DNA-protein biomarkers for immunotherapy in the era of precision oncology

The use of biomarkers to guide patient and therapy selection has gained much attention to increase the scope and complexity of targeted therapy options and immunotherapy. Clinical trials provide a basis for discovery of biomarkers, which can then aid in development of new drugs. To that end, samples from cancer patients, including DNA, RNA, protein, and the metabolome isolated from cancer tissues and blood or urine, are analyzed in various ways to identify relevant biomarkers. In conjunction with nucleotide-based, high-throughput, next-generation sequencing techniques, therapy-guided biomarker assays relying on protein-based immunohistochemistry play a pivotal role in cancer care. In this review, we discuss the current knowledge regarding DNA and protein biomarkers for cancer immunotherapy

Organizing pneumonia as the initial presentation of systemic lupus erythematosus in a Korean adolescent

Organizing pneumonia is characterized histologically by the formation of granulation-tissue plugs within the lumens of small airways. It was reported in association with various disorders including infection, drug reactions and collagen vascular diseases. However, there have been only a few reports on organizing pneumonia accompanied by systemic lupus erythematosus (SLE), especially in the pediatric population. Herein, we report a case of an adolescent with SLE who initially developed respiratory illnesses due to organizing pneumonia. A 14-year-old girl was referred to our clinic for protracted cough with fever, dyspnea, and hemoptysis. Her chest x-ray revealed predominant multifocal consolidations in bilateral lung fields with pleural effusion. Computed tomography scan showed patchy consolidations with surrounding ground-glass opacities and a crazy paving appearance with multiple centrilobular nodules. Laboratory tests exhibited pancytopenia, elevated blood urea nitrogen and creatinine, proteinuria, low serum levels of complements, and positivity for antinuclear antibody and anti-double-stranded DNA antibody, which were suggestive of SLE. Lung biopsy was performed to exclude the possibility of vasculitis and other mixed connective tissue diseases, which confirmed focal organizing pneumonia. Systemic steroid therapy, including high-dose methylprednisolone, was started. After the treatment, her respiratory symptoms and radiologic findings showed significant improvements. The patient has been followed up so far, and she has remined disease-free. This pediatric case of organizing pneumonia as the initial presentation of SLE alerts clinicians to consider thorough assessment of pulmonary manifestations of SLE in children.

Prognostic Factors for Absence Epilepsy in Childhood / 대한소아신경학회지

PURPOSE@#Childhood absence epilepsy (CAE) is a common form of idiopathic generalized epilepsy with onset middle childhood and has typically a good prognosis, but remission rates vary. We aimed to analyze unfavorable prognostic factors in children initially diagnosed with CAE.@*METHODS@#We retrospectively reviewed 48 patients under 13 years of age who were diagnosed with CAE at the Severance Children's Hospital, Seoul, Korea. We analyzed clinical information including comorbidity through neuropsychological test.@*RESULTS@#Thirteen of the 48 patients (27%) showed an unfavorable prognosis, with clinical seizures or seizure waves on electroencephalogram persistent even after 12 months of anticonvulsant therapy. The mean age at absence seizure onset was 6.51±2.36 years. The most commonly used antiepileptic drug (AED) was ethosuximide, and the median duration of initial AEDs was 25.63±24.41 months. The presence of comorbidity and clinical absence seizures after 6 months of AEDs correlated with an unfavorable prognosis. Motor seizures were the most unfavorable prognostic factor during follow-up.@*CONCLUSION@#This study shows that clinical absence seizures after 6 months of AED, comorbidity, and motor seizure are the most important predictive factors of an unfavorable prognosis for absence epilepsy in childhood. This study suggests that when these factors are observed, early intervention needs to be considered.

