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Poly(2-methoxyethyl acrylate) (PMEA) and poly(ethylene oxide) (PEO) have protein-antifouling properties and blood compatibility. ABA triblock copolymers (PMEA l -PEO 11340 -PMEA m (MEOM n ; n is average value of l and m )) were prepared using single-electron transfer-living radical polymerization (SET-LRP) using a bifunctional PEO macroinitiator. Two types of MEOM n composed of PMEA blocks with degrees of polymerization (DP = n ) of 85 and 777 were prepared using the same PEO macroinitiator. MEOM n formed flower micelles with a hydrophobic PMEA (A) core and hydrophilic PEO (B) loop shells in diluted water with a similar appearance to petals. The hydrodynamic radii of MEOM 85 and MEOM 777 were 151 and 108 nm, respectively. The PMEA block with a large DP formed a tightly packed core. The aggregation number ( N agg ) of the PMEA block in a single flower micelle for MEOM 85 and MEOM 777 was 156 and 164, respectively, which were estimated using a light scattering technique. The critical micelle concentrations (CMCs) for MEOM 85 and MEOM 777 were 0.01 and 0.002 g/L, respectively, as determined by the light scattering intensity and fluorescence probe techniques. The size, N agg , and CMC for MEOM 85 and MEOM 777 were almost the same independent of hydrophobic DP of the PMEA block.

Objectives: Since carbonized clots and tissue (debris) tend to adhere firmly to the tip of the endoscopic submucosal dissection (ESD) knife as the procedure proceeds, manual removing the firm debris is often challenging and time-consuming. Recently, effective ultrasonic cleaning for other medical devices has been reported. The aim of the present study was to clarify whether ultrasonic cleaning is effective in removing the debris on the insulation-tipped diathermic (IT) knife-2., Methods: This study was an ex-vivo experimental randomized study. A total of 40 IT knife-2 knives with debris on their tip surfaces were prepared and randomly assigned to two groups (Group A and Group B). The knives in Group A were cleaned using the conventional scrubbing method for 30 s (conventional cleaning method), while those in Group B were cleaned using a combined method of scrubbing for 20 s and ultrasonic cleaning for 10 s (combined ultrasonic cleaning method). The tip electrode of the knife after cleaning was photographed under a microscope (40x). The 40 images of the knives were evaluated by independent three endoscopists and two clinical engineers using the five-step evaluation criteria ranging from cleaning score 1 (dirty) to 5 (clean)., Results: The mean cleaning score of 3.78 (range: 2.33-4.67) in Group B was significantly higher than that of 1.68 (range: 1.00-2.83) in Group A., Conclusions: The combined ultrasonic cleaning method could remove debris adhering to the IT knife-2 more effectively than the conventional cleaning method. Ultrasonic cleaning may be applied for real-world ESD., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: Endoscopic submucosal dissection (ESD) is widely accepted as a local treatment for gastrointestinal tract tumors. As a simplified endoscopic procedure, hybrid ESD (H-ESD) has been performed for colorectal neoplasms in recent times. However, whether H-ESD is superior to conventional ESD (C-ESD) for patients with early gastric neoplasms (EGN) remains unclear. In this trial, we will compare the treatment outcomes of H-ESD and C-ESD. We hypothesize that the procedure time for H-ESD is shorter than that for C-ESD., Methods: This is an investigator-initiated, multi-center, prospective, randomized, open-label, parallel-group trial to be conducted beginning in August 2020 at nine institutions in Japan. We will determine if H-ESD is superior to C-ESD in terms of procedure time in patients with EGN diagnosed as macroscopically intramucosal (T1a) differentiated carcinoma ≤ 20 mm in diameter without ulcerative findings according to current Japanese gastric cancer treatment guidelines. A total of 82 patients will be recruited and randomly assigned to either the C-ESD or the H-ESD group. The primary outcome is ESD procedure time. Secondary outcomes include mucosal incision, time and speed of submucosal dissection, en bloc resection, complete resection, curability, adverse events related to the ESD procedure, extent of dissection before snaring, volume of injection solution, number and time of hemostasis, thickness of the submucosal layer in the resected specimen, and handover to another operator. The stated sample size was determined based on the primary outcome. According to a previous report comparing the procedure times of C-ESD and H-ESD, we hypothesized that H-ESD would provide a 0.2 reduction in logarithmically concerted procedure time (-37%). We estimated that a total of 82 participants were needed to reach a power of 80% for a t-test with a significance level of 0.05 and considering a 10% dropout., Discussion: This trial will provide high-quality data on the benefits and risks of H-ESD for EGN patients. The results of this study could lead to improved outcomes in patients with EGN undergoing ESD. The results will be presented at national and international meetings and published in peer-reviewed journals., Trial Registration: UMIN-CTR UMIN000041244 . Registered on July 29, 2020., (© 2022. The Author(s).)

Despite improvements in diagnosis and treatment, the 5-year survival of oral squamous cell carcinoma (OSCC), no matter the location, remains low, averaging 50%. Telomerase is expressed in 85% of malignancies and may play an important role in human carcinogenesis. Its catalytic component is human telomerase reverse transcriptase (hTERT), which has been thought, but not proven, to be involved in survival with OSCC. We investigated whether hTERT protein was a prognostic factor in OSCC by evaluating its association with clinicopathologic findings and OSCC survival. We found that in comparison to patients with high hTERT expression, patients with low hTERT expression survived significantly longer, including a longer 5-year overall survival. In addition, overall survival was significantly correlated to hTERT expression and the histologic grade and N status of the tumor. Disease-free survival was significantly related to hTERT expression, the histologic grade and N status of the tumor, and mode of invasion. These results suggest that hTERT protein is involved in cervical lymph node metastasis, that its levels may be increased during carcinogenesis, and that it may influence tumor invasion. We believe that this study is the first to demonstrate that OSCC with high hTERT expression carries a worse prognosis than cases with low hTERT expression., Competing Interests: None., (IJCEP Copyright © 2022.)

An improved method is described for the determination of methylmercury (MeHg) in human hair that is based on thin-layer chromatography and thermal decomposition gold amalgamation atomic absorption spectrophotometry. The dithizone extraction and application procedure of this technique were optimized, thus improving its sensitivity and robustness and enabling the use of less toxic solvents than other approaches. The limit of detection was 0.18 ng MeHg (as Hg), corresponding to 0.018 mg MeHg kg -1 of hair relative to a 10 mg sample. This method is appropriate for detecting MeHg in hair at the approximate reference dose level established by the United States Environmental Protection Agency., (© 2022. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the approach to patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). This study retrospectively analyzed patients treated with commercially available tisagenlecleucel at our hospital and evaluated its safety and effectiveness. Of the 21 patients evaluated, any grade and grade ≥3 cytokine release syndrome (CRS) occurred in 85.7% and 9.5% of the patients, respectively. A total of 66.7% received tocilizumab and 28.6% received glucocorticoids for the treatment of CRS. The complete response (CR) rate at 3 months was 61.9% (95% confidence interval [CI] 38.4-81.9). After a median follow-up of 6.3 months following CAR-T infusion, the progression-free survival (PFS) and overall survival rates at 6 months were 53.1% (95%CI 28.3-72.7) and 69.2% (95%CI 43.7-84.9), respectively. Severe cytopenia and hypogammaglobulinemia occurred frequently following CAR-T infusion. Eight patients (38.1%) had comorbidities that would have made them ineligible for leukapheresis in the JULIET trial. However, the presence of comorbidities at the time of leukapheresis had no significant effect on the rates of CR, PFS, and adverse events. Tisagenlecleucel for r/r DLBCL in the real-world setting showed high efficacy and manageable safety profile comparable with the pivotal trial.

