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Background: The genetic etiology of schizophrenia (SCZ) overlaps with that of other major psychiatric disorders in samples of European ancestry. The present study investigated transethnic polygenetic features shared between Japanese SCZ or their unaffected first-degree relatives and European patients with major psychiatric disorders by conducting polygenic risk score (PRS) analyses., Methods: To calculate PRSs for 5 psychiatric disorders (SCZ, bipolar disorder [BIP], major depressive disorder, autism spectrum disorder, and attention-deficit/hyperactivity disorder) and PRSs differentiating SCZ from BIP, we utilized large-scale European genome-wide association study (GWAS) datasets as discovery samples. PRSs derived from these GWASs were calculated for 335 Japanese target participants [SCZ patients, FRs, and healthy controls (HCs)]. We took these PRSs based on GWASs of European psychiatric disorders and investigated their effect on risk in Japanese SCZ patients and unaffected first-degree relatives., Results: The PRSs obtained from European SCZ and BIP patients were higher in Japanese SCZ patients than in HCs. Furthermore, PRSs differentiating SCZ patients from European BIP patients were higher in Japanese SCZ patients than in HCs. Interestingly, PRSs related to European autism spectrum disorder were lower in Japanese first-degree relatives than in HCs or SCZ patients. The PRSs of autism spectrum disorder were positively correlated with a young onset age of SCZ., Conclusions: These findings suggest that polygenic factors related to European SCZ and BIP and the polygenic components differentiating SCZ from BIP can transethnically contribute to SCZ risk in Japanese people. Furthermore, we suggest that reduced levels of an ASD-related genetic factor in unaffected first-degree relatives may help protect against SCZ development., (© The Author(s) 2020. Published by Oxford University Press on behalf of CINP.)

Background and Purpose: According to recent news, patients with concurrent tuberculosis (TB) and human immunodeficiency virus (HIV) infection are increasingly common worldwide. This study aimed to investigate whether TB/HIV co-infected patients are visiting Hokkaido., Method: We conducted a questionnaire survey regarding foreign patients infected with TB or TB/HIV who visited Hokkaido between January 2001 and September 2014. We mailed questionnaires to health centers, AIDS treatment care hospitals, and TB hospitals in Hokkaido prefecture., Results: Seventy-one TB patients were of foreign nationality according to the answers obtained from health centers. Most of them were foreign students or occupational trainees between 20-30 years old. Approximately half these patients were from East Asia, and 7 patients were from Africa. As 21 % of the patients with TB who visited medical examination were over 1 month from disease onset, and the delay in visiting was recognized. The TB infection was mostly detected coincidentally during the physician visit. In the hospital survey, four TB patients with HIV were of foreign nationality. They were also of the age group from 20-30 years and hailed from sub-Saharan Africa., Discussion: During immigration, medical examination by performing a chest radiograph is important. If the immigrant hails from an area where TB and HIV co-infection is common, it is necessary to confirm whether HIV infection is present.

Objective: There are differences between Europe and Japan in the incidence and antineutrophil cytoplasmic antibody (ANCA) serotype of patients with microscopic polyangiitis (MPA). However, differences in phenotype or outcome have not been explored. We aimed to identify differences in phenotype and outcome of MPA between Europe and Japan., Methods: Sequential cohorts of patients with MPA and renal limited vasculitis were collected from European and Japanese centers (n = 147 and n = 312, respectively). Trial databases from the European Vasculitis Society and the Japanese patients with Myeloperoxidase (MPO)-ANCA-Associated Vasculitis (JMAAV) trial were studied (n = 254 and n = 48, respectively). We evaluated baseline characteristics including ANCA status and organ involvement, treatment, survival, and renal survival. Differences in survival and renal survival were studied using multivariate analysis., Results: The non-trial cohorts showed patients with MPA in Japan had a higher age at onset, more frequent MPO-ANCA positivity, lower serum creatinine, and more frequent interstitial pneumonitis than those in Europe (all p < 0.01). Comparisons between the trial databases demonstrated similar results. Cumulative patient survival and renal survival rates were not different between Europe and Japan (p = 0.71 and p = 0.38, respectively). Multivariate analysis identified age at onset, serum creatinine, gastrointestinal, and respiratory involvement as factors with higher risk of death. For endstage renal failure, serum creatinine and use of plasma exchange were identified as factors with higher risk, and immunosuppressant use as lower risk factors., Conclusion: Phenotypes in patients with MPA were different between Europe and Japan. However, the outcomes of patient survival and renal survival were similar.

Objective: To examine associations between various dietary markers and mortality from ischemic heart disease (IHD) and stroke., Design and Setting: A multi-center cross-sectional study, involved 25 co-operative study centers in 16 countries., Method: In the report, data for males (n = 2462), aged 48-56 years, from 25 centers were included. Various dietary markers were measured from individual's blood and 24-h urine samples. Age-standardized male mortality rates for IHD and stroke were collected for the region encompassing each study center. Ecological cross-center associations between dietary markers and the mortality were analyzed using univariate and multivariate analysis techniques., Results: Bivariate correlation analyses showed that IHD mortality was associated positively with body mass index (BMI), serum total cholesterol (TC), urinary potassium (K) and serum phospholipid palmitic acid, and negatively with urinary taurine, sodium (Na) and Na/K (potassium) ratio, n-3 polyunsaturated (n-3PU) fatty acids and polyunsaturated-to-saturated (P/S) fatty acid ratio. Stroke mortality was associated positively with Na and Na/K ratio and phospholipid arachidonic acid (AA), and negatively with TC and K. Stepwise linear regression analyses indicated that 59% of the variance in IHD mortality could be explained by the variance in taurine and P/S ratio and that 57% of stroke mortality could be explained by Na/K ratio and phospholipid AA., Conclusion: Although ecological associations do not necessarily imply causality, and the present findings are limited to male samples only, the study extends our understanding of dietary markers in relation to worldwide IHD and stroke mortality rates, and indicates useful avenues for further study on IHD and stroke prevention.

Objective: S-1 is an oral anticancer agent combining tegafur (FT), a prodrug of 5-fluorouracil (5-FU), with potassium oxonate (oteracil) and gimeracil (CDHP) respectively to mitigate gastrointestinal toxicity and increase the half-life of 5-FU. This article presents a population pharmacokinetic analysis of these four compounds in Western cancer patients. The second objective was to compare the pharmacokinetics of S-1 in Western and Japanese patients., Methods: A single dose (25-45 mg/m2) of S-1 was administered to 60 patients. In each patient, 6 concentrations of FT, 5-FU, oteracil and CDHP were measured over 24 hr. Using NONMEM, oteracil and CDHP were analyzed separately, and the individual estimates of CDHP parameters were included in the joint analysis of FT and 5-FU. We used validation techniques to assess differences between the two populations, and finally we compared the exposures in Western and Japanese patients using simulations., Results: A compartmental model describing the PK of the 4 compounds was developed. The influence of CDHP on the elimination of 5-FU was well described by an enzymatic inhibition model. The model provided a good fit for all compounds. The pharmacokinetics for 5-FU and oteracil were similar between Western and Japanese patients, but apparent differences in exposure to 5-FU resulted from different total doses due to different body sizes.