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DSA processing is not applied to the coronary artery because heavy artifacts will be generated in DSA images by heart beats and breathing of the patient. However, DSA images of coronary artery contribute to the accuracy of diagnosis and elucidating new pathogenesis of coronary artery diseases. On the other hand, deep learning techniques have been improved and shown to have a high performance. The purpose of this study was to develop a DSA method available for coronary arteries using deep learning techniques.We developed a convolutional neural network (CNN) -based model for this study. A total of 29 cases of coronary angiograms were used. We carried out training of the model using 21025 image patches consisting of pairs after contrast-enhanced images and before contrast-enhanced images. To obtain DSA images, we derived mask images by inputting live images to the trained model. Finally, we obtained DSA images subtracting mask images from live images. We evaluated the proposed method using subjective evaluation, which is based on human observation, and objective evaluation, which is based on standard deviation of the pixel value.The results of both the subjective evaluation and the objective evaluation confirmed the effectiveness of the proposed method in clinical cases.We proposed new DSA techniques for coronary arteries using deep learning. Motion artifacts caused by heart beats and breathing were reduced, and vessel visibility was improved by the proposed DSA. By applying the technique to the area of other organs, DSA study without stopping breathe during X-ray exposure can be realized in clinical situations.

Bisphenol F diglycidyl ether (BFDGE) is widely used in the synthesis process of plastic products. While exposure to Bisphenol A diglycidyl ether (BADGE), which has a similar structure to BFDGE and which is used for the same purpose, has been reported to cause health risks, there is still little information on BFDGE. Because it is estimated that the industrial workers are exposed to large amounts of BFDGE, the health risks associated with BFDGE exposure need to be clarified. We investigated the toxicity of cutaneous exposure to BFDGE using an in vitro evaluation system and an mouse exposure model. The tumorigenic potential of BFDGE was confirmed by the Bhas 42 cell transformation assay, which showed that BFDGE has both promoter and initiator activity, in vitro. A single dermal application of BFDGE was associated with minor contact hypersensitivity symptoms. In contrast, repeated dermal exposure to BFDGE for two weeks induced persistent acute inflammation with features similar to inflammation in human psoriasis. This is the first report evaluating the toxicity of BFDGE in animals, and we showed that BFDGE carries a health risk of inducing skin dermatitis similar to that in human psoriasis in an exposure period-dependent manner. This article is protected by copyright. All rights reserved.

AIMS The tumor budding (TB); poorly differentiated cluster (PDC); desmoplastic reaction (DR); and microcystic, elongated, and fragmented (MELF) patterns of invasion are pathological findings at the tumor invasion front associated with epithelial-to-mesenchymal transition. This study aimed to clarify the clinical significance of the TB, PDC, DR, and MELF patterns in endometrioid endometrial carcinomas (EEC). METHODS Two hundred and eight cases of histologically proven EEC retrieved from the archives of the Department of Pathology, Fukui Prefectural Hospital, and diagnosed between January 2000 and August 2020 were retrospectively analyzed. RESULTS The TB, PDC, DR, and MELF patterns were identified in 29 (13.9%), 47 (22.6%), 45 (21.6%), and 23 (11.1%) cases, respectively. Kaplan-Meier curve analysis with log-rank test demonstrated that TB, PDC, and DR were associated with a lower progression-free survival (p = 0.010, 0.002, and

Although the human papillomavirus (HPV) vaccine is effective for preventing cervical cancers, this vaccine does not eliminate pre-existing infections, and alternative strategies have been warranted. Here, we report that FOXP4 is a new target molecule for differentiation therapy of cervical intraepithelial neoplasia (CIN). An immunohistochemical study showed that FOXP4 was expressed in columnar epithelial, reserve, and immature squamous cells, but not in mature squamous cells of the normal uterine cervix. In contrast with normal mature squamous cells, FOXP4 was expressed in atypical squamous cells in CIN and squamous cell carcinoma lesions. The FOXP4-positive areas significantly increased according to the CIN stages from CIN1 to CIN3. In monolayer cultures, downregulation of FOXP4 attenuated proliferation and induced squamous differentiation in CIN1-derived HPV 16-positive W12 cells via an ELF3-dependent pathway. In organotypic raft cultures, FOXP4-downregulated W12 cells showed mature squamous phenotypes of CIN lesions. In human keratinocyte-derived HaCaT cells, FOXP4 downregulation also induced squamous differentiation via an ELF3-dependent pathway. These findings suggest that downregulation of FOXP4 inhibits cell proliferation and promotes the differentiation of atypical cells in CIN lesions. Based on these results, we propose that FOXP4 is a novel target molecule for nonsurgical CIN treatment that inhibits CIN progression by inducing squamous differentiation.

