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The aim of this study is to estimate the lifetime and 12-month prevalence, severity and treatment of Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV) mental disorders in Japan based on the final data set of the World Mental Health Japan Survey conducted in 2002-2006. Face-to-face household interviews of 4130 respondents who were randomly selected from Japanese-speaking residents aged 20 years or older were conducted from 2002 to 2006 in 11 community populations in Japan (overall response rate, 56%). The World Mental Health version of the World Health Organization Composite International Diagnostic Interview (WMH-CIDI), a fully structured, lay administered psychiatric diagnostic interview, was used for diagnostic assessment. Lifetime/12-month prevalence of any DSM-IV common mental disorders in Japan was estimated to be 20.3/7.6%. Rank-order of four classes of mental disorders was anxiety disorders (8.1/4.9%), substance disorders (7.4/1.0%), mood disorders (6.5/2.3%) and impulse control disorders (2.0/0.7%). The most common individual disorders were alcohol abuse/dependence (7.3/0.9%), major depressive disorder (6.1/2.2%), specific phobia (3.4/2.3%) and generalized anxiety disorder (2.6/1.3%). While the lifetime prevalence of any mental disorder was greater for males and the middle-aged, the persistence (proportion of 12-month cases among lifetime cases) of any mental disorder was greater for females and younger respondents. Among those with any 12-month disorder, 15.3% were classified as severe, 44.1% moderate and 40.6% mild. Although a strong association between severity and service use was found, only 21.9% of respondents with any 12-month disorder sought treatment within the last 12 months; only 37.0% of severe cases received medical care. The mental health specialty sector was the most common resource used in Japan. Although the prevalence of mental disorders were quite low, mental disorders were the second most prevalent cause of severe role impairment among chronic physical and mental disorders. These results suggest lower prevalence of mental disorders in Japan than that in Western countries, although the general pattern of disorders, risk factors and unmet need for treatment were similar to those in other countries. Greater lifetime prevalence for males and greater persistence for females seems a unique feature of Japan, suggesting a cultural difference in gender-related etiology and course of disorders. The treatment rate in Japan was lower than that in most other high-income countries in WMH surveys.

Tissue macrophages in many adult organs originate from yolk sac (YS) progenitors, which invade the developing embryo and persist by means of local self-renewal. However, the route and characteristics of YS macrophage trafficking during embryogenesis are incompletely understood. Here we show the early migration dynamics of YS-derived macrophage progenitors in vivo using fate mapping and intravital microscopy. From embryonic day 8.5 (E8.5) CX 3 CR1+ pre-macrophages are present in the mouse YS where they rapidly proliferate and gain access to the bloodstream to migrate towards the embryo. Trafficking of pre-macrophages and their progenitors from the YS to tissues peaks around E10.5, dramatically decreases towards E12.5 and is no longer evident from E14.5 onwards. Thus, YS progenitors use the vascular system during a restricted time window of embryogenesis to invade the growing fetus. These findings close an important gap in our understanding of the development of the innate immune system. Tissue-resident macrophages are derived from yolk sac progenitors but how and when these progenitors enter is unclear. Here the authors use fate mapping and intravital microscopy to track the movement of resident macrophage precursors from the yolk sac to fetal tissues during development.

Ruthenium compounds serve as a platform for fundamental concepts such as spin-triplet superconductivity1, Kitaev spin liquids2–5 and solid-state analogues of the Higgs mode in particle physics6,7. However, basic questions about the electronic structure of ruthenates remain unanswered, because several key parameters (including Hund’s coupling, spin–orbit coupling and exchange interactions) are comparable in magnitude and their interplay is poorly understood, partly due to difficulties in synthesizing large single crystals for spectroscopic experiments. Here we introduce a resonant inelastic X-ray scattering (RIXS)8,9 technique capable of probing collective modes in microcrystals of 4d electron materials. We observe spin waves and spin-state transitions in the honeycomb antiferromagnet SrRu2O6 (ref. 10) and use the extracted exchange interactions and measured magnon gap to explain its high Néel temperature11–16. We expect that the RIXS method presented here will enable momentum-resolved spectroscopy of a large class of 4d transition-metal compounds.Resonant inelastic X-ray scattering at the 4d-edge reveals dispersive magnetic excitations in SrRu2O6, providing insight into the origin of its high Néel temperature.

