記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Hypertension (HT), dyslipidemia (DL), and diabetes mellitus (DM) are major risk factors for cardiovascular diseases. Despite the wide availability of medications to reduce this risk, poor adherence to medications remains an issue. The aim of this study is to evaluate medication adherence of prevalent users in these disease medications (HT, DL, DM) using claims data. Factors associated with non-adherence were also examined. METHODS: Of 7538 participants of the Tsuruoka Metabolomics Cohort Study, 3693 (HT: 2702, DL: 2112, DM: 661) were identified as prevalent users of these disease medications. Information on lifestyle was collected through a questionnaire. Adherence was assessed by a proportion of days covered (PDC) and participants with PDC ≥0.8 were defined as adherent. Predictors of non-adherence were determined by performing multivariable logistic regression. RESULTS: Medication adherence differed by treatment status. Among those without comorbidities, those with HT-only showed the highest adherence (90.2%), followed by those with DM-only (81.2%) and those with DL-only (80.8%). Factors associated with non-adherence in each medication group were skipping breakfast and poor understanding of medications among those with HT medications, females, having comorbidities, having a history of heart disease, and drinking habit among those with DL medications, and good sleep quality and skipping breakfast among those with DM medications. CONCLUSION: While participants showed high medication adherence, differences were observed across medication groups. The identified predictors of non-adherence could help target those in need of adherence support.

DOI： 10.1002/pds.5855

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Healthcare (Switzerland)  

Survival analysis is a set of methods for statistical inference concerning the time until the occurrence of an event. One of the main objectives of survival analysis is to evaluate the effects of different covariates on event time. Although the proportional hazards model is widely used in survival analysis, it assumes that the ratio of the hazard functions is constant over time. This assumption is likely to be violated in practice, leading to erroneous inferences and inappropriate conclusions. The accelerated failure time model is an alternative to the proportional hazards model that does not require such a strong assumption. Moreover, it is sometimes plausible to consider the existence of cured patients or long-term survivors. The survival regression models in such contexts are referred to as cure models. In this study, we consider the accelerated failure time cure model with frailty for uncured patients. Frailty is a latent random variable representing patients’ characteristics that cannot be described by observed covariates. This enables us to flexibly account for individual heterogeneities. Our proposed model assumes a shifted gamma distribution for frailty to represent uncured patients’ heterogeneities. We construct an estimation algorithm for the proposed model, and evaluate its performance via numerical simulations. Furthermore, as an application of the proposed model, we use a real dataset, Specific Health Checkups, concerning the onset of hypertension. Results from a model comparison suggest that the proposed model is superior to existing alternatives.

DOI： 10.3390/healthcare10081383

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BMJ open  

OBJECTIVES: To date, the association between accumulated unhealthy behaviours and insomnia in individuals stratified according to the presence or absence of major cardiovascular risk factors is unclear. This study aimed to examine the effect of accumulated unhealthy behaviours on insomnia in Japanese dwellers. DESIGN: Cross-sectional study. SETTING: Baseline data between April 2012 and March 2015. PARTICIPANTS: Our study used cross-sectional data among Japanese aged 35-74 years in a rural community (N=9565), the attendees of annual municipal or work site health check-up programmes. MAIN OUTCOME MEASURES: Insomnia was assessed by Athens Insomnia Scale, which was set at 6 points and greater; other scales were given. Participants were categorised into three groups by their number of unhealthy behaviours (no exercise habit, smoking, alcohol drinking, skipping breakfast and obesity): 0-1, 2-3, 4 or more. The association between accumulated unhealthy behaviours and insomnia was estimated by logistic regression analysis. Further analysis was done after stratification of cardiovascular risk factors assessed by anthropometrics and clinical biochemistry measurements. RESULTS: The overall prevalence of insomnia was 13.3% for men and 19.3% for women. Men with unhealthy behaviour factors were more likely to have insomnia after adjusting for potential confounders, compared with the least unhealthy group (trend p=0.013). Women with four or more unhealthy behaviour factors were more likely to have insomnia, compared with the lowest groups (OR 1.175, 95% CI 1.077 to 1.282). Insomnia has an association with the unhealthy behaviours among men without cardiovascular risk factors (lowest groups: OR 1.133, 95% CI 1.037 to 1.238, trend p=0.026). Women without hypertension were more likely to have suspected insomnia, compared with the lowest group (OR 1.215, 95% CI 1.101 to 1.341). CONCLUSION: The results showed accumulated unhealthy behaviours were associated with increased risk of insomnia in Japanese dwellers. For healthy population without cardiovascular risk factors, unhealthy behaviours should be considered as background conditions for insomnia.

DOI： 10.1136/bmjopen-2021-052787

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

BACKGROUND: Emerging evidence has shown that charged metabolites, such as amino acids, may play an important role in the pathogenesis of various metabolic disorders, many of which women in the postmenopausal period are at high risk of developing. This study examined the metabolic profile of middle-aged Japanese women to investigate alterations in charged metabolites induced by menopausal transition. METHODS: The participants were 1193 female residents aged 40-60 at the baseline survey of the Tsuruoka Metabolomics Cohort Study. We investigated the cross-sectional association of menopausal status with 94 metabolomic biomarkers assayed in fasting plasma samples via capillary electrophoresis time-of-flight mass spectrometry using linear regression analysis. RESULTS: Among the participants, 529 were premenopausal, 132 were in menopausal transition (MT), and 532 were postmenopausal. Significant differences were found in age, blood pressure, glucose and lipid levels, and smoking and drinking habits among the three groups. The concentrations of 5 metabolites in the MT group and 15 metabolites in the postmenopausal group were significantly higher than those in the premenopausal group after adjusting for confounding factors. When classified into pathways, these metabolites were related to the tricarboxylic cycle, urea cycle, and homocysteine metabolism, some of which are linked to arteriosclerosis. CONCLUSION: Multiple charged metabolites were associated with women's menopausal status, showing a gradual increase as women shifted from pre-, to peri-, to postmenopause. These findings might reflect the early changes behind the increased risk of dyslipidemia, diabetes, cardiovascular disease, and osteoporosis in later life.

DOI： 10.1016/j.maturitas.2021.10.004

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: To explore the individual factors (such as gender, division of household labor, childcare and elder care) and their impact on research activities in the Japanese nursing research community during the early stage of the COVID-19 pandemic from April to June in 2020. DESIGN: Cross-sectional study. METHODS: An online survey with a self-reported questionnaire was conducted on Japan Academy of Nursing Science members to explore the impacts of individual factors among Japanese nursing researchers from April to June 2020. A multivariate logistic regression model was used for data analysis. RESULTS: A total of 1,273 participants (90.7% female, 85.8% university faculty) were included in the analysis. This survey showed that no evidence of a significant gender gap was found in research activities in Japanese nursing researchers during the COVID-19 pandemic. Research activities during the pandemic were associated with time and motivation.

DOI： 10.1371/journal.pone.0271001

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

<title>Abstract</title>Currently, large-scale cohort studies for metabolome analysis have been launched globally. However, only a few studies have evaluated the reliability of urinary metabolome analysis. This study aimed to establish the reliability of urinary metabolomic profiling in cohort studies. In the Tsuruoka Metabolomics Cohort Study, 123 charged metabolites were identified and routinely quantified using capillary electrophoresis-mass spectrometry (CE-MS). We evaluated approximately 750 quality control (QC) samples and 6,720 participants’ spot urine samples. We calculated inter- and intra-batch coefficients of variation in the QC and participant samples and technical intraclass correlation coefficients (ICC). A correlation of metabolite concentrations between spot and 24-h urine samples obtained from 32 sub-cohort participants was also evaluated. The coefficient of variation (CV) was less than 20% for 87 metabolites (70.7%) and 20–30% for 19 metabolites (15.4%) in the QC samples. There was less than 20% inter-batch CV for 106 metabolites (86.2%). Most urinary metabolites would have reliability for measurement. The 96 metabolites (78.0%) was above 0.75 for the estimated ICC, and those might be useful for epidemiological analysis. Among individuals, the Pearson correlation coefficient of 24-h and spot urine was more than 70% for 59 of the 99 metabolites. These results show that the profiling of charged metabolites using CE-MS in morning spot human urine is suitable for epidemiological metabolomics studies.

DOI： 10.1038/s41598-021-86600-9

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その他リンク： http://www.nature.com/articles/s41598-021-86600-9

記述言語：英語   掲載種別：研究論文（学術雑誌）  

RATIONALE: Epidemiological evidence indicates ambient exposure to PM2.5 have adverse effects on lung function growth in children, but it is not actually clear whether exposure to low level PM2.5 results in long-term decrements in lung function growth in pre- to early adolescent schoolchildren. OBJECTIVES: To examine long-term effects of PM2.5 within the 4-yr concentration range of 10 to 19 μg/m3 on lung function growth with repeated measurements of lung function tests. METHODS: Longitudinal analysis of 6,233 lung function measurements in 1,466 participants aged 8 to 12 from 16 school communities in 10 cities around Japan, covering a board area of the country to represent concentration range of PM2.5, was done with multilevel linear regression model. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and maximal expiratory flow at 50% of FVC (V50) were used as lung function indicators to examine effects of 10-μg/m3 increases in PM2.5 concentration on relative growth per 10-cm increase in height. RESULTS: Overall annual mean PM2.5 concentration was 13.5 μg/m3 (range: 10.4 to 19.0 µg/m3). We found no association between any of the lung function growth indicators and increases in PM2.5 levels in children of either sex, even after controlling for potential confounders. Analysis with two-pollutant models with O3 or NO2 did not change the null results. CONCLUSIONS: This nationwide longitudinal study suggests that concurrent, long-term exposure to PM2.5 at concentrations ranging from 10.4 to 19.0 μg/m3 has little effect on lung function growth in pre-adolescent boys and pre- to early adolescent girls. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (https://creativecommons.org/licenses/by-ncnd/4.0/).

