Homogenic Evaluation for Spatial Distribution in Osteoclast Differentiation.

BACKGROUND: Cells have heterogeneous cellular diversity in size, morphology, cell cycle, metabolism, differentiation degree, and spatial distribution. The shift of specific cells towards the desired cells is crucial for maintaining uniform cellular function and can be represented by homogeneity and heterogeneity. Here, we developed a simple and direct method for evaluating the homogeneous distribution of desired cells in a constant region. METHODS: We differentiated osteoclast progenitors into bone-resorbing multinucleated giant osteoclasts in a 2-dimensional culture plate under 2 conditions. Cells were stained with tartrate-resistant acid phosphatase to assess osteoclast differentiation, images were taken using a microscope and divided into sectors, and the number of osteoclasts (≥3 nuclei) in each sector was counted. To assess the homogeneity of the spatial distribution of osteoclasts, the standard deviation (SD) was calculated from the mean number of osteoclasts within each sector. RESULTS: From the 2 groups, a value with a SD close to 0 indicates high spatial homogeneity while a relatively high SD represents low spatial homogeneity. CONCLUSIONS: Our findings suggest that spatial homogeneity can be represented as SD.

Descriptive epidemiology of cancer of unknown primary in South Korea, 1999-2017.

BACKGROUND: Cancers of unknown primary (CUPs) are tumors found after metastasizing from unidentified primary sites; these tumors generally have unknown treatment strategies, expected treatment results, and prognosis. We assessed the epidemiological characteristics of CUPs in Korea. METHODS: We extracted records for 1999 through 2017 from the Korea Central Cancer Registry using the International Statistical Classification of Diseases and Related Health Problems (10th revision) codes for CUP as defined by the International Agency for Research on Cancer. Age-standardized rates and relative survival rates were calculated. RESULTS: The CUPs constituted 2.1 % of the total number of cancer registrations in 1999, declining to 0.7 % in 2017. The incidence rate decreased for both sexes (5.35 to 2.20 for men, 3.15 to 1.77 for women). Patients aged 80 years and older had the highest incidence rate at 40.2, and 86.3 % of CUPs occurred in those 50 years of age or older. The cases of retroperitoneum and peritoneum sites increased over time. Cases diagnosed by microscopic methods and death certification only were 62.3 % and 7.9 %, respectively. The malignant neoplasm of the retroperitoneum and peritoneum and unknown primary site had the highest and lowest survival rates, respectively. The 5-year relative survival rate increased over time from 14.2 % (1999-2002) to 27.3 % (2013-2017). CONCLUSIONS: Our analysis of data from the Korea Central Cancer Registry found decreasing rates of CUP, although with consistent disparities by patient age and sex. Advancements in diagnostic technology may be decreasing the number of CUP diagnoses. Expanding the amount of information recorded in the registry may further improve diagnostic accuracy.

Survey of Potential Cancer Registry Items to Enhance the Usefulness of Cancer Registry Data.

BACKGROUND: Cancer registry data can help plan for cancer services and to identify where further progress is needed, in order to improve the lives of patients with cancer. This study investigated the possibility of collecting additional information and the priority of the information by examining other cancer registry items. We aimed to suggest additional data items to be collected to enhance the usefulness of cancer registry data. METHODS: We examined items that could potentially be added by comparing the cancer registration items in five foreign registries and large hospitals in Korea. Based on the foreign and domestic hospital cancer registry data, a questionnaire survey was administered to 272 cancer registry workers nationwide and 10 cancer experts to investigate the possibility of expanding the variables. The proportion and rank of each item were analyzed. RESULTS: There were similar items for demographic information and cancer diagnosis between foreign cancer registries and the Korea Central Cancer Registry (KCCR). However, the KCCR had fewer items for staging, treatment, and follow-up. There were 29 items to be collected with high priority. Items under demographic information included date of birth, race and country of birth. Items for cancer diagnosis included type of cancer, smoking history and type of pathologic test. Treatment information included the date of treatment, chemotherapy and radiation. Items under the stage and prognostic factors included TNM stage, collaborative stage, and comorbidities. Finally, items under follow-up information included survival, cancer state and recurrence information. CONCLUSIONS: Cancer registration workers and cancer experts generally agreed on the need to expand the essential items for cancer registration. The findings of this study will be useful for devising plans to expand cancer registration items.

