Search

The skin is a very suitable organ for the induction of immune responses to vaccine antigens. Antigen delivery systems to the skin by needle and syringe directly deposit the antigen into the epidermal-dermal compartment, one of the most immunocompetent sites due to the presence of professional antigen-presenting cells aimed at the induction of antigen-specific T cells. In this study, we analyzed the amount of ovalbumin as an antigen delivered to the skin by a microneedle. When ovalbumin protein as an antigen was delivered to the skin of mice using a dissolving microneedle, it induced an immune response through the enhanced proliferation and cytokines production by the splenocytes and lymph nodes. Also, it effectively increased the ovalbumin-specific CD8+ T cell and CD4+ T cell population and induced an ovalbumin-specific CTL response against the graft of ovalbumin-expressing EG7 tumor cells in the immunized mice. Also, we identified the inhibition of tumor growth and prevention of tumor formation in the context of the therapeutic and prophylactic vaccine, respectively through EG-7 tumor mouse model. Finally, these data show the potential of patches as attractive antigen delivery vehicles. [ABSTRACT FROM AUTHOR]

Fabrication of a spherical multi-compartment MRI phantom is demonstrated that can be used to validate magnetic resonance (MR)-based susceptibility imaging reconstruction. The phantom consists of a 10 cm diameter gelatin sphere that encloses multiple smaller gelatin spheres doped with different concentrations of paramagnetic contrast agents. Compared to previous multi-compartment phantoms with cylindrical geometry, the phantom provides the following benefits: (1) no compartmental barrier materials are used that can introduce signal voids and spurious phase; (2) compartmental geometry is reproducible; (3) spherical susceptibility boundaries possess a ground-truth analytical phase solution for easy experimental validation; (4) spherical geometry of the overall phantom eliminates background phase due to air-phantom boundary in any scan orientation. The susceptibility of individual compartments can be controlled independently by doping. During fabrication, formalin cross-linking and water-proof surface coating effectively blocked water diffusion between the compartments to preserve the phantom's integrity. The spherical shapes were realized by molding the inner gel compartments in acrylic spherical shells, 3 cm in diameter, and constructing the whole phantom inside a larger acrylic shell. From gradient echo images obtained at 3T, we verified that the phantom produced phase images in agreement with the theoretical prediction. Factors that limit the agreement include: air bubbles trapped at the gel interfaces, imperfect magnet shimming, and the susceptibility of external materials such as the phantom support hardware. The phantom images were used to validate publicly available codes for quantitative susceptibility mapping. We believe that the proposed phantom can provide a useful testbed for validation of MR phase imaging and MR-based magnetic susceptibility reconstruction. [ABSTRACT FROM AUTHOR]

Telomere length (TL) is a prognostic indicator in Caucasian chronic lymphocytic leukemia (CLL), but its significance in Asian CLL remains unknown. To investigate the prognostic significance of TL and its correlation with cytogenetic aberrations and somatic mutations, we analyzed TL measurements at the cellular level by interphase fluorescence in situ hybridization in patients with CLL in Korea. The present study enrolled 110 patients (41 females and 69 males) diagnosed with CLL according to the World Health Organization criteria (2001–2017). TLs of bone marrow nucleated cells at the single-cell level were measured by quantitative fluorescence in situ hybridization (Q-FISH) in 71 patients. The correlations of TL with clinical characteristics, cytogenetic aberrations, genetic mutations, and overall survival were assessed. The median value of mean TL in CLL patients (T/C ratio 7.46 (range 1.19–18.14) was significantly shorter than that in the normal controls (T/C ratio 15.28 (range 8.59–24.93) (p < 0.001). Shorter TLs were associated with complex karyotypes (p = 0.030), del(11q22) (p = 0.023), presence of deletion and/or mutation in ATM and/or TP53 (p = 0.019), and SH2B3 mutation (p = 0.015). A shorter TL was correlated with lower hemoglobin levels and adverse survival (mean TL < 9.35, p = 0.021). When the proportion of cells with extremely short TLs (< 7.61) was greater than 90%, CLL patients showed poor survival (p = 0.002). Complex karyotypes, TP53 mutation, and the number of mutated genes were determined to be significant adverse variables by multivariable Cox analysis (p = 0.011, p = 0.002, and p = 0.002, respectively). TL was attrited in CLL, and attrited telomeres were correlated with adverse survival and other well-known adverse prognostic factors. We infer that TL is an independent adverse prognostic predictor in Korean CLL. [ABSTRACT FROM AUTHOR]

Purpose: This study compares the plan quality of magnetic-resonance image (MRI)-based intensity modulated radiation therapy (IMRT) using a linac (MR-linac-IMRT), MRI-based IMRT using tri-Co-60 sources (MR-Co-60-IMRT), and volumetric modulated arc therapy (VMAT) for spine stereotactic ablative radiotherapy (SABR). Methods: Twenty patients with thoracic spine metastasis were retrospectively selected for this study. For each patient, the MR-linac-IMRT, MR-Co-60-IMRT, and VMAT plans were generated using an identical CT image set and structures, except for the spinal cord and spinal cord planning organ-at-risk volume (PRV). Those two structures were contoured based on CT image sets for VMAT planning while those were contoured based on MR image sets for MR-linac-IMRT and MR-Co-60-IMRT planning. The initial prescription doses were 18 Gy in a single fraction for every plan in this study. If the tolerance level of the spinal cord was not met, the prescription doses were reduced to meet the tolerance level of the spinal cord. Dose-volumetric parameters of each plan were analyzed. Results: The average spinal cord volumes contoured based on the CT and MR images were 3.8±1.6 cm3 and 1.1±1.0 cm3, respectively (p<0.001). For four patients, the prescription doses of VMAT plans were reduced to 16 Gy to satisfy the spinal cord tolerance level. For thirteen patients, the prescription doses of MR-Co-60-IMRT plans were reduced to be less than 16 Gy to meet the spinal cord tolerance level. However, for every MR-linac-IMRT plan, the initial prescription doses of 18 Gy could be delivered to the target volume while satisfying the spinal cord tolerance. The average values of D10%, V10Gy, and V14Gy of the spinal cord PRV consistently indicated that the doses to the spinal cord PRV in the MR-linac-IMRT plans were the lowest among three types of plans in this study (all with p≤0.003). Conclusion: MR-linac-IMRT appears promising for spine SABR. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate the probiotic characteristics of certain microbial strains for potential use as feed additives. Three bacterial strains and a yeast previously isolated from different environments were investigated. The strains were subjected to molecular identification and established as Lactobacillus paracasei CP133, Lactobacillus plantarum CP134, Bacillus subtilis CP350 and Saccharomyces cerevisiae CP605. Lactobacillus sp. CP133 and CP134 exhibited antibiosis, antibiotic activity, and relative odor reduction ability. Bacillus subtilis CP350 was thermotolerant, reduced hydrogen sulfide gas and showed significant proteolytic activity, whereas Saccharomyces cerevisiae CP605 exhibited high acid and bile salt tolerance. In general, the isolates in this study demonstrated improved functional characteristics, particularly acid and bile tolerance and relative cell adhesion to HT-29 monolayer cell line. Results in this work provides multifunctional probiotic characteristics of the strains for potential development of probiotics and cleaning of the environment. [ABSTRACT FROM AUTHOR]