Peroxisome proliferator-activated receptor γ (PPARγ) modulators are expected to exert anti-diabetic effects without PPARγ-related adverse effects, such as fluid retention, weight gain, and bone loss. The present study showed that the novel tetrazole derivative KY-903 exerted similar selective PPARγ partial agonist properties to INT-131, a known PPARγ modulator, in transactivation assays, and decreased plasma glucose and triglyceride levels with increases in adiponectin levels in diabetic KK-Ay mice. These effects were similar to those of pioglitazone. Pioglitazone, but not KY-903, increased adipose tissue and heart weights. In pre-adipocytes (3T3-L1), KY-903, in contrast to pioglitazone, increased adiponectin mRNA levels without adipocyte differentiation, indicating anti-diabetic effects via adiponectin without adipogenesis. In ovariectomized rats fed a high-fat diet (OVX/HFD), KY-903 and pioglitazone decreased plasma triglyceride and non-esterified fatty acid levels and increased adiponectin levels, indicating insulin sensitization via adiponectin. KY-903 reduced body weight gain and adipose tissue weight, while pioglitazone increased heart weight and markedly reduced bone mineral density. In mesenchymal stem cell-like ST2 cells, KY-903 slightly reduced osteoblast differentiation without adipocyte differentiation, while pioglitazone markedly reduced it with adipocyte differentiation. In conclusion, KY-903 is a novel PPARγ modulator that exerts anti-diabetic effects without body weight gain or cardiac hypertrophy in diabetic mice and anti-obesity effects with minor bone loss in OVX/HFD, possibly due to increases in adiponectin levels without adipogenesis.

Glioblastoma (GBM) is the most malignant form of glioma. Glioma stem cells (GSCs) contribute to the initiation, progression, and recurrence of GBM as a result of their self-renewal potential and tumorigenicity. Cyclin-dependent kinase 8 (CDK8) belongs to the transcription-related CDK family. Although CDK8 has been shown to be implicated in the malignancy of several types of cancer, its functional role and mechanism in gliomagenesis remain largely unknown. Here, we demonstrate how CDK8 plays an essential role in maintaining stemness and tumorigenicity in GSCs. The genetic inhibition of CDK8 by shRNA or CRISPR interference resulted in an abrogation of the self-renewal potential and tumorigenicity of patient-derived GSCs, which could be significantly rescued by the ectopic expression of c-MYC, a stem cell transcription factor. Moreover, we demonstrated that the pharmacological inhibition of CDK8 significantly attenuated the self-renewal potential and tumorigenicity of GSCs. CDK8 expression was significantly higher in human GBM tissues than in normal brain tissues, and its expression was positively correlated with stem cell markers including c-MYC and SOX2 in human GBM specimens. Additionally, CDK8 expression is associated with poor survival in GBM patients. Collectively, these findings highlight the importance of the CDK8-c-MYC axis in maintaining stemness and tumorigenicity in GSCs; these findings also identify the CDK8-c-MYC axis as a potential target for GSC-directed therapy.

We compared the toxicokinetics of methylmercury (MeHg) in KK-Ay type 2 diabetic mice and C57BL/6J mice to evaluate how metabolic changes associated with diabetes affect MeHg toxicokinetics. A single dose of MeHg (0.2, 1, or 5 mg mercury/kg) was administered orally to 12-week-old KK-Ay and C57BL/6J male mice. Total mercury concentrations in plasma, blood cells, whole blood, and tissues (brain, kidneys, liver, and pancreas) were measured after 4, 7, 11, and 14 days. The volume of distribution/bioavailability and the elimination rate constant per day were higher in KK-Ay mice, while the terminal elimination half-life was lower in almost all samples of KK-Ay mice. The area under the curve was lower in all blood and almost all tissue samples from KK-Ay mice. Total clearance/bioavailability was lower in all blood and tissue samples of KK-Ay mice at all MeHg doses. These results indicate that MeHg is more rapidly absorbed by, and eliminated from, the blood cells, brain, liver, kidney, and pancreas of KK-Ay mice under the experimental conditions. Different patterns of tissue-to-plasma and tissue-to-whole blood partition coefficients suggest that notable differences in MeHg transfer between plasma and blood cells affect its distribution in tissues of the two mouse strains. These findings are useful to understand the selective distribution of MeHg to target organs and the sensitivity to MeHg in pathological states.

