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Background: Skin inflammation and dermal injuries are a major clinical problem because current therapies are limited to treating established scars, and there is a poor understanding of healing mechanisms. Mussel adhesive proteins (MAPs) have great potential in many tissue engineering and biomedical applications. It has been successfully demonstrated that the redesigned hybrid type MAP (fp-151) can be utilized as a promising adhesive biomaterial. The aim of this study was to develop a novel recombinant protein using fp-151 and vitronectin (VT) and to elucidate the anti-inflammatory effects of this recombinant protein on macrophages and keratinocytes., Methods: Lipopolysaccharide (LPS) was used to stimulate macrophages and UVB was used to stimulate keratinocytes. Inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 were analyzed by Western Blot. Inflammatory cytokines and NO and ROS production were analyzed., Result: In macrophages stimulated by LPS, expression of the inflammatory factors iNOS, COX-2, and NO production increased, while the r-fp-151-VT-treated groups had suppressed expression of iNOS, COX-2, and NO production in a dose-dependent manner. In addition, keratinocytes stimulated by UVB and treated with r-fp-151-VT had reduced expression of iNOS and COX-2. Interestingly, in UVB-irradiated keratinocytes, inflammatory cytokines, such as interleukin (IL)-1b, IL-6, and tumor necrosis factor (TNF)-a, were significantly reduced by r-fp-151-VT treatment., Conclusions: These results suggest that the anti-inflammatory activity of r-fp-151-VT was more effective in keratinocytes, suggesting that it can be used as a therapeutic agent to treat skin inflammation.

Background: We determined the characteristics and evaluated associated risks of sprayed pesticide exposure among workers cultivating Korean cabbage. The test pesticide, a mixture of 3% chlorantraniliprole and 4% indoxacarb wettable granules diluted 2000 times, was sprayed on Korean cabbage within a 3000 m 2 area in Goesan, Korea. Dermal exposures were measured using a whole-body dosimetry method., Results: Exposure to chlorantraniliprole was observed among ten individuals, ranging from 140.4 to 4234.0 µg person -1 . The legs were the most prominent exposure area (86.35%), with the face being the least exposed (0.06%). Exposure risk was assessed by calculating the margin of safety (MOS) on the exposure amount for each body part. The MOS based on dermal and inhalation exposure doses ranged from 59 to 1765., Conclusion: Exposure was the greatest for the legs, probably as a result of the low height of the crop and the use of a long-wand sprayer. An MOS value >1 indicates a low risk for applicators using this method of application. However, with tall crops, exposure level and MOS values can vary widely, as MOS increases or decreases based on exposure dose. Therefore, future research is needed to better understand appropriate safety precautions when working with potent pesticides. © 2018 Society of Chemical Industry., (© 2018 Society of Chemical Industry.)

Immunomodulatory drugs (IMiDs) exert anti-myeloma activity by binding to the protein cereblon (CRBN) and subsequently degrading IKZF1/3. Recently, their ability to recruit E3 ubiquitin ligase has been used in the proteolysis targeting chimera (PROTAC) technology. Herein, we design and synthesize a novel IMiD analog TD-106 that induces the degradation of IKZF1/3 and inhibits the proliferation of multiple myeloma cells in vitro as well as in vivo. Moreover, we demonstrate that TD-428, which comprises TD-106 linked to a BET inhibitor, JQ1 efficiently induce BET protein degradation in the prostate cancer cell line 22Rv1. Consequently, cell proliferation is inhibited due to suppressed C-MYC transcription. These results, therefore, firmly suggest that the newly synthesized IMiD analog, TD-106, is a novel CRBN modulator that can be used for targeted protein degradation., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Heart rate (HR) change during sleepy driving has never been investigated. Healthy volunteers who planned to drive a long distance were recruited and monitored with a 24-hour Holter. Six healthy volunteers were enrolled. Their mean driving time was 297.7 ± 111 minutes. Mean duration of sleepy time while driving was 27 ± 24.5 minutes. Driving HR showed a trend for increment as compared to day time mean HR, from 85 ± 5.6 to 89.8 ± 5.6 beats/min (by 7%) ( P = 0.093). Mean HR while sleepy driving significantly decreased to 81.5 ± 9.2 beats/min by 9.3% ± 7.4% ( P = 0.046). This pilot study for the first time demonstrated that HR decreased while sleepy driving., Competing Interests: Disclosures: The authors have no potential conflicts of interest to disclose.

