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BACKGROUND Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) results in poor survival outcome. This study assessed the clinical outcomes of pulmonary metastasectomy in LT recipients with pulmonary metastasis of HCC in a high-volume transplant center and analyzed factors prognostic of survival following metastasectomy. MATERIAL AND METHODS This study analyzed outcomes in 52 patients who underwent pulmonary resection due to pulmonary metastasis as the first recurrence of HCC after LT from January 2004 to December 2017 in a single center. RESULTS The 52 enrolled patients included 46 men and 6 women, aged 56.0±6.6 years. Their 1-, 3-, and 5-year survival rates after pulmonary resection were 75.0%, 43.5%, and 33.9%, respectively. The 1-, 3-, and 5-year survival rates were 85.3%, 47.1%, and 34.2%, respectively, in patients with further metastases and 55.6%, 38.1%, and 38.1%, respectively, in patients without further metastases (P=0.45). The size and number of pulmonary metastatic nodules were unrelated to survival rates (all P>0.10). A shorter recurrence-free period after LT (hazard ratio [HR]=0.553, P=0.006), elevated alpha-fetoprotein concentration at metastasectomy (HR=2.142, P=0.03), and adjuvant chemotherapy after metastasectomy (HR=3.79, P=0.003) were independent risk factors for survival after metastasectomy. CONCLUSIONS Pulmonary metastasectomy for HCC recurrence in LT recipients showed favorable survival outcomes. Independent risk factors for survival after metastasectomy included recurrence-free survival after LT, alpha-fetoprotein level at metastasectomy, and adjuvant chemotherapy after metastasectomy.

Objectives: To investigate lymph node (LN) metastasis according to tumour location and assess the impact of lobe-specific LN dissection on survival in stage IA non-small-cell lung cancer (NSCLC)., Methods: We retrospectively analysed the data of patients with clinical stage IA NSCLC treated with lobectomy and systematic LN dissection at Asan Medical Center (Seoul, Korea) between June 2005 and April 2017. Patients who received neoadjuvant therapy had multiple primary tumours or missed the follow-up during the first postoperative year were excluded. The patients were divided into five groups according to involved lung lobes: right upper lobe (RUL), right middle lobe (RML), right lower lobe (RLL), left upper lobe (LUL) and left lower lobe (LLL), which were further divided into subgroups according to LN station metastasis. Overall survival (OS) and the incidence of metastasis were calculated for each subgroup. Efficacy indices (EIs) were calculated to determine the correlation between each lung lobe and LN station, and the impact of the dissection of these stations on survival., Results: A total of 1202 patients were analysed. The 5-year OS in the RUL, RML, RLL, LUL and LLL groups was 74%, 88%, 78%, 80% and 75%, respectively. The incidence of single LN station metastasis was 11%, 10%, 10%, 16% and 14%, respectively. The lobe-specific LNs for RUL, RML, RLL, LUL and LLL were stations 2/3/4, 4/7, 2/4/7, 4/5/6 and 6/7/9, respectively. Moreover, the LN stations with high EIs for RUL, RML, RLL, LUL and LLL were 4, 7, 7, 5 and 7, respectively. In the RUL group, the incidence of metastasis to stations 2, 3 and 4 was 2.3%, 0.5% and 7.6%, and the EI was 0.8, 0.3 and 4.3, respectively. In RML, the incidence of metastasis to stations 4 and 7 was 4% and 6%, and the EI was 1.3 and 2.4, respectively. In RLL, the incidence of metastasis to stations 2, 4 and 7 was 4.4%, 5.6% and 8.3%, and the EI was 1.3, 1.4 and 3.3, respectively. In LUL, the incidence of metastasis to stations 4, 5 and 6 was 1.4%, 11.8% and 2.5%, and the EI was 0.4, 7.1 and 0.5, respectively. In LLL, the incidence of metastasis to stations 6, 7 and 9 was 1.1%, 5.7% and 1.7%, and the EI was 0.6, 2.3 and 0.5, respectively. Furthermore, the OS of patients with lobe-specific LN metastasis was statistically significantly different from that of the non-lobe-specific LN metastasis group with P-values of <0.001 for RUL, 0.002 for RML, 0.002 for RLL, 0.001 for LUL and 0.003 for LLL., Conclusions: Our findings support the use of lobe-specific LN dissection in stage IA NSCLC. When LN stations with high EI were negative, LN metastasis in other stations was unlikely. The incidence of LN metastasis beyond lobe-specific LN stations was ∼1% in all subgroups. Dissection of non-lobe-specific LNs may not improve the OS; however, prospective randomized controlled trials are needed to modify the standard approach., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Metal-mediated self-assembly of chelating double-hydrophilic block copolymer has become a facile preparation strategy of great importance for the metal-chelated hybrid nanostructures. Herein, we present a delicate control over the morphology regulation of metal-chelated nanostructures by a terminal modification of polymer building blocks with mesogenic cholesterol. Such a molecular design motif at an end of chelating linear/brush-type block copolymer imparts not only additional hydrophobicity for enhanced cohesive force to facilitate the metal-mediated self-assembly, but also significant morphological alteration of a metal-chelated core that otherwise generally forms a spherical interior with cholesterol-free block copolymers. The presence of cholesterol entities localized at the central core further allows for the density modulation of the final Pt II -chelated nanostructures while maintaining the colloidal stability, comparable to that of the cholesterol-free nanoparticles in physiological conditions. This metal-mediated assembly strategy with modified polymer building blocks can provide a potential platform for the delivery of inorganic agents.

Renal function declines after partial nephrectomy due to ischemic reperfusion injury induced by surgical insult or renal artery clamping. The effect of remote ischemic preconditioning (RIPC) on reducing renal injury after partial nephrectomy has not been studied regarding urinary biomarkers. Eighty-one patients undergoing partial nephrectomy were randomly assigned to either RIPC or the control group. RIPC protocol consisted of four cycles of five-min inflation and deflation of a blood pressure cuff to 250 mmHg. Serum creatinine levels were compared at the following time points: preoperative baseline, immediate postoperative, on the first and third days after surgery, and two weeks after surgery. The incidence of acute kidney injury, other surgical complication rates, and urinary biomarkers, including urine creatinine, β-2 microglobulin, microalbumin, and N-acetyl-beta-D-glucosaminidase were compared. Split renal functions measured by renal scan were compared up to 18 months after surgery. There was no significant difference in the serum creatinine level on the first postoperative day (median (interquartile range) 0.87 mg/dL (0.72-1.03) in the RIPC group vs. 0.92 mg/dL (0.71-1.12) in the control group, p = 0.728), nor at any other time point. There was no significant difference in the incidence of acute kidney injury. Secondary outcomes, including urinary biomarkers, were not significantly different between the groups. RIPC showed no significant effect on the postoperative serum creatinine level of the first postoperative day. We could not reveal any significant difference in the urinary biomarkers and clinical outcomes. However, further larger randomized trials are required, because our study was not sufficiently powered for the secondary outcomes.

