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We performed a comprehensive systematic review and meta-analysis comparing initiation of full solid diet (FSD) versus stepwise diet to better define the management of patients with mild acute pancreatitis (AP).Electronic databases were searched through August 2, 2021 for trials comparing initial FSD versus stepwise advancement in patients with mild AP on length of hospital stay (LOHS). We stratified by whether diet was initiated early (within 24 h or immediately upon presence of bowel sounds).We identified seven RCTs that compared LOHS in AP patients who received initial oral intake with solid diet versus stepwise diet. Across the studies a total of 305 patients were randomized to immediate FSD and 308 patients to sequential advancement. Patients who were initiated on a FSD had a significant reduction in total LOHS (Standardized Mean Difference (SMD) -0.52 [95% CI -0.69, -0.36]). There was no difference in post refeeding abdominal pain, tolerance of diet, or necessity to cease diet between the two groups. Sub-analysis of three studies that initiated FSD early reduced total LOHS (OR -0.95 [95% CI -1.26, -0.65]) compared to those who received graded diet advancement as well as higher likelihood of tolerating the assigned diet (OR 6.8 [95% CI 1.2, 39.2]).Our meta-analysis shows that initiation of FSD reduces total LOHS in patients with mild AP and does not increase post refeeding abdominal pain. Though additional high-quality studies are needed, these findings support initial solid diet for AP and consideration of feeding within the first 24 h.

BACKGROUND AND OBJECTIVES Patients who undergo total knee arthroplasty (TKA) have a risk of postoperative anaemia. This observational study evaluated whether single-dose intravenous ferric carboxymaltose (FCM) administered immediately after TKA facilitates the correction of anaemia. MATERIALS AND METHODS We retrospectively analysed 722 patients who underwent primary TKA. The FCM group receiving 1000 mg intravenous FCM within one postoperative hour was compared with the non-FCM group that did not receive the medication. A propensity score matching with multiple logistic regression analysis was used to minimize intergroup differences in the baseline characteristics and postoperative blood loss. The rate and severity of postoperative anaemia were compared between the groups, along with haemoglobin (Hb) value, transfusion rate and complications. RESULTS After propensity score matching, 231 patients were included in each group. In the FCM group, the rate of anaemia at postoperative day (POD) 7 (p = 0.021) and postoperative week (POW) 5 (p

Background Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide, and liver cancer has increased in mortality due to liver cancer because it was detected at an advanced stages in patients with liver dysfunction, making HCC a lethal cancer. Accordingly, we aim to new targets for HCC drug discovery using HCC tumor spheroids. Methods Our comparative proteomic analysis of HCC cells grown in culture as monolayers (2D) and spheroids (3D) revealed that argininosuccinate synthase 1 (ASS1) expression was higher in 3D cells than in 2D cells due to upregulated endoplasmic reticulum (ER) stress responses. We investigated the clinical value of ASS1 in Korean patients with HCC. The mechanism underlying ASS1-mediated tumor suppression was investigated in HCC spheroids. ASS1-mediated improvement of chemotherapy efficiency was observed using high content screening in an HCC xenograft mouse model. Results Studies of tumor tissue from Korean HCC patients showed that, although ASS1 expression was low in most samples, high levels of ASS1 were associated with favorable overall survival of patients. Here, we found that bidirectional interactions between ASS1 ER stress responses in HCC-derived multicellular tumor spheroids can limit HCC progression. ASS1 overexpression effectively inhibited tumor growth and enhanced the efficacy of in vitro and in vivo anti-HCC combination chemotherapy via activation of the PERK/eIF2α/ATF4/CHOP axis, but was not dependent on the status of p53 and arginine metabolism. Conclusions These results demonstrate the critical functional roles for the arginine metabolism–independent tumor suppressor activity of ASS1 in HCC and suggest that upregulating ASS1 in these tumors is a potential strategy in HCC cells with low ASS1 expression.

Background and Objectives: Some of the postoperative complications following orthopaedic surgeries are associated with a systemic inflammatory response (SIR), which varies depending on the anaesthetic technique. We aimed to compare the effects of general and spinal anaesthesia on the SIR after total knee arthroplasty (TKA), based on C-reactive protein (CRP) levels, the platelet-lymphocyte ratio (PLR), and the neutrophil-lymphocyte ratio (NLR). Materials and Methods: Patients who underwent TKA between January 2014 and December 2018 were included. Electronic medical records of the patients were retrospectively reviewed and analysed. To reduce the impact of potential confounding factors, we performed propensity score matching according to the anaesthetic technique. Results: A total of 1311 TKA cases were analysed. After propensity score matching, the maximal CRP value and changes in CRP levels in the general anaesthesia group were higher than those in the spinal anaesthesia group. However, the maximal NLR and PLR and the changes in NLR and PLR were not different between the two groups. There were no differences in postoperative clinical outcomes. Conclusion: Spinal anaesthesia tended to induce a lower inflammatory response than general anaesthesia when considering CRP levels in patients undergoing TKA. However, the effects of anaesthetic techniques on the overall outcomes were not significant.

Background Incorrect use of inhalers among asthma and COPD patients is very prevalent. Yet, no single intervention is considered standard of care. We aimed to conduct a COPD-specific investigation of active one-on-one coaching as the educational intervention to improve pressurized metered dose inhaler (pMDI) technique and COPD symptoms management. Methods COPD patients who have pMDI in their treatment regimen were enrolled in this prospective study using the Global Initiative for Chronic Obstructive Lung Disease criteria. After rapid cognitive screen, inhaler technique was assessed and an active one-on-one coaching was provided utilizing the 12-step American Thoracic Society instructions. Patients’ inhaler technique was assessed and scored again at their regular follow-up visits. Results One hundred and one patients participated in the study. The percentage of pMDI misuse decreased from 43.5% pre-teaching to 12.9% post-teaching (binomial test p value p value Conclusions This study reveals that many COPD patients have incorrect pMDI techniques that can be improved with a short training in the clinic. Trial Registration: Not applicable.

Background Mitogen-activated protein kinases (MEK 1/2) are central components of the RAS signalling pathway and are attractive targets for cancer therapy. These agents continue to be investigated in KRAS mutant colon cancer but are met with significant resistance. Clinical investigations have demonstrated that these strategies are not well tolerated by patients. Methods We investigated a biomarker of response for MEK inhibition in KRAS mutant colon cancers by LC-MS/MS analysis. We tested the MEK inhibitor in PIK3CA wild(wt) and mutant(mt) colon cancer cells. In addition, we tested the combinational effects of MEK and TNKS inhibitor in vitro and in vivo. Results We identified β-catenin, a key mediator of the WNT pathway, in response to MEK inhibitor. MEK inhibition led to a decrease in β-catenin in PIK3CA wt colon cancer cells but not in mt. Tumour regression was promoted by combination of MEK inhibition and NVP-TNS656, which targets the WNT pathway. Furthermore, inhibition of MEK promoted tumour regression in colon cancer patient-derived xenograft models expressing PIK3CA wt. Conclusions We propose that inhibition of the WNT pathway, particularly β-catenin, may bypass resistance to MEK inhibition in human PIK3CA mt colon cancer. Therefore, we suggest that β-catenin is a potential predictive marker of MEK inhibitor resistance.