To investigate the undesired irradiations outside of the treatment field by electron streams in air (air-electron-stream) during magnetic-resonance image-guided radiation therapy (MR-IGRT). A custom-made support phantom adjusting angles between the beam central axis (CAX) and the phantom surface (termed phantom-angles), were used. Using the ViewRay system, a rectangular parallelepiped phantom placed on the support phantom, was irradiated with field sizes of 6.3 cm × 6.3 cm (FS6.3) and 12.6 cm × 12.6 cm (FS12.6) at gantry angles of 0°, 30°, and 330°, and phantom-angles of 10°, 20°, and 30°. For each beam delivery, the isocenter was located at the center of mass of the phantom and 3 Gy was delivered to the isocenter (prescription dose = 3 Gy). The doses given by the air-electron-streams were measured using the EBT3 films on the panels placed orthogonal to the direction of the magnetic field at distances of 10 and 17 cm from CAX. Two dose distributions per irradiation were measured on the panel facing the phantom surface of the incident beam (front panel) and on the panel facing the phantom surface of the beam exit (end panel). We investigated the doses by the air-electron-streams by calculating the average doses inside the circles drawn around a point of the maximum dose with radii of x cm (DRx) from the dose distributions on the panels (x = 1–5 cm). The largest value of DRx was DR1 (1.64 Gy, 55% of the prescription dose) at 10 cm distance from CAX, with FS12.6, at 30° phantom-angle and 330° gantry angle. The average difference of the DR1 at the end panels (FS12.6) between the calculations and measurements was 1.36 Gy. The average global gamma passing rate with 3%/3 mm on the dose distributions at the end panels (FS12.6) was 40.3%. The calculated dose distributions on both panels were not coincident with the measured dose distributions. The Spearman’s rank correlation coefficients between the projected areas and the DRx values were always higher than 0.75 (all with p < 0.001). The doses by the air-electron-streams increased with the projected areas of the cross-sections of the treatment beams on the panels. [ABSTRACT FROM AUTHOR]

Chemicals interact with genes in the process of disease development and treatment. Although much biomedical research has been performed to understand relationships among genes, chemicals, and diseases, which have been reported in biomedical articles in Medline, there are few studies that extract disease–gene–chemical relationships from biomedical literature at a PubMed scale. In this study, we propose a deep learning model based on bidirectional long short-term memory to identify the evidence sentences of relationships among genes, chemicals, and diseases from Medline abstracts. Then, we develop the search engine DigChem to enable disease–gene–chemical relationship searches for 35,124 genes, 56,382 chemicals, and 5,675 diseases. We show that the identified relationships are reliable by comparing them with manual curation and existing databases. DigChem is available at . [ABSTRACT FROM AUTHOR]