East Asian patients have reduced anti-ischemic benefits and increased bleeding risk during antithrombotic therapies compared with Caucasian patients. As potent P2Y 12 receptor inhibitors (e.g., ticagrelor and prasugrel) and direct oral anticoagulants are commonly used in current daily practice, the unique risk-benefit trade-off in East Asians has been a topic of emerging interest. In this article, we propose updated evidence and future directions of antithrombotic treatment in East Asian patients., Competing Interests: S.G. is a consultant for Janssen and Bristol-Myers Squibb. S.G. received research grant from Sanofi, Pfizer, and Ono, and independent research grant support from Bristol-Myers Squibb (33999603). S.G. also received personal fee from Thrombosis Research Institute (London, United Kingdom) as a member of Steering Committee for GARFIELD-AF and GARFIELD-VTE and from the American Heart Association as an associate editor. T.G. research is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) TRR 240 “Platelets—Molecular, Cellular and Systemic Functions in Health and Disease” (Project number 374031971). T.G. received personal fees from Astra Zeneca, Boehringer Ingelheim, Chiesi, Ferrer, and Pfizer, and research grants and personal fees from Bayer Healthcare, Bristol-Myers Squibb, Daiichi Sankyo, and Eli Lilly. D.A.G. reports institutional grants from Bayer and BMS, and speaker fees from Bayer and AstraZeneca. G.Y.H. is a consultant for Bayer/Janssen, BMS/Pfizer, Medtronic, Boehringer Ingelheim, Novartis, Verseon, and Daiichi-Sankyo; speaker for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim, and Daiichi-Sankyo. No fees were directly received personally. D.A.J. has received consulting fees or honoraria from Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, and The Medicines Company, and has received payments for participation in review activities from CeloNova and St. Jude Medical. He also declares that his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, Osprey Medical, Renal Guard Solutions, and the Scott R. MacKenzie Foundation. G.P.A.G. reports serving as a consultant and receiving fees/honoraria from Daiichi Sankyo, Bayer, AstraZeneca, Merck, Boehringer, New Haven Pharmaceuticals, Janssen, and CSL, and receiving grants from the National Institutes of Health, Daiichi Sankyo, CSL, AstraZeneca, Harvard Clinical Research Institute, Haemonetics, New Haven Pharmaceuticals, Duke Clinical Research Institute, Sinnowa, and Coramed. P.A.G. has patents in the field of platelet function testing. M.H.J. has received honoraria for lectures from AstraZeneca, Sanofi-Aventis, Daiichi Sankyo/Lilly, Haemonetics, Otsuka, Han-mi Pharmaceuticals, and Yuhan Pharmaceuticals, and research grants or support from AstraZeneca, Korean Society of Interventional Cardiology, Han-mi Pharmaceuticals, Yuhan Pharmaceuticals, Otsuka, and Haemonetics. The other authors report no conflicts of interest., (Thieme. All rights reserved.)

We investigated whether two needle insertion techniques for ultrasound-guided internal jugular vein (IJV) catheterization differ in the number of needling attempts and complication rate between inexperienced and experienced practitioners. A total of 308 patients requiring IJV catheterization were randomly assigned into one of four groups: IJV catheterization performed by inexperienced practitioners using either Seldinger (IE-S; n = 78) or modified Seldinger technique (IE-MS; n = 76) or IJV catheterization performed by experienced practitioners using either Seldinger (E-S; n = 78) or modified Seldinger technique (E-MS; n = 76). All catheterizations were performed under the real-time ultrasound guidance. The number of needling attempts was not significantly different between the two techniques within each experience group (between IE-S vs. IE-MS P = 0.550, between E-S and E-MS P = 0.834). Time to successful catheterization was significantly shorter in the E-S group compared to E-MS group (P < 0.001) while no significant difference between IE-S and IE-MS groups (P = 0.226). Complication rate was not significantly different between the two techniques within each experience group. Practitioner's experience did not significantly affect the clinical performance of needle insertion techniques during ultrasound-guided IJV catheterization except the time to successful catheterization. Regarding the number of needling attempts and complication rate, both techniques could be equally recommended regardless of practitioner's experience.Trial registration: clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT03077802).

This study developed and evaluated a behavior model for permeable non-spherical micro-plastic aggregates in a turbulent flow of freshwater based on fractal theory, as conducting experimental and modeling studies. Laboratory-scale experiments evaluated attachment efficiency α to aggregation kinetics in an aquatic environment (pH 6, 20 ℃) of the electrolyte (Al 3+ ). The experimental α was dependent on characteristics of plastics (type, size, and density) and ranged from 0.062 to 0.2772 (averaging 0.1) with a high correlation with the modeled α (R 2 > 0.92). Model validation was conducted under two simulation conditions: one drawn from a previously published study of impermeable spherical aggregates and the other based on fractal theory. The simulations verified the limited primary particle size with the lowest retention rate based on the previous study but it was difficult to determine the specific particle size with the lowest retention rate as a limiting factor. The sum of residual errors for aggregation/sedimentation between the two types of structures showed an overestimation of spherical structures. Such overestimation influenced the aggregate number concentration and distribution pattern. Therefore, the model needs to more detailed express the aggregation mechanism of permeable non-spherical aggregate structures in terms of surface growth., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aims: Potent P2Y12 inhibitors for dual antiplatelet therapy (DAPT) is crucial for managing acute myocardial infarction; however, the selection of drugs is based on limited clinical information such as age and body weight. The current study sought to develop and validate a new risk scoring system that can be used to guide the selection of potent P2Y12 inhibitors by balancing ischaemic benefit and bleeding risk., Methods and Results: Derivation cohort of 10 687 patients who participated in the Korea Acute Myocardial Infarction Registry-National Institutes of Health study was used to construct a new scoring system. We combined the ischaemic and bleeding models to establish a simple clinical prediction score. Among the low score group (n = 1764), the observed bleeding risk (8.7% vs. 4.4%, P < 0.001) due to potent P2Y12 inhibitors exceeded ischaemic benefit (1.3% vs. 2.2%, P = 0.185) during 12 months. Conversely, the high score group (n = 1898) showed an overall benefit from taking potent P2Y12 inhibitors from the standpoint of observed ischaemic (17.1% vs. 8.6%, P < 0.001) and bleeding events (10.1% vs. 6.8%, P = 0.073). The performance of ischaemic [integrated area under the curve (iAUC) = 0.809] and bleeding model (iAUC = 0.655) was deemed to be acceptable., Conclusion: The new scoring system is a useful clinical tool for guiding DAPT by balancing ischaemic benefit and bleeding risk, especially among Asian populations. Further validation studies with other cohorts will be required to verify that the new system meets the needs of real clinical practice., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Abstract: Appropriate risk stratification and timely revascularization of acute myocardial infarction (AMI) are available in percutaneous coronary intervention (PCI) - capable hospitals (PCHs). This study evaluated whether direct admission vs inter-hospital transfer influences cardiac mortality in patients with AMI. This study was conducted in the PCH where the patients were able to arrive within an hour. The inclusion criteria were AMI with a symptom onset time within 24 hours and having undergone PCI within 24 hours after admission. The cumulative incidence of cardiac death after percutaneous coronary intervention was evaluated in the direct admission versus inter-hospital transfer groups. Among the 3178 patients, 2165 (68.1%) were admitted via inter-hospital transfer. Patients with ST-segment elevation myocardial infarction (STEMI) in the direct admission group had a reduced symptom onset-to-balloon time (121 minutes, P < .001). With a median period of 28.4 (interquartile range, 12.0-45.6) months, the cumulative incidence of 2-year cardiac death was lower in the direct admission group (NSTEMI, 9.0% vs 11.0%, P = .136; STEMI, 9.7% vs 13.7%, P = .040; AMI, 9.3% vs 12.3%, P = .014, respectively). After the adjustment for clinical variables, inter-hospital transfer was the determinant of cardiac death (hazard ratio, 1.59; 95% confidence interval, 1.08-2.33; P = .016). Direct PCH admission should be recommended for patients with suspected AMI and could be a target for reducing cardiac mortality., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

To assess the temporal trends of bleeding episodes during half- vs. standard-dose ticagrelor in acute coronary syndrome (ACS) patients with low platelet reactivity (LPR) during standard-dose ticagrelor (90 mg bid). ACS Patients with LPR (<85 P2Y 12 reaction units) ( n = 122) were randomly assigned to receive either half-dose (45 mg bid) or standard-dose ticagrelor (90 mg bid). The primary endpoint was incidence of Bleeding Academic Research Consortium (BARC) bleeding at 1 week, 1, 3 and 6 months. Dyspnea and ischemic events were also evaluated. Bleeding episodes were most commonly observed at 1 month and then decreased over time. Half-dose ticagrelor did not reduce any BARC bleeding (odds ratio [OR] 0.900, 95% confidence interval [CI] 0.563-1.440, p = 0.661). However, serious bleeding (BARC type ≥2) occurred less often in half-dose ticagrelor (OR 0.284, 95% CI 0.088-0.921, p = 0.036). The rate of moderate-to-severe dyspnea was highest at 1 month, then decreased over time. Half-dose ticagrelor did not decrease moderate-to-severe dyspnea (Borg scale ≥ 3) (OR 1.066, 95% CI 0.322-3.530, p = 0.916). The risk of ischemic events was also similar between the groups. In conclusions, compared with standard-dose ticagrelor, half-dose ticagrelor reduced serious bleeding events during early period of dual-antiplatelet therapy in ACS patients with LPR; however, the risk of any bleeding events and dyspnea did not differ according to ticagrelor dose. Clinical registration: KCT0004640.

