BACKGROUND: The burden of dementia is growing rapidly and has become a medical and social problem in Japan. Prospective cohort studies have been considered an effective methodology to clarify the risk factors and the etiology of dementia. We aimed to perform a large-scale dementia cohort study to elucidate environmental and genetic risk factors for dementia, as well as their interaction. METHODS: The Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD) is a multisite, population-based prospective cohort study of dementia, which was designed to enroll approximately 10,000 community-dwelling residents aged 65 years or older from 8 sites in Japan and to follow them up prospectively for at least 5 years. Baseline exposure data, including lifestyles, medical information, diets, physical activities, blood pressure, cognitive function, blood test, brain magnetic resonance imaging (MRI), and DNA samples, were collected with a pre-specified protocol and standardized measurement methods. The primary outcome was the development of dementia and its subtypes. The diagnosis of dementia was adjudicated by an endpoint adjudication committee using standard criteria and clinical information according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd Revised Edition. For brain MRI, three-dimensional acquisition of T1-weighted images was performed. Individual participant data were pooled for data analyses. RESULTS: The baseline survey was conducted from 2016 to 2018. The follow-up surveys are ongoing. A total of 11,410 individuals aged 65 years or older participated in the study. The mean age was 74.4 years, and 41.9% were male. The prevalence of dementia at baseline was 8.5% in overall participants. However, it was 16.4% among three sites where additional home visit and/or nursing home visit surveys were performed. Approximately two-thirds of dementia cases at baseline were Alzheimer's disease. CONCLUSIONS The prospective cohort data from the JPSC-AD will provide valuable insights regarding the risk factors and etiology of dementia as well as for the development of predictive models and diagnostic markers for the future onset of dementia. The findings of this study will improve our understanding of dementia and provide helpful information to establish effective preventive strategies for dementia in Japan.
Aged ; Alzheimer Disease/genetics* ; Dementia/genetics* ; Environment ; Female ; Humans ; Incidence ; Japan/epidemiology* ; Male ; Middle Aged ; Prevalence ; Prospective Studies ; Risk Factors

Cerebral air embolism caused by lung cancer is extremely rare, especially if not associated with invasive procedures such as needle biopsy. We describe the case of an 86-year-old man with squamous cell lung carcinoma of the left lung. He developed a bad cough and subsequently suffered left hemiplegia. Brain computed tomography (CT) on admission showed no abnormal findings. Diffusion-weighted magnetic resonance (MR) imaging revealed high intensity lesions in the right frontal lobe and right parietal lobes. Repeated brain CT revealed air densities around the high intensity lesions on previous MR imaging, compatible with air embolism causing cerebral infarction. Chest CT confirmed a left pulmonary hilar mass invading the left pulmonary vein, left atrium, and main bronchus. Air densities were found in the left heart ventricle. These radiological findings were attributed to cerebral air embolism associated with advanced lung cancer. Shortly afterwards he died of progressive respiratory failure. Our case reveals two important aspects. First, cerebral air embolism can be caused by lung cancer invading the pulmonary vein, left atrium, and main bronchus without iatrogenic causes. Therefore, we should pay special attention to the etiology when the patients with lung cancer in the advanced stage developed cerebral infarction. Second, repeated CT is recommended if cerebral air embolism is suspected because initial head CT does not always reveal air bubbles.

OBJECTIVE: Programmed cell death-ligand 1 (PD-L1) is expressed in tumor cells and has been shown to predict clinical outcomes of several types of malignancies. The aim of this study was to investigate the effects of carbon-ion (C-ion) beam irradiation on PD-L1 expression in human uterine cervical adeno/adenosquamous carcinoma (UCAA) cells and clinical samples and to identify the prognostic factors for outcomes after C-ion radiotherapy (CIRT).METHODS: The effects of C-ion irradiation on PD-L1 expression in human UCAA and cervical squamous cell carcinoma cells were examined by flow cytometry. We examined PD-L1 expression in UCAA biopsy specimens from 33 patients before CIRT started (pre-CIRT) and after 12 Gy (relative biological effectiveness [RBE]) irradiation (post-12Gy-C) in 4 fractions of CIRT to investigate the correlation between PD-L1 status and clinical outcomes.RESULTS: The PD-L1 expression was upregulated by C-ion beam in a dose-dependent manner in HeLa and SiHa cells through phosphorylated Chk1. The overall frequencies of pre-CIRT and post-12Gy-C PD-L1 positivity were 45% (15/33) and 67% (22/33), respectively. The post-12Gy-C PD-L1 expression was significantly elevated compared to the pre-CIRT PD-L1 expression. There was no significant relationship between the pre-CIRT PD-L1 status and clinical outcomes, such as local control (LC), progression-free survival (PFS), and overall survival (OS). However, the post-12Gy-C PD-L1 expression had better correlation with PFS, but not with LC and OS.CONCLUSION: CIRT can induce PD-L1 expression in UCAA and we propose that PD-L1 expression after starting CIRT may become as a predictive prognostic marker in CIRT for UCAA.
Antigens, CD274 ; Biopsy ; Carcinoma, Squamous Cell ; Disease-Free Survival ; Flow Cytometry ; Heavy Ion Radiotherapy ; Humans ; Radiotherapy ; Treatment Outcome ; Uterine Cervical Neoplasms