Background:A lack of opportunities for vocalization can lead to a decline in vocal cord function, and oral function, as well as cognitive function, and a reduction in social connections. Consequently, oral, cognitive, and social frailty are expected to increase. When oral function declines, the amount of food intake decreases, potentially resulting in weight loss (one of the CHS criteria for frailty) and muscle mass loss (sarcopenia). Indeed, it was reported that the elderly people with declining oral function were at a higher risk of developing physical frailty, sarcopenia, nursing care requirements, and even death, compared with those without such decline [1]. On the other hand, rheumatoid arthritis (RA) is one of the causative diseases for frailty [2].Objectives:In this study, we investigated the association between frailty and vocalization in RA patients.Methods:Among 696 RA patients visited in 2023, 661 patients were available for the investigation of patient backgrounds, including Clinical Disease Activity Index (CDAI) and the Kihon Checklist (KCL), which was an evaluation method for frailty, and their responses to a questionnaire regarding vocalization. Frequency of vocalization was categorized into four levels: “every day”, “1-5 times a week”, “1-3 times a month”, and “almost never”. Frailty was defined as a KCL score of 8 points or higher. Odds ratios associated with frailty were calculated using multivariable logistic regression analysis.Results:Among 661 RA patients (474 women, 71.8%), 261 (39.5%) patients exhibited frailty. The mean age (± standard deviation) was 73.6 ± 11.9/65.2 ± 13.5 years (frailty group/non-frailty group), disease duration was 14.7 ± 10.8/11.4 ± 9.2 years, and CDAI was 9.1 ± 9.2/4.5 ± 5.9, both of which were higher significantly in the frailty group. The proportion of methotrexate (MTX) use was 68.8/48.3%, which were higher significantly in the non-frailty group. Frequency of vocalization (“every day”/“1-5 times a week”/“1-3 times a month”/“almost never”) was 37.2%/25.7%/11.1%/26.1% in the frailty group and 62.5%/20.5%/7.8%/9.2% in the non-frailty group, and frequency of vocalization was lower in the frailty group. Factors significantly associated with frailty were age (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.04-1.08), MTX use (OR 0.63, 95%CI 0.41-0.94), CDAI (OR 1.10, 95%CI 1.07-1.13) and “infrequent vocalization (1-3 times a month, almost never)” (OR 2.67, 95%CI 1.75-4.08).Conclusion:In this study, frailty was significantly associated with a lack of opportunities for vocalization, as well as disease activity in RA patients. For patients, oral, cognitive, and social frailty are difficult to recognize. These results suggest that encouraging the recognition of vocalization and supporting patients in vocalizing may be beneficial in preventing frailty.REFERENCES:[1] Tanaka T, et al. Oral Frailty as a Risk Factor for Physical Frailty and Mortality in Community-Dwelling Elderly. J Gerontol A Biol Sci Med Sci. 2018;73:1661-1667.[2] Sobue Y, et al. Relationship between locomotive syndrome and frailty in rheumatoid arthritis patients by locomotive syndrome stage. Mod Rheumatol. 2021;32:546-53.Table 1.Demographics and clinical characteristics of subjectsVariablesFrailty (n=261)Non-frailty (n=400)p valueAge (years)Mean (SD)73.6 (11.9)65.2 (13.5)<0.001*Duration of disease (years)Mean (SD)14.7 (10.8)11.4 (9.2)<0.001*Sex, female (%)70.172.90.479BMI (kg/m2)Mean (SD)22.2 (4.1)22.1 (3.5)0.607Married (%)57.868.50.006*Steinbrocker stage (3/4) (%)48.531.2<0.001*Rheumatoid factor positive (%)69.963.00.077Glucocorticoid use (%)36.822.5<0.001*Methotrexate use (%)48.368.8<0.001*bDMARD use (%)3332.81.000tsDMARD use (%)14.26.50.002*CDAIMean (SD)9.1 (9.2)4.5 (5.9)<0.001*Frequency of vocalization(“every day”/“1-5 times a week”/“1-3 times a month”/“almost never”) (%)37.2/25.7/11.1/26.162.5/20.5/7.8/9.2<0.001*Frailty, The Kihon Checklist (KCL) ≥8 points; BMI, body mass index; bDMARD, biological disease-modifying antirheumatic drug; tsDMARD, targeted synthetic DMARD; CDAI, Clinical Disease Activity Index; SD, standard deviation. *p<0.05.