A nationwide trend analysis in the incidence and mortality of Creutzfeldt-Jakob disease in Japan between 2005 and 2014

In the era of hyper-ageing, Creutzfeldt-Jakob disease (CJD) can become more prevalent as an important cause of dementia. This study aimed to evaluate the trends in crude and age-adjusted CJD-associated mortality and incidence rates in Japan using national vital statistics data on CJD-associated deaths among individuals aged over 50 years, as well as the government-funded nationwide CJD surveillance data (pertaining to the years 2005-2014) in Japan. The data were analysed using the Joinpoint Regression Program to estimate the long-term trends and average annual percentage changes (AAPCs). Overall, the AAPCs of age-adjusted CJD-associated mortality rates rose significantly over the study period (3.2%; 95% confidence interval [CI] 1.4-5.1%). The AAPC of the age-adjusted incidence rates also increased (overall 6.4%; 95% CI 4.7-8.1%). The CJD-associated increases in the mortality and incidence rates were especially prominent among adults over the age of 70 years. Given this trend in aging of population, the disease burden of CJD will continue to increase in severity. Our findings thus recommend that policymakers be aware of the importance of CJD and focus on preparing to address the increasing prevalence of dementia

TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice

Excess production of reactive oxygen species (ROS) caused by hyperglycemia is a major risk factor for heart failure. We previously reported that transient receptor potential canonical 3 (TRPC3) channel mediates pressure overload-induced maladaptive cardiac fibrosis by forming stably functional complex with NADPH oxidase 2 (Nox2). Although TRPC3 has been long suggested to form hetero-multimer channels with TRPC6 and function as diacylglycerol-activated cation channels coordinately, the role of TRPC6 in heart is still obscure. We here demonstrated that deletion of TRPC6 had no impact on pressure overload-induced heart failure despite inhibiting interstitial fibrosis in mice. TRPC6-deficient mouse hearts 1 week after transverse aortic constriction showed comparable increases in fibrotic gene expressions and ROS production but promoted inductions of inflammatory cytokines, compared to wild type hearts. Treatment of TRPC6-deficient mice with streptozotocin caused severe reduction of cardiac contractility with enhancing urinary and cardiac lipid peroxide levels, compared to wild type and TRPC3-deficient mice. Knockdown of TRPC6, but not TRPC3, enhanced basal expression levels of cytokines in rat cardiomyocytes. TRPC6 could interact with Nox2, but the abundance of TRPC6 was inversely correlated with that of Nox2. These results strongly suggest that Nox2 destabilization through disrupting TRPC3-Nox2 complex underlies attenuation of hyperglycemia-induced heart failure by TRPC6.Fil: Oda, Sayaka. Okazaki Institute for Integrative Bioscience; Japón. SOKENDAI; JapónFil: Numaga Tomita, Takuro. Okazaki Institute for Integrative Bioscience; Japón. SOKENDAI; JapónFil: Kitajima, Naoyuki. Okazaki Institute for Integrative Bioscience; Japón. Kyushu University; JapónFil: Tomizaki, Takashi. Okazaki Institute for Integrative Bioscience; Japón. Kyushu University; Japón. University of Tsukuba; JapónFil: Harada, Eri. Ajinomoto Co.; Japón. EA Pharma Co.; JapónFil: Shimauchi, Tsukasa. Okazaki Institute for Integrative Bioscience; Japón. Kyushu University; JapónFil: Nishimura, Akiyuki. Okazaki Institute for Integrative Bioscience; Japón. SOKENDAI; Japón. Ajinomoto Co.; JapónFil: Ishikawa, Tatsuya. Kyushu University; Japón. Ajinomoto Co.; Japón. EA Pharma Co.; JapónFil: Kumagai, Yoshito. University of Tsukuba; JapónFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Nishida, Motohiro. Okazaki Institute for Integrative Bioscience; Japón. SOKENDAI; Japón. Kyushu University; Japón. PRESTO; Japó

