Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

The detection and quantification of hepatitis B virus (HBV) DNA plays an important role in diagnosing and monitoring HBV infection as well as in assessing the therapeutic response. We compared the analytical performance of a random access, fully automated HBV assay—DxN VERIS Molecular Diagnostics System (Beckman Coulter, Brea, CA, USA)—with that of Abbott RealTime HBV assay (Abbott Laboratories, Des Plaines, IL, USA). The between-day precision of the VERIS assay ranged from 0.92% (mean 4.68 log IU/mL) to 4.15% (mean 2.09 log IU/mL) for pooled sera from HBV patients. HBV DNA levels measured by the VERIS HBV assay correlated with the calculated HBV DNA levels (r²=0.9994; P < 0.0001). The lower limit of quantification was estimated as 8.76 IU/mL (Probit analysis, 95% confidence interval: 7.32–12.00 IU/mL). Passing-Bablok regression analysis showed good concordance between the VERIS and RealTime assays for 187 chronic HBV samples (y=−0.2397+0.9712x; r=0.981), as well as for 20 drug-resistant HBV genotype C positive samples (y=−0.5415+0.9954x; r=0.961). The VERIS assay demonstrated performance similar to the RealTime assay and is suitable for high-throughput HBV DNA monitoring in large hospital laboratories.
DNA ; Genotype ; Hepatitis B virus* ; Hepatitis B* ; Hepatitis* ; Humans ; Laboratories, Hospital ; Pathology, Molecular

PURPOSE: The optimal cytotoxic regimens have not been established for patients with non-small cell lung cancer (NSCLC) who develop disease progression on first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). MATERIALS AND METHODS: We conducted a multi-center randomized phase II trial to compare the clinical outcomes between pemetrexed plus cisplatin combination therapy followed by maintenance pemetrexed (PC) and pemetrexed monotherapy (P) after failure of first-line EGFR-TKI. The primary objective was progression-free survival (PFS), and secondary objectives included overall response rate (ORR), overall survival (OS), health-related quality of life (HRQOL), and safety and toxicity profiles. RESULTS: A total of 96 patientswere randomized, and 91 patientswere treated at 14 centers in Korea. The ORR was 34.8% (16/46) for the PC arm and 17.8% (8/45) for the P arm (p=0.066). With 23.4 months of follow-up, the median PFS was 5.4 months in the PC arm and 6.4 months in the P arm (p=0.114). The median OS was 17.9 months and 15.7 months in PC and P arms, respectively (p=0.787). Adverse events ≥ grade 3 were reported in 12 patients (26.1%) in the PC arm and nine patients (20.0%) in the P arm (p=0.491). The overall time trends of HRQOL were not significantly different between the two arms. CONCLUSION: The outcomes of pemetrexed therapy in NSCLC patients with disease progression after firstline EGFR-TKI might not be improved by adding cisplatin.
Arm ; Carcinoma, Non-Small-Cell Lung ; Cisplatin ; Disease Progression ; Disease-Free Survival ; Epidermal Growth Factor ; Follow-Up Studies ; Humans ; Korea ; Lung Neoplasms ; Lung ; Pemetrexed ; Protein-Tyrosine Kinases ; Quality of Life ; Receptor, Epidermal Growth Factor ; Tyrosine