Methylmercury (MeHg) is a well-known neurotoxin of the central nervous system (CNS). Neuroinflammation is one of the main pathways of MeHg-induced CNS impairment. This study aims to investigate the expressions of IL-6, MIP-2, and MCP-5, as biomarkers in relation with MeHg-induced CNS impairment and N-acetyl-L-cysteine (NAC) treatment in mice, as well as histopathological changes of brain tissue and clinical symptom such as ataxia. Twenty male Balb/c mice, aged 8–9 weeks, were divided into 4 groups and treated with saline (control), NAC [150 mg/kg body weight (BW) day], MeHg (4 mg Hg/kg BW), or a combination of MeHg and NAC for 17 days. MeHg induced the expression of IL-6, MIP-2, and MCP-5 in the serum, with median values (those in controls) of 55.06 (9.44), 15.94 (9.30), and 458.91 (239.91) mg/dl, respectively, and a statistical significance was observed only in IL-6 expression (p

Background: Metal exposures could possibly affect allergic responses in pregnant women, although no studies have yet shown a clear relationship between the two, and such exposures might also affect the development of allergic diseases in children. Methods: We investigated the relationship between metal concentrations in whole blood and immunoglobulin E (IgE; total and specific) in 14,408 pregnant women who participated in the Japan Environment and Children’s Study. The subjects submitted self-administered questionnaires, and blood samples were collected from them twice, specifically, during the first trimester and again during the second=third trimester. Concentrations of the metals Cd, Pb, Hg, Se, and Mn, as well as serum total and allergen-specific IgEs for egg white, house dust-mites (HDM), Japanese cedar pollen (JCP), animal dander, and moth, were measured. Allergen-specific IgE(s) were divided based on concentrations, This work was supported by the Ministry of the Environment, Japan., Supplementary data related to this article can be found at https://doi.org/10.2188/jea.JE20180098.

The developing perinatal brain is vulnerable to methylmercury (MeHg) exposure. The contribution of breast milk to tissue MeHg levels in offspring is a significant public health concern because breast milk contains a certain amount of MeHg. Here, the contribution of MeHg transferred via breast milk to the Hg levels in the tissues of pups (Wistar rats) was investigated. Mated maternal rats were fed a MeHg (2 ppm)-supplemented or a control diet during pregnancy. Following parturition, male neonates from each group were cross-fostered between exposed or control dams, and they were further raised by dams fed a MeHg-supplemented diet or a control diet during lactation. Consequently, we evaluated three pup groups, which were raised by dams exposed to MeHg during pregnancy (P pups), lactation (L pups), or pregnancy and lactation (PL pups). Total mercury (THg) concentrations in the tissues of the offspring were measured at birth (postnatal day 0 [PD0]), during lactation (PD6, PD12, and PD19), and after weaning (PD29 and PD36). Blood and brain THg levels in the P and PL pups declined dramatically during lactation, however, there were no considerable differences between the two groups at PD6 and PD12. In contrast, blood and brain THg levels in the L pups increased slightly during lactation. The increase in the THg levels in the blood and brain of L pups at PD12 were approximately 3.3% and 1.5%, respectively, compared to the corresponding THg levels in the neonates in the P and PL groups. Our results suggest that if the MeHg exposure level during pregnancy is not high enough to cause neuronal development defects in the fetus, the exposure via breast milk is not a significant concern.

Massive ovarian edema (MOE) is a rare non-neoplastic clinicopathologic disease that is characterized by stromal edema and is caused by the partial or intermittent obstruction of venous and lymphatic drainage. The literature on MOE contains approximately 200 cases, but only 12 cases of MOE during pregnancy have been reported to date. We report a case of MOE at 22 weeks of gestation that was diagnosed preoperatively, and the patient underwent laparoscopic surgery. Accurate preoperative diagnosis of MOE is important because it enables the selection of a therapeutic option, such as fundamental surgery, including adnexectomy; conservative surgery, including the release of torsion and ovarian biopsy; and conservative treatment without surgery. MOE should be considered as a differential diagnosis for an enlarged ovary during pregnancy. Laparoscopic surgery may be a useful therapeutic option for MOE, especially during pregnancy., Highlights • Massive ovarian edema is a rare non-neoplastic clinicopathologic disease. • Massive ovarian edema should be considered as a differential diagnosis for an enlarged ovary during pregnancy. • Laparoscopic surgery may be a useful therapeutic option for massive ovarian edema, especially during pregnancy.