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Rheumatoid arthritis (RA) patients have a higher incidence of depression than the general population [1]. It has been reported that depression is associated with physical function in RA patients [2]. The decline in physical function can lead to various poor health outcomes. On the other hand, laughter has been reported to be effective in improving health outcomes, including depression [3].Objectives:This study aimed to investigate the relationship between laughter and physical function in RA patients.Methods:Among patients who visited consecutively from June to August 2023, 667 RA patients were available for investigating patient backgrounds, including Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire Disability Index (HAQ-DI). HAQ-DI is widely used as an index of physical function and patient reported outcomes in RA patients. In the present study, HAQ-DI≤0.5 was defined as functional remission. Laughter frequency was divided into two groups: “every day, 1-5 times a week” and “1-3 times a month, almost never”. The odds ratio (OR) of laughter related to physical function (functional remission) was calculated using multivariable logistic regression analysis.Results:446 (66.9%) were RA patients with HAQ remission. Age (HAQ remission group/non-HAQ remission group) was 66.9±13.7/71.8±12.6 years, disease duration was 10.9±8.7/16.4±11.3 years, and CDAI was 4.0±5.1/11.1±9.6, all of which were significantly higher in non-HAQ remission group. The laughter frequency (“every day”/“1-5 times a week”/“1-3 times a month”/“almost never”) was 55.4%/33.0%/8.1%/3.6% in HAQ remission group and 35.7%/38.5%/12.7%/13.1% in non-HAQ remission group, with significantly less frequency in non-HAQ remission group. Adjusted for age, disease duration, sex, and CDAI, less frequent laughter (“1-3 times a month, almost never”) was identified as significantly associated factors with non-HAQ remission (OR 2.25, 95% confidence interval 1.31-3.85).Conclusion:In this study, laughter was significantly associated with physical function in RA patients.REFERENCES:[1] Waraich P, et al. Prevalence and incidence studies of mood disorders: a systematic review of the literature. Can J Psychiatry. 2004;49(2):124-38.[2] Kojima M, et al. Depression, physical function, and disease activity associated with frailty in patients with rheumatoid arthritis. Mod Rheumatol. 2021;31(5):979-986.[3] Shahidi M, et al. Laughter yoga versus group exercise program in elderly depressed women: a randomized controlled trial. Int J Geriatr Psychiatry. 2011;26(3):322-7.Table 1.Demographics and clinical characteristics of subjectsVariablesHAQ remission (n=446)Non-HAQ remission (n=221)p valueAge (years)Mean (SD)66.9 (13.7)71.8 (12.6)<0.001*Duration of disease (years)Mean (SD)10.9 (8.7)16.4 (11.3)<0.001*Sex, female (%)69.076.00.069BMI (kg/m2)Mean (SD)22.2 (3.5)22.2 (4.3)0.760Steinbrocker stage (3/4) (%)28.257.7<0.001*Rheumatoid factor positive (%)62.471.80.019*Glucocorticoid use (%)25.334.40.018*Methotrexate use (%)65.949.3<0.001*bDMARD use (%)31.235.70.255tsDMARD use (%)5.816.7<0.001*CDAIMean (SD)4.0 (5.1)11.1 (9.6)<0.001*Laughter frequency(“every day”/“1-5 times a week”/“1-3 times a month”/“almost never”) (%)55.4/33.0/8.1/3.635.7/38.5/12.7/13.1<0.001*HAQ-DI, Health Assessment Questionnaire Disability Index; HAQ remission, HAQ-DI≤0.5; BMI, body mass index; bDMARD, biological disease-modifying antirheumatic drug; tsDMARD, targeted synthetic DMARD; CDAI, Clinical Disease Activity Index; SD, standard deviation. *p<0.05.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background Despite the availability of potent antifungal compounds, invasive fungal disease poses significant morbidity and mortality in immunocompromised patients. Candida albicans is one of the leading pathogens in this setting, and may affect the central nervous system (CNS), which is an extremely severe form of the infection. As the exact pathogenesis of Candida CNS infection is not clear, we investigated the mechanisms and effects of C. albicans transmigration into the CNS, which will be helpful for diagnosis, prevention and treatment. Methods We used a human in vitro model of the