‐cancer non‐vascular mortality in real‐world patients with type 2 diabetes. Materials and Methods A total of 1,902 patients with type 2 diabetes were enrolled from 1995 to 1999 and followed to 2017. At baseline, DR was diagnosed in 374 patients, DKD in 529, vision‐threatening DR in 123 and advanced DKD in 287. Patients were classified by the status of DR and DKD. Multivariate Cox regression analysis was carried out. Results There were 266 deaths during a median follow‐up period of 18.6 years. Among these, 92 were from cancer, 78 were from vascular causes and 82 were from non‐cancer non‐vascular causes. DR and/or DKD predicted all‐cause, vascular and non‐cancer non‐vascular mortality, but not cancer mortality. Similarly, vision‐threatening DR and/or advanced DKD predicted all‐cause, vascular and non‐cancer non‐vascular mortality, but not cancer mortality. Hazard ratios for all‐cause, vascular and non‐cancer non‐vascular mortality were highest in the DR(+)DKD(+) group, and higher in the DR(−)DKD(+) and the DR(+)DKD(−) groups than in the DR(−)DKD(−) group. The results for vision‐threatening DR and advanced DKD were similar. The interaction for non‐cancer non‐vascular mortality, but not all‐cause and vascular mortality, between DR and DKD and between vision‐threatening DR and advanced DKD might be significant. Conclusions DR and DKD may be jointly and independently associated with all‐cause, vascular and non‐cancer non‐vascular mortality, but not cancer mortality, according to their severity in real‐world patients with type 2 diabetes.

Abstract Aims/Introduction There is little evidence on the role of postprandial glycemia in the incidence of diabetic retinopathy (DR) in a real‐world setting. We aimed to assess the effect of postprandial hyperglycemia at clinic visits on the incidence of DR in patients with type 2 diabetes, and whether its effect differs depending on glycated hemoglobin (HbA1c) values and age. Materials and Methods Intrapersonal mean blood glucose levels at 1–2 h post‐breakfast (1–2h‐PBBG), post‐lunch (1–2 h‐PLBG) and both (1–2h‐PBLBG) during 2 years from the first visit were used as baseline data. This retrospective cohort study enrolled 487, 323 and 406 patients who had 1–2h‐PBLBG, 1–2h‐PBBG and 1–2h‐PLBG measurements, respectively. These three groups were followed from 1999 up through 2017. Results DR occurred in 145, 92 and 126 patients in the 1–2h‐PBLBG, 1–2h‐PBBG and 1–2h‐PLBG groups, respectively. Multivariate Cox regression analysis showed that the mean 1–2h‐PBLBG, 1–2h‐PBBG and 1–2h‐PLBG levels were significant predictors of DR, independent of mean HbA1c. In patients with mean HbA1c

Background: The present study aimed to examine the association between the presence/absence of help-seeking behavior (ie, behavior aimed at obtaining assistance from others to improve a situation or problem) and psychological distress among private and public employees by age group using a nationally representative sample of the Japanese population. Methods: The present study analyzed data obtained from the 2016 Comprehensive Survey of Living Conditions, a nationwide cross-sectional survey. Of 568,426 participants, 78,284 private and public employees aged 20 to 59 years, who were receiving no mental health services at the time of the survey and reported at least one stressor in daily life, were eligible. The primary outcome measure was self-rated psychological distress as measured by the Kessler Psychological Distress Scale. Multiple logistic regression analyses were carried out separately by age group, adjusting for sociodemographic and job/life-related factors. Results: The proportion of participants not showing help-seeking behavior was significantly higher among those aged 40–59 years compared to those aged 20–39 (30.5% and 22.7%, respectively; P < 0.001). Participants without help-seeking behavior had significantly higher odds ratios (ORs) for psychological distress, regardless of age group (OR = 1.9 [95% confidence interval (CI), 1.6–2.0] and OR = 1.6 [95% CI, 1.4–1.7] for the age 20–39 years and 40–59 years groups, respectively), compared to those showing help-seeking behavior. Conclusions: Participants not showing help-seeking behavior were more likely to have severe psychological distress, and this trend appeared to be slightly stronger among those aged 20–39 years. These findings suggest that promoting help-seeking behavior is important for improving mental health among workers.

