Search

Active pharmaceutical ingredients (APIs) have become a public concern owing to their possible adverse effects on aquatic organisms. Ministry of Health, Labor and Welfare in Japan (MHLW) issued "Guidance on the Environmental Risk Assessment (ERA) in new pharmaceutical development" in 2016. To evaluate the validity of phase 1 in the MHLW's ERA guidance, we monitored the measured environmental concentrations (MECs) of approved APIs in urban rivers and sewage treatment plants (STPs) in Japan and compared these MECs with the predicted environmental concentration (PEC). We collected water samples from urban seven rivers and three STPs during each season. Fifty-one APIs for human and veterinary use and the artificial sweetener sucralose were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Forty-four APIs were observed in the rivers and 42 were found in the influent and effluent of STPs, with levels ranging from nanograms to micrograms per liter. The action limit in phase I of the MHLW's guidance was set to 10 ng/L, and there was no API except for ketoprofen, for which PEC of the MHLW's guidance (PECjapan) was lower than 10 ng/L and the maximum MEC (MECmax) was 10 ng/L or greater. Almost all APIs also had median MECs that were lower than those of the respective PECjapan. These results indicate that the PECjapan values in phase I of the MHLW's guidance were appropriate. However, some APIs had MECmax values that were greater than those of the respective PECjapan due to overestimation of the dilution factor of river water and/or underestimation of API production.

ObjectivesWe examined the association of workplace social capital (WSC), including structural and cognitive dimensions, with refraining from seeking medical care (RSMC) among Japanese employees.DesignOne-year prospective cohort study.Setting and participantsWe surveyed 8770 employees (6881 men and 1889 women) aged 18–70 years from 12 firms in Japan using a self-administered questionnaire comprising the WSC scale and the items on potential confounders (ie, age, educational attainment and equivalent annual household income) at baseline (from April 2011 to March 2013).Outcome measuresAt a 1-year follow-up, we measured RSMC using a single-item question ‘In the past year, have you ever refrained from visiting a hospital, clinic, acupuncturist or dentist despite your sickness (including a slight cold or cavity) or injury?’ResultsThe results of Cox regression with robust variance showed that, after adjusting for potential confounders, the low WSC group (ie, the lowest tertile group) had a significantly higher relative risk (RR) of RSMC compared with the high WSC group (ie, the highest tertile group) among both men and women (overall WSC: RR 1.09 (95% CI 1.01 to 1.17) and 1.20 (95% CI 1.06 to 1.37); structural dimension: RR 1.13 (95% CI 1.04 to 1.22) and 1.25 (95% CI 1.07 to 1.45); and cognitive dimension: RR 1.11 (95% CI 1.03 to 1.20) and 1.21 (95% CI 1.06 to 1.38), respectively). Trend analysis using a continuous score of the WSC scale also showed a significant association of low WSC with a higher risk of RSMC among both men and women.ConclusionsOur findings suggest that the lack of social capital in the workplace is associated with RSMC among Japanese employees.

Background and Aim: Helicobacter pylori infection is a primary cause of gastroduodenal ulcers. To investigate whether there is an association between H. pylori infection and small intestinal mucosal injury. Methods: Patients were selected from a general pool of subjects who underwent capsule endoscopy for current or past obscure gastrointestinal bleeding. Characteristics including age, gender, history, treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and/or acid suppressant, diagnosis, and H. pylori infection were investigated. Patients infected with H. pylori had positive test result, ranging 30 days before to 30 days after capsule endoscopy. Patients diagnosed with inflammatory diseases, malignant tumors, etc. were excluded. All video images were re-evaluated to count small intestinal mucosal breaks. Eligible patient variables were compared. Results: A total of 92 patients (30 infected with H. pylori/62 uninfected) were eligible. By univariate analysis of the number of mucosal breaks, patients treated with NSAIDs were found to have more mucosal breaks than patients untreated (38%: 8/21 vs. 18%: 13/71; p = 0.004), and the possible association was detected between patients infected with H. pylori and those who were not (67%: 14/21 vs. 37%: 26/71; p = 0.081). When comparing the H. pylori infected and uninfected patients, the rate of patients with mucosal breaks was greater in infected patients (47%: 14/30 vs. 11%: 7/62; p = 0.001). After excluding patients treated with NSAIDs, the number of mucosal breaks was also greater in patients infected with H. pylori (1.2 ± 1.5 vs. 0.38 ± 0.62; p = 0.001). Conclusion: There is a possibility that H. pylori infection induces small intestinal mucosal injury.