The first highly diastereoselective synthesis of β-anomers of 4'-thionucleosides has been carried out by means of electrophilic glycosidation utilizing 3,5-O-(di-tertbutylsilylene) (DTBS)-4-thiofuranoid glycal as a glycosyl donor. The resulting glycosides were transformed into ribo-, 2'-deoxy-, and arabinofuranosyl nucleosides through a chemical transformation of the 2'-substituent. The additive Pummerer reaction of the glycal Soxide gave 1,2-di-O-acetyl-3,5-O-DTBS-4-thioribofuranose. The utility of the DTBSprotected 4-thioribofuranose has been demonstrated by the preparation of 4'-thio analogues of pyrimidine- and purine-4'-thioribonucleosides based on the Vorbrüggen glycosidation. Synthesis of 4'-thio-counterpart of C-nucleoside antibiotic tiazofurin has also been carried out. α-Face selective hydroboration of 1-C-aryl- or 1-C-heteroaryl-glycals obtained by cross-coupling of 1-tributylstannylglycal has furnished the respective β- anomer of 4'-thio-C-ribonucleosides, including 4'-thio analogue of nucleoside antibiotic pseudouridine and 9-deazaadenosine. On the basis of lithiation chemistry, 1-C- and 2-Ccarbon- carbon-substituted 3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3- diyl) (TIPDS)- 4- thiofuranoid glycal were synthesized. These glycals enabled us to prepare 1'-C- and 2'-β- C-carbon-substituted 2'-deoxy-4'-thionucleosides, including thio-counterpart of antitumor nucleoside antibiotic angustmycin C. Furthermore, 1'-C-methyl-4'-thiothymidine emerged as a potent inhibitor of angiogenesis. In addition, 1'-C-methyl-4'-thiothymidine exhibited more potent inhibitory activity against thymidine kinase-deficient mutant of herpes virus than that of ganciclovir. Among the 4'-substituted 4'-thiothymidines, the 4'- C-cyano- and 4'-C-ethynyl derivatives inhibited replication of HIV variant resistant to 3TC (HIVM184V) as potently as HIV-1IIIB. In terms of the value of selectivity index (SI), 4'-C-cyano-4'-thiothymidine showed a 3-fold selective index (SI) than that of the corresponding thymidine derivative. Furthermore, 4'-C-ethynyl-2'-deoxy-4'-thioguanosine has a 20-fold better value (>18,200) than that of 2'-deoxyguanosine counterpart (933). Furthermore, 4'-azido-4'-thiothymidine emerged as a selective and potent anti-EBV agent. In terms of antineoplastic activity, 4'-azido- and 4'-C-fluoromethyl-2'-deoxy-4'-thiocytidine inhibited proliferation of human B-cell (CCRF-SB) and T-cell leukemia (Molt-4) cell lines, although the parent compound 2'-deoxy-4'-thiocytidine did not exhibit any cytotoxicity up to 100 μM. These facts concerning the biological activities suggested that replacement of the furanose oxygen with a sulfur atom is a promising approach for the development of less toxic antiviral and antineoplastic nucleoside antimetabolites. 4'- Thionucleoside also acts as a monomer for oligonucleotides (ONs) therapeutics, exhibiting superior biological properties. Therefore, this review provides a wide range of potential monomers for antisense ON and siRNA., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A 35-year-old man was admitted to our department for loss of consciousness. CT and MRI revealed diffuse enhancement of the subarachnoid space surrounding the brainstem and the cerebellar sulci, without any parenchymal lesions in the brain or the spinal cord. Furthermore, gadolinium-enhanced MRI revealed a nodular lesion with heterogeneous enhancement in the right prepontine cistern, at the site from which a biopsy was obtained via right lateral suboccipital craniotomy on the day following admission. Histopathological examination of the resected specimen revealed glioblastoma multiforme. Based on the radiological and histopathological findings, the patient was diagnosed with primary leptomeningeal gliomatosis (PLG). The patient received temozolomide chemotherapy with concurrent radiotherapy and showed radiological remission, 12 months after diagnosis. However, he developed local recurrence 6 months later and died 23 months after diagnosis. Autopsy findings showed tumor cell infiltration of the leptomeninges, as well as the brain and spinal parenchyma. PLG should be considered in the differential diagnosis in patients with diffuse leptomeningeal enhancement even without parenchymal lesions on radiological imaging. A surgical biopsy is recommended for prompt and accurate diagnosis in such cases.