[Development and Effects of a Hand-washing Program using Role-playing for Preschool Children]. / í•™ë ¹ì „ê¸° 아동의 ì—­í• ë†€ì´ë¥¼ 이용한 손 씻기 프로그램 개발 및 효과.

PURPOSE: A hand-washing program using role-playing was developed for preschool children and tested to verify its usefulness. METHODS: The participants were 46 preschool children (experimental group, 23; control group, 23). Data were collected from August 7, 2017 to September 20, 2017. The first posttest was carried out on the day after the initial intervention was completed, and the second posttest was performed after a month. Data were analyzed using the x 2 test, Fisher exact test, Shapiro-Wilk test, Mann-Whitney test, and Friedman test. RESULTS: In the experimental group, the frequency of practicing hand-washing was significantly higher than in the control group on the next day (z=-4.94, p<.001) and after a month (z=-3.15, p=.002). The accuracy of hand-washing was significantly higher in the experimental group than in the control group on the next day (z=-4.02, p<.001) and after a month (z=-3.86, p<.001). CONCLUSION: The hand-washing program developed in this study was found to be an effective intervention strategy for improving the frequency and accuracy of hand-washing among preschool children.

Qualitative Improvement Methods Through Analysis of Inquiry Contents for Cancer Registration

Background: In Korea, the national cancer database was constructed after the initiation of the national cancer registration project in 1980, and the annual national cancer registration report has been published every year since 2005. Consequently, data management must begin even at the stage of data collection in order to ensure quality. Objectives: To determine the suitability of cancer registries' inquiry tools through the inquiry analysis of the Korea Central Cancer Registry (KCCR), and identify the needs to improve the quality of cancer registration. Methods: Results of 721 inquiries to the KCCR from 2000 to 2014 were analyzed by inquiry year, question type, and medical institution characteristics. Using Stata version 14.1, descriptive analysis was performed to identify general participant characteristics, and chi-square analysis was applied to investigate significant differences in distribution characteristics by factors affecting the quality of cancer registration data. Results: The number of inquiries increased in 2005­2009. During this period, there were various changes, including the addition of cancer registration items such as brain tumors and guideline updates. Of the inquirers, 65.3% worked at hospitals in metropolitan cities and 60.89% of hospitals had 601­1000 beds. Tertiary hospitals had the highest number of inquiries (64.91%), and the highest number of questions by type were 353 (48.96%) for histological codes, 92 (12.76%) for primary sites, and 76 (10.54%) for reportable. Conclusions: A cancer registration inquiry system is an effective method when not confident about codes during cancer registration, or when confronting cancer cases in which previous clinical knowledge or information on the cancer registration guidelines are insufficient.

Cancer Registration Manual Understanding by Medical Record Administrators

Background: This study examined: (a) whether medical record administrators (MRAs) properly understand and apply a cancer registration manual; (b) weaknesses in cancer registration: and (c) factors influencing the accuracy of cancer registration. Methods: MRAs dealing with cancer registration in 81 national member hospitals were asked by mail to answer 17 questions about cancer information among registration items. After calculating rates of correct and incorrect answers to each question, an analysis was conducted of whether they were related to particular factors (hospital type, hospital location, number of hospital beds, experience of cancer registration, and experience of consulting cancer registration). Results: A total of 45.7% of the participants gave approximately 90% correct answers. The rates for correct answers about general rules were under 90% for objectives of cancer registration and treatment. The rate concerning histologic type was over 90%, while few correct answers exceeded 50% to questions concerning newly revised rules for the colorectal system. For questions about initial treatment, date of diagnosis, and method of final diagnosis, as well as four questions on checking the validity of registered data, the correct answer rates were 70-90%. Regarding the features of hospitals and respondents, number of hospital beds and prior experience in cancer registration questions were found to contribute to the high rate of correct answers. Conclusion: To improve the accuracy of cancer registration, the manual needs to be supplemented in areas demonstrating low correct answer rates. Education opportunities and methods for MRAs should be diversified.

