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Introduction: Systemic chemotherapy is typically administered following radical gastrectomy for advanced stage. To attenuate systemic side effects, we evaluated the effectiveness of regional chemotherapy using paclitaxel, albumin-paclitaxel, and liposome-encapsulated albumin-paclitaxel via subserosal injection in rat models employing nuclear medicine and molecular imaging technology.Method: Nine Sprague Dawley rats were divided into three groups: paclitaxel (n = 3), albumin-paclitaxel nano-particles (APNs; n = 3), and liposome-encapsulated APNs (n = 3). [123I]Iodo-paclitaxel ([123I]I-paclitaxel) was synthesized by conventional electrophilic radioiodination using tert-butylstannyl substituted paclitaxel as the precursor. Albumin-[123I]iodo-paclitaxel nanoparticles ([123I]APNs) were prepared using a desolvation technique. Liposome-encapsulated APNs (L-[123I]APNs) were prepared by thin-film hydration using DSPE-PEG2000, HSPC, and cholesterol. The rats in each group were injected with each test drug into the subserosa of the stomach antrum. After predetermined times (30 min, 2, 4, 8 h, and 24 h), molecular images of nuclear medicine were acquired using single-photon emission computed tomography/computed tomography.Results: Paclitaxel, APNs, and L-APNs showed a high cumulative distribution in the stomach, with L-APNs showing the largest area under the curve. Most drugs administered via the gastric subserosal route are distributed in the stomach and intestines, with a low uptake of less than 1% in other major organs. The time to reach the maximum concentration in the intestine for L-APNs, paclitaxel, and APNs was 6.67, 5.33, and 4.00 h, respectively.Conclusion: These preliminary results imply that L-APNs have the potential to serve as a novel paclitaxel preparation method for the regional treatment of gastric cancer.

This study aims to analyze the operation of fire emergency dispatch, understand the impact of golden time on fire emergency dispatch, and identify factors and improvement measures for effective fire emergency dispatch with in prime time. According to the results of the study, rescue dispatch activities varies depending on the nature of the incident. The summer season had a higher number of calls than other seasons, and Saturday was the day of the week with the highest number of calls (i.e., Spring: 13,189, Summer: 15,652, Fall: 13,128, Winter: 14,545). When analyzing the spatial distribution of rescue incidents, it is found that rescue incidents were concentrated in some areas. In particular, the arrival time tended to be relatively long in areas south of the Han River and in areas where some fire stations or safety centers were not deployed. Results showed that rescue incidents dispatched by the stations other than neighboring stations were also concentrated in certain points. Based on these findings, the following policy implications can be drawn: first, the location of fire stations or safety centers should be adjusted; second, dispatch personnel and equipment should be strengthened; third, interagency cooperation should be strengthened; and fourth, prevention and education programs should be strengthened. Implementing these policy recommendations will improve fire emergency services' efficiency and response capabilities and minimize the occurrence and damage of life-saving events.

Abstract Although aptamers have shown excellent target specificity in preclinical and clinical studies either by themselves or as aptamer‐drug conjugates, their in vivo tissue pharmacokinetic (PK) analysis is still problematic. We aimed to examine the utility of image‐based positron emission tomography (PET) to evaluate in vivo tissue PK, target specificity, and applicability of oligonucleotides. For this, fluorine‐18‐labeled aptamers with erb‐b2 receptor tyrosine kinase 2 (ERBB2)‐specific binding were synthesized by base‐pair hybridization using a complementary oligonucleotide platform. To investigate the PKs and properties of in vivo tissue, usefulness of in vivo PET imaging in the development of an oligonucleotide‐based drug as an assessment tool was evaluated in normal and tumor xenografted mice. ERBB2‐cODN‐idT‐APs‐[18F]F ([18F]1), injected intravenously showed significant and rapid uptake in most tissues except for the initial brain and muscle; the uptake was highest in the heart, followed by kidneys, liver, lungs, gall bladder, spleen, and stomach. The main route of excretion was through the renal tract ~77.8%, whereas about 8.3% was through the biliary tract of the total dose. The estimated effective dose for an adult woman was 0.00189 mGy/MBq, which might be safe. ERBB2‐positive tumor could be well visualized in the KPL4 xenograft animal model by in vivo PET imaging. Consequently, the distribution in each organ including ERBB2 expression could be well determined and quantified by PET with fluorine‐18‐labeled aptamers. In vivo PK parameters such as terminal half‐life, time to maximum concentration, area under the curve, and maximum concentration, were also successfully estimated. These results suggest that image‐based PET with radioisotope‐labeled aptamers could be provide valuable information on properties of oligonucleotide‐based drugs in drug discovery of targeted therapeutics against various diseases.