The present study comparatively examined carcinogenicity of 7 different multi-wall carbon nanotubes (MWCNTs) with different physicochemical characteristics. Physicochemical characteristics of MWCNTs (referred to as M-, N-, WL-, SD1-, WS-, SD2- and T-CNTs in the present study) were determined using scanning electron and light microscopes and a collision type inductively coupled plasma mass spectrometer. Male Fischer 344 rats (10 weeks old, 15 animals per group) were administered MWCNTs at a single intraperitoneal dose of 1 mg/kg body weight, and sacrificed up to 52 weeks after the commencement. Fibers of M-, N-, WL- and SD1-CNTs were straight and acicular in shape, and contained few agglomerates. They were relatively long (38-59% of fibers were longer than 5 μm) and thick (33% to more than 70% of fibers were thicker than 60 nm). All of these 4 MWCNTs induced mesotheliomas at absolute incidences of 100%. Fibers of WS-, SD2- and T-CNTs were curled and tightly tangled to form frequent agglomerates. They were relatively short and thin (more than 90% of measured fibers were thinner than 50 nm). WS- CNT did not induce mesothelioma, and only one of 15 rat given SD2- or T-CNT developed tumor. Any correlations existed between the metal content and neither the size or form of fibers, nor the carcinogenicity. It is thus indicated that the physicochemical characteristics of MWCNTs are critical for their carcinogenicity. The straight and acicular shape without frequent agglomerates, and the relatively long and thick size, but not the iron content, may be critical factors. The present data can contribute to the risk management, practical use and social acceptance of MWCNTs.

An 81-year-old man was admitted with upper abdominal pain and weight loss. Esophagogastroduodenoscopy revealed a large tumor located from the gastric angle to the body. Histological analysis of a biopsy revealed a moderately differentiated adenocarcinoma. Computed tomography revealed metastases in the liver and lung and the patient was subsequently diagnosed with metastatic advanced gastric cancer. He was treated with chemotherapy using S-1 (80 mg/m2) and cisplatin (CDDP) (60 mg/m2). Twenty-two months after chemotherapy, the gastric tumor, and the nodules in the liver and lung, had disappeared. We subsequently diagnosed a clinical complete response. The patient was treated with further S-1 monotherapy for 7 months after complete response assessment. He has lived for more than 7 years since the initial diagnosis without recurrence. Chemotherapy using S-1 and CDDP may be a potent strategy for improving survival in elderly patients with advanced gastric cancer.

Helicobacter pylori infection is a primary cause of gastroduodenal ulcers. To investigate whether there is an association between H. pylori infection and small intestinal mucosal injury.Patients were selected from a general pool of subjects who underwent capsule endoscopy for current or past obscure gastrointestinal bleeding. Characteristics including age, gender, history, treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and/or acid suppressant, diagnosis, and H. pylori infection were investigated. Patients infected with H. pylori had positive test result, ranging 30 days before to 30 days after capsule endoscopy. Patients diagnosed with inflammatory diseases, malignant tumors, etc. were excluded. All video images were re-evaluated to count small intestinal mucosal breaks. Eligible patient variables were compared.A total of 92 patients (30 infected with H. pylori/62 uninfected) were eligible. By univariate analysis of the number of mucosal breaks, patients treated with NSAIDs were found to have more mucosal breaks than patients untreated (38%: 8/21 vs. 18%: 13/71; p = 0.004), and the possible association was detected between patients infected with H. pylori and those who were not (67%: 14/21 vs. 37%: 26/71; p = 0.081). When comparing the H. pylori infected and uninfected patients, the rate of patients with mucosal breaks was greater in infected patients (47%: 14/30 vs. 11%: 7/62; p = 0.001). After excluding patients treated with NSAIDs, the number of mucosal breaks was also greater in patients infected with H. pylori (1.2 ± 1.5 vs. 0.38 ± 0.62; p = 0.001).There is a possibility that H. pylori infection induces small intestinal mucosal injury.