We are developing a Moodle plug-in, which is an AES (automated essay scoring) support system for the basic education of university students. Our system evaluates essays based on rubric, which has five evaluation viewpoints “Contents, Structure, Evidence, Style, and Skill”. Vocabulary level is one of the scoring items of Skill. It is calculated using Japanese Language Learners’ Dictionaries constructed by Sunakawa et al. Since this does not fully cover the words used in the student-level essays, we found that there is a problem with the accuracy of the vocabulary level scoring. In this paper, we propose to construct comprehensive Japanese vocabulary difficulty level dictionaries using Japanese Wikipedia as the corpus. We apply Latent Dirichlet Allocation (LDA) to the Wikipedia corpus and find the word appearance probability as one of the indexes of word difficulty. We use the TF-IDF value instead of the LDA value of the words, which rarely appears. As a result, we constructed highly comprehensive Japanese vocabulary difficulty level dictionaries. We confirmed that the vocabulary level can be scored for all words in the test dataset by using the constructed dictionaries.

Osteoporosis increases the risk of bone fractures (e.g., the femur), reduces a person's activities of daily living (ADL) and increases the likelihood of being bedridden. Therapeutic drugs for osteoporosis include oral bisphosphonates and intravenous receptor activator of nuclear factor-κB ligand (RANKL) antibodies, both of which suppress osteoclast activity, as well as the subcutaneously administered recombinant human parathyroid hormone (PTH), which activates osteoblasts. However, there is currently no oral osteogenesis-promoting drug. In the present study, we found a low-molecular-weight compound, KY-273, with osteogenesis promoting effects. KY-273 induced osteoblast differentiation in ST2 cells and in rat bone marrow-derived mesenchymal stem cells at a dose of 0.1 μM. On the other hand, KY-273 did not clearly exert differentiation effects in osteoclasts, chondrocytes, adipocytes, or myoblasts. In ovariectomized rats, KY-273 clearly increased serum bone alkaline phosphatase (ALP) by at a dose of 3 mg/kg for 8 weeks, and increased both the cortical bone volume and medullary volume of the diaphyseal and epiphyseal regions of femoral bone, but did not affect trabecular bone. Although alendronate (used to decrease bone loss) increased trabecular bone, it did not have any significant effects on cortical bone. PTH increased epiphysis cortical and trabecular bone volume, and reduced medullary volume. KY-273 also displayed good oral absorption in rats. In conclusion, KY-273 is a promising candidate for use as an oral anti-osteoporosis drug with osteogenesis promoting effects.

To clarify whether microplastics contribute to elevated bioaccumulation of methylmercury (MeHg) in aquatic organisms, we studied the sorption pattern of MeHg on polystyrene beads (PBs) and evaluated MeHg accumulation, via uptake of MeHg-adsorbed PB, in the oyster Crassostrea gigas. MeHg-cysteine conjugates were added to seawater at 10, 100, and 1000 µg/L as Hg. Polystyrene beads (φ = 0.02, 0.2, and 2 µm) were immersed in the seawater for 24 h. The concentrations of total mercury (T-Hg) adsorbed onto the PBs were then measured using the reduction vaporization method. T-Hg concentrations for the PBs with diameters of 0.02, 0.2, and 2 µm were 10.6 ± 0.4, 1.8 ± 0.1, and 1.3 ± 0.1 ng/mg-PBs, respectively, when immersed in 2 mL of MeHg-added seawater (100 µg/L as Hg). Thus, the adsorption efficiency of MeHg onto PBs was higher in the presence of smaller diameter PBs. Next, 1 mg of PBs immersed in 2 mL of seawater containing 100 µg/L of MeHg for 24 h was added to an oyster tank containing 1 L of seawater. The T-Hg concentration of the oysters was measured after 6 h of exposure. No significant difference was found in the T-Hg concentration of oysters in the presence of PBs (0.30 ± 0.01 to 0.37 ± 0.05 ng/mg as dry weight) with MeHg and in the absence of PBs (0.36 ± 0.03 ng/mg as dry weight). Our results suggest that the presence of PBs in seawater has little effect on MeHg uptake by oysters.