Despite advancements in pharmacotherapy and interventional strategies, patients with acute coronary syndrome (ACS) remain at risk of recurrent thrombotic events. In addition to an enhanced tendency to thrombus formation, impairment in the ability to naturally dissolve or lyse a developing thrombus, namely impaired endogenous fibrinolysis, is responsible for a major part of this residual risk regardless of optimal antiplatelet medication. Global assessment of endogenous fibrinolysis, including a point-of-care assay, can identify patients with ACS at persistent high cardiovascular risk and might play an important role in allowing the personalisation of potent antithrombotic therapy to enhance fibrinolytic status, providing precision treatment of ACS to improve long-term outcome.

Arterial and venous atherothrombotic events are finely regulated processes involving a complex interplay between vulnerable blood, vulnerable vessel, and blood stasis. Vulnerable blood ('thrombogenicity') comprises complex interactions between cellular components and plasma factors (inflammatory, procoagulant, anticoagulant, and fibrinolytic factors). The extent of thrombogenicity may determine the progression of atheroma and the clinical manifestation of atherothrombotic events, with the highest thrombogenicity in African Americans and lowest in East Asians. Inherent thrombogenicity may influence clinical efficacy and safety of specific antithrombotic treatments in high-risk patients, which may in part explain the observation that East Asian patients have reduced anti-ischemic benefits and elevated bleeding risk with antithrombotic therapy compared to Caucasian patients. In this review, we discuss available evidence regarding the racial differences in thrombogenicity and its impact on clinical outcomes among patients with atherosclerotic cardiovascular disease., Competing Interests: Dr. Geisler T received personal fees from Astra Zeneca, Boehringer Ingelheim, Chiesi, Ferrer, and Pfizer, research grants from Bayer Healthcare, Bristol-Myers Squibb, Daiichi Sankyo, and Eli Lilly, and funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation TRR 240 "Platelets - Molecular, cellular and systemic functions in health and disease" (project No. 374031971). Dr. Gorog DA reports institutional grants from Bayer and BMS, and speaker fees from Bayer and Astra-Zeneca. Dr. Gurbel PA reports grants and personal fees from Bayer HealthCare LLC, Otitopic Inc, Amgen, Janssen, US WorldMeds LLC; grants from Instrumentation Laboratory, Hikari Dx, Haemonetics, Medicure, Idorsia pharmaceuticals, and personal fees from Up-To-Date. Gurbel has a patent, detection of restenosis risk in patients issued and a patent, assessment of cardiac health and thrombotic risk in a patient. Dr. Jeong has received honoraria for lectures from AstraZeneca, Daiichi Sankyo, Sanofi-Aventis, Han-mi Pharmaceuticals and Yuhan Pharmaceuticals; and research grants or support from Yuhan Pharmaceuticals and U&I Corporation. The other authors have no financial conflicts of interest., (Copyright © 2021. The Korean Society of Cardiology.)

In this study, with the motivation of developing low temperature sintered Pb-free ceramics for use in piezoelectric actuators, 0.97(Na 0.52 K 0.443 Li 0.037 )(Nb 0.923 Sb 0.04 Ta 0.037 )O₃ - 0.03 (Bi 0.5 Na 0.5 ) 0.9 (Sr) 0.1 ZrO₃ ceramics were manufactured and their piezoelectric properties analyzed. All specimens doped with boron oxide showed a typical pure perovskite structure. The ceramics with x = 0.1 composition showed a co-existence of R-T phases. When boron oxide is doped at 0.1 wt%, excellent physical properties of d 33 = 270 pC/N ε r = 1386, k p = 0.416, and Q m = 130 were obtained making the ceramic ideal for use in piezoelectric actuators.

For patients undergoing robot-assisted radical prostatectomy, the pneumoperitoneum with a steep Trendelenburg position could worsen intraoperative respiratory mechanics and result in postoperative atelectasis. We investigated the effects of individualized positive end-expiratory pressure (PEEP) on postoperative atelectasis, evaluated using lung ultrasonography. Sixty patients undergoing robot-assisted radical prostatectomy were randomly allocated into two groups. Individualized groups ( n = 30) received individualized PEEP determined by a decremental PEEP trial using 20 to 7 cm H 2 O, aiming at maximizing respiratory compliance, whereas standardized groups ( n = 30) received a standardized PEEP of 7 cm H 2 O during the pneumoperitoneum. Ultrasound examination was performed on 12 sections of thorax, and the lung ultrasound score was measured as 0-3 by considering the number of B lines and the degree of subpleural consolidation. The primary outcome was the difference between the lung ultrasound scores measured before anesthesia induction and just after extubation in the operating room. An increase in the difference means the development of atelectasis. The optimal PEEP in the individualized group was determined as the median (interquartile range) 14 (12-18) cm H 2 O. Compared with the standardized group, the difference in the lung ultrasound scores was significantly smaller in the individualized group (-0.5 ± 2.7 vs. 6.0 ± 2.9, mean difference -6.53, 95% confidence interval (-8.00 to -5.07), p < 0.001), which means that individualized PEEP was effective to reduce atelectasis. The lung ultrasound score measured after surgery was significantly lower in the individualized group than the standardized group (8.1 ± 5.7 vs. 12.2 ± 4.2, mean difference -4.13, 95% confidence interval (-6.74 to -1.53), p = 0.002). However, the arterial partial pressure of the oxygen/fraction of inspired oxygen levels during the surgery showed no significant time-group interaction between the two groups in repeated-measures analysis of variance ( p = 0.145). The incidence of a composite of postoperative respiratory complications was comparable between the two groups. Individualized PEEP determined by maximal respiratory compliance during the pneumoperitoneum and steep Trendelenburg position significantly reduced postoperative atelectasis, as evaluated using lung ultrasonography. However, the clinical significance of this finding should be evaluated by a larger clinical trial.

Compared with Caucasian patients, East Asian patients with coronary artery disease (CAD) have demonstrated better clinical outcomes. We sought to compare the viscoelastic properties of clot formation and their impact on clinical outcomes in East Asian vs. Caucasian patients. We analyzed age- and sex-matched East Asian and Caucasian patients with stable CAD (n = 249 each). Viscoelastic properties of clot formation were assessed with thromboelastography (TEG), and 3-year clinical outcomes were recorded. Major adverse cardiovascular events (MACE) were defined as a composite of cardiovascular death, myocardial infarction, or stroke. Compared with Caucasians, East Asians showed lower platelet-fibrin clot strength (PFCS) (maximum amplitude [MA]: 61.8 ± 7.9 vs. 65.4 ± 5.0 mm, p < 0.001). In a multivariate analysis, high PFCS (defined as MA ≥ 68 mm) was significantly associated with MACE occurrence (odds ratio 6.27, 95% CI 2.41 to 16.30, p < 0.001). East Asians vs. Caucasians had lower prevalence of high PFCS (odds ratio 0.50, 95% CI 0.27 to 0.93, p = 0.028). In conclusion, this is the first study to demonstrate different viscoelastic properties of clot between East Asian and Caucasian patients with stable CAD. The platelet-fibrin clot strength was significantly associated with MACE in these patients and was significantly lower in East Asians. Future studies are warranted to further explore the mechanistic explanation and clinical importance of these findings.