The present study reports on the occurrence and chiral behavior of the anti-inflammatory drug (S)-naproxen (NAP)—(S)-2-(6-methoxynaphthalen-2-yl)propionic acid—in an aquatic environment under both field and laboratory conditions. In influents and effluents of sewage treatment plants (STPs) in the Tama River basin (Tokyo), (S)-NAP was detected at concentrations of 0.03 µg L−1 to 0.43 µg L−1 and 0.01 µg L−1 to 0.11 µg L−1, respectively. The concentrations of a major metabolite, 6-O-desmethyl NAP (DM-NAP) were up to 0.47 µg L−1 and 0.56 µg L−1 in influents and effluents, respectively. (R)-naproxen was not detected in STP influents, although it was present in effluents, and the enantiomeric faction (= S/[S + R]) of NAP ranged from 0.88 to 0.91. Under laboratory conditions with activated sludge from STPs, rapid degradation of (S)-NAP to DM-NAP and chiral inversion of (S)-NAP to (R)-NAP were observed. During river die-away experiments, degradation and chiral inversion of NAP were extremely slow. In addition, chiral inversion of (S)-NAP to (R)-NAP was not observed during photodegradation experiments. In the river receiving STP discharge, NAP and DM-NAP concentrations reached 0.08 µg L−1 and 0.16 µg L−1, respectively. The enantiomeric faction of NAP in the river ranged from 0.84 to 0.98 and remained almost unchanged with the increasing contribution of rainfall to the river water. These results suggest that the absence and decrease of (R)-NAP in river waters could indicate the inflow of untreated sewage. Environ Toxicol Chem 2014;33:2671–2678. © 2014 SETAC

Occupational conditions, together with socioeconomic status, may modulate sleep. This study examined the association of occupational conditions and socioeconomic status with actigraphic measures of sleep in workers. Fifty-five employees (40 ± 12 years) wore a wrist actigraph during sleep for seven consecutive nights. Sleep variables addressed included total sleep time, sleep efficiency, mean activity during sleep, sleep-onset latency, and wake after sleep onset. We also measured household income, occupational class, work schedule, weekly work hours, job demand, job control, worksite social support, effort-reward imbalance, organizational justice, and workplace social capital. Multiple linear regression models were used to determine the association of occupational indicators, socioeconomic status, as well as age and gender with each sleep variable. Higher workplace social capital was associated consistently with longer total sleep time (P < 0.001), higher sleep efficiency (P < 0.05) and lower mean activity during sleep (P < 0.07). Low occupational class (P < 0.01), higher job demand (P < 0.05) and lower job control (P < 0.05) were associated with longer total sleep time. No associations were significant for sleep-onset latency or wake after sleep onset. These preliminary results suggest that enhanced workplace social capital is closely associated with better quality and quantity of sleep.