Aim: Although the atheroprotective effects of statins and angiotensin II receptor blockers (ARBs) are well-established, little is known about their additive effects, especially during the early period of atherosclerosis. The aim of this study was to investigate whether combination of a statin and an ARB exerts synergistic anti-atherosclerotic effects, and to elucidate the mechanisms of combined effects. Methods: Atherosclerotic plaques were developed in arteries of 23 rabbits using a high-cholesterol diet (HCD) and intra-arterial balloon inflation. Rabbits received one of five different treatment strategies for 4 weeks: positive control [n = 5, HCD]; negative control [n = 3, regular chow diet]; statin [n = 5, HCD and rosuvastatin 10 mg]; ARB [n = 5, HCD and olmesartan 20 mg]; and combination [n = 5, HCD and statin+ARB]. Results: Histological analysis demonstrated that development of atherosclerotic plaques was inhibited more in combination group than in statin group (P = 0.001). Although macrophage infiltration identified by RAM11 staining was not significantly different between combination and individual treatment groups (31.76±4.84% [combination] vs. 38.11±6.53% [statin; P = 0.35] or 35.14±2.87% [ARB; P = 0.62]), the relative proportion of pro-inflammatory M1-macrophages was significantly lower in combination group than in ARB group (3.20±0.47% vs. 5.20±0.78%, P = 0.02). Furthermore, M2-macrophage polarization was higher in combination group than in statin group (17.70±3.04% vs. 7.86±0.68%, P = 0.001). Conclusion: Combination treatment with a statin and an ARB produced synergistic protective effects for atherosclerosis initiation and progression, which may be attributed to modulation of macrophage characteristics in the early period of atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Long-term variability of cardiometabolic risk factors have been suggested as the risk factors for cardiovascular disease and mortality. However, the effect of long-term variability of total cholesterol (TC) on incident atrial fibrillation (AF) has not been examined. Methods and findings: We explored whether visit-to-visit TC variability are associated with the risk of incident AF in 160,165 Korean adults, using the population-based Korean National Health Insurance Service–Health Screening Cohort (NHIS-HEALS) database, over a median duration of 8.4 years. TC variability was measured as coefficients of variance (TC-CV), standard deviation (TC-SD), and variability independent of the mean (TC-VIM). Kaplan–Meier analysis demonstrated a decreased disease-free probability in the highest quartile group of TC variability compared to that in the other groups. In the multivariate Cox proportional hazard analysis, the risk of AF increased significantly in the highest quartile group of TC variability. After multivariate adjustment for confounding variables including mean TC levels, the hazard ratio for incident AF was 1.15 (95% confidence interval 1.05–1.25; P = 0.0035) when comparing the highest with the lowest TC variability quartile (TC-CV). These relationships were consistent with TC variability defined using TC-SD or TC-VIM. Subgroup analyses, including age, sex, body mass index, and cardiometabolic disorders, showed similar results. Conclusions: The present study is the first to demonstrate that high TC variability was associated with an increased risk of AF. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of posterior capsulotomy by analyzing the long-term visual outcomes in patients with rhegmatogenous retinal detachment (RD), who underwent combined phaco-vitrectomy with or without primary posterior capsulotomy. Methods: A retrospective longitudinal cohort analysis was performed by using data of rhegmatogenous RD patients undergoing combined phaco-vitrectomy. Patients were divided into two groups; Group A (68 eyes of 68 patients) with capsulotomy, and Group B (39 eyes of 39 patients) without capsulotomy. We reviewed the best-corrected visual acuity (BCVA), incidence of posterior capsule opacification (PCO), clinical features at the diagnosis of rhegmatogenous RD, and intraoperative or postoperative complications following posterior capsulotomy. Results: The modified BCVA measured by the logarithm of the minimum angle of resolution at initial diagnosis and 3, 6, and 12 months after surgery was 0.67 in Group A versus 0.85 in Group B (p = 0.258), 0.40 in Group A versus 0.50 in Group B (p = 0.309), 0.27 in Group A versus 0.45 in Group B (p = 0.055), and 0.21 in Group A versus 0.47 in Group B (p = 0.014), respectively. In subgroup with macula-on RRD, Group A exhibited better visual outcomes compared to Group B at 6(0.17 versus 0.40 [p = 0.037]) and at 12 months(0.14 versus 0.39 [p = 0.030]). The incidence of PCO in Group B was higher than Group A(28.2% versus 4.4% (p < 0.001)). There were no complications associated with posterior capsulotomy. Conclusions: A primary posterior capsulotomy during combined phaco-vitrectomy using a 23-gauge vitreous cutter was a safe and effective surgical procedure in patients with RRD patients for preventing postoperative intraocular lens-related PCO. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to determine the prognostic factors of progression-free survival (PFS) and overall survival (OS) in non-nephrectomized patients with synchronous metastatic renal cell carcinoma (mRCC) receiving first-line vascular endothelial growth factor (VEGF)-targeted therapy or immunotherapy. Methods: Of 70 patients, 57 (81.4%) were treated with targeted therapy, including 5 (7.1%) with previous immunotherapy and 13 (18.6%) with immunotherapy only. The medical records of patients were retrospectively reviewed and analyzed to determine factors of PFS and OS using the Cox proportional hazards model with a statistical significance p-value <0.05. Results: The median treatment and follow-up periods were 3.9 and 30.9 months, respectively. Disease progression was reported in 90.0% of patients, with an objective response rate and clinical benefit rate of 26.1% and 76.8%, respectively. The lung (77.1%) was the most common site of metastasis. Multivariable analysis showed that poor Heng risk (hazard ratio [HR]: 2.37) and liver metastasis (HR: 2.34) were significant prognostic factors for PFS, and female sex (HR: 2.13), poor Heng risk (HR: 3.14), and liver metastasis (HR: 2.78) were significant prognostic factors for OS (p < 0.05). A subset analysis of risk factors among patients without previous history of immunotherapy also showed poor Heng risk (HR 2.92 and HR 4.24 for PFS) and liver metastasis (HR 2.87 and HR 4.81 for OS) as significant factors for both PFS and OS (p<0.05). Conclusion: Poor Heng risk, sex, and liver metastasis were associated with survival outcomes after first-line systemic therapy in patients with non-nephrectomized synchronous mRCC. [ABSTRACT FROM AUTHOR]

Background: Nationwide and regional interventions can help improve bystander cardiopulmonary resuscitation (CPR) awareness, knowledge, and the willingness. Periodic community investigation will help monitor the effect. This study aimed to compare the experience of CPR education, CPR knowledge, and CPR willingness, during a 5-year interval. Methods: This is a pre and post study. Two surveys were done in February 2012 and December 2016. National and regional intervention including legislation promoting public involvement, standardizing CPR education programs, training CPR instructors, and installing supporting organizations were done at the period. In both surveys, respondents were selected via quota sampling in Daegu Metropolitan City and answered the survey through face-to-face interview. Respondents’ general demographic characteristics, CPR educational experience, CPR knowledge and CPR willingness were questioned. Results: Total of 2141 respondents (1000 in 2012, 1141 in 2016) were selected. The percentage of respondents who received CPR education itself and recent education were higher after intervention compared to before intervention (36.2% vs. 55.1%, 16.9% vs. 30.1%, respectively). Correct knowledge of performing CPR seems to be improved overall (1.6% vs. 11.7%, odd ratio 14.28, 95% confidence interval 5.68–35.94). However, less respondents were willing to perform CPR on strangers (54.5% vs 35.0%). Conclusion: Nationwide and regional interventions to promote bystander CPR and CPR education were associated with increased CPR education experience and improved correct CPR knowledge in performing bystander CPR. Willingness to perform bystander CPR on family did not increase significantly and CPR willingness to strangers was decreased. Additional legal and technological measures should be implemented to promote bystander CPR. [ABSTRACT FROM AUTHOR]