The degradation of SARS-CoV-2 specific ribonucleic acid (RNA) was investigated by a numerical modeling approach based on nucleic acid amplification test (NAAT) results utilizing the SmartAmp technique. The precision of the measurement was verified by the relative standard deviation (RSD) of repeated measurements at each calibration point. The precision and detection limits were found to be 6% RSD (seven repeated measurements) and 94 copies/tube, respectively, at the lowest calibration point. RNA degradation curves obtained from NAAT data on four different temperatures were in good agreement with the first-order reaction model. By referring to rate constants derived from the results, the Arrhenius model was applied to predict RNA degradation behavior. If the initial RNA concentration was high enough, such as in samples taken from infected bodies, the NAAT results were expected to be positive during testing. On the other hand, if initial RNA concentrations were relatively low, such as RNA in residual viruses on environmental surfaces, special attention should be paid to avoid false-negative results. The results obtained in this study provide a practical guide for RNA sample management in the NAAT of non-human samples.

Abstract Background No study to date has followed disease progression in patients with neurofibromatosis type 1 (NF1), including the incidence of various manifestations, using a national registry. Here we examined the state of NF1 progression using a nationwide registry of patients who submitted claims to receive medical expense subsidies for NF1 in Japan over a five-year period. A total of 342 eligible patients (194 females and 148 males) with NF1 who newly submitted claims for medical expense subsidies in Japan in 2008 were followed until 2012. Results More than half of the patients were classified as Stage 5 in 2008. Of the eligible patients, 205 (60%) submitted claims to renew the subsidies between 2009 and 2012. During the study period, NF1 stage progressed in 30 patients, yielding an overall stage progression rate of 19% and progression incidence rate per 100 person-years of 12.2. Both stage progression rate and progression incidence rate were the highest in the 0–19 year age group at the time of registration and, as compared to other age groups, progression of neurological and bone manifestations was more prevalent in this age group. Conclusions The progression of neurological and bone manifestations was more prevalent in the 0–19 year age group compared to other age groups. The registry we used in the present study is useful for understanding the characteristics of patients with uncommon conditions, such as NF1. Our findings also highlight the feasibility of conducting quality research using registries of patients with rare diseases, such as NF1, that were not designed specifically for scientific research.

Abstract Background The persuasive effect of health messages can depend on message features, audience characteristics, and target behaviors. The objective of this study was to compare the responses to persuasive messages encouraging professional help seeking for depression between individuals with and without psychological distress. Methods A cross-sectional web-based survey was conducted on Japanese adults aged 35–45 years, who randomly received one of three persuasive messages that aimed to promote help-seeking intentions for depression. The primary message statements were as follows: (1) depression can happen to anyone, (2) depression needs treatment, and (3) depression improves with treatment. Participants rated the messages in terms of comprehensibility, persuasiveness, emotional response, and intended future use. Help-seeking intention for depression was measured using vignette methodology before and after exposure to the messages. Eligible participants who had not received medical treatment for their mental disorders were classified as either distressed (K6 score ≥ 5, N = 824) or non-distressed (K6 score

