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Arsine is one of the most potent hemolytic agents. It is important to clarify arsine metabolism as well as its chemical interactions with biological components. The aim of the present study was to clarify arsine metabolism by arsenic speciation analysis in serum and urine from an acute poisoning patient with hematuria, anemia, and renal and liver dysfunction. Speciation analysis of arsenics in serum and urine was performed using HPLC-ICP-MS. The total arsenic (T-As) concentration in serum was 244.8 μg/l at admission and 97.1 μg/l at discharge. In the speciation analysis, four kinds of As compounds derived from arsine metabolism were detected in serum and urine. The concentration of arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) in serum at admission were 45.8, 5.2, 17.9 and 9.3 μg/l, respectively. The concentrations of AsIII, AsV, and MMA decreased with biological half time (BHT) of 30.1, 43.0, and 96.3 h, respectively. Only DMA was increased at discharge. The urinary AsIII, AsV, MMA and DMA concentrations were 223.0, 12.1, 317.5 and 1053.5 μg/l at discharge, and decreased with BHT of 15.1, 20.8, 14.7, and 16.0 d, respectively. The results indicate that arsine was quickly metabolized to AsIII and subsequently up to DMA, with the result that the toxic effects of inorganic arsenic were added to those of arsine toxicity.

Seaweed contains large amounts of various arsenic compounds such as arsenosugars (AsSugs), but their relative toxicities have not yet been fully evaluated. A risk evaluation of dietary arsenic would be necessary. After developing an arsenic speciation analysis of wakame seaweed (Undaria pinnatifida), we conducted a wakame ingestion experiment using volunteers. Five volunteers ingested 300 g of commercial wakame after refraining from seafood for 5 days. Arsenic metabolites in the urine were monitored over a 5-day period after ingestion. Total arsenic concentration of the wakame seaweed was 34.3 ± 2.1 mg arsenic/kg (dry weight, n = 3). Two AsSugs, 3-[5′-deoxy-5′-(dimethyl-arsinoyl)-β-ribofuranosyloxy]-propylene glycol (AsSug328) and 3-[5′-deoxy-5′-(dimethyl-arsinoyl)-β- ribofuranosyl-oxy]-2-hydroxypropyl-2,3-dihydroxy-propyl phosphate (AsSug482) were detected, but arsenobetaine, dimethylarsinic acid (DMA), monomethylarsonic acid, and inorganic arsenics (iAs) were not detected. The major peak was AsSug328, which comprised 89% of the total arsenic. Approximately 30% of the total arsenic ingested was excreted in the urine during the 5-day observation. Five arsenic compounds were detected in the urine after ingestion, the major one being DMA, which comprised 58.1 ± 5.0% of the total urinary arsenic excreted over the 5 days. DMA was believed to be metabolized not from iAs but from AsSugs, and its biological half-time was approximately 13 h.