Sacrococcygeal teratoma (SCT) is the most common teratoma presenting at birth. Life-threatening bleeding is a major complication during tumor excision in children. In this study we demonstrate our technique for laparoscopic division of median sacral artery (MSA) during dissection of SCT in 2 pediatric patients as a safe technique to minimize risk of hemorrhage.Two female infants diagnosed with types III and IV SCTs underwent preoperative evaluation in the postnatal period. The first patient was an 18-month-old girl who presented with metastatic type IV teratoma, resected after neoadjuvant therapy, and the second patient was a 6-day-old girl with prenatal diagnosis of cystic type III teratoma. Using laparoscopy in both patients, the presacral space was reached by opening the peritoneal reflection with blunt dissection and the MSA was identified. Then it was carefully isolated and divided with 3 or 5 mm sealing device. The pelvic components of the tumors were partially dissected using laparoscopy. The first patient's tumor resection was completed using a posterior sagittal approach and the second patient required a standard Chevron incision. Along with the description of our technique, a review of the current literature for the management of SCT and MSA was performed.Both patients underwent successful laparoscopic division of the MSA and resection of the SCTs without complications.Laparoscopic MSA division before SCT excision offers a safe approach that can reduce the risk of hemorrhage during surgery.

Purpose: This study aimed to analyze how a private high school in Seoul developed and executed a “school disinfection strategy” to ensure the students' right to study in a safe environment, and also to analyze the lessons learned from this process.Methods: This was a case study of school health in a community-based school reopening during the COVID-19 pandemic. The study target was a 64-year-old private high school with 12 classes for each grade with a total of 1,100 students.Results: A “school disinfection strategy” was set up at individual and class environment levels to protect students from the risk of infection. In addition, school health activities were carried out with a “personal protection safety belt” and “community protection safety belt” for effective implementation. To ensure a safe educational environment for high school students and to ensure smooth execution of face-to-face classes (in-person teaching), the “prevention safety belt strategy” was introduced in accordance with governmental guidelines to sequentially implement various preventive measures necessary to guarantee environmental safety of schools. Activating personal prevention safety belts by checking the symptoms of students when entering the school and during each class, and providing self-made disinfectants by spraying alcohol on wet-wipes were cost-effective and sustainable methods used in this school to prevent the spread of infection.Conclusions: The experience of developing a prevention safety belt strategy to adapt the guidelines of the local education office to the school situation was presented. Focusing on the school community, as well as individual students and teachers, the concept of prevention safety belts helped to unite and stimulate voluntary participation of students in health promotion activities.

At centers with pressure on rapid operating room turnover, onset time is one of the important considerations for choosing a local anesthetic drug. To hasten the onset of the block, higher concentrations of local anesthetics are sometimes used. However, the use of diluted local anesthetics may be safer. Therefore, we aimed to compare the onset times of equipotential levobupivacaine and ropivacaine at low concentrations for infraclavicular brachial plexus block. Adult patients undergoing upper extremity surgery under ultrasound-guided infraclavicular brachial plexus block at our center were randomly allocated to the levobupivacaine and ropivacaine groups. Infraclavicular brachial plexus block was induced with 0.25% levobupivacaine or 0.375% ropivacaine depending on the assigned group. The degrees of sensory and motor blockade were assessed for 40 min after the administration of local anesthetics. A total of 46 patients were included in the analysis. Infraclavicular brachial plexus block with 0.25% levobupivacaine and 0.375% ropivacaine provided sufficient surgical anesthesia. The sensory onset time of 0.375% ropivacaine was shorter than that of 0.25% levobupivacaine (group R, 15 [15.0–22.5] min; group L, 30 [17.5–35.0] min, p = 0.001). There were no significant differences in other block characteristics and clinical outcomes between the two groups. Thus, when a quicker block onset is required, 0.375% ropivacaine is a better choice than 0.25% levobupivacaine.Trial registration ClinicalTrials.gov (NCT03679897).

BackgroundThe renoprotective effect of water intake remains unclear. We aimed to investigate the relationship between water intake and renal impairment in the Korean general population, focusing on individual differences in body fluid distribution and risk of chronic dehydration.MethodsWe conducted a cross-sectional analysis of the 2008–2017 Korea National Health and Nutrition Examination Survey (KNHANES). Adult participants who had body weight and serum creatinine data and had answered 24-h recall nutritional survey were included. Four water intake groups were defined by daily total water intake per body weight: lowest (2) according to water intake.ResultsIn total of 50,113 participants, 3.9% had renal impairment. The risk of renal impairment gradually decreased as water intake increased. After adjustment of sodium intake, the trend of renoprotective effect was remained in low-moderate and high-moderate water intake group compared to low intake group, whereas no significant impact was observed with the highest water intake due to concurrent intake of high sodium. In subgroup analysis, the renoprotective effect of water intake was significant in the participants with elderly, male and daily sodium intake over 2 g/day.ConclusionsHigh daily water intake is renoprotective. Our data may provide an important basis for determining the amount of water intake needed to prevent renal impairment, considering variations in body weight, body composition and risk of chronic dehydration.

Background: School-based health promotion can be particularly valuable in developing countries. However, there is a lack of information about the health needs of Peruvian school students. The purpose of this study was to conduct a health needs assessment to develop strategies for a school health promotion program in a jungle and indigent region in Chanchamayo, Peru. Methods: This study was conducted using a mixed method approach that included a literature review, national and local statistics, stakeholder interviews, and a survey. Participants of the survey were 210 teachers, 2,504 elementary school students, and 2,834 secondary school students from six 'schools in two planned project implementation regions. A self-administered questionnaire for students was developed based on WHO's Global School-based Student Health Survey. Collected data were analyzed using descriptive statistics, chi-square tests, and t-tests for the survey data and content analysis for the interviews. Results: Weak school health systems were identified, including school health policies, curriculum, trained health care personnel, and health-related facilities and equipment. Common health problems of students were anemia, nutritional deficiency, infectious diseases, tuberculosis, drug abuse, poor hygiene, and sex-related problems. High absence rates from school due to family problems and high dropout rates due to pregnancy were also critical issues. Teachers identified personal hygiene, nutrition, reproductive health, and sex education as high priorities for school health education, while students identified prevention of infectious diseases, nutrition education, psychological health, and healthy lifestyles as priorities. Identified strategies included: establishment of school health policies, curriculum-based interventions, increasing community participation and raising school health awareness, capacity building for health care promotors, training of trainers, and partnership between schools and communities. Conclusions: Findings from this study will help guide the development and implementation of a school-based health promotion program in Chanchamayo. Multicomponent school-based interventions that consider feasibility and sustainability will be developed and evaluated based on WHO's Health Promoting School concepts.

Background Cerebral state index (CSI) is an anesthesia depth monitor alternative to bispectral index (BIS). Published comparative studies have used propofol or sevoflurane. However, studies using desflurane have not been reported yet. Different volatile anesthetics have different electroencephalography signatures. The performance of CSI may be different in desflurane anesthesia. Therefore, the objective of this study was to compare CSI and BIS during desflurane anesthesia. Methods Thirty-three patients were recruited. Desflurane and remifentanil were used to maintain general anesthesia. BIS and CSI were recorded simultaneously every minute. End-tidal concentration of desflurane was maintained at 4% from the beginning of surgery for 5 minutes. Pairwise data of CSI and BIS were obtained five times at one-minute intervals. This process was repeated in the order of 6%, 8%, and 10%. Results BIS and CSI were negatively correlated with the end-tidal concentration of desflurane with a similar degree of correlation (correlation coefficient BIS: -0.847, CSI: -0.844). The relationship between CSI and BIS had a good linearity with a slope close to 1 (R2 = 0.905, slope = 1.01). For the relationship between CSI and BIS at each end-tidal concentration of desflurane, CSI and BIS showed good linearity in 4% and 10% (R2 = 0.559, 0.540). However, the linearity and slope were decreased in 6% and 8% (R2 = 0.163, 0.014). Conclusions CSI showed an equivalent degree of overall performance compared to BIS in desflurane anesthesia. Accounting for previous literature, CSI can be used as a good substitute for BIS regardless of the kind of anesthetics used.