Background and Aims: Since clinical characteristics and prognosis of patients with multi-vessel vasospastic angina (VSA) are not clear, we investigated the nature and prognosis of multi-vessel VSA in Koreans., Methods: Among 2960 patients enrolled in the VA-KOREA (Vasospastic Angina in Korea) registry, 104 definite multi-vessel VSA patients, 163 single vessel VSA patients and 737 non-VSA patients were identified using the intracoronary ergonovine provocation test., Results: Multi-vessel VSA and single vessel VSA groups showed similar baseline characteristics and medical treatment on discharge, but different from the non-VSA group. The primary composite endpoint (cardiac death, acute coronary syndrome, and symptomatic new onset arrhythmia) over a 36-month follow-up period was significantly higher in the multi-vessel VSA group than in the single vessel VSA and non-VSA groups (8.7% vs. 1.8% and 1.1%, each log-rank p < 0.05, respectively). The rate of death and acute coronary syndrome of the multi-vessel VSA group was higher than in the single vessel VSA and non-VSA groups (5.8% vs. 1.2% and 0.9%, each log-rank p < 0.05, respectively). In addition, multi-vessel VSA was an independent predictor of the primary composite endpoint at 36 months (HR 8.5, 95% CI [2.6-27.2], p < 0.0001)., Conclusions: Patients with multi-vessel VSA had worse clinical outcomes than single vessel VSA and non-VSA groups, suggesting that the existence of multi-vessel VSA itself is highly prognostic., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Rapid and efficient detection of pathogenic bacteria from food is critical to prevent epidemic food poisoning. However, the isolation of pathogenic bacteria from spoiled food is hampered by the lack of proper cell cultivation and/or isolation methods. Most of currently used methods suffer from complex, time-consuming culturing steps, low scalability, and high operation cost. Herein, we developed an alternative approach for the isolation of pathogenic bacteria directly from food using a surface-modified, highly porous sponge via initiated chemical vapor deposition (iCVD) process. A hydrophobic polymer, poly(2,4,6,8-tetravinyl-2,4,6,8-tetramethyl cyclotetra-siloxane) (pV4D4), was deposited conformally on amphiphilic 3-dimensional (3D) melamine sponge to incorporate hydrophobicity as well as oleophilicity to the porous sponge surface, which is appropriate for absorbing oil component selectively from food extracts. Furthermore, the surface-modified sponge was capable of the isolation of Escherichia coli O157:H7 (E. coli O157:H7) from heterogeneous mixture with oil/water/food particles with undistinguisible efficiency compare to artificial model system. The surface-modified sponge developed in this study will be a novel platform for oil/water separation and isolation of foodborne pathogens directly from heterogeneous mixture to enhance the efficiency of molecular diagnostics., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: To investigate the changes in ocular higher-order aberrations (HOA) after trabeculectomy using mitomycin-C (MMC)., Methods: We retrospectively reviewed data for 63 eyes from 63 glaucoma patients who had undergone MMC augmented trabeculectomy. We measured intraocular pressure (IOP), refractive errors, anterior chamber depth (ACD), and HOA before surgery and 1, 2, and 4 weeks postoperatively. The patients were divided into two groups on the basis of preoperative lens status: phakic and pseudophakic group. We used a paired t test to compare preoperative and postoperative HOA values. Regression analysis was used to compare higher-order total (HOT) change and factors including ACD and age., Results: For entire eye aberrations, coma-like and total HOT were significantly increased postoperatively at 1 week (P = 0.029, P = 0.005, respectively), but not after 2 or 4 weeks in the phakic group and were not significant at any time in the pseudophakic group. Corneal HOA were significantly increased postoperatively after 1, 2 weeks, but not after 4 weeks in the phakic group and were not significant in the pseudophakic group. For internal optics aberrations, HOA were significantly increased postoperatively at 1, 2, and 4 weeks in the phakic group, but were not significant at any time in the pseudophakic group. However, HOT aberration change showed no correlation with age, ACD, IOP change in either group., Conclusion: Following trabeculectomy, HOA changes were significantly increased postoperatively at 1, 2 weeks in the phakic group. Therefore, visual complaint-related HOA changes after trabeculectomy may be more profound in phakic patients.