BACKGROUND AND OBJECTIVES: Impaired recovery from left ventricular (LV) dysfunction is a major prognostic factor after myocardial infarction (MI). Because P2Y12 receptor blockade inhibits myocardial injury, ticagrelor with off-target properties may have myocardial protection over clopidogrel. In animal models, ticagrelor vs. clopidogrel protects myocardium against reperfusion injury and improves remodeling after MI. We aimed to investigate the effect of ticagrelor on sequential myocardial remodeling process after MI. METHODS: High platelet inhibition with ticagrelor to improve LV remodeling in patients with ST-segment elevation MI (HEALING-AMI) is an investigator-initiated, randomized, open-label, assessor-blinded, multi-center trial done at 10 sites in Korea. Patients will be enrolled if they have ST-segment elevation MI (STEMI) treated with primary percutaneous coronary intervention and a planned duration of dual antiplatelet treatment of at least 6 months. Screened patients will be randomly assigned (1:1) using an internet-based randomization with a computer-generated blocking with stratification across study sites to either ticagrelor or clopidogrel treatment. The co-primary primary endpoints are LV remodeling index with three-dimensional echocardiography and the level of N-terminal prohormone B-type natriuretic peptide (NT-proBNP) at 6 months representing post-MI remodeling processes. Changes of LV end-systolic/diastolic volume indices and LV ejection fraction between baseline and 6-month follow-up will be also evaluated. Analysis is per protocol. CONCLUSIONS: HEALING-AMI is testing the effect of ticagrelor in reducing adverse LV remodeling following STEMI. Our trial would show the benefit of ticagrelor vs. clopidogrel related to the recovery of post-MI LV dysfunction beyond potent platelet inhibition. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02224534
Blood Platelets ; Echocardiography, Three-Dimensional ; Follow-Up Studies ; Humans ; Korea ; Models, Animal ; Myocardial Infarction ; Myocardium ; Natriuretic Peptide, Brain ; Percutaneous Coronary Intervention ; Random Allocation ; Reperfusion Injury ; Ventricular Remodeling

BACKGROUND AND OBJECTIVES: Impaired recovery from left ventricular (LV) dysfunction is a major prognostic factor after myocardial infarction (MI). Because P2Y12 receptor blockade inhibits myocardial injury, ticagrelor with off-target properties may have myocardial protection over clopidogrel. In animal models, ticagrelor vs. clopidogrel protects myocardium against reperfusion injury and improves remodeling after MI. We aimed to investigate the effect of ticagrelor on sequential myocardial remodeling process after MI. METHODS: High platelet inhibition with ticagrelor to improve LV remodeling in patients with ST-segment elevation MI (HEALING-AMI) is an investigator-initiated, randomized, open-label, assessor-blinded, multi-center trial done at 10 sites in Korea. Patients will be enrolled if they have ST-segment elevation MI (STEMI) treated with primary percutaneous coronary intervention and a planned duration of dual antiplatelet treatment of at least 6 months. Screened patients will be randomly assigned (1:1) using an internet-based randomization with a computer-generated blocking with stratification across study sites to either ticagrelor or clopidogrel treatment. The co-primary primary endpoints are LV remodeling index with three-dimensional echocardiography and the level of N-terminal prohormone B-type natriuretic peptide (NT-proBNP) at 6 months representing post-MI remodeling processes. Changes of LV end-systolic/diastolic volume indices and LV ejection fraction between baseline and 6-month follow-up will be also evaluated. Analysis is per protocol. CONCLUSIONS HEALING-AMI is testing the effect of ticagrelor in reducing adverse LV remodeling following STEMI. Our trial would show the benefit of ticagrelor vs. clopidogrel related to the recovery of post-MI LV dysfunction beyond potent platelet inhibition.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02224534