Background: This study aimed to evaluate the prognostic value of pretreatment 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) in patients with localized primary gastrointestinal stromal tumors (GISTs) and to compare the predictive values of 18 F-FDG PET/CT parameters with those of clinicopathological prognostic factors., Methods: Sixty-two localized GIST patients who underwent staging with 18 F-FDG PET/CT from January 2007 to December 2013 before surgery were retrospectively enrolled. A volume of interest with a standardized uptake value (SUV) threshold of 2.5 was used to determine the metabolic tumor volume (MTV) and total lesion glycolysis (TLG). These metabolic indices, along with the maximum SUV (SUVmax), were analyzed to evaluate recurrence-free survival (RFS). Other significant clinical and pathologic indices were also retrospectively reviewed for RFS analysis., Results: Patients were followed up for a median of 42.0 months (range, 5.6-111.5). During the follow-up period, 13 patients (21.0%) experienced disease recurrence. In univariate analysis, tumor size (> 5 cm), mitotic count (> 5/high-power field), modified National Institutes of Health (NIH) consensus criteria, adjuvant imatinib treatment, SUVmax (≥ 7.04), MTV (≥ 50.76 cm 3 ), and TLG (≥ 228.79 g) were significant prognostic factors affecting RFS (p < 0.05). In multivariate analysis, only MTV (hazard ratio, 17.69; 95% confidence interval [CI], 2.03-154.17, p = 0.009) and TLG (hazard ratio, 20.48; 95% CI, 2.19-191.16, p = 0.008) were independent prognostic factors for RFS. The 5-year RFS rates were 96.4% and 96.6% in patients with a low MTV and TLG and 27.3% and 23.6% in patients with a high MTV and TLG, respectively (p < 0.001)., Conclusion: MTV and TLG are independent prognostic factors for predicting recurrence in patients with localized primary GIST. Patients with a high MTV or TLG are at risk for poor prognosis and should be closely observed for disease recurrence.

Lately, in orthodontic treatments, the use of transparent aligners for the correction of malocclusions has become prominent owing to their intrinsic advantages such as esthetics, comfort, and minimal maintenance. Attempts at improving upon this technology by varying various parameters to investigate the effects on treatments have been carried out by several researchers. Here, we aimed to investigate the biomechanical and clinical effects of aligner thickness on stress distributions in the periodontal ligament and changes in the tooth's center of rotation. Dental finite element models comprising the cortical and cancellous bones, gingiva, teeth, and nonlinear viscoelastic periodontal ligaments were constructed, validated, and used together with aligner finite element models of different aligner thicknesses to achieve the goal of this study. The finite element analyses were conducted to simulate the actual orthodontic aligner treatment process for the correction of malocclusions by generating pre-stresses in the aligner and allowing the aligner stresses to relax to induce tooth movement. The results of the analyses showed that orthodontic treatment in lingual inclination and axial rotation with a 0.75 mm-thick aligner resulted in 6% and 0.03% higher principal stresses in the periodontal ligament than the same treatment using a 0.05 mm-thick aligner, respectively. Again, for both aligner thicknesses, the tooth's center of rotation moved lingually and towards the root direction in lingual inclination, and diagonally from the long axis of the tooth in axial rotation. Taken together, orthodontic treatment for simple malocclusions using transparent aligners of different thicknesses will produce a similar effect on the principal stresses in the periodontal ligament and similar changes in the tooth's center of rotation, as well as sufficient tooth movement. These findings provide orthodontists and researchers clinical and biomechanical evidence about the effect of transparent aligner thickness selection and its effect on orthodontic treatment.

Competing Interests: Dr. Kreutz has received consulting fees from Haemonetics. Dr. Jeong has received honoraria for lectures from AstraZeneca, Sanofi-Aventis, Daiichi Sankyo/Lilly, Haemonetics, Otsuka, Han-mi Pharmaceuticals and Yuhan Pharmaceuticals; and research grants or support from AstraZeneca, Korean Society of Interventional Cardiology, Han-mi Pharmaceuticals, Yuhan Pharmaceuticals, Otsuka and Haemonetics. Dr. Levy reports honoraria for advisory boards from Instrumentation Labs, Merck, Octapharma, and Janssen. Dr. Gurbel reports grants and personal fees from Bayer HealthCare LLC, Otitopic Inc, Amgen, Janssen, and US WorldMeds LLC; grants from Instrumentation Laboratory, Haemonetics, Medicure Inc, Idorsia Pharmaceuticals, and Hikari Dx; personal fees from UpToDate; Dr Gurbel is a relator and expert witness in litigation involving clopidogrel; in addition, Dr. Gurbel has two patents, Detection of restenosis risk in patients and Assessment of cardiac health and thrombotic risk in a patient. Other authors report no disclosure.

Background: Pu'er tea, a type of post-fermented tea made from Camellia sinensis leaves, has long been widely used in East Asian countries. It is mainly produced in southern China and is effective in preventing obesity due to its ability to break down fat. However, the effects of Pu'er tea on cognitive impairment or neuroinflammation by endotoxin have not yet been studied., Purpose: Here, we assessed the inhibitory activity of Pu'er tea hot water extract (PTW) on neuroinflammation and cognitive impairment and explored its mechanism., Study Design: The ability of PTW to inhibit cognitive impairment was investigated in a mouse model of lipopolysaccharide (LPS)-induced neuroinflammation and murine microglia BV2 cells., Methods: We examined whether oral administration of PTW prevented cognitive impairment and LPS-induced neuroinflammation using behavioral tests, Nissl staining, immunohistochemistry, western blotting, real-time reverse transcription-polymerase chain reaction (real-time RT-PCR), Griess assay, and enzyme-linked immunosorbent assay (ELISA)., Results: First, Morris water maze (MWM) and passive avoidance (PA) tests demonstrated that oral administration of PTW effectively attenuated LPS-induced spatial memory loss and inhibited neuronal damage of mouse brains. Histopathological analysis showed that PTW repressed LPS-induced expression of the activation markers ionized calcium-binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP). Furthermore, PTW inhibited the expression of amyloidogenesis proteins such as amyloid-β precursor protein (APP), C99, and β-secretase-1 (BACE-1); production of inflammatory proteins such as Iba-1, GFAP, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2; activation of inflammatory pathways; and expression of inflammatory mediator mRNAs in hippocampal tissue. In cultured microglia, PTW treatment inhibited the generation of various inflammatory factors activated by LPS., Conclusion: Our results in vivo and in vitro demonstrate that PTW effectively prevents cognitive impairment caused by neuroinflammation and is, therefore, a potential candidate for the development of a therapeutic agent for neurodegenerative diseases., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-3066). Dr. YHJ reports personal fees from AstraZeneca, personal fees from Sanofi-Aventis, personal fees from Daiichi Sankyo, grants and personal fees from Han-mi Pharmaceuticals, grants and personal fees from Yuhan Pharmaceuticals, grants from U&I Corporation, non-financial support from Haemonetics, during the conduct of the study. The other authors have no conflicts of interest to declare.