Synchronized Cell Cycle Arrest Promotes Osteoclast Differentiation.

Osteoclast progenitors undergo cell cycle arrest before differentiation into osteoclasts, induced by exposure to macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). The role of such cell cycle arrest in osteoclast differentiation has remained unclear, however. We here examined the effect of synchronized cell cycle arrest on osteoclast formation. Osteoclast progenitors deprived of M-CSF in culture adopted a uniform morphology and exhibited cell cycle arrest at the G0-G1 phase in association with both down-regulation of cyclins A and D1 as well as up-regulation of the cyclin-dependent kinase inhibitor p27(Kip1). Such M-CSF deprivation also promoted the differentiation of osteoclast progenitors into multinucleated osteoclasts expressing high levels of osteoclast marker proteins such as NFATc1, c-Fos, Atp6v0d2, cathepsin K, and integrin ß3 on subsequent exposure to M-CSF and RANKL. Our results suggest that synchronized arrest and reprogramming of osteoclast progenitors renders them poised to respond to inducers of osteoclast formation. Further characterization of such effects may facilitate induction of the differentiation of heterogeneous and multipotent cells into desired cell lineages.

Novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivative, MHY-449, induces cell cycle arrest and apoptosis via the downregulation of Akt in human lung cancer cells.

The anticancer properties of MHY-449, a novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivative, in various human cancer cell lines have been previously reported. The aim of the present study was to investigate the activities of MHY-449 on human lung cancer cells in order to elucidate its underlying molecular mechanisms of action. The result showed that MHY-449 treatment inhibited cell growth in a time- and concentration­dependent manner. Specifically, MHY-449 induced cell cycle arrest at the S phase, and the resulting increased sub-G1 fraction led to the induction of apoptosis, as determined by flow cytometric analysis and DNA fragmentation. In addition, MHY-449 was shown to induce alterations in the ratio of Bax/Bcl-2 protein expression, and contribute to the loss of mitochondrial membrane potential. These cellular events then triggered the caspase cascade and subsequent poly(ADP­ribose) polymerase cleavage. The apoptotic cell death induced by MHY-449 was inhibited by pretreatment with Z-VAD­FMK, a pan-caspase inhibitor. Moreover, MHY-449 downregulated the phosphorylation of Akt, and the phosphatidylinositol-3 kinase/Akt inhibitor LY294002 was found to enhance its induction of apoptosis. Taken together, the results suggested that MHY-449 exerts anticancer effects by promoting cell cycle arrest and apoptosis via the downregulation of Akt. Based on these data, MHY-449 serves as a potential candidate in the chemoprevention and/or treatment of lung cancer.

MHY-449, a novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivative, mediates oxidative stress-induced apoptosis in AGS human gastric cancer cells.

MHY-449 is a novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivative designed and synthesized as a potential anticancer agent. The present study aimed to examine the anticancer activity and underlying mechanism of MHY-449. The cell viability assay performed in AGS human gastric carcinoma cells demonstrated that MHY-449 inhibited cell proliferation in a concentration-dependent manner. MHY-449 induced AGS cell death via apoptosis. The underlying molecular mechanism of MHY-449-mediated apoptosis was also investigated. MHY-449 promoted the upregulation of Fas and Fas-ligand, and activation of caspase-8, suggesting the involvement of a Fas-mediated extrinsic pathway in MHY-449-induced apoptosis. In addition, it was found that MHY-449-induced apoptosis was accompanied by the upregulation of Bax, p21(WAF1/CIP1), p27(KIP1), and p53 and suppression of Bcl-2. MHY-449 exposure activated the caspase cascade and subsequent poly(ADP-ribose) polymerase (PARP) cleavage. Furthermore, the pan-caspase inhibitor, Z-VAD-FMK, significantly attenuated MHY-449-induced apoptosis, indicating that the apoptosis was caspase-dependent. Moreover, the apoptogenic effect of MHY-449 was reactive oxygen species (ROS)-dependent. This result was confirmed by the induction of ROS by MHY-449 and by evidence that the scavenging of ROS by N-acetyl-L-cysteine inhibited MHY-449-induced cell death. Taken together, these results demonstrated that MHY-449 triggers apoptosis via caspase activation and ROS production. This result provides a novel mechanistic explanation and a basis for developing this compound as a novel candidate for human cancer therapy.