Blood-Cerebrospinal Fluid Barrier (BCSFB), and we investigated the mechanisms of Candida albicans translocation into the CNS. Translocation was evaluated using immunofluorescence analysis focusing on tight and adherens junctions and the actin cytoskeleton. Barrier integrity was monitored via measurement of transepithelial resistance and the paracellular permeability of dextran. LIVE/DEAD assays were applied for viability controls and a cytometric bead array was performed to detect cytokine secretion of plexus epithelial cells. Results Translocation at low doses occurs transcellularly in the absence of cytotoxicity or secretion of proinflammatory cytokines. This is accomplished by the formation of a tunnel-like structure exploiting the actin cytoskeleton. With higher infection doses of Candida albicans , a reduction in barrier integrity due to disruption of tight and adherens junctions was observed and cytotoxicity also increased. Conclusion Our findings reveal that Candida albicans can use transcellular translocation to invade into the CNS and is able to circumvent major host immune response, which may impact on diagnostic and preventive strategies.

It has been hypothesized that horizontal gene/chromosome transfer and parasexual recombination following hyphal fusion between different strains may contribute to the emergence of wide genetic variability in plant pathogenic and other fungi. However, the significance of vegetative (heterokaryon) incompatibility responses, which commonly result in cell death, in preventing these processes is not known. In this study, we have assessed this issue following different types of hyphal fusion during colony initiation and in the mature colony. We used vegetatively compatible and incompatible strains of the common bean pathogen Colletotrichum lindemuthianum in which nuclei were labelled with either a green or red fluorescent protein in order to microscopically monitor the fates of nuclei and heterokaryotic cells following hyphal fusion. As opposed to fusion of hyphae in mature colonies that resulted in cell death within 3 h, fusions by conidial anastomosis tubes (CAT) between two incompatible strains during colony initiation did not induce the vegetative incompatibility response. Instead, fused conidia and germlings survived and formed heterokaryotic colonies that in turn produced uninucleate conidia that germinated to form colonies with phenotypic features different to those of either parental strain. Our results demonstrate that the vegetative incompatibility response is suppressed during colony initiation in C. lindemuthianum. Thus, CAT fusion may allow asexual fungi to increase their genetic diversity, and to acquire new pathogenic traits.

With the increase in media reports and rapid diffusion of the Internet, the skills in finding and utilizing health information (health literacy; HL) are becoming important in maintaining and promoting health. This study aimed to examine the psychometric properties of a brief measure to assess major components of communicative and critical HL among Japanese office workers, in order to consider its applicability to health promotion at workplace. The participants were 190 male office workers at a Japanese company. A self-administered questionnaire was distributed at the annual health checkup, in which HL, health-related behaviors and coping with job stress were asked. Also, the number of somatic symptoms reported by the worker was counted out of the eight symptoms in the health checkup questionnaire. The higher HL group was more likely to have regular eating patterns and exercise weekly, and tended to be a never smoker. In coping with job stress, those with higher HL were more likely to actively solve the problems or seek support from others, whereas those with lower HL were more likely to be resigned to the situation. Further, lower HL group reported significantly greater number of somatic symptoms than higher HL group. These findings were generally as hypothesized, supporting the validity of the HL scale among office workers. Further research on HL is needed to explore the extent and impact of HL on health outcomes.