Although pretransplant cardiac dysfunction is considered a major predictor of poor outcomes after liver transplantation (LT), the ability of left ventricular (LV) systolic/diastolic function (LVSF/LVDF), together or individually, to predict mortality after LT is poorly characterized. We retrospectively evaluated pretransplant clinical and Doppler echocardiographic data of 839 consecutive LT recipients from 2009 to 2012 aged 18–60 years. The primary endpoint was all-cause mortality at 4 years. The overall survival rate was 91.2%. In multivariate Cox analysis, reduced LV ejection fraction (LVEF, P = 0.014) and decreased transmitral E/A ratio(P = 0.022) remained significant prognosticators. In LVSF analysis, patients with LVEF≤60% (quartile [Q]1) had higher mortality than those with LVEF>60% (hazard ratio = 1.90, 95% confidence interval = 1.15–3.15, P = 0.012). In LVDF analysis, patients with an E/A ratio<0.9(Q1) had a 2.19-fold higher risk of death (95% confidence interval = 1.11–4.32, P = 0.024) than those with an E/A ratio>1.4(Q4). In combined LVDF and LVSF analysis, patients with an E/A ratio<0.9 and LVEF≤60% had poorer survival outcomes than patients with an E/A ratio≥0.9 and LVEF>60% (79.5% versus 93.3%, P = 0.001). Patients with an early mitral inflow velocity/annular velocity (E/e’ ratio)>11.5(Q4) and LV stroke volume index (LVSVI)<33mL/m2(Q1) showed worse survival than those with an E/e’ ratio≤11.5 and LVSVI ≥33mL/m2(78.4% versus 92.2%, P = 0.003). A combination of LVSF and LVDF is a better predictor of survival than LVSF or LVDF alone. [ABSTRACT FROM AUTHOR]

Purpose: To compare the outcomes of robotic partial nephrectomy (RPN) with those of open PN (OPN) in patients with highly complex renal tumors defined as RENAL nephrometry score ≥ 10 Materials and methods: We analyzed clinical data from a total of 149 patients who underwent OPN or RPN for a highly complex renal mass at our institution between 2003 and 2017. Perioperative data, complication profiles, functional outcomes, pathologic variables, and oncologic outcomes were evaluated in both groups. Results: The median (interquartile range, IQR) patient age was 52.0 (42.0–59.0) years, and the median (IQR) follow-up period was 30.0 (7.0–54.0) months. Among the patients, 64 (43.0%) and 85 (57.0%) underwent OPN and RPN, respectively. The RPN group showed higher rates of clinical T1b and ≥ T2 than the OPN group (p = 0.019). There were no significant differences between the groups in terms of intraoperative outcomes such as operation time, estimated blood loss, warm ischemic time, and transfusion. Notably, the RPN group showed significantly shorter length of hospital stay than the OPN group (p < 0.001). Regarding the complication profiles and renal functional outcomes, no significant differences were reported between the groups. The estimated glomerular filtration rate decline from baseline at the last follow-up showed no significant differences between the two groups (p = 0.351). Kaplan-Meier survival analysis also showed no significant differences in survival outcomes between the groups (log-rank test, all p > 0.05). Conclusions: RPN performed in patients with highly complex renal tumors offers perioperative, functional, and oncologic outcomes comparable to those associated with OPN. [ABSTRACT FROM AUTHOR]

Background: The failure rate of epidural anesthesia using the loss of resistance technique is 13–23%. Objectives: To investigate the efficacy of epidural electric stimulation-guided epidural analgesia in vaginal delivery. Study design: An open label randomized prospective study. Methods: Laboring women were randomized to two groups: epidural catheter insertion using only a loss of resistance technique or a loss of resistance technique with confirmation by electric stimulation. Catheters in both groups were initially tested with 3 ml of 1% lidocaine and those with any evidence of motor blockade were considered intrathecal. Sensory blockade and an 11 point numerical rating score for pain were assessed 30 minutes after administration of an epidural bolus of 10 ml of 0.22% ropivacaine with fentanyl. Successful epidural analgesia was defined as a decrease of 2 or more in the pain score and a bilateral L1-T10 sensory blockade. Results: Thirty-one patients were randomized to each group. The first 20 patients in each group were enrolled in a pilot study and were also included in the final analysis. One patient in the electric stimulation group was excluded owing to dural puncture by the Tuohy needle. One patient in each group demonstrated motor blockade after test dose and were considered failures. The number (% (95% confidence interval)) of successful cases were 29 out of 30 (97% (85, 100%)) in the electric stimulation group and 24 out of 31 (77% (61, 89%)) in the loss of resistance group (P = 0.053). However, analysis of only patients with absence of motor blockade revealed that 29 out of 29 (100% (92, 100%)) patients in the electric stimulation group and 24 of 29 (80% (63, 91%)) patients in the loss of resistance group had adequate analgesia (P = 0.024). Conclusions: Although limited by lack of blinding, small study size and inclusion of pilot study data, this study suggests epidural electric stimulation improves the success rate of subsequent labor analgesia. [ABSTRACT FROM AUTHOR]