Embryonic expression of a hemichordate distal-less gene

Hemichordates occupy a critical phylogenetic position among deuterostomes because they exhibit echinoderm-like larval morphology and chordate-like adult morphology. Analyses of the expression and function of hemichordate developmental genes will therefore provide insight into the evolution of deuterostome body plans. The distal-less/dlx gene encodes a homeodomain transcription factor and plays roles in the development of appendages and the brain in a variety of animals. Here we have characterized a distal-less gene (Pf-dlx) of the hemichordate Ptychodera flava. During embryogenesis, Pf-dlx is expressed in the whole aboral ectoderm of the blastula and gastrula. Later, its expression appears in several cells in the boundary region between the oral and aboral ectoderm. The tornaria larvae express Pf-dlx in some specific cells of the ciliary band. The results are discussed in terms of an ancestral function of the distal-less/dlx gene in the formation of the nervous system

Trends in Head and Neck Cancer Mortality from 1999 to 2019 in Japan : An Observational Analysis

The number of cases of head and neck cancer (HNC) and related deaths has recently increased worldwide. To the best of our knowledge, few studies have examined crude or age-adjusted HNC mortality rates in Japan. Therefore, this study aimed to determine the trends in crude and age-adjusted mortality rates for HNC per million individuals in Japan from 1999 to 2019. In Japan, the number of HNC-related deaths increased 1.48-fold. Age-adjusted mortality rates for HNC were four times higher in men than in women, and the rates for both men and women decreased over the 21-year period. This study clarifies the changes in age-adjusted mortality rates of HNC in Japan over time and will aid in developing targeted screening and prevention programs for HNC.Globally, the numbers of head and neck cancer (HNC) cases and related deaths have recently increased. In Japan, few studies have examined crude or age-adjusted HNC mortality rates. Therefore, this study aimed to determine the trends in crude and age-adjusted mortality rates for HNC per million individuals in Japan from 1999 to 2019. Data on HNC-associated deaths were extracted from the national death certificate database using the International Classification of Diseases, Tenth Revision (n = 156,742). HNC mortality trends were analysed using joinpoint regression models to estimate annual percentage change (APC) and average APC (AAPC). Among men, no significant change was observed in the age-adjusted death rate trend from 1999 to 2014; however, a marked decrease was observed from 2014 to 2019. No changing point was observed in women. Age-adjusted mortality rates continuously decreased over the 21-year period, with an AAPC of −0.7% in men and −0.6% in women. In conclusion, the overall trend in age-adjusted rates of HNC-associated deaths decreased, particularly among men, in the past 5 years. These results will contribute to the formulation of medical policies to develop targeted screening and prevention programmes for HNC in Japan and determine the direction of treatment strategies

A Randomized Phase II Study of S-1 Adjuvant Chemotherapy With or Without Hochu-ekki-to, a Japanese Herbal Medicine, for Stage II/III Gastric Cancer: The KUGC07 (SHOT) Trial

Objectives: A multicenter randomized phase II study was conducted to evaluate the effects of Hochu-ekki-to (TJ-41) for reducing adverse reactions and increasing compliance with S-1 adjuvant therapy for advanced gastric cancer.Methods: The eligibility criteria were pathological stage II/III after R0 resection. Patients received adjuvant therapy with S-1 alone (group S) or S-1 with TJ-41 (group ST) for 1 year. The primary endpoint was the completion rate of S-1. Secondary endpoints were adverse events, relative dose intensity, relapse-free survival (RFS), and overall survival (OS).Results: We randomly assigned 56 patients to group ST and 57 patients to group S. The completion rates of S-1 were 54.5 and 50.9%, the median relative dose intensities were 89.2 and 71.9%, and adverse events of grade 3 or 4 occurred in 45.5 and 54.5% in groups ST and S, respectively. There was no significant difference in 3-year OS or RFS between the two groups.Conclusions: TJ-41 does not increase relative dose and completion rate of S-1 significantly. J-41 may reduce toxic effects, but our findings do not support routine use of TJ-41 after gastrectomy