DOI： 10.1513/AnnalsATS.202104-511OC

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2188/jea.JE20210075

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0259430

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2188/jea.JE20210109

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although self-reported questionnaires are widely employed in epidemiologic studies, their validity has not been sufficiently assessed. The aim of this study was to evaluate the validity of a self-reported questionnaire on medication use by comparison with health insurance claims and to identify individual determinants of discordance in the Tsuruoka Metabolomics Cohort Study. METHODS: Participants were 2,472 community-dwellers aged 37 to 78 years from the Tsuruoka Metabolomics Cohort Study. Information on lifestyle and medications was collected through a questionnaire. Sensitivity and specificity were determined using health insurance claims from November 2014 to March 2016, which were used as a standard. Potential determinants of discordance were assessed using multivariable logistic regression. RESULTS: The self-reported questionnaire on medication use showed high validity. Sensitivity and specificity were 0.95 (95% CI, 0.93-0.96) and 0.97 (95% CI, 0.96-0.98) for antihypertensive medications, 0.94 (95% CI, 0.91-0.97) and 0.98 (95% CI, 0.98-0.99) for diabetes medications, and 0.84 (95% CI, 0.82-0.87) and 0.98 (95% CI, 0.97-0.99) for dyslipidemia medications, respectively. Males without high education and those who currently smoke cigarettes were found to be associated with discordant reporting which affected sensitivity, especially those with medication use for dyslipidemia. CONCLUSIONS: In this population-based cohort study, we found that the self-reported questionnaire on medication use was a valid measure to capture regular medication users. Sensitivity for dyslipidemia medications was lower than those for the other medications. Type of medication, sex, education years, and smoking status influenced discordance, which affected sensitivity in self-reporting.

DOI： 10.2188/jea.JE20200089

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記述言語：英語  

DOI： 10.1093/ije/dyab168.261

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記述言語：日本語   出版者・発行元：日本臨床腎移植学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: The categories in the comprehensive lipid and risk management guidelines were proposed by the Japan Atherosclerosis Society (JAS Guidelines 2017), which adopted the estimated 10 year absolute risk of coronary artery disease (CAD) incidence in the Suita score. We examined whether those categories were concordant with the degree of arterial stiffness. METHODS: In 2014, the cardio-ankle vascular index (CAVI), an arterial stiffness parameter, was measured in 1,972 Japanese participants aged 35-74 years in Tsuruoka City, Yamagata Prefecture, Japan. We examined the mean CAVI and the proportion and odds ratios (ORs) of CAVI ≥ 9.0 on the basis of the following three management classifications using the analysis of variance and logistic regression: "Category I (Low risk)," "Category II (Middle risk)," and "Category III (High risk)." RESULTS: The mean CAVI and proportion of CAVI ≥ 9.0 were 8.6 and 34.8% among males and 8.1 and 18.3% among females, respectively. The mean CAVI and proportion of CAVI ≥ 9.0 were associated with an estimated 10 year absolute risk for CAD among males and females, excluding High risk for females. These results were similar to the management classification by the guideline: the multivariable-adjusted ORs (95% confidence intervals) of CAVI ≥ 9.0 among Category II and Category III compared with those among Category I were 2.96 (1.61-5.43) and 7.33 (4.03-13.3) for males and 3.99 (2.55-6.24) and 3.34 (2.16-5.16) for females, respectively. CONCLUSIONS: The risk stratification, which was proposed in the JAS Guidelines 2017, is concordant with the arterial stiffness parameter.

DOI： 10.5551/jat.58719

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Nine bladder cancer (BCa) cases were reported among aromatic amine-exposed male workers at a factory manufacturing organic dye/pigment intermediates in Japan. We aimed to evaluate the characteristics of aromatic amine-exposed workers by cross-sectional observation, and the risk of BCa by assessing the standardized incidence ratio (SIR). METHODS: In the cross-sectional study, our subjects were: 9 BCa patients, 36 aromatic amine-exposed non-patients, and 79 non-exposed workers from 3 factories. We evaluated the subjects' medical history, urinalysis, qualitative determination of nuclear matrix protein 22, and urinary cytology. For SIR assessment, 98 aromatic amine-exposed workers from 1 factory were included, and the Japanese general male population was used as a referent population. Since no direct aromatic amine-exposure data were available, we calculated surrogate exposure levels using information on job sites, exposure potency, and duration. RESULTS: Coexistent aromatic amines were ortho-toluidine (OT), aniline, para-toluidine, ortho-anisidine, 2,4-xylidine, and ortho-chloroaniline. The prevalence rates of cystitis and bladder lesion-related symptoms in both BCa patients and aromatic amine-exposed non-patient workers were significantly higher than those of non-exposed workers. Overall, the SIR for BCa in OT-exposed workers was 56.8 (95% CI 27.7-104.3) and apparent dose-response relationships were revealed between the SIR and the surrogate exposure level in the 0-10-year lagged analyses. Overall, SIRs in other aromatic amine-exposed workers were also significantly high but no or unclear dose-response relationships were observed. CONCLUSIONS: We conclude that OT may be responsible for the increased risk of BCa. Regular monitoring of bladder lesion-related symptoms is essential for the early identification of BCa.

DOI： 10.1007/s00420-021-01658-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: To examine the association between long-term exposure to suspended particulate matter (SPM) and cardiovascular mortality in Japan after controlling for known major confounding factors among a large middle and elderly cohort study in Ibaraki Prefecture, Japan. METHODS: We followed 91,808 residents (men 34%) who undertook a national health check-up at age 40-79 years for 17 years (1993-2010). Two different exposure indices were adopted: baseline SPM concentration (in the year 1990) and average SPM concentration for the first (average of 1990 and 1995) and the second half (average of 2005 to 2009) of the study period. Sex-specific adjusted risk ratios (RRs) for cardiovascular mortality were calculated using general mixed Poisson regression models after adjusting the age, BMI, history of diabetes mellitus and hypertension, creatinine, glutamic pyruvic transaminase, total cholesterol, high-density lipoprotein cholesterol, smoking, alcohol, and temperature. The variation between seven medical administration areas was also taken into account as a random effect. RESULTS: Baseline SPM concentration was associated with an increased risk of mortality from all cardiovascular diseases, coronary artery disease, and stroke. The adjusted RRs (95% confidence interval [CI]) per 10 µg/m3 increase in SPM concentration for all cardiovascular mortality were 1.147 (1.014-1.300) for men and 1.097 (0.985-1.222) for women. The point estimate of RR was highest for non-hemorrhagic stroke in men (1.248 [0.991-1.571]), although CI overlapped the unity. The RRs seemed slightly lower in the second half than in the first half, though the CIs widened in the second half. CONCLUSION: Our results suggest that long-term exposure to SPM is associated with an increased risk of all cardiovascular mortality for men in Ibaraki, Japan.

DOI： 10.5551/jat.54148

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Japan Atherosclerosis Society  

DOI： 10.5551/jat.54148

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

There has been little study on the effect of Asian dust exposure on respiratory symptoms among children who are vulnerable to environmental factors. In this panel study, we investigated the effect of Asian dust on respiratory symptoms among children with and without asthma, and their sensitivity. Children attending two elementary schools (137 total), and 23 children with asthma from cooperating medical institutions in Fukuoka prefecture were recruited. Subjects measured peak expiratory flow rate (PEF), and recorded asthma-like symptoms, cough, nasal symptoms and use of medication in a diary from April 1, 2013 to June 30, 2013. To assess exposure to Asian dust, we used Light Detection and Ranging (LIDAR) data. For the analysis of the association between Asian dust and respiratory symptoms, the case-crossover design and generalized estimating equation (GEE) models were used. Taking individual sensitivity to respiratory aggravation into consideration, the subjects were classified into three groups: children without asthma, children with asthma who do not use long-term preventive medication (CA) and children with asthma who use long-term preventive medication (CA-LTM). For CA, Asian dust exposure was significantly associated with asthma-like symptoms, with a hazard ratio of 5.17 (95%CI: 1.02=26.12) at Lag0, and the change in %maxPEF, -1.65% (95%CI:-2.82, -0.48) at Lag0. For children without asthma, a statistically significant association was found between Asian dust exposure and the change in %maxPEF, -0.56% (95%CI: -1.31, -0.08) at Lag1. However, no adverse effects were observed in CA-LTM. Temperature had significant effects on %maxPEF for three groups. Asian dust, photochemical oxidant and pollen caused simultaneously additive adverse effects on nasal symptoms for children without asthma. This study suggests the possibility that long-term preventive medication to manage asthma may suppress aggravation of respiratory symptoms due to Asian dust and may be an effective prevention.

DOI： 10.1016/j.scitotenv.2020.141585

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Nosocomial spread of coronavirus disease 2019 (COVID-19) causes clusters of infection among high-risk individuals. Controlling this spread is critical to reducing COVID-19 morbidity and mortality. We describe an outbreak of COVID-19 in Keio University Hospital, Japan, and its control and propose effective control measures. Methods: When an outbreak was suspected, immediate isolation and thorough polymerase chain reaction (PCR) testing of patients and health care workers (HCWs) using an in-house system, together with extensive contact tracing and social distancing measures, were conducted. Nosocomial infections (NIs) were defined as having an onset or positive test after the fifth day of admission for patients and having high-risk contacts in our hospital for HCWs. We performed descriptive analyses for this outbreak. Results: Between March 24 and April 24, 2020, 27 of 562 tested patients were confirmed positive, of whom 5 (18.5%) were suspected as NIs. For HCWs, 52 of 697 tested positive, and 40 (76.9%) were considered NIs. Among transmissions, 95.5% were suspected of having occurred during the asymptomatic period. Large-scale isolation and testing at the first sign of outbreak terminated NIs. The number of secondary cases directly generated by a single primary case found before March 31 was 1.74, compared with 0 after April 1. Only 4 of 28 primary cases generated definite secondary infection; these were all asymptomatic. Conclusions: Viral shedding from asymptomatic cases played a major role in NIs. PCR screening of asymptomatic individuals helped clarify the pattern of spread. Immediate large-scale isolation, contact tracing, and social distancing measures were essential to containing outbreaks.