Background: We evaluated optimal duration of dual antiplatelet therapy (DAPT) after second-generation drug-eluting stent (DES) implantation in acute coronary syndrome (ACS). Material and methods: From pooled analysis of three randomized clinical trials (EXCELLENT, IVUS-XPL, RESET), a total of 2,216 patient with ACS undergoing second-generation DES implantation were selected. Each study randomized patients to a short-duration DAPT arm (n = 1119; ≤6 months) or a standard-duration DAPT arm (n = 1097; ≥12 months). Two-thirds of patients were male, and their mean age was 63 years. Mean DAPT durations were 164 ±76 and 359 ±68 days, respectively. The primary endpoint was composite of cardiac death, myocardial infarction, stent thrombosis, stroke or major bleeding during the first 12 months after implantation, analyzed according to the intention-to-treat population. Results: Demographic characteristics were balanced between groups. Mean DAPT duration was 164 and 359 days, respectively. Primary endpoint occurred in 22 patients with short-DAPT and 21 patients with standard-DAPT (2.0% versus 1.9%; hazard ratio [HR] 1.03; 95% confidence interval [CI] 0.56–1.86; p = 0.94). Landmark analysis after six-months, no significant difference in primary endpoint between short and standard duration DAPT (1.0% versus 0.8%; HR 1.22; 95% CI 0.51–2.95; p = 0.66). Conclusions: Short-duration DAPT (≤6 months) demonstrated a similar incidence of net adverse cardiovascular and clinical events at 12 months after second-generation DES in ACS compared with standard duration DAPT (≥12 months). Clinical trial registration: EXCELLENT (ClinicalTrials.gov, ), RESET (ClinicalTrials.gov, ), IVUS-XPL (ClinicalTrials.gov, ) [ABSTRACT FROM AUTHOR]

Objective: Data concerning the effect of current smoking on solely new-generation drug-eluting stents (DES) are limited. We investigated the impact of current smoking on 2-year clinical outcomes between durable-polymer (DP)-coated DES (zotarolimus-eluting [ZES] and everolimus eluting [EES]) and biodegradable-polymer (BP)-coated biolimus-eluting stent (BES) in acute myocardial infarction (AMI) patients after successful percutaneous coronary intervention (PCI). Methods: Finally, a total of 8357 AMI patients with current smoking underwent successful PCI with new-generation DES (ZES, EES, and BES) were enrolled and divided into three groups as ZES (n = 3199), EES (n = 3987), and BES group (n = 1171). The primary endpoint was the occurrence of major adverse cardiac events (MACE) defined as all-cause death (cardiac death [CD] or non-cardiac death), recurrent AMI (re-MI), any revascularization (target lesion revascularization [TLR], target vessel revascularization [TVR], and non-TVR). The secondary endpoint was the incidence of definite or probable stent thrombosis (ST). Results: The 2-year adjusted hazard ratio (HR) of MACE for ZES vs. EES (1.055; 95% confidence interval [CI], 0.843–1.321; p = 0.638), ZES vs. BES (HR, 0.885; 95% CI, 0.626–1.251; p = 0.488), EES vs. BES (HR, 0.889; 95% CI, 0.633–1.250; p = 0.499), and ZES/EES vs. BES (HR, 0.891; 95% CI, 0.648–1.126; p = 0.480) were similar. The occurrence of ST after adjustment were also comparable. In addition, the 2-year adjusted HR for all-cause death, CD, re-MI, TLR, TVR, and non-TVR were not different. Conclusions: In this study, DP-DES and BP-DES showed comparable safety and efficacy during 2-year follow-up periods. Therefore, DP-DES or BP-DES are equally acceptable in AMI patients with current smoking undergoing PCI. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare the inverse planning simulated annealing (IPSA) stochastic algorithm with the hybrid inverse planning and optimization (HIPO) algorithm for interstitial tongue high-dose-rate (HDR) brachytherapy. Methods: Twenty patients who received radiotherapy for tongue cancer using interstitial HDR brachytherapy were retrospectively selected for this study. Oncentra Brachy v. 4.3 was used for IPSA and HIPO planning. Four to eight fixed catheter configurations were determined according to the target shape. During the optimization process, predetermined constrain values were used for each IPSA and HIPO plan. The dosimetric parameters and dwell time were analyzed to evaluate the performances of the plans. Results: The total dwell time using IPSA was 4 seconds longer than that of HIPO. The number of active positions per catheter for the IPSA plans were approximately 2.5 fewer than those of the HIPO plans. The dose-volumetric parameters related to the clinical target volume with IPSA were lower than those with HIPO. In terms of the dose-volumetric parameters related to normal tissue, HIPO tended to associate with slightly higher values than IPSA, without statistical significance. After GrO, the target coverages were satisfied to clinical goal for all patients. The total dwell times was approximately increased by 10%. Conclusions: The IPSA and HIPO dose optimization algorithms generate similar dosimetric results. In terms of the dwell time, HIPO appears to be more beneficial. [ABSTRACT FROM AUTHOR]

Fibrates are used in patients with dyslipidemia and high cardiovascular risk. However, information regarding drug response to fibrate has been highly limited. We investigated treatment results and factors associated with triglyceride reduction after fenofibrate therapy using large-scale real-world data. Patients with one or more cardiovascular risk factors, at low-density lipoprotein-cholesterol goal but with triglyceride level ≥150 mg/dL, and undergoing treatment with fenofibrate 135–160 mg for the first time were included in this retrospective observational study. The outcome variable was the percentage changes of TG levels. The achievement rate of triglyceride <150 mg/dL was additionally analyzed. Factors associated with treatment results were also analyzed. Among 2546 patients who were initially screened, 1113 patients were enrolled (median age: 61 years; male: 71%). After median follow-up of 4 months, the median change in triglyceride was -60%, and 49% of the patients reached triglyceride <150 mg/dL. After adjusting for confounding variables, female sex, non-diabetic status, coronary artery disease, lower baseline triglyceride, and no statin use were identified to be independently associated with achievement of triglyceride <150 mg/dL. Among them, female sex, non-diabetic status, and coronary artery disease were also related to median or greater percentage reduction of triglyceride. In conclusion, only half of the study patients reached triglyceride levels <150 mg/dL after real-world fenofibrate therapy. This study indicates that more attention is needed on some subgroups to obtain optimal triglyceride levels when treating with fenofibrate. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the accuracy of CT for small, hypervascular hepatocellular carcinomas (HCCs) and assess the enhancement patterns on CT. Materials and methods: Ninety-nine patients who underwent cone-beam CT hepatic arteriography (CBCT-HA) during initial chemoembolization for HCC suspected on CT were enrolled in this study. A total of 297 hypervascular HCCs (142 ≥ 1 cm, 155 < 1 cm) were confirmed as HCCs based on two-year follow-up CT and CBCT-HA images. During the two-year follow-up, pre-existing hypervascular foci on CBCT-HA were regarded as HCCs at the initial presentation. Two radiologists categorized HCCs according to the following enhancement patterns on CT: type I, arterial enhancement and washout; type II, arterial enhancement without washout; and type III, no arterial enhancement. Two blinded reviewers rated the possibility of HCC. Results: For the 297 HCCs, the enhancement patterns according to size were as follows: type I ≥1 cm in 114 HCCs; type I <1 cm in 40 HCCs; type II ≥1 cm in 16 HCCs; type II <1 cm in 37 HCCs; type III ≥1 cm in 12 HCCs; and type III <1 cm in 10 HCCs. The remaining 68 HCCs (22.9%) were not detected on CT. The detection rates of HCCs ≥ 1 cm were 83.1%, 76.8%, and 83.1% in the formal report for reviewer 1 and reviewer 2. In comparison, the detection rates of HCCs < 1 cm were 20.6%, 17.4%, and 17.4% in the formal report for reviewer 1 and reviewer 2. Conclusion: Many subcentimeter sized hypervascular HCCs were frequently missed or not evident on CT at the initial diagnostic workup. CT has limitations for diagnosing HCCs that are <1 cm in size or have atypical enhancement patterns. [ABSTRACT FROM AUTHOR]