Background/aims: There have been numerous efforts to reduce mother-to-child transmission (MTCT) of hepatitis B virus (HBV) with antiviral agents during pregnancy. However, there are limited data regarding the outcomes of pregnant women after delivery. This study was performed to evaluate the efficacy of antiviral agents in preventing MTCT of HBV and maternal long-term outcomes., Methods: The HBV-infected pregnant women treated with antiviral agents to prevent MTCT were retrospectively reviewed. Forty-one pregnant women who received telbivudine or tenofovir during late pregnancy (28-34 week) were analyzed. Hepatitis B virus surface antibody (HBsAb) positivity was tested in 43 infants after 7 months of birth. Eleven mothers were followed >1 year after delivery., Results: The mean HBV DNA titer before antiviral therapy was 8.67 (6.60-9.49) log copies/mL, and the median age at delivery was 32 years (range, 22-40). Eleven patients were treated with tenofovir and 30 with telbivudine. The median duration was 57 days (range, 23-100), and the median HBV DNA titer at birth was 5.06 log copies/mL (range, 2.06-6.50). Antiviral treatments were associated with significant HBV DNA reduction (P<0.001). Among 43 infants (two cases of twins), HBsAb was not detected in two, subsequently confirmed to have HBV infection. Biochemical flare was observed in two of 11 mothers followed >12 months, and an antiviral agent was administered., Conclusion: Antiviral treatment during late pregnancy effectively reduced MTCT. Long-term follow-up should be required in such cases. In addition, given that maternal biochemical flare occurred in 18% of mothers, re-administration of antiviral agents might be required.

The priority of synaptic device researches has been given to prove the device potential for the emulation of synaptic dynamics and not to functionalize further synaptic devices for more complex learning. Here, we demonstrate an optic-neural synaptic device by implementing synaptic and optical-sensing functions together on h-BN/WSe 2 heterostructure. This device mimics the colored and color-mixed pattern recognition capabilities of the human vision system when arranged in an optic-neural network. Our synaptic device demonstrates a close to linear weight update trajectory while providing a large number of stable conduction states with less than 1% variation per state. The device operates with low voltage spikes of 0.3 V and consumes only 66 fJ per spike. This consequently facilitates the demonstration of accurate and energy efficient colored and color-mixed pattern recognition. The work will be an important step toward neural networks that comprise neural sensing and training functions for more complex pattern recognition.