Marine animals, plants or bacteria are a source of bioactive naturally-occurring halogenated compounds (NHCs) such as bromophenols (BPs), bromoanisoles (BAs) and hydroxylated or methoxylated analogues of polybrominated diphenyl ethers (HO-PBDEs, MeO-PBDEs) and bromobiphenyls (HO-BBs, MeO-BBs). This study applied a comprehensive screening approach using liquid chromatography high-resolution mass spectrometry and combining target, suspect and non-target screening with the aim to identify new hydroxylated NHCs which might be missed by commonly applied gas chromatographic methods. 24 alga samples, 4 sea sponge samples and 7 samples of other invertebrates were screened. Target screening was based on 19 available reference standards of BPs, (di)OH-BDEs and diOH-BBs and yielded seven unequivocally identified compounds. 6-OH-BDE47 was the most frequently detected compound with a detection frequency of 31%. Suspect screening yielded two additional compounds identified in alga samples as well as 17 and 8 compounds identified in sea sponge samples of Lamellodysidea sp. and Callyspongia sp., respectively. The suspect screening results presented here confirmed the findings of previous studies conducted on sea sponge samples of Lamellodysidea sp. and Callyspongia sp. Additionally, in Lamellodysidea sp. and Callyspongia sp. 13 and 4 newly identified NHCs are reported including heptabrominated diOH-BDE, monochlorinated pentabrominated diOH-BDE, hexabrominated OH-MeO-BDE and others. Non-target screening allowed the identification of 31 and 20 polyhalogenated compounds in Lamellodysidea sp. and Callyspongia sp. samples, respectively. Based on the obtained fragmentation spectra, polybrominated dihydroxylated diphenoxybenzenes (diOH-PBDPBs), such as hepta-, octa- and nonabrominated diOH-BDPBs, could be identified in both species. To our knowledge, this study is the first report on the environmental presence of OH-PBDPBs., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Fraction flow reserve (FFR) derived from computed tomography (FFR CT ) has been proposed to be an effective gatekeeper for invasive angiographic referral. The purpose of the present study is to examine the real-world diagnostic performance of FFR CT and myocardial perfusion imaging as well as to assess the utility of FFR CT as a gatekeeper for invasive coronary angiography in patients suspected of having obstructive coronary artery disease. Total of 146 consecutive patients underwent both single-photon emission computed tomography (SPECT) and invasive FFR were evaluated. An FFR CT value 1 to 2 cm distal to a stenosis ≤0.80 was defined as positive for ischemia and a summed stress score ≥2 or transient ischemic dilatation ≥1.2 were positive for ischemia with the invasive FFR value of <0.80 serving as the gold standard. The patient-based sensitivity of FFR CT was significantly higher than SPECT (91 vs 52%, p <0.001) and exhibited similar positive predictive value (82 vs 82%, p = 0.91). These trends were observed even in patients with multivessel and left main trunk disease and those with severe coronary calcification. In conclusion, our data suggest that FFR CT has higher diagnostic performance characteristics than SPECT and details the superior FFR CT analysis in detecting patients with hemodynamically significant coronary artery disease. Our results support the clinical utility of FFR CT analysis as a gatekeeper for invasive coronary angiography in clinical practice., Competing Interests: Disclosures All authors have no conflict of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Rationale: Chimeric antigen receptor (CAR) T-cell therapy is effective in treating relapsed and refractory B-cell non-Hodgkin lymphoma. However, because of the mortality risk associated with immune effector cell-associated neurotoxicity syndrome and pseudoprogression, patients with central nervous system (CNS) involvement are less likely to receive CAR T-cell therapy., Patients Concerns: We report a case of a 61-year-old, male patient with intravascular large B-cell lymphoma who suffered a CNS relapse after standard chemotherapy., Diagnosis: A diagnosis of intravascular large B-cell lymphoma with CNS involvement was made., Interventions: We treated the patient using CAR T-cell therapy following a conditioning regimen consisting of thiotepa and busulfan and autologous stem cell transplantation. Although he experienced grade 1 cytokine release syndrome, no other serious adverse events, such as immune effector cell-associated neurotoxicity syndrome or pseudoprogression, were observed., Outcomes: The patient achieved complete remission after the CAR T-cell infusion., Lessons: CAR T-cell therapy following autologous stem cell transplantation is a viable option for relapsed/refractory lymphoma with CNS infiltration. Further clinical studies are warranted to verify its safety and efficacy., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To report the 3-year results of Innova™ stent implantation for the treatment of femoropopliteal (FP) lesions in a real-world setting., Methods: This single-arm, retrospective, multicenter clinical study analyzed 481 lesions from 453 consecutive patients with symptomatic peripheral artery diseases (Rutherford category 1-6) who underwent endovascular therapy with implantation of Innova™ self-expanding nitinol stent for FP lesions. The primary outcome measure was the 3-year restenosis rate based on doppler-ultrasound or angiographic criteria. The secondary outcome measures included the rates of 3-year major amputation and major adverse limb events., Results: Restenosis following Innova™ implantation was found in 61% of the cases at 3 years. At the end of 3 years, the rates of major amputations and major adverse limb events were 3 and 31%, respectively. In cases free from restenosis at 1 year, no predictive factors for restenosis at 3 years could be determined., Conclusion: The present study demonstrated mid-term clinical outcomes after Innova™ stent implantation for the treatment of FP lesions in a real-world population. The Innova™ stent demonstrated acceptable clinical outcomes in a real-world setting., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Background: The optimal site for measuring computed tomography (CT)-derived fractional flow reserve (FFR CT ) to detect significant coronary artery disease (CAD) remains unknown. We investigated how diagnostic performance changes with FFR CT measurement site. Methods and Results: The diagnostic performance of FFR CT , measured 1-2 cm distal to the stenosis vs. a far-distal site, in detecting significant CAD with invasive fractional flow reserve ≤0.8 was evaluated in 254 diseased vessels from 146 patients with stable or suspected CAD diagnosed by coronary CT angiography. Receiver operating characteristic curve analysis revealed a significantly larger area under the curve for FFR CT measured 1-2 cm distal to the stenosis than at a far-distal site (0.829 vs. 0.791, respectively; P=0.0305). The rate of reclassification of positive FFR CT was 19% for measurements made 1-2 cm distal to the stenosis, and diagnostic accuracy for FFR CT 0.71-0.80 improved from 36% to 58% (P=0.0052). Vessel-based diagnostic accuracy of FFR CT 1-2 cm distal to the stenosis and at a far-distal site was 75% and 65%, respectively (P<0.0001), with corresponding sensitivity of 87% and 94% (P=0.0039), specificity of 60% and 29% (P<0.0001), a positive predictive value of 73% and 62% (P=0.028), and a negative predictive value of 78% and 79% (P=0.958). Conclusions: Our data suggest measuring FFR CT 1-2 cm distal to the stenosis has better diagnostic performance for detecting physiologically significant CAD., Competing Interests: All authors have no conflicts of interest to disclose., (Copyright © 2021, THE JAPANESE CIRCULATION SOCIETY.)

Verapamil-sensitive atrial tachycardia originating from the atrioventricular node vicinity (AVN-AT) can be eliminated with radiofrequency energy (RF) deliveries targeting either the entrance or exit of its reentry circuit. However, the outcome of these different approaches has not been clarified well. Thus, we compared the catheter ablation outcome targeting the entrance of reentry circuit, identified by the entrainment method (Ent-Group; 21 patients) with that targeting the earliest atrial activation site (EAAS) during AT (Exit-Group; 16 patients). There was no significant difference in the tachycardia cycle length (441.4 ± 87.4 vs. 392.8 ± 64.8 ms, p = 0.0704) or distance from the His bundle (HB) site to the EAAS (6.5 ± 2.0 vs. 7.6 ± 1.8 mm, p = 0.0822) between the Ent- and Exit-Groups. However, distance from the successful ablation site to the HB site in the Ent-Group was significantly longer than that in the Exit-Group (13.4 ± 3.1 vs. 7.6 ± 1.8 mm, p < 0.0001), resulting in more frequent transient atrioventricular block episodes in the Exit-Group than Ent-Group (31.3 vs. 0%, p < 0.01). Initial ATs (AT1s) were terminated in all patients in both Groups. However, ATs accompanied by shifting in the EAAS (AT2) were induced more frequently in the Exit-Group than Ent-Group (50.0 vs. 14.3%, p < 0.02) after eliminating AT1. RF deliveries to the EAAS eliminated all AT2s. The number of RF deliveries was greater in the Exit-Group than Ent-Group (6.9 ± 3.3 vs. 3.9 ± 1.6, p < 0.001). In conclusion, RF ablation targeting the entrance sites can avoid AVN injury and is superior in reducing the number of RF deliveries and occurrence of different ATs than targeting the exit sites in the AVN-AT.