OBJECTIVE: Programmed cell death-ligand 1 (PD-L1) is expressed in tumor cells and has been shown to predict clinical outcomes of several types of malignancies. The aim of this study was to investigate the effects of carbon-ion (C-ion) beam irradiation on PD-L1 expression in human uterine cervical adeno/adenosquamous carcinoma (UCAA) cells and clinical samples and to identify the prognostic factors for outcomes after C-ion radiotherapy (CIRT). METHODS: The effects of C-ion irradiation on PD-L1 expression in human UCAA and cervical squamous cell carcinoma cells were examined by flow cytometry. We examined PD-L1 expression in UCAA biopsy specimens from 33 patients before CIRT started (pre-CIRT) and after 12 Gy (relative biological effectiveness [RBE]) irradiation (post-12Gy-C) in 4 fractions of CIRT to investigate the correlation between PD-L1 status and clinical outcomes. RESULTS: The PD-L1 expression was upregulated by C-ion beam in a dose-dependent manner in HeLa and SiHa cells through phosphorylated Chk1. The overall frequencies of pre-CIRT and post-12Gy-C PD-L1 positivity were 45% (15/33) and 67% (22/33), respectively. The post-12Gy-C PD-L1 expression was significantly elevated compared to the pre-CIRT PD-L1 expression. There was no significant relationship between the pre-CIRT PD-L1 status and clinical outcomes, such as local control (LC), progression-free survival (PFS), and overall survival (OS). However, the post-12Gy-C PD-L1 expression had better correlation with PFS, but not with LC and OS. CONCLUSION CIRT can induce PD-L1 expression in UCAA and we propose that PD-L1 expression after starting CIRT may become as a predictive prognostic marker in CIRT for UCAA.

　The education program in all medical schools in Japan has been studied and analyzed every 2 years since 1974 by the curriculum committee of the Association of Japan Medical Colleges. Based on the most recent analysis in 2015, the marked innovation of medical education, such as an integrated curriculum, active learning, and clinical clerkship, was recognized.

Introduction : The purpose of this study was to clarify the antimicrobial susceptibility of Haemophilus influenzae in central Tokyo over a ten-year period.
Methods : We investigated the susceptibility of Haemophilus influenzae isolated in Tokyo Saiseikai Central Hospital for 10 years from 2004 through 2013.
Results : Significant increases in the proportion of strains resistant to ampicillin, ampicillin / sulbactam and cefditoren pivoxil were noted for some years in comparison to the first year studied. There were no significant changes in the susceptibility to levofloxacin and clarithromycin. The proportion of strains resistant to ampicillin and cefditoren pivoxil showed statistically significant increases during the study period. The proportion of the strains resistant to ampicillin / sulbactam isolated from children was greater than from adults for every year studied. Levofloxacin resistant strains were isolated only from adults. The proportion of strains resistant to clarithromycin were about 1% in Japanese national surveillance data, but the proportions in this study were over 9%.
Conclusion : Over a ten-year period in central Tokyo, Haemophilus influenzae strains resistant to ampicillin and cefditoren pivoxil increased. Strains resistant to clarithromycin occurred at a higher rate than nationally.

OBJECTIVE: To determine the interleukin (IL)-6 levels in gingival crevicular fluid (GCF) of patients with severe root resorption after orthodontic treatment and investigate the effects of different static compressive forces (CFs) on IL-6 production by human periodontal ligament (hPDL) cells and the influence of IL-6 on osteoclastic activation from human osteoclastic precursor (hOCP) cells in vitro. METHODS: IL-6 levels in GCF samples collected from 20 patients (15 and 5 subjects without and with radiographic evidence of severe root resorption, respectively) who had undergone orthodontic treatment were measured by ELISA. The levels of IL-6 mRNA in hPDL cells and IL-6 protein in conditioned medium after the application of different uniform CFs (0, 1.0, 2.0, or 4.0 g/cm2 for up to 72 h) were measured by real-time PCR and ELISA, respectively. Finally, the influence of IL-6 on mature osteoclasts was investigated by using hOCP cells on dentin slices in a pit-formation assay. RESULTS: Clinically, the IL-6 levels were significantly higher in the resorption group than in the control group. In vitro, IL-6 mRNA expression significantly increased with increasing CF. IL-6 protein secretion also increased in a time- and magnitude-dependent manner. Resorbed areas on dentin slices were significantly greater in the recombinant human IL-6-treated group and group cultured in hPDL cell-conditioned medium with CF application (4.0 g/cm2) than in the group cultured in hPDL cell-conditioned medium without CF application. CONCLUSIONS: IL-6 may play an important role in inducing or facilitating orthodontically induced inflammatory root resorption.
Culture Media, Conditioned ; Dentin ; Enzyme-Linked Immunosorbent Assay ; Gingival Crevicular Fluid ; Humans* ; Interleukin-6* ; Interleukins ; Osteoclasts ; Periodontal Ligament ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Root Resorption*