OBJECTIVE: It has been reported that moderate alcohol consumption decreased the risk of type 2 diabetes but that elevated liver enzymes increased it. The comparative importance of alcohol consumption and liver enzymes as predictors of type 2 diabetes remains unconfirmed. RESEARCH DESIGN AND METHODS: The participants included 8,576 Japanese men, aged 40-55 years, without type 2 diabetes at entry. Type 2 diabetes was diagnosed if a fasting plasma glucose level was >or=126 mg/dl or if participants were taking oral hypoglycemic medications or insulin. RESULTS: During the 4-year follow-up period, we confirmed 878 cases. In multivariate models, moderate daily alcohol consumption (16.4-42.6 g ethanol/day) decreased the risk of type 2 diabetes, and higher levels of gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT) increased the risk. In joint analyses of alcohol consumption and liver enzymes, moderate drinkers with the lowest tertile of GGT had the lowest risk of type 2 diabetes. Compared with them, nondrinkers with the highest GGT had the highest risk of type 2 diabetes (odds ratio 3.18 [95% CI 1.75-5.76]). At every level of GGT, moderate or heavy alcohol drinkers (>or=42.7 g ethanol/day) had a lower risk of type 2 diabetes than nondrinkers. The relationship of ALT and daily alcohol consumption with the risk of type 2 diabetes was almost the same as that of GGT. CONCLUSIONS: GGT, ALT, and daily alcohol consumption were independently associated with the risk of type 2 diabetes. Nondrinkers with the highest GGT or ALT had a high risk of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: We prospectively assessed whether the combined measurements of fasting plasma glucose (FPG) and A1C were effective for predicting type 2 diabetes.Research Design and Methods: Study participants included 6,736 nondiabetic Japanese men aged 40-55 years. Type 2 diabetes was diagnosed in those who had an FPG >or=126 mg/dl or who were being treated with an oral antidiabetic agent or insulin. The models including FPG, A1C, and both were compared using the area under the receiver operating characteristic (AUROC) curves.Results: During the 4-year follow-up period, we confirmed 659 diabetes cases. In multivariate analysis, both FPG and A1C were independently associated with the risk of type 2 diabetes. The model including both FPG and A1C had a greater AUROC curve than that including FPG alone (0.853 vs. 0.818; P < 0.001) or A1C alone (0.853 vs. 0.771; P < 0.001).Conclusions: The combined measurement of FPG and A1C was effective for predicting type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: Because skeletal muscle is one of the target tissues for insulin, skeletal muscle mass might be associated with type 2 diabetes. Serum creatinine is a possible surrogate marker of skeletal muscle mass. The purpose of this study was to determine whether serum creatinine level is associated with type 2 diabetes.Research Design and Methods: The study participants were nondiabetic Japanese men (n = 8,570) aged 40-55 years at entry. Type 2 diabetes was diagnosed if fasting plasma glucose was >or=126 mg/dl or if participants were taking oral hypoglycemic medication or insulin.Results: During the 4-year follow-up period, 877 men developed type 2 diabetes. Lower serum creatinine was associated with an increased risk of type 2 diabetes. The multiple-adjusted odds ratio for those who had serum creatinine levels between 0.40 and 0.60 mg/dl was 1.91 (95% CI 1.44-2.54) compared with those who had levels between 0.71 and 0.80 mg/dl.Conclusions: Lower serum creatinine increased the risk of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: This research aimed to develop a reliable gas chromatography-mass spectrometry (GC-MS) method for detecting urinary benzyl alcohol (BeOH) concentrations and assess its suitability as a biomarker for occupational BeOH exposure., Methods: Thirteen male participants exposed to BeOH during paint stripping work provided preshift and postshift urine samples, and their personal exposure concentrations were measured. Meanwhile, a control group of 10 nonexposed workers contributed urine samples. The newly developed GC-MS method met regulatory guidelines., Results: The personal exposure concentrations of BeOH ranged from 8.4 to 45.2 mg/m3. Postshift urine samples from exposed participants showed significant BeOH and hippuric acid (HA) concentration increases compared to preshift samples (BeOH, post-/pre-shift geometric mean (GM) ratio = 7.5-7.8, p < 0.001; HA, post-/pre-shift GM ratio = 4.3-4.5, p < 0.001). These levels were considerably higher than those in postshift samples from the nonexposed control group (BeOH, exposed-/nonexposed-workers GM ratio = 14.8-19.0, p < 0.001; HA, exposed-/nonexposed-workers GM ratio = 12.1-15.3, p < 0.001), even after urine density correction., Conclusions: Urinary BeOH and HA can serve as potential biomarkers of occupational exposure to BeOH. More specifically, BeOH might serve as a superior biomarker than HA because it is apparently less influenced by confounding factors such as dietary intake and genetic polymorphism of low-Km aldehyde dehydrogenase (ALDH2). The findings will improve workplace safety measures and protocols, assisting healthcare professionals in diagnosing and managing exposure-related health issues, thereby potentially reducing the risk of occupational exposure to BeOH., (© The Author(s) [2024]. Published by Oxford University Press on behalf of Journal of Occupational Health.)

We herein present the first known case of bacteremia caused by Kluyvera georgiana in a 67-year-old female undergoing chemotherapy for recurrent pancreatic cancer. The patient underwent choledochojejunotomy and thereafter developed ascending cholangitis. The diagnosis of K. georgiana was confirmed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. A literature review of Kluyvera spp. infections indicated potential risk factors including an underlying malignancy and immunosuppression. Although Kluyvera spp. infections are typically sensitive to antibiotics, multidrug resistance is possible. This case highlights the importance of the early diagnosis and treatment of K. georgiana and its associated risk factors.