Accessory parotid gland tumors are relatively rare; hence, adequately detailed clinical analyses of these tumors are difficult to perform at a single institution. In this report, we describe the findings for 65 patients [29 men, 36 women; median age, 51 (9-81) years] with accessory parotid gland tumors, consisting of 4 cases documented by us and 61 cases previously reported by other Japanese authors. Approximately 50% of the patients were treated in an otolaryngology department, while the remaining patients were treated in plastic surgery, oral surgery, or dermatology departments. In 4 patients, the results of preoperative fine-needle aspiration cytology indicated that the tumor was benign; however, the postoperative histopathology results revealed malignant tumors. The frequencies of malignant and benign tumors were 44.6% (n = 29) and 55.4% (n = 36), respectively. Mucoepidermoid carcinoma and pleomorphic adenoma were the most frequent types of malignant and benign accessory parotid gland tumors, respectively. Among the various surgical methods that were used, such as direct cheek and intraoral incisions, a standard parotidectomy incision was the most preferred treatment approach for these tumors. Recently, an endoscopic approach has also been found to yield satisfactory results. An optimal approach should be selected after evaluating the advantages and disadvantages of these methods. No definite guidelines are available regarding the choice of elective neck dissection and postoperative radiation therapy for malignant accessory parotid gland tumors. Although tumor resection (plus elective neck dissection) and postoperative radiation therapy have been frequently performed for various kinds of malignant accessory parotid gland tumors to date, additional studies are needed regarding the criteria for selecting elective neck dissection and postoperative radiation therapy. Since the malignancy rate for accessory parotid gland tumors is higher than that for parotid gland tumors, the possibility of malignancy (especially mucoepidermoid carcinoma and carcinoma ex pleomorphic adenoma) should be considered when resecting accessory parotid gland tumors, even if the results of preoperative fine-needle aspiration cytology indicate that the tumor is benign.

The formation potentials of 24 disinfection by-products, six indicators of organic matter and the number of algae were measured in raw water once a month for one year from October 2006 to September 2007 in order to investigate the quality of water in the two water purification plants on the Ogasawara Islands. It was estimated that the main source of organic matter in raw water on the Ogasawara Islands was not autochthonous organic matter but allochthonous organic matter that flows from streams into reservoirs, as determined from the correlations between the parameters of water quality, the relationship between rainfall and water quality, UV absorbance: TOC ratio and other factors. The mean annual formation potentials of disinfection by-products in filtered raw water on Chichijima Island and Hahajima Island were as follows: total haloacetic acid: 286, 194 μg·L-1, total trihalomethane: 227, 190 μg·L-1, total haloacetonitrile: 13 μg·L-1, and chloral hydrate: 13, 9 μg·L-1, respectively. The total trihalomethane formation potentials were at the maximum levels in our country and the formation potentials of other disinfection by-products were also presumed to be their maximum levels. The formation potentials of the brominated disinfection by-products in most months were higher than those of the nonbrominated disinfection by-products. The correlations of total trihalomethane formation potential (mole concentration) with color, TOC, KMnO4 consumption and UV absorbance were lower than those of the formation potentials of total haloacetic acid, total haloacetonitrile and chloral hydrate in raw water. KMnO4 consumption and UV absorbance were effective indicators of disinfection by-product formation potential for these high correlations (P

Goals The aim is to elucidate the efficacy and safety of double-balloon endoscopy (DBE) for small bowel capsule endoscopy (SBCE) retrieval from small bowel stricture and to follow the outcome of the stricture where the SBCE was entrapped. Background The retention of SBCE is a serious adverse event and most retained capsules are retrieved by surgery. There is still no report analyzing the follow-up of patients with stricture after retrieval of entrapped SBCEs by DBE. Methods This study was designed a retrospective cohort study. Subjects were 12 consecutive patients with small bowel stricture where retrieval of entrapped SBCE was attempted using DBE. Success rate of the SBCE retrieval by DBE, surgical rate of the small bowel stricture, adverse events of DBE, and outcomes in the follow-up period were evaluated. Results Diagnoses were Crohn's disease, nonsteroidal anti-inflammatory drugs-induced enteropathy, ischemic enteritis, and carcinoma in 8, 2, 1, and 1 patients, respectively. SBCE was successfully retrieved in 11 of the 12 patients (92%). No adverse events were encountered in all endoscopic procedures such as retrieval of SBCEs and dilation of the strictures. Nine of the 12 patients (75%) did not undergo surgical treatment for the stricture where SBCE was entrapped through the follow-up period (mean, 1675±847 d). Conclusions Retrieval of SBCEs using DBE was safe, had a high success rate, and was useful to evaluate the need for surgery. Seventy-five percent of patients with small bowel stricture where the SBCE was entrapped did not require surgery through approximately 5 years.