This study aimed to determine serial changes in self-assessed goal achievement (SAGA) and treatment satisfaction after HoLEP, to identify correlations between the two, and to compare them with results assessed by traditional outcome measures. For a total of 170 patients, outcomes were evaluated serially at postoperative 1-, 3-, 6-, and 12-months using IPSS, OABSS, SAGA questionnaires and uroflowmetry. The SAGA questionnaire consisted of five questions including one open-ended question (self-assessed goals and degree of SAGA) and another question regarding treatment satisfaction. The number of self-assessed treatment goals was two or more in 74.1% of the patients. Most common treatment goal was relief from straining/hesitancy, followed by increased daytime frequency, nocturia and feeling of incomplete emptying. Degree of achievement for the first or second goal and treatment satisfaction tended to increase with time throughout the follow-up period. Patients with the greatest treatment satisfaction scores showed greater improvement by traditional outcome parameters including quality of life (QOL) index, total OABSS, maximum flow rate (Qmax), post-void residual urine volume (PVR) and bladder voiding efficiency (BVE) compared to those without treatment satisfaction. After adjusting for other influential variables, the improvements in subjective outcome parameters including total IPSS, QOL index and total OABSS were significantly associated with treatment satisfaction, but improvements in objective outcome parameters including Qmax, PVR and BVE were not. In addition, the degree of SAGA for the first goal or second goal was more predictive in determining treatment satisfaction than the traditional outcome measures. In conclusion, treatment goals of patients with lower urinary tract symptoms (LUTS)/BPH vary from individual to individual. The degree of SAGA and treatment satisfaction for HoLEP tends to increase with time throughout the follow-up period. Compared to the traditional outcome measures, the degree of goal achievement can be more predictive when assessing patient-centered outcomes such as treatment satisfaction. [ABSTRACT FROM AUTHOR]

Hemi-ablation of prostate cancer (PCa) requires an accurate prediction of laterality. Recently, multi-parametric magnetic resonance imaging (mpMRI) has recently been increasingly used to enhance clinical staging and characterization of tumor foci. Thus, we tried to investigate the real-life accuracy of combinatory approach of using both transrectal ultrasound (TRUS)-guided prostatic biopsy and mpMRI in predicting the laterality of PCa. We reviewed the records of 335 men who were suspected of having unilateral PCa on multi (≥ 12)-core TRUS-guided biopsy and preoperative mpMRI and subsequently had undergone radical prostatectomy (RP) at our institution. Based on the analysis of pathologic outcomes from RP, the performance of the combinatory approach in predicting the pathological laterality of PCa was evaluated. Pathology was classified to be unfavorable when showing a Gleason pattern of 4/5 or pT3/N1 features. Significant cancer was defined as non-organ-confined disease, having a Gleason pattern of 4/5, or showing a cancer volume of ≥ 0.5 mL. Among the 335 unilateral lobes not suspected to harbor tumor from either the TRUS biopsy or mpMRI, the actual absence rate of malignancy was only 13.7% from a pathologic analysis of RP specimens. Even among the 115 D’Amico low-risk group, the absence rate of malignancy was only 26.1% in unilateral lobes not suspected to harbor tumor. Among the 335 lobes, unfavorable pathology and significant cancer were not observed in 36.1% and 30.7%, respectively. The absence rates of unfavorable pathology and significant cancer among the D’Amico low risk group were 56.5% and 47.8%, respectively. Meanwhile, the absence rate of dominant Gleason pattern 4 or 5 was 74.9% among the 335 total subjects. Our real-life clinical experience showed that the combination of multi-core TRUS-guided biopsy and mpMRI did not provide reliable accuracy in the prediction of true unilaterality of PCa. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) computational aortic models have been established to reproduce aortic diseases such as aortic aneurysm and dissection; however, no such models have been developed to study diabetes mellitus (DM). To characterize biomechanical properties of the human aorta with DM, reconstructed aortic CT images were converted into DICOM format, and imported into the 3D segmentation using Mimics software. This resulted in a 3D reconstruction of the complete aorta, including three branches. We applied a pulsatile blood pressure waveform for the ascending aorta to provide a biomimetic environment using COMSOL Multiphysics software. Hemodynamics were compared between the control and DM models. We observed that mean blood flow velocity, aortic pressure, and von Mises stress values were lower in the DM model than in the control model. Furthermore, the range of aortic movement was lower in the DM model than in the control model, suggesting that the DM aortic wall is more susceptible to rupture. When comparing biomechanical properties in discrete regions of the aorta, all values were higher in the ascending aorta for both control and DM models, corresponding to the location of most aortic lesions. We have developed a compute based that integrates advanced image processing strategies and computational techniques based on finite element method to perform hemodynamics analysis based on CT images. Our study of image-based CFD analysis hopes to provide a better understanding of the relationship between aortic hemodynamic and developing pathophysiology of aortic diseases. [ABSTRACT FROM AUTHOR]