Background: Cholinergic interneurons (ChINs) in the nucleus accumbens (NAc) play critical roles in processing information related to reward. However, the contribution of ChINs to the emergence of addiction-like behaviors and its underlying molecular mechanisms remain elusive., Methods: We employed cocaine self-administration to identify two mouse subpopulations: susceptible and resilient to cocaine seeking. We compared the subpopulations for physiological responses with single-unit recording of NAc ChINs, and for gene expression levels with RNA sequencing of ChINs sorted using fluorescence-activated cell sorting. To provide evidence for a causal relationship, we manipulated the expression level of dopamine D 2 receptor (DRD2) in ChINs in a cell type-specific manner. Using optogenetic activation combined with a double whole-cell recording, the effect of ChIN-specific DRD2 manipulation on each synaptic input was assessed in NAc medium spiny neurons in a pathway-specific manner., Results: Susceptible mice showed higher levels of nosepoke responses under a progressive ratio schedule, and impairment in extinction and punishment procedures. DRD2 was highly abundant in the NAc ChINs of susceptible mice. Elevated abundance of DRD2 in NAc ChINs was sufficient and necessary to express high cocaine motivation, putatively through reduction of ChIN activity during cocaine exposure. DRD2 overexpression in ChINs mimicked cocaine-induced effects on the dendritic spine density and the ratios of excitatory inputs between two distinct medium spiny neuron cell types, while DRD2 depletion precluded cocaine-induced synaptic plasticity., Conclusions: These findings provide a molecular mechanism for dopaminergic control of NAc ChINs that can control the susceptibility to cocaine-seeking behavior., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Patients with peripheral artery disease (PAD) have shown the increased risk of cardiovascular (CV) morbidity and mortality. This study sought to evaluate the impact of clot strength on prevalence and major adverse CV events (MACE) of PAD in high-risk patients. We enrolled patients undergoing percutaneous coronary intervention (PCI) (n = 1667) with available platelet-fibrin clot strength [thrombin-induced maximal amplitude (MA thrombin ) measured by thromboelastography] and inflammation [high sensitivity C-reactive protein (hs-CRP)]. PAD was defined with abnormal ankle-brachial index (≤ 0.9 or > 1.4). MACE was defined as a composite of CV death, myocardial infarction or stroke. PAD was observed in 201 patients (12.1%). In the multivariate analysis, high clot strength [MA thrombin  ≥ 68 mm: odds ratio (OR) 1.70, 95% confidence interval (CI) 1.20 to 2.41, p = 0.003] and enhanced inflammation (hs-CRP ≥ 3.0 mg/L: OR 2.30, 95% CI 1.56 to 3.41, p < 0.001) were associated with PAD occurrence. During the follow-up post-PCI (median, 25 months), MACE was more frequently occurred in patients with vs. without PAD (18.7% vs. 6.4% at 3 years; hazard ratio 1.72, 95% CI 1.03 to 2.87, p = 0.039). Furthermore, combined presence of PAD and high clot strength significantly increased the risk of MACE. In conclusion, this study is the first to show the impact of clot strength on prevalence and clinical outcomes of PAD in coronary artery disease patients undergoing PCI. Whether antithrombotic strategy according to level of this biomarker can improve clinical outcomes in PAD patients deserves the further study.

Background: Dobutamine stress echocardiography (DSE) and coronary computed tomography angiography (CTA) can provide perioperative prognostic information in risk stratification of patients undergoing noncardiac surgery. This study directly compared the prognostic value of DSE and CTA in patients undergoing noncardiac surgery., Methods: Between 2014 and 2016, 215 patients with more than one clinical risk factor for perioperative cardiovascular (CV) events were enrolled prospectively. They received both DSE and CTA before noncardiac surgery. Perioperative clinical risk was classified according to the revised cardiac risk index (RCRI), DSE results were categorized as abnormal (inducible ischemia and/or nonviable infarction) or not. CTA results were assessed using the severity of stenosis, with significant stenosis being ≥50% of the luminal diameter). After the exclusion, a total of 206 patients remained. Perioperative CV events were defined as CV death, non-fatal myocardial infarction (MI), myocardial injury, pulmonary edema, non-fatal stroke, and systemic embolism within 30 days after surgery., Results: Twenty-four patients (12%) had perioperative cardiac events (1 cardiac death, 10 non-fatal MI, 8 myocardial injury, 11 pulmonary edema, 1 non-fatal stroke, and 1 pulmonary embolism). Following adjustment for baseline RCRI score, abnormal result on DSE (OR, 6.08, 95% CI, 2.41 to 15.31, P < 0.001), significant CAD on CTA (OR, 18.79; 95% CI, 5.24 to 67.42, P < 0.001), and high CACS (OR, 4.19; 95% CI, 1.39 to 12.60, P = 0.011) remained significant predictors of perioperative CV events., Conclusions: DSE and CTA are independent predictive factors of events in patients undergoing noncardiac surgery. Among them, assessment of significant CAD using CTA might show a higher prognostic value compared with DSE before noncardiac surgery., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02250963., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Atopic dermatitis (AD) is an inflammatory skin disease caused by an imbalance between Th1 and Th2 cells. AD patients suffer from pruritus, excessive dryness, red or inflamed skin, and complications such as sleep disturbances and depression. Although there are currently many AD treatments available there are insufficient data on their long-term stability and comparative effects. Moreover, they have limitations due to various side effects. Multipotent mesenchymal stem cells (M-MSCs) might have potential for next-generation AD therapies. MSCs are capable of immune function regulation and local inflammatory response inhibition. M-MSCs, derived from human embryonic stem cells (hESC), additionally have a stable supply. In L507 antibody array, M-MSCs generally showed similar tendencies to bone marrow-derived mesenchymal stem cells (BM-MSCs), although the immunoregulatory function of M-MSCs seemed to be superior to BM-MSCs. Based on the characteristics of M-MSCs on immunoregulatory functions, we tested a M-MSC conditioned media concentrate (MCMC) in mice with AD lesions on their dorsal skin. MCMC significantly decreased RNA expression levels of inflammatory cytokines in the mouse dorsal skin. It also suppressed serum IgE levels. In addition, significant histopathologic alleviation was identified. In conclusion, secretions of M-MSCs have the potential to effectively improve AD-related inflammatory lesions. M-MSCs showed potential for use in next-generation AD treatment.

Nonalcoholic fatty liver disease (NAFLD) is associated with progressive metabolic diseases. Estrogen deficiency increases the NAFLD risk among postmenopausal women. Thus, effective agents to prevent and treat NAFLD in postmenopausal women are required. Quercitrin (Quer) is a natural glycosylated flavonoid with antimicrobial, anti-inflammatory, and hypolipidemic effects. This study investigated whether Quer improves dysregulated lipid metabolism and suppresses hepatic steatosis in ovariectomized (OVX) mice as an experimental model mimicking postmenopausal women. Mice were assigned to the following four groups: SHAM, OVX, OVX + β-estradiol (0.4 mg/kg diet), and OVX + Quer (500 mg/kg diet). Mice were administered a diet with or without Quer for three months. OVX mice displayed significantly higher body mass, epidermal fat, and liver weights than those of SHAM mice. However, these levels were reduced in Quer-treated mice. Quer treatment reduced the levels of serum lipid metabolites, including triglycerides, total cholesterol, and low-density lipoprotein cholesterol. Furthermore, Quer reduced liver lipid steatosis and inhibited the expression of proinflammatory cytokines, such as tumor necrosis factor-α, IL-6, and IL-1β. The results of the present study indicate that Quer improves dysregulated lipid metabolism and reduces hepatic steatosis and inflammation by compensating for estrogen deficiency, suggesting that Quer may potentially exert protective effects during hepatic steatosis in postmenopausal women.

