The association between economic uncertainty and suicide in Japan by age, sex, employment status, and population density: an observational study.

Background: Suicide is one of the ten leading causes of death globally, and previous research has revealed a link between economic conditions and mental health. However, the literature has focused primarily on recessions and unemployment, i.e. actual economic developments, as opposed to uncertainty, which relates to economic developments that have not (yet) materialised. This study examines the differential association between economic uncertainty and suicide in Japan, depending on age, sex, employment status, and population density, in order to identify the groups that are affected the most. Methods: Using monthly prefectural suicide mortality data from the Ministry of Health, Labour and Welfare and a monthly economic uncertainty index for the period 2009 to 2019, we employed a fixed effects panel data approach to examine the association between uncertainty and suicide by population group. Findings: We found that a 1% increase in economic uncertainty is associated with a 0.061 increase in the monthly number of suicides per 100,000 people per prefecture, on average (coefficient: 6.08; 95% CI: 5.07-7.08), which constitutes a 3.62% increase. Self-employed people, as well as men in their 50s and unemployed men, experience the highest additional risk of suicide when uncertainty increases. The association was approximately three times stronger for males than for females, and a strong association was observed for self-employed males living in more densely-populated areas. Interpretation: Uncertainty appears to relate to suicides for most groups, but self-employed people, males, and those living in more densely populated areas appear to be more at risk of suicide in periods of increased economic uncertainty. Our results provide an indication of which groups mental health services and prevention strategies can focus on in times of economic uncertainty. Funding: None.

Pannexin1 channel-dependent secretome from apoptotic tumor cells shapes immune-escape microenvironment.

Apoptotic cell death is a critical step in organism development and tissue homeostasis. Apoptotic cells affect immune cell activities in normal tissues. It is not clear whether similar cell death machinery causes tumor environments to evade anti-tumor immune responses. Here, using a mouse transplant model, we found a large number of tumor cells undergoing intrinsic apoptosis in tumors derived from the 4T1 breast cancer cell line, where neutrophils significantly accumulated. Interestingly, these apoptotic 4T1 tumor cells directly induced neutrophil extracellular traps (NETs) in a pannexin 1 (Panx1) channel-dependent manner, and knockdown of Panx1 in 4T1 cells led to a reduction in tumor size. Spermidine released through Panx1 from apoptotic 4T1 cells induced NETs in bone marrow-derived neutrophils in vitro. In addition, inhibition of spermidine synthesis suppressed tumor growth in the mouse transplant model. Collectively, our data suggested a new immune-escape mechanism for tumors by Panx1-mediated secretome from intrinsic apoptotic cells, which may provide a new therapeutic target for cancer.

A new susceptibility index to predict the risk of severe herpes zoster-associated pain: A Japanese regional population-based cohort study, the Shizuoka study.

BACKGROUND: Approximately 7-20% of patients with herpes zoster (HZ) develop zoster-associated pain (ZAP). ZAP not only impairs quality of life and psychological well-being, but also can reduce work effectiveness, which has negative economic effects. Reports of ZAP risk factors are inconsistent. OBJECTIVE: To confirm risk factors for the development of severe ZAP in HZ patients in Japan using a large-scale database, the Shizuoka Kokuho Database. METHODS: A population-based cohort study using the Shizuoka Kokuho Database was conducted. Of 792,647 patients, 7491 (0.95%) experienced "severe ZAP" (as defined in this study). We developed a ZAP risk prediction scoring system by identifying risk factors using logistic regression analysis of several candidate risk factors for severe ZAP: age, sex, seasonality, and presence of comorbidities (using the Charlson comorbidity index), excluding HIV/AIDS. RESULTS: We identified peripheral vascular disease and the onset from October to December as novel risk factors for severe ZAP, in addition to the previously reported risk factors of age and comorbidities (cerebral vascular disease, chronic pulmonary disease, rheumatic disease, peptic ulcer, liver disease, diabetes, and malignant neoplasms with/without metastasis). In contrast, dementia was found to reduce ZAP risk. We developed a susceptibility index to predict the risk of ZAP. CONCLUSION: We newly demonstrated that peripheral vascular disease and the onset from October to December are ZAP risk factors. Our comorbidity findings support previous observations. The susceptibility index proposed here provides a new approach to the prevention of ZAP using early intervention for high-risk patients.