Phytoremediation is a cost-effective and eco-friendly alternative method for arsenic (As) contaminated water treatment. This study conducted a two-year year-round field study (cycle1 and cycle2) in a temperate area (Sendai, Japan) using small As-hyperaccumulator Pteris vittata seedlings to reduce pre-cultivation time and associated costs. The number of seedlings was changed from 256 in the cycle1 period to 165 in the cycle2 period to evaluate the As removal efficiency of P. vittata for As-contaminated water in field conditions with different plant densities. Before the winter season, with continuously increasing fronds, rhizomes, and roots growth, this reduction did not affect the plant's As removal efficiency for As-contaminated water to decrease the As concentration from 30 μg/L to the environmental quality standard for As in water, set at 10 μg/L in Japan. During the winter season, we found that cold weather caused P. vittata to wither and release the accumulated As into water without a greenhouse (cycle1). In the meantime, the bioaccumulation factor (BAF) and the translocation factor (TF) values for fronds of P. vittata decreased (BAF for fronds: from 66,089 to 8,460; TF for fronds: from 13.4 to 3.4). On the other hand, with greenhouse protection (cycle2), P. vittata did not severely wither and kept accumulating As. Moreover, BAF and TF values for fronds of P. vittata increased (BAF for fronds: from 24,372 to 36,740; TF for fronds: from 5.2 to 17.2). Maintaining the air temperature inside the greenhouse, particularly around the rhizomes, above 0 °C may be the reason why P. vittata remained alive and functional during the cold winter. These results indicate that a single-layer polyethylene greenhouse was sufficient for the tropical-subtropical As-hyperaccumulator fern P. vittata to survive the cold winter and snow in the temperate area, enabling year-round phytoremediation treatment of As-contaminated water in the open field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aim: Comprehensive genomic profiling (CGP) test for solid tumors is now increasingly utilized in clinical practice, especially in pancreatobiliary cancer, and specimens obtained by endoscopic ultrasound-guided tissue acquisition (EUS-TA) are often submitted for tissue-based CGP test. In this study, we evaluated the feasibility of EUS-TA using a 22-gauge Franseen needle for the CGP test., Methods: Consecutive patients with solid tumors who underwent EUS-TA using a 22-gauge Franseen needle, and whose tissue samples were pre-checked for suitability for CGP test, were included in this single-center, retrospective analysis. The success rates of appropriate sample collection for CGP evaluated by pathologists (1st quality control) and CGP test (2nd quality control) were evaluated. In addition, The EUS-TA slides were evaluated for the tissue area and tumor area content, using the image software., Results: A total of 50 cases, with 78% of pancreatic cancer, were included in the analysis. A median of 3 passes of EUS-TA were performed with an adverse event rate of 4%. The success rates for 1st and 2nd quality control for CGP tests were 86% and 76%, respectively. The image analyses suggested EUS-TA specimen did not always fulfill CGP test criteria, with 18% of tissue area ≥16 mm 2 and 38% of tumor area content ≥20%, even in cases with successful CGP tests. The suction method yielded a significantly larger amount of DNA but without a significant difference in the multivariate analysis., Conclusions: The present study demonstrated the feasibility of EUS-TA using a 22-gauge Franseen needle for CGP test., Competing Interests: Yousuke Nakai is an Associate Editor of Digestive Endoscopy. YN received a research grant from Boston Scientific Japan, Fujifilm Corporation, and honoraria from Boston Scientific Japan, Fujifilm Corporation, and Olympus Corporation. MF received a research grant from Olympus Corporation, Fujifilm Corporation, and honoraria from Fujifilm Corporation, Olympus Corporation., (© 2024 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: Endoscopic self-expandable metal stent (SEMS) placement is a current mainstay for malignant gastric outlet obstruction (GOO), but symptomatic recurrence due to initial SEMS dysfunction commonly occurs. We aimed to compare the safety and effectiveness of second SEMS for recurrent GOO (RGOO). Methods: Between April 2006 and December 2022, a total of 95 cases with malignant RGOO undergoing second endoscopic SEMS placement were enrolled. Technical and clinical success rates, RGOO, time to RGOO (TRGOO), stent patency rate, adverse events (AE), and overall survival (OS) were retrospectively compared between covered and uncovered SEMS (cSEMS/uSEMS) groups. Risk factors for TRGOO were also explored. Results: Baseline characteristics were well balanced between cSEMS ( n = 48) and uSEMS ( n = 47) groups, except for the causes of the initial SEMS dysfunction. High technical and clinical success rates with a similar incidence of AE (15% vs. 17%, p = 0.78) and OS (median of 101 vs. 102 days, p = 0.68) were achieved in both groups. There were no statistical differences in cumulative incidence of RGOO (19% vs. 13%, p = 0.58), TRGOO (median, not reached in both groups, p = 0.57), and stent patency rates at 1, 2, and 3 months between the groups (60%, 47% and 26%, respectively vs. 70%, 55% and 38%, respectively). However, TRGOO tended to be longer in cSEMS in cases with RGOO due to tumor ingrowth (median, not reached vs. 111 days, p = 0.19). A Cox regression analysis demonstrated that chemotherapy after second SEMS placement was significantly associated with an improved TRGOO (the hazard ratio of 0.27 [95% confidence interval, 0.08-0.93], p = 0.03). Conclusions: Regardless of the type of SEMS, second SEMS placement was similarly safe and effective for RGOO. The type of second SEMS might be considered based on the cause of initial SEMS dysfunction.

Background: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is widely used for the pathological diagnosis of solid pancreatic lesions but in cases with obstructive jaundice, transpapillary sampling can be performed during endoscopic retrograde cholangiopancreatography with transpapillary biliary stent placement. Thus, it is still controversial whether EUS-FNA should be performed prior to endoscopic retrograde cholangiopancreatography with biliary stent placement or only after negative transpapillary sampling., Methods: The accuracy, sensitivity, and specificity of EUS-FNA for solid pancreatic lesions with or without indwelling biliary stents were retrospectively studied in patients undergoing EUS-FNA between January 2017 and December 2021. We also conducted a meta-analysis including our data to compare the accuracy and sensitivity of EUS-FNA with or without biliary stents., Results: A total of 509 patients (40 with biliary stents and 469 without biliary stents) were included. The accuracy (77.5% vs. 94.5%, p < 0.001) and sensitivity (71.0% vs. 91.7%, p < 0.001) were lower in EUS-FNA with biliary stents. A meta-analysis confirmed that accuracy (odds ratio [OR] of 0.43, 95% confidence interval [CI] 0.29-0.62, p < 0.001) and sensitivity (OR of 0.46, 95% CI 0.33-0.64, p < 0.001) were lower in EUS-FNA with biliary stents. There were no statistically significant differences between plastic stents and self-expandable metallic stents for accuracy or sensitivity., Conclusions: The presence of biliary stents had a negative impact on the diagnostic performance of EUS-FNA, and EUS-FNA prior to endoscopic retrograde cholangiopancreatography with biliary stent placement should be considered in cases with obstructive jaundice., Competing Interests: Author Mitsuhiro Fujishiro has received honoraria from Fujifilm Corporation and Olympus Corporation and research grants from Fujifilm Corporation and Olympus Corporation. Author Yousuke Nakai is an editorial board member of Digestive Endoscopy and has received honoraria from Boston Scientific Japan, Gadelius medical corporation, Olympus Corporation, and research grants from Fujifilm Corporation and HOYA Corporation., (© 2023 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