DOI： 10.1093/ofid/ofaa512

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: There is growing evidence of an association between cadmium (Cd) and unfavorable birth outcomes. The effect of Cd exposure on anthropometric measures at birth or small for gestational age (SGA) infants in a large, nationwide Japanese cohort remains to be clarified. OBJECTIVES: To analyze the association between maternal blood Cd levels at different sampling times and sex-dependent infant birth size, weight, body length, chest, and head circumferences, in addition to SGA. METHODS: Data of 17,584 pregnant women in the Japan Environment and Children's Study were analyzed for anthropometric measurements. For SGA determination, 13,969 cases of vaginal delivery were analyzed after excluding infants born by cesarean section. Maternal blood Cd levels were categorized into quartiles (Q1-Q4), and the Q1 was used as a reference. Multiple linear regression analysis was performed for anthropometric measurements, and multiple logistic regression analysis was used to investigate the association of maternal blood Cd levels with the risk of SGA. RESULTS: Birth weight tended to decrease according to the increase in quartiles of blood Cd levels (15.63 g decrease [95% confidence level (CI): -33.26, 2.01] for Q4). The overall analysis revealed no decreases in body length and head and chest circumference, but subgroup analysis revealed that chest circumference tended to decrease according to the increase in quartiles in the female sex/third-trimester stratification (0.16 cm decrease [95% CI: -0.32, 0.00] for Q4). SGA risk was also higher and paralleled the increase in blood Cd levels associated with the female sex/third-trimester group (Odds Ratio 1.90 [95% CI: 1.23, 2.94] for Q4). CONCLUSION: Our results provide further evidence of sex-specific health risks associated with Cd exposure in early life in a large Japanese pregnancy cohort.

DOI： 10.1016/j.envres.2020.110007

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

STUDY DESIGN: This was a case-control study. OBJECTIVE: The objective of this study was to clarify the surgical outcomes after cervical posterior decompression in patients who smoked. SUMMARY OF BACKGROUND DATA: Smoking is associated with poor outcomes in the field of spinal surgery. However, the impact of tobacco smoking on the outcomes after posterior decompression surgery has not been fully evaluated in patients with cervical spondylotic myelopathy. MATERIALS AND METHODS: In this retrospective multicenter study, 587 patients with cervical spondylotic myelopathy were enrolled at 17 institutions in Japan. Patients underwent cervical laminoplasty or laminectomy and were followed up for at least 1 year after surgery. Outcome measures were: preoperative smoking status, perioperative complications, the Japanese Orthopedic Association scale, and the Visual Analog Scale for neck pain. After adjusting for age and sex by exact matching, smoking and nonsmoking groups were compared using an unpaired t test for continuous variables or a χ test for categorical variables. RESULTS: There were 182 (31%) current smokers and 405 (69%) nonsmokers including previous smokers. After matching, 158 patients were extracted from each group. Demographic data and surgical information were almost the same between the groups. Regarding postoperative complications, there was no significant difference in the rate of surgical site infection, cerebrospinal fluid leakage, hematoma, segmental motor paralysis, or neurological deficit. However, smokers showed a significantly higher risk for delirium (3.8% vs. 0.0%, P=0.039). Smokers and nonsmokers showed comparable changes in functional recovery according to Japanese Orthopedic Association scores (3.2±2.1 vs. 3.0±2.1, P=0.425) and in neck pain reduction using the Visual Analog Scale (-1.7±3.1 vs. -1.4±2.8, P=0.417) at the final follow-up. CONCLUSIONS: Smokers exhibited functional restoration and neck pain reduction after cervical posterior decompression. Attention is required, however, for the postoperative complication of delirium, which could be caused by the acute cessation of tobacco smoking after admission. LEVEL OF EVIDENCE: Level III.

DOI： 10.1097/BSD.0000000000000984

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0238723

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jlumin.2020.117209

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.hpb.2019.10.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/plants9060707

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Studies on the adverse effects of Asian dust (AD) on respiratory function in children are scarce. The objective of this study was to examine the association between AD and respiratory function by measuring peak expiratory flow rates (PEFRs) in asthmatic children. METHODS: The study was carried out from March to May from 2014 through 2016. One hundred ten children with bronchial asthma were recruited from four hospitals in the Goto Islands and south Nagasaki area in Nagasaki prefecture. The parents were asked to record their children's PEFRs every morning/evening and clinical symptoms in an asthma diary. AD was assessed from light detection and ranging data, and a linear mixed-effects model was used to estimate the effects of AD on daily PEFR. Time-stratified case-crossover analyses were performed to examine the association between AD and asthma attacks defined by reduction levels in PEFR. RESULTS: AD was detected on 11 days in the Goto Islands, and on 23 days in the south Nagasaki area. After adjusting for age, sex, temperature, and daily oxidants, we found a consistent association between AD and a 1.1% to 1.7% decrease in PEFR in the mornings and a 0.7% to 1.3% decrease in the evenings at a lag of 0 to 5 days. AD was not associated with the number of asthma attacks, respiratory symptoms, or other symptoms at any lag days examined. CONCLUSIONS: Exposure to AD was associated with reduced PEFR, although the effects were not large enough to induce clinically apparent symptoms, in clinically well-controlled asthmatic children.

DOI： 10.1186/s12199-020-00846-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3748/wjg.v26.i7.725

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Clinical Lipidology  

DOI： 10.1016/j.jacl.2019.09.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Exposure Science and Environmental Epidemiology  

DOI： 10.1038/s41370-019-0139-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/1348-9585.12073

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Environmental Research  

BACKGROUND: Manganese (Mn) is both an essential element and a potential toxicant. Although a few studies have suggested a nonlinear relationship between the maternal whole blood Mn level at delivery and infant birth weight, little is known about the effects of Mn levels during pregnancy on fetal growth, particularly with regard to sex-specific differences. METHODS: In this nationwide birth cohort study, we examined the association of maternal blood Mn level during pregnancy with infant birth weight, length, and head circumference in 16,473 mother-infant pairs. Pregnant women living in 15 regions across Japan were recruited between January 2011 and March 2014. The analysis of birth size (8,484 males and 7,989 females) was conducted using a nonlinear spline, followed by the use of quadratic regression or linear regression models. The analysis of small-for-gestational-age (SGA) (6,962 males and 6,528 females born vaginally) was conducted using multivariate logistic regression. Additionally, subgroup analysis was conducted according to the timing of blood sampling. RESULTS: The median maternal blood Mn level during pregnancy (i.e., 2nd and 3rd trimesters) was 16.2 µg/L (range, 4.3-44.5 µg/L). A positive linear association between the log blood Mn level and head circumference was observed in both male and female infants. However, a nonlinear relationship between the log blood Mn level and birth weight was observed only in male infants, such that the birth weight increased up to a blood Mn level of 18.6 µg/L. In the subgroup analysis stratified by the timing of maternal blood sampling, this nonlinear relationship was obvious only when sampling was performed in the 3rd trimester. Male infants in the lowest blood Mn level quartile (≤ 13.2 µg/L) faced an increased risk of SGA (odds ratio [95% confidence interval] = 1.35 [1.04-1.74]), as did those in the highest blood Mn level quartile (≥ 21.0 µg/L) when sampling was performed during the 3rd trimester (odds ratio [95% confidence interval] = 1.62 [1.10 to 2.39]), compared to those in the third blood Mn level quartile (the category including 18.6 µg/L). No association of blood Mn level with birth weight was observed among female infants, and blood Mn level was not associated with birth length in either male or female infants. CONCLUSION: A low blood Mn level during pregnancy or a high blood Mn level during the 3rd trimester was associated with a lower birth weight and increased risk of SGA in male infants, but not in female infants. A low blood Mn level was found to correlate slightly with a small head circumference among infants of both sexes.

DOI： 10.1016/j.envres.2019.02.007

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3171/2019.1.SPINE18854

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1200/JCO.18.00771

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Therapeutic hypothermia following neonatal encephalopathy is neuroprotective. However, approximately one in two cooled infants still die or develop permanent neurological impairments. Further understanding of variables associated with the effectiveness of cooling is important to improve the therapeutic regimen. To identify clinical factors associated with short-term outcomes of cooled infants, clinical data of 509 cooled infants registered to the Baby Cooling Registry of Japan between 2012 and 2014 were evaluated. Independent variables of death during the initial hospitalization and survival discharge from the cooling hospital at ≤28 days of life were assessed. Death was associated with higher Thompson scores at admission (p < 0.001); higher heart rates after 3-72 hours of cooling (p < 0.001); and higher body temperature after 24 hours of cooling (p = 0.002). Survival discharge was associated with higher 10 minutes Apgar scores (p < 0.001); higher blood pH and base excess (both p < 0.001); lower Thompson scores (at admission and after 24 hours of cooling; both p < 0.001); lower heart rates at initiating cooling (p = 0.003) and after 24 hours of cooling (p < 0.001) and lower average values after 3-72 hours of cooling (p < 0.001); higher body temperature at admission (p < 0.001); and lower body temperature after 24 hours and lower mean values after 3-72 hours of cooling (both p < 0.001). Survival discharge was best explained by higher blood pH (p < 0.05), higher body temperature at admission (p < 0.01), and lower body temperature and heart rate after 24 hours of cooling (p < 0.01 and <0.001, respectively). Lower heart rate, higher body temperature at admission, and lower body temperature during cooling were associated with favorable short-term outcomes.

DOI： 10.1089/ther.2018.0019

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Global Spine Journal  

© The Author(s) 2018. Study Design: Retrospective multicenter study. Objectives: To evaluate the outcomes of posterior cervical decompression for cervical spondylotic myelopathy (CSM) when performed by board-certified spine (BCS) or non-BCS (NBCS) surgeons. Methods: We reviewed outcomes for 675 patients who underwent surgery for CSM, were followed at least 1 year after surgery, and were assessed preoperatively and at final follow-up by Japanese Orthopaedic Association (JOA) scores and by the visual analog scale (VAS) for the neck. Cervical alignment was assessed on radiographs by C2-C7 angles, and range of motion (ROM) by extension minus flexion C2-C7 angles. We compared outcomes for BCS surgeons, who must meet several requirements, including experience in more than 300 spinal surgeries, and for NBCS surgeons. Results: BCS surgeons performed 432 of 675 laminoplasties. NBCS surgeons were primary in 243 surgeries, of which 187 were directly supervised by a BCS surgeon. BCS surgeons required significantly less time in surgery (98.0 ± 39.5 vs 108.1 ± 49.7 min; P <.01). BCS and NBCS surgeons had comparable perioperative complications rates, and preoperative-to-postoperative changes in JOA scores (2.9 ± 2.1 vs 3.1 ± 2.3; P =.40) and VAS (−1.5 ± 2.9 vs −1.4 ± 2.5; P =.96). Lordotic cervical alignment and ROM were maintained after operations by both groups. Conclusions: Surgical outcomes such as functional recovery, complication rates, and cervical dynamics were comparable between the BCS and NBCS groups. Thus, posterior cervical decompression for CSM is safe and effective when performed by junior surgeons who have been trained and supervised by experienced spine surgeons.