Electronic spectroscopy of Mg-phthalocyanine embedded in cold hydrogen clusters produced by a pulsed nozzle.

Cold clusters of molecular hydrogen were created using a pulsed nozzle. The thermodynamical states of the clusters were characterized by measuring the cluster beam velocity and the laser-induced fluorescence (LIF) spectra of embedded molecules. Two distinct velocity components were identified in the beam that originates from different clustering mechanisms. The fast velocity component corresponds to the expansion of H2 from the gas phase, while the slow velocity component corresponds to the expansion from the liquid phase. The velocity distribution of these two components showed no significant difference between the expansions of para and normal hydrogen. In this study, LIF spectroscopy of single Mg-phthalocyanine molecules embedded in the H2 clusters consisting of 105 H2 molecules was used to investigate the properties of the fast component. The observed peak frequencies of the LIF signals, compared to those observed in helium droplets, were used to infer the possible presence of the liquid phase in the fast component of the H2 clusters below 5 K. The shift, linewidth, and splitting in the spectra, which strongly depend on the ortho/para ratio, are attributed to the local configurations of hydrogen in the vicinity of the probe molecules.

Late-onset development of psoriasis in Japan: a population-based cohort study.

BACKGROUND: Evidence of factors associated with psoriasis from large population-based cohort studies is scarce. OBJECTIVE: We aimed to explore the risk factors of late-onset psoriasis. METHODS: This study included 487,835 Japanese participants aged 40-107 years, who were followed prospectively from 2012 to 2018 using individually linked databases between annual health checkups and medical claims. RESULTS: During the study period, 2793 patients (0.57%) newly developed psoriasis; 13.8% had moderate-to-severe psoriasis. In the multivariate analysis, factors associated with psoriasis onset were age (hazard ratio [HR] 1.11 {95% confidence interval [CI]: 1.06-1.16}), male sex (HR: 1.11 [95% CI: 1.02-1.21]), body mass index (HR: 1.09 [95% CI: 1.05-1.14]), smoking (HR: 1.46 [95% CI: 1.31-1.63]), not exercising ≥1 hour per week (HR: 1.13 [95% CI: 1.05-1.22]), and gamma-glutamyl transpeptidase (HR: 1.04 [95% CI: 1.01-1.06]). When we used weight increment of ≥10 kg since the age of 20 years instead of body mass index in the multivariate model, this was also a risk factor (HR: 1.12 [95% CI: 1.04-1.21]). LIMITATIONS: This study targeted people aged >40 years, thereby narrowing the search to the risk factors of late-onset psoriasis. CONCLUSION: We showed that increasing age, male sex, body mass index, smoking, low physical activity, weight gain, and gamma-glutamyl transpeptidase are associated with late-onset development of psoriasis and revealed a relationship between liver dysfunction and psoriasis development.

Perineal pyoderma gangrenosum in pregnancy: A case report.

Pyoderma gangrenosum is a rare ulcerating neutrophilic dermatosis. We describe the case of a 28-year-old woman with pyoderma gangrenosum in the perineal region during pregnancy. Cytological analysis of a skin biopsy specimen showed neutrophilic infiltrates across all the layers of the dermis, confirming the diagnosis of pyoderma gangrenosum. Determining a management plan, including the mode of delivery, was difficult. Oral prednisolone was started and her ulcer started to improve, but she still had the ulcer when she reached full term. Because there was a concern that the ulcer would be worsened by vaginal delivery, cesarean section was performed. After her delivery, pyoderma gangrenosum had not appeared at the cesarean incision and the ulcer in the perineal region had improved. Obstetricians should be aware of pyoderma gangrenosum as a differential diagnosis when vulvar ulceration develops during pregnancy.

Direct observation of ultrafast many-body electron dynamics in an ultracold Rydberg gas.