Background and Aims: Little information exists on the prevalence of metabolic syndrome (MetS) in Korea since 2007. We aimed to provide up-to-date estimates of the prevalence of MetS and its trend in the general adult population in Korea., Methods: We compared the prevalence and pattern of MetS among participants in the Korean National Health and Nutrition Examination Surveys (KNHANES) IV (2007-2009), V (2010-2012), and VI (2013-2015), aged ≥19 years. Data from the 2005 census of the Korean population were presented according to age standardization., Results: The overall age-standardized prevalence of MetS in 2013-2015 was 20.3% (95% confidence interval [CI], 19.6%-21%). Since 2007, the overall prevalence of MetS has remained stable, whereas the prevalences among men and women, respectively, have increased and decreased slightly. By contrast, the prevalence of MetS among men aged 19-49 years has shown an increasing tendency since 2007. Moreover, nearly 40% of women aged ≥60 years had MetS in 2013-2015. Among the five components of MetS, only elevated fasting glucose level has shown an increasing trend since 2007 in both men and women. As the family income and educational level decreased, the prevalence of MetS increased., Conclusions: The overall prevalence of MetS has remained stable since 2007. However, the prevalence of MetS was higher in middle-aged men and women aged ≥60 years. Considering the close association between MetS and socioeconomic status, age- and sex-specific strategies should be developed at the national level for the treatment and prevention of MetS in Korea., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Proton beam irradiation is a next-generation technique to develop mutant crop varieties. The mutagenic effects and molecular mechanisms of radiation are important multi-disciplinary research subjects. This study was conducted to investigate the types of mutations induced in the soybean genome by proton beam irradiation. In total, 22 plants, including 10 M 2 plants treated with proton beam irradiation at 118 and 239 Gy, each, and two wild-type plants (Daepung) were sequenced by genotyping-by-sequencing (GBS). In total, 7453 single nucleotide polymorphisms (SNPs) were detected in the 20 M 2 plants, compared with the two wild-type controls. The SNP frequency was 1/36,976 bp with proton beam irradiation at 118 Gy, and 1/32,945 bp at 239 Gy. Of these, 3569 SNPs were detected in genic regions. We observed that proton beam irradiation induced more substitutions than small insertion-deletions (INDELs). Based on the mutagenic effect of proton beam irradiation, the frequency of transition mutations was shown to be higher than that of transversions. The proton beam-induced SNPs were distributed uniformly in most of the chromosomes. Gene ontology (GO) analysis showed that there were many genes involved in protein metabolic process under biological process, intracellular membrane-bounded organelle under cellular component, and nucleic acid binding under molecular function. This study could provide valuable information for investigating the potential mechanisms of mutation, and guidance for developing soybeans cultivars using mutation breeding.

Although calcific aortic stenosis is a very common disease with major adverse cardiovascular events and healthcare costs, there are no effective medical interventions to delay or halt its progression. Cardiometabolic risk factors, including smoking and male sex, are linked to aortic stenosis. Emerging studies have identified important regulatory roles for immunological and inflammatory responses, including oxidized lipids, various cytokines, and biomineralization. Recent clinical and experimental studies in atherosclerosis and osteoporosis have demonstrated that oxidative stress and oxidized lipids decrease bone formation in the skeletal system while they increase bone formation in the cardiovascular system. Multidisciplinary factors contribute to vascular calcification, including inflammation and metabolic regulation of osteogenesis in the cardiovascular system via similar signaling pathways as bone formation. Calcific aortic valve disease (CAVD) is no longer considered a simple passive process of calcium deposition that occurs with advanced age. Biomineralization in CAVD is a complex, regulated process that involves valvular, circulating, bone marrow-derived cells, macrophage heterogeneity and genetic factors along with biochemical and mechanical factors. The current review will discuss the recently discovered important role of inflammation, metabolic risk factors, and molecular and cellular mechanisms that promote CAVD, as well as the link between osteogenic signals in the skeletal and cardiovascular systems. This may inform future therapeutic strategies for CAVD progression., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A highly stable and reversible n-type doping technique for molybdenum disulfide (MoS 2 ) transistors and photodetectors is developed in this study. This doping technique is based on triphenylphosphine (PPh 3 ) and significantly improves the performance of MoS 2 transistor and photodetector devices in terms of the on/off-current ratio (8.72 × 10 4 → 8.70 × 10 5 ), mobility (12.1 → 241 cm 2 /V·s), and photoresponsivity ( R) (2.77 × 10 3 → 3.92 × 10 5 A/W). The range of doping concentrations is broadly distributed between 1.56 × 10 11 and 9.75 × 10 12 cm -2 and is easily controlled by adjusting the temperature at which the PPh 3 layer is formed. In addition, this doping technique provides two interesting properties that have not been reported for previous molecular doping techniques: (i) high stability leading to small variations in device performance after exposure to air for 14 days (on-current: 1.34% and photoresponsivity: 1.58%) and (ii) reversibility enabling the repetitive formation and removal of PPh 3 molecules (doping and dedoping).