Background:A previous study reported that 70% of 4,793 Japanese rheumatoid arthritis (RA) patients had 25(OH) vitamin D (25(OH) D) deficiency[1]). We have also reported that 82% of 122 RA patients in our rheumatic center had 25(OH) D deficiency[2]). In a report on the effectiveness of 25(OH) D-containing Japanese cakes in 28 volunteers, the rate of 25(OH) D deficiency decreased from 93% to 36%[3]). However, there have been no reports on the effectiveness of nutritional guidance for improving 25(OH) D deficiency. During the study, Japan experienced serious supply shortages of both alfacalcidol and eldecalcitol. In Japan, unlike Western countries, cholecalciferol cannot be prescribed alone. Instead, only calcium carbonate, cholecalciferol, and magnesium carbonate (Ca/VD) are allowed to be prescribed when denosumab is used.Objectives:To analyze 25(OH) D deficiency and shortage and investigate the effectiveness of nutritional guidance in patients with rheumatic diseases.Methods:We measured 25(OH) D levels in 688 patients (male, n=161; female, n=527; mean age, 65.6±4.9 years) and provided nutritional guidance to patients with a deficiency (less than 20 ng/ml) or shortage (greater than 20 ng/ml, less than 30 ng/ml) of 25(OH) D. The doctors in charge of the outpatient ward provided most of the nutritional guidance. A small number of patients received nutritional guidance from nutritionists. The recommended foods included milk, eggs, fish (especially salmon), and mushrooms (especially dried shiitake mushrooms). It was also suggested that patients consume milk or yogurt containing 25(OH) D. We initiated denosumab and Ca/VD therapy in patients with osteoporosis (according to Japanese guidelines) diagnosed based on bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA). Patients with osteoporosis who had already been treated with drugs with other modes of action were switched to denosumab or Ca/VD.Results:Among the 688 patients, there were 515 patients with RA, 37 patients with systemic sclerosis,34 patients with polymyalgia rheumatica, and others (n=102). 25(OH) D deficiency was observed in 475 patients (69. 0%) and shortage was observed in 171 patients (24.9%). Only 42 patients (6.1 %) had a normal level of 25(OH) D. The mean age of patients with deficiency (63.9±15.4 years) was younger than that of patients with a shortage (68.5±13.6 years; p<0.001) and normal patients (72.5±9.4 years; p=0.002). Patients with a 25(OH) D shortage were younger than normal patients (p=0.0015). In 413 patients with deficiency, who received only nutritional guidance (patients who started Ca/VD were excluded), the mean 25 (OH) D level significantly increased from 13.2±4.2 to 18.3±6.7 (p<0.001) after one year; 140 patients (20.3%) had a shortage, while the levels of 18 patients (26.1%) normalized. Based on the results of DXA, 53 of 688 patients (7.7 %) started denosumab and Ca/VD. Thirty-nine patients (5.6%) did not use glucocorticoids and BMD was not measured. Thirty-one patients were identified with 25 (OH) D deficiency and 10 with a shortage.Conclusion:Many patients with rheumatic diseases suffer from a deficiency or shortage of 25(OH) D. The measurement of BMD is a good screening tool for osteoporosis in these patients especially those who are not using glucocorticoids when the doctors in charge are not concerned about osteoporosis. Patients were able to increase their 25(OH) D levels without medication with nutritional guidance. The effectiveness of denosumab and Ca/VD should be clarified in follow-up studies.REFERENCES:[1]  Furuya T, Hosoi T, Tanaka E, et al. Prevalence of and factors associated with vitamin D deficiency in 4,793 Japanese patients with rheumatoid arthritis. Clin Rheumatol 32::1081-7, 2013.[2] Ito S, Sato H, Narita I, et al. An analysis of the level of serum 25(OH) vitamin D in patients with rheumatoid arthritis. J New Rem & Clin 69: 1176-1187, 2020 (in Japanese).[3] Fujii M, Miyakoshi N, Owan I, et al. A new idea for improving serum vitamin D by taking natural vitamin D (Cholecalciferol) -supplemented bun with sweet paste. Jpn J orthopedic Surgery 7: 59-67, 2021 (in Japanese with English abstract).Acknowledgements:NIL.Disclosure of Interests:None declared.