Abstract Background There are few prospective studies on the correlations between MRI features and whole RNA-sequencing data in breast cancer according to molecular subtypes. The purpose of our study was to explore the association between genetic profiles and MRI phenotypes of breast cancer and to identify imaging markers that influences the prognosis and treatment according to subtypes. Methods From June 2017 to August 2018, MRIs of 95 women with invasive breast cancer were prospectively analyzed, using the breast imaging-reporting and data system and texture analysis. Whole RNA obtained from surgical specimens was analyzed using next-generation sequencing. The association between MRI features and gene expression profiles was analyzed in the entire tumor and subtypes. Gene networks, enriched functions, and canonical pathways were analyzed using Ingenuity Pathway Analysis. The P value for differential expression was obtained using a parametric F test comparing nested linear models and adjusted for multiple testing by reporting Q value. Results In 95 participants (mean age, 53 years ± 11 [standard deviation]), mass lesion type was associated with upregulation of CCL3L1 (sevenfold) and irregular mass shape was associated with downregulation of MIR421 (sixfold). In estrogen receptor-positive cancer with mass lesion type, CCL3L1 (21-fold), SNHG12 (11-fold), and MIR206 (sevenfold) were upregulated, and MIR597 (265-fold), MIR126 (12-fold), and SOX17 (fivefold) were downregulated. In triple-negative breast cancer with increased standard deviation of texture analysis on precontrast T1-weighted imaging, CLEC3A (23-fold), SRGN (13-fold), HSPG2 (sevenfold), KMT2D (fivefold), and VMP1 (fivefold) were upregulated, and IGLC2 (73-fold) and PRDX4 (sevenfold) were downregulated (all, P

Abstract We aimed to compare cervical elastographic parameters based on a previous loop electrosurgical excision procedure (LEEP) and to determine whether they can predict preterm delivery in pregnant women with a history of LEEP. This multicenter prospective case–control study included 71 singleton pregnant women at 14–24 weeks of gestation with a history of LEEP and 1:2 gestational age-matched controls. We performed cervical elastography using E-cervix and compared maternal characteristics, delivery outcomes, cervical length (CL), and elastographic parameters between the two groups. The median mid-trimester CL was significantly shorter in the LEEP group. Most elastographic parameters, including internal os (IOS), external os (EOS), elasticity contrast index (ECI), and hardness ratio (HR), were significantly different in the two groups. In the LEEP group, the sPTD group compared to the term delivery (TD) group showed a higher rate of previous sPTD (50% vs. 1.7%, p

Jeju is the largest island in Korea and one of its key tourist attractions. As the number of foreign tourists steadily increases, so does the number of injuries incurred there. Accordingly, this study aimed to describe and compare the characteristics of injuries suffered by foreign tourists versus those of domestic tourists. As a cross-sectional study of a retrospective medical record survey, the study was conducted with reference to the Jeju Injury Surveillance System from the 11-year period of January 2008 to December 2018. The following factors were investigated: demographic data, mechanism of injury, place of occurrence, activity when injured, patient outcome, and mortality. A total of 92,095 injured Jeju Island visitors was recorded during this time, a number that included 88,050 Koreans and 4,045 foreigners. The gender ratio showed similar patterns between the two groups and there were no significant age differences. In both groups, the most common mechanism of injury was collisions/cuts. Also, more foreigners experienced falls than Koreans. Regarding the location, Koreans had the most road accidents, while foreigners were most likely to be injured at outdoor locations, such as seas and rivers. Furthermore, more foreigners experienced severe injuries requiring hospitalization. Notably, this study showed the differences in injury between foreign and Korean tourists visiting Jeju Island and its findings lend support to targeted safety promotion programs.