DOI： 10.1177/2192568218756329

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1039/c8pp00426a

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Clinical Oncology  

© 2019 by American Society of Clinical Oncology. PURPOSE Although gene expression profiling is a promising diagnostic technique to determine the tissue of origin for patients with cancer of unknown primary site (CUP), no clinical trial has evaluated yet site-specific therapy directed by this approach compared with empirical chemotherapy. We therefore performed a randomized study to assess whether such site-specific therapy improves outcome compared with empirical chemotherapy in previously untreated patients with CUP. PATIENTS AND METHODS Comprehensive gene expression profiling was performed by microarray analysis, and an established algorithm was applied to predict tumor origin. Patients with CUP were randomly assigned (1:1) to receive standard site-specific therapy or empirical paclitaxel and carboplatin (PC). The primary end point was 1-year survival rate. RESULTS One hundred thirty patients were randomly assigned and had sufficient biopsy tissue for molecular analysis. Efficacy analysis was performed for 50 and 51 patients in the site-specific therapy and empirical PC arms, respectively. Cancer types most commonly predicted were pancreatic (21%), gastric (21%), and lymphoma (20%). The 1-year survival rate was 44.0% and 54.9% for site-specific treatment and empirical PC (P = .264), respectively. Median overall and progression-free survival were 9.8 and 5.1 months, respectively, for site-specific treatment versus 12.5 and 4.8 months for empirical PC (P = .896 and .550, respectively). Median overall survival (16.7 v 10.6 months; P = .116) and progression-free survival (5.5 v 3.9 months; P = .018) were better for predicted more-responsive than less-responsive tumor types. CONCLUSION Site-specific treatment that was based on microarray profiling did not result in a significant improvement in 1-year survival compared with empirical PC, although prediction of the original site seemed to be of prognostic value.

DOI： 10.1200/JCO.18.00771

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記述言語：英語   出版者・発行元：Journal of Dermatology  

© 2018 Japanese Dermatological Association Trichoblastoma (TB) is a benign cutaneous adnexal neoplasm. The lesion typically presents as a slow-growing, solitary, well-circumscribed nodule measuring up to 3 cm in diameter. On rare occasions, TB causes malignant transformation into an aggressive form described as high-grade trichoblastic carcinoma. Four such cases have been reported to date; all were described as high-grade trichoblastic carcinomas. Here, we describe the case of a 72-year-old Japanese male patient with a rapidly enlarging subcutaneous tumor on his lower back, which was diagnosed as high-grade trichoblastic carcinoma. Histopathologically, the tumor featured both benign and malignant components, and a transition zone between these states was clearly evident. In the immunohistochemical analysis, a malignant component was positive for p53 and showed stronger staining of phospho-RAC-α serine/threonine-protein kinase (AKT) Ser473 in comparison with a benign component. These results suggest that loss of p53 function and activation of phosphatidylinositol 3-kinase–AKT signaling pathways played important pathogenic roles in malignant transformation of the present case.

DOI： 10.1111/1346-8138.14686

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Trichoblastoma (TB) is a benign cutaneous adnexal neoplasm. The lesion typically presents as a slow-growing, solitary, well-circumscribed nodule measuring up to 3 cm in diameter. On rare occasions, TB causes malignant transformation into an aggressive form described as high-grade trichoblastic carcinoma. Four such cases have been reported to date; all were described as high-grade trichoblastic carcinomas. Here, we describe the case of a 72-year-old Japanese male patient with a rapidly enlarging subcutaneous tumor on his lower back, which was diagnosed as high-grade trichoblastic carcinoma. Histopathologically, the tumor featured both benign and malignant components, and a transition zone between these states was clearly evident. In the immunohistochemical analysis, a malignant component was positive for p53 and showed stronger staining of phospho-RAC-alpha serine/threonine-protein kinase (AKT) Ser473 in comparison with a benign component. These results suggest that loss of p53 function and activation of phosphatidylinositol 3-kinase-AKT signaling pathways played important pathogenic roles in malignant transformation of the present case.

DOI： 10.1111/1346-8138.14686

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記述言語：英語  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：一般社団法人日本衛生学会  

<p>Asian dust is a phenomenon involving the long-range transport of atmospheric pollutants originating from the desert areas of China and Mongolia. In recent years, the health effects of Asian dust have raised public concerns. Numerous studies on the health effects of Asian dust have been published since the last review in 2010. Thus, a literature review was conducted to shed light on the latest epidemiologic findings. PubMed and Science Direct databases were used for the review of epidemiologic studies published between June 2009 and April 2018. We identified 53 epidemiologic studies. Mortality, ambulance transportation, hospitalization/medical examination, changes in symptomatic, functional, and examination findings, as well as birth outcomes have been reported as outcomes. When the outcomes were categorized by disease, the effects of Asian dust on respiratory, cardiovascular, and allergic diseases raised concerns. The common evidences of causation between Asian dust and these diseases were the consistency of findings and temporal sequence of association. As results of research on dose-response relationships have become available, and the possibility that the health effects of Asian dust may vary depending on its chemical composition has been pointed out, further research using the exposure level indicators of Asian dust or its chemical composition should be conducted. Furthermore, with focus on the crucial issue of reducing exposure, research related to prevention and raising awareness should be further promoted.</p>

DOI： 10.1265/jjh.19010

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This cross-sectional study investigated the associations of business type with the prevalence of metabolic syndrome (MetS) and lifestyle characteristics among workers in small- and medium-sized enterprises. In total, data from 167,736 workers (114,746 men and 52,990 women) who participated in health checkups in 2013 were analyzed using multilevel logistic regression models. The odds ratios (ORs) of having MetS, defined based on the criteria of the joint interim statement, were significantly higher in employees of transportation businesses (reference OR =1) than in other business types among men (OR: 0.67-0.85) and similar result was observed among women (OR: 0.70-0.88). The prevalence of a smoking habit was significantly higher in transportation workers than in employees of other businesses for both men and women. Furthermore, male transportation workers were more likely to skip breakfast, engage in <1 h/day of walking, walk at a slower speed, and eat dinner just before going to bed. Female transportation workers were more likely to have gained 10 kg since the age of 20 years. In conclusion, the prevalence of MetS was higher in transportation workers than in workers from other busi

DOI： 10.2302/kjm.2018-0007-OA

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nature Publishing Group  

DOI： 10.1038/s41598-017-18487-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Spine  

STUDY DESIGN: A retrospective study. OBJECTIVE: To identify the radiographic differences between Chinese and Japanese patients with cervical ossification of the posterior longitudinal ligament (OPLL) using computed tomography (CT) and magnetic resonance imaging (MRI), and to compare the characteristics of OPLL between the two nationalities. SUMMARY OF BACKGROUND DATA: OPLL has a high prevalence in East Asia. However, the differences between Chinese and Japanese OPLL patients are poorly known. METHODS: This was a retrospective study of Chinese (n = 300) and Japanese (n = 102) consecutive patients who received a diagnosis of cervical OPLL between January 2010 and December 2014. All patients underwent CT and MRI. The type and distribution of OPLL were determined. Spinal compression was assessed by MRI. OPLL type, distribution, comorbidity, and compression of the spinal cord were examined. The ossification index (OP-index) was used to evaluate the OPLL. Factors contributing to the OP-index were examined by multivariate analysis. RESULTS: The Chinese patients were younger than the Japanese patients (P < 0.0001), and there were more women among the Chinese patients (P = 0.0002). The OP-index was higher among the Japanese patients (median, 5 vs. 4, P = 0.003). Among men, OPLL lesions were more frequent in the under 55-year-old Japanese at C7 (P = 0.04), in the 55 to 64-year-old Japanese at C4, C5, and C6 (all P < 0.05), and in the over 64-year-old Japanese at C3/4 (P = 0.01), compared with their Chinese counterparts. Among women, OPLL lesions were more frequent in the 55 to 64-year-old Japanese at C6 (P = 0.04). The multivariate analysis showed that only age was independently associated with the OP-index (odds ratio [OR] = 1.023, 95% confidence interval [CI]: 1.002-1.045, P = 0.034). CONCLUSION: Japanese patients had a higher frequency of OPLL lesions at C5, C6, and C7. Age was independently associated with OPLL.3.

DOI： 10.1097/BRS.0000000000002707

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：European Journal of Cancer  

INTRODUCTION: There have been no reports about predicting survival of patients with advanced cancer constructed entirely with objective variables. We aimed to develop a prognostic model based on laboratory findings and vital signs using a fractional polynomial (FP) model. METHODS: A multicentre prospective cohort study was conducted at 58 specialist palliative care services in Japan from September 2012 to April 2014. Eligible patients were older than 20 years and had advanced cancer. We developed models for predicting 7-day, 14-day, 30-day, 56-day and 90-day survival by using the FP modelling method. RESULTS: Data from 1039 patients were analysed to develop each prognostic model (Objective Prognostic Index for advanced cancer [OPI-AC]). All models included the heart rate, urea and albumin, while some models included the respiratory rate, creatinine, C-reactive protein, lymphocyte count, neutrophil count, total bilirubin, lactate dehydrogenase and platelet/lymphocyte ratio. The area under the curve was 0.77, 0.81, 0.90, 0.90 and 0.92 for the 7-day, 14-day, 30-day, 56-day and 90-day model, respectively. The accuracy of the OPI-AC predicting 30-day, 56-day and 90-day survival was significantly higher than that of the Palliative Prognostic Score or the Prognosis in Palliative Care Study model, which are based on a combination of symptoms and physician estimation. CONCLUSION: We developed highly accurate prognostic indexes for predicting the survival of patients with advanced cancer from objective variables alone, which may be useful for end-of-life management. The FP modelling method could be promising for developing other prognostic models in future research.