Two New Caffeoyl Threonate Esters from the Leaves of Toxicodendron vernicifluum

Toxicodendron vernicifluum, also called as Rhus verniciflua is a deciduous tree belonging to Anacardiaceae family. Two new caffeoyl threonate esters, rhuseols A (1) and B (2), together with 5-O-(E)-caffeoylquinic acid methyl ester (3) were isolated from the leaves of T. vernicifluum. The structures of isolated compounds were established by using 1D and 2D NMR in combination with HR-ESI-MS. Compounds 1 – 3 showed DPPH radical scavenging effects with IC₅₀ values of 47.9, 107.8 and 15.4 µM, respectively. Taken together, these compounds might contribute to the antioxidant properties of the leaves of T. vernicifluum, which will be useful for various oxidative stress mediated diseases.

A Proposal for Modification of the Barcelona Clinic Liver Cancer Staging System Considering the Prognostic Implication of Performance Status

BACKGROUND/AIMS: Barcelona Clinic Liver Cancer (BCLC) C stage demonstrates considerable heterogeneity because it includes patients with either symptomatic tumors (performance status [PS], 1–2) or with an invasive tumoral pattern reflected by the presence of vascular invasion (VI) or extrahepatic spread (EHS). This study aimed to derive a more relevant staging system by modification of the BCLC system considering the prognostic implication of PS. METHODS: A total of 7,501 subjects who were registered in the Korean multicenter hepatocellular carcinoma (HCC) registry database from 2008 to 2013 were analyzed. The relative goodness-of-fit between staging systems was compared using the Akaike information criterion (AIC) and integrated area under the curve (IAUC). Three modified BCLC (m-BCLC) systems (#1, #2, and #3) were devised by reducing the role of PS. RESULTS: As a result, the BCLC C stage, which includes patients with PS 1–2 without VI/EHS, was reassigned to stage 0, A, or B according to their tumor burden in the m-BCLC #2 model. This model was identified as the most explanatory and desirable model for HCC staging by demonstrating the smallest AIC (AIC=70,088.01) and the largest IAUC (IAUC=0.722), while the original BCLC showed the largest AIC (AIC=70,697.17) and the smallest IAUC (IAUC=0.705). The m-BCLC #2 stage C was further subclassified into C1, C2, C3, and C4 according to the Child-Pugh score, PS, presence of EHS, and tumor extent. The C1 to C4 subgroups showed significantly different overall survival distribution between groups (p<0.001). CONCLUSIONS: An accurate and relevant staging system for patients with HCC was derived though modification of the BCLC system based on PS.

Association between prehospital i-gel insertion and PCO₂ in patients with out-of-hospital cardiac arrest

OBJECTIVE: This study examined the initial partial pressure of carbon dioxide (PCO₂) as a possible indicator of prehospital ventilation and its association with prehospital i-gel in out-of-hospital cardiac arrest (OHCA) patients. METHODS: The demographics and arrest parameters, including i-gel insertion and initial arterial blood gas analysis, of OHCA patients who visited the emergency department were analyzed retrospectively. Linear regression analysis was performed to examine the association between i-gel insertion and the initial PCO₂. RESULTS: A total of 106 patients were investigated. Fifty-six patients had prehospital i-gel insertion and 50 patients did not have a prehospital advanced airway. The initial PCO₂ was higher in the i-gel group than the no advanced airway group (105.2 mmHg [77.5–134.9] vs. 87.5 mmHg [56.8–115.3], P=0.03). Prehospital i-gel insertion was associated with a higher initial PCO₂ level (βcoefficient, 20.3; 95% confidence interval, 2.6–37.9; P=0.03). CONCLUSION: Prehospital insertion of i-gel was associated with higher initial PCO₂ values in OHCA patients compared to no advanced airway.