Objective To evaluate the clinical significance of soft markers for aneuploidy screening in Korean women. Methods We retrospectively reviewed the medical records of 5,428 singleton pregnant women who underwent sonography during the second trimester at seven institutions in South Korea. We evaluated the prevalence of the following soft markers: intracardiac echogenic focus, choroid plexus cysts, pyelectasis, echogenic bowel, and mild ventriculomegaly. We developed best-fitted regression equations for the fetal femur and humerus length using our data and defined a short femur and humerus as both long bones below the fifth centile. The results of genetic testing and postnatal outcomes were investigated in patients who had been diagnosed with aforementioned soft markers. Results The median maternal age of our study population was 33 years, and the median gestational age at the time of ultrasonographic examination was 21 weeks. We detected soft markers in 10.0% (n=540) of fetuses: 9.3% (n=504) were isolated cases and 0.7% (n=36) of cases had two or more markers. We identified only two aneuploides (trisomy 18, 46,XX,t[8;10][q22.1;p13]), of which one was clinically significant. We presented the neonatal outcomes of the fetuses with the respective soft markers. Preterm delivery, low birth weight, and small-for-gestational-age (SGA) were significantly more common in women with a shortened fetal femur (P

Abstract Background The effect of menopausal hormone therapy (MHT) on gastrointestinal (GI) cancers is controversial, and no research has been conducted in the East. This study investigates the association between MHT and GI cancer risks in South Korea. Methods A prescription-based cohort study was conducted using the NHIS Sample Cohort (2002–2013) of Korea. We used 1:5 propensity score matching, and 22,577 MHT users and 111,113 non-users were selected. Kaplan–Meier survival curves with log-rank tests were used. Cox proportional hazard models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI). Landmark analysis was used to determine dose–response relationship. Results The median follow-up was 79.6 of months. Kaplan–Meier survival curve showed less frequent GI cancer diagnoses in MHT users compared to non-users (0.13 vs. 0.16 per 100,000 person-years). Menopausal hormone therapy was associated with decreased incidence of GI cancer (HR = 0.809, 95%CI = 0.691–0.946) and colorectal cancer (CRC) (HR = 0.757, 95%CI = 0.577–0.995). Gastric cancer (GC) incidence showed marginal significance (HR = 0.787, 95%CI = 0.605–1.023). The mortality from GI cancer was lower in MHT users than in non-users (HR = 0.737, 95%CI = 0.547–0.993). The relationship between MHT and GI cancer was stronger with increasing MHT dose in terms of both incidence (P trend = 0.0002) and mortality (P trend = 0.0064). Conclusions The association between MHT use and reduced risks of GI cancers was attributed to CRC and GC and showed a dose–response relationship in a population-based cohort study.

Abstract DHP107 is a newly developed lipid‐based oral formulation of paclitaxel. We evaluated the in vivo tissue pharmacokinetics (PKs) of DHP107 in mice and patients using positron emission tomography (PET). Radioisotope‐labeled [3H]DHP107 and [18F]DHP107 for oral administration were formulated in the same manner as the manufacturing process of DHP107. In vivo tissue PK were assessed in healthy ICR mice and breast cancer xenografted SCID mice. Two patients with metastatic breast cancer were clinically evaluated for absorption at the target lesion after internal absorbed dose estimation. Whole‐body PET/computed tomography data were acquired in healthy and xenografted mice and in patients up to 10–24 h after administration. Tissue [18F]DHP107 signals were plotted against time and PK parameters were determined. The amounts of radioactivity in various organs and excreta were determined using a beta‐counter and are expressed as the percentage of injected dose (ID). Oral [18F]DHP107 was well‐absorbed and reached the target lesion in mice and patients with breast cancer. Significant amounts of radioactivity were found in the stomach, intestine, and liver after oral administration of [3H]‐ and [18F]DHP107 in healthy mice. The [18F]DHP107 reached a peak distribution of 0.7–0.8%ID in the tumor at 5.6–7.3 h in the xenograft model. The [18F]DHP107 distribution in patients with metastatic breast cancer was the highest at 3–4 h postadministration. Systemic exposures after administration of a DHP107 therapeutic dose were comparable with those in previous studies. PET using radioisotope‐labeled drug candidates is useful for drug development and can provide valuable information that can complement plasma PK data, particularly in early phase clinical trials.