DOI： 10.1016/j.ejca.2018.09.037

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Pancreas  

© 2018 Wolters Kluwer Health, Inc. All rights reserved. Objectives The aim of this study was to determine whether computer-assisted digital analysis and acoustic radiation force impulse (ARFI) imaging were useful for assessing pancreatic fibrosis, and if ARFI imaging predicted postoperative pancreatic fistula (POPF). Methods Seventy-eight patients scheduled to undergo pancreatic resection were enrolled. Shear wave velocity (SWV) at the pancreatic neck was measured preoperatively using ARFI imaging. Pancreatic tissue components on a whole slide image were quantified using an automatic image processing software. The relationship between SWV, fibrotic tissue content, and POPF incidence and clinical severity was analyzed. Results The median collagen fiber, fatty tissue, and acinar cell contents were 11.6%, 8.5%, and 61.3%, respectively. Unlike fatty tissue, collagen fiber content and acinar cells were correlated with SWV (ρ = 0.440, P &lt; 0.001 and ρ =-0.428, P &lt; 0.001, respectively). Although collagen fiber content and SWV were associated with the overall incidence of POPF (P = 0.004 and 0.001, respectively), collagen fiber content and SWV had no statistical correlation with clinical

DOI： 10.1097/MPA.0000000000001179

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出版者・発行元：Pancreas  

© 2018 Wolters Kluwer Health, Inc. All rights reserved. Objectives The aim of this study was to determine whether computer-assisted digital analysis and acoustic radiation force impulse (ARFI) imaging were useful for assessing pancreatic fibrosis, and if ARFI imaging predicted postoperative pancreatic fistula (POPF). Methods Seventy-eight patients scheduled to undergo pancreatic resection were enrolled. Shear wave velocity (SWV) at the pancreatic neck was measured preoperatively using ARFI imaging. Pancreatic tissue components on a whole slide image were quantified using an automatic image processing software. The relationship between SWV, fibrotic tissue content, and POPF incidence and clinical severity was analyzed. Results The median collagen fiber, fatty tissue, and acinar cell contents were 11.6%, 8.5%, and 61.3%, respectively. Unlike fatty tissue, collagen fiber content and acinar cells were correlated with SWV (ρ = 0.440, P &lt; 0.001 and ρ =-0.428, P &lt; 0.001, respectively). Although collagen fiber content and SWV were associated with the overall incidence of POPF (P = 0.004 and 0.001, respectively), collagen fiber content and SWV had no statistical correlation with cl

DOI： 10.1097/MPA.0000000000001179

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DOI： 10.1016/j.ejca.2018.09.037

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Clinical Spine Surgery  

STUDY DESIGN: This was a retrospective multicenter study. OBJECTIVE: To clarify the progression of diffuse idiopathic skeletal hyperostosis (DISH) using whole-spine computed tomography in patients with cervical ossification of the posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: DISH and cervical OPLL frequently coexist, and can cause ankylosing spinal fractures due to biomechanical changes and fragility of the affected vertebrae. The epidemiology and pathophysiology of DISH occurring with cervical OPLL are unclear. MATERIALS AND METHODS: We used whole-spine computed tomography to determine the prevalence of DISH in 234 patients with a diagnosis of cervical OPLL based on plain cervical radiographs. We established a novel system for grading the progression of DISH based on a cluster analysis of the DISH distribution along the spine. We calculated the correlation coefficient between this grading system and patient age. RESULTS: The prevalence of DISH in patients with cervical OPLL was 48.7%. Patients with DISH were significantly older than those who did not have DISH (67.3 vs. 63.4 y; P=0.005). Cluster analysis classified the DISH distribution into 6 regions, based on the levels affected: C2-C5, C3-T1, C6-T5, T3-10, T8-L2, and T12-S1. DISH was observed most frequently at T3-T10. We defined a system for grading DISH progression based on the number of regions involved, from grade 0 to 6. DISH was distributed at T3-T10 in >60% of the grade 1 patients, whereas most patients with DISH at the cervical or lumbar spine were grade 4 or 5. There was a weak but significant correlation between the DISH grade and patient age. CONCLUSIONS: DISH was present in nearly half of the patients with cervical OPLL. DISH was more common in older patients. DISH developed at the thoracic level and progressed into the cervical and/or lumbar spine with age. LEVEL OF EVIDENCE: Level III.

DOI： 10.1097/BSD.0000000000000701

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Investigational New Drugs  

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Background Post-progression survival (PPS) could be a confounding element in interpreting data from clinical trials of second-line chemotherapy in patients with advanced pancreatic cancer (PC) previously treated with gemcitabine (GEM) because a recent meta-analysis of oxaliplatin combination therapy showed statistical heterogeneity for overall survival (OS) but not for progression-free survival (PFS). This study aimed to improve the understanding of the impact of PPS on OS in this setting. Methods Databases were searched to identify randomized controlled trials (RCTs) in the salvage setting. We evaluated relationships between OS and PFS, PPS, and other variables. Results Totally, 17 RCTs with 3253 patients were identified. Median OS was strongly and moderately associated with median PPS and PFS, respectively (r = 0.913; p &lt; 0.001 and 0.780; p &lt; 0.001, respectively). The proportion of patients with good performance status was significantly associated with both PPS and PFS (r = 0.574, p &lt; 0.001 and 0.492, p &lt; 0.001, respectively). The induction rate of subsequent chemotherapy was related to the duration of PPS an

DOI： 10.1007/s10637-018-0589-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s12199-018-0733-0

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その他リンク： https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85053384882&origin=inward

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s12199-018-0733-0

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DOI： 10.1097/BSD.0000000000000701

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1539/joh.2018-0137-OP

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/BRS.0000000000002707

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer New York LLC  

DOI： 10.1007/s10637-018-0589-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：British Journal of Cancer  

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has very poor prognosis despite existing multimodal therapies. This study aimed to investigate whether KRAS mutations at codons 12/13 in cell-free DNA (cfDNA) from preoperative and postoperative sera from patients with PDAC can serve as a predictive biomarker for treatment response and outcomes after surgery. METHODS: Preoperative and postoperative serum samples obtained from 45 patients with PDAC whom underwent curative pancreatectomy at our institution between January 2013 and July 2016 were retrospectively analysed. Peptide nucleic acid-directed PCR clamping was used to identify KRAS mutations in cfDNA. RESULTS: Among the 45 patients enrolled, 11 (24.4%) and 20 (44.4%) had KRAS mutations in cfDNA from preoperative and postoperative sera, respectively. Multivariate analysis revealed that KRAS mutations in postoperative serum (hazard ratio (HR)=2.919; 95% confidence interval (CI)=1.109-5.621; P=0.027) are an independent prognostic factor for disease-free survival. Furthermore, the shift from wild-type KRAS in preoperative to mutant KRAS in postoperative cfDNA (HR=9.419; 95% Cl=2.015-44.036; P=0.004) was an independent prognostic factor for overall survival. CONCLUSIONS: Changes in KRAS mutation status between preoperative and postoperative cfDNA may be a useful predictive biomarker for survival and treatment response.

DOI： 10.1038/bjc.2017.479

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DOI： 10.1038/bjc.2017.479

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記述言語：日本語   出版者・発行元：(一社)日本衛生学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Preventive Medicine  

Very few community intervention studies that promote physical activity (PA) using guidelines and its dissemination and implementation have been conducted. Consequently, we evaluated the effectiveness of a community-wide intervention (CWI) of PA with adults based on the Japanese guidelines for promoting PA. This was a non-randomized controlled trial, with four administrative districts in Fujisawa city assigned to the intervention group and nine to the control group. The CWI, conducted from 2013 to 2015, comprised information dissemination, education, and community support. The primary outcome was change in PA participation. Secondary outcomes were CWI awareness and PA guideline knowledge. Outcomes were assessed using questionnaires distributed to two independent, random samples of 3000 community-based adults (aged ≥20years). Two separate samples-1230 adults at baseline and 1393 at the two-year follow-up-responded to the survey. The median time spent in PA did not differ between intervention and control groups after adjusting for potential confounders (adjusted difference between groups=-0.02min/day [95% confidence interval (CI): -0.11, 0.10]). However, intervention group participants were more aware of the CWI (33.8%) than were control group participants (25.2%) at the two-year follow-up (odds ratio=1.44 [95% CI: 1.06, 1.95]). A significant difference was also observed in participants' PA guideline knowledge (adjusted difference between groups=0.82% [95% CI: 0.33, 1.31]). Although significant differences in awareness and knowledge were observed between groups, this CWI did not change PA levels over two years. Future studies should investigate the long-term effects of CWIs beyond two years. TRIAL REGISTRATION NUMBER: UMIN-CTR UMIN000018389.

DOI： 10.1016/j.ypmed.2017.11.008

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記述言語：日本語   出版者・発行元：日本毒性学会  

<p>トキシコロジストは毒性の検出、機序の解明と化学物質の管理までを含む広い範囲に及ぶ専門的な知識と高い技術を要求される。この基準を満たす専門家を認定するため、日本、アメリカ及びヨーロッパでは、各国の毒性関連学会による認定トキシコロジスト制度が設けられている。アメリカにおける認定トキシコロジスト資格であるDiplomate of the American Board of Toxicology（DABT）については日本においても取得者がおり、よく知られているが、ヨーロッパの認定トキシコロジスト資格についてはあまり知られていない。そこで今回、ヨーロッパの状況について紹介する。</p><p>ヨーロッパにおける認定トキシコロジスト制度は、イギリス（British Toxicology Society：BTS）、ドイツ（Deutschen Gesellschaft für Pharmakologie und Toxikologie：DGPT）、オランダ（Nederlandse Vereniging voor Toxicologie：NVT）、フランス（Société Française de Toxicologie：SFT）等、国ごとに各主催学会で認定される資格と、ヨーロッパ全体としてEUROT

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nihon eiseigaku zasshi. Japanese journal of hygiene  

In this review, we present an initial plan for exposure assessment in the Japan Environment and Children's Study (JECS) by focusing on a biomonitoring technique and discuss the challenges encountered when using the biomonitoring technique for exposure measurements. JECS registered 103,099 pregnant mothers and has been following children born to them. Various biological samples were collected from mothers during pregnancy (blood and urine), at birth (blood and hair) and at check-up one month after birth (breast milk). Samples were also collected from children at birth (cord blood) and at check-up one month after birth (hair and blood spot). Those samples will be used to assess maternal and foetal exposures to chemical substances. Measurement reliability, i.e., intraclass correlation coefficient (ICC), and attenuation bias related to low ICCs should be taken into consideration when using the biomonitoring results. Along with the biomonitoring technique, simulation models, pharmacokinetic (PK) models and exposomics techniques are under development in JECS. New analytical techniques include deciduous teeth measurements and -omics analyses. In particular, PK models and sensor technologies are one of the most important methodologies for future JECS exposure analyses. Statistical methods for examining the effects of intercorrelated multiple exposures as well as nondetection data should also be explored.