Computer-Aided Diagnosis of Thyroid Nodules via Ultrasonography: Initial Clinical Experience

OBJECTIVE: To prospectively evaluate the diagnostic performance of computer-aided diagnosis (CAD) for detection of thyroid cancers via ultrasonography (US). MATERIALS AND METHODS: This study included 50 consecutive patients with 117 thyroid nodules on US during the period between June 2016 and July 2016. A radiologist performed US examinations using real-time CAD integrated into a US scanner. We compared the diagnostic performance of radiologist, the CAD system, and the CAD-assisted radiologist for the detection of thyroid cancers. RESULTS: The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the CAD system were 80.0, 88.1, 83.3, 85.5, and 84.6%, respectively, and were not significantly different from those of the radiologist (p > 0.05). The CAD-assisted radiologist showed improved diagnostic sensitivity compared with the radiologist alone (92.0% vs. 84.0%, p = 0.037), while the specificity and PPV were reduced (85.1% vs. 95.5%, p = 0.005 and 82.1% vs. 93.3%, p = 0.008). The radiologist assisted by the CAD system exhibited better diagnostic sensitivity and NPV than the CAD system alone (92.0% vs. 80.0%, p = 0.009 and 93.4% vs. 88.9%, p = 0.013), while the specificities and PPVs were not significantly different (88.1% vs. 85.1%, p = 0.151 and 83.3% vs. 82.1%, p = 0.613, respectively). CONCLUSION: The CAD system may be an adjunct to radiological intervention in the diagnosis of thyroid cancer.

The Risk of Microalbuminuria by Obesity Phenotypes according to Metabolic Health and Obesity: The Korean National Health and Nutrition Examination Survey 2011–2014 / 가정의학회지

BACKGROUND: The present study aimed at identifying the difference in the risk of microalbuminuria among individuals with various obesity phenotypes in terms of metabolic health and obesity. METHODS: This cross-sectional study included 15,268 individuals and used data from the National Health and Nutrition Survey conducted from 2011 to 2014. Obesity was defined as body mass index ≥25 kg/m2. Metabolically unhealthy was defined as meeting two or more of the following criteria: systolic and diastolic blood pressure ≥130/85 mm Hg or current use of hypertensive drugs; triglyceride level ≥150 mg/dL; high-density lipoprotein level < 40/50 mg/dL (in both men and women); and fasting blood glucose level ≥100 mg/dL or current use of oral antidiabetic medications. The participants were further classified into four subgroups: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO). RESULTS: A significant difference was observed in the microalbuminuria ratio among the four groups. The MHNO group was considered as the reference group, and the MHO, MUNO, and MUO groups were at an increased risk for microalbuminuria by 1.42 fold (95% confidence interval [95% CI], 1.03–1.96), 2.02 fold (95% CI, 1.61–2.53), and 3.40 fold (95% CI, 2.70–4.26), respectively, after adjusting confounding factors. CONCLUSION: The MUNO group had a higher risk of developing microalbuminuria than the MHNO group. Thus, based on this result, differences were observed in the risk of developing microalbuminuria among individuals with various obesity subtypes.

Accuracy Analysis of Embletta X100 for the Diagnosis of Obstructive Sleep Apnea and the Assessment of Sleep Structure

BACKGROUND AND OBJECTIVES: To measure the accuracy of Embletta X100, a level 2 portable sleep monitoring device, for diagnosis of obstructive sleep apnea and assessment of sleep structure. MATERIALS AND METHOD: We enrolled 200 consecutive patients who had been referred due to habitual snoring or witnessed apnea during sleep and had undergone standard polysomnography (PSG). We created a simulated situation similar to that of the Embletta X100 using only data from PSG and scored the sleep stage and the apnea-hypopnea index (AHI). Thereafter, the results of PSG and simulated Embletta X100 were compared. RESULTS: Sensitivity, specificity, and positive and negative predictive values of simulated Embletta X100 based on PSG were nearly 100% at three different cutoff values of AHI (5, 15, and 30). Intraclass correlation (ICC) of simulated Embletta X100 based on PSG was also excellent (≥0.9) for most of the sleep-related parameters and respiratory index. However, ICC of sleep stage percent was variable according to sleep stage (>0.9 for N1 and N2, 0.664 for N3, and 0.864 for R). CONCLUSION: Although sleep staging is not very precise, Embletta X100 matches well with PSG overall.