This study aimed to examine whether muscle force and tendon stiffness in a muscle-tendon complex alter synchronously following 8-week whole-body vibration (WBV) training in older people. Forty older women aged 65 years and older were randomly assigned into control (CON, n = 15) and whole-body vibration (WBV) training groups (exposure time, n = 13; vibration intensity, n = 12). For the training groups, a 4-week detraining period was completed following the training period. Throughout the training/detraining period, force of the medial gastrocnemius (MG) muscle and stiffness of the Achilles tendon were assessed four times (0, 4, 8, and 12 weeks) using a combined system of dynamometer and ultrasonography. While muscle force gradually increased throughout the training period (p < .05), a significant increase in tendon stiffness was observed after 8 weeks (p < .05). These findings indicated that, during the early phase of WBV training, muscle force and tendon stiffness changed asynchronously, which might be a factor in possible musculotendinous injuries.

Hepatocellular carcinoma (HCC) is the seventh most common malignant tumor and the third leading cause of cancer-related death in the world. Cancer stem cells (CSCs) are small subpopulation of cells within tumors that drive chemoresistance and tumor recurrence in various cancers. We characterized CSCs in primary HCC and identified CD133 as a CSC surface marker. CD133+ HCC cells displayed more stem cell-like properties, tumor spheroid-forming ability, chemoresistance, migration ability, and tumorigenic capacity than CD133- HCC cells. The biological function and molecular mechanism of CD133 remain unclear. HCC cell lines with a high level of CD133 expression overexpressed EGFR, which is overexpressed in approximately 70% of conventional HCCs. CD133 depletion destabilized EGFR by augmenting EGFR internalization and thus inhibited EGFR-AKT signaling. CD133 would therefore serve to sustain aberrant EGFR-mediated oncogenic signaling. Furthermore, EGFR-deficient CD133+ HCC cells manifested greater sensitivity to anticancer drugs and less spheroid-formation capacity than control CD133+ HCC cells. Our results strongly indicate that CD133 facilitates CSC-like properties by stabilizing EGFR-AKT signaling in HCC. It might therefore be feasible to use CD133 as a novel target to sensitize HCC cells that manifest resistance to EGFR-targeted therapy.

Hepatocellular carcinoma (HCC) is resistant to conventional chemotherapeutic agents and remains an unmet medical need. Here, we demonstrate a mechanism of cell adhesion-mediated drug resistance using a variety of HCC spheroid models to overcome environment-mediated drug resistance in HCC. We classified spheroids into two groups, tightly compacted and loosely compacted aggregates, based on investigation of dynamics of spheroid formation. Our results show that compactness of HCC spheroids correlated with fibroblast-like characteristics, collagen 1A1 (COL1A1) content, and capacity for chemoresistance. We also showed that ablation of COL1A1 attenuated not only the capacity for compact-spheroid formation, but also chemoresistance. Generally, connective tissue growth factor (CTGF) acts downstream of transforming growth factor (TGF)-β and promotes collagen I fiber deposition in the tumor microenvironment. Importantly, we found that TGF-β-independent CTGF is upregulated and regulates cell adhesion-mediated drug resistance by inducing COL1A1 in tightly compacted HCC spheroids. Furthermore, losartan, which inhibits collagen I synthesis, impaired the compactness of spheroids via disruption of cell-cell contacts and increased the efficacy of anticancer therapeutics in HCC cell line- and HCC patient-derived tumor spheroids. These results strongly suggest functional roles for CTGF-induced collagen I expression in formation of compact spheroids and in evading anticancer therapies in HCC, and suggest that losartan, administered in combination with conventional chemotherapy, might be an effective treatment for liver cancer.

BackgroundNurses have a primary role in providing palliative and end-of-life (EOL) care. Their knowledge of EOL care, attitudes toward care of the dying, and palliative care self-efficacy are important in care delivery. Little is known regarding palliative care preparedness among Mongolian nurses. This study examines palliative care knowledge, attitude towards death and dying, and self-efficacy among Mongolian nurses, and examines predictors of self-efficacy.MethodsA cross-sectional descriptive study was conducted. Participants were 141 nurses employed at the National Cancer Center in Mongolia. Data was collected using a self-administered questionnaire.ResultsThe median score for the knowledge of palliative care was 8.0/20. "Psychosocial and spiritual care" was the lowest score on the palliative care knowledge subscale. The mean score for attitude toward care of the dying was 69.1%, indicating positive attitudes. The mean score for the palliative care self-efficacy was 33.8/48. Nurses reported low self-efficacy toward communicating with dying patients and their families, and managing delirium. Palliative care knowledge and duration of experience as an oncology nurse significantly predicted self-efficacy toward palliative care, accounting for 14.0% of the variance.ConclusionsPalliative education for nurses should address the knowledge gaps in EOL care and focus in increasing palliative care self-efficacy. Considering palliative care knowledge and nursing experience as an oncology nurse were significant predictors of self-efficacy toward palliative care, more effort is needed to fill the knowledge gaps in EOL care among nurses, especially for less experienced nurses.

Introduction: Although rare, major complications after gastrostomy tube placement are a significant source of morbidity in children. The purpose of this study was to identify predictors of...

Purpose Pediatric tonsillectomy is a highly common surgery for children. The inclusion of tonsillectomy in the diagnosis-related group payment system in Korea has resulted in a shorter hospital stay for patients who undergo tonsillectomy. This, in turn, provides parents with additional caregiver roles in the home. Objectives This study aimed to investigate the effects of a postdischarge management program (PDMP) using Mobile Instant Messenger (MIM) on parents' knowledge and state anxiety about postoperative care, and their children's compliance with care instructions at home, frequency of bleeding, and pain intensity after tonsillectomy. Design and methods A nonequivalent control group nonsynchronized design. Settings and participants Participants were 52 tonsillectomy children aged 3-7 years and their 52 parents (27 for the experimental group and 25 for the control group) from a hospital, in Korea. The control group received a routine written and oral predischarge education, while the experimental group received a predischarge education and a daily MIM for 7 days. For the experimental group, bidirectional communication between the nurse and parent when necessary using MIM are available during the intervention period. Results Parents in the experimental group reported a significantly higher knowledge about postdischarge management and lower state anxiety than the control group. Children in the experimental group showed a significantly greater improvement in compliance with the care instructions at home than the control group. However, bleeding frequency and pain intensity were not significantly lower in the experimental group than that in the control group. Practical implications Nurses play a critical role in preventing and managing the complications of tonsillectomy. Providing proper parental education about pediatric posttonsillectomy care at home is critical for a successful recovery. With the explosion of smartphone technology, the MIM-based PDMP is a useful and effective strategy in helping parents and children in posttonsillectomy care at home.