Abstract [68Ga]PSMA-11 is a prostate-specific membrane antigen (PSMA)-targeting radiopharmaceutical for diagnostic PET imaging. Its application can be extended to targeted radionuclide therapy (TRT). In this study, we characterize the biodistribution and pharmacokinetics of [68Ga]PSMA-11 in PSMA-positive and negative (22Rv1 and PC3, respectively) tumor-bearing mice and subsequently estimated its internal radiation dosimetry via voxel-level dosimetry using a dedicated Monte Carlo simulation to evaluate the absorbed dose in the tumor directly. Consequently, this approach overcomes the drawbacks of the conventional organ-level (or phantom-based) method. The kidneys and urinary bladder both showed substantial accumulation of [68Ga]PSMA-11 without exhibiting a washout phase during the study. For the tumor, a peak concentration of 4.5 ± 0.7 %ID/g occurred 90 min after [68Ga]PSMA-11 injection. The voxel- and organ-level methods both determined that the highest absorbed dose occurred in the kidneys (0.209 ± 0.005 Gy/MBq and 0.492 ± 0.059 Gy/MBq, respectively). Using voxel-level dosimetry, the absorbed dose in the tumor was estimated as 0.024 ± 0.003 Gy/MBq. The biodistribution and pharmacokinetics of [68Ga]PSMA-11 in various organs of subcutaneous prostate cancer xenograft model mice were consistent with reported data for prostate cancer patients. Therefore, our data supports the use of voxel-level dosimetry in TRT to deliver personalized dosimetry considering patient-specific heterogeneous tissue compositions and activity distributions.

The rhesus macaque is an important model species in several branches of science, but the utility of this model would be enhanced by the ability to measure behaviour throughout pose. Here, the authors describe a deep learning-based markerless motion capture system for estimating 3D pose in freely moving macaques.

ObjectiveTo provide a standardized protocol for the measurement of cervical strain elastography, present its reproducibility, and analyze baseline clinical factors affecting the measurement of elastographic parameters.MethodsThis study was performed by the Korean Research Group of Cervical Elastography. We enrolled pregnant women according to our study protocol. After measuring the cervical length, elastography was performed using the E-Cervix™ quantification tool to measure the strain of the cervix using intrinsic compression. We evaluated 5 elastographic parameters, namely, the strain of the internal os of the cervix (IOS), strain of the external os of the cervix (EOS), ratio of the strain of IOS and EOS, elasticity contrast index, and hardness ratio. For baseline clinical factors, we examined the maternal body mass index, blood pressure, heart rate, uterine artery Doppler indices, and fetal presentation.ResultsWe established a specific protocol for the measurement of cervical elastography using the E cervix program. For all elastographic parameters, the intra-observer intraclass correlation coefficient (ICC) ranged from 0.633 to 0.723 for single measures and from 0.838 to 0.887 for average measures, and the inter-observer ICC ranged from 0.814 to 0.977 for single measures and from 0.901 to 0.988 for average measures. Regression analysis showed that the measurement of the elastographic parameter was not affected by baseline clinical factors.ConclusionWe present a standardized protocol for the measurement of cervical elastography using intrinsic compression. According to this protocol, reproducibility was acceptable and the measurement of elastographic parameters was not affected by the baseline clinical factors studied.

Abstract Background Soft tissue asymmetry such as lip canting or deviation of the philtrum is an important influencing factor for unbalanced facial appearance. Lip canting could be improved by the correction of the occlusal canting or positional change of the mentum. Although there are many studies about changes of lip canting, however, postoperative changes of philtrum deviation have not been yet reported. In this study, we investigate the positional change of the philtrum after orthognathic surgery and influencing factors. Methods Positional change of the philtrum was evaluated in 41 patients with facial asymmetry who underwent bimaxillary surgery, in relation to other anatomical soft tissue landmarks using a frontal clinical photo. The surgical movement of the maxillary and mandibular dental midline and canting were measured in postero-anterior cephalogram before and 1 day after surgery. The same procedure was repeated in patients with more than 1.5 mm perioperative change of the mandibular dental midline after bimaxillary surgery. Results Maxillary dental midline shifting and canting correction did not have a significant correlation with lateral movement of the philtrum midline. However, the mandibular shift had a statistically significant correlation with a lateral movement of the philtrum (p