Corneal plaque containing levofloxacin in a dog.

A 13-year-old castrated male Yorkshire terrier developed a corneal ulcer 2 weeks after intracapsular lens extraction (ICLE) in the right eye. The corneal ulcer was treated with levofloxacin eye drops. A plaque with a white luster developed in the central cornea 2 weeks after treatment with levofloxacin eye drops. The corneal plaque was surgically removed under inhalant anesthesia. The corneal plaque displayed antimicrobial activity against Escherichia coli. Furthermore, levofloxacin content in the plaque was confirmed by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry (MS). The corneal ulcer completely resolved 2 weeks after the surgical removal of the corneal lesion and replacement of levofloxacin eye drops with tobramycin eye drops. Although the topical use of levofloxacin is unlikely to lead to corneal chemical deposits due to the high water solubility of the drug compared to other topical fluoroquinolones, this patient developed corneal plaque of the antibiotic drop.

Implementation plans for the Korean certified tumor registrar qualification system.

BACKGROUND: Cancer registration data is used to understand the nation's cancer burden, and to provide significant baseline data for cancer control efforts, as well as, research on cancer incidence, mortality, survival, and prevalence. A system that approves, assesses, and manages the qualification of specialists, responsible for performing cancer registration, has not been developed in Korea. This study presents ways to implement a certification system designed for the qualification of tumor registrars in Korea. MATERIALS AND METHODS: Requirements for implementing a certified tumor registrar qualification system were determined by reviewing the system for establishing qualifications in Korea and the American qualification system via the National Cancer Registrars Association (NCRA). Moreover, a survey was conducted on Korean medical records administrators, who had taken the U.S. Certified Tumor Registrar (CTR) examination, in order to review their opinions regarding these requirements. RESULTS: This study verified the feasibility of a qualification examination based on the opinions of CTR specialists by determining the following: items, and the associated ratings, of the qualifications necessary to register individuals as certified tumor registrars in a private qualification system; status of human resources required for the examination or training processes; plans regarding the organization needed for management, and operation of qualifications, examination standards, subject areas, examination methods, examination qualifications, or education and training programs. CONCLUSIONS: The implementation of a certified tumor registrar qualification system will lead to enhanced job competency for specialists and a qualitative improvement of cancer registration data. It will also reliably foster human resources that will lay the groundwork needed to establish scientific and reasonable national cancer management policies.

Improving accuracy and completeness in the collaborative staging system for stomach cancer in South Korea.

BACKGROUND: Cancer staging enables planning for the best treatments, evaluation of prognosis, and predictions for survival. The Collaborative Stage (CS) system makes it possible to significantly reduce the proportion of patients labeled at an "unknown" stage as well as discrepancies among different staging systems. This study aims to analyze the factors that influence the accuracy and validity of CS data. MATERIALS AND METHODS: Data were randomly selected (233 cases) from stomach cancer cases enrolled for CS survey at the Korea Central Cancer Registry. Two questionnaires were used to assess CS values for each case and to review the cancer registration environment for each hospital. Data were analyzed in terms of the relationships between the time spent for acquisition and registration of CS information, environments relating to cancer registration in the hospitals, and document sources of CS information for each item. RESULTS: The time for extracting and registering data was found to be shorter when the hospitals had prior experience gained from participating in a CS pilot study and when they were equipped with full-time cancer registrars. Evaluation of the CS information according to medical record sources found that the percentage of items missing for Site Specific Factor (SSF) was 30% higher than for other CS variables. Errors in CS coding were found in variables such as "CS Extension," "CS Lymph Nodes," "CS Metastasis at Diagnosis," and "SSF25 Involvement of Cardia and Distance from Esophagogastric Junction (EGJ)." CONCLUSIONS: To build CS system data that are reliable for cancer registration and clinical research, the following components are required: 1) training programs for medical records administrators; 2) supporting materials to promote active participation; and 3) format development to improve registration validity.