Purpose. To report one-year outcomes of a modified version of two-stage multimodal surgical protocol for moderate keratoconus which has been suggesting promising preliminary results. Materials and Methods. 30 eyes of 25 patients with moderate keratoconus who exhibited visual complaints and/or disease progression were included for this retrospective case study. Approximately 3 months after implantation of intracorneal ring segment (Intacs SK™), a combination of corneal wavefront-guided transepithelial photorefractive keratectomy (CWG-transPRK, Schwind Amaris® 1050, and Schwind Sirius) and accelerated collagen cross-linking (accCXL, Avedro KXL™) was performed. Patients were examined for uncorrected and corrected distance visual acuity (UDVA; CDVA), keratometric power (K), corneal thickness, and corneal higher-order aberrations (HOAs) preoperatively and at postoperative 1, 3, 6, and 12 months. Results. The median UDVA and mean CDVA were enhanced from 6/38 to 6/12 and from 6/19 to 6/7.5, respectively, through 12 months after CWG-transPRK/accCXL. The 12-month CDVA of all patients was better than 6/12 Snellen, and no subject lost one or more lines of CDVA. The magnitudes of both myopia and corneal steepness were decreased in turn by Intacs SK implantation and also by CWG-transPRK/accCXL, but the reduction in HOA was largely the result of CWG-transPRK/accCXL. The magnitude of corneal thinning stabilized within 3 months after CWG-transPRK/accCXL. Conclusion. This approach may allow patients with moderate keratoconus to obtain satisfactory vision without the need for contact lens wear. This surgery appeared to be effective and safe through 1 year of follow-up.

Background This study aimed to identify clinical nurses’ evidence-based practice (EBP) knowledge, beliefs, organizational readiness, and EBP implementation levels, and to determine the factors that affect EBP implementation in order to successfully establish EBP. This study was conducted at a university-affiliated tertiary hospital located in a provincial area in Korea. The research design was based on Melnyk and Fineout-Overholt’s Advancing Research & Clinical Practice through Close Collaboration model as the first step. Methods A descriptive and cross-sectional design was conducted and a convenience sample of 521 full-time registered nurses from an 849-bed tertiary hospital were included. Structured questionnaires were used to assess EBP knowledge, EBP beliefs, organizational culture & readiness and EBP implementation. Data were analyzed using SPSS V 25.0 by using descriptive and inferential statistics and hierarchical multiple regression was performed to determine the factors affecting the implementation of EBP. Results Our findings showed that the clinical nurses had a positive level of EBP beliefs, but the level of EBP knowledge, organizational readiness and EBP implementation were insufficient. EBP knowledge, beliefs, and organizational readiness were significantly positively correlated with EBP implementation. In the final model, EBP knowledge and organizational readiness were significant predictors of EBP implementation; the model predicted 22.2% of the variance in implementation. Conclusions Based on these results, the main focus of the study was the importance of individual nurses' efforts in carrying out EBP, but above all efforts to create an organizational culture to prepare and support EBP at the nursing organization level. In the initial process of introducing and establishing EBP, nurse administrators will need to minimize expected barriers, enhance facilitators, and strive to build an infrastructure based on vision, policy-making, budgeting, excellent personnel and facilities within the organization.

Methanol ingestion is neurotoxic in humans due to its metabolites, formaldehyde and formic acid. Here, we compared the cytotoxicity of methanol and its metabolites on different types of cells. While methanol and formic acid did not affect the viability of the cells, formaldehyde (200-800 μg/mL) was strongly cytotoxic in all cell types tested. We investigated the effects of formaldehyde on oxidative stress, mitochondrial respiratory functions, and apoptosis on the sensitive neuronal SK-N-SH cells. Oxidative stress was induced after 2 h of formaldehyde exposure. Formaldehyde at a concentration of 400 μg/mL for 12 h of treatment greatly reduced cellular adenosine triphosphate (ATP) levels. Confocal microscopy indicated that the mitochondrial membrane potential (MMP) was dose-dependently reduced by formaldehyde. A marked and dose-dependent inhibition of mitochondrial respiratory enzymes, viz., NADH dehydrogenase (complex I), cytochrome c oxidase (complex IV), and oxidative stress-sensitive aconitase was also detected following treatment with formaldehyde. Furthermore, formaldehyde caused a concentration-dependent increase in nuclear fragmentation and in the activities of the apoptosis-initiator caspase-9 and apoptosis-effector caspase-3/-7, indicating apoptosis progression. Our data suggests that formaldehyde exerts strong cytotoxicity, at least in part, by inducing oxidative stress, mitochondrial dysfunction, and eventually apoptosis. Changes in mitochondrial respiratory function and oxidative stress by formaldehyde may therefore be critical in methanol-induced toxicity.

Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and has poor prognosis. Specially, patients with HCC usually have poor tolerance of systemic chemotherapy, because HCCs develop from chronically damaged tissue that contains considerable inflammation, fibrosis, and cirrhosis. Since HCC exhibits highly heterogeneous molecular characteristics, a proper in vitro system is required for the study of HCC pathogenesis. To this end, we have established two new hepatitis B virus (HBV) DNA-secreting HCC cell lines from infected patients. Methods Based on these two new HCC cell lines, we have developed chemosensitivity assays for patient-derived multicellular tumor spheroids (MCTSs) in order to select optimized anti-cancer drugs to provide more informative data for clinical drug application. To monitor the effect of the interaction of cancer cells and stromal cells in MCTS, we used a 3D co-culture model with patient-derived HCC cells and stromal cells from human hepatic stellate cells, human fibroblasts, and human umbilical vein endothelial cells to facilitate screening for optimized cancer therapy. Results To validate our system, we performed a comparison of chemosensitivity of the three culture systems, which are monolayer culture system, tumor spheroids, and MCTSs of patient-derived cells, to sorafenib, 5-fluorouracil, and cisplatin, as these compounds are typically standard therapy for advanced HCC in South Korea. Conclusion In summary, these findings suggest that the MCTS culture system is the best methodology for screening for optimized treatment for each patients with HCC, because tumor spheroids not only mirror the 3D cellular context of the tumors but also exhibit therapeutically relevant pathophysiological gradients and heterogeneity of in vivo tumors. Electronic supplementary material The online version of this article (10.1186/s13046-018-0752-0) contains supplementary material, which is available to authorized users.

Inhibitor of apoptosis proteins (IAPs) plays an important role in controlling cancer cell survival. IAPs have therefore attracted considerable attention as potential targets in anticancer therapy. In this study, we investigated the anti-tumor effect of AZD5582, a novel small-molecule IAP inhibitor, in human pancreatic cancer cells. Treating human pancreatic cancer cells with AZD5582 differentially induced apoptosis, dependent on the expression of p-Akt and p-XIAP. Moreover, the knockdown of endogenous Akt or XIAP via RNA interference in pancreatic cancer cells, which are resistant to AZD5582, resulted in increased sensitivity to AZD5582, whereas ectopically expressing Akt or XIAP led to resistance to AZD5582. Additionally, AZD5582 targeted cIAP1 to induce TNF-α-induced apoptosis. More importantly, AZD5582 induced a decrease of Mcl-1 protein, a member of the Bcl-2 family, but not that of Bcl-2 and Bcl-xL. Interestingly, ectopically expressing XIAP and cIAP1 inhibited the AZD5582-induced decrease of Mcl-1 protein, which suggests that AZD5582 elicits Mcl-1 decrease for apoptosis induction by targeting of XIAP and cIAP1. Taken together, these results indicate that sensitivity to AZD5582 is determined by p-Akt-inducible XIAP phosphorylation and by targeting cIAP1. Furthermore, Mcl-1 in pancreatic cancer may act as a potent marker to analyze the therapeutic effects of AZD5582.