Background/Aim: Cecal intubation during colonoscopy is prone to be prolonged in women, which may be related to frequent exposure to pelvic/abdominal surgery. We evaluated the association between Cecal Intubation Time (CIT) and prior episodes of pelvic/abdominal surgery in women. Patients and Methods: A cross-sectional study was conducted on screening participants who underwent colonoscopy. Multivariate regression with parameter estimates (β) was performed to determine the factors affecting CIT, including age, body mass index (BMI), bowel preparation, sedation, diverticulosis, experience of colonoscopists, and a surgical history. Also, subgroup analyses according to type of surgery were performed. Results: A total of 835 women were enrolled. The mean CIT was 5.82 ± 3.40 min. 323 females (38.7%) had episodes of surgery. The CIT was prolonged in cases performed by non-experienced trainees (β = 3.61, P< 0.001) and with a history of gynecological surgery (β = 0.97, P = 0.001). In the subgroup of non-experienced trainees, lower BMI, poor preparation, and a history of cesarean section significantly prolonged the CIT. Also, the risk for difficult colonoscopy (CIT ≥ 15 min) was increased with a history of cesarean section (odds ratio = 4.43, P= 0.024). Conclusion: A prior episode of gynecological surgery prolonged CIT. Also, cesarean section history was associated with difficult colonoscopy in the examination by non-experienced trainees.

Abstract In this research, a cable-type wall system that could replace the conventional aluminum curtain wall system for reinforced concrete high-rise buildings is proposed. The cable-type wall system is a newly developed system, which could be used as an existing exterior skin system, and can effectively support the wind load acting on the exterior of the high-rise buildings by the pre-induced initial tension force to the cable supporting the glass. The main advantages of the cable-type wall system are that the expense of construction could be reduced due to the simplicity of the construction. The experiment of structural analysis and air/water tightness was performed to evaluate its feasibility of industrialization. The structural performance of the cable-type wall system was evaluated through the structural analysis and the full-scale experiment to predict the initial pre-tension force and the design load displacement of the vertical one-way cable-type wall system that can be used for a typical floor of the high-rise building. The initial pre-tension force and structural behavior of the cable were analyzed by using the structural design program MIDAS-Gen. The maximum deformation value in the structural test was found to satisfy the AAMA condition, which is equal to the size of the facade skin system. The air/water tightness test was conducted to verify the performance. Test results show that the cable-type wall system satisfies the air/water tightness performance standards ASTM E283, E331 and AAMA 501.1-05 which are the most basic standards that the facade system must provide. As a result of this study, it is expected that the proposed cable-type wall system could be used for facade system, not only the structural performance but also air/water tightness performance are secured.

Fas-associated factor 1 (FAF1), a Fas-binding protein, is implicated in neuronal cell death in Parkinson’s disease (PD). We examined the effects of a novel FAF1 inhibitor, KM-819, in dopaminergic neurons in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model using [18F]FE-PE2I positron emission tomography (PET). The MPTP model was generated with subacute MPTP treatment (20 mg/kg/day, i.p.) for 5 consecutive days in C57bl/6J mice. This study included three groups: the control group (treatment with saline only), the MPTP model group with KM-819 treatment (20 mg/kg/day p.o.) for 6 days, and the MPTP model group without KM-819 treatment. [18F]FE-PE2I PET studies were conducted in the same animals before and after MPTP with or without KM-819 treatment to monitor changes in striatal dopamine transporter activity indicated by non-displaceable binding potential (BPND) of [18F]FE-PE2I, and the expression levels of tyrosine hydroxylase were assessed using immunohistochemistry before and after KM-819 treatment. After MPTP injection, decreased striatal BPND was observed in the MPTP model group compared with the control group. Striatal BPND increased in the MPTP model group with KM-819 treatment, but not in the MPTP model group without KM-819 treatment. The tyrosine hydroxylase expression levels also significantly increased in the MPTP model group with KM-819 treatment compared with the control group. This study indicates that inhibition of the Fas-mediated cell death pathway by KM-819 has neurorestorative effects in striatal dopamine neurons in the MPTP model. Further studies would be needed to investigate the potential of KM-819 as a therapeutic drug for PD treatment.