The human myeloid leukemia cell line HL-60 differentiate into monocytes following treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). However, the mechanism underlying the differentiation of these cells in response to TPA has not been fully elucidated. In this study, we performed ChIP-seq profiling of RNA Pol II, HDAC2, Acetyl H3 (AcH3), and H3K27me3 and analyzed differential chromatin state changes during TPA-induced differentiation of HL-60 cells. We focused on atypically active genes, which showed enhanced H3 acetylation despite increased HDAC2 recruitment. We found that HDAC2 positively regulates the expression of these genes in a histone deacetylase activity-independent manner. HDAC2 interacted with and recruited paired box 5 (PAX5) to the promoters of the target genes and regulated HL-60 cell differentiation by PAX5-mediated gene activation. Taken together, these data elucidated the specific-chromatin status during HL-60 cell differentiation following TPA exposure and suggested that HDAC2 can activate transcription of certain genes through interactions with PAX5 in a deacetylase activity-independent pathway. [ABSTRACT FROM AUTHOR]

Dengue fever is a major international public health concern, with more than 55% of the world population at risk of infection. Recent climate changes related to global warming have increased the potential risk of domestic outbreaks of dengue in Korea. In this study, we develop a two-strain dengue model associated with climate-dependent parameters based on Representative Concentration Pathway (RCP) scenarios provided by the Korea Meteorological Administration. We assess the potential risks of dengue outbreaks by means of the vector capacity and intensity under various RCP scenarios. A sensitivity analysis of the temperature-dependent parameters is performed to explore the effects of climate change on dengue transmission dynamics. Our results demonstrate that a higher temperature significantly enhances the potential threat of domestic dengue outbreaks in Korea. Furthermore, we investigate the effects of countermeasures on the cumulative incidence of humans and vectors. The current main control measures (comprising only travel restrictions) for infected humans in Korea are not as effective as combined control measures (travel restrictions and vector control), dramatically reducing the possibilities of dengue outbreaks. [ABSTRACT FROM AUTHOR]

Radiation-induced lung damage is an important treatment-related toxicity after lung stereotactic ablative radiotherapy (SABR). After implementing a tri-60Co magnetic-resonance image guided system, ViewRayTM, we compared the associated early radiological lung density changes to those associated with a linear accelerator (LINAC). Eight patients treated with the tri-60Co system were matched 1:1 with patients treated with LINAC. Prescription doses were 52 Gy or 60 Gy in four fractions, and lung dose-volumetric parameters were calculated from each planning system. The first two follow-up computed tomography (CT) were co-registered with the planning CT through deformable registration software, and lung density was measured by isodose levels. Tumor size was matched between the two groups, but the planning target volume of LINAC was larger than that of the tri-60Co system (p = 0.036). With regard to clinically relevant dose-volumetric parameters in the lungs, the ipsilateral lung mean dose, V10Gy and V20Gy were significantly poorer in tri-60Co plans compared to LINAC plans (p = 0.012, 0.036, and 0.017, respectively). Increased lung density was not observed in the first follow-up scan compared to the planning scan. A significant change of lung density was shown in the second follow-up scan and there was no meaningful difference between the tri-60Co system and LINAC for all dose regions. In addition, no patient developed clinical radiation pneumonitis until the second follow-up scan. Therefore, there was no significant difference in the early radiological lung damage between the tri-60Co system and LINAC for lung SABR despite of the inferior plan quality of the tri-60Co system compared to that of LINAC. Further studies with a longer follow-up period are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Aims: Atherosclerosis is a well-known cause of cardiovascular disease and is associated with a variety of inflammatory reactions. However, an adequate large-animal model of advanced plaques to investigate the pathophysiology of atherosclerosis is lacking. Therefore, we developed and assessed a swine model of advanced atherosclerotic plaques with macrophage polarization. Methods: Mini-pigs were fed a 2% high-cholesterol diet for 7 weeks followed by withdrawal periods of 4 weeks. Endothelial denudation was performed using a balloon catheter on 32 coronary and femoral arteries of 8 mini-pigs. Inflammatory proteins (high-mobility group box 1 [HMGB1] or tumor necrosis factor alpha (TNF-α) were injected via a micro-infusion catheter into the vessel wall. All lesions were assessed with angiography and optical coherence tomography and all tissues were harvested for histological evaluation. Results: Intima/plaque area was significantly higher in the HMGB1- and TNF-α-injected groups compared to the saline-injected group (p = 0.002). CD68 antibody detection and polarization of M1 macrophages significantly increased in the inflammatory protein-injected groups (p<0.001). In addition, advanced atherosclerotic plaques were observed more in the inflammatory protein-injected groups compared with the control upon histologic evaluation. Conclusion: Direct injection of inflammatory proteins was associated with acceleration of atherosclerotic plaque formation with M1 macrophage polarization. Therefore, direct delivery of inflammatory proteins may induce a pro-inflammatory response, providing a possible strategy for development of an advanced atherosclerotic large-animal model in a relatively short time period. [ABSTRACT FROM AUTHOR]