PURPOSE To report the use of neodymium:yttrium-aluminum-garnet (Nd:YAG) laser internal limiting membranotomy to successfully treat the first reported case of subinternal limiting membrane (sub-ILM) hemorrhage that developed after coil embolization of a cerebral aneurysm. CASE REPORT A 59-year-old Korean woman visited our clinic complaining of central scotoma in her left eye, which developed shortly after stent-assisted coil embolization of an unruptured internal carotid artery aneurysm. Fundus examination revealed a sub-ILM hemorrhage in her left eye, and after 2 days, a Nd:YAG laser membranotomy was performed with a single 4.5-mJ burst. There was a marked reduction in the sub-ILM hemorrhage 1 day after Nd:YAG laser membranotomy, and after 1 month, her best-corrected visual acuity improved to 20/20, with complete resolution of the sub-ILM hemorrhage. CONCLUSIONS Sub-ILM hemorrhage can develop after coil embolization of a cerebral aneurysm, and Nd:YAG laser internal limiting membranotomy can be a useful noninvasive treatment alternative to surgical intervention.

We describe 2 cases of traumatized and torn laser in situ keratomileusis (LASIK) flaps, partially flipped anteriorly or posteriorly, fixed for 8 months or 4 months, and accompanied by epithelial ingrowth. The 2 patients had had uneventful bilateral LASIK 6 years and 1 year before the trauma. In Case 1, the anteriorly flipped flap was removed with transepithelial phototherapeutic keratectomy. Next, mitomycin-C 0.04% was applied for 30 seconds. In Case 2, the portion of the flap that was flipped posteriorly and buried under the remaining intact LASIK flap was restored to its original normal position and epithelial ingrowth was removed mechanically with a microcurette. Irrigation with 20% ethanol was performed to inhibit the recurrence of interfacial epithelial ingrowth. The stretched amniotic membrane overlay over the cornea and sclera was sutured tightly to the episclera as the biologic pressure patch for the inhibition of epithelial re-ingrowth. Good visual acuity was restored in both cases. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Background CD133-positive cells in hepatocellular carcinoma (HCC) exhibit cancer stem cell (CSC)-like properties as well as resistance to chemotherapeutic agents and ionizing radiation; however, their function remains unknown. In this paper, we identified a hitherto unknown mechanism to overcome CD133-induced resistance to anticancer therapy. Methods We applied an alternative approach to enrich the CD133-positive HCC population by manipulating 3D culture conditions. Defense mechanisms against reactive oxygen species (ROS) in CSC spheroids were evaluated by fluorescence image-based phenotypic screening system. Further, we studied the effect of sulfasalazine on ROS defense system and synergistic therapeutic efficacy of anticancer therapies both in culture and in vivo HCC xenograft mouse model. Results Here, we found that oxidative stress increase CD133 expression in HCC and increased CD133 expression enhanced the capacity of the defense system against ROS, and thereby play a central role in resistance to liver cancer therapy. Moreover, ablation of CD133 attenuated not only the capacity for defense against ROS, but also chemoresistance, in HCC through decreasing glutathione (GSH) levels in vitro. Sulfasalazine, a potent xCT inhibitor that plays an important role in maintaining GSH levels, impaired the ROS defense system and increased the therapeutic efficacy of anticancer therapies in CD133-positive HCC but not CD133-negative HCC in vivo and in vitro. Conclusion These results strongly indicate functional roles for CD133 in ROS defense and in evading anticancer therapies in HCC, and suggest that sulfasalazine, administered in combination with conventional chemotherapy, might be an effective strategy against CD133-positive HCC cells. Electronic supplementary material The online version of this article (doi:10.1186/s13046-017-0511-7) contains supplementary material, which is available to authorized users.

This study aimed to identify the factors influencing Korean mothers' intentions to vaccinate their daughters against human papillomavirus (HPV). In Korea, a mother's will is a key determinant for daughters receiving the cervical cancer vaccine. The factors influencing mothers' intentions to vaccinate their daughters against HPV were the perceived benefits of the vaccine, having acquaintances with cervical cancer experiences, awareness of the cervical cancer vaccine, believing that one's daughter needs regular Pap smears, and occupation; these variables explained 32% of the variance. The perceived benefits of the vaccine were the strongest predictor of mothers' intentions. The findings of the current study suggested that mothers' perceived benefits about the HPV vaccine play an important role in their choice to vaccinate their daughters.

Background Although inhibitors of the proto-oncogene BRAF have shown excellent antitumor activity against malignant melanoma, their efficacy is limited by the development of acquired drug resistance, a process in which reactivation of MAP kinase (MEK) is known to play an important role. In this study, we evaluated the efficacy of AS703026, a new MEK inhibitor, in BRAF inhibitor–resistant melanoma cell lines. Methods Two melanoma cells lines, RPMI-7951 and SK-MEL5, harboring an activating mutation of BRAF (V600E) were treated with the BRAF inhibitor PLX4032 to select a BRAF inhibitor–resistant cell line for further study. Cell viability assay was determined with MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay and trypan blue exclusion method; apoptosis assay was performed by annexin-V staining. Knockdown of BRAF was investigated by small interfering RNA. Results RPMI-7951 cells exhibited an increased sensitivity to combined treatment with PLX4032 and AS703026 compared to either drug alone. Consistent with this, the combination of PLX4032 and AS703026 significantly induced apoptosis, whereas each drug used alone did not, as demonstrated by a flow cytometric analysis of annexin-V/propidium iodide–stained cells and Western blot analysis of cleaved caspase-3. Notably, immunoblot analyses also showed a depletion of phosphorylated-ERK with combined drug treatment. In addition, AS703026 synergized with small interfering RNA–mediated downregulation of BRAF to produce results similar to those of combined treatment with PLX4032 and AS703026. Conclusions Our results suggest that combined treatment with AS703026 and a BRAF inhibitor overcomes the resistance to BRAF inhibitors in malignant melanoma cells harboring a mutant form of BRAF.

To evaluate changes in the tear film lipid layer thickness (LLT) after cataract surgery and the effects of cataract surgery on dry eye syndrome (DES) and meibomian gland dysfunction (MGD).LLT measurements obtained using the LipiView interferometer, tear break-up time (TBUT) measurements, Schirmer's tests, Oxford staining scores, lid margin and meibomian gland findings, and the Ocular Surface Disease Index (OSDI) questionnaire scores were evaluated before and one and three months after cataract surgery.Forty-three eyes (43 patients) were included. LLT was significantly thinner one month after surgery than at baseline (P = 0.004). TBUT was significantly shorter at both one (P0.001) and three (P0.001) months after surgery than at baseline. OSDI scores were significantly higher (P0.001) and the meibum quality was significantly poorer (P = 0.001) at one month after surgery than at baseline. TBUT was significantly and positively correlated with LLT (r = 0.29, P0.001), while the OSDI (r = -0.38, P0.001) and Oxford staining (r = -0.30, P = 0.001) scores and the meibum quality (r = -0.21, P = 0.01) were significantly and negatively correlated with LLT.The tear film LLT was significantly thinner and DES and MGD parameters showed deterioration after cataract surgery. In addition, LLT was significantly correlated with DES and MGD parameters. These results suggest that clinicians should consider the tear film lipid layer while managing the exacerbation of DES after cataract surgery.