To examine the safety and feasibility of total laparoscopic retrograde hysterectomy (TLreH) in patients with obliterated cul-de-sac due to severe endometriosis.This retrospective case-control observational study was performed at the Yokohama Municipal Citizen's Hospital between January 2014 and December 2019. Ninety-two women who underwent TLreH and who had uterine fibroids, adenomyosis, or both with obliterated cul-de-sac due to severe endometriosis were enrolled.Surgical outcomes were retrospectively analyzed. The median operation time was 122 (range, 54-312) min, and the median blood loss was 150 (range, 0-1420) mL. Perioperative complications (Clavien-Dindo classification ≥Ⅲ) occurred in 3 cases (3.3 %). There were no cases of transition to open surgery. Blood transfusion was required in 1 case. The operation time and estimated blood loss volume were significantly correlated with the weight of the uterus (p0.01). The subjects were divided into two groups: uteri weighing ≥600 g group and those weighing600 g group. In the ≥600 g group, the median operation time and median estimated blood loss volume were 130 (81-312) min and 265 (70-1420) mL, respectively. There was no difference in the frequency of perioperative complications or blood transfusions between the groups.Our study demonstrated that TLreH for severe endometriosis with obliterated cul-de-sac was feasible and safe. It could be safely performed for large uteri (≥600 g) with obliterated cul-de-sac due to severe endometriosis.

Minimally invasive surgery including lymphadenectomy for endometrial cancer is widely standardized for the management of endometrial cancer in recent decades. However, the learning curve for laparoscopic para-aortic lymphadenectomy is poorly reported, specifically that for the extraperitoneal approach.We examined the learning curve for laparoscopic extraperitoneal para-aortic lymphadenectomy by cumulative sum (CUSUM) analysis by retrospectively analyzing 134 patients with early-stage endometrial cancer who had undergone laparoscopic extraperitoneal para-aortic lymphadenectomy, including the first case. Data on the surgical factors that improved and were statistically correlated with the number of procedures experienced were extracted and used to create CUSUM curves.The average time for para-aortic lymphadenectomy was 149.4 min to harvest an average of 65.3 para-aortic lymph nodes. Intra- and postoperative complications were observed in nine cases (6.7%). A switch to the transperitoneal approach was necessary in three cases (2.2%). The number of harvested para-aortic lymph nodes and the procedure time were strongly correlated with the number of procedures the patient underwent (p 0.01). The CUSUM curve of the number of harvested para-aortic lymph nodes indicated an inflection point at the 51st case. The procedure time for para-aortic lymphadenectomy stabilized after the 59th case. CUSUM analysis of "unexpected events," including intra- and postoperative complications and switch to the transperitoneal approach, showed an improved incidence at 60 cases and later.Gaining proficiency in laparoscopic extraperitoneal thorough para-aortic lymphadenectomy is associated with a long learning curve of over 60 procedures. Careful management is required when introducing the procedure.

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 mgkg -1; /inc. 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.

Heavy metals are widely distributed in the environment. Recent reports have demonstrated the risk of preterm birth following heavy metal exposure. Preterm births are classified as early and late, depending on the duration of pregnancy, and are associated with increased risk of congenital illnesses such as heart failure, asthma, etc. Particularly, early preterm births carry a higher risk of mortality; however, the differential effects of heavy metal exposure on early and late preterm births are unknown.To analyze the association between maternal whole blood concentrations of heavy metals, such as cadmium (Cd), lead (Pb), mercury (Hg), selenium (Se), and manganese (Mn) that are common toxicants in Japan, and early and late preterm births.The data of 14,847 pregnant women who were participants of the Japan Environment and Children's Study were used. Data of the self-questionnaire pertaining to the first trimester (T1), second/third trimester (T2), and medical records after delivery were analyzed. We divided preterm birth into two groups: early preterm (22 to34 weeks) and late preterm (34 to37 weeks). Maternal blood samples for measuring heavy metal concentrations were collected in T2 (pregnancy weeks: 14-39). The participants were classified into four quartiles (Q1-Q4) according to increasing heavy metal levels.The rate of preterm birth was 4.5%. After controlling for confounding factors, such as age, pre-pregnancy body mass index, smoking, partner's smoking, drinking habits, gravidity, parity, number of cesarean deliveries, uterine infections, household income, educational levels, and sex of infant, Cd levels were found, by multivariable logistic regression analysis, to be significantly associated with early preterm birth (p = 0.002), with odds ratio for early preterm birth of 1.91 (95% confidence interval: 1.12-3.27, P = 0.018) in subjects of Q4 compared with in subjects with term birth (≧ 37 weeks).Maternal blood Cd levels during pregnancy are positively associated with the risk of early preterm birth among Japanese women. Identification of the main source of maternal Cd exposure may contribute to the prevention of early preterm births and health maintenance of mothers and their infants in the future.