Establishment of Maximum Surgical Blood Order Schedule (MSBOS) and Evaluation of Effective Blood Usage in Major Surgery / 대한수혈학회지

BACKGROUND: For effective blood usage and reduction of unnecessary workload at blood banks, we established the maximum surgical blood order schedule (MSBOS) for major elective surgeries and evaluated indicators, including the rate of returned red blood cells (RBCs). METHODS: During August 2016 and May 2017, MSBOS for neurosurgery, thoracic surgery, orthopedic surgery, and general surgery was established using two formulas: the mean units of transfusion per procedure (MSBOS 1) and the mean units of transfusion in transfused patients per procedure (MSBOS 2). The crossmatch to transfusion (C/T) ratio, transfusion probability, and rate of returned RBCs were calculated and analyzed. RESULTS: Based on MSBOS 1, type and screen can be applied to all elective surgeries of the general surgery department. MSBOS 2 was higher than MSBOS 1 in most surgeries ranging from 1 to 3 units. The C/T ratio and transfusion probability of surgery exhibited similar tendencies, and the general surgery department was over-prescribed compared to the actual transfusion requirement. The rate of returned RBCs was the highest in thoracic surgery (32/101, 32%), and the total number of returned RBC unit was the highest in orthopedic surgery (276 of 1131 units). CONCLUSION: MSBOS 1 was the formula corresponding to the purpose of the maximum blood application protocol. Application of an appropriate MSBOS protocol and concurrent utilization of C/T ratio, probability of transfusion, and rate and number of returned units of RBCs will further aid the efficiency of blood bank resources.

Factors Affecting Hemagglutinations Strength in ABO Blood Group Typing Test Using the Tube Method

BACKGROUND: The ABO blood group typing test (ABO test) is an initial pre-transfusion test based on hemagglutination. Although various factors affect hemagglutination strength, few studies have examined how these factors can be applied in clinical laboratories and their effects on hemagglutination. This study was conducted to analyze the factors affecting hemagglutination strength in the ABO test using a tube method applied in many laboratories. METHODS: We conducted a detailed questionnaire survey of 51 laboratories which use the ABO test with a tube method. We also analyzed the results of the ABO test (cell and serum typing) with 40 specimens using factors affecting hemagglutination at a tube method and applied differently in each laboratory. RESULTS: Each laboratory used various methods to prepare red cell suspensions as specimens or reagents and used different reagent to sample ratios, centrifugation protocols, and shaking test tubes before evaluating hemagglutination strength. By testing various combinations of these factors, direct sampling from the red cell layer of the original specimen was found to have the largest effect on lowering hemagglutination strength in cell typing tests. In serum typing tests, various factors influenced hemagglutination strength, including shaking the tube before analysis and the concentration of a home-made red cell suspension used as a reagent. CONCLUSIONS: To achieve accurate results in the ABO test by the tube method, detailed guidelines that include the factors affecting hemagglutination strength determined in this study should be established.

Item development process and analysis of 50 case-based items for implementation on the Korean Nursing Licensing Examination / 보건의료교육평가