Aims and objectives. The aim of this study was to test the initial psychometric properties of the Emotional Reactions Instrument-English with hospitalised American children, ages 7–12 years, in the USA. Background. Children’s negative emotional responses have been a subject of concern for paediatric clinicians and researchers, especially because negative emotional responses following or during hospitalisation are associated with adverse patient outcomes. Existing self-report paediatric instruments have a number of limitations including lack of clinical feasibility and psychometric evidence. Design. A survey and psychometric approach was used to test initial reliability and validity of the Emotional Reactions Instrument-English. Methods. Two hundred hospitalised American children, 7–12 years of age, who were admitted to a Children’s Hospital in the USA were recruited for this study. The children were administered the Emotional Reactions Instrument-English, the Facial Affective Scale, and a demographic form. Results. Internal consistency was supported by a Cronbach’s alpha of 0·83 for the total scale. Alpha coefficients for subscales ranged from 0·59–0·82. Construct validity was tested with exploratory factor analysis. Through principal component analysis, four factors were identified that explained 64% of the variance. Concurrent validity was supported by most items in the Emotional Reactions Instrument-English being significantly correlated with the Facial Affective Scale (r = 0·18–0·59). The instrument can be administered to hospitalised children in 5–10 minutes. Conclusions. The results of this exploratory study provide initial support for the psychometric adequacy of the Emotional Reactions Instrument-English with hospitalised American children ages 7–12 years. Further testing of the Emotional Reactions Instrument-English is required to validate the subscales and evaluate the instrument’s use with children of different ages, race and ethnicity. Relevance to clinical practice. This study introduces a new, clinically feasible instrument to measure children’s diverse emotional responses to hospitalisation.

The purpose of this study was to test psychometric properties of the Emotional Reactions Instrument—Korean (ERI-K). A convenience sample of 170 hospitalized Korean children was recruited. Each child was asked to describe how she or he felt during hospitalization, through the ERI-K and the Facial Affective Scale. Surprisingly, children reported lower levels of negative emotions and physical discomfort and a moderate level of positive emotion ( Happy, Good). Internal consistency reliability of .88 for the 14-item scale provides strong support for reliability. Construct validity was supported by item-to-total correlations ranging between .42 and .65. Exploratory factor analysis identified two factors that explained 54% of the variance. Further testing of the ERI-K is recommended to provide additional evidence of psychometric adequacy across Korean populations.

Background and Objectives Twenty haemophiliacs were diagnosed as infected with human immunodeficiency virus 1 (HIV-1), 1 to 2 years after exposure to clotting factor 9 manufactured in Korea, beginning in early 1990. This study assessed the genetic relationships between viruses found in plasma donors and haemophiliacs. Materials and Methods Sequencing of the nef and pol genes of viruses from infected haemophiliacs, plasma donors whose plasma was used in domestic clotting factor manufacture, haemophiliacs infected outside Korea, and local controls were determined by nested polymerase chain reactions and direct DNA sequencing. Phylogenetic analysis was used to investigate the relationships among the sequences. Results Both plasma donors and the haemophiliacs were infected with a subclade of subtype B that is a founder effect lineage in Korea. Conclusion Our data indicate that HIV-1 transmission to 20 haemophiliacs occurred through intravenous injection of Korean-made clotting factor. Summary A clotting factor made in Korea from blood from cash-paid donors infected at least 20 haemophiliacs with HIV-1 subtype B.

Background Although many pregnant women experience back pain, it has not considered an important health problem. No study has investigated the effects of a back-pain-reducing program (BPRP) during pregnancy for Korean women. Objective The purpose of this study was to evaluate the effect of a program designed to reduce back pain in pregnant women. Methods A non-equivalent control-group pretest–posttest design was used. Pregnant women who attended an antenatal clinic and experienced back pain during their pregnancy were included in an intervention group ( n = 2 9 ), and their intensity of back pain, functional limitation and anxiety were compared with women in a control group from another antenatal clinic ( n = 2 7 ). The data were collected at three time points: prior to intervention, and 6 and 12 weeks after intervention. Results At 12 weeks after intervention, the intensity of back pain experienced by the intervention group was significantly lower than that of the control group. However, there were no statistically significant differences between the groups with respect to functional limitations and anxiety. Conclusions The findings show that the pain-reducing program developed for this study was effective in reducing the intensity of back pain experienced by pregnant women. Promoting good posture and regular exercise can be recommended as a method to relieve back pain in pregnancy women. Further studies are needed to confirm the effect of the BPRP during pregnancy.

The purpose of this study was to compare the histomorphometric from sinus augmentation with calcium-phosphate nanocrystal-coated bovine bone (Biocera) and anorganic bovine bone matrix (Bio-Oss).Bilateral maxillary sinus augmentations were performed on 5 patients with delayed placement of implants. The lateral bony window was created using a piezoelectric saw, and the sinus membrane was elevated to make a new compartment. Bio-Oss was grafted in one sinus as the control group and Biocera was grafted in the opposite sinus as the test group. The bony window was repositioned over the bone graft. In all cases, samples were taken for biopsy at the time of implant placement, 6 to 8 months after the grafting procedure. Independent t tests were used to examine between-group differences.None of the 5 patients had complications during healing period. Histomorphometrically, the Bio-Oss group showed 28.46% (±5.28%) of newly formed bone. Biocera group showed 29.94% (±8.72%) of newly formed bone. Newly formed bone along inner surface of repositioned bony window area showed more mature and dense bone structure than new bone formed along bone graft.This study revealed that both bovine bone grafts were considered as suitable bone graft materials for maxillary sinus augmentation.

Background: A blended learning can be a useful learning strategy to improve the quality of fever and fever management education for pediatric nurses. Aim: This study compared the effects of a blended and face-to-face learning program on pediatric nurses’ childhood fever management, using theory of planned behavior. Methods/Design: A nonequivalent control group pretest–posttest design was used. A fever management education program using blended learning (combining face-to-face and online learning components) was offered to 30 pediatric nurses, and 29 pediatric nurses received face-to-face education. Results/Findings: Learning outcomes did not significantly differ between the two groups. However, learners’ satisfaction was higher for the blended learning program than the face-to-face learning program. Conclusion: A blended learning pediatric fever management program was as effective as a traditional face-to-face learning program. Therefore, a blended learning pediatric fever management-learning prog...

Amlodipine, a dihydropyridine calcium channel antagonist, is prescribed for the management of angina and hypertension. It is used therapeutically as a racemic mixture, composed of S- and R-enantiomers, but its calcium channel-blocking effect is confined to S-amlodipine; R-amlodipine has 1000-fold less activity than its S-enantiomer.The objective of this study was to compare the pharmacokinetic and pharmacodynamic properties and safety profiles of a newly developed amlodipine formulation, composed wholly of S-amlodipine, with those of the conventionally prescribed racemic formulation.This randomized, open-label, 2-period, comparative, crossover study was conducted with healthy volunteers at the Gil Medical Center and Gachon Medical School, Incheon, Korea. Male subjects, aged 20 to 50 years, were eligible to participate if their weight was within 20% of ideal body weight and if they were judged by physicians to be healthy. All subjects were randomly assigned in a 1:1 ratio to 1 of 2 treatment sequences: (1) a single dose of the test amlodipine formulation (S-enantiomer amlodipine 5 mg p.o.) (Lodien [Hanlim Pharmaceutical Co., Seoul, Korea]) in the first study period, followed by a single dose of the reference amlodipine formulation (racemate 10 mg p.o.) (Norvasc [Pfizer Pharmaceuticals Korea Ltd., Seoul, Korea]) in the second study period, or (2) a single dose of the reference formulation in the first study period, followed by a single dose of the test formulation in the second period. A 3-week washout occurred between study periods. Blood samples for pharmacokinetic analysis of S-amlodipine were collected at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours after drug administration. Pharmacodynamic variables (ie, systolic and diastolic blood pressure and heart rate) were measured at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 48, and 72 hours after administration. Safety profiles were also assessed. Hematology, biochemistry, electrocardiography, and urinalysis were performed at baseline and end of study. Adverse events were monitored throughout the study period. Pharmacokinetic characteristics were compared using noncompartmental analysis. Pharmacokinetic equivalence was concluded if the geometric mean ratios of the plasma Cmax and AUC were within the predetermined range of 80% to 125%.Twenty-six healthy Korean male volunteers were screened and 18 subjects (mean [SD] age, 23.4 [1.5] years [range, 21-26 years]; mean [SD] weight, 69.3 [6.8] kg [range, 60-88 kg]) were enrolled and completed the study. The plasma concentration-time profiles of S-amlodipine were comparable after administration of both formulations. The mean (SD) values for Cmax AUC from time 0 to the last available measurement (AUC(last)), and AUC from 0 to infinity (AUC(0-infinity)) for the reference formulation (3.0 [0.6] ng/mL, 151.4 [35.7] ng x h/mL, and 175.3 [45.1] ng x h/mL, respectively) did not differ significantly from those for the test formulation (3.1 [0.6] ng/mL, 139.7 [40.3] ng x h/mL, and 161.7 [43.8] ng x h/mL, respectively). The calculated 90% Cls for the corresponding ratios of log-transformed Cmax, AUCO(0-infinity), and AUC(last) were 97.56% to 112.51%, 86.31% to 98.74%, and 83.46% to 100.04%, respectively, which met the predetermined criteria for pharmacokinetic equivalence. Despite the single administration, significant changes in maximal blood pressure and heart rate were observed after drug administration for both formulations, compared with baseline values (all, P0.001). However, no significant differences were observed between the 2 formulations in terms of pharmacodynamic profiles, and no clinically relevant changes were observed for either formulation with respect to physical examination, hematology, biochemistry, electrocardiography, or urinalysis. Neither formulation caused any serious adverse events.Two amlodipine formulations were found to be equivalent in terms of the pharmacokinetics of S-amlodipine. The newly developed formulation, comprised of only S-amlodipine, had pharmacodynamic profiles comparable to those of the conventional racemic amlodipine formulation in these healthy Korean male subjects. Both formulations were well tolerated.