Apigenin-induced apoptosis is enhanced by inhibition of autophagy formation in HCT116 human colon cancer cells.

Apigenin (4',5,7-trihydroxyflavone) is a natural flavonoid, shown to have chemopreventive and/or anticancer properties in a variety of human cancer cells. The involvement of autophagy in apigenin-induced apoptotic cell death of HCT116 human colon cancer cells was investigated. Apigenin induced suppression of cell growth in a concentration-dependent manner in HCT116 cells. Flow cytometric analyses indicated that apigenin resulted in G2/M phase arrest. This flavone also suppressed the expression of both cyclin B1 and its activating partners, Cdc2 and Cdc25c, whereas the expression of cell cycle inhibitors, such as p53 and p53-dependent p21(CIP1/WAF1), was increased after apigenin treatment. Apigenin induced poly (ADP-ribose) polymerase (PARP) cleavage and decreased the levels of procaspase-8, -9 and -3. In addition, the apigenin-treated cells exhibited autophagy, as characterized by the appearance of autophagosomes under fluorescence microscopy and the accumulation of acidic vesicular organelles by flow cytometry. Furthermore, the results of the western blot analysis revealed that the levels of LC3-II, the processed form of LC3-I, was increased by apigenin. Treatment with the autophagy inhibitor 3-methyladenine (3-MA) significantly enhanced the apoptosis induced by apigenin, which was accompanied by an increase in the levels of PARP cleavage. These results indicate that apigenin has apoptosis- and autophagy-inducing effects in HCT116 colon cancer cells. Autophagy plays a cytoprotective role in apigenin-induced apoptosis, and the combination of apigenin and an autophagy inhibitor may be a promising strategy for colon cancer control.

Herbal medicines for treating tic disorders: a systematic review of randomised controlled trials.

BACKGROUND: It was reported that 64% of tic disorder patients used complementary and alternative medicine. This review aims to evaluate the efficacy of herbal medicines in treating tic disorders. METHODS: We searched eight databases including MEDLINE and CINAHL from their respective inceptions up to September 2013. The search terms were related to the concept of "herbal medicine" AND "tic disorder OR Tourette's syndrome". We included randomised controlled trials (RCTs) of any type of herbal medicines. We assessed the methodological quality of the trials according to the Cochrane risk of bias criteria. RESULTS: Sixty one studies were identified, and four RCTs met the inclusion criteria. Two types of herbal medicines, Qufeng Zhidong Recipe (QZR) decoction and Ningdong (ND) granules, were used in the included RCTs. All four RCTs had a high risk of bias. Two RCTs tested the effects of QZR on the Yale Global Tic Severity Scale (YGTSS) score and response rate compared with conventional medicine. The meta-analysis showed significant effects of QZR on the YGTSS score with high statistical heterogeneity (n = 142; weighted mean difference: -18.34; 95% confidence interval (CI): -23.07 to -13.60; I2 = 97%) and the response rate (n = 142; risk ratio: 1.69; 95% CI: 1.39 to 2.06; I2 = 0%). One RCT compared ND granules with placebo and showed significant effects on the YGTSS score and response rate. The other RCT show significant effects of ND granules plus conventional medicine on the response rate compared with conventional medicine only. CONCLUSION: This systematic review provided first piece of limited meta-analytic evidence for the effectiveness of herbal medicines in improving the symptoms of tic disorders.

MHY-449, a novel dihydrobenzofuro[4,5-b][1,8] naphthyridin-6-one derivative, induces apoptotic cell death through modulation of Akt/FoxO1 and ERK signaling in PC3 human prostate cancer cells.