The Illumina MiSeq platform has been widely used as a standard method for studying the rumen microbiota. However, the low resolution of taxonomic identification is the only disadvantage of MiSeq amplicon sequencing, as it targets a part of the 16S rRNA gene. In the present study, we performed three experiments to establish a high-resolution and high-throughput rumen microbial profiling approach using a combination of MinION platform and buccal swab sample, which is a proxy for rumen contents. In experiment 1, rumen contents and buccal swab samples were collected simultaneously from cannulated cattle ( n  = 6) and used for microbiota analysis using three different analytical workflows: amplicon sequencing of the V3-V4 region of the 16S rRNA gene using MiSeq and amplicon sequencing of near full-length 16S rRNA gene using MinION or PacBio Sequel II. All reads derived from the MinION and PacBio platforms were classified at the species-level. In experiment 2, rumen fluid samples were collected from beef cattle ( n  = 28) and used for 16S rRNA gene amplicon sequencing using the MinION platform to evaluate this sequencing platform for rumen microbiota analysis. We confirmed that the MinION platform allowed species-level taxa assignment for the predominant bacterial groups, which were previously identified at the family- and genus-level using the MiSeq platform. In experiment 3, buccal swab samples were collected from beef cattle ( n  = 30) and used for 16S rRNA gene amplicon sequencing using the MinION platform to validate the applicability of a combination of the MinION platform and buccal swab samples for rumen microbiota analysis. The distribution of predominant bacterial taxa in the buccal swab samples was similar to that in the rumen samples observed in experiment 2. Based on these results, we concluded that the combination of the MinION platform and buccal swab samples may be potentially applied for rumen microbial analysis in large-scale studies., Competing Interests: YO and KIw are affiliated with MEIJI FEED. CO., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Miura, Takeda, Yamaguchi, Ohtani, Endo, Masuda, Ito, Nagura, Iwashita, Mitani, Suzuki, Kobayashi and Koike.)

Objectives: We aimed to develop a method to determine workers' personal exposure levels to N-(phosphonomethyl)glycine (glyphosate) for their risk assessments., Methods: The proposed method was assessed as follows: recovery, stability of samples on storage, method limit of quantification, and reproducibility. Glyphosate in air was sampled using an air-sampling cassette containing a glass fiber filter. Ultrapure water was used to extract glyphosate from sampler filters. After derivation with 9-fluorenylmethyloxycarbonyl chloride, samples were analyzed by high-performance liquid chromatography using a fluorescence detector., Results: Spiked samples indicated an overall recovery of 101%. After 7 days of storage at 4°C, recoveries were approximately 100%. The method limit of quantification was 0.060 μg/sample. Relative standard deviations representing overall reproducibility, defined as precision, were 1.4%-1.8%., Conclusions: The method developed in this study allows 4-h personal exposure monitoring of glyphosate at 0.250-500 μg/m 3 . Thus, this method can be used to estimate worker exposure to glyphosate., (© 2022 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.)

Pteris vittata is an arsenic (As) hyperaccumulator plant that accumulates a large amount of As into fronds and rhizomes (around 16,000 mg/kg in both after 16 weeks hydroponic cultivation with 30 mg/L arsenate). However, the sequence of long-distance transport of As in this hyperaccumulator plant is unclear. In this study, we used a positron-emitting tracer imaging system (PETIS) for the first time to obtain noninvasive serial images of As behavior in living plants with positron-emitting 74 As-labeled tracer. We found that As kept accumulating in rhizomes as in fronds of P. vittata, whereas As was retained in roots of a non-accumulator plant Arabidopsis thaliana. Autoradiograph results of As distribution in P. vittata showed that with low As exposure, As was predominantly accumulated in young fronds and the midrib and rachis of mature fronds. Under high As exposure, As accumulation shifted from young fronds to mature fronds, especially in the margin of pinna, which resulted in necrotic symptoms, turning the marginal color to gray and then brown. Our results indicated that the function of rhizomes in P. vittata was As accumulation and the regulation of As translocation to the mature fronds to protect the young fronds under high As exposure.

The comparative severity of patent foramen ovale (PFO)-related stroke in patients without atrial fibrillation (AF) and AF-related stroke in patients without PFO is unknown. Therefore, we compared the severity of PFO-related stroke and AF-related stroke. Twenty-six patients who underwent transesophageal echocardiography (TEE) were diagnosed with cardioembolic stroke from July 2018 to March 2020. Cases with AF detected by electrocardiograms or thrombus in the left atrium or left atrial appendage on TEE were included in the AF-related stroke group. Cases with a positive microbubble test on the Valsalva maneuver during TEE, and with no other factors that could cause stroke, were included in the PFO-related stroke group. This study was designed as a single-center, small population pilot study. The stroke severity of the two groups by the National Institute of Health Stroke Scale (NIHSS) score was compared by statistical analysis. Of the 26 cases, five PFO-related stroke patients and 21 AF-related stroke patients were analyzed. The NIHSS score was 2.2 ± 2.8 and 11.5 ± 9.2 ( p -value < 0.01), the rate of hypertension was 20.0% and 85.7% ( p -value = 0.01), and the HbA1c value was 5.5 ± 0.2% and 6.3 ± 1.3% ( p -value = 0.02) in the PFO-related and AF-related stroke groups, respectively. Compared with AF-related stroke patients, stroke severity was low in PFO-related stroke patients.