Background: Hybrid endoscopic submucosal dissection (ESD) that comprises mucosal incision and partial submucosal dissection followed by snaring in a planned manner, has been developed for endoscopic resection of gastrointestinal neoplasms to overcome the technical barrier of ESD. Although the superiority of hybrid ESD with SOUTEN, a single multifunctional device, over conventional ESD has been indicated, the actual effect of snaring itself remains unclear since SOUTEN could be applied to hybrid ESD group, but not to the conventional ESD group, due to ethical issue in clinical practice., Aim: To determine whether and how hybrid ESD was superior to conventional ESD in the endoscopic treatment of gastric lesions in an ex vivo porcine model basic study., Methods: Sixteen endoscopists participated in this basic study in August 2020 at Kyushu University, performing 32 procedures each for hybrid ESD and conventional ESD. Mock lesions (10-15 mm, diameter) were created in the porcine stomach. The primary outcome was total procedure time and secondary outcomes were en bloc or complete resection, perforation, procedure time/speed for both, mucosal incision, and submucosal dissection. Factors associated with difficulty in ESD including longer procedure time, incomplete resection, and perforation, were also investigated. Categorical and continuous data were analyzed using the chi-square test or Fisher's exact test and the Mann-Whitney U test, respectively., Results: The median total procedure time of hybrid ESD was significantly shorter than that of conventional ESD (median: 8.3 min vs 16.2 min, P < 0.001). Time, speed, and the amount of hyaluronic acid during submucosal dissection were more favorable in hybrid ESD than conventional ESD (time, 5.2 min vs 10.4 min, P < 0.001; speed, 43.7 mm 2 /min vs 23.8 mm 2 /min, P < 0.00; injection volume, 1.5 mL vs 3.0 mL, P < 0.001), although no significant differences in those factors were observed between both groups during mucosal incision. There was also no significant difference between both groups in the en bloc /complete resection rate and perforation rate (complete resection, 93.8% vs 87.5%, P = 0.67; perforation, 0% vs 3.1%, P = 1). Selection of conventional ESD as the treatment method was significantly associated with difficulties during ESD (odds ratio = 10.2; highest among factors)., Conclusion: Hybrid ESD with SOUTEN improves the treatment outcomes of gastric lesions. It also has the potential to reduce medical costs since SOUTEN is a single multifunctional device that is inexpensive., Competing Interests: Conflict-of-interest statement: Eikichi Ihara participated in the funded research of Takeda Pharmaceutical Co., Ltd. and belongs to the endowed course supported by the companies mentioned, including Ono Pharmaceutical Co., Ltd., Miyarisan Pharmaceutical Co. Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Otsuka Pharmaceutical Factory, Inc., Fujifilm Medical Co., Ltd., Termo Corporation, Fancl Corporation, and Ohga Pharmacy. Eikichi Ihara received a lecture fee from Takeda Pharmaceutical Co. Yoshihiro Ogawa is conducting a joint study with Fancl Corporation and Fujifilm Medical Co., Ltd. Other authors have no conflicts of interest or financial ties to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Fetuses are a high-risk group for methylmercury (MeHg) exposure. The main objective of this study was to compare the characteristic profiles of total mercury (THg), inorganic mercury (IHg), MeHg, and selenium in plasma and red blood cells (RBCs) between maternal and cord blood at parturition collected from a group of Japanese women. Furthermore, correlations of THg in RBCs, which is a biomarker of MeHg, and THg in plasma, which is an IHg exposure biomarker, were examined in maternal and cord blood. Fifty-five pairs of maternal and cord blood samples obtained at parturition were collected from pregnant women in Fukuoka, Japan. THg in RBCs and plasma were significant correlated between maternal and cord blood. THg in RBCs was 13.9 ng/mL for cord and 9.16 ng/mL for maternal blood, with a cord:maternal RBCs ratio for THg of 1.58, suggesting that MeHg is actively transferred from the mother to the fetus via the placenta. THg in plasma showed a positive correlation with THg in RBCs for maternal and cord blood. This result suggests that measuring THg in plasma can overestimate the exposure level to IHg in fish-eating populations. The percentages of IHg in cord plasma and RBCs were 31% and 1.7%, respectively, and those in maternal plasma and RBCs were 46% and 5.9%, respectively. These results suggest that cord blood is rich in MeHg and can easily transfer to the fetal brain. Selenium in cord plasma was 67 ng/mL and that in maternal plasma was 97 ng/mL, with a cord:maternal plasma ratio for Se of 0.69, suggesting that the protective effects of Se against MeHg toxicity in fetuses may be weaker than those expected in adult mothers., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The widespread occurrence of persistent organic pollutants (POPs) in the environment is a matter of concern. In this study, selected organohalogenated contaminants, including dichlorodiphenyltrichloroethane and its metabolites (DDTs) polychlorinated biphenyls (PCBs), chlordanes (CHLs), hexachlorobenzene (HCB), polybrominated diphenyl ethers (PBDEs), hexabromocyclododecanes (HBCDs), tetrabromobisphenol A (TBBPA), 2,4,6-tribromophenol (TBP), were measured in complete meal sets (24-h duplicate-diet) of Japanese infants to investigate the levels, profiles, and possible sources of contamination. In total, 46 whole-day meals of infants (7-24-months old) were collected during 2017 from Fukuoka, Japan. To the best of our knowledge, this is the first report based on the duplicate-diet method for infants. The median intakes among the POP groups were highest for ΣDDTs (18 ng/day, maximum 251 ng/day), followed by ΣPCBs (17 ng/day, maximum 198 ng/day), ΣCHLs (14 ng/day, maximum 105 ng/day), HCB (11 ng/day, maximum 64 ng/day), TBP (3.5 ng/day, maximum 109 ng/day), ΣHBCDs (1.9 ng/day, maximum 70 ng/day), TBBPA (0.72 ng/day, maximum 34 ng/day), and ΣPBDEs (0.11 ng/day, maximum 4.5 ng/day). Among the PCBs, PCB-138 and PCB-153 were the most abundant congeners (27% and 23%, respectively). p,p'-DDE, the major DDT metabolite, accounted for 96% of total DDTs. Among PBDEs, BDE47 was the only detected congener (present in 4% of the samples). The dietary intake of the targeted compounds was lower than the intake via breast milk, suggesting that the exposure from baby food was limited. In the principal component analysis, chlorinated and brominated compounds were separated on principal component 1, while TBP and α-HBCD were separated on principal component 2, likely suggesting a differing emission time trend or source. PCB-153, PCB-138, trans-chlordane, cis-chlordane, and trans-nonachlor were correlated with seafood consumption (Spearman's ρ = 0.45 to 0.57, p < 0.05), while TBP was correlated with seaweed consumption (Spearman's ρ = 0.46, p < 0.05). Also, four species of commercial edible seaweed in Japan were analyzed to confirm the findings of the duplicate-diet study. The relatively high concentration of TBP (5.5 ± 6.6 ng/g wet weight) was observed in the seaweed samples, indicating that seaweed is a potential exposure source of TBP., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A novel framework for inverse quantitative structure-activity relationships (inverse QSAR) has recently been proposed and developed using both artificial neural networks and mixed integer linear programming. However, classes of chemical graphs treated by the framework are limited. In order to deal with an arbitrary graph in the framework, we introduce a new model, called a two-layered model, and develop a corresponding method. In this model, each chemical graph is regarded as two parts: the exterior and the interior. The exterior consists of maximal acyclic induced subgraphs with bounded height, the interior is the connected subgraph obtained by ignoring the exterior, and the feature vector consists of the frequency of adjacent atom pairs in the interior and the frequency of chemical acyclic graphs in the exterior. Our method is more flexible than the existing method in the sense that any type of graphs can be inferred. We compared the proposed method with an existing method using several data sets obtained from PubChem database. The new method could infer more general chemical graphs with up to 50 non-hydrogen atoms. The proposed inverse QSAR method can be applied to the inference of more general chemical graphs than before.

Objectives: We evaluated the relationships between depth of invasion (DOI) of tongue cancer, as measured with preoperative T1- and T2-weighted magnetic resonance imaging (MRI) and postoperative histopathologic (Path) specimens, with cervical lymph node metastasis (CLNM) and tumor stage. We also calculated the correlation of MRI and Path DOI measurements., Study Design: This retrospective study included 101 patients who had squamous cell carcinoma of the tongue and were treated surgically. Two observers measured DOI on all 3 modalities., Results: DOI thresholds for predicting CLNM with high diagnostic efficacy were 6.99 mm and 8.32 mm for MRI and 5 mm for Path. DOI values from all modalities were significantly different for tumors with and without CLNM (P < .01) and for the 4 TNM stages (P ≤ .05), with increasing values corresponding to advancement in tumor stage. Addition of DOI changed the T level of many tumors based on the new TNM (tumor-node-metastasis) classification. The correlation coefficient between DOI calculated on each MRI sequence and Path was 0.90., Conclusions: MRI-derived DOI accurately reflected the subsequent metastatic status and degree of progression of tumor stages, with a strong positive correlation to Path values, and may be considered a predictor of tumor stage and CLNM., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in nonremission acute myeloid leukemia (AML) are dismal [2-year overall survival (OS): 20-30%]. Though several risk classifications have been used, some factors are unavailable until the start of conditioning or transplantation. We analyzed prognostic gene mutations by targeted next-generation sequencing to identify predisposing factors for predicting OS at 1 month before transplantation. We enrolled 120 patients with nonremission AML who underwent first allo-HSCT between 2005 and 2018. Mutations were found in 98 patients; frequently mutated genes were FLT3-ITD, TP53, RUNX1, and WT1. TP53 mutation was detected in 21 patients and was the only predictor of poor OS. Multivariate analysis using Cox regression hazard model revealed primary AML, monosomal karyotype (MK), and TP53 mutation as independent factors for predicting poor OS. Based on these, patients were stratified into three groups. The low-risk group included patients with prior myeloid disorder without MK (n = 26). Among the rest, patients with TP53 mutation were assigned to the high-risk group (n = 19) and the rest into the intermediate-risk group (n = 75). Two-year OS in low-, intermediate-, and high-risk groups differed significantly (50.0%, 24.9%, and 0%, respectively). This suggests that the indication of allo-HSCT should be carefully judged for high-risk patients.