Previously, we reported on the anticancer effect of the diastereoisomeric compound MHY-449, a novel dihydro-benzofuro[4,5-b][1,8] naphthyridin-6-one derivative, in HCT116 human colon cancer cells. In the current study, we investigated whether MHY-449 has anticancer effect in prostate cancer cells, and if so, what the molecular mechanisms are. We examined the growth inhibitory effect of MHY-449 on p53 wild­type (p53-wt) LNCaP (androgen­dependent) and p53-null PC3 (androgen-independent) prostate cancer cells. MHY-449 treatment in androgen-independent and p53-null PC3 cells resulted in inhibition of cell growth and induction of apoptosis in a concentration-dependent manner. However, MHY-449 did not show any significant effects on the growth inhibition and apoptotic cell death in androgen-dependent and p53-wt LNCaP cells. Therefore, we used PC3 cells for further studies. The induction of apoptosis in PC3 cells was observed by decreased viability, DNA fragmentation, cleavage of poly (ADP-ribose) polymerase, activations of caspase-3, -8 and -9, and alteration in the ratio of Bax/Bcl-2 protein expression. In addition, MHY-449 induced increase of late apoptosis and sub-G1 DNA which were observed by flow cytometry analysis. Furthermore, MHY-449 reduced the phosphorylation of Akt and FoxO1 and induced the translocation of FoxO1 from cytoplasm to nucleus as shown by western blot analysis. MHY-449 treatment activated extracellular signal-regulated kinase (ERK) signaling in a concentration-dependent manner. MHY-449-induced apoptosis was partially prevented by pretreatment with the ERK inhibitor PD98059 suggesting involvement of ERK in the MHY-449-induced apoptosis. Taken together, these findings suggest that MHY-449 induces apoptosis via downregulation of the Akt/FoxO1 and activation of ERK in androgen-independent, p53-null and PTEN-negative PC3 human prostate cancer cells.

α-Lipoic acid attenuates coxsackievirus B3-induced ectopic calcification in heart, pancreas, and lung.

Ectopic mineralization of soft tissues is known to be a typical response to systemic imbalance of various metabolic factors as well as tissue injury, leading to severe clinical consequences. In this study, coxsackievirus B3 (CVB3) infection in mice resulted in significant tissue injury, especially in the heart and pancreas. Inflammatory damage and apoptotic cell death were observed in CVB3-infected heart and pancreas tissues. Along with tissue damage, substantial ectopic calcification was detected in CVB3-infected heart, pancreas, and lung tissues, as determined by von Kossa staining and calcium content quantification. In addition, CVB3 infection induced upregulation of osteogenic signals, including six genes (BMP2, SPARC, Runx2, osteopontin, collagen type I, and osterix) in the heart, three genes (SPARC, osteopontin, and collagen type I) in the pancreas, and two genes (BMP2 and alkaline phosphatase) in the lung, as determined by quantitative real-time PCR analysis. Intriguingly, we showed that α-lipoic acid diminished CVB3-mediated inflammatory and apoptotic tissue damage, subsequently ameliorating ectopic calcification via the suppression of osteogenic signals. Collectively, our data provide evidence that ectopic calcification induced by CVB3 infection is implicated in the induction of osteogenic propensity, and α-lipoic acid may be a potential therapeutic agent to ameliorate pathologic calcification.

Nacre-driven water-soluble factors promote wound healing of the deep burn porcine skin by recovering angiogenesis and fibroblast function.

To assess the recovery effect of water-soluble components of nacre on wound healing of burns, water-soluble nacre (WSN) was obtained from powdered nacre. Alterations to WSN-mediated wound healing characteristics were examined in porcine skin with deep second-degree burns; porcine skin was used as a proxy for human. When WSN was applied to a burned area, the burn-induced granulation sites were rapidly filled with collagen, and the damaged dermis and epidermis were restored to the appearance of normal skin. WSN enhanced wound healing recovery properties for burn-induced apoptotic and necrotic cellular damage and spurred angiogenesis. Additionally, WSN-treated murine fibroblast NIH3T3 cells showed increased proliferation and collagen synthesis. Collectively, the findings indicate that WSN improves the process of wound healing in burns by expeditiously restoring angiogenesis and fibroblast activity. WSN may be useful as a therapeutic agent, with superior biocompatibility to powdered nacre, and evoking less discomfort when applied to a wounded area.