We performed in vivo PET imaging with 3-[18F]F-CP118,954 (1) for acetylcholinesterase (AChE) and [18F]fluoromethyl-PBR28-d2 (2) for translocator protein 18-kDa (TSPO) to investigate the inflammatory brain response after stroke. Imaging studies were performed in the middle cerebral artery occlusion (MCAO) Sprague-Dawley rat model for a period of three weeks. The percentage injected dose per tissue weight (%ID/g) of striatum of 1, and cortex of 2 were obtained, respectively. To trace the sequential inflammatory responses, AChE imaging of 1 was done on post-MCAO day 2, after giving cold PK-11195 for 1 day, and TSPO imaging of 2 was carried out on post-MCAO day 11, after giving donepezil for 10 days. AChE activity in the MCAO-lesioned side were significantly higher than that of the contralateral side on day one, and TSPO activity was highest on day 11. TSPO inhibitor, PK-11195 did not affect AChE activity on day two, while AChE inhibitor, donepezil significantly lowered TSPO binding on day 12. Our study demonstrates that AChE level is elevated in the early course of brain ischemia as a trigger for the inflammatory response, and TSPO level is elevated persistently throughout the post-ischemic injury in the brain. Also, the AChE inhibitor may be able to inhibit or delay neurotoxic inflammatory responses and serve as a beneficial treatment option.

Objectives: Oldenlandia diffusa is traditionally used to relieve the symptoms of and to treat various diseases, but its anti-cancer activity has not been well studied. In the present study, the authors investigated the anti-cancer effects of an ethanol extract of Oldenlandia diffusa (EOD) on HT-29 human adenocarcinoma cells. Methods: Cells were treated with different concentrations of an EOD, and cell death was assessed by using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Analyses of the sub G1 peak, the caspase-3 and -9 activities, and the mitochondrial membrane depolarizations were conducted to confirm cell death by apoptosis. Also, intracellular reactive oxygen species (ROS) generation was determined using carboxy-H2DCFDA (5-(and-6)-carboxy-20,70-dichlorodihydrofluorescein diacetate). Results: EOD inhibited the proliferation of HT-29 cells for 24 hours by 78.6% ± 8.1% at 50 μg/mL, 74.4% ± 4.6% at 100 μg/mL, 65.9% ± 5.2% at 200 μg/mL, 51.4% ± 6.2% at 300 μg/mL, and by 41.7% ± 8.9% at 400 μg/mL, and treatment for 72 hours reduced the proliferation at the corresponding concentrations by 43.3% ± 8.8%, 24.3 ± 5.1 mV, 13.5 ± 3.2 mV, 6.5 ± 2.3 mV, and by 2.6 ± 2.3 mV. EOD increased the number of cells in the sub-G1 peak in a dose-dependent manner. The mitochondrial membrane depolarization was elevated by EOD. Also, caspase activities were dose-dependently elevated in the presence of EOD, and these activities were repressed by a pan-caspase inhibitor (zVAD-fmk). The ROS generation was significantly increased by EOD and N-acetyl-L-cysteine (NAC; a ROS scavenger) remarkably abolished EOD-induced cell death. In addition, a combination of sub-optimal doses of EOD and chemotherapeutic agents noticeably suppressed the growth of HT-29 cancer cells. Conclusion: These results indicate that EOD might be an effective chemotherapeutic for the treatment of human colorectal cancer.