PURPOSE: The goal of this study was to investigate the utility of DNA vaccines encoding Ebola virus glycoprotein (GP) as a vaccine type for the production of GP-specific hybridomas and antibodies. MATERIALS AND METHODS: DNA vaccines were constructed to express Ebola virus GP. Mice were injected with GP DNA vaccines and their splenocytes were used for hybridoma production. Enzyme-linked immunosorbent assays (ELISAs), limiting dilution subcloning, antibody purification methods, and Western blot assays were used to select GP-specific hybridomas and purify monoclonal antibodies (MAbs) from the hybridoma cells. RESULTS: Twelve hybridomas, the cell supernatants of which displayed GP-binding activity, were selected by ELISA. When purified MAbs from 12 hybridomas were tested for their reactivity to GP, 11 MAbs, except for 1 MAb (from the A6-9 hybridoma) displaying an IgG2a type, were identified as IgM isotypes. Those 11 MAbs failed to recognize GP. However, the MAb from A6-9 recognized the mucin-like region of GP and remained reactive to the antigen at the lowest tested concentration (1.95 ng/mL). This result suggests that IgM-secreting hybridomas are predominantly generated by DNA vaccination. However, boosting with GP resulted in greater production of IgG-secreting hybridomas than GP DNA vaccination alone. CONCLUSION: DNA vaccination may preferentially generate IgM-secreting hybridomas, but boosting with the protein antigen can reverse this propensity. Thus, this protein boosting approach may have implications for the production of IgG-specific hybridomas in the context of the DNA vaccination platform. In addition, the purified monoclonal IgG antibodies may be useful as therapeutic antibodies for controlling Ebola virus infection.
Animals ; Antibodies ; Antibodies, Monoclonal ; Antibody Formation ; Blotting, Western ; Clinical Coding* ; DNA* ; Ebolavirus* ; Enzyme-Linked Immunosorbent Assay ; Glycoproteins* ; Hemorrhagic Fever, Ebola ; Hybridomas* ; Immunization* ; Immunoglobulin G ; Immunoglobulin M ; Mice ; Vaccination ; Vaccines, DNA*

BACKGROUND/AIMS: The delay between the onset of myocardial infarction symptoms and primary percutaneous coronary intervention (PCI) is an important prognostic factor in patients with ST-segment elevation acute myocardial infarction (STEMI). We reviewed this delay in patients with STEMI and analyzed clinical outcomes. METHODS: The study enrolled 3,399 patients (age, 61.4 +/- 12.8 years; 25.6% women) with STEMI who underwent primary PCI within 12 hours of symptom onset between October 2005 and February 2008 from the Korea Acute Myocardial Infarction Registry. The patients were divided into two groups according to the symptom-to-balloon time: group I (< or = 3 hours, n = 955) and group II (> 3 hours, n = 2444). The in-hospital mortality rates and 1-year mortality and major adverse cardiac event (MACE) rates were compared between the two groups. RESULTS: The mean time interval from the onset of symptoms to arrival at the emergency room (ER) was 188.0 +/- 133.6 minutes (median, 152 minutes). The mean time interval from the ER to reperfusion (door-to-balloon time) was 97.8 +/- 67.9 minutes (median, 80 minutes). The mean time interval from the onset of symptoms to reperfusion (symptom-to-balloon time) was 285.8 +/- 146.2 minutes (median 250 minutes). The in-hospital mortality rate was significantly lower in group I as compared with group II (3.6% versus 5.2%, p = 0.044). The 1-year mortality rate was also significantly lower in group I (4.7% versus 7.2%, p = 0.012), while the 1-year MACE rate was not significantly different between groups (17.9% versus 20.4%, p = 0.179). CONCLUSIONS: This study demonstrates that there is a significant pre-hospital time delay in patients with STEMI in Korea and this time delay is associated with increased 1-year mortality.
Angioplasty ; Emergencies ; Hospital Mortality ; Humans ; Korea ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Reperfusion ; Time Factors

BACKGROUND: Freshmen maladaptation to university life has brought a lot of attention recently. Therefore, we intended to investigate about the relationship between anxiety, depression, stress and freshmen adaptation to university life. METHODS: We recruited 861 freshmen of a university located in Gyeongju, Gyeongbuk, and measured their degree of anxiety, depression, and stress by questionnaire from March 10 to 14, 2008. After 8 weeks, we examined their adaptation to university life by questionnaire and finally, analyzed the data of 600 freshmen. RESULTS: Among the freshmen, 285 (47.5%) had anxiety, 95 (15.8%) depression, and 70 (11.7%) stress. Adaptation to university life significantly associated with college-entrance exam experience, the number of close friends in class, willingness to join the club, major satisfaction and distance from the university to hometown, in addition to anxiety, depression, and stress. Risk factors of maladaptation to university life were stress (odds ratio: 2.66, 95% confidence interval: 1.60 to 4.45), depression (2.45; 1.56 to 3.84), one experience of college entrance exam (1.83; 1.24 to 2.69), anxiety (1.73; 1.27 to 2.37) and fewer than 5 close friends (1.60; 1.17 to 2.20). Short distance from the university to hometown (0.72; 0.53 to 0.98), willingness to join the club (0.60; 0.41 to 0.87) and major satisfaction (0.42; 0.29 to 0.61) were identified as lowering the risk of maladaptation to university life. CONCLUSION: Anxiety, depression, and stress closely related to freshmen adaptation to university life. During freshmen's health examination, we need to identify the degree of anxiety, depression and stress in order to predict maladaptation to university life.
Anxiety ; Depression ; Friends ; Humans ; Risk Factors