Efficacy of Bispectral Index Monitoring for Midazolam and Meperidine Induced Sedation during Endoscopic Submucosal Dissection: A Prospective, Randomized Controlled Study.

BACKGROUND/AIMS: Propofol induced sedation with bispectral index (BIS) monitoring has been reported to lead to higher satisfaction in patients and endoscopists during endoscopic submucosal dissection (ESD) procedures. There are no data, however, regarding the efficacy of midazolam and meperidine (M/M) induced sedation with BIS monitoring during ESD. The purpose of this study was to evaluate whether M/M induced sedation with BIS monitoring could improve satisfaction and reduce the dose of M/M required during ESD. METHODS: Between September 2009 and January 2010, 56 patients were prospectively enrolled and randomly assigned to a BIS group (n=28) and a non-BIS group (n=28). Patient and endoscopist satisfaction scores were assessed using the visual analog scale (0 to 100) following the ESD. RESULTS: The mean satisfaction scores did not significantly differ between the BIS and non-BIS groups (92.3±16.3 vs 93.3±15.5, p=0.53) or endoscopists (83.1±15.4 vs 80.0±16.7, p=0.52). Although the mean meperidine dose did not differ (62.5±27.6 vs 51.0±17.3, p=0.18) between the two groups, the mean dose of midazolam in the non-BIS group was lower than in the BIS group (6.8±2.0 vs 5.4±2.1, p=0.01). CONCLUSIONS: BIS monitoring during ESD did not increase the satisfaction of endoscopists or patients and did not lead to an M/M dose reduction. These results demonstrate that BIS monitoring provides no additional benefit to M/M induced sedation during ESD.

Systemic transplantation of human adipose-derived stem cells stimulates bone repair by promoting osteoblast and osteoclast function.

Systemic transplantation of adipose-derived stem cells (ASCs) is emerging as a novel therapeutic option for functional recovery of diverse damaged tissues. This study investigated the effects of systemic transplantation of human ASCs (hASCs) on bone repair. We found that hASCs secrete various bone cell-activating factors, including hepatocyte growth factor and extracellular matrix proteins. Systemic transplantation of hASCs into ovariectomized mice induced an increased number of both osteoblasts and osteoclasts in bone tissue and thereby prevented bone loss. We also observed that conditioned medium from hASCs is capable of stimulating proliferation and differentiation of osteoblasts via Smad/extracellular signal-regulated kinase (ERK)/JNK (c-jun NH(2) -terminal kinase) activation as well as survival and differentiation of osteoclasts via ERK/JNK/p38 activation in vitro. Overall, our findings suggest that paracrine factors secreted from hASCs improve bone repair and that hASCs can be a valuable tool for use in osteoporosis therapy.

Mitotic catastrophe induced by overexpression of budding yeast Rad2p.

Mitotic catastrophe provokes endopolyploidy, giant cell formation and, eventually, delayed cell death. Mitotic catastrophe is induced by defective cell cycle checkpoints and by some anticancer drugs, ionizing radiation and microtubule-destabilizing agents. RAD2 is a yeast homologue of XPG, which is a human endonuclease involved in nucleotide excision repair. Here we show that Rad2p overexpression alone, in the absence of extrinsic DNA damage, causes cell growth arrest and mitotic catastrophe. Interestingly, Rad2p-induced cell growth arrest is not caused by the catalytic activity of Rad2p but rather by its C-terminal region. Cells growth-arrested by Rad2p induction do not show apoptotic phenotypes and deletion of YCA1, a yeast caspase homologue, does not affect cell growth arrest by Rad2p induction. However, Rad2p-induced cell growth arrest is released by rad9 deletion but is not affected by downstream DNA damage checkpoint genes. These observations suggest that RAD2 has a function in coordinating cell cycle regulation and damaged DNA repair.