Drug Repositioning for Cardiac Arrest

The survival rate of cardiac arrest patients is less than 10%; therefore, development of a therapeutic strategy that improves their prognosis is necessary. Herein, we searched data collected from medical facilities throughout Japan for drugs that improve the survival rate of cardiac arrest patients. Candidate drugs, which could improve the prognosis of cardiac arrest patients, were extracted using “TargetMine,” a drug discovery tool. We investigated whether the candidate drugs were among the drugs administered within 1 month after cardiac arrest in data of cardiac arrest cases obtained from the Japan Medical Data Center. Logistic regression analysis was performed, with the explanatory variables being the presence or absence of the administration of those candidate drugs that were administered to ≥10 patients and the objective variable being the “survival discharge.” Adjusted odds ratios for survival discharge were calculated using propensity scores for drugs that significantly improved the proportion of survival discharge; the influence of covariates, such as patient background, medical history, and treatment factors, was excluded by the inverse probability-of-treatment weighted method. Using the search strategy, we extracted 165 drugs with vasodilator activity as candidate drugs. Drugs not approved in Japan, oral medicines, and external medicines were excluded. Then, we investigated whether the candidate drugs were administered to the 2,227 cardiac arrest patients included in this study. The results of the logistic regression analysis showed that three (isosorbide dinitrate, nitroglycerin, and nicardipine) of seven drugs that were administered to ≥10 patients showed significant association with improvement in the proportion of survival discharge. Further analyses using propensity scores revealed that the adjusted odds ratios for survival discharge for patients administered isosorbide dinitrate, nitroglycerin, and nicardipine were 3.35, 5.44, and 4.58, respectively. Thus, it can be suggested that isosorbide dinitrate, nitroglycerin, and nicardipine could be novel therapeutic agents for improving the prognosis of cardiac arrest patients

TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice

Excess production of reactive oxygen species (ROS) caused by hyperglycemia is a major risk factor for heart failure. We previously reported that transient receptor potential canonical 3 (TRPC3) channel mediates pressure overload-induced maladaptive cardiac fibrosis by forming stably functional complex with NADPH oxidase 2 (Nox2). Although TRPC3 has been long suggested to form hetero-multimer channels with TRPC6 and function as diacylglycerol-activated cation channels coordinately, the role of TRPC6 in heart is still obscure. We here demonstrated that deletion of TRPC6 had no impact on pressure overload-induced heart failure despite inhibiting interstitial fibrosis in mice. TRPC6-deficient mouse hearts 1 week after transverse aortic constriction showed comparable increases in fibrotic gene expressions and ROS production but promoted inductions of inflammatory cytokines, compared to wild type hearts. Treatment of TRPC6-deficient mice with streptozotocin caused severe reduction of cardiac contractility with enhancing urinary and cardiac lipid peroxide levels, compared to wild type and TRPC3-deficient mice. Knockdown of TRPC6, but not TRPC3, enhanced basal expression levels of cytokines in rat cardiomyocytes. TRPC6 could interact with Nox2, but the abundance of TRPC6 was inversely correlated with that of Nox2. These results strongly suggest that Nox2 destabilization through disrupting TRPC3-Nox2 complex underlies attenuation of hyperglycemia-induced heart failure by TRPC6

経頸静脈的肝内門脈大循環短絡術が著効した難治性腹水の1例

京都府立医科大学附属北部医療センター放射線科京都府立医科大学附属北部医療センター外科京都府立医科大学大学院医学研究科放射線診断治療学京都府立医科大学大学院医学研究科消化器外科学市立福知山市民病院腫瘍内科市立福知山市民病院放射線科Department of Radiology, North Medical Center, Kyoto Prefectural University of MedicineDepartment of Surgery, North Medical Center, Kyoto Prefectural University of MedicineDepartment of Radiology, Kyoto Prefectural University of MedicineDepartment of Digestive Surgery, Kyoto Prefectural University of MedicineDepartment of Medical Oncology, Fukuchiyama City HospitalDepartment of Medical Radiology, Fukuchiyama City Hospital切除不能肝内胆管癌の58 歳男性に難治性腹水を生じ、著明な腹部膨満感に対し頻回な穿刺排液を要した。腹水性状は漏出性で進行した肝病変による門脈圧亢進症に起因すると判断した。介入治療として経頸静脈的肝内門脈大循環短絡術を適用した。腹部膨満感のNRS は9 から1 に低下し、35 日後の原病死まで有害事象や症状再発なく経過した。難治性腹水に対する介入治療には、腹水の性状診断を含めて治療方針を決定することが重要である