Abstract In 1952, the Japanese Society for Hygiene had once passed a resolution at its 22nd symposium on population control, recommending the suppression of population growth based on the idea of cultivating a healthier population in the area of eugenics. Over half a century has now passed since this recommendation; Japan is witnessing an aging of the population (it is estimated that over 65-year-olds made up 27.7% of the population in 2017) and a decline in the birth rate (total fertility rate 1.43 births per woman in 2017) at a rate that is unparalleled in the world; Japan is faced with a “super-aging” society with low birth rate. In 2017, the Society passed a resolution to encourage all scientists to engage in academic researches to address the issue of the declining birth rate that Japan is currently facing. In this commentary, the Society hereby declares that the entire text of the 1952 proposal is revoked and the ideas relating to eugenics is rejected. Since the Society has set up a working group on the issue in 2016, there have been three symposiums, and working group committee members began publishing a series of articles in the Society’s Japanese language journal. This commentary primarily provides an overview of the findings from the published articles, which will form the scientific basis for the Society’s declaration. The areas we covered here included the following: (1) improving the social and work environment to balance between the personal and professional life; (2) proactive education on reproductive health; (3) children’s health begins with nutritional management in women of reproductive age; (4) workplace environment and occupational health; (5) workplace measures to counter the declining birth rate; (6) research into the effect of environmental chemicals on sexual maturity, reproductive function, and the children of next generation; and (7) comprehensive research into the relationship among contemporary society, parental stress, and healthy child-rearing. Based on the seven topics, we will set out a declaration to address Japan’s aging society with low birth rate.

Summary: Little is known about the effect of latent-phase herpesviruses on their host. Human herpesvirus 6B (HHV-6B) is one of the most ubiquitous herpesviruses, and olfactory astrocytes are one of the most important sites of its latency. Here, we identified SITH-1, an HHV-6B latent protein specifically expressed in astrocytes. Mice induced to produce SITH-1 in their olfactory astrocytes exhibited olfactory bulb apoptosis, a hyper-activated hypothalamic-pituitary-adrenal (HPA) axis and depressive symptoms. The binding of SITH-1 to the host protein calcium-modulating ligand (CAML) to form an activated complex promoted the influx of extracellular calcium. The serum antibody titers for depressive patients with respect to this activated complex were significantly higher than for normal controls (p = 1.78 × 10−15), when the antibody positive rates were 79.8% and 24.4%, respectively, and the odds ratio was 12.2. These results suggest that, in the latent phase, HHV-6B may be involved in the onset of depression.

Background: Pretesting is the key to understanding how the intended audience will react to the message. Resistant reactions affect message processing or can lead to undesirable boomerang effects. The objective of this study was to develop a rating scale for measuring active (reactance) and passive (disengagement) resistance to persuasive health messages. Methods: Six candidate items (3 items for disengagement and 3 items for reactance) were generated based on literature review. A web-based survey was conducted among Japanese adults aged 25–64 years to verify the reliability and validity of the 6-item resistance scale. Participants were asked to rate one of the advance care planning (ACP) promotion messages. All scale items were scored on a 1-to-5 point Likert scale and they were averaged to produce the resistance score. Results: Explanatory factor analysis revealed a two-factor solution that agreed with the disengagement and reactance domains, respectively. Correlation coefficients between each set of items ranged between 0.30–0.69. Cronbach alpha (0.86) indicated satisfactory internal consistency of the set of items. Confirmatory factor analysis showed a good fit of the two-factor model with CFI = 0.998, SRMR = 0.011, and RMSEA = 0.041. The resistance score showed a moderate positive correlation with negative emotional responses (displeasure γ = 0.55, anger γ = 0.53) and was significantly inversely related to the persuasiveness score (γ = −0.50). Multivariable logistic regression analysis showed that the odds ratio for ACP intention per 1-point increase in the resistance score was 0.47 (95% confidence interval 0.40–0.56) with adjustment for the persuasiveness score. Conclusion: The 6-item resistance scale exhibited adequate reliability and validity for measuring audience resistance when applied to the ACP promotion messages in Japanese people. The scale will be useful for pretesting health messages to make them more acceptable to the intended audience. Trial registration: Not applicable; this is not a report of intervention trial.