Polymerase proofreading-associated polyposis, caused by germline variants in the exonuclease domains of POLD1 and POLE, is a dominantly inherited rare condition characterized by oligo-adenomatous polyposis and increased risk of colorectal cancer, endometrial cancer and brain tumours. We report the first Japanese case of polymerase proofreading-associated polyposis carrying a POLD1 variant. The proband was a Japanese woman who had undergone resections of early colorectal carcinomas repeatedly and a hysterectomy with bilateral oophorectomy for endometrial cancer, all of which were diagnosed within 2 years after the first colectomy at 49 year old. Colonoscopic examinations demonstrated at least 14 non-cancerous polypoid lesions, some of which were histologically confirmed to be adenoma. Multigene panel sequencing identified a missense variant in POLD1 (c.1433G>A). Although her relatives did not undergo genetic testing, her father and paternal grandfather died of brain tumours at 53 and ~30 years of age, respectively., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We herein report a case of gastrointestinal (GI) Kaposi's sarcoma (KS) without cutaneous involvement in a 73-year-old man who had received immunosuppressive drugs for granulomatosis with polyangiitis. After one year of prednisolone use, he presented with tarry stool and severe anemia. Endoscopic and pathological examinations revealed bright-reddish protruding lesions with proliferating spindle cells positive for D2-40, CD34, and HHV-8, which are definitively diagnostic of GI-KS. Drug-induced KS without HIV infection or transplantation is extremely rare, and its clinical features remain unknown. Therefore, we conducted a literature review of steroid-induced KS.

Objectives: The aim of this study was to develop and validate a simple and reliable gas chromatography-mass spectrometry (GC-MS) method to simultaneously determine urinary 1-naphthol (1-NAP) and 2-naphthol (2-NAP) for biological monitoring of occupational exposure to naphthalene., Methods: NAPs were derivatized in situ with acetic anhydride after enzymatic hydrolysis, extracted with n-hexane, and analyzed using GC-MS. Validation of the proposed method was conducted in accordance with US Food and Drug Administration guidance. A final validation was performed by analyzing a ClinChek ® -Control for phenolic compounds., Results: The linearity of calibration curves was indicated by a high correlation coefficient (>0.999) in the concentration range 1-100 μg/L for each NAP. The limits of detection and quantification for each NAP were 0.30 and 1.00 μg/L, respectively. The recovery was 90.8%-98.1%. The intraday and interday accuracies, expressed as the deviation from the nominal value, were 92.2%-99.9% and 93.4%-99.9%, respectively. The intraday and interday precision, expressed as the relative standard deviation, was 0.3%-3.9% and 0.4%-4.1%, respectively. The ClinChek ® values obtained using our method were sufficiently accurate., Conclusions: The proposed method is simple, reliable, and appropriate for routine analyses, and is useful for biological monitoring of naphthalene exposure in occupational health practice., (© 2020 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.)

A novel Tn MERI 1-like transposon designated as Tn MARS 1 was identified from mercury resistant Bacilli isolated from Minamata Bay sediment. Two adjacent ars operon-like gene clusters, ars1 and ars2 , flanked by a pair of 78-bp inverted repeat sequences, which resulted in a 13.8-kbp transposon-like fragment, were found to be sandwiched between two transposable genes of the Tn MERI 1-like transposon of a mercury resistant bacterium, Bacillus sp. MB24. The presence of a single transcription start site in each cluster determined by 5'-RACE suggested that both are operons. Quantitative real time RT-PCR showed that the transcription of the arsR genes contained in each operon was induced by arsenite, while arsR2 responded to arsenite more sensitively and strikingly than arsR1 did. Further, arsenic resistance complementary experiments showed that the ars2 operon conferred arsenate and arsenite resistance to an arsB -knocked out Bacillus host, while the ars1 operon only raised arsenite resistance slightly. This transposon nested in Tn MARS 1 was designated as Tn ARS 1. Multi-gene cluster blast against bacteria and Bacilli whole genome sequence databases suggested that Tn MARS 1 is the first case of a Tn MERI 1-like transposon combined with an arsenic resistance transposon. The findings of this study suggested that Tn MERI 1-like transposons could recruit other mobile elements into its genetic structure, and subsequently cause horizontal dissemination of both mercury and arsenic resistances among Bacilli in Minamata Bay.

Seaweeds contain large amounts of organoarsenic compounds, mostly arsenosugars (AsSug) and arsenolipids (AsLipid). AsSug is mainly metabolized into dimethylarsinic acid (DMA V ) in humans. However, this metabolic process is not well understood. We investigated the metabolism of an AsSug, 3-[5'-deoxy-5'-(dimethylarsinoyl)-β-ribofuranosyloxy]-2-hydroxypropylene glycol (AsSug328), in the gastrointestinal tract using an in vitro artificial gastrointestinal digestion system. AsSug328 was incubated with gastric juice for 4 h, with bile-pancreatic juice for 0.5 h, and finally with enteric bacteria solution for 24 h. The conversion of arsenic compounds after artificial digestion was analyzed by HPLC-ICP-MS and HPLC-ESI-Q-TOF-MS. Our results show that artificial gastrointestinal digestion converted AsSug328 into thio-AsSug328. However, no formation of DMA V was detected. Under the artificial digestion system, the 5-deoxyribofuranose structure of AsSug was maintained. Therefore, AsSug should be absorbed in the intestinal tract after its sugar moiety is partially decomposed. They are then possibly metabolized to DMA V in the liver and subsequently excreted through urine.

