Radiation exposure and circulatory disease risk: Hiroshima and Nagasaki atomic bomb survivor data, 1950-2003

Objective To investigate the degree to which ionising radiation confers risk of mortality from heart disease and stroke

The Timescale of Emergence and Spread of Turnip Mosaic Potyvirus

Plant viruses have important global impacts on crops, and identifying their centre and date of emergence is important for planning control measures. Turnip mosaic virus (TuMV) is a member of the genus Potyvirus in the family Potyviridae and is a major worldwide pathogen of brassica crops. For two decades, we have collected TuMV isolates, mostly from brassicas, in Turkey and neighbouring countries. This region is thought to be the centre of emergence of this virus. We determined the genomic sequences of 179 of these isolates and used these to estimate the timescale of the spread of this virus. Our Bayesian coalescent analyses used synonymous sites from a total of 417 novel and published whole-genome sequences. We conclude that TuMV probably originated from a virus of wild orchids in Germany and, while adapting to wild and domestic brassicas, spread via Southern Europe to Asia Minor no more than 700 years ago. The population of basal-B group TuMVs in Asia Minor is older than all other populations of this virus, including a newly discovered population in Iran. The timescale of the spread of TuMV correlates well with the establishment of agriculture in these countries.This work was in part funded by Saga University and supported by JSPS KAKENHI Grant numbers 18405022, 24405026 and 16K14862 and Grant-in-Aid for JSPS Research Fellow Grant number 16J04390

Lipid Accumulation in Peripheral Blood Dendritic Cells and Anticancer Immunity in Patients with Lung Cancer

We studied the subsets of peripheral blood dendritic cells (DCs) and lipid accumulation in DCs to investigate the involvement of DCs in the decreased anticancer immunity of advanced lung cancer patients. We analyzed the population of DC subsets in peripheral blood using flow cytometry. We then determined lipid accumulation in the DCs using BODIPY 650/665, a fluorophore with an affinity for lipids. Compared with healthy controls, the number of DCs in the peripheral blood of treatment-naive cancer patients was significantly reduced. In patients with stage III + IV disease, the numbers of myeloid DCs (mDCs) and plasmacytoid DCs were also significantly reduced. Lipid accumulation in DCs evaluated based on the fluorescence intensity of BODIPY 650/665 was significantly higher in stage III + IV lung cancer patients than in the controls. In the subset analysis, the fluorescence was highest for mDCs. The intracellularly accumulated lipids were identified as triglycerides. A decreased mixed leukocyte reaction was observed in the mDCs from lung cancer patients compared with those from controls. Taken together, the results show that lung cancer patients have a notably decreased number of peripheral blood DCs and their function as antigen-presenting cells is decreased due to their high intracellular lipid accumulation. Thereby, anticancer immunity is suppressed

Measurement of Fractional Exhaled Nitric Oxide with a Stationary Analyzer（NOA280i®）or Hand-held Analyzer（NIOX MINO®）Shows a Strong Correlation but Weaker Correlation at Higher Levels

This study investigated the difference of measured values between two types of analyzer over a wider range of fractional exhaled nitric oxide （FeNO） levels than in previous reports because some asthma patients have high FeNO levels. The equation for conversion of measured FeNO levels between the two analyzers was also determined.Methods：Patients underwent assessment of FeNO for the diagnosis and management of asthma or for differential diagnosis of cough, FeNO levels were measured sequentially using both a stationary analyzer（NOA280i®, Sievers Inc, USA） and a hand-held analyzer（NIOX MINO®, Aerocrine Inc, Sweden）. FeNO levels were measured in a total of 167 subjects. Regression analysis of the FeNO data showed a strong positive correlation between values obtained with the two analyzers （r＝0.938, p＜0.0001）, and the regression line was calculated as：FeNO （NOA280i®）×0.63＋3.79＝FeNO （NIOX MINO®）. The correlation between the two analyzers was strongest at low FeNO values and it decreased as the FeNO level increased ［FeNO （NOA280i®）£50 （r＝0.730, p＜0.0001） FeNO （NOA280i®） 50 to £100 （r＝0.641, p＜0.0001）, FeNO （NOA280i®）＞100 to £150 （r＝0.607, p＝0.0008）, and FeNO （NOA280i®）＞150 （r＝0.523, p＝0.0180）］. Bland-Altman plot analysis between the two analyzers was 0.167 （95％ confidence interval＝－0.038 to 0.357, suggesting a positive difference.Some caution is needed because the correlation between the two analyzers is weaker when the FeNO level exceeds 150