OBJECTIVES An exaggerated blood pressure (BP) response to exercise is associated with adverse cardiovascular outcomes, even in normotensive individuals. The purpose of this study was to compare myocardial function between normotensive individuals with and without an exaggerated BP response. METHODS We evaluated global myocardial function using speckle tracking echocardiography in normotensive individuals. Two-dimensional speckle tracking echocardiography and a treadmill exercise test were performed simultaneously in 171 normotensive individuals (mean age: 48 ± 8 years; 97 men) without any structural heart disease. RESULTS Among 171 normotensive individuals, 19 (11%) exhibited an exaggerated BP response (≥200 mmHg for men and ≥190 mmHg for women) during the treadmill test. Conventional echocardiographic parameters were similar between the two groups. However, on strain analyses, the systolic and early diastolic global longitudinal strains of the left ventricle (LV) and left atrium were lower in individuals with an exaggerated BP response to exercise. The peak SBP during exercise was inversely related to systolic global longitudinal strain of the LV (r = -0.35, P

BACKGROUND Little is known about racial differences in health status and health behaviors of older adults, especially among the oldest old. OBJECTIVES To investigate racial differences in health status and health behaviors of African American and Caucasian older adults and to identify factors that influence health behaviors of older adults. METHOD A descriptive comparative study using data from the Georgia Centenarian Study was conducted. The subjects were 248 older adults (181 Caucasians and 67 African Americans) ranging in age from 60 to 107 years. Demographic characteristics, health status, and four health behaviors were assessed. RESULTS African Americans had significantly lower mental health (p < .001) and poorer self-perceived health (p < .01) than did their Caucasian counterparts; however, when covaried with education and income, racial differences in self-perceived health were eliminated, and differences in mental health decreased but remained significant (p < .05). Using univariate analyses, only two health behaviors, physical activity and eating breakfast regularly, showed significant racial differences. Relatively few older adults participated in leisure-time physical activity. Logistic regression analyses indicated that race was not significantly related to any health behaviors. Age, gender, and physical health status were most frequently related to health behaviors. CONCLUSION The findings indicated no robust racial differences in health status and health behaviors, especially when education and income were controlled. More research is recommended to clarify the factors that explain health behaviors of older adults.

The MET proto-oncogene product, which is the receptor for hepatocyte growth factor (HGF), has been implicated in tumorigenesis and metastatic progression. Point mutations in MET lead to the aberrant activation of the receptor in many types of human malignancies, and the deregulated activity of MET has been correlated with tumor growth, invasion, and metastasis. MET has therefore attracted considerable attention as a potential target in anticancer therapy. Here, we report that a novel MET kinase inhibitor, NPS-1034, inhibits various constitutively active mutant forms of MET as well as HGF-activated wild-type MET. NPS-1034 inhibited the proliferation of cells expressing activated MET and promoted the regression of tumors formed from such cells in a mouse xenograft model through anti-angiogenic and pro-apoptotic actions. NPS-1034 also inhibited HGF-stimulated activation of MET signaling in the presence or absence of serum. Furthermore, when tested on 27 different MET variants, NPS-1034 inhibited 15 of the 17 MET variants that exhibited autophosphorylation with nanomolar potency; only the F1218I and M1149T variants were not inhibited by NPS-1034. Notably, NPS-1034 inhibited three MET variants that are resistant to the MET inhibitors SU11274, NVP-BVU972, and PHA665752. Together, these results suggest that NPS-1034 can be used as a potent therapeutic agent for human malignancies bearing MET point mutations or expressing activated MET.

Recently, we reported that an ethanol extract of Iris nertschinskia induces p53-dependent apoptosis in the MCF7 human breast cancer cell line. However, the detailed mechanisms were not fully explored. Here, we demonstrate another aspect of the activity of I. nertschinskia in breast cancer cells. We compared the response to an ethanol extract of I. nertschinskia in two different human breast cancer cell lines, Hs578Tand MDA-MB231, respectively with relatively low and high AKT1/2 activity by trypan blue exclusion assay and FACS analysis. Knockdown of endogenous AKT1 or AKT2 in breast cancer cells by RNA interference determined the sensitivity to I. nertschinskia ethanol extract compared to control cells. The I. nertschinskia ethanol extract induced cell death in a manner that depended on the level of phosphorylated AKT1/2 protein and was associated with a significant increase in the sub-G1 cell population, indicative of apoptosis. Our results indicate that an ethanol extract of I. nertschinskia differentially induces cell death in breast cancer cells depending on their level of phosphorylated AKT1/2.

The purposes were to examine Korean school health teachers' knowledge and attitudes toward human papillomavirus (HPV) and HPV vaccination, identify factors associated with their intention to recommend the HPV vaccine, and characterize school health teachers' communication with students or parents regarding the HPV vaccine.The online survey involved 119 school health teachers in Korea.Factors associated with an intention to recommend the HPV vaccine were perceived benefits, desiring more education regarding HPV and the HPV vaccine, and age of school health teachers.Findings suggest a need for more education to promote a greater understanding of HPV and HPV vaccination among Korean school health teachers.