Background: Ginseng belongs to the genus Panax. Its main active ingredients are the ginsenosides. Interstitial cells of Cajal (ICCs) are the pacemaker cells of the gastrointestinal (GI) tract. To understand the effects of ginsenoside Re (GRe) on GI motility, the authors investigated its effects on the pacemaker activity of ICCs of the murine small intestine. Methods: Interstitial cells of Cajal were dissociated from mouse small intestines by enzymatic digestion. The whole-cell patch clamp configuration was used to record pacemaker potentials in cultured ICCs. Changes in cyclic guanosine monophosphate (cGMP) content induced by GRe were investigated. Results: Ginsenoside Re (20–40μM) decreased the amplitude and frequency of ICC pacemaker activity in a concentration-dependent manner. This action was blocked by guanosine 5′-[β-thio]diphosphate [a guanosine-5'-triphosphate (GTP)-binding protein inhibitor] and by glibenclamide [an adenosine triphosphate (ATP)-sensitive K+ channel blocker]. To study the GRe-induced signaling pathway in ICCs, the effects of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (a guanylate cyclase inhibitor) and RP-8-CPT-cGMPS (a protein kinase G inhibitor) were examined. Both inhibitors blocked the inhibitory effect of GRe on ICC pacemaker activity. L-NG-nitroarginine methyl ester (100μM), which is a nonselective nitric oxide synthase (NOS) inhibitor, blocked the effects of GRe on ICC pacemaker activity and GRe-stimulated cGMP production in ICCs. Conclusion: In cultured murine ICCs, GRe inhibits the pacemaker activity of ICCs via the ATP-sensitive potassium (K+) channel and the cGMP/NO-dependent pathway. Ginsenoside Re may be a basis for developing novel spasmolytic agents to prevent or alleviate GI motility dysfunction.

Objective One of the most important and basic variables in emergency department (ED) operations is patient visit volumes. This variable is usually predicted on the basis of the average ED patient visit volume over a certain period. However, ED patient visit variability is poorly understood. Therefore, we evaluated ED patient visit variability in order to determine if the average can be used to operate EDs. Methods Nationwide ED patient visit data were from the standard emergency patient data of the National Emergency Department Information System. The data are transferred automatically by 141 EDs nationwide. The hourly ED visit volumes over 365 days were determined, and the variability was analyzed to evaluate the representativeness of the average. Results A total of 4,672,275 patient visits were collected in 2013. The numbers of daily ED patient visits were widely dispersed and positively skewed rather than symmetric and narrow with a normal distribution. Conclusion The daily variability of ED visit is too large and it did not show normal distribution. The average visit volume does not adequately represent ED operation.

Objectives: Rheum undulatum L. has traditionally been used for the treatment of many diseases in Asia. However, its anti-proliferative activity in cancer has still not been studied. In the present study, we investigated the anti-cancer effects of methanol extract of Rheum undulatum L. (MERL) on human adenocarcinoma gastric cell lines (AGS). Methods: To investigate the anti-cancer effect of MERL on AGS cells, we treated the AGS cells with varying con¬centrations of MERL and performed 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays. Cell cycle analyses, measurements of the mitochondrial membrane potential (MMP), caspase activity assays and Western blots were conducted to determine whether AGS cell death occurred by apoptosis. Results: Treatment with MERL significantly inhibited growth of AGS cells in a concentration dependent manner. MERL treatment in AGS cells leaded to increased accumulation of apoptotic sub G1 phase cells in a concentration dependent manner. In control cultures, 5.38% of the cells were in the sub G1 phase. In MERL treated cells, however, this percentage was significantly increased (9.95% at 70 μg/mL, 15.94% at 140 μg/mL, 26.56% at 210 μg/mL and 38.08% at 280 μg/mL). MERL treatment induced the decreased expression of pro-caspase-8 and -9 in a concentration dependent manner, whereas the expression of the active form of caspase-3 was increased. A subsequent Western blot analysis revealed increased cleaved levels of poly (ADP-ribose) polymerase (PARP) protein. Also, treatment with MERL increased the activities of caspase-3 and -9 compared with the control. MERL treatment increased the levels of the pro-apoptotic truncated Bid (tBid) and Bcl2 Antagonist X (Bax) proteins and decreased the levels of the anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein, whose is the stabilization of mitochondria. However, inhibitions of p38, extracellular signal regulated kinases (ERKs) and C-Jun N-terminal kinases (JNK) by MERL treatment did not affect cell death. Conclusion: These results suggest that MERL mediated cell death is associated with an intrinsic apoptotic pathway in AGS cells.

A 42-year-old man visited the emergency department complaining of lower extremity swelling and myalgia. His influenza A antigen test was positive, and he was admitted for supportive care of severe myalgia. On the first hospital day, the swelling in his lower legs was aggravated with intolerable pain, and his creatine phosphokinase and hemoglobin levels were elevated. He was treated with massive hydration, albumin replacement, continuous venovenous hemofiltration, phlebotomy, and oseltamivir. The swelling and pain in his extremities were decreased without renal dysfunction, even though peripheral neuropathy and muscular complication persisted. Systemic capillary leak syndrome is a rare but life-threatening condition. The diagnosis is made clinically based on a classic triad of hypotension, hypoalbuminemia, and hemoconcentration. In our case, the influenza A infection was related to the capillary leakage.