Cancer-associated fibroblasts (CAFs) are important at all tumor stages. CSL/RBPJκ suppresses the gene expression program leading to CAF activation and associated metabolic reprogramming, as well as autophagy. Little is known about CSL protein turnover, especially in the tumor microenvironment. We report that, in human dermal fibroblasts (HDFs), conditions inducing autophagy-often found in tumor stroma-down-regulate CSL protein levels but do not affect its mRNA levels. Genetic or pharmacologic targeting of the autophagic machinery blocks CSL down-modulation. Mechanistically, endogenous CSL associates with the autophagy and signaling adaptor p62/SQSTM1, which is required for CSL down-modulation by autophagy. This is functionally significant, because both CSL and p62 levels are lower in skin cancer-derived CAFs, in which autophagy is increased. Increasing cellular CSL levels stabilizes p62 and down-modulates the autophagic process. We reveal here an autophagy-initiated mechanism for CSL down-modulation, which could be targeted for stroma-focused cancer prevention and treatment., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: To determine whether the effectiveness and safety of fixed-dose combinations (FDCs) of amlodipine orotate/valsartan (AML/VAL) 5/160 mg are noninferior to those of valsartan/hydrochlorothiazide (VAL/HCTZ) 160/12.5 mg in hypertensive patients with inadequate response to valsartan 160 mg monotherapy., Methods: This 8-week, active-controlled, parallel-group, fixed-dose, multicenter, double-blind randomized controlled, and noninferiority trial was conducted at 17 cardiovascular centers in the Republic of Korea. Eligible patients had mean sitting diastolic blood pressure (msDBP) ≥90 mm Hg despite monotherapy with valsartan 160 mg for 4 weeks. Patients were randomly assigned to treatment with AML/VAL 5/160 mg FDC (AML/VAL) group or VAL/HCTZ 160/12.5 mg FDC (VAL/HCTZ) group once daily for 8 weeks. A total of 238 patients were enrolled (AML/VAL group, n = 121; VAL/HCTZ group, n = 117), of whom 228 completed the study., Results: At 8 weeks after randomization, msDBP was significantly decreased in both groups (-9.44 ± 0.69 mm Hg in the AML/VAL group and -7.47 ± 0.71 mm Hg in the VAL/HCTZ group, both P < .001 vs baseline). Between group difference was -1.96 ± 1.00 mm Hg, indicating that AML/VAL 5/160 mg FDC was not inferior to VAL/HCTZ 160/12.5 mg FDC at primary efficacy endpoint. Control rate of BP defined as the percentage of patients achieving mean sitting SBP (msSBP) <140 mm Hg or msDBP <90 mm Hg (target BP) from baseline to week 8 was significantly higher in the AML/VAL group than that in the VAL/HCTZ group (84.3% [n = 102] in the AML/VAL group vs 71.3% [n = 82] in the VAL/HCTZ group, P = .016). At 8 weeks after randomization, mean uric acid level was significantly increased in the VAL/HCTZ group compared to that at baseline (0.64 ± 0.08 mg/dL; P < .001). However, it was slightly decreased from baseline in the AML/VAL group (-0.12 ± 0.08 mg/dL; P = .085). The intergroup difference was significant (P < .001)., Conclusion: The effectiveness and safety AML/VAL 5/160 mg FDC are noninferior to those of VAL/HCTZ 160/12.5 mg FDC in patients with hypertension inadequately controlled by valsartan 160 mg monotherapy.