Toxic metals/metalloid contaminations of estuarine sediments due to compromised tributaries arouse significant interest in studying bacterial community that triggers natural attenuation processes. Geo-accumulation index (I geo ), contamination factor (CF), pollution load index (PLI), and Hakanson potential ecological risk index (RI) as a sum of risk factors (Er) were used to quantify toxic metal/metalloid-pollution status of Lagos Lagoon (2W) and 'Iya-Alaro' tributary (4W) sediments in comparison with pristine 'Lekki Conservation Centre' sediment (L1-B). Bacteriology of the ecosystems was based on culture-independent analyses using pyrosequencing. 2W and 4W were extremely contaminated with mercury (I geo  > 7), whereas, cadmium contamination was only observed in 4W. The two ecosystems were polluted with toxic metal based on PLI, where mercury (Er = 2900 and 1900 for 4W and 2W, respectively) posed very high ecological risks. Molecular fingerprinting revealed that Proteobacteria, Firmicutes, and Acidobacteria predominately contributed the 20 most abundant genera in the two ecosystems. The 240 and 310 species present in 2W and 4W, respectively, but absent in L1-B, thrive under the metal concentrations in the polluted hydrosphere. Whereas, the 58,000 species missing in 2W and 4W but found in L1-B would serve as indicators for systems impacted with metal eco-toxicity. Despite toxic metal pollution of the ecosystems understudied, bacterial communities play vital roles in self-recovery processes occurring in the hydrosphere., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective The updated guidelines of 2015 for cardiopulmonary resuscitation (CPR) do not recommend the routine use of atropine for cardiopulmonary arrest. Methods The study population included out-of-hospital cardiac arrest (OHCA) patients with non-shockable rhythm who were encountered at a Japanese community hospital between October 1, 2012 and April 30, 2017. Results At the outcome, the epinephrine with atropine and epinephrine-only groups had a similar survival rate to that at hospital admission (28.7% vs. 26.7%: p=0.723). The odds ratio (OR) for the survival to hospital admission after the administration of atropine with epinephrine was 1.33 (95% CI 1.09-1.62; p<0.01), while that after the administration of epinephrine was 0.64 (95% CI: 0.55-0.74, p<0.01). The ORs for the survival to hospital admission for patients with pulseless electrical activity in the epinephrine-alone group and the atropine with epinephrine group were 0.62 (95% CI 0.49-0.78; p<0.01) and 1.35 (95% CI 0.99-1.83; p=0.06), respectively, and those for such patients with asystole in the epinephrine-alone group and the atropine with epinephrine group were 0.64 (95% CI 0.53-0.76; p<0.01) and 1.39 (95% CI 1.10-1.77; p<0.01), respectively. The OR for the survival to hospital admission after the administration of atropine sulfate (1 mg) was 2.91 (95% CI 1.49-5.67; p<0.01), while that for the survival to hospital admission after the administration of 0, 2 and ≥3 mg atropine sulfate was 0.38 (95% CI 0.29-0.50; p<0.01), 1.54 (95% CI 0.58-4.08; p=0.38) and 0.23 (95% CI 0.09-0.60; p<0.01), respectively. Conclusion The addition of atropine (within 2 mg) following epinephrine was a comprehensive independent predictor of the survival to hospital admission for non-shockable (especially asystole) OHCA adults.

Objectives: The purpose of this study was to develop a simple and accurate gas chromatography-mass spectrometry (GC-MS) method for simultaneous determination of four urinary metabolites from four organic solvents, that is, hippuric acid (HA) from toluene, methylhippuric acid (MHA) from xylene, and mandelic acid (MA) and phenylglyoxylic acid (PGA) from styrene or ethylbenzene for biological monitoring., Methods: The four metabolites were directly methyl-esterified with 2,2-dimethoxypropane and analyzed using GC-MS. The proposed method was validated according to the US Food and Drug Administration guidance. The accuracy of the proposed method was confirmed by analyzing a ClinChek ® -Control for occupational medicine (RECIPE Chemicals +Instruments GmbH)., Results: Calibration curves showed linearity in the concentration range of 10-1000 mg/L for each metabolite, with correlation coefficients >0.999. For each metabolite, the limits of detection and quantification were 3 mg/L and 10 mg/L, respectively. The recovery was 93%-117%, intraday accuracy, expressed as the deviation from the nominal value, was 92.7%-103.0%, and intraday precision, expressed as the relative standard deviation (RSD), was 1.3%-4.7%. Interday accuracy and precision were 93.4%-104.0% and 1.2%-9.5%, respectively. The analytical values of ClinChek obtained using the proposed method were sufficiently accurate., Conclusions: The proposed method is a simple and accurate which is suitable for routine analyses that could be used for biological monitoring of occupational exposure to four organic solvents., (© 2019 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.)