Aim: To compare the low-profile visualized intraluminal support (LVIS or LVIS Jr.) stent, which is a braided microstent, and Enterprise Vascular Reconstructive Device (VRD), which is fabricated using laser cutting technology, in the treatment of internal carotid artery aneurysms., Material and Methods: We investigated 49 unruptured aneurysm cases in which follow-up digital subtraction angiography had been performed. Results of the occlusion were divided into classes 1, 2, and 3 of the Raymond-Roy Occlusion Classification. Statistical significance was defined as p < 0.05., Results: In the 49 aneurysm cases, we achieved class 1 in 23 (47%; LVIS or LVIS Jr., 7; Enterprise, 16; p=0.76), class 2 in 13 (27%; LVIS or LVIS Jr., 5; Enterprise, 8; p=0.74), and class 3 in 13 (27%; LVIS or LVIS Jr., 5; Enterprise, 8; p=0.74). Based on the follow-up imaging of the 49 aneurysms, we achieved class 1 in 32 cases (65%; LVIS or LVIS Jr., 16; Enterprise, 16; p < 0.01), class 2 in 7 (14%; LVIS or LVIS Jr., 0; Enterprise, 7; p < 0.01), and class 3 in 10 (20%; LVIS or LVIS Jr., 1; Enterprise, 9; p=0.13)., Conclusion: Recently, the flow diversion effect of stents has garnered more attention compared to coil embolization. LVIS or LVIS Jr. exerts a higher flow diversion effect than other stents and may improve the Raymond-Roy Occlusion Classification. In the future, the role of stents in the treatment of aneurysms will become more important.

Fractional flow reserve (FFR) has become an increasingly important index for decision making concerning coronary revascularization. It is commonly accepted that significant improvement in FFR following percutaneous coronary intervention (PCI) is associated with better symptomatic relief and a lower event rate. However, in lesions with insufficient FFR improvement, PCI may not improve prognosis. Leading to the observation that the clinical and angiographic characteristics associated with insufficient FFR improvement have not been fully explored. The purpose of this study was to investigate the factors associated with insufficient improvement in FFR. Using our own PCI database, established between January 2014 and December 2018, we identified 220 stable coronary artery lesions, which had been evaluated for both pre- and post-PCI FFR values. All 220 of these lesions were included in this study. The improvement in FFR (ΔFFR) was calculated in each lesion with the lowest quartile of ΔFFR being defined as the lowest ΔFFR group, and the other quartiles being defined as the intermediate-high ΔFFR group. The mean ΔFFR in the lowest and intermediate-high ΔFFR groups was 0.07 ± 0.02 and 0.21 ± 0.11, respectively. In multivariate logistic regression analysis, a short total stent length (10 mm increase: OR 0.67, 95% CI 0.47-0.96, P = 0.030), higher pre-PCI FFR (0.1 increase: OR 4.07, 95% CI 1.83-9.06, P = 0.001), in-stent restenosis (ISR) (OR 8.02, 95% CI 1.26-51.09, P = 0.028), myocardial infarction (MI) in the target vessel (OR 6.87, 95% CI 1.19-39.69, P = 0.031) and non-use of intravascular imaging (OR 0.35, 95% CI 0.12-0.99, P = 0.048) were significantly associated with the lowest ΔFFR group. The use of short stents, higher pre-PCI FFR values, ISR, MI in the target vessel, and non-use of intravascular imaging were significantly associated with insufficient FFR improvement. It was conversely suggested that full coverage and adequate dilatation of the lesions under an intravascular imaging guidance might contribute to an improvement in FFR.

A 23-year-old woman was referred to our hospital with progressive headache and back pain. Cerebrospinal fluid(CSF)analysis revealed hypoglycorrhachia and pleocytosis. However, imaging studies did not reveal evidence of subarachnoid hemorrhage(SAH), and she was diagnosed with bacterial meningitis. CSF analysis repeated after antibiotic treatment continued to show evidence of blood. Spinal SAH was suspected, and MRI revealed a spinal arteriovenous malformation(AVM). Spinal digital subtraction angiography revealed the nidus and a feeder aneurysm, which was implicated as the source of bleeding;therefore, she was diagnosed with spinal SAH secondary to spinal intramedullary AVM(SAVM). She underwent endovascular treatment for the spinal aneurysm and was discharged without worsening neurological symptoms. SAVMs presenting without neurological findings and/or evidence of bleeding on plain CT images are diagnostically challenging;notably, findings on CSF analysis could mimic those observed in cases of infectious disease. We should cite vascular diseases such as SAVM.

Enteroviruses are one of the most important causes of viral encephalitis in the neonatal period. However, the non-specificity of the symptoms presented renders its diagnosis challenging. Intracranial MRI has been reported to be a very useful imaging modality that can detect the characteristic white matter lesions around the periventricular regions. In this study, we report a case of a patient with neonatal encephalitis who presented with normal white blood cell counts in the initial cerebrospinal fluid analysis. A lumbar puncture retap identified pleocytosis, and polymerase chain reaction assays detected enterovirus 71 in the blood and stool samples. Furthermore, MRI revealed atypical disseminated cortical and subcortical white matter lesions on diffusion weighted images, and neuroradiological re-evaluation showed necrotic changes 2 weeks later. This unique case expands our knowledge of the spectrum of neurological disorders due to enterovirus 71 infection in neonatal period.

We performed a detailed investigation of the uptake of sulfobromophthalein (BSP) from the apical membrane of Caco-2 cells, which is a substrate for organic anion transporting polypeptides (OATPs), and calculated the kinetic parameters of BSP uptake as follows: K m  = 13.9 ± 1.3 μM, V max  = 1.15 ± 0.07 nmol (mg protein) -1 (5 min) -1 , and k d  = 38.2 ± 0.53 μL (mg protein) -1 (5 min) -1 . Coincubation with medium-chain (C7-C11) perfluoroalkyl carboxylic acids (PFCAs), such as perfluoroheptanoic acid (PFHpA, C7), perfluorooctanoic acid (PFOA, C8), perfluorononanoic acid (PFNA, C9), perfluorodecanoic acid (PFDA, C10) and perfluoroundecanoic acid (PFUnDA, C11), significantly decreased BSP uptake by 27-55%, while coincubation with short- (C3-C6) and long-chain (C12-C14) PFCAs decreased the uptake only slightly. Dixon plotting suggested that PFOA, PFNA and PFDA competitively inhibited the BSP uptake with inhibition constant (K i ) values of 62.2 ± 1.3 μM, 35.3 ± 0.1 μM and 43.2 ± 0.3 μM, respectively. PFCAs with medium-chains could be substrates for OATPs, probably OATP2B1, which is the most abundantly expressed OATP isoform in Caco-2 cells., Competing Interests: The authors declare that there are no conflicts of interest., (© 2020 The Authors.)