PURPOSE To determine the effects of clinical variables, including age, sex, history of refractive or cataract surgery, contact lens use, and ocular surface and meibomian gland parameters on the lipid layer thickness (LLT) in normal subjects and patients with dry eye syndrome (DES). METHODS A total of 64 normal subjects and 326 patients with DES were enrolled, and they underwent measurements of LLT with a LipiView interferometer and tear meniscus height using optical coherence tomography, tear film break-up time (TBUT) determination, ocular surface staining, Schirmer's test, examination of the lid margins and meibomian glands, and assessment using the Ocular Surface Disease Index (OSDI). RESULTS In normal subjects, the median (range) LLT was 67 (33-100) nm, and age was the only factor that was significantly associated with LLT (β = 0.678, P = 0.028). In patients with DES, the median (range) LLT was 84 (20-100) nm, and 79.0% of the participants fulfilled the diagnostic criteria for meibomian gland dysfunction (MGD). In a multivariate analysis, increased age and female sex were significantly related to increased LLT (β = 0.282, P = 0.005 and β = 11.493, P < 0.001), and hypersecretory MGD and lid margin inflammation were independently associated with increased LLT (β = 11.299, P = 0.001 and β = 12.747, P = 0.001). CONCLUSIONS Lipid layer thickness measurements using a new interferometer are significantly affected by demographic factors such as age, sex, ocular surgical history, and MGD type. Therefore, all of these factors must be considered in the diagnosis of ocular surface diseases.

The purpose of this study was to examine knowledge about the human papillomavirus and attitudes toward human papillomavirus and human papillomavirus vaccination among Korean female undergraduate students. Moreover, this study sought to identify factors associated with intention to obtain the human papillomavirus vaccine. A cross-sectional study was conducted with 297 Korean female undergraduate students. Data were collected using a self-administered questionnaire. Collected data were analyzed with descriptive statistics, t-test or ANOVA, and stepwise multiple regression analysis. Only 37.8% of the participants were aware of human papillomavirus. The percentage of correct answers for knowledge about human papillomavirus was 40.6%. Factors associated with intention to obtain the human papillomavirus vaccine were: wanting more education about the vaccine, disease severity, knowledge of human papillomavirus, awareness of the human papillomavirus vaccine, human papillomavirus attributes, and susceptibility; these variables accounted 31.6% of the variance in scores for intention to obtain human papillomavirus vaccination. Findings from this study suggested a need for more active education to reduce the risk of human papillomavirus infection among female undergraduate students. Educational programs should be developed and evaluated, specifically focused on disease severity, susceptibility, awareness of human papillomavirus vaccine, and attributes of human papillomavirus.

This study examined the effects of spinal health educational programs.A nonequivalent control-group pretest-posttest design was used. Participants were 88 fifth-grade elementary schoolchildren. Three groups were compared: a Web-based program group, a traditional face-to-face program group, and a control group.In both intervention groups, the changes for spinal health knowledge and self-efficacy were significantly higher than those of the control group. However, the changes of spinal health practices were not significantly different.A Web-based spinal health education program is a convenient and flexible health educational approach that was as effective in this study as traditional face-to-face instruction.

Objective We investigated the prevalence, risk factors and impact of major depressive disorder (MDD) and minor depressive disorder (MnDD) in a randomly selected community-dwelling Korean elderly population. Method This study was conducted as a part of the Korean Longitudinal Study on Health and Aging (KLoSHA). A study population of 1118 Korean elders was randomly sampled from residents of Seongnam, Korea aged 65 years or older. Standardized face-to-face interviews and neurological and physical examinations were conducted on 714 respondents using the Korean version of Mini International Neuropsychiatric Interview. MDD was diagnosed according to the DSM-IV criteria, and MnDD according to research criteria proposed in Appendix B of the DSM-IV criteria. Results Age-, gender- and education-standardized prevalence rates in Korean elders aged 65 years or older were estimated as 5.37% (95% CI = 3.72–7.03) for MDD, 5.52% (95% CI = 3.84–7.19) for MnDD, and 10.89% (95% CI = 8.60–13.17) for overall late-life depression (LLD). A prior MDD episode (OR = 3.07, 95% CI = 1.38–6.82 in MDD, OR = 3.44, 95% CI = 1.49–7.94 in MnDD), female gender (OR = 3.55, 95% CI = 1.53–8.24 in MDD, OR = 2.68, 95% CI = 1.19–6.04 in MnDD) and history of stroke or TIA (OR = 3.45, 95% CI = 1.62–7.35 in MDD, OR = 2.95, 95% CI = 1.34–6.52 in MnDD) were associated with the risks of both MDD and MnDD. Lack of formal education (OR = 2.75, 95% CI = 1.30–5.85) and low income (OR = 2.83, 95% CI = 1.02–7.88) were associated with the risk of MDD only. Quality of life (QOL) of the MDD and MnDD patients was worse than that of non-depressed elders ( P Conclusion MnDD was as prevalent as MDD in Korean elders and impacted QOL as MDD did. MnDD patients may increase in the future with accelerated population aging and westernization of lifestyle in Korea.

We performed this study to investigate the vascular response in early period after zotarolimus-eluting stent (ZES) (Endeavor Sprint, Medtronic CardioVascular, Minneapolis, Minnesota) implantation.The ZES has different characteristics, with biocompatible polymer and rapid drug-elution, compared with the first-generation drug-eluting stents (DES).The ENDEAVOR OCT (Evaluation in 3 Months Duration of Neointimal Coverage after Zotarolimus-Eluting Stent Implantation by Optical Coherence Tomography) trial is a prospective, single-center study evaluating vascular healing patterns with optical coherence tomography (OCT) at 3 months after stent implantation. A total of 31 ZES in 30 patients underwent serial OCT at immediate post-intervention and 3 months. Neointimal growth and malapposition were analyzed at each stent strut of cross-sectional OCT images with 0.5-mm intervals.The incidence of malapposition at post-intervention and 3 months was 6.0% and 0.2%, respectively. However, late acquired malapposition was not detected at 3 months. Of 31 stents, 27 stents (87.1%) were covered completely with neointima, but the remaining 4 stents had 2 (0.8%), 4 (0.9%), 4 (1.2%), and 6 (1.4%) uncovered struts. Overall mean percentage of covered stent struts was 99.9 +/- 0.4%. This finding was consistent among groups with acute coronary syndrome and stable angina pectoris (99.9 +/- 0.3% vs. 99.9 +/- 0.4%, p = 0.92). Intracoronary thrombus was documented in 1 stent (3.2%) among 31 stents.Most of the stent struts were covered with neointima, and late acquired malapposition was not found at 3 months after ZES implantation. Therefore, the current study demonstrated that ZES might have a favorable in vivo vascular response at 3 months after stent implantation. (Evaluation of Zotarolimus Eluting Stent at 3 Months Using Optical Coherence Tomography [ENDEAVOR OCT]; NCT00815139).

A 61-year-old woman was admitted for intermittent chest discomfort that had been present for 2 months. She was normotensive and denied any past history of medical illness. On physical examination, grade 2 systolic click murmur at the left ventricular (LV) apex was auscultated. A routine electrocardiogram (Panel A) revealed ST-segment …

PURPOSE Despite the high prevalence of back pain and its subsequent effects in post-partum women, intervention programs are scarce. The purpose of this study was to test the effects of a back-pain-reducing program on post-partum women who experienced low-back pain during pregnancy. METHODS A non-equivalent control-group pretest-posttest design was used. Pregnant women who attended a hospital for prenatal check-ups and experienced back pain participated in an intervention program (n=27), and the results were compared with women in a control group from another hospital (n=25). RESULTS At 8 weeks post-partum, the pain intensity, functional limitations were lower in the intervention group than in the control group. However, differences in mean change of the pain intensity and functional limitations between 36 and 39 weeks of gestation and at 8 weeks post-partum were not statistically significant between the groups. Moreover, the flexibility, post-partum functional status, and post-partum depression did not differ significantly between the groups. CONCLUSIONS A back-pain-relief program in this study was not effective to reduce the back-pain intensity in post-partum women and to decrease the associated functional limitations. The implications for nursing practice and directions for future research are discussed.