Abstract Background Communicating health messages is an important way to influence people’s behaviors towards health issues. Providers need to incorporate audience’s perspective to design more persuasive messages. This study aimed to develop rating scales for measuring audience’s perception of effectiveness of health messages in Japanese people. Methods The comprehensibility scale including five items and the persuasiveness scale including seven items were designed based on literature review. A cross-sectional web-based survey was conducted among Japanese adults aged 35–45 years to assess the reliability and validity of the scales. Participants were asked to rate a text message that encouraged help-seeking intention for insomnia. All scale items were scored on a 1-to-5 point Likert scale, and they were averaged to produce an overall score for each scale. Results Explanatory factor analysis revealed a two-factor solution that agreed with the comprehensibility and persuasiveness scales, respectively. Correlation coefficients between each set of items ranged between 0.63–0.87 for the comprehensibility scale and 0.37–0.76 for the persuasiveness scale. Cronbach alpha (0.88) indicated satisfactory internal consistency of the set of items. The mean (SD) of the comprehensibility and persuasiveness scores were 3.70 (0.82) and 3.15 (0.61), respectively, without ceiling or floor effects. These scores were significantly associated with intended future use of the message. The proportion of participants who reported a positive help-seeking intention for insomnia was significantly higher in the higher score groups for both scales. Multiple logistic regression analysis showed that the comprehensibility and persuasiveness scores were significantly associated with the help-seeking intention for insomnia. Conclusion The proposed rating scales exhibited adequate reliability and validity for measuring the comprehensibility and persuasiveness of insomnia health-seeking message in middle-aged Japanese people. Further studies are needed to confirm the generalizability of the results, but these scales may be useful for pretesting a health message with audience members to make it more acceptable and persuasive to the intended audience. Trial registration Not applicable; this is not a report of intervention trial.

Long working hours and a lack of sleep have been suggested to negatively affect the safety of workers. Here, we examined the association between long working hours/sleep-related problems and near-misses/injuries in industrial settings using a nationally representative sample of workers in Japan. Based on the composition ratio of workers by industry, sex, and age in Japan, data from a web-based cross-sectional survey for 18,682 participant full-time workers (7,098 female and 11,584 male; mean age, 43.7 [standard deviation 11.1] years) were analyzed. Nearly 30% and 5% of participants reported any types of near-misses during the past six months and injuries during the past year, respectively. For all types of near-misses and some types of injuries, a significant difference in frequency distribution was observed by industry. After adjustment for demographic, job-, and life-related variables, participants who worked long hours (i.e., more than 51 hours per week) were more likely to report job-related near-misses/injuries than those who worked 35-40 hours per week. The presence of sleep-related problems was also significantly related to near-misses and injuries. However, while sleep-related problems were significantly associated with near-misses/injuries in all industries, the association between long working hours and near-misses/injuries differed by industry. Odds ratios for near-misses/injuries were strongly significant in the "transport/postal services" industry for those who worked more than 51 hours per week compared to those who worked 35-40 hours per week. Comprehensive protective measures for workers, including (1) reducing total hours of service/job-related fatigue, (2) maintaining sufficient sleep hours/good sleep, and (3) increasing awareness about the impact of overwork/long working hours and sleep-related problems on workers' safety among employers, workers, clients/customers, and the general public might be effective for preventing near-misses and injuries in industrial settings among workers, especially those who work long hours in the "transport/postal services" industry.