PURPOSE: The purpose of this study was to improve the quality of items on the Korean Nursing Licensing Examination by developing and evaluating case-based items that reflect integrated nursing knowledge. METHODS: We conducted a cross-sectional observational study to develop new case-based items. The methods for developing test items included expert workshops, brainstorming, and verification of content validity. After a mock examination of undergraduate nursing students using the newly developed case-based items, we evaluated the appropriateness of the items through classical test theory and item response theory. RESULTS: A total of 50 case-based items were developed for the mock examination, and content validity was evaluated. The question items integrated 34 discrete elements of integrated nursing knowledge. The mock examination was taken by 741 baccalaureate students in their fourth year of study at 13 universities. Their average score on the mock examination was 57.4, and the examination showed a reliability of 0.40. According to classical test theory, the average level of item difficulty of the items was 57.4% (80%–100% for 12 items; 60%–80% for 13 items; and less than 60% for 25 items). The mean discrimination index was 0.19, and was above 0.30 for 11 items and 0.20 to 0.29 for 15 items. According to item response theory, the item discrimination parameter (in the logistic model) was none for 10 items (0.00), very low for 20 items (0.01 to 0.34), low for 12 items (0.35 to 0.64), moderate for 6 items (0.65 to 1.34), high for 1 item (1.35 to 1.69), and very high for 1 item (above 1.70). The item difficulty was very easy for 24 items (below −2.0), easy for 8 items (−2.0 to −0.5), medium for 6 items (−0.5 to 0.5), hard for 3 items (0.5 to 2.0), and very hard for 9 items (2.0 or above). The goodness-of-fit test in terms of the 2-parameter item response model between the range of 2.0 to 0.5 revealed that 12 items had an ideal correct answer rate. CONCLUSION: We surmised that the low reliability of the mock examination was influenced by the timing of the test for the examinees and the inappropriate difficulty of the items. Our study suggested a methodology for the development of future case-based items for the Korean Nursing Licensing Examination.

NanoString nCounter® Approach in Breast Cancer: A Comparative Analysis with Quantitative Real-Time Polymerase Chain Reaction, In Situ Hybridization, and Immunohistochemistry / 한국유방암학회지

PURPOSE: Accurate testing for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) is essential for breast cancer treatment. At present, immunohistochemistry (IHC)/florescence in situ hybridization (FISH) are widely accepted as the standard testing methods. To investigate the value of NanoString nCounter®, we performed its comparative analysis with IHC/FISH and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) for the assessment of ER, PR, and HER2. METHODS: Data on IHC/FISH results for ER, PR, and HER2 in 240 patients from a single tertiary hospital in Korea were collected and compared with NanoString nCounter® and qRT-PCR results at a single institution. RESULTS: Expression levels for each gene using NanoString nCounter® showed good correlation with the corresponding data for protein expression by IHC (p<0.001) and gene amplification status for HER2 (p<0.001). Comparisons between gene expression and IHC data showed good overall agreement with a high area under the curve (AUC) for ESR1/ER (AUC=0.939), PgR/PR (AUC=0.796), and HER2/HER2 (AUC=0.989) (p<0.001). CONCLUSION: The quantification of ER, PgR, and HER2 mRNA expression with NanoString nCounter® may be a viable alternative to conventional IHC/FISH methods.

Occult HBV among Anti-HBc Alone: Mutation Analysis of an HBV Surface Gene and Pre-S Gene

PURPOSE: The aim of this study is to investigate the molecular characteristics of occult hepatitis B virus (HBV) infection in ‘anti-HBc alone’ subjects. MATERIALS AND METHODS: Twenty-four patients with ‘anti-HBc alone’ and 20 control patients diagnosed with HBV were analyzed regarding S and pre-S gene mutations. All specimens were analyzed for HBs Ag, anti-HBc, and anti-HBs. For specimens with an anti-HBc alone, quantitative analysis of HBV DNA, as well as sequencing and mutation analysis of S and pre-S genes, were performed. RESULTS: A total 24 were analyzed for the S gene, and 14 were analyzed for the pre-S gene through sequencing. A total of 20 control patients were analyzed for S and pre-S gene simultaneously. Nineteen point mutations of the major hydrophilic region were found in six of 24 patients. Among them, three mutations, S114T, P127S/T, M133T, were detected in common. Only one mutation was found in five subjects of the control group; this mutation was not found in the occult HBV infection group, however. Pre-S mutations were detected in 10 patients, and mutations of site aa58–aa100 were detected in 9 patients. A mutation on D114E was simultaneously detected. Although five mutations from the control group were found at the same location (aa58–aa100), no mutations of occult HBV infection were detected. CONCLUSION: The prevalence of occult HBV infection is not low among ‘anti-HBc alone’ subjects. Variable mutations in the S gene and pre-S gene were associated with the occurrence of occult HBV infection. Further larger scale studies are required to determine the significance of newly detected mutations.