Objectives: The aim of this study was to evaluate the effect of ticagrelor versus clopidogrel on left ventricular (LV) remodeling after reperfusion of ST-segment elevation myocardial infarction (STEMI) in humans., Background: Animal studies have demonstrated that ticagrelor compared with clopidogrel better protects myocardium against reperfusion injury and improves remodeling after myocardial infarction., Methods: In this investigator-initiated, randomized, open-label, assessor-blinded trial performed at 10 centers in Korea, patients were enrolled if they had naive STEMI successfully treated with primary percutaneous coronary intervention (PCI) and at least 6-month planned duration of dual-antiplatelet treatment. The coprimary endpoints were LV remodeling index (LVRI) (a relative change of LV end-diastolic volume) measured on 3-dimensional echocardiography and N-terminal pro-B-type natriuretic peptide level at 6 months., Results: Among initially enrolled patients with STEMI (n = 336), 139 in each group completed the study. LVRI at 6 months was numerically lower with ticagrelor versus clopidogrel (0.6 ± 18.6% vs. 4.5 ± 16.5%; p = 0.095). Ticagrelor significantly reduced the 6-month level of N-terminal pro-B-type natriuretic peptide (173 ± 141 pg/ml vs. 289 ± 585 pg/ml; p = 0.028). These differences were prominent in patients with pre-PCI TIMI (Thrombolysis In Myocardial Infarction) flow grade 0. By multivariate analysis, ticagrelor versus clopidogrel reduced the risk for positive LV remodeling (LVRI >0%) (odds ratio: 0.56; 95% confidence interval: 0.33 to 0.95; p = 0.030). The LV end-diastolic volume index remained unchanged during ticagrelor treatment (from 54.7 ± 12.2 to 54.2 ± 12.2 ml/m 2 ; p = 0.629), but this value increased over time during clopidogrel treatment (from 54.6 ± 11.3 to 56.4 ± 13.9 ml/m 2 ; p = 0.056) (difference -2.3 ml/m 2 ; 95% confidence interval: -4.8 to 0.2 ml/m 2 ; p = 0.073). Ticagrelor reduced LV end-systolic volume index (from 27.0 ± 8.5 to 24.7 ± 8.4 ml/m 2 ; p < 0.001), whereas no reduction was seen with clopidogrel (from 26.2 ± 8.9 to 25.6 ± 11.0 ml/m 2 ; p = 0.366) (difference -1.8 ml/m 2 ; 95% confidence interval: -3.5 to -0.1 ml/m 2 ; p = 0.040)., Conclusions: Ticagrelor was superior to clopidogrel for LV remodeling after reperfusion of STEMI with primary PCI. (High Platelet Inhibition With Ticagrelor to Improve Left Ventricular Remodeling in Patients With ST Segment Elevation Myocardial Infarction [HEALING-AMI]; NCT02224534)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Clinical practice guidelines published by the European Society of Cardiology and the American College of Cardiology/American Heart Association summarize the available evidence and provide recommendations for health professionals to enable appropriate clinical decisions and improve clinical outcomes for patients with acute myocardial infarction (AMI). However, most current guidelines are based on studies in non-Asian populations in the pre-percutaneous coronary intervention (PCI) era. The Korea Acute Myocardial Infarction Registry is the first nationwide registry to document many aspects of AMI from baseline characteristics to treatment strategies. There are well-organized ongoing and published randomized control trials especially for antiplatelet therapy among Korean patients with AMI. Here, members of the Task Force of the Korean Society of Myocardial Infarction review recent published studies during the current PCI era, and have summarized the expert consensus for the pharmacotherapy of AMI., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2020. The Korean Society of Cardiology.)

Competing Interests: The authors have no potential conflicts of interest to disclose.

Neuromuscular disorders (NMDs) are diseases involving the upper and lower motor neurons and muscles. In patients with NMDs, cervical spinal deformities are a very common issue; however, unlike thoracolumbar spinal deformities, few studies have investigated these disorders. The patients with NMDs have irregular spinal curvature caused by poor balance and poor coordination of their head, neck, and trunk. Particularly, cervical deformity occurs at younger age, and is known to show more rigid and severe curvature at high cervical levels. Muscular physiologic dynamic characteristics such as spasticity or dystonia combined with static structural factors such as curvature flexibility can result in deformity and often lead to traumatic spinal cord injury. In addition, postoperative complication rate is higher due to abnormal involuntary movement and muscle tone. Therefore, it is important to control abnormal involuntary movement perioperatively along with strong instrumentation for correction of deformity. Various methods such as botulinum toxin injection, physical therapy, muscle division technique, or intrathecal baclofen pump implant may help control abnormal involuntary movements and improve spinal stability. Surgical management for cervical deformities associated with NMDs requires a multidisciplinary effort and a customized strategy.

Monoamine oxidase (MAO) has been implicated in neuroinflammation, and therapies targeting MAO are of interest for neurodegenerative diseases. The small-molecule drug tranylcypromine, an inhibitor of MAO, is currently used as an antidepressant and in the treatment of cancer. However, whether tranylcypromine can regulate LPS- and/or Aβ-induced neuroinflammation in the brain has not been well-studied. In the present study, we found that tranylcypromine selectively altered LPS-induced proinflammatory cytokine levels in BV2 microglial cells but not primary astrocytes. In addition, tranylcypromine modulated LPS-mediated TLR4/ERK/STAT3 signaling to alter neuroinflammatory responses in BV2 microglial cells. Importantly, tranylcypromine significantly reduced microglial activation as well as proinflammatory cytokine levels in LPS-injected wild-type mice. Moreover, injection of tranylcypromine in 5xFAD mice (a mouse model of AD) significantly decreased microglial activation but had smaller effects on astrocyte activation. Taken together, our results suggest that tranylcypromine can suppress LPS- and Aβ-induced neuroinflammatory responses in vitro and in vivo.

Background: Vitrification is the most promising technology for successful cryopreservation of living organisms without ice crystal formation. However, high concentrations (up to ~ 6-8 M) of cryoprotective agents (CPAs) used in stem cell induce osmotic and metabolic injuries. Moreover, the application of conventional slow-freezing methods to cultures of 3-D organoids of stem cells in various studies, is limited by their size., Results: In this study, we evaluated the effect of high concentrations of CPAs including cytotoxicity and characterized human mesenchymal stem cell (MSC) at single cell level. The cell viability, cellular damage, and apoptotic mechanisms as well as the proliferation capacity and multipotency of cells subjected to vitrification were similar to those in the slow-freezing group. Furthermore, we identified the possibility of vitrification of size-controlled 3-D spheroids for cryopreservation of organoid with high survivability., Conclusions: Our results demonstrate successful vitrification of both single cell and spheroid using high concentration of CPAs in vitro without cytotoxicity.

P2X5 is a member of the P2X purinergic receptor family of ligand-gated cation channels and has recently been shown to regulate inflammatory bone loss. In this study, we report that P2X5 is a protective immune regulator during Listeria monocytogenes infection, as P2X5-deficient mice exhibit increased bacterial loads in the spleen and liver, increased tissue damage, and early (within 3-6 d) susceptibility to systemic L. monocytogenes infection. Whereas P2X5-deficient mice experience normal monocyte recruitment in response to L. monocytogenes , P2X5-deficient bone marrow-derived macrophages (BMMs) exhibit defective cytosolic killing of L. monocytogenes We further showed that P2X5 is required for L. monocytogenes -induced inflammasome activation and IL-1β production and that defective L. monocytogenes killing in P2X5-deficient BMMs is substantially rescued by exogenous IL-1β or IL-18. Finally, in vitro BMM killing and in vivo L. monocytogenes infection experiments employing either P2X7 deficiency or extracellular ATP depletion suggest that P2X5-dependent anti- L. monocytogenes immunity is independent of the ATP-P2X7 inflammasome activation pathway. Together, our findings elucidate a novel and specific role for P2X5 as a critical mediator of protective immunity., (Copyright © 2020 by The American Association of Immunologists, Inc.)

In accordance with requirements of the ICH S7B safety pharmacology guidelines, numerous next-generation cardiotoxicity studies using human stem cell-derived cardiomyocytes (CMs) are being conducted globally. Although several stem cell-derived CMs are being developed for commercialization, there is insufficient research to verify if these CMs can replace animal experiments. In this study, in vitro high-efficiency CMs derived from human embryonic stem cells (hESC-CMs) were compared with Sprague-Dawley rats as in vivo experimental animals, and primary cultured in vitro rat-CMs for cardiotoxicity tests. In vivo rats were administrated with two consecutive injections of 100 mg/kg isoproterenol, 15 mg/kg doxorubicin, or 100 mg/kg nifedipine, while in vitro rat-CMs and hESC-CMs were treated with 5 μM isoproterenol, 5 μM doxorubicin, and 50 μM nifedipine. We have verified the equivalence of hESC-CMs assessments over various molecular biological markers, morphological analysis. Also, we have identified the advantages of hESC-CMs, which can distinguish between species variability, over electrophysiological analysis of ion channels against cardiac damage. Our findings demonstrate the possibility and advantage of high-efficiency hESC-CMs as next-generation cardiotoxicity assessment. [BMB Reports 2020; 53(8): 437-441].