Background: The selection of endoscopic treatments for superficial non-ampullary duodenal epithelial tumors (SNADETs) is controversial., Aim: To compare the efficacy and safety of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for SNADETs., Methods: We retrospectively analyzed the data of patients with SNADETs from a database of endoscopic treatment for SNADETs, which included eight hospitals in Fukuoka, Japan, between April 2001 and October 2017. A total of 142 patients with SNADETs treated with EMR or ESD were analyzed. Propensity score matching was performed to adjust for the differences in the patient characteristics between the two groups. We analyzed the treatment outcomes, including the rates of en bloc /complete resection, procedure time, adverse event rate, hospital stay, and local or metastatic recurrence., Results: Twenty-eight pairs of patients were created. The characteristics of patients between the two groups were similar after matching. The EMR group had a significantly shorter procedure time and hospital stay than those of the ESD group [median procedure time (interquartile range): 6 (3-10.75) min vs 87.5 (68.5-136.5) min, P < 0.001, hospital stay: 8 (6-10.75) d vs 11 (8.25-14.75) d, P = 0.006]. Other outcomes were not significantly different between the two groups ( en bloc resection rate: 82.1% vs 92.9%, P = 0.42; complete resection rate: 71.4% vs 89.3%, P = 0.18; and adverse event rate: 3.6% vs 17.9%, P = 0.19, local recurrence rate: 3.6% vs 0%, P = 1; metastatic recurrence rate: 0% in both). Only one patient in the ESD group underwent emergency surgery owing to intraoperative perforation., Conclusion: EMR has significantly shorter procedure time and hospital stay than ESD, and provides acceptable curability and safety compared to ESD. Accordingly, EMR for SNADETs is associated with lower medical costs., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: Although some authors proposed that coil embolization in middle cerebral artery (MCA) aneurysms is a useful and effective alternative, the characteristics of the aneurysms may be different at each location. We compared the results of coil embolization of proximal middle cerebral artery aneurysms with those of other middle cerebral artery aneurysms., Methods: Data from 46 patients with 50 aneurysms were retrospectively evaluated. We defined the aneurysms inside of the insular cortex as proximal MCA (pMCA) aneurysms and those outside of the insular cortex as non-proximal MCA (npMCA) aneurysms. The results of the occlusion were divided into classes 1, 2, and 3 of the Raymond scale. We collected the results of the occlusion from the operative notes supplied by a neuroendovascular specialist., Results: Univariate analysis identified favorable results for pMCA aneurysms (class 1: pMCA = 22 npMCA = 11; P < 0.01). In the radiological follow-up results, we achieved class 1 in 29 patients (69%; pMCA = 21 and npMCA = 8; P < 0.01). Side wall type aneurysms (pMCA = 14, npMCA = 2; P < 0.01) and the number of branches from the neck of ≤1 (pMCA = 14, npMCA = 2; P < 0.01) were significantly recognized at the pMCA., Conclusions: Proximal middle cerebral artery aneurysm clipping is difficult because the origin of the lenticulostriate arteries is often hidden behind the aneurysmal dome. In the present study, endovascular coil embolization for pMCA aneurysms obtained better results than that for npMCA aneurysms because of the morphological characteristics. Endovascular coil embolization seems to be efficacious for pMCA aneurysms as compared with npMCA aneurysms.

A certified reference material, NIMD-01, was developed for the analysis of mercury speciation in human hair. We collected the hair of Vietnamese males from a barbershop in Hanoi in 2016 and prepared 1200 bottles containing 3 g of sieved and blended hair powder. The certified value was given on a dry-mass basis, with the moisture content obtained by drying at 85°C for 4 h. Certified values with the expanded uncertainties (coverage factor, k = 2) were as follows: methylmercury, 0.634 ± 0.071 mg kg -1 as mercury; total mercury, 0.794 ± 0.050 mg kg -1 ; copper, 12.8 ± 1.4 mg kg -1 ; zinc, 234 ± 29 mg kg -1 ; selenium, 1.52 ± 0.29 mg kg -1 . An indicative arsenic concentration of 0.17 ± 0.03 mg kg -1 was measured. Extended uncertainties were estimated by sample homogeneity, long- and short-term stabilities, and a characterization from measurements made by collaborating laboratories.

[Purpose] In this study, we aimed to determine which typical postures or an arm-supported posture were more comfortable and conducive to respiratory function, during seated defecation. [Participants and Methods] In 73 healthy adults, we measured and compared respiratory function and subjective contentment associated with 3 sitting defecation postures: upright, forward-leaning, and arm-supported forward-leaning. [Results] Vital capacity (VC), forced vital capacity (FVC), maximal expiratory pressure (MEP), and subjective comfort were significantly greater in the arm-supported forward-leaning position than in the other 2 positions. [Conclusion] The arm-supported forward-leaning position for defection increased the VC and was subjectively comfortable. Moreover, the high MEP in this position, compared with the other 2 positions, may have facilitated strain. A detailed examination of the cause for the observed increase in comfort was beyond the scope of this study; therefore, this effect requires further investigation., (2020©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Perfluoroalkyl carboxylic acids (PFCAs), such as perfluorooctanoic acid (PFOA, C8), are a group of industrial chemicals that are detected in the serum of people throughout the world. Long-chain PFCAs (C9 to C13) have high lipophilicity, therefore they may have a high transfer rate to breast milk. This study investigated the lactational transfer of PFCAs with carbon chain lengths of 8 to 13 in mice. Lactating dams were given a single intravenous administration of PFCAs (C8 to C13) during the postnatal period (8-13 days after delivery). Milk was collected from the dam 24 h after administration using a milking device built in-house. Plasma was obtained from the dam at the same time as milk collection. The observed milk/plasma (M/P) concentration ratios were 0.32 for C8, 0.30 for C9, 0.17 for C10, 0.21 for C11, 0.32 for C12, and 0.49 for C13. These results indicate that the M/P concentration ratio is not related to the lipophilicity of PFCAs. However, estimated relative daily intake, an indicator of how much PFCA is transferred from dams to pups per body weight, increased with chain length: 4.16 for C8, 8.98 for C9, 9.35 for C10, 9.51 for C11, 10.20 for C12, and 10.49 for C13, which may be related to the lower clearance of long-chain PFCAs. These results indicate the importance of future risk assessment of long-chain PFCAs.

Background: Gastric subepithelial lesions, including gastrointestinal stromal tumors, are often found during routine gastroscopy. While endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) has been the gold standard for diagnosing gastric subepithelial lesions, alternative open biopsy procedures, such as mucosal incision-assisted biopsy (MIAB) has been reported useful. The aim of this study is to evaluate the efficacy of MIAB for the diagnosis of gastric SELs compared with EUS-FNAB., Methods: We retrospectively analyzed medical records of 177 consecutive patients with gastric SELs who underwent either MIAB or EUS-FNAB at five hospitals in Japan between January 2010 and January 2018. Diagnostic yield, procedural time, and adverse event rates for the two procedures were evaluated before and after propensity-score matching., Results: No major procedure-related adverse events were observed in either group. Both procedures yielded highly-accurate diagnoses once large enough samples were obtained; however, such successful sampling was more often accomplished by MIAB than by EUS-FNAB, especially for small SELs. As a result, MIAB provided better diagnostic yields for SELs smaller than 20-mm diameter. The diagnostic yields of both procedures were comparable for SELs larger than 20-mm diameter; however, MIAB required significantly longer procedural time (approximately 13 min) compared with EUS-FNAB., Conclusions: Although MIAB required longer procedural time, it outperformed EUS-FNAB when diagnosing gastric SELs smaller than 20-mm diameter.

An alternative method for the preparation of 2'-bromo- ( 5b ) and 2'-iodo- ( 5c ) 1',2'-unsaturated uracil nucleosides has been developed. The protocol was on the basis of the syn -elimination of pivalic acid from 2'-bromo-( 7a,b ) and 2'-iodo-( 9a,b ) 1'-pivaloyloxy-2'-deoxyuridine derivatives, which were derived from the halo-pivaloyloxylation of 3',5'-bis- O -TBDMS-1',2'-unsaturated uridine 1 . Compounds 5b and 5c were shown to serve as versatile synthons for the respective 2'- C -branched 1',2'-unsaturated uracil nucleosides, through palladium-catalyzed cross-coupling or halogen-lithium exchange reactions.