BACKGROUND: Peripheral venous catheterization (PVC) is a less invasive and time consuming technique than central venous catheterization (CVC); however, for patients in circulatory collapse or receiving cardiopulmonary resuscitation (CPR), PVC cannot be achieved easily. CVC can provide not only a more effective administration route for medication, but also important hemodynamic information. Owing to the possibility of CPR interruptions and complications, CVC is recommended only after the failure of PVC. This observational study is aimed to evaluate the risks and benefits of CVC during CPR. METHODS: This retrospective observational study was performed in the emergency department (ED) of a university hospital. Adult patients without a pulse on arrival were consecutively enrolled if subclavian CVC was performed at the beginning of CPR. Patients who already had an established intravenous route or had severe chest injuries on arrival were excluded. Closed-circuit television was used to evaluate the frequency of compression interruption. The incidence of iatrogenic pneumothorax, an acute mechanical complication associated with subclavian CVC, was investigated using chest X-ray after CPR. RESULTS: During a 6-month period, 35 patients underwent CPR and 31 of these received subclavian CVC. Among the patients, one patient experienced iatrogenic pneumothorax (3.8%), and 13 CPR interruptions occurred in 10 subjects during subclavian CVC. CONCLUSIONS: During CPR in 31 patients, one iatrogenic pneumothorax was caused by subclavian CVC, and CPR interruptions were observed in approximately 30% of cases.

The present study investigated possible mechanisms on the apoptosis induction of human leukemic cells by fucoidan, a sulfated polysaccharide found in marine algae. Fucoidan treatment of cells resulted in inhibition of growth and induction of apoptosis, as measured by 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyl-tetrazolium (MTT) assay, fluorescence microscopy, DNA fragmentation, and flow cytometry analysis. The increase in apoptosis was associated with the proteolytic activation of caspases, Bid cleavage, insertion of pro-apoptotic Bax into the mitochondria, release of cytochrome c from mitochondria to cytosol, and loss of mitochondria membrane potential (MMP) in U937 cells. However, apoptosis induced by fucoidan was attenuated by caspase inhibitors, indicating that fucoidan-induced apoptosis was dependent on the activation of caspases. Furthermore, fucoidan treatment effectively activated the p38 mitogen-activated protein kinase (MAPK) and p38 MAPK inhibitor, SB203580, and significantly reduced fucoidan-induced apoptosis through inhibition of Bax translocation and caspases activation, suggesting that the activation of p38 MAPK may play a key role in fucoidan-induced apoptosis. In addition, the authors found fucoidan-induced significantly attenuated in Bcl-2 overexpressing U937 cells, and pretreatment with fucoidan and HA 14-1, a small-molecule Bcl-2 inhibitor, markedly increased fucoidan-mediated apoptosis in Bcl-2 overexpressing U937 cells. Our findings imply that we may attribute some of the biological functions of p38 MAPK and Bcl-2 to their ability to inhibit fucoidan-induced apoptosis.

High-level expression of recombinant human growth hormone (hGH) in Escherichia coli (E. coli) leads to the formation of insoluble aggregates as inclusion bodies devoid of biological activity. Until recently, significant efforts have been made to improve the recovery of active hGH from inclusion bodies. Here, we developed an efficient procedure for the production of completely soluble hGH by minimizing the formation of inclusion bodies and optimizing protein purification conditions. Under the newly established conditions we were able to obtain most of the total hGH in the soluble fraction. We show that the soluble protein can be efficiently purified in high yield by a series of chromatographic procedures. We analyzed the resulting hGH using various analytical techniques such as reversed-phase high-performance liquid chromatography (RP-HPLC), size-exclusion chromatography (SEC), matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry, and circular dichroism (CD). These multiple analyses support the conclusion that we obtained highly pure hGH with the expected molecular mass and intact secondary structure. The biological activity of purified hGH was also confirmed by evaluating its growth-promoting effect using a cell proliferation assay. Taken together, we describe a straightforward strategy for the production of completely soluble and biologically active hGH in E. coli.