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Zinc deficiency, affecting more than 2 billion people globally, poses a significant public health burden due to its numerous unfavorable effects, such as impaired immune function, taste and smell disorders, pneumonia, growth retardation, visual impairment, and skin disorders. Despite its critical role, extensive large-scale studies investigating the correlation between patient characteristics and zinc deficiency still need to be completed. We conducted a retrospective, cross-sectional observational study using a nationwide Japanese claims database from January 2019 to December 2021. The study population included 13,100 patients with available serum zinc concentration data, excluding individuals under 20 and those assessed for zinc concentrations after being prescribed zinc-containing medication. Significant associations with zinc deficiency were noted among older adults, males, and inpatients. Multivariate analysis, adjusting for age and sex, indicated significant associations with comorbidities, including pneumonitis due to solids and liquids with an adjusted Odds Ratio (aOR) of 2.959; decubitus ulcer and pressure area (aOR 2.403), sarcopenia (aOR 2.217), COVID-19 (aOR 1.889), and chronic kidney disease (aOR 1.835). Significant association with medications, including spironolactone (aOR 2.523), systemic antibacterials (aOR 2.419), furosemide (aOR 2.138), antianemic preparations (aOR 2.027), and thyroid hormones (aOR 1.864) were also found. These results may aid clinicians in identifying patients at risk of zinc deficiency, potentially improving care outcomes.

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PURPOSE: To elucidate the risk factors associated with the onset of glioblastoma (GBM) utilizing a comprehensive administrative claims database from a major governmental district in Japan. METHODS: Using the Shizuoka Kokuho Database (SKDB) for the period from April 2012 to September 2021, we conducted a retrospective analysis of 1,465,353 participants, identifying GBM cases using specific Japanese disease codes in conjunction with associated treatments. Risk factors were assessed using both univariable and multivariable Cox proportional hazards models. RESULTS: Within the cohort, 182 participants (0.012%) received a GBM diagnosis during the study period, resulting in an incidence rate of 2.1 per 100,000 person-years. The multivariable analysis revealed that older age, male sex, and peripheral vascular disease (PVD) significantly influenced the risk of GBM onset. No clear link was found between allergic conditions and GBM risk, in contrast to some previous research. CONCLUSION: Employing a robust health insurance database, this study revealed significant associations between GBM and factors such as age, male sex, and PVD within the Japanese population. It provides key insights into GBM epidemiology and underscores the potential of health insurance databases for large-scale oncological research.

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Hip fractures are common in patients of advanced age and are associated with excess mortality. Rapid and accurate prediction of the prognosis using information that can be easily obtained before surgery would be advantageous to clinical management. We performed a population-based retrospective cohort study using an 8.5-year Japanese claims database (April 2012-September 2020) to develop and validate a predictive model for long-term mortality after hip fracture. The study included 43,529 patients (34,499 [79.3%] women) aged ≥65 years with first-onset hip fracture. During the observation period, 43% of the patients died. Cox regression analysis identified the following prognostic predictors: sex, age, fracture site, nursing care certification, and several comorbidities (any malignancy, renal disease, congestive heart failure, chronic pulmonary disease, liver disease, metastatic solid tumor, and deficiency anemia). We then developed a scoring system called the Shizuoka Hip Fracture Prognostic Score (SHiPS); this system was established by scoring based on each hazard ratio and classifying the degree of mortality risk into four categories based on decision tree analysis. The area under the receiver operating characteristic (ROC) curve (AUC) (95% confidence interval [CI]) of 1-year, 3-year, and 5-year mortality based on the SHiPS was 0.718 (95% CI, 0.706-0.729), 0.736 (95% CI, 0.728-0.745), and 0.758 (95% CI, 0.747-0.769), respectively, indicating good predictive performance of the SHiPS for as long as 5 years after fracture onset. Even when the SHiPS was individually applied to patients with or without surgery after fracture, the prediction performance by the AUC was >0.7. These results indicate that the SHiPS can predict long-term mortality using preoperative information regardless of whether surgery is performed after hip fracture.

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INTRODUCTION: Acquired haemophilia A (AHA) is a rare disease. The risk factors have yet to be studied. AIM: We aimed to identify risk factors for late-onset AHA in Japan. METHODS: A population-based cohort study was conducted using data from the Shizuoka Kokuho Database. The study population was defined as individuals aged ≥60 years. Cause-specific Cox regression analysis was performed to calculate hazard ratios. RESULTS: Of 1,160,934 registrants, there were 34 patients with newly diagnosed AHA. The mean follow-up period was 5.6 years, and the incidence of AHA was 5.21 per million person-years. Myocardial infarction, diabetes mellitus, solid tumors, antimicrobial agents, phenytoin and anti-dementia drugs, which showed significant differences in the univariate analysis, were excluded from the multivariable analysis because of the small number of cases. Multivariable regression analysis showed that the presence of Alzheimer's disease (hazard ratio [HR]:4.28, 95% confidence interval [CI]:1.67-10.97) and rheumatic disease (HR:4.65, 95% CI:1.79-12.12) increased the risk of AHA development. CONCLUSION: We found that comorbid Alzheimer's disease is a risk factor of AHA incidence in the general population. Our findings provide insight into the etiology of AHA, and the proof of the coexistence of Alzheimer's disease may support the recent notion that Alzheimer disease is an autoimmune disease.

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During the early formation of the dorsal aorta, the first-forming embryonic vessel in amniotes, a subset of somitic cells selected as presumptive angioblasts, migrates toward the dorsal aorta, where they eventually differentiate into endothelial cells. We have recently shown that these processes are controlled by Notch signals (Sato, Y., Watanabe, T., Saito, D., Takahashi, T., Yoshida, S., Kohyama, J., Ohata, E., Okano, H., and Takahashi, Y., 2008. Notch mediates the segmental specification of angioblasts in somites and their directed migration toward the dorsal aorta in avian embryos. Dev. Cell 14, 890-901.). Here, we studied a possible link between Notch and chemokine signals, SDF1/CXCR4, the latter found to be dominantly expressed in developing aorta/somites. Although CXCR4 overexpression caused a directed migration of somitic cells to the aortic region in a manner similar to Notch, no positive epistatic relationships between Notch and SDF1/CXCR4 were detected. After reaching the aortic region, the CXCR4-electroporated cells exhibited no endothelial character. Importantly, however, once provided with Notch activity, they could successfully be incorporated into developing vessels as endothelial cells. These findings were obtained combining the tetracycline-inducible gene expression method with the transposon-mediated stable gene transfer technique. We conclude that Notch activation is sufficient to direct naïve mesenchymal cells to differentiate into endothelial cells once the cells are conveyed to the aortic region.

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We studied, using avian embryos, mechanisms underlying the three-dimensional assembly of the dorsal aorta, the first-forming embryonic vessel in amniotes. This vessel originates from two distinct cell populations, the splanchnic and somitic mesoderms. We have unveiled a role for Notch signaling in the somitic contribution. Upon activation of Notch signaling, a subpopulation of cells in the posterior half of individual somites migrates ventrally toward the primary dorsal aorta of splanchnic origin. After reaching the primary aorta, these somitic cells differentiate into the definitive aortic endothelial cells. This Notch-induced ventral migration is mediated by EphrinB2 and by an attractant action of the primary aorta. Furthermore, long-term chasing of cells by transposon-mediated gene transfer reveals that the segmentally provided endothelial cells of somitic origin in the dorsal aorta ultimately populate the entire region of the vessel. We demonstrate the molecular and cellular mechanisms underlying the formation of embryonic blood vessels from mesenchymal cells.

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