Hepatitis B virus (HBV) infection is a major worldwide health problem that requires the development of improved antiviral therapies. Here, a series of 4'-Azido-thymidine/4'-Azido-2'-deoxy-5-methylcytidine derivatives ( 6 , 10-15 ) were synthesized, and their anti-HBV activities evaluated. Compounds 10-15 were synthesized via an S N Ar reaction of 18 , in which the 4-position of the thymine moiety was activated as the 2,4,6-triisopropylbenzenesulfonate. Compounds 11-15 showed no antiviral activity. However, 4'-Azido thymidine ( 6 ) and 4'-Azido-2'-deoxy-5-methylcytidine ( 10 ) displayed significant anti-HBV activity (EC 50 = 0.63 and 5.99  µ M, respectively) with no detectable cytotoxicity against MT-2 cells up to 100  µ M.

Background: Persistent primitive trigeminal artery (PPTA), which is a fetal carotid-basilar anastomosis, is the most common embryologic vascular remnant persisting in adults. Aneurysms can arise between the internal carotid artery (ICA) and PPTA. Here we present a case of ICA-PPTA aneurysm treated with a flow-diverter stent., Case Description: A 52-year-old woman had left abducens nerve palsy. Imaging detected a large left ICA-PPTA aneurysm, which we chose to treat with a flow-diverter stent after embolizing the PPTA with a coil. Although the abducens nerve palsy did not change, there were no signs of cerebral infarction, and no new symptoms appeared postoperatively. Blood flow in the aneurysm had disappeared on digital subtraction angiography after 6 months., Conclusions: This is the first case report of ICA-PPTA aneurysm successfully treated with a flow-diverter stent. We could stop blood flow from the posterior circulation by embolizing the PPTA with a coil, allowing the use of a flow-diverter stent. This report can be used as a reference for the procedure in future work., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The effects of Kanechlor-500 (KC500) on the levels of serum total thyroxine (T 4 ) and hepatic T 4 in wild-type C57BL/6 (WT) and its transthyretin (TTR)-deficient (TTR-null) mice were comparatively examined. Four days after a single intraperitoneal injection with KC500 (100 mg/kg body weight), serum total T 4 levels were significantly decreased in both WT and TTR-null mice. The KC500 pretreatment also promoted serum [ 125 I]T 4 clearance in both strains of mice administrated with [ 125 I]T 4 , and the promotion of serum [ 125 I]T 4 clearance in WT mice occurred without inhibition of the [ 125 I]T 4 -TTR complex formation. Furthermore, the KC500 pretreatment led to significant increases in liver weight, steady-state distribution volume of [ 125 I]T 4 , hepatic accumulation level of [ 125 I]T 4 , and concentration ratio of the liver to serum in both strains of mice. The present findings indicate that the KC500-mediated decrease in serum T 4 level occurs in a TTR-unrelated manner and further suggest that KC500-promoted T 4 accumulation in the liver occurs through the development of liver hypertrophy and the promotion of T 4 transportation from serum to liver., (© 2019 John Wiley & Sons, Ltd.)

A 3-year-old girl was admitted to our hospital with symptoms including headache, nausea, and vomiting. Head CT scan showed subarachnoid hemorrhage in the right carotid cistern. Digital subtraction angiography revealed right internal caortid artery(ICA)malformation at the C1 segment with collateral plexiform arterial network. The right ICA branched into posterior communicating artery and anterior choroidal artery(AChoA)and the ICA was decreased in caliber. The distal portion of the C1 segment of the ICA continued to the collateral plexiform arterial network, forming a saccular aneurysm. The plexiform arterial network connected to the right AChoA and the anterior communicating artery and continued to the distal portion of the right M1 segment. Right cervical carotid artery was normal. There was no transdural collateral flow from the right external carotid artery. Genetic analysis of a variant of RING finger protein 213 was negative. We diagnosed this patient with C1 dysplasia. We performed coil embolization for the aneurysm. The patient was discharged without any neurological deficit. Four months after the surgery, recurrence of the aneurysm was observed. We suspected that the aneurysm was formed due to hemodynamic mechanism and vulnerability of the collateral plexiform arterial network.

Background and Aim: The Japan Narrow-Band Imaging (NBI) Expert Team (JNET) classification is a recently proposed NBI magnifying endoscopy-based classification system for colorectal tumors. Although the usefulness of this system has been reported by JNET experts, its objective validity remains unclear. We tested its validity and usefulness for the diagnosis of colorectal polyps by including colonoscopy experts and non-experts as test participants., Methods: Forty NBI images of polyps of various JNET types were shown to 22 doctors (11 experts and 11 non-gastrointestinal [GI] trainees) who had not examined the patients. The doctors diagnosed the polyps based solely on the surface and vessel patterns in the magnified images and the JNET classification system. Concordance rates of their diagnoses with the pathological findings of the polyps were determined, and the results for experts and non-GI trainees were compared., Results: Both for colonoscopy experts and non-GI trainees, the JNET classification system was particularly useful for classifying polyps as benign or malignant. Although the accuracy rates for classifying polyps into each JNET type varied among colonoscopy experts, those who were familiar with the JNET classification system were able to diagnose polyps with approximately 90% accuracy. Common mistakes were attributable to misunderstandings of the wording in the JNET classification chart and lack of proper training., Conclusion: The JNET classification system is a practical approach for the diagnosis of colorectal polyps. Training is required even for experienced colonoscopists to adopt the system properly. Common pitfalls must be shared among colonoscopists to improve the accuracy of the diagnosis., (© 2019 Japan Gastroenterological Endoscopy Society.)