Narrow-diameter implants with conical connection for restoring the posterior edentulous region / 대한악안면성형재건외과학회지

BACKGROUND: The objective of this retrospective study was to show results from platform-switched narrow-diameter implants in the posterior edentulous region, which we followed up for more than 1 year after functional loading. METHODS: Ninety-eight narrow implants were inserted into 66 patients. After healing, fixed implant-supported prostheses were delivered to the patients, and Periotest and radiographic examinations were performed. After the first year of loading, the implant outcome was again evaluated clinically and radiographically using the Periotest analysis. Crestal bone loss and Periotest values (PTVs) were used to evaluate the effect of surgery, prosthesis, implant, and a host-related factor. A general linear model was used to statistically detect variables statistically associated with crestal bone loss and Periotest value. RESULTS: We followed up on the implants over 1 to 4 years after loading; their survival rate was 100%, and pronounced differences from PTVs were noted among jaw location, bone quality, and loading period. No difference was detected in bone loss among the variables studied. Bone loss after functional loading was 0.14 ± 0.39 mm. The stability value from the Periotest was −3.29 ± 0.50. CONCLUSIONS: Within the limitations of this study, judicious use of platform-switched narrow implants with a conical connection must be considered an alternative for wide-diameter implants to restore a posterior edentulous region.

Prevalence and Antibiotic Susceptibility of Mycoplasma hominis and Ureaplasma urealyticum in Pregnant Women

Mycoplasma hominis (M. hominis) and Ureaplasma urealyticum (U. urealyticum) are important opportunistic pathogens that cause urogenital infections and complicate pregnancy. The aim of this study was to investigate the prevalence, effects on pregnancy outcomes, and antimicrobial susceptibilities of M. hominis and U. urealyticum. We tested vaginal swabs obtained from 1035 pregnant women for the presence of genital mycoplasmas between June 2009 and May 2014. The laboratory and clinical aspects of genital mycoplasmas infection were reviewed retrospectively, and the identification and antimicrobial susceptibility of genital mycoplasmas were determined using the Mycoplasma IST-2 kit. A total of 571 instances of M. hominis and/or U. urealyticum were detected. Of them, M. hominis was detected in two specimens, whereas U. urealyticum was detected in 472 specimens. The remaining 97 specimens were positive for both M. hominis and U. urealyticum. Preterm deliveries were frequently observed in cases of mixed infection of M. hominis and U. urealyticum, and instances of preterm premature rupture of membrane were often found in cases of U. urealyticum. The rates of non-susceptible isolates to erythromycin, empirical agents for pregnant women, showed increasing trends. In conclusion, the prevalence of M. hominis and/or U. urealyticum infections in pregnant women is high, and the resistance rate of antimicrobial agents tends to increase. Therefore, to maintain a safe pregnancy, it is important to identify the isolates and use appropriate empirical antibiotics immediately.

Relevance of the test content of the Korean Nursing Licensing Examination to nursing job / 보건의료교육평가

PURPOSE: This study aimed at identifying if there is a relevance of content of the Korean Nursing Licensing Examination (KNLE) revised in 2014 to nursing job. It will be able to provide the validity of revised content of the KNLE. METHODS: From October 13 to November 13, 2015, print version of 8 duties with 49-tasks, 155-job item questionnaires were distributed to 1,305 hospital nurses and 202 nursing faculties in Korea. Results were treated by descriptive statistics and comparison analysis. There were responses from 946 nurses or professors (72.5%). RESULTS: The relevance of test content of KNLE to nursing job was shown to be valid with over 3 points out of 4 point Likert scale in all items: from 3.23 at lowest to 3.64 at top. CONCLUSION: Above results showed that the revised version of KNLE in 2014 was valid to test the nursing students' knowledge for job performance.