Ecotoxicological implications of mercury (Hg) pollution of hydrosphere require effective Hg-removal strategies as antidote to the environmental problems. Mercury-tolerant yeasts, Yarrowia spp. Idd1 and Idd2 strains, were studied for intracellular accumulation and extracellular micro-precipitation of Hg during growth stage of the yeast strains. In a liquid medium containing 870 (±23.6) µg of bioavailable Hg 2+ , 419.0 µg Hg 2+ (approx.) was taken up by the wet biomasses of the yeast strains after 48 h post-inoculation. Large portion of the adsorbed Hg was found in cell wall (approx. 49-83 %) and spheroplast (approx. 62-89 %). Negligible quantities of Hg were present in the mitochondria (0.02-0.02 %), and appreciable amount of Hg was observed in nuclei and cell debris (15.2-65.3 %) as evidence of bioaccumulation. Extracellular polymeric substances (EPS) produced by the growing Yarrowia cells was a complex of protein, carbohydrates and other substances, immobilizing 43.8 (±0.7)-58.7 (±1.0) % of initial Hg in medium as micro-precipitates, while 10.13 ± 0.4-39.2 ± 4.3 % Hg content was volatilized. Transmission electron microscopy coupled with X-ray energy dispersive spectrophotometry confirmed the cellular removal of Hg and formation of EPS-Hg complex colloids in the surrounding bulk solution as micro-precipitates in form of extracellular Hg-nanoparticles. Hg mass balance in the bio-sequestration experiment revealed excellent Hg removal (>97 %) from the medium (containing ≤16 μg ml -1 Hg 2+ ) by the yeast strains via bioaccumulation, volatilization and micro-precipitation. The yeast strains are also effectively applicable in biological purification technology for Hg contaminated water because of their high self-aggregation activity and separatability from the aquatic environments. Graphical abstract Yarrowia species are oligotrophic marine yeasts that exhibited great potentials for mercuric ion remediation technologies, which are classified into four categories based on the process acting on the metal. These include immobilization through biosorption, compartmentation via bioaccumulation, separation from bulk solution via micro-precipitation upon EPS-Hg complex formation, and destruction that is a process to reduce the mercuric ion to metallic mercury.

Exopolymeric substances (EPS) produced by highly mercury-resistant strains of the yeast Yarrowia spp. (Idd1 and Idd2) were isolated and studied for their mercury binding potential. Excellent yield (approximately 0.3 g EPS per gram biomass) of soluble EPS in medium with 3% glucose was observed in the Yarrowia cultures 7 day post-inoculation. A gram dry weight of the EPS consists mainly of carbohydrates (0.4 g), protein (0.3-0.4 g), uronic acid (0.02 g), and nucleic acids (0.002 g). Mercury interactions with the biopolymer were measured as uptake kinetics from a simulated aquatic system and modelled with thermodynamics and calculated mass action equilibria. The EPS forms a complex with Hg 2+ in water with small activation energy (≤2 kJ mol -1 ), achieving about 30 mg Hg 2+ adsorption per gram dry weight of EPS. The adsorption models confirmed complexation of Hg 2+ by the EPS via heterogeneous multilayer adsorption that obey second-order kinetics at constant rate of 4.0 and 8.1 mg g -1  min -1 . The EPS used chemisorption as rate-limiting step that controls the uptake of Hg 2+ from aquatic systems during micro-precipitation as bio-removal strategy. The EPS are promising biotechnological tools to design bioreactors for treatment of mercury-rich industrial wastewater., (Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Background: In 2013, an unusually high incidence of biliary tract cancer among current or former workers of the offset color proof printing department of a printing company in Osaka, Japan, was reported. The purpose of this study was to examine whether distance from the printing factory was associated with incidence of biliary tract cancer and whether incident biliary tract cancer cases clustered around the printing factory in Osaka using population-based cancer registry data., Methods: We estimated the age-standardized incidence ratio of biliary tract cancer according to distance from this printing factory. We also searched for clusters of biliary tract cancer incidence using spatial scan statistics., Results: We did not observe statistically significantly high or low standardized incidence ratios for residents in each area categorized by distance from the printing factory for the entire sample or for either sex. The scan statistics did not show any statistically significant clustering of biliary tract cancer incidence anywhere in Osaka prefecture in 2004-2007., Conclusions: There was no statistically significant clustering of biliary tract cancer incidence around the printing factory or in any other areas in Osaka, Japan, between 2004 and 2007. To date, even if some substances have diffused outside this source factory, they do not appear to have influenced the incidence of biliary tract cancer in neighboring residents.

Objectives: The sum of urinary inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) concentrations is used for the biological monitoring of occupational iAs exposure. Although DMA is a major metabolite of iAs, it is an inadequate index because high DMA levels are present in urine after seafood consumption. We estimated the urinary iAs+MMA concentration corresponding to iAs exposure., Methods: We used data from two arsenic speciation analyses of urine samples from 330 Bangladeshi with oral iAs exposure and 172 Japanese workers without occupational iAs exposure using high-performance liquid chromatography with inductively coupled plasma mass spectrometry., Results: iAs, MMA, and DMA, but not arsenobetaine (AsBe), were detected in the urine of the Bangladeshi subjects. The correlation between iAs+MMA+DMA and iAs+MMA was obtained as log (iAs+MMA) = 1.038 log (iAs+MMA+DMA) -0.658. Using the regression formula, the iAs+MMA value was calculated as 2.15 and 7.5 μg As/l, corresponding to 3 and 10 μg As/m(3) of exposures, respectively. In the urine of the Japanese workers, arsenic was mostly excreted as AsBe. We used the 95th percentile of iAs+MMA (12.6 μg As/l) as the background value. The sum of the calculated and background values can be used as a biological indicator of iAs exposure., Conclusion: We propose 14.8 and 20.1 μg As/l of urinary iAs+MMA as the biological indicators of 3 and 10 μg As/m(3) iAs exposure, respectively.