Objectives Recent epidemiological research in Europe has reported that two groups of job demands, i.e., challenges and hindrances, are differently associated with work engagement. The purpose of the present study was to replicate the cross-sectional association of workload and time pressure (as a challenge) and role ambiguity (as a hindrance) with work engagement among Japanese employees. Methods Between October 2010 and December 2011, a total of 9,134 employees (7,101 men and 1,673 women) from 12 companies in Japan were surveyed using a self-administered questionnaire comprising the Job Content Questionnaire, National Institute for Occupational Safety and Health Generic Job Stress Questionnaire, short 10-item version of the Effort-Reward Imbalance Questionnaire, short nine-item version of the Utrecht Work Engagement Scale, and demographic characteristics. Multilevel regression analyses with a random intercept model were conducted. Results After adjusting for demographic characteristics, workload and time pressure showed a positive association with work engagement with a small effect size (standardized coefficient [β] = 0.102, Cohen’s d [d] = 0.240) while role ambiguity showed a negative association with a large effect size (β = −0.429, d = 1.011). After additionally adjusting for job resources (i.e., decision latitude, supervisor support, co-worker support, and extrinsic reward), the effect size of workload and time pressure was not attenuated (β = 0.093, d = 0.234) while that of role ambiguity was attenuated but still medium (β = −0.242, d = 0.609). Conclusions Among Japanese employees, challenges such as having higher levels of workload and time pressure may enhance work engagement but hindrances, such as role ambiguity, may reduce it.

The present study reports on the occurrence and chiral behavior of the anti-inflammatory drug (S)-naproxen (NAP)-(S)-2-(6-methoxynaphthalen-2-yl)propionic acid-in an aquatic environment under both field and laboratory conditions. In influents and effluents of sewage treatment plants (STPs) in the Tama River basin (Tokyo), (S)-NAP was detected at concentrations of 0.03 µg L(-1) to 0.43 µg L(-1) and 0.01 µg L(-1) to 0.11 µg L(-1), respectively. The concentrations of a major metabolite, 6-O-desmethyl NAP (DM-NAP) were up to 0.47 µg L(-1) and 0.56 µg L(-1) in influents and effluents, respectively. (R)-naproxen was not detected in STP influents, although it was present in effluents, and the enantiomeric faction (= S/[S + R]) of NAP ranged from 0.88 to 0.91. Under laboratory conditions with activated sludge from STPs, rapid degradation of (S)-NAP to DM-NAP and chiral inversion of (S)-NAP to (R)-NAP were observed. During river die-away experiments, degradation and chiral inversion of NAP were extremely slow. In addition, chiral inversion of (S)-NAP to (R)-NAP was not observed during photodegradation experiments. In the river receiving STP discharge, NAP and DM-NAP concentrations reached 0.08 µg L(-1) and 0.16 µg L(-1) , respectively. The enantiomeric faction of NAP in the river ranged from 0.84 to 0.98 and remained almost unchanged with the increasing contribution of rainfall to the river water. These results suggest that the absence and decrease of (R)-NAP in river waters could indicate the inflow of untreated sewage. E

Background/Aim: Previous studies have reported small intestinal lesions in patients with portal hypertensive disease. However, the etiology of these lesions is not clear, as portal venous pressure was not measured in any of these studies. The aim of this study is to clarify the association between small intestinal lesions and hepatic venous pressure gradient (HVPG), which correlates well with portal venous pressure. Methods: Thirty-five patients with liver cirrhosis were evaluated by capsule endoscopy for small intestinal lesions. HVPG was measured within 3 days of capsule endoscopy. Blood tests, clinical symptoms, Child-Pugh classification and HVPG were analyzed against small intestinal lesions such as edemas, red spots, angiodysplasia and varices. Lesions were categorized according to their location in the duodenum, jejunum or ileum. Edema was evaluated using a 4-grade capsule endoscopy scoring index. Results: HVPG and edema scores increased with Child-Pugh scores. Red spots and angiodysplasia did not correlate with HVPG. Varices were detected in only 5 patients. The edema score was the factor which most strongly correlated with HVPG by multivariate analysis (p = 0.0008). There was also a strong linear relation between edema scores and HVPG (R = 0.75, p < 0.0001). Conclusion: Small intestinal edemas showed the strongest correlation with HVPG among all small intestinal lesions.