Methylmercury (MeHg) is known to cause neurobehavioral impairment in human and experimental animals. We previously reported that MeHg (5 mg Hg/kg) induced severe neurobehavioral dysfunction in 4-week-old KK-Ay mice, although it is difficult to evaluate quantitatively the neurobehavioral impairment in MeHg-treated KK-Ay mice because of their obesity. The aim of this study was to evaluate MeHg-induced neurobehavioral dysfunction in KK-Ay mice using the dynamic weight-bearing test, which analyzes the animal's weight distribution between the four limbs. Male 12-week-old KK-Ay mice were treated with MeHg (5 mg Hg/kg) three times per week for 5 weeks. Body weight loss began after approximately 2 weeks of MeHg treatment, and decreased significantly at 4 weeks. Seven of the nine MeHg-treated mice exhibited overt neurological symptoms such as ataxia and gait disturbance. The weight-bearing load was lower for the forelimb than for the hindlimb at baseline and until 1 week after MeHg treatment was initiated. In weeks 2-4, the dynamic weight-bearing loads on the forelimb and hindlimb were similar. The load on the forelimb exceeded the load on the hindlimb after 5 weeks of treatment. This finding indicates that the dynamic weight-bearing test is useful for semi-quantitative evaluation of neurobehavioral impairment in MeHg-treated rodents, and is less stressful for the animals. Infiltration of CD204-positive macrophages was observed in the sciatic nerve of MeHg-treated mice, suggesting that CD204 can serve as a useful marker of tissue injury in peripheral nerves and a possible target in regenerating peripheral nerves and controlling neuropathies.

Macrophages play an important role in neurotoxicity caused by methylmercury exposure through inflammatory responses. Methylmercury is known to demethylate to inorganic mercury in the brain, and macrophages are likely to be involved in this process. However, the inflammatory responses of macrophages against exposure to inorganic mercury are unclear. In the present study, inflammatory cytokine expression profiles were examined in the presence of non-toxic doses of inorganic mercury (Hg2+) using RAW264.7 macrophages, focusing on the expression of C-X-C motif chemokine 2 (MIP-2)/platelet-derived growth factor-inducible protein KC (KC) and C-C motif chemokine 12 (MCP-5). Furthermore, the suppressive effect of N-acetyl-L-cysteine (NAC) on inorganic mercury-induced MIP-2 expression was also examined. Inorganic mercury-induced mRNA expression was measured using reverse transcription-quantitative PCR. The mRNA expression of MIP-2 and MCP-5 was significantly upregulated by exposure to 20 µM Hg2+ (non-toxic levels), but not that of KC. The suppressive effect of NAC on these cytokine expression levels was examined by its addition to the culture medium together with Hg2+ (co-treatment), and pre- and post-treatments in which the cells were treated with NAC before and after Hg2+ exposure, respectively. Hg2+-upregulated MIP-2 expression was suppressed by NAC regardless of the time sequence of the treatment, suggesting that the suppressive role of NAC in Hg2+-induced inflammation manifests as a possible chelator and antioxidant/reactive oxygen species scavenger.