Phase I Trial of Pemetrexed in Combination with Carboplatin Followed by Pemetrexed Maintenance Therapy in Elderly Patients with Advanced Non-small Cell Lung Cancer

Introduction： A phase I trial was conducted to evaluate the feasibility of pemetrexed in combination with carboplatin followed by pemetrexed maintenance therapy in elderly patients with advanced non-small cell lung cancer （NSCLC）. The primary objective of this study was to determine the maximum tolerated dose （MTD） and the recommended dose （RD） of pemetrexed in combination with carboplatin.Methods：Chemotherapy-naïve elderly 13 patients （age, ≥70 years） with stage IIIB/IV non-squamous NSCLC were enrolled and received pemetrexed 500 mg/m2 and carboplatin at an area under the curve （AUC）dose of 5 mg/ml/min（level 1）or 6 mg/ml/min （level 2）. Pemetrexed with carboplatin was administered on day 1 of the 21-day cycle. The treatment schedule consisted of four cycles of pemetrexed with carboplatin. Patients who did not have progressive disease after completion of four cycles subsequently received pemetrexed maintenance therapy （500 mg/m2 every three weeks） until disease progression or unacceptable toxicity was noted.Results：Three patients were enrolled in level 1, in which no dose-limiting toxicity（DLT）was observed. The carboplatin dose was escalated to AUC 6. Two of 3 patients treated in level 2 had grade 4 thrombocytopenia of DLT. MTD was determined as level 2. Consequently, pemetrexed 500 mg/m2 with carboplatin AUC 5 was recommended as the dose for elderly patients with advanced non-squamous NSCLC. An additional 7 patients who received RD showed no DLT. Nine of 13 patients received 4 cycles of combination therapy, and 5 patients were continuously treated with pemetrexed maintenance therapy. Six patients achieved a partial response, and another 6 showed stable disease. The response rate and disease control rate were 46.2％ and 92.3％, respectively. The median progression-free survival for the enrolled patients was 134 days （95％ CI, 95 to 231 days）, and the median overall survival was 346 days （95％ CI, 151 to 549 days）.Conclusions：The combination therapy of pemetrexed 500 mg/m2 with carboplatin AUC 5 followed by pemetrexed maintenance therapy showed no severe adverse events and was feasible and well-tolerated for elderly patients with advanced non-squamous NSCLC

Effects of thienopyridine class antiplatelets on bleeding outcomes following robot-assisted radical prostatectomy

Abstract This study aimed to assess the effects of thienopyridine-class antiplatelet agents (including ticlopidine, clopidogrel, and prasugrel) on bleeding complications in patients who underwent robot-assisted radical prostatectomy. This cohort study used a database for robot-assisted radical prostatectomy at 23 tertiary centers nationwide between 2011 and 2022. Patients who received thienopyridines (thienopyridine group) were compared with those who received aspirin monotherapy (aspirin group). The primary outcome was the incidence of bleeding complications. High-grade complications were defined as Clavien–Dindo grade III or higher. The risks of these outcomes were evaluated using inverse probability of treatment weighted regression models. The study results demonstrated that thienopyridine therapy was associated with a higher risk of overall bleeding complications (OR: 3.62, 95%CI 1.54–8.49). The increased risks of the thienopyridine group were detected for low-grade bleeding complications (OR: 3.20, 95%CI 1.23–8.30) but not for high-grade bleeding complications (OR: 5.23, 95%CI 0.78–34.9). The increased risk of bleeding complications was not observed when thienopyridine was discontinued (OR: 2.52, 95%CI 0.83–7.70); however, it became apparent when it was continued perioperatively (OR: 4.35, 95%CI 1.14–16.61). In conclusion, thienopyridine increased the incidence of bleeding complications, particularly low-grade bleeding complications, following robot-assisted radical prostatectomy. These bleeding effects emerged when thienopyridine was continued perioperatively