Many-body correlations govern a variety of important quantum phenomena such as the emergence of superconductivity and magnetism. Understanding quantum many-body systems is thus one of the central goals of modern sciences. Here we demonstrate an experimental approach towards this goal by utilizing an ultracold Rydberg gas generated with a broadband picosecond laser pulse. We follow the ultrafast evolution of its electronic coherence by time-domain Ramsey interferometry with attosecond precision. The observed electronic coherence shows an ultrafast oscillation with a period of 1 femtosecond, whose phase shift on the attosecond timescale is consistent with many-body correlations among Rydberg atoms beyond mean-field approximations. This coherent and ultrafast many-body dynamics is actively controlled by tuning the orbital size and population of the Rydberg state, as well as the mean atomic distance. Our approach will offer a versatile platform to observe and manipulate non-equilibrium dynamics of quantum many-body systems on the ultrafast timescale.

Theoretical/numerical study on strong-laser-induced interference in the B state of I2.

In the B state of I2, strong-laser-induced interference (SLI) was recently observed in the population of each vibrational eigenstate within a wave packet, which was initially prepared by a pump pulse and then strongly modulated by an intense femtosecond near-infrared (NIR) laser pulse. It was suggested that the interference as a function of the time delay occurs between the eigenstate reached by Rayleigh scattering and that by Raman scattering. To verify this mechanism and further discuss its characteristics, we theoretically/numerically study the SLI by adopting a two-electronic-state model of I2. Numerical simulation reasonably reproduces the experimental signals and confirms the theoretical consequences, which include the π-phase shifts between Stokes and anti-Stokes transitions and (practically) no contribution from the energy shifts induced by the NIR pulse.

Second-phase validation study of short time exposure test for assessment of eye irritation potency of chemicals.

A Short Time Exposure (STE) test is a cytotoxicity test that uses SIRC cells (rabbit corneal cell line) to assess eye irritation potency following a 5-min chemical exposure. This second-phase validation study assessed the predictive capacity of the STE test using 40 coded test substances at three laboratories. A Validation Management Team (VMT) then evaluated the predictivity of the STE test for United Nation (UN) Globally Harmonized System (GHS) categories using 63 test substances including the results of the first-phase validation study. The STE test can assess not only the severe or corrosive ocular irritants (corresponding to the UN GHS Category 1) but also non-irritant (corresponding to UN GHS Non Category) from other toxicity classes, especially for limited types of test substances. The predictivity by STE test, however, was insufficient for identification of UN GHS categories (Category 1, Category 2, or Non Category). These results suggest that the STE test can be recommended as an initial step in a top-down approach to identification of severe irritants and test substances that require classification for eye irritation (UN GHS Category 1) as well as an initial step in a bottom-up approach to identification of test substances that do not require classification for eye irritation (UN GHS Non Category) from other toxicity classes, especially for limited types of test substances. On the other hand, the STE test is not considered adequate for the identification of mild or moderate irritants (i.e., UN GHS Categories 2A and 2B) and severe irritants (UN GHS Category 1).

Gut colonization by Candida albicans aggravates inflammation in the gut and extra-gut tissues in mice.

We examined whether Candida albicans gut colonization aggravates immune diseases in mice. Chronic and latent C. albicans gut colonization was established by the intragastric inoculation of C. albicans in mice fed as part of a purified diet. Allergic diarrhea was induced by repetitive intragastric administration of ovalbumin in sensitized BALB/c mice. Contact hypersensitivity was evaluated by measuring ear swelling after topical application of 2, 4-dinitrofluorobenzene in NC/Nga mice. Arthritis was induced by intradermal injection of bovine type-II collagen emulsified with complete Freund's adjuvant in DBA/1J mice. C. albicans gut colonization increased the incidence of allergic diarrhea, which was accompanied by gut hyperpermeability, as well as increased infiltration of inflammatory cells in the colon. Contact hypersensitivity was also exacerbated by C. albicans gut colonization, as demonstrated by increased swelling, myeloperoxidase activity, and proinflammatory cytokines in ear auricles. Furthermore, C. albicans gut colonization promoted limb joint inflammation in collagen-induced arthritis, in an animal model of rheumatoid arthritis. These findings suggest that C. albicans gut colonization in mice aggravates inflammation in allergic and autoimmune diseases, not only in the gut but also in the extra-gut tissues and underscores the necessity of investigating the pathogenic role of C. albicans gut colonization in immune diseases in humans.

Effects of fructo-oligosaccharide on DSS-induced colitis differ in mice fed nonpurified and purified diets.