本研究は保育者養成課程における運動遊びに着目し、女子大学生の意欲的な学習の取り組み、学生の技術習得、子どもの理解、および運動遊びの指導の関係を調べた。「幼児体育Ⅱ」の授業の運動遊び「チャレンジシリーズ」（けん玉・竹馬・お手玉・フラフープ・紐ごま）を対象としてアンケート調査を行った。授業内で運動遊びの各種目に繰り返し取り組むことで、学生自身ができた喜びを実感し、学んだことを友達に伝えたり、コツをわかりやすく伝えたりしていた。意欲的に取り組んだ学生は、自分なりに運動遊びのコツをつかみ、保育者を目指す上での大切な経験と学びをしていた。一方、運動遊びのコツがつかめず上達しなかった学生もいた。授業を進める上で、学生の意欲をより高め、到達目標に向かって努力することができるよう段階を踏んだ取り組みに配慮し、学生同士のつながりと学び合いを深めていく必要がある

A ternary copper(II) complex with sulfamethizole (SMZ, C9H10N4O2S2) and 1,10-phenantroline (phen), [Cu(SMZ)2(phen)], and a silver(I) complex with sulfamethizole, Ag-SMZ, are presented. Elemental analyses indicate a 2:1:1 SMZ/copper/phen composition for the [Cu(SMZ)2(phen)] complex and a 1:1 silver/SMZ composition for the Ag-SMZ complex. Mass spectrometric analyses permitted identifying the [Cu(SMZ)2(phen)+H]+ and [Ag(SMZ)+H]+ ions at m/z 782.0297 and m/z 378.9371, respectively, confirming the proposed compositions. Theoretical isotopic patterns match with the experimental ones for the copper and silver complexes. 1H and {15N,1H} HMBC nuclear magnetic resonance (NMR), and infrared (IR) spectroscopic measurements evidence the coordination of sulfamethizole to silver(I) by the SO2-N group, and indicate the participation of the 5-membered heterocyclic ring 5-methyl-1,3,4-thiadiazole in coordination. The [Cu(SMZ)2(phen)] crystal structure was determined by single crystal X-ray diffractometry, attesting the N-coordination of sulfamethizole to copper(II) by the nitrogen of the 5-methyl-1,3,4-thiadiazole heterocyclic ring. Electronic paramagnetic resonance (EPR) indicates a square pyramidal geometry around the copper(II) ion for the [Cu(SMZ)2(phen)] complex. Biological studies showed the antibacterial activity of the Ag-SMZ and [Cu(SMZ)2(phen)] complexes over Gram-positive and Gram-negative bacteria. Both complexes have shown to be more active against Gram-negative Pseudomonas aeruginosa ATCC bacterial strain, with minimum inhibitory concentration (MIC) values of 0.41 mmol L−1 for the silver(I) complex and 1.60 mmol L−1 for the copper(II) complex.

Objective Stimulating communication is an important workplace issue. We investigated the effects of a brief communication skills training (CST) program based on the principles of cognitive behavioral therapy (CBT). Methods A randomized controlled trial was conducted on 206 white-collar workers. The intervention group underwent a 2-hour CST group training conducted by an occupational physician. Result The results of the intention-to-treat analysis using a mixed-effects model showed that there was a significant interaction between group and time observed for the item "thinking together to solve problems and issues" (P = 0.02). The effect size (Cohen d) was 0.35 (95% confidence interval, 0.07 to 0.62). Conclusions The present study suggests that a brief CST based on the principles of CBT could improve the communication behavior of workers.

The Japanese shrimp industry depends on importing shrimp from other countries. However, little information is available on mercury speciation and selenium (Se) concentrations in commercial shrimp available in Japan. The present study determined the concentrations of total mercury (T-Hg), methylmercury (MeHg), and Se in the muscles (wet weight) of imported and domestic commercial shrimp from Kumamoto and Kagoshima prefectures to obtain information for assessing the risk of MeHg exposure. The median concentrations of T-Hg, MeHg and Se in shrimp imported from three different countries were, respectively: black tiger shrimp (n = 18), 15.8, 14.4, and 415 ng/g; Vannamei shrimp (n = 25), 11.4, 11.2, and 292 ng/g; and white shrimp (n = 26), 26.8, 26.1, and 396 ng/g. There were significant differences in T-Hg and MeHg concentrations between shrimp imported from different countries. The median concentrations of T-Hg, MeHg and Se in shrimp of Japanese origin were, respectively: Shiba shrimp (n = 10), 15.9, 15.0, and 270 ng/g; Kuruma shrimp (n = 10), 79.9, 75.9, and 390 ng/g; and Ashiaka shrimp (n = 10), 36.1, 34.1, and 303 ng/g. The percentages of MeHg in T-Hg were between 90% and 99%, with MeHg levels in the imported and domestic commercial shrimp lower than the Japanese regulation of 300 ng/g for fish. The mean Se/T-Hg molar ratios (16-160) were comparatively higher than those previously reported in fish. Overall, this survey suggests that shrimp commercially available in Japan will not pose a particularly high risk regarding MeHg exposure to consumers.