The concentrations and fluxes of airborne phthalates were measured from five types of polyvinyl chloride (PVC) consumer products (vinyl flooring, wallcovering, child's toy, yoga mat, and edge protector) using a small chamber (impinger) system. Airborne phthalates released from each of those PVC samples were collected using sorbent (Tenax TA) tubes at three temperature control intervals (0, 3, and 6 h) under varying temperature conditions (25, 40, and 90 °C). A total of 11 phthalate compounds were quantified in the five PVC products examined in this study. To facilitate the comparison of phthalate emissions among PVC samples, their flux values were defined for total phthalates by summing the average fluxes of all 11 phthalates generated during the control period of 6 h. The highest flux values were seen in the edge protector sample at all temperatures (0.40 (25 °C), 9.65 (40 °C), and 75.7 μg m -2 h -1 (90 °C)) of which emission was dominated by dibutyl isophthalate. In contrast, the lowest fluxes were found in wallcovering (0.01 (25 °C) and 0.05 μg m -2 h -1 (40 °C)) and child's toy (0.23 μg m -2 h -1 (90 °C)) at each temperature level. The information regarding phthalate composition and emission patterns varied dynamically with type of PVC sample, controlled temperature, and duration of control., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This study investigated the emission characteristics of glass particles resulting from smoking electronic cigarettes (ECs). First, the most suitable filter for the collection of glass particles was explored by examining the performance (reliability) of various types of filters. A polycarbonate filter was determined as the optimum choice to collect glass particles in EC aerosol. A cartomizer was filled with EC refill solution composed of an equal volume of propylene glycol (PG) and vegetable glycol (VG). To simulate the potential conditions for glass particle emission, EC vaped aerosols were collected at three distinctive puffing intervals: (1) 0-10 puffs, (2) 101-110 puffs, and (3) 201-210 puffs (flow rate of 1 L min -1 , 2 s per puff, and 10 puffs per sample). Glass particles were observed as early as after 100 times puffing from certain products, while after 200 from others. Thus, glass particles were generated by increasing the number of puffs and usage of the EC cartomizer. The analysis of glass particles collected onto polycarbonate filters by scanning electron microscopy (SEM)/energy dispersive X-ray spectroscopy (EDS) confirmed the presence of glass particles in samples collected after puffing 100-200 times. The study demonstrated that the possibility of glass particle emissions from the EC device increased considerably with the increasing number of total puffs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The efficacy of a combination of a calcium channel blocker (CCB) plus chlorthalidone (diuretic) versus a CCB plus an angiotensin receptor blocker (ARB) in patients not responding to CCB monotherapy has not been evaluated previously. We plan to compare the efficacy and safety of S-amlodipine (CCB) plus chlorthalidone versus S-amlodipine plus telmisartan (ARB) combinations among hypertension patients unresponsive to amlodipine monotherapy., Methods/design: This study is a prospective, randomized, double-blind, multicenter, parallel, non-inferiority phase 4 study. Hypertension patients who have been treated with amlodipine (5 mg) or S-amlodipine (2.5 mg) monotherapy for ≥2 weeks and whose mean diastolic blood pressure (DBP) is greater than 90 mmHg will be randomized to either S-amlodipine (2.5 mg) plus chlorthalidone (25 mg) or S-amlodipine (2.5 mg) plus telmisartan (40 mg) therapy. The primary efficacy endpoint is mean sitting DBP change after 12 weeks of treatment. The study objective is to prove the non-inferiority of the former combination (test drug) as compared to the latter one (control) with a non-inferiority margin of 3 mmHg in mean DBP change. The secondary endpoints are 6-week DBP change, 6- and 12-week sitting systolic BP (SBP) change, and the attainment of the target BP (SBP < 140 mmHg or DBP < 90 mmHg). Urine albumin, albumin/creatinine ratio (ACR), pulse wave velocity, central BP, 24-h ambulatory BP monitoring, and body fluid composition analysis will be performed at each hospital's discretion. The sample size was estimated as 170 in total with 1:1 randomization., Discussion: This is the first study comparing the efficacy of a CCB plus chlorthalidone versus a CCB plus an ARB in patients who are not responding to CCB single therapy. The study result will help clinicians to choose between chlorthalidone and telmisartan in CCB-unresponsive patients., Trial Registration: ClinicalTrials.gov , NCT03226340. Registered on 2 December 2015.