NiO thin films with various strains were grown on SrTiO 3 (STO) and MgO substrates using a pulsed laser deposition technique. The films were characterized using an x-ray diffraction, atomic force microscopy, and infrared reflectance spectroscopy. The films grown on STO (001) substrate show a compressive in-plane strain which increases as the film thickness is reduced resulting in an increase of the NiO phonon frequency. On the other hand, a tensile strain was detected in the NiO film grown on MgO (001) substrate which induces a softening of the phonon frequency. Overall, the variation of in-plane strain from -0.36% (compressive) to 0.48% (tensile) yields the decrease of the phonon frequency from 409.6 cm -1 to 377.5 cm -1 which occurs due to the ∼1% change of interatomic distances. The magnetic exchange-driven phonon splitting Δ ω in three different samples, with relaxed (i.e. zero) strain, 0.36% compressive strain and 0.48% tensile strain, was measured as a function of temperature. The Δ ω increases on cooling in NiO relaxed film as in the previously published work on a bulk crystal. The splitting increases on cooling also in 0.48% tensile strained film, but Δ ω is systematically 3-4 cm -1 smaller than in relaxed film. Since the phonon splitting is proportional to the non-dominant magnetic exchange interaction J 1 , the reduction of phonon splitting in tensile-strained film was explained by a diminishing of J 1 with lattice expansion. Increase of Δ ω on cooling can be also explained by rising of J 1 with reduced temperature., (© 2020 IOP Publishing Ltd.)

Banhasasim-tang (BHS) is an herbal medicine that has been widely used in East Asia to treat various symptoms associated with upper abdomen swelling. BHS has not been studied previously for neuroinflammation or cognitive disorder. Here, we use a lipopolysaccharide (LPS) model to investigate the effects and mechanisms of BHS in neuroinflammation and cognitive impairment of mice. We used a mouse model of LPS-induced cognitive impairment and neuroinflammation and examined whether administration of BHS prevents these deficits via Morris water maze test, passive avoidance test, histopathological analysis, Western blotting, and real-time reverse transcription polymerase chain reaction (RT-qPCR). We found via behavioral tests that BHS treatment effectively prevented LPS-induced memory loss and neuronal damage in mice. Histopathological analysis of mouse brains revealed that BHS inhibited LPS-induced expression of microglial and astrocyte activation markers. Furthermore, BHS inhibits the production of markers related to neurodegeneration, amyloidogenesis, and inflammation, and mRNA expression of inflammatory mediators in mouse brain tissue. Additionally, BHS pretreatment effectively inhibited generation of inflammatory factors and pathways in BV2 microglial cells stimulated by LPS. These observations indicate that BHS is effective in preventing cognitive impairment caused by neuroinflammation and has strong potential as a candidate treatment for neuronal inflammatory diseases.

Little is known of plasma-mediated relations between major food components and their biological capacities. In the present work, the effects of dielectric barrier discharge (DBD) plasma irradiation on pure sesamol and sesame oil were investigated using spectroscopic (LC-MS, NMR) and bioassay methods. Sesamol was degraded when subjected to plasma irradiation for 40 min, and the exposed products exhibited improved anti-glycation capacities against advanced glycation end products (AGEs) formation and better ONOO - scavenging ability. Structures of newly formed compounds were determined spectroscopically. Quantitative LC-MS analysis of the major products generated in sesamol and sesame oil was achieved using isolates 1-4 of purified sesamol plasma treated for 40 min. These results indicate that the predominant chemical changes induced in sesamol and sesame oil by DBD plasma treatment might enhance biological properties., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Endothelial progenitor cells (EPCs) have the potential to protect against atherothrombotic event occurrences. There are no data to evaluate the impact of cilostazol on EPC levels in high-risk patients., Methods: We conducted a randomized, double-blind, placebo-controlled trial to assess the effect of adjunctive cilostazol on EPC mobilization and platelet reactivity in patients with acute myocardial infarction (AMI). Before discharge, patients undergoing percutaneous coronary intervention (PCI) were randomly assigned to receive cilostazol SR capsule (200-mg) a day ( n = 30) or placebo ( n = 30) on top of dual antiplatelet therapy (DAPT) with clopidogrel and aspirin. Before randomization (baseline) and at 30-day follow-up, circulating EPC levels were analyzed using flow cytometry and hemostatic measurements were evaluated by VerifyNow and thromboelastography assays. The primary endpoint was the relative change in EPC levels between baseline and 30-day., Results: At baseline, there were similar levels of EPC counts between treatments, whereas patients with cilostazol showed higher levels of EPC counts compared with placebo after 30 days. Cilostazol versus placebo treatment displayed significantly higher changes in EPC levels between baseline and follow-up (ΔCD133 + /KDR + : difference 216%, 95% confidence interval (CI) 44~388%, p = 0.015; ΔCD34 + /KDR + : difference 183%, 95% CI 25~342%, p = 0.024). At 30-day follow-up, platelet reactivity was lower in the cilostazol group compared with the placebo group (130 ± 45 versus 169 ± 62 P2Y12 Reaction Unit, p = 0.009). However, there were no significant correlations between the changes of EPC levels and platelet reactivity., Conclusion: Adjunctive cilostazol on top of clopidogrel and aspirin versus DAPT alone is associated with increased EPC mobilization and decreased platelet reactivity in AMI patients, suggesting its pleiotropic effects against atherothrombotic events (NCT04407312).

Poststroke complex regional pain syndrome (CRPS) is characterized by swelling, pain, and changes in the skin that appear on the affected wrist and hand. In this retrospective study, we analyzed the relationship between poststroke CRPS and the location of stroke lesion. From all patients admitted to our hospital from 2009 to 2019, we recruited 80 patients affected by their first unilateral stroke who met the inclusion/exclusion criteria. Thirty-eight patients diagnosed with CRPS after stroke were assigned to the experimental group according to the "Budapest criteria" adopted by the International Association for the Study of Pain, and 42 patients without CRPS were included as controls. Regions of interest were manually drawn on T1-weighted magnetic resonance images, and data were normalized to a standard brain template. In the poststroke CRPS group, the relationship between the location of brain lesion and pain severity was analyzed using Freedman-Lane multivariable regression adjusting for Medication Quantification Scale rating, which was the only parameter to show a statistically significant correlation with pain intensity. A threshold of P < 0.01 was considered statistically significant for all voxel-based lesion symptom mapping tests, corrected for multiple comparisons with 5000 permutations. Analyses using voxel-wise subtraction and Liebermeister statistics indicated that the corticospinal tract (CST) was associated with the development of poststroke CRPS. Statistically significant correlations were found between pain intensity and the CST and the adjacent lentiform nucleus. Our results suggest that the CST may be a relevant neural structure for development of poststroke CRPS and the intensity of pain caused by the syndrome.

A shared neuropathological hallmark in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is nuclear clearance and cytoplasmic aggregation of TARDBP/TDP-43 (TAR DNA binding protein). We previously showed that the ability of TARDBP to repress nonconserved cryptic exons was impaired in brains of patients with ALS and FTD, suggesting that its nuclear depletion contributes to neurodegeneration. However, the critical pathways impacted by the failure to repress cryptic exons that may contribute to neurodegeneration remain undefined. Here, we report that transcriptome analysis of TARDBP-deficient neurons revealed downregulation of ATG7 , a critical gene required for macroautophagy/autophagy. Mouse and Drosophila models lacking TARDBP/TBPH in motor neurons exhibiting age-dependent neurodegeneration and motor deficits showed reduction of ATG7 and accumulation of SQSTM1/p62 inclusions. Importantly, genetic upregulation of the autophagy pathway improved motor function and survival in TBPH-deficient flies. Together with our observation that ATG7 is reduced in ALS-FTD brain tissues, these findings identify the autophagy pathway as one key effector of nuclear depletion of TARDBP that contributes to neurodegeneration. We thus suggest that the autophagy pathway is a therapeutic target for ALS-FTD and other disorders exhibiting TARDBP pathology. Abbreviations: ALS: amyotrophic lateral sclerosis; ANOVA: analysis of variance; ChAT: choline acetyltransferase; CTSD: cathepsin D; FTD: frontotemporal dementia; LAMP1: lysosomal associated membrane protein 1; NMJ: neuromuscular junction; RBFOX3/NeuN: RNA binding fox-1 homolog 3; SQSTM1: sequestosome 1; TARDBP/TDP-43: TAR DNA binding protein 43.