The job analysis of Korean nurses as a strategy to improve the Korean Nursing Licensing Examination / 보건의료교육평가

PURPOSE: This study aimed at characterizing Korean nurses' occupational responsibilities to apply the results for improvement of the Korean Nursing Licensing Examination. METHODS: First, the contents of nursing job were defined based on a focus group interview of 15 nurses. Developing a Curriculum (DACOM) method was used to examine those results and produce the questionnaire by 13 experts. After that, the questionnaire survey to 5,065 hospital nurses was done. RESULTS: The occupational responsibilities of nurses were characterized as involving 8 duties, 49 tasks, and 303 task elements. Those 8 duties are nursing management and professional development, safety and infection control, the management of potential risk factors, basic nursing and caring, the maintenance of physiological integrity, medication and parenteral treatments, socio-psychological integrity, and the maintenance and improvement of health. CONCLUSION: The content of Korean Nursing Licensing Examination should be improved based on 8 duties and 49 tasks of the occupational responsibilities of Korean nurses.

Impact of Nursing Students' Emotional Labor on Burnout during Nursing Practice in a Hospital: Moderating Effect of Emotional Intelligence / 간호행정학회지

PURPOSE: This study was done to: (a) identify levels of emotional labor that nursing students perceived when caring for patients in the hospital during their nursing practicum, (b) examine the impact of emotional labor on burnout, and (c) identify the possible moderating effect of emotional intelligence on the relationship between emotional labor and burnout for nursing students. METHODS: A descriptive study was conducted with a sample of 171 students enrolled in a 4-year undergraduate nursing program in one university located in Korea, and had a practicum experience at least one semester before the study began. Data were collected with self-report questionnaire, and analyzed with SPSS 21.0 program, using hierarchical multiple regression. RESULTS: Mean score for emotional labor was 3.17 with a range of 1 to 5. For nursing students, emotional labor significantly affected burnout in the nursing practicum (F=15.763, p<.001), and explained 30.1% of the variance in burnout. The degree of emotional intelligence acted as a moderator on the relationship between emotional labor and burnout at significant level (F=15.345, p<.001). CONCLUSION: This research shows that nurse managers as well as nurse educators need to pay attention to nursing students' emotional labor during nursing practicum in the care units of hospitals.

Comparison of Three BRAF Mutation Tests in Formalin-Fixed Paraffin Embedded Clinical Samples

BACKGROUND: Recently, BRAF inhibitors showed dramatic treatment outcomes in BRAF V600 mutant melanoma. Therefore, the accuracy of BRAF mutation test is critical. METHODS: BRAF mutations were tested by dual-priming oligonucleotide-polymerase chain reaction (DPO-PCR), direct sequencing and subsequently retested with a real-time PCR assay, cobas 4800 V600 mutation test. In total, 64 tumors including 34 malignant melanomas and 16 papillary thyroid carcinomas were analyzed. DNA was extracted from formalin-fixed paraffin embedded tissue samples and the results of cobas test were directly compared with those of DPO-PCR and direct sequencing. RESULTS: BRAF mutations were found in 23 of 64 (35.9%) tumors. There was 9.4% discordance among 3 methods. Out of 6 discordant cases, 4 cases were melanomas; 3 cases were BRAF V600E detected only by cobas test, but were not detected by DPO-PCR and direct sequencing. One melanoma patient with BRAF mutation detected only by cobas test has been on vemurafenib treatment for 6 months and showed a dramatic response to vemurafenib. DPO-PCR failed to detect V600K mutation in one case identified by both direct sequencing and cobas test. CONCLUSIONS: In direct comparison of the currently available DPO-PCR, direct sequencing and real-time cobas test for BRAF mutation, real-time PCR assay is the most sensitive method.