BACKGROUND: Angiotensin converting enzyme inhibitors (ACEIs) or Angiotensin II type 1 receptor blockers (ARBs) are compelling indication drugs for hypertensive patients with diabetes mellitus. But prescription rate in 2005 year study of Pohang . Gyeongju area was only 30.8%. Therefore, a study on the change of prescription rate in the same area after 3 years was done. METHODS: During three months from January 2008, 152 hypertensive patients with diabetes mellitus on their prescribed antihypertensive medications by 9 family physicians in visiting order were analyzed. After the analysis, the infl uencing factors for such prescriptions were ascertained by directly visiting each physicians who prescribed them. RESULTS: A regimen of 16 antihypertensive agents were prescribed by these family physicians. Prescription count of ACEIs or ARBs was 101 cases (66.4%). ACEIs single therapy was 19 cases (12.5%), ACEIs combination therapy was 7 cases (4.6%), ARBs single therapy was 31 cases (20.4%) and ARBs combination therapy was 44 cases (28.9%). The ACEIs or ARBs which were selected by physicians that followed "compelling indication" was 5 (55.6%), "excellent reduce pressure effect" was 3 (33.3%) and "public relations of new medicine" was 1 (11.1%). CONCLUSION: In prescribing antihypertensive agents for patients with diabetes mellitus, selection of ACEIs or ARBs was increased from 30.8% to 66.4%. Education of recommended standard by participating in such study and developing of excellent new medicines may increase such change.
Angiotensin II Type 1 Receptor Blockers ; Angiotensin-Converting Enzyme Inhibitors ; Antihypertensive Agents ; Diabetes Mellitus ; Humans ; Hypertension ; Physicians, Family ; Prescriptions ; Primary Health Care

OBJECTIVES: Impaired processing of facial information is one of the broad ranges of cognitive deficits seen in patients with schizophrenia. We aimed to elucidate the differences in brain activities involved in the process of facial working memory between schizophrenic patients and healthy comparison subjects. METHODS: Twelve patients with schizophrenia were recruited along with twelve demographically matched healthy volunteers as a comparison group. Functional magnetic resonance imaging (fMRI) was used to assess cortical activities during the performance of a 2-back working memory paradigm using images of neutral faces as mnemonic content. RESULTS: The patient group performed the tasks with reduced accuracy. Group analysis revealed that the left fusiform gyrus, the right superior frontal gyrus, the bilateral middle frontal gyri/insula, the left middle temporal gyrus, the precuneus, the quadrangular lobules and the vermis of cerebellum showed decreased cortical activities in the patient group. On the other hand, an increased level of activation in the lateral prefrontal cortex and the parietal lobule was observed from the patient group, all in the right hemisphere. CONCLUSION: A decreased level of activity in the left fusiform gyrus among the patient group implicates inefficient processing of facial information. An increased level of activation in prefrontal and parietal neural networks from the patient group confirms earlier findings on the impaired working memory of patients with schizophrenia.
Brain ; Cerebellum ; Hand ; Healthy Volunteers ; Humans ; Magnetic Resonance Imaging* ; Memory ; Memory, Short-Term* ; Prefrontal Cortex ; Rabeprazole ; Schizophrenia*