In this study, we analyzed over 30 types of PFCs, including precursors in both the dissolved phase and particle solid phase, in 50 samples of river water collected from throughout the Tokyo Bay basin. PFCs were detected in suspended solids (SSs) at levels ranging from −1 (0.11–2470 ng g −1 dry weight). The concentrations of PFCs in the SS were one to two order(s) of magnitude lower than those of PFCs in the dissolved phase. Relatively high levels of PFCs (total of 35 PFCs) in SS were observed in urbanized areas. The concentration of PFCAs, including PFOA and PFNA, were significantly correlated with the geographic index as artificial area ( R 2 of the linear regression curve in a double logarithmic plot: 0.09–0.55). Conversely, PFOS and FOSA were significantly correlated with the arterial traffic area ( R 2 in a double logarithmic plot: 0.29–0.55). Those spatial trends were similar to the trends in dissolved PFCs. We estimated the loading amount of PFCs into Tokyo Bay from six main rivers and found that more than 90% of the total PFCs reached Tokyo Bay in the dissolved phase. However, 40.0–83.5% of the long chain PFCAs (C12–C15), were transported as particle sorbed PFCs. Rain runoff events might increase the loading amount of PFCs in SS. Overall, the results presented herein indicate that greater attention should be given to PFCs, especially for longer chain PFCs in SS in addition to dissolved PFCs.

Pollution from 35 perfluorinated compounds (PFCs) in the water of the Tokyo Bay basin was examined. The water in the basin contained relatively high levels of perfluorononanoate (PFNA), perfluorooctanoate (PFOA), and perfluorooctane sulfonate (PFOS) compared to the other PFCs, which were present at concentrations of 20.1 ng/L, 6.7 ng/L, and 5.8 ng/L, respectively. In contrast, the concentrations of their precursors and degradation products were an order of magnitude lower. Sewage treatment plant (STP) effluent in the area also contained high levels of PFNA compared with the river water samples (Mann-Whitney U-test, p0.0002). From a spatial aspect, increases in PFC pollution levels correlated with increased urbanization in the study area suggested that there are nonpoint source contributors to the PFC pollution in this area. Branched isomers of the PFCs were also quantified. Samples that contained high concentrations of perfluoroalkyl carboxylates (PFCA) showed lower proportions of its branched isomer. This indicates that the branched isomers are more prominent in the area with lower PFC pollution. This analysis was beneficial for estimating the individual contributions of different PFCA production processes. This survey provided new information on the sources, spatial distribution, and behavioral characteristics of PFC pollutants in this area.

Magnesium (Mg) is essential for cell functions such as the transport of calcium and potassium ions, and modulates signal transduction, energy metabolism, and cell proliferation. Although mice have been used as models of various neurological diseases of humans, and for investigating the therapeutic effects of Mg, neither the normal concentration of Mg in cerebrospinal fluid (CSF), nor its response to alteration of the serum level of Mg has yet been reported. The present study investigated the normal Mg concentration in the CSF of C57BL/6J (B6) and ICR mice and its response to elevation of the serum Mg level in B6 mice. In B6 mice, the normal Mg concentration in the CSF was 0.89 ± 0.11 mM, being lower than that in serum, which was 1.38 ± 0.12 mM, whereas in ICR mice the corresponding values were 1.00 ± 0.12 mM and 1.10 ± 0.09 mM, respectively. No significant alteration was found in the CSF of B6 mice injected intraperitoneally with Mg, even though the serum Mg concentration was significantly increased.