DOI： 10.1265/jjh.73.156

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PLoS ONE  

BACKGROUND: Cohort studies with metabolomics data are becoming more widespread, however, large-scale studies involving 10,000s of participants are still limited, especially in Asian populations. Therefore, we started the Tsuruoka Metabolomics Cohort Study enrolling 11,002 community-dwelling adults in Japan, and using capillary electrophoresis-mass spectrometry (CE-MS) and liquid chromatography-mass spectrometry. The CE-MS method is highly amenable to absolute quantification of polar metabolites, however, its reliability for large-scale measurement is unclear. The aim of this study is to examine reproducibility and validity of large-scale CE-MS measurements. In addition, the study presents absolute concentrations of polar metabolites in human plasma, which can be used in future as reference ranges in a Japanese population. METHODS: Metabolomic profiling of 8,413 fasting plasma samples were completed using CE-MS, and 94 polar metabolites were structurally identified and quantified. Quality control (QC) samples were injected every ten samples and assessed throughout the analysis. Inter- and intra-batch coefficients of variation of QC and participant samples, and technical intraclass correlation coefficients were estimated. Passing-Bablok regression of plasma concentrations by CE-MS on serum concentrations by standard clinical chemistry assays was conducted for creatinine and uric acid. RESULTS AND CONCLUSIONS: In QC samples, coefficient of variation was less than 20% for 64 metabolites, and less than 30% for 80 metabolites out of the 94 metabolites. Inter-batch coefficient of variation was less than 20% for 81 metabolites. Estimated technical intraclass correlation coefficient was above 0.75 for 67 metabolites. The slope of Passing-Bablok regression was estimated as 0.97 (95% confidence interval: 0.95, 0.98) for creatinine and 0.95 (0.92, 0.96) for uric acid. Compared to published data from other large cohort measurement platforms, reproducibility of metabolites common to the platforms was similar to or better than in the other studies. These results show that our CE-MS platform is suitable for conducting large-scale epidemiological studies.

DOI： 10.1371/journal.pone.0191230

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記述言語：日本語   出版者・発行元：一般社団法人日本衛生学会  

<p>In this review, we present an initial plan for exposure assessment in the Japan Environment and Children’s Study (JECS) by focusing on a biomonitoring technique and discuss the challenges encountered when using the biomonitoring technique for exposure measurements. JECS registered 103,099 pregnant mothers and has been following children born to them. Various biological samples were collected from mothers during pregnancy (blood and urine), at birth (blood and hair) and at check-up one month after birth (breast milk). Samples were also collected from children at birth (cord blood) and at check-up one month after birth (hair and blood spot). Those samples will be used to assess maternal and foetal exposures to chemical substances. Measurement reliability, i.e., intraclass correlation coefficient (ICC), and attenuation bias related to low ICCs should be taken into consideration when using the biomonitoring results. Along with the biomonitoring technique, simulation models, pharmacokinetic (PK) models and exposomics techniques are under development in JECS. New analytical techniques include deciduous teeth measurements and -omics analyses. In particular, PK models and sensor techn

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.scitotenv.2017.06.228

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/cam4.1178

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1539/joh.17-0148-OP

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Tokyo  

DOI： 10.1007/s10157-016-1309-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Verlag  

DOI： 10.1007/s00280-017-3263-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier B.V.  

DOI： 10.1016/j.kint.2016.09.015

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/srep39508

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記述言語：日本語   出版者・発行元：一般社団法人 日本健康心理学会  

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記述言語：日本語   出版者・発行元：公益社団法人 日本看護科学学会  

<p>目的：本研究は2010年と2014年に全国調査を行い，退院支援看護師（DPN）の実践状況を明らかにすることを目的とした．</p><p>方法：全国の100床以上の病院に勤務するDPNに，2010年は819名，2014年は948名に質問紙調査を行った．調査項目はDPNの基本属性，DPNとしての実践能力（Nurses’ Discharge Planning Ability Scale：NDPASの得点）等．</p><p>結果：2010年はDPN461名（回答率56.3%），2014年は479名（50.5%）を分析対象とした．両年とも平均年齢は約47歳で，DPNの平均経験年数は2010年が2.5年，2014年が3.1年であった．また，2014年の方がNDPASの〈A．退院後のケアバランスの見積力〉の得点が高かったが，残り3つの能力の得点については両年で有意差がなかった．</p><p>結論：DPNによる支援の質を保証する為には，系統的・継続的な人材育成の必要性が示唆された．</p>

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記述言語：日本語   出版者・発行元：技術情報協会  

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記述言語：日本語   出版者・発行元：日本臨床腎移植学会  

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記述言語：英語  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0164877

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記述言語：英語  

DOI： 10.1007/s12199-016-0519-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: The aim of the study was to investigate the associations of amino acids and other polar metabolites with metabolic syndrome (MetS) in postmenopausal women in a lean Asian population. METHODS: The participants were 1,422 female residents enrolled in a cohort study from April to August 2012. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III modified for Japanese women. Associations were examined between MetS and 78 metabolites assayed in fasting plasma samples using capillary electrophoresis-mass spectrometry. Replication analysis was performed to confirm the robustness of the results in a separate population created by random allocation. RESULTS: Analysis was performed for 877 naturally postmenopausal women, including 594 in the original population and 283 in the replication population. The average age, body mass index, and levels of high- and low-density lipoprotein cholesterol of the entire population were 64.6 years, 23.0 kg/m, 72.1 mg/dL, and 126.1 mg/dL, respectively. There was no significant difference in low-density lipoprotein cholesterol levels between women with and without MetS. Thirteen metabolites were significantly related to MetS: multiple plasma amino acids were elevated in women with MetS, including branched-chain amino acids, alanine, glutamate, and proline; and alpha-aminoadipate, which is generated by lysine degradation, was also significantly increased. CONCLUSIONS: Our large-scale metabolomic profiling indicates that Japanese postmenopausal women with MetS have abnormal polar metabolites, suggesting altered catabolic pathways. These results may help to understand metabolic disturbance, including in persons with normal body mass index and relatively high levels of high-density lipoprotein cholesterol, and may have clinical utility based on further studies.

DOI： 10.1097/GME.0000000000000630

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記述言語：英語  

DOI： 10.1007/s12199-016-0519-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: The aim of the study was to investigate the associations of amino acids and other polar metabolites with metabolic syndrome (MetS) in postmenopausal women in a lean Asian population. METHODS: The participants were 1,422 female residents enrolled in a cohort study from April to August 2012. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III modified for Japanese women. Associations were examined between MetS and 78 metabolites assayed in fasting plasma samples using capillary electrophoresis-mass spectrometry. Replication analysis was performed to confirm the robustness of the results in a separate population created by random allocation. RESULTS: Analysis was performed for 877 naturally postmenopausal women, including 594 in the original population and 283 in the replication population. The average age, body mass index, and levels of high- and low-density lipoprotein cholesterol of the entire population were 64.6 years, 23.0 kg/m, 72.1 mg/dL, and 126.1 mg/dL, respectively. There was no significant difference in low-density lipoprotein cholesterol levels between women with and without MetS. Thirteen metabolites were signific

DOI： 10.1097/gme.0000000000000630

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記述言語：英語  

DOI： 10.1200/JCO.2016.34.15_suppl.e15687

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Verlag  

DOI： 10.1007/s00520-015-2788-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s12199-015-0494-y

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DOI： 10.1007/s00520-015-2788-4

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OBJECTIVE: Metabolomics is a promising approach to the identification of biomarkers in plasma. Here, we performed a population-based, cross-sectional study to identify potential biomarkers of alcohol intake and alcohol-induced liver injury by metabolomic profiling using capillary electrophoresis-mass spectrometry (CE-MS). METHODS: Fasting plasma samples were collected from 896 Japanese men who participated in the baseline survey of the Tsuruoka Metabolomics Cohort Study, and 115 polar metabolites were identified and absolutely quantified by CE-MS. Information on daily ethanol intake was collected through a standardized, self-administered questionnaire. The associations between ethanol intake and plasma concentration of metabolites were examined. Relationships between metabolite concentrations or their ratios and serum liver enzyme levels in the highest ethanol intake group (>46.0 g/day) were then examined by linear regression analysis. Replication analysis was conducted in 193 samples collected from independent population of this cohort. RESULTS: Nineteen metabolites were identified to have an association with daily alcohol consumption both in the original and replication population. Three of these metabolites (threonine, glutamine, and guanidinosuccinate) were found to associate well with elevated levels of serum liver enzymes in the highest ethanol intake group, but not in the non-drinker group. We also found that the glutamate/glutamine ratio had a much stronger relation to serum gamma-glutamyltransferase, aspartate transaminase, and alanine transaminase than glutamate or glutamine alone (standardized beta = 0.678, 0.558, 0.498, respectively). CONCLUSIONS: We found 19 metabolites associated with alcohol intake, and three biomarker candidates (threonine, guanidinosuccinate and glutamine) of alcohol-induced liver injury. Glutamate/glutamine ratio might also be good biomarker.

DOI： 10.1007/s12199-015-0494-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2188/jea.

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その他リンク： http://orcid.org/0000-0003-4720-1750

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier Inc.  

DOI： 10.1016/j.amjcard.2015.09.035

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.amjcard.2015.09.035

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記述言語：日本語   出版者・発行元：一般社団法人 日本医療薬学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Academic Press Inc.  