The accumulation of macrophages has been observed around lesions of the brain in patients with Minamata disease. In this condition, mercury has been detected histochemically in macrophages throughout the brain. However, the role of macrophages in the neurotoxicity of methylmercury (MeHg) and the molecular mechanisms of their response to MeHg exposure remain to be elucidated. Here, we investigated how MeHg affects the expression of proinflammatory cytokines such as interleukin (IL)-6 and IL-8 in cultured human U937 macrophages. Compared with controls, IL-6 and IL-8 mRNA expression was maximally induced in U937 macrophages after treatment with 10 μM MeHg for 6 h. The protein secretion of IL-6 and IL-8 was significantly stimulated by MeHg in U937 macrophages. Results from luciferase reporter assay indicated functional activation of nuclear factor kappa B and the involvement of subunit RelA and p50 in MeHg-induced IL-6 and IL-8 activation, which was confirmed by siRNA knockdown experiments. MeHg exposure at 4 μM also significantly induced IL-8 expression in U-87 MG cells at mRNA and protein level, indicating that IL-8 induction might be a general mode of action of MeHg treatment among different cell types. These results indicate a possible involvement of an early inflammatory response, including IL-6 and IL-8 expression in the pathogenesis of MeHg. N-acetyl-l-cysteine suppressed MeHg-induced activation of IL-6 and IL-8 mRNA expression in U937 macrophages, indicating the effectiveness of N-acetyl-l-cysteine as a therapeutic drug in MeHg-induced inflammation. Copyright © 2016 John Wiley & Sons, Ltd.

Recurrent corneal erosion (RCE) is a common disorder causing ocular pain, tearing, photophobia, and visual impairments. Various factors such as ocular trauma, ocular surgery, corneal dystrophy, contact lens wear, and diabetes mellitus (DM) can cause RCE. The purpose of this study was to determine the causative factors and clinical course of RCE. We retrospectively examined 21 eyes of 21 patients with RCE and investigated the patients’ background, type of treatments, and clinical course after the treatments. All patients were treated with eye drops, ocular lubrication, or contact lens bandage for the RCE. Among the 21 patients with RCE, 9 were caused by trauma (Trauma group), 8 by DM (DM group), 1 by bacterial corneal ulcer, 1 by lagophthalmus and bacterial corneal ulcer, 1 by bandkeratopathy, and 1 by eyelid tumor (one eye). The mean age of the patients was 57.8 years with a range 34–91 years. The mean duration from the trauma to the onset of RCE was 5.2 ± 5.0 months (mean ± SD). The time required for a complete recovery of RCE was longer in the DM group (10.3 ± 3.1 weeks) than in the Trauma group (2.7 ± 1.1 weeks, P

Osteoporosis increases the risk of bone fractures (e.g., the femur), reduces a person's activities of daily living (ADL) and increases the likelihood of being bedridden. Therapeutic drugs for osteoporosis include oral bisphosphonates and intravenous receptor activator of nuclear factor-κB ligand (RANKL) antibodies, both of which suppress osteoclast activity, as well as the subcutaneously administered recombinant human parathyroid hormone (PTH), which activates osteoblasts. However, there is currently no oral osteogenesis-promoting drug. In the present study, we found a low-molecular-weight compound, KY-273, with osteogenesis promoting effects. KY-273 induced osteoblast differentiation in ST2 cells and in rat bone marrow-derived mesenchymal stem cells at a dose of 0.1 μM. On the other hand, KY-273 did not clearly exert differentiation effects in osteoclasts, chondrocytes, adipocytes, or myoblasts. In ovariectomized rats, KY-273 clearly increased serum bone alkaline phosphatase (ALP) by at a dose of 3 mg/kg for 8 weeks, and increased both the cortical bone volume and medullary volume of the diaphyseal and epiphyseal regions of femoral bone, but did not affect trabecular bone. Although alendronate (used to decrease bone loss) increased trabecular bone, it did not have any significant effects on cortical bone. PTH increased epiphysis cortical and trabecular bone volume, and reduced medullary volume. KY-273 also displayed good oral absorption in rats. In conclusion, KY-273 is a promising candidate for use as an oral anti-osteoporosis drug with osteogenesis promoting effects.