We investigated whether feeding a purified compared with nonpurified diet supplemented with or without fructo-oligosaccharide (FOS; 50 g/kg diet) altered the response of C57BL/6 mice to DSS-induced diarrhea. In Expt. 1, we examined disease severity in mice receiving DSS (2% in drinking water) for 5 d. In Expt. 2, we measured cecal organic acid concentrations and fecal water-holding capacity (WHC). In Expts. 3 and 4, we tested whether polycarbophil calcium (PC), a water-absorbing polymer, altered fecal WHC and disease severity. FOS exacerbated diarrhea and weight loss in mice fed the purified diet and reduced fecal bleeding in mice fed the nonpurified diet (P < 0.05). Without DSS administration, cecal acetate and butyrate concentrations were higher in mice fed the nonpurified diet than in mice fed the purified diet (P < 0.05). Fecal WHC was higher in mice fed the nonpurified diet than in mice fed the purified diet (P < 0.05). One day after starting DSS administration, cecal succinate concentrations were higher in mice fed the FOS-supplemented purified diet than in mice fed the other 3 diets, whereas SCFA concentrations were higher in mice fed the nonpurified diet than in mice fed the purified diet (P < 0.05). PC supplementation increased fecal WHC and prevented FOS exacerbation of diarrhea in mice fed the purified diet (P < 0.05). We conclude that the effects of FOS on DSS-induced diarrhea differ in mice fed the purified and nonpurified diets. The protective effect of nonpurified diet was associated with increased production of organic acids and WHC in the intestinal contents.

Comparison of gut microbiota and allergic reactions in BALB/c mice fed different cultivars of rice.

Our preliminary clinical trial showed that consumption of cooked rice of a Japanese common cultivar Yukihikari improved atopic dermatitis associated with a suspected rice allergy, although the underlying mechanisms remain unclear. We hypothesised that the ameliorating effect of Yukihikari on atopic dermatitis is associated with the gut microbiota. BALB/c mice were fed a synthetic diet supplemented with uncooked and polished white rice powder prepared from one of four different cultivars: Yukihikari, rice A (common rice), rice B (brewery rice) and rice C (waxy rice). Denaturing gradient gel electrophoresis of PCR-amplified 16S rRNA gene fragments showed that the composition of faecal microbiota was different between mice fed Yukihikari and those fed rice A. Analysis of the 16S rRNA clone library and species-specific real-time PCR showed that the abundance of Akkermansia muciniphila, a mucin degrader, tended to be lower in mice fed Yukihikari. The incidence of allergic diarrhoea induced by oral administration of ovalbumin in systemically immunised mice was lower in mice fed Yukihikari, albeit with no difference in serum antibodies specific to ovalbumin. In a separate experiment, serum antibody levels specific to orally administered ovalbumin were lower in mice fed Yukihikari. Additionally, the translocation of horseradish peroxidase in isolated segments of ileum and colon tended to be lower in mice fed Yukihikari, suggesting a reduction in gut permeability in mice fed Yukihikari. These data indicate that changes in the gut microbiota of mice fed Yukihikari could be advantageous in the prevention of food allergy.

Laser induced fluorescence of Mg-phthalocyanine in He droplets: evidence for fluxionality of large H2 clusters at 0.38 K.

The formation of Ar and H2 clusters, having up to 900 particles in helium droplets, has been studied via laser induced fluorescence of attached Mg-phthalocyanine (Mg-Pc) molecules. In the experiments, one Mg-Pc molecule in average was added to each He droplet either before or after the cluster species, and the shift of the spectrum of the Mg-Pc molecules was studied as a function of the cluster size. For Ar clusters, about a factor of 2 smaller matrix shift was observed for the late pickup of the Mg-Pc molecules as compared with the prior pickup, indicating that in the former case, the Mg-Pc molecules reside on the surface of the preformed Ar clusters. On the other hand, the spectra of the Mg-Pc molecules attached to H2 clusters are independent of the pickup order, which is consistent with Mg-Pc molecules residing near the center of the H2 clusters in both cases. Therefore H2 clusters remain fluxional in helium droplets at T=0.38 K. No significant differences in the spectra were observed between the para-H2 and ortho-H2 clusters.