Notch 1/2 genes play tumor-suppressing functions in squamous cell carcinoma (SCC), a very common malignancy in skin and internal organs. In contrast with Notch, we show that the transcription factor CSL (also known as RBP-Jκ), a key effector of canonical Notch signaling endowed with intrinsic transcription-repressive functions, plays a tumor-promoting function in SCC development. Expression of this gene decreased in upper epidermal layers and human keratinocytes (HKCs) undergoing differentiation, while it increased in premalignant and malignant SCC lesions from skin, head/neck, and lung. Increased CSL levels enhanced the proliferative potential of HKCs and SCC cells, while silencing of CSL induced growth arrest and apoptosis. In vivo, SCC cells with increased CSL levels gave rise to rapidly expanding tumors, while cells with silenced CSL formed smaller and more differentiated tumors with enhanced inflammatory infiltrate. Global transcriptomic analysis of HKCs and SCC cells with silenced CSL revealed major modulation of apoptotic, cell-cycle, and proinflammatory genes. We also show that the histone demethylase KDM6B is a direct CSL-negative target, with inverse roles of CSL in HKC and SCC proliferative capacity, tumorigenesis, and tumor-associated inflammatory reaction. CSL/KDM6B protein expression could be used as a biomarker of SCC development and indicator of cancer treatment.

An increase in the ratio of the brachial pre-ejection period to brachial ejection time [pre-ejection period (PEP)/ET] is correlated with a decrease of left ventricular ejection fraction (LVEF). The current study was designed to test the hypothesis that the change value (Δ) of PEP/ET is a useful indicator of Δ LVEF in patients with left ventricular systolic dysfunction.We consecutively enrolled 104 patients with left ventricular systolic dysfunction (LVEF < 45%). PEP/ET, B-type natriuretic peptide (BNP), and LVEF were evaluated at baseline and at 6-month follow-up. Compared with the baseline measurements, the 6-month values of ΔLVEF, ΔBNP, and ΔPEP/ET were 9.8% ± 9.0% (from 36.3% ± 9.2% to 46.3% ± 12.5%, P < 0.001), -168.5 ± 255.4 (from 271.4 ± 282.5 to 104.1 ± 129.6, P < 0.001), and -0.060 ± 0.069 (from 0.413 ± 0.097 to 0.358 ± 0.079, P < 0.001), respectively. There were significant correlations between LVEF and PEP/ET and between LVEF and BNP in both the initial (r = -0.316, P = 0.001 and r = -0.598, P < 0.001, respectively) and 6-month follow-up (r = -0.307, P = 0.003 and r = -0.701, P < 0.001, respectively). The Steiger's Z test showed that BNP had a significantly stronger correlation with LVEF compared with the correlations between LVEF and PEP/ET in both the initial and 6-month studies (Z = 2.471, P = 0.013 and Z = 3.575, P < 0.001, respectively). There were also significant correlations between ΔLVEF and ΔPEP/ET (r = -0.515, P < 0.001) and between ΔLVEF and ΔBNP (r = -0.581, P < 0.001); however, there was no difference between the correlations for ΔLVEF and ΔPEP/ET versus ΔLVEF and ΔBNP (Steiger's Z = 0.600, P = 0.545).In patients with left ventricular systolic dysfunction not only ΔBNP but also ΔPEP/ET could be a simple indicator of predicting change of LVEF.