Objectives: The sensitivity for tumor spread through air space (STAS), an independent risk factor for locoregional recurrence after sublobar resection for lung cancer, has been relatively low in frozen sections. We aimed to determine predictors with high negative predictive value for the presence of STAS and to provide the flowchart in combination with these predictors for the decision-making for sublobar resection., Materials and Methods: Between July 2015 and December 2017, 387 patients who underwent surgery for non-small cell lung cancer (NSCLC) with pathologic findings of the total masses measuring ≤ 2 cm were enrolled. The lesions were divided into two groups according to presence of STAS. We compared the preoperative characteristics, operative data, and developed a flowchart for STAS prediction using receiver operator characteristic curve analysis and multivariable logistic regression., Results: The STAS-positive group (N = 111) had a significantly higher preoperative tumor size (1.70 [1.5] vs 1.50 [0.69], p < 0.001) and standardized uptake value tumor-to-liver (SUV T/L) ratio (1.40 [1.60] vs 0.60 [1.10], p < 0.001) and a significantly lower two-dimensional ground-glass opacity (GGO) percentage (35.86 [61.00] vs 78.14 [39.00], p < 0.001). Meanwhile, the STAS-negative group (N = 286) had higher lepidic predominance (41.6% vs. 1.8%, p < 0.001). We developed a flowchart for predicting STAS in combination with two-dimensional GGO percentage on computed tomography (CT), SUV T/L ratio on positron-emission CT, and lepidic predominant pattern. The sensitivity, specificity, and negative predictive value for STAS positivity were 79.3%, 68.5%, and 89.5%, respectively., Conclusions: The stepwise flowchart using two-dimensional GGO percentage on CT, maximum SUV, and lepidic predominance might be helpful in selecting patients with early NSCLC for sublobar resection., Competing Interests: Declaration of Competing Interest None., (Published by Elsevier B.V.)

Purpose: This study aimed to identify factors-both infant-related and maternal-associated with pressure to eat as a feeding practice among mothers with infants., Methods: This study used a cross-sectional design and included 163 mothers of infants aged 2~12 months. Of the 180 self-reported questionnaires that were distributed, 163 (91%) were included in the data analysis. Multiple regression analysis was used to identify the factors associated with pressure to eat as a feeding practice among the mothers., Results: Infant's temperament (β=-.17, p =.035), mother's body mass index (β=-.16, p =.048), and concern about the infant being underweight (β=.30, p =.001) were associated with pressure to eat as a feeding practice among mothers. The explanatory power of these variables in the predictive model was 19.2%., Conclusion: Educational programs should be developed for improving mother's awareness of cues from infants with difficult temperament. In addition, educational interventions regarding the correct evaluation of infant's weight are needed to relieve mother's concern about their infant's being underweight. These interventions might be helpful to reduce the prevalence of pressure to eat as a feeding practice among mothers with infants., Competing Interests: No existing or potential conflict of interest relevant to this article was reported., (Copyright © 2020 Korean Academy of Child Health Nursing. All rights reserved.)

Mechanical testing based on ISO 14801 standard is generally used to evaluate the performance of the dental implant system according to material and design changes. However, the test method is difficult to reflect on the clinical environment because the ISO 14801 standard does not take into account the various loads from different directions during chewing motion. In addition, the fracture pattern of the implant system can occur both in the horizontal and the vertical directions. Therefore, the purpose of this study was to compare fatigue characteristics and fracture patterns between single directional loading conditions based on the ISO 14801 standard and multi-directional loading condition. Firstly, the static test was performed on five specimens to derive the fatigue load, and the fatigue load was chosen as 40% of the maximum load measured in the static test. Subsequently, the fatigue test was performed considering the single axial/occlusal (AO), AO with facial/lingual (AOFL) and AO with mesial/distal (AOMD) directions, and five specimens were used for each fatigue loading modes. In order to analyze the fatigue characteristics, the fatigue cycle at the time of specimen fracture and displacement change of the specimen every 500 cycles were measured. Field emission scanning electron microscopy (FE-SEM) was used to analyze the fracture patterns and the fracture surface. Compared to the AO group, the fatigue cycle of the AOFL and AOMD groups showed lower about five times, while the displacement gradually increased with every 500 cycles. From FE-SEM results, there were no different surface morphology characteristics among three groups. However, the AOMD group showed a vertical slip band. Therefore, our results suggest that the multi-directional loading mode under the worst-case environment can reproduce the vertical fracture pattern in the clinical situation and may be essential to reflect on the dental implant design including connection types and surface treatments.

Background: Although ankle-brachial index and brachial-ankle pulse wave velocity measurement are well-established modalities for assessing peripheral artery disease and arterial stiffness and predicting cardiovascular events, it is unclear which one is more important or if a combination of the two is more effective for determining prognosis among patients with acute myocardial infarction., Methods: Patients with acute myocardial infarction (n = 889) were stratified into four groups according to a brachial-ankle pulse wave velocity (cut-off value: 1684 cm/s) and ankle-brachial index (cut-off value: 0.98): group I (high ankle-brachial index and low brachial-ankle pulse wave velocity, n = 389), group II (high ankle-brachial index and high brachial-ankle pulse wave velocity, n = 281), group III (low ankle-brachial index and low brachial-ankle pulse wave velocity, n = 103), group IV (low ankle-brachial index and high brachial-ankle pulse wave velocity, n = 116). The mean follow-up duration was 348 days., Results: Major adverse cardiovascular events or cardiac death occurred in 64 (7.2%) and 26 patients (2.9%), respectively. In multivariable analysis, group III and IV had a significant high hazard ratio for major adverse cardiovascular events (5.93, 5.43) and cardiac death (13.51, 19.06). Additionally, ankle-brachial index had a higher hazard ratio than brachial-ankle pulse wave velocity for major adverse cardiovascular events (3.38 vs. 1.40) and cardiac death (6.21 vs. 2.40). When comparing receiver operating characteristic curves of the combined models of risk factors, brachial-ankle pulse wave velocity, and ankle-brachial index, pulse wave velocity plus ankle-brachial index or pulse wave velocity plus ankle-brachial index plus risk factors were significantly more predictive of major adverse cardiovascular events than risk factors., Conclusion: Our findings indicate that ankle-brachial index is a strong independent prognostic factor and adding a brachial-ankle pulse wave velocity measurement to ankle-brachial index increases the prognostic power for cardiac events in patients with acute myocardial infarction, while ankle-brachial index and pulse wave velocity showed additive value to risk factors.

Circadian gene expression is defined by the gene-specific phase and amplitude of daily oscillations in mRNA and protein levels. D site-binding protein mRNA ( Dbp mRNA) shows high-amplitude oscillation; however, the underlying mechanism remains elusive. Here, we demonstrate that heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a key regulator that activates Dbp transcription via the poly(C) motif within its proximal promoter. Biochemical analyses identified hnRNP K as a specific protein that directly associates with the poly(C) motif in vitro Interestingly, we further confirmed the rhythmic binding of endogenous hnRNP K within the Dbp promoter through chromatin immunoprecipitation as well as the cycling expression of hnRNP K. Finally, knockdown of hnRNP K decreased mRNA oscillation in both Dbp and Dbp -dependent clock genes. Taken together, our results show rhythmic protein expression of hnRNP K and provide new insights into its function as a transcriptional amplifier of Dbp ., (Copyright © 2020 American Society for Microbiology.)