Background: T helper (Th)- and regulatory T (Treg) cell-related immune molecules are implicated in ulcerative colitis (UC). However, the association between their mucosal expression during remission and the subsequent clinical course of UC is unknown., Methods: The expression of cytokines and transcription factors related to Th1, Th2, Th17, and Treg in endoscopic mucosal biopsy specimens from 40 UC patients in clinical remission and 9 controls was measured by quantitative polymerase chain reaction. The relationship between their expression patterns, as stratified by Mayo Endoscopic Subscore (MES), and any future relapse was evaluated by univariate and multivariate analyses., Results: Six of 40 patients (baseline MES 0/1/2, 22/14/4) experienced a relapse during the study period (median, 37 months). At baseline, even in the MES0 patients, the interleukin (IL)-17A of the patients was significantly upregulated in comparison with controls (P = 0.0351). Future relapse was associated with a higher baseline expression of IL-17A, IL-17F, and IL-21 in MES0/1, and the upregulation of IL-17F and IL-21 remained statistically significant when limited to MES0 patients. Kaplan-Meier analysis revealed that as a single marker, a higher IL-21 level best grouped patients with an increased risk of relapse (P = 0.0042). Furthermore, a multivariate model that consisted of IL-21 and T-bet showed an even greater value (P = 0.0001)., Conclusions: The profiles of Th/Treg-related gene expression in the colonic mucosa are altered, even during clinical and endoscopic remission of UC, with a detectable Th17-predominant profile predicting future relapse. This association might represent latent immune dysregulation during disease quiescence and has the potential to be utilized to improve patient care., (© 2018 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We investigated the profiles and levels of perfluoroalkyl carboxylic acid (PFCA) contamination in Pacific cod (Gadus macrocephalus) from the North Pacific Ocean. The mean concentrations of PFCAs containing 8 to 14 carbon atoms (C8-C14) in edible Pacific cod muscle ranged from 216 to 670 pg g -1 wet weight in the Northeast Pacific Ocean (Seattle, Vancouver, Alaska, and Russia), from 819 to 1710 pg g -1 wet weight in Japanese coastal waters (Hokkaido, Aomori, Iwate, Miyagi, Tottori, and Shimane), and from 288 to 892 pg g -1 wet weight in Korean waters (Sokcho, Busan, and Yeosu). These results indicate there are geographical differences in the distribution of PFCAs. The long-chain PFCAs (C9-C14) contributed 96% of the total PFCA concentration across Japan, whereas they contributed only 33% of the total PFCA concentration in the USA and Canada. Long-chain PFCA concentrations in cod samples collected in Japanese and Korean waters were about three to four times those in samples from the USA, Canada, and Russia. Because seafood is considered an important dietary source of PFCAs, high concentrations of long-chain PFCAs in Pacific cod from Japanese and Korean waters may affect human dietary exposure and blood concentrations of long-chain PFCAs., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Peripheral arterial disease (PAD) has increased in association with the increase in the numbers of patients with kidney disease or diabetes. The aim of this study was to assess the prevalence of PAD in hemodialysis patients with diabetes., Methods: To examine the usefulness of the cardio-ankle vascular index (CAVI) to screen for the presence of PAD, cross-sectional studies of 100 patients undergoing chronic hemodialysis were performed. The CAVI and other inflammatory markers were evaluated., Results: The CAVI was markedly elevated in patients with a history of PAD or cardiovascular disease. When dialysis patients were classified on the basis of CAVI quartiles, increased CAVI was associated with other risk factors for PAD., Conclusion: The prevalence of PAD is high in elderly diabetic patients on hemodialysis. The present findings suggest that the CAVI can be a useful index that predicts the occurrence of macrovascular complications in dialysis patients with diabetes., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Background/aim: Pancreatic ductal adenocarcinoma (PDA) remains one of the most aggressive tumors with a dismally poor prognosis. Although surgical resection remains the only potentially curative treatment, most PDAs are not surgically resectable at diagnosis. Therefore, multimodal therapy is urgently needed to improve the long-term survival of PDA patients., Methods: Six eligible PDA patients underwent multimodal therapy comprising dendritic cells (DCs) pulsed with Wilms' tumor 1 (WT1) peptide (DC/WT1-I) restricted by the human leukocyte antigen (HLA) class I (A*24:02 or A*02:06) allele, chemotherapy, radiation, and/or surgery. Patient laboratory data, DC/WT1-I-specific delayed-type hypersensitivity (DTH) reactions, and WT1-specific immune responses were analyzed to assess the prognostic markers of multimodal therapy., Results: Compared to 2-treatment type combinations, multimodal therapy involving 3 to 4 treatment types was significantly associated with longer overall survival (p = 0.0177). Moreover, after 7 DC/WT1-I vaccinations, the progression-free survival (PFS) of PDA patients with a neutrophil to lymphocyte ratio (NLR) or C-reactive protein (CRP) level less than the median was superior to that of PDA patients with values above the median (p = 0.0246). PDA patients with an overall survival (OS)>1000 days had significantly more lymphocytes after one DC/WT1-I vaccination course than did those with an OS<1000 days., Conclusion: Multimodal therapy involving the DC/WT1-I vaccination may benefit patients with advanced PDA. However, comparing the limited number of PDA patients in terms of survival is difficult because the patients were at different disease stages and received different treatments. Further studies are needed to evaluate the clinical benefits of this multimodal therapy.

A 51-year-old man underwent allogeneic bone marrow transplantation (BMT) for recurrent acute myeloid leukemia. Although the patient developed slight edema, pleural effusion, and cardiac effusion 6 months after BMT, his clinical condition improved with furosemide treatment. The patient was transfused with red blood cells for the management of anemia 8 months after BMT. He developed acute respiratory failure with pulmonary alveolar hemorrhage 80 min after the transfusion. He was diagnosed with transfusion-associated circulatory overload (TACO) due to the presence of acute pulmonary congestion and depressed left ventricular systolic function. Reduced circulatory load due to sufficient furosemide led to ventilator weaning 3 days later. Other causes of pulmonary alveolar hemorrhage were excluded, and the patient's condition improved by cardiac failure treatment only. This clinical course indicated that pulmonary alveolar hemorrhage would breakdown the blood vessels due to acute pulmonary congestion. Chemotherapy and prolonged anemia are high risks for cardiac failure in patients with hematological malignancies. Therefore, the possibility of cardiac failure is considered when patients with hematological malignancies have fluid retention, such as cardiac enlargement, edema, and pleural effusion. Moreover, the body fluids should be monitored before and after blood transfusion.

Synthesis of 3'-halogeno analogues ( 5a - d ) of 9-[ c -4, t -5-bis(hydroxymethyl)-cyclopent-2-en- r -1-yl]-9 H -adenine (BCA, 3 ) was accomplished by means of dual utilization of the vinyl sulfone functional moieties in both 10 and 16 utilizing a S N 2' conjugate-addition reaction and a sulfur-extrusive stannylation, respectively. Evaluation of the antiviral activities of 5a - d revealed that introduction of a halogeno-substituent into the 3'-position of (-)-BCA diminished its anti-HIV-1 activity but increased the inhibitory activity for the reverse transcriptase of HBV in that the 3'-fluorinated BCA 5d exhibited the highest activity without significant cytotoxicity., Competing Interests: The authors declare no competing financial interest.

Levels and profiles of naturally produced halogenated bipyrroles (Br 4 Cl 2 -DBP and Cl 7 -MBP), methoxylated tetrabromodiphenyl ethers (6-MeO-BDE47), anthropogenic perfluoroalkyl substances (PFASs) and legacy persistent organic pollutants (POPs) were investigated in the livers of 14 cetaceans from the Sea of Japan and the North Pacific Ocean. The concentrations of Br 4 Cl 2 -DBP (4 to 4900 ng/g-wet), Cl 7 -MBP (16 to 3960 ng/g-wet) and 6-MeO-BDE47 (7 to 190 ng/g-wet) were higher in the order of killer whales > toothed whales > baleen whales. Profiles of PFASs were dominated by perfluoroundecanoic and perfluorotridecanoic acids (10 to 540 ng/g-wet), sum of which accounted for 70% of total measured PFASs. Regional difference was observed for Cl 7 -MBP and PFASs, which were higher in the Sea of Japan, whereas Br 4 Cl 2 -DBP was in the North Pacific Ocean. Specific accumulation pattern of these natural contaminants in cetaceans around northern Japan could help compare the exposure profile of PFASs and POPs among other geographic regions., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Tubulinopathies include a wide spectrum of disorders ranging from abnormal ocular movement to severe brain malformations, and typically present as diffuse agyria or perisylvian pachygyria with microcephaly, agenesis of the corpus callosum, and cerebellar hypoplasia. They are caused by the dysfunction of tubulins encoded by tubulin-related genes, and the TUBA1A gene encoding alpha-1A tubulin is most frequently responsible for this clinical entity. Porencephaly is relatively rare among patients with the TUBA1A mutations. Mild case of tubulinopathy associated with porencephaly caused by a novel TUBA1A mutation., Case Report: The patient, a 10-month-old girl, presented with gross motor delay at 4 months of age and convulsions at 7 months of age. Brain magnetic resonance imaging showed porencephaly, occipital polymicrogyria, hypoplasia of the corpus callosum, volume loss of the white matter, dysgenesis of anterior limbs of internal capsules, non-separative basal ganglia, cerebellar hypoplasia, and dysplastic brainstem. We identified a novel de novo heterozygous missense mutation in the TUBA1A gene, c.381C > A (p.Asp127Glu), by whole-exome sequencing., Discussion: Microtubules composed of tubulins regulate not only neuronal migration but also cell division or axon guidance. Accordingly, tubulinopathy affects the cortical lamination, brain size, callosal formation, and white matter as seen in the present case. In contrast to the previously reported cases, the present case showed milder cortical dysgenesis with a rare manifestation of porencephaly. The genotype-phenotype correlation is still unclear, and this study expands the phenotypic range of tubulinopathy., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)