A kinetic model for the competitions was applied to understand the reductive dechlorination of tertiary DNAPL mixtures containing PCE, TCE, and 1,1,1-TCA. The model assumed that the mass transfer rates were sufficiently rapid that the target compounds in the solution and the DNAPL mixture were in phase equilibrium. Dechlorination was achieved using either a mixture of Fe(II), Fe(III), and Ca(OH) 2 (Fe(II/III)-L) or a mixture of Fe(II) and Portland cement (Fe(II)-C). PCE in the DNAPL mixtures was gradually reduced and it was reduced more rapidly using Fe(II)-C than Fe(II/III)-L. A constant total TCE concentration in the DNAPL mixtures was observed, which implied that the rate of loss of TCE by dechlorination and possibly other processes was equal to the rate of production of TCE by PCE dechlorination. On the other hand, 1,1,1-TCA in the DNAPL mixtures was removed rapidly and its degradation rate by Fe(II/III)-L was faster than by Fe(II)-C. The coefficients in the kinetic model (k i , K i ) were observed to decrease in the order 1,1,1-TCA>PCE>TCE, for both Fe(II/III)-L and Fe(II)-C. The concentrations of target compounds in solution were the effective solubilities, because of the assumption of phase equilibrium and were calculated with Rault's Law. The concentration changes observed were an increase and then a decrease for PCE, a sharp and then gradual increase for TCE, and a dramatic decrease for 1,1,1-TCA. The fraction of initial and theoretical reductive capacity revealed that Fe(II)-C had ability to degrade target compounds., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We present an 8x four-group zoom lens system for a compact camera without any moving groups by employing a focus tunable lens (FTL). We locate the FTLs at the second and fourth groups as a variator and a compensator. In the initial design stage, paraxial analysis for the zoom position was numerically determined by examining the solutions for various first group and third group powers, to achieve a physically meaningful and compact zoom system at a zoom ratio of 8x. The designed zoom lens has focal lengths of 4-31 mm and the apertures of F/3.5 to F/4.5 at wide and tele positions, respectively.

The purpose of this study was to measure the level of new bone formation induced by various bone graft materials to provide clinicians with more choices. The samples were divided into three groups: group 1 ( n = 9: allograft + xenograft, DBX &reg; , San Francisco, CA, USA + Bio-Oss &reg; , Princeton, NJ, USA), group 2 ( n = 10: xenograft, Bio-Oss &reg; ), and group 3 ( n = 8: autogenous tooth bone graft, AutoBT &reg; , Korea Tooth Bank, Seoul, Korea). The average duration of evaluation was 9.56, 2.50, and 3.38 months, respectively. A tissue sample was taken from 27 patients during the second implant surgery. New bone formation was measured via histomorphometry, using a charge-coupled device camera, adaptor, and image analysis software. Total bone area, total area, and ((total bone area/total area) &times; 100) was measured to determine the extent of new bone formation. The mean value of the total bone area was 152,232.63 &mu;m²; the mean value of the total area was 1,153,696.46 &mu;m²; and the mean total bone area/total area ratio was 13.50%. In each comparison, there was no significant difference among the groups; no inflammation or complications were found in any of the groups. AutoBT &reg; , an autogenous tooth bone graft, resulted in a level of bone formation similar to that using allografts and xenografts.

Background: Life history characteristics are considered important factors influencing the evolutionary processes of natural populations, including the patterns of population genetic structure of a species. The sister species Cottus hangiongensis and C. koreanus are small bottom-dwelling freshwater sculpin fishes from South Korea that display marked life history divergence but are morphologically nearly indistinguishable. Cottus hangiongensis evolved an 'amphidromous' life history with a post-hatching pelagic larval phase. They spawn many small eggs in the low reaches of rivers, and hatched larvae migrate to the sea before returning to grow to maturity in the river mouth. In contrast, C. koreanus evolved a 'fluvial' landlocked type with benthic larvae. They release a smaller number of larger eggs, and the larvae undergo direct development, remaining benthic in the upstream rivers throughout their entire lives. We tested whether there were differences in patterns and levels of within-population genetic diversities and spatial population structure between the two closely related Korean sculpins using mitochondrial DNA control region sequences and seven nuclear microsatellite loci., Results: The combined analyses of both marker sets revealed that C. hangiongensis harboured