Objectives: Minimally invasive epiduroscopy has recently been reported as an effective treatment procedure for chronic and intractable low back pain. However, no study has determined safe anesthetics for monitored anesthesia care during epiduroscopy. We aimed to compare and evaluate conventional monitored anesthesia care drugs with dexmedetomidine. Methods: A retrospective study including all patients who underwent epiduroscopy at the JR Tokyo General Hospital from April 2011 to March 2016 was designed. The epiduroscopy procedures were performed under anesthesia with dexmedetomidine plus fentanyl (dexmedetomidine group) or droperidol plus fentanyl (neuroleptanalgesia group). Patients who received analgesics other than fentanyl, another analgesic combined with fentanyl, any sedative other than dexmedetomidine or droperidol, or who had incomplete data were excluded. We compared (1) the type and dose of medication during the epiduroscopy and (2) the incidence of postoperative nausea and vomiting. Results: We identified 45 patients (31 and 14 in the dexmedetomidine and neuroleptanalgesia groups, respectively) with a mean age of 69.0 years. The two groups had comparable characteristics, such as age, sex, body mass index, the American Society of Anesthesiologists Physical Status, analgesics used in the clinic, comorbidities, history of smoking, and the duration of anesthesia. The dexmedetomidine group received a significantly lower fentanyl dose during surgery (126 ± 14 vs 193 ± 21 µg, mean ± standard deviation, p = 0.014) and exhibited a significantly lower incidence of postoperative nausea and vomiting (1 vs 3, p = 0.047) than the neuroleptanalgesia group. Conclusion: This study involved elderly patients, and the use of dexmedetomidine in monitored anesthesia care during epiduroscopy procedures in these patients may reduce the required fentanyl dose during surgery and the incidence of postoperative nausea and vomiting. This strategy may help prevent respiratory depression and aspiration.

This study was conducted with the aim of achieving the simultaneous screening of various additives in polymer materials by utilizing a solvent-free pyrolyzer/thermal desorption gas chromatography mass spectrometry (Py/TD-GC–MS) method. As a first step to achieve this goal, simultaneous screening has been examined by selecting major substances representing plasticizers and flame retardants, such as short chain chlorinated paraffins (SCCPs), decabromodiphenyl ether (DecaBDE), hexabromocyclododecane (HBCDD), and di(2-ethylhexyl) phthalate (DEHP). A quantitative MS analysis was performed to check for the peak areas and sensitivities. Since Py/TD-GC–MS is fraught with the risk of thermal degradation of the sample, temperatures during the analytical process were finely tuned for securing reliable results. The instrumental sensitivity was confirmed by the S/N ratio on each component. The detection limits of all components were less than 50 mg/kg, which are sufficiently lower than the regulatory criteria. With regard to reproducibility, a relative standard deviation (RSD) of about 5% was confirmed by employing a spike recovery test on a polystyrene polymer solution containing mixed standard solution (ca. 1000 mg/kg). In conclusion, the results obtained in this study indicate that Py/TD-GC–MS is applicable for the screening of major flame retardants and plasticizers in real samples with sufficient reproducibility at regulatory levels.

BACKGROUND: Imaging the behavior of RNA in a living cell is a powerful means for understanding RNA functions and acquiring spatiotemporal information in a single cell. For more distinct RNA imaging in a living cell, a more effective chemical method to fluorescently label RNA is now required. In addition, development of the technology labeling with different colors for different RNA would make it easier to analyze plural RNA strands expressing in a cell. METHODOLOGY/PRINCIPAL FINDINGS: Tag technology for RNA imaging in a living cell has been developed based on the unique chemical functions of exciton-controlled hybridization-sensitive oligonucleotide (ECHO) probes. Repetitions of selected 18-nucleotide RNA tags were incorporated into the mRNA 3'-UTR. Pairs with complementary ECHO probes exhibited hybridization-sensitive fluorescence emission for the mRNA expressed in a living cell. The mRNA in a nucleus was detected clearly as fluorescent puncta, and the images of the expression of two mRNAs were obtained independently and simultaneously with two orthogonal tag-probe pairs. CONCLUSIONS/SIGNIFICANCE: A compact and repeated label has been developed for RNA imaging in a living cell, based on the photochemistry of ECHO probes. The pairs of an 18-nt RNA tag and the complementary ECHO probes are highly thermostable, sequence-specifically emissive, and orthogonal to each other. The nucleotide length necessary for one tag sequence is much shorter compared with conventional tag technologies, resulting in easy preparation of the tag sequences with a larger number of repeats for more distinct RNA imaging.