DOI： 10.1016/j.envres.2015.08.024

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出版者・発行元：Elsevier {BV}  

DOI： 10.1016/j.envres.2015.08.024

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Bailliere Tindall Ltd  

DOI： 10.1016/j.tvjl.2015.05.001

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier {BV}  

DOI： 10.1016/j.tvjl.2015.05.001

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記述言語：日本語   出版者・発行元：専修大学社会知性開発研究センター  

CiNii Books

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2188/jea.JE20140186

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その他リンク： http://orcid.org/0000-0002-6630-8337

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BMJ  

DOI： 10.1136/jech-2014-203961

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記述言語：日本語   出版者・発行元：統計数理研究所  

要旨あり

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記述言語：日本語   出版者・発行元：統計数理研究所  

要旨あり

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記述言語：日本語  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2188/jea.JE20130051

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その他リンク： http://orcid.org/0000-0003-1025-0807

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/1471-2458-14-25

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その他リンク： http://orcid.org/0000-0002-6630-8337

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Nature  

DOI： 10.1007/s12199-014-0439-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: There is insufficient evidence of preventive effect of probiotics on upper respiratory tract infections (URTIs) in an elderly population. METHODS: We conducted a multicenter, double-blinded, randomized, placebo-controlled parallel group study. Elderly persons had participated who used day care at 4 facilities in Tokyo. We used fermented milks containing Lactobacillus casei strain Shirota (LcS) and placebo drinks as test drinks. RESULTS: A total of 154 subjects was analyzed. The number of persons diagnosed with an acute URTIs was almost identical in both groups (LcS: 31, placebo: 32), whereas the number of acute URTIs events (LcS: 68, placebo: 51) and the symptom score (LcS: 425, placebo: 396) were both higher in the LcS group. Permutation tests performed using the total number of acute URTIs infection events/total days of observation and the total symptom score/total days of observation found no statistically significant difference respectively (P values of .89 and .64, respectively). Comparing the mean duration of infection per infection event found a shorter mean duration in the LcS group (LcS: 3.71 days, placebo: 5.40 days), and the difference was statistically significant. CONCLUSION: The results suggest that fermented milk containing LcS probably reduces the duration of acute URTIs.

DOI： 10.1016/j.ajic.2013.04.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.tvjl.2012.11.018

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10661-013-3211-6

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その他リンク： http://orcid.org/0000-0003-1025-0807

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: To determine the cost-benefits of primary prevention programs for mental health at the workplace, we conducted a meta-analysis of published studies in Japan. METHODS: We searched the literature, published as of 16 November 2011, using the Pubmed database and relevant key words. The inclusion criteria were: conducted in the workplace in Japan; primary prevention focus; quasi-experimental studies or controlled trials; and outcomes including absenteeism or presenteeism. Four studies were identified: one participatory work environment improvement, one individual-oriented stress management, and two supervisor education programs. Costs and benefits in yen were estimated for each program, based on the description of the programs in the literature, and additional information from the authors. The benefits were estimated based on each program's effect on work performance (measured using the WHO Health and Work Performance Questionnaire in all studies), as well as sick leave days, if available. The estimated relative increase in work performance (%) in the intervention group compared to the control group was converted into labor cost using the average bonus (18% of the total annual salary) awarded to employees in Japan as a base. Sensitive analyses were conducted using different models of time-trend of intervention effects and 95% confidence limits of the relative increase in work performance. RESULTS: For the participatory work environment improvement program, the cost was estimated as 7,660 yen per employee, and the benefit was 15,200-22,800 yen per employee. For the individual-oriented stress management program, the cost was 9,708 yen per employee, and the benefit was 15,200-22,920 yen per employee. For supervisor education programs, the costs and benefits were respectively 5,209 and 4,400-6,600 yen per employee, in one study, 2,949 and zero yen per employee in the other study. The 95% confidence intervals were wide for all these studies. CONCLUSIONS: For the point estimates based on these cases, the participatory work environment improvement program and the individual-oriented stress management program showed better cost-benefits. For the supervisor education programs, the costs were almost equal to or greater than the benefits. The results of the present study suggest these primary prevention programs for mental health at the workplace are economically advantageous to employers. Because the 95% confidence intervals were wide, further research is needed to clarify if these interventions yield statistically significant cost-benefits.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The present report describes a rare case of spontaneous hemangiosarcoma in a nine-week-old male Sprague-Dawley rat. At necropsy, multiple white nodules of various sizes were observed on and within the enlarged spleen and liver and were histopathologically determined to be composed of spindle- to oval-shaped cells that showed invasive growth without encapsulation and were arranged solidly but partially in whorls or faint alveolar patterns with vascular-like spaces containing small clefts or erythrocytes in the tumor mass. Immunohistochemical analysis revealed that most of the tumor cells were strongly positive for vimentin, von Willebrand factor (vWF) and CD34 but negative for podoplanin. In addition, electron microscopic examination revealed the presence of Weibel-Palade bodies in the cytoplasm of the tumor cells. Based on these findings, this case was diagnosed as a hemangiosarcoma. The splenic masses were larger than the hepatic ones, with tumor cells mainly observed at periportal regions with tumor embolism in the liver, suggesting that primary hemangiosarcoma initially developed in the spleen before metastasizing.

DOI： 10.1293/tox.25.273

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To elucidate whether adjuvant taxane monotherapy is a feasible and tolerable for postoperative breast cancer patients, we evaluated the severity of chemotherapy-induced peripheral neuropathy (CIPN) and the relative tolerability of regimens by health-related quality of life (HRQOL) assessment in node-positive breast cancer patients treated with taxane-containing regimens. METHODS: We evaluated CIPN and HRQOL in the first 300 patients enrolled in a larger (1,060 total) multicenter phase III trial randomized to one of four adjuvant regimens: (1) anthracycline-cyclophosphamide followed by paclitaxel (ACP), (2) AC followed by docetaxel (ACD), (3) paclitaxel alone (PTX), or (4) docetaxel alone (DTX). CIPN was assessed by the Patient Neurotoxicity Questionnaire (PNQ) and the National Cancer Institute Common Toxicity Criteria, and HRQOL by Functional Assessment of Cancer Therapy-General (FACT-G). CIPN and HRQOL scores were compared between ACP and ACD vs. PTX and DTX, and ACP and PTX vs. ACD and DTX. RESULTS: PNQ sensory scores were significantly higher in patients treated with taxane monotherapy compared to treatment with AC followed by taxane (P = .003). No significant differences in PNQ sensory scores were observed between the ACP and PTX vs. ACD and DTX regimens (P = .669). Regardless of taxane regimen, PNQ severity scores for CIPN appear to be largely reversible within 1 year of adjuvant treatment. No significant difference in FACT-G scores was observed between any regimens during the study treatments. CONCLUSIONS: Patient-reported CIPN was significantly more severe with single-agent adjuvant taxane compared to AC followed by taxane treatment; however, the HRQOL findings support that single-agent taxane treatment is tolerable.

DOI： 10.1007/s00520-012-1492-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/j.2040-1124.2011.00170.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Several lines of evidence have suggested that maintenance of atrial fibrillation (AF) depends on reentrant mechanisms. Maintenance of reentry necessitates a sufficiently short refractory period and/or delayed conduction, and AF has been associated with both alterations. Fibrosis, cellular dysfunction, and gap junction protein alterations occur in AF and cause conduction delay. We performed this study to test the hypothesis that gap junction protein overexpression would improve conduction and prevent AF. METHODS AND RESULTS: Thirty Yorkshire swine were randomized into 2 groups (sinus rhythm and AF), and each group into 3 subgroups: sham-operated control, gene therapy with adenovirus expressing connexin (Cx) 40, and gene therapy with adenovirus expressing Cx43 (n=5 per subgroup). All animals had epicardial gene painting; the AF group had burst atrial pacing. All animals underwent terminal study 7 days after gene transfer. Sinus rhythm animals had strong transgene expression but no atrial conduction changes. In AF animals, controls had reduced and lateralized Cx43 expression, and Cx43 gene transfer restored expression and cellular location to sinus rhythm control levels. In the AF group, both Cx40 and Cx43 gene transfer improved conduction and reduced AF relative to controls. CONCLUSIONS: Connexin gene therapy preserved atrial conduction and prevented AF.

DOI： 10.1161/CIRCULATIONAHA.111.053272

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To elucidate the time course of taxane-induced edema which may affect the patients' quality of life (QOL). PATIENTS AND METHODS: Our study included the first 300 Japanese patients assigned to 1 of 4 regimens using docetaxel (DTX) or paclitaxel (PTX) by 1:1:1:1 in a randomized controlled trial to evaluate the efficacy of adjuvant therapies for node-positive breast cancer. Patients' QOL was prospectively assessed by the functional assessment of cancer therapy (FACT)-breast and -taxane (FACT-T) subscale. The scores of FACT items regarding edema and body weight were used as indicators of edema. RESULTS: The scores for 'anasarca', 'edema of the hands' and 'edema of the legs and feet' of the FACT-T subscale worsened up to 1-2 months after chemotherapy, and body weights increased remarkably until cycle 8 in patients treated with DTX alone (75 mg/m(2), 8 cycles, every 3 weeks). Edema-related symptoms and body weight were relatively stable in the other treatment groups. There were statistically significant differences in the scores of those items and in the changes of body weight both between the DTX-alone group and the other three groups combined, and between the groups using DTX and those using PTX. CONCLUSION: Many patients receiving DTX for >4 cycles suffered significantly from edema.

DOI： 10.1159/000336480

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Evaluation of ovarian toxicity requires an understanding of the physiological changes related to the estrous cycle in the ovary. The authors investigated the transitional gene expression profile of ovulatory follicles in rats that show normal estrous cyclicity. Ovaries were collected at 10:00 and 22:00 on the proestrus day and at 10:00 on the estrus day. Ovarian follicles or early corpora lutea were isolated using laser microdissection, and extracted total RNA was analyzed using microarray technology. Clustering analysis revealed four different expression patterns: transient up- or down-regulation only at 22:00 on the proestrus day (pattern 1), up- or down-regulation only at 10:00 on the estrus day (pattern 2), continuous increase at 22:00 on the proestrus day and at 10:00 on the estrus day (pattern 3), and up- or down-regulation at 22:00 on the proestrus day and level maintenance at 10:00 on the estrus day (pattern 4). In addition, these probe sets were functionally categorized in each pattern using the Ingenuity Pathways Analysis database. These data will aid in understanding the physiology of ovulation and may be useful in assessing ovarian toxicity and its mechanism, such as in investigations of chemical-induced ovulatory impairment.