Enzymes isolated from organisms found in cold habitats generally exhibit higher catalytic activity at low temperatures than their mesophilic homologs and are therefore known as cold-active enzymes. Cold-active proteases are very useful in a variety of biotechnological applications, particularly as active ingredients in laundry and dishwashing detergents, where they provide strong protein-degrading activity in cold water. We identified a cold-active protease (Pro21717) from a psychrophilic bacterium, Pseudoalteromonas arctica PAMC 21717, and determined the crystal structure of its catalytic domain (CD) at a resolution of 1.4 Å. The Pro21717-CD structure shows a conserved subtilisin-like fold with a typical catalytic triad (Asp185, His244, and Ser425) and contains four calcium ions and three disulfide bonds. Interestingly, we observed an unexpected electron density at the substrate-binding site from a co-purified peptide. Although the sequence of this peptide is unknown, analysis of the peptide-complexed structure nonetheless provides some indication of the substrate recognition and binding mode of Pro21717. Moreover, various parameters, including a wide substrate pocket size, an abundant active-site loop content, and a flexible structure provide potential explanations for the cold-adapted properties of Pro21717. In conclusion, this is first structural characterization of a cold-adapted subtilisin-like protease, and these findings provide a structural and functional basis for industrial applications of Pro21717 as a cold-active laundry or dishwashing detergent enzyme. [ABSTRACT FROM AUTHOR]

Lung cancer specialists play an important role in designing and implementing lung cancer screening. We aimed to describe their 1) attitudes toward low-dose lung computed tomography (LDCT) screening, 2) current practices and experiences of LDCT screening and 3) attitudes and opinions towards national lung cancer screening program (NLCSP). We conducted a national web-based survey of pulmonologists, thoracic surgeons, medical oncologists, and radiological oncologists who are members of Korean Association for Lung Cancer (N = 183). Almost all respondents agreed that LDCT screening increases early detection (100%), improves survival (95.1%), and gives a good smoking cessation counseling opportunity (88.6%). Most were concerned about its high false positive results (79.8%) and the subsequent negative effects. Less than half were concerned about radiation hazard (37.2%). Overall, most (89.1%) believed that the benefits outweigh the risks and harms. Most (79.2%) stated that they proactively recommend LDCT screening to those who are eligible for the current guidelines, but the screening propensity varied considerably. The majority (77.6%) agreed with the idea of NLCSP and its beneficial effect, but had concerns about the quality control of CT devices (74.9%), quality assurance of radiologic interpretation (63.3%), poor access to LDCT (56.3%), and difficulties in selecting eligible population using self-report history (66.7%). Most (79.2%) thought that program need to be funded by a specialized fund rather than by the National Health Insurance. The opinions on the level of copayment for screening varied. Our findings would be an important source for health policy decision when considering for NLCSP in Korea. [ABSTRACT FROM AUTHOR]

Importance: This review provides a comprehensive comparison of treatment outcomes between robot-assisted laparoscopic surgery (RLS) and conventional laparoscopic surgery (CLS) based on randomly-controlled trials (RCTs). Objectives: We employed RCTs to provide a systematic review that will enable the relevant community to weigh the effectiveness and efficacy of surgical robotics in controversial fields on surgical procedures both overall and on each individual surgical procedure. Evidence review: A search was conducted for RCTs in PubMed, EMBASE, and Cochrane databases from 1981 to 2016. Among a total of 1,517 articles, 27 clinical reports with a mean sample size of 65 patients per report (32.7 patients who underwent RLS and 32.5 who underwent CLS), met the inclusion criteria. Findings: CLS shows significant advantages in total operative time, net operative time, total complication rate, and operative cost (p < 0.05 in all cases), whereas the estimated blood loss was less in RLS (p < 0.05). As subgroup analyses, conversion rate on colectomy and length of hospital stay on hysterectomy statistically favors RLS (p < 0.05). Conclusions: Despite higher operative cost, RLS does not result in statistically better treatment outcomes, with the exception of lower estimated blood loss. Operative time and total complication rate are significantly more favorable with CLS. [ABSTRACT FROM AUTHOR]

Inflammation is a commonly observed immune reaction, and rheumatoid arthritis is a particularly severe inflammatory disease. In this study, we used an air pouch mouse model to evaluate the anti-inflammatory potential of Allium hookeri, which has both been used as a culinary material and a traditional medicine in south-eastern Asia for many years. Allium hookeri suppressed typical symptoms of inflammation, such as condensation of the air pouch membrane, and inhibited the expression of several inducible proinflammatory cytokines such as IL-1β, IL-6, IL-13, and TNF-α. In order to determine the molecules modulating the inflammatory effect of carrageenan treatment, the components in Allium hookeri were analyzed by GC-MS, and linoleic acid, which have anti-inflammatory effect, was detected. From the results, we concluded that the anti-inflammatory effect of Allium hookeri might be attributed to linoleic acid, which could be promising candidates for anti-inflammatory drugs that have no adverse effects. [ABSTRACT FROM AUTHOR]

The white blood cell differential count of the bone marrow provides information concerning the distribution of immature and mature cells within maturation stages. The results of such examinations are important for the diagnosis of various diseases and for follow-up care after chemotherapy. However, manual, labor-intensive methods to determine the differential count lead to inter- and intra-variations among the results obtained by hematologists. Therefore, an automated system to conduct the white blood cell differential count is highly desirable, but several difficulties hinder progress. There are variations in the white blood cells of each maturation stage, small inter-class differences within each stage, and variations in images because of the different acquisition and staining processes. Moreover, a large number of classes need to be classified for bone marrow smear analysis, and the high density of touching cells in bone marrow smears renders difficult the segmentation of single cells, which is crucial to traditional image processing and machine learning. Few studies have attempted to discriminate bone marrow cells, and even these have either discriminated only a few classes or yielded insufficient performance. In this study, we propose an automated white blood cell differential counting system from bone marrow smear images using a dual-stage convolutional neural network (CNN). A total of 2,174 patch images were collected for training and testing. The dual-stage CNN classified images into 10 classes of the myeloid and erythroid maturation series, and achieved an accuracy of 97.06%, a precision of 97.13%, a recall of 97.06%, and an F-1 score of 97.1%. The proposed method not only showed high classification performance, but also successfully classified raw images without single cell segmentation and manual feature extraction by implementing CNN. Moreover, it demonstrated rotation and location invariance. These results highlight the promise of the proposed method as an automated white blood cell differential count system. [ABSTRACT FROM AUTHOR]