Objective: To examine cross-sectionally whether intraabdominal fat area (IAFA), i.e., visceral fat, and liver fat assessed by computed tomography (CT) are independently associated with hyperuricemia., Methods: Subjects were 801 Japanese men not taking antidiabetic, antihypertensive, or urate-lowering medications, without any history of renal disease, cardiovascular disease, or cancer, and with serum creatinine <1.5 mg/dl. Abdominal, thoracic, and thigh fat areas were measured by CT. Total fat area (TFA) was the sum of these fat areas. Total subcutaneous fat area (TSFA) was TFA minus IAFA. Liver fat was assessed by liver-to-spleen (L/S) ratio measured by CT. Hyperuricemia was defined as serum uric acid level >7.0 mg/dl. Its association with adiposity was tested using logistic regression., Results: The prevalence of hyperuricemia was 19.6% (157 men). Both greater IAFA and lower L/S ratio were independently associated with hyperuricemia in models that simultaneously included IAFA and L/S ratio: multiple-adjusted odds ratios of hyperuricemia for quintiles 3, 4, and 5 of IAFA were 2.16 (95% confidence interval [95% CI] 1.02-4.59), 2.41 (95% CI 1.13-5.16), and 4.00 (95% CI 1.81-8.85), respectively, compared to quintile 1, and the L/S ratios for quintiles 3, 2, and 1 were 2.34 (95% CI 1.16-4.75), 2.15 (95% CI 1.06-4.34), and 2.79 (95% CI 1.35-5.76), respectively, compared to quintile 5. Both IAFA and L/S ratio remained significant even after adjusting for abdominal subcutaneous fat area, TFA, TSFA, body mass index, or waist circumference. Of all fat measurements, IAFA had the strongest association with hyperuricemia by Akaike's information criteria., Conclusion: Greater amounts of both visceral fat and liver fat were independently associated with hyperuricemia., (© 2016, American College of Rheumatology.)

Objectives: Arsine is an arsenic compound generated as a by-product in metal refineries. Accidental poisoning occurs sporadically; however, the administrative level for workers has not been established. Thus, it is essential to identify a highly specific biomarker for risk management in the workplace. The aim of this study was to identify an arsenic adduct, a potential biomarker, in the plasma., Methods: Preserved mouse blood was exposed to arsine in vitro, and the plasma was separated. The residual clot of the control sample was hemolyzed using ultrapure water, and the supernatant was collected. Plasma from mice exposed to arsine in vivo was also separated from blood. Immunoprecipitation assays were conducted using all samples after ultrafiltration, and three fractions were collected. The total arsenic concentration in each fraction was quantified using inductively coupled plasma mass spectrometry (ICP-MS). The three in vitro samples and the eluate fraction from immunoprecipitation were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS)., Results: In the exposed samples, the arsenic concentration in the fraction containing immunocomplexes was higher when immunoprecipitation was conducted with an anti-globin antibody. Three peaks were specifically observed in arsine-exposed samples after MALDI-TOF-MS analysis. Two of them were around m/z 15,000, and the other was m/z 15,700. The latter peak was confirmed even after immunoprecipitation., Conclusions: Globin forms an adduct with arsenic after both in vitro and in vivo exposure to arsine. This adduct together with hemoglobinuria could be a candidate biomarker of acute arsine poisoning in plasma.

Objective: This study aimed to identify the chemicals used by five printing workers and one coating worker who developed cholangiocarcinoma and estimate the workers' levels of chemical exposure., Methods: We obtained information on chemicals from the Ministry of Health, Labour and Welfare, Japan, and estimated working environment concentrations of the chemicals in printing and coating rooms and exposure concentrations during the ink and dirt removal processes. We also calculated shift time-weighted averages of exposure concentrations., Results: All five printing workers were exposed to both 1,2-dichloropropane (1,2-DCP) and dichloromethane (DCM). The estimated maximum exposure concentrations for each of the five workers were 190 to 560 ppm for 1,2-DCP and 300 to 980 ppm for DCM, and the estimated shift average exposure concentrations were 0 to 230 ppm for 1,2-DCP and 20 to 470 ppm for DCM. The coating worker was exposed to 1,2-DCP, but not DCM. He did not use ink, and thus was subjected to different conditions than the printing workers. The estimated maximum exposure concentration of 1,2-DCP was 150 ppm, and the estimated shift time-weighted average exposure concentration was 5 to 19 ppm., Conclusions: Our findings support the notion that 1,2-DCP contributes to the development of cholangiocarcinoma in humans and the notion that DCM may also be a contributing factor. The finding that the coating worker was exposed to 1,2-DCP at a lower exposure concentration is important for determining the occupational exposure limit. Furthermore, the subject did not use ink, which suggests that ink did not contribute to the development of cholangiocarcinoma.