DOI： 10.1177/0192623311406932

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/nsmb.1875

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

GOALS: The aim of the study was to determine the feasibility and validity of a newly developed patient-based instrument--the Patient Neurotoxicity Questionnaire (PNQ)--for grading chemotherapy-induced peripheral neuropathy (CIPN). PATIENTS AND METHODS: We prospectively collected data from 300 female patients who were treated with taxane chemotherapy for primary breast cancer as part of a national multicenter phase III randomized trial (N-SAS BC 02). We evaluated patient compliance with the PNQ and several validation parameters, including concordance between CIPN grades noted by physicians (National Cancer Institute Common Toxicity Criteria) and patients (PNQ), and the concurrent validity and responsiveness of the PNQ versus the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) utilizing data at pre-treatment and before three, five, and seven treatment cycles. MAIN RESULTS: The questionnaire completion rate was >90% at all assessments. Evaluation by physicians always resulted in lower neuropathy assessment scores compared with those reported directly by patients (weighted kappa coefficients, 0.02-0.06). Both PNQ sensory and motor scores were significantly correlated with the FACT/GOG-Ntx (r = 0.66 and 0.51, respectively). In the repeated measures analysis of variance model, PNQ grades increased considerably as treatment continued, indicating progressively worsening CIPN over time. CONCLUSIONS: The PNQ has an applicable degree of feasibility and validity, useful for the diagnosis of CIPN as well as for clinical treatment decision-making, where the development of CIPN is a potential treatment-limiting consideration. Physicians underreport and underestimate the severity of CIPN symptoms compared with patients, thereby supporting the importance of assessing patient-reported outcomes using the PNQ.

DOI： 10.1007/s00520-009-0613-7

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3155/1047-3289.59.10.1212

Web of Science

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Algal growth inhibition tests for environmental risk assessment require improved efficiency to evaluate large numbers of chemicals. As an endpoint for rapid estimation of the effect concentration of test chemicals, we propose the delayed fluorescence (DF) measurement from an alga 24 h after exposure. Eight chemicals (bifenox, bromoxynil, bensulfuronmethyl, diuron, diflufenican, thiobencarb, m-chlorophenylhydrazone and 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone) were tested. The EC50 values from the 24 h DF measurement were similar to those from the conventional 72 h growth test for seven tested chemicals excepting thiobencarb. We conclude that 24 h DF measurement is a possible endpoint for rapid estimation of the EC50 values obtained in the 72 h growth test for those seven chemicals.

DOI： 10.1007/s00128-009-9826-1

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Small particles can reach alveoli without being trapped in the upper respiratory tract and may have a greater impact on health than larger particles. Given the limited knowledge on health effects of fine particulate matter (PM2.5) in Japan, the short-term effects of PM2.5 on daily mortality using the generalized additive model (GAM), generalized linear model (GLIM), and time-stratified case-crossover analysis were estimated. Daily mortality data were obtained from the Ministry of Health, Labor, and Welfare. Air pollution and meteorological data in 20 areas were obtained from the National Institute for Environmental Studies and the Japan Meteorological Agency, respectively. The three methods were compared, adjusting for meteorological variables and co-pollutants, for area-specific analyses and combined area-specific results using meta-analysis with a random-effects model. Daily mortality for elderly aged 65 and over varied from 0.5 to 127.3 by area. The 24-hr mean concentration of PM2.5 ranged from 11.8 to 22.8 microg/m3. Area-specific analyses revealed regional heterogeneity. Furthermore, combined results showed that a 10-microg/m3 increase in PM2.5 for the single-pollutant model at lag1 was associated with a 0.53, 0.77, and 0.88% increase in all-cause mortality for the GAM, GLIM, and case-crossover analysis, respectively. These findings provide robust evidence for the short-term effects of air pollutants on daily mortality in Japan and suggest that differences in estimates obtained from different statistical models should be considered when multipollutant models are used.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

GOALS OF WORK: The aim of this study was to prospectively evaluate chemotherapy-induced peripheral neuropathy (CIPN) using a patient-based instrument, the Patient Neurotoxicity Questionnaire (PNQ) and a physician-based instrument, the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) in patients with advanced or metastatic breast cancer who were treated with weekly paclitaxel. MATERIALS AND METHODS: CIPN symptoms were prospectively assessed in 35 patients using the PNQ, NCI-CTC, and the Functional Assessment of Cancer Therapy (FACT)-Taxane including neurotoxicity component (Ntx) at the baseline, and 8 and 16 weeks after starting chemotherapy. RESULTS: For sensory neuropathy symptoms, the reported incidence of CIPN was significantly increased during active treatment in terms of both the PNQ and NCI-CTC assessments. In contrast, there was a notable increase of patient motor neuropathy symptoms that were elucidated only by the PNQ. The PNQ grades of CIPN were widely distributed in the patient population as compared with the NCI-CTC grades for both sensory and motor neuropathy. The sensory PNQ grade was correlated with sensory NCI-CTC grade (r = 0.58) and Ntx (r = 0.51), and the motor PNQ grade was correlated with Ntx (r = 0.57). CONCLUSIONS: The PNQ appears to be more sensitive and responsive than the NCI-CTC for CIPN; the PNQ appears to have diagnostic validity for evaluating CIPN in patients who are receiving neurotoxic chemotherapy.

DOI： 10.1007/s00520-008-0550-x

PubMed

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記述言語：英語  

Myocardial necrosis is a serious adverse effect that results from the administration of some medications; therefore, when it is observed during preclinical studies it becomes a major drug development concern. Although data from preclinical monkey studies are generally extrapolated to predict effects in humans, few reports have described any mechanism that might explain the occurrence of myocardial necrosis. For this reason, we examined the association between hypokalemia and myocardial necrosis in monkeys. Four female cynomolgus monkeys (Macaca fascicularis) were treated with 50 mg/kg/day hydrochlorothiazide (a thiazide diuretic used for antihypertensive therapy) for 1 or 2 weeks. Clinical, hematological, plasma biochemical, and pathological examinations were conducted. Two animals were kept in a hypokalemic state from day 3 of dosing on, and their mean plasma potassium levels were 2.52 +/- 0.24 and 2.60 +/- 0.24 mmol/l. These animals were necropsied after 1 week of dosing due to an aggravated general condition. A flattened T-wave was noted during electrocardiography. A transient increase in plasma cardiac-specific troponin-I and multifocal myocardial necrosis also occurred. The rest of the animals were occasionally hypokalemic, with mean plasma potassium levels of 3.13 +/- 0.31 or 2.96 +/- 0.30 mmol/l. These animals were necropsied after 2 weeks of dosing. One animal showed evidence of focal myocardial necrosis and a transient increase in plasma cardiac-specific troponin-I. These data suggest that the severe hypokalemia induced by hydrochlorothiazide is likely to be associated with myocardial necrosis in monkeys.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Since there is now growing interest in the incorporation of patient-reported outcome measures in cancer clinical trials, a patient-based questionnaire, the Patient Neurotoxicity Questionnaire (PNQ) was developed to quantify the symptoms and severity of chemotherapy-induced peripheral neuropathy (CIPN). The aim of this study was to evaluate the physicians' perspectives regarding the utility and diagnostic value of PNQ. METHODS: A questionnaire was sent to 61 physicians who participated in a Phase III randomized trial of adjuvant chemotherapy in breast cancer (AC followed by taxane versus taxane alone) that used the PNQ to assess CIPN. RESULTS: Forty-seven out of 61 physicians (77%) responded. The majority considered neurosensory symptoms the diagnostic hallmark for CIPN and most regarded interference with activities of daily living (ADLs) as definite justification for treatment modifications. For neurosensory disturbance, the majority of physicians indicated that Grade D severity (moderate to severe symptoms interfering with ADLs) should result in treatment postponement and Grade E severity (severe symptoms preventing most ADLs) should result in treatment discontinuation. Similarly, for neuromotor disturbance, over half of the physicians replied that Grade C (moderate symptoms not interfering with ADLs), D and E severity should result in dose reduction, treatment postponement and treatment discontinuation, respectively. Eighty-four percentage of the physicians reported that the use of the PNQ was helpful in the diagnosis and assessment of patients at risk of CIPN. CONCLUSIONS: The PNQ appears to be a useful instrument for the diagnosis and grading of CIPN, as well as for clinical decision-making regarding treatment modifications secondary to CIPN.

DOI： 10.1093/jjco/hyn100

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2108/zsj.20.1243

Web of Science

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ZOOLOGICAL SOC JAPAN  

Megalodicopia hians Oka is a solitary ascidian belonging to the family Octacnemidae inhabiting the bathyal/abyssal zone as well as other octacnemid ascidians. The phylogenetic relationship of octacnemids is open to argument because of its extraordinary morphological features due to habitat adaptation, e.g., a pharynx lacking ciliated stigmata. Aggregations of M. hians were discovered by the manned submersible Shinkai 2000 in the bathyal seafloor of Toyama Bay, Japan Sea, in 2000; this was the first in situ observation of M. hians in the Japanese coastal waters. In 2001, a total of 36 M. hians specimens were collected from the bay (592-978 m deep). In situ observation indicated that M. hians usually opens its large oral apertures to engulf the drifting food particles in the water current. Microscopical observation of the gut contents also showed that M. hians is a non selective macrophagous feeding on small crustaceans, diatoms, detritus, and so on. Along with the position of the intestinal loop and gonad, the morphological characteristics of the tunic (integument of ascidians) suggest that M. hians is closely related to Cionidae and/or Corellidae. Some symbiotic/parasitic organisms

DOI： 10.2108/zsj.19.1181

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その他リンク： http://dl.ndl.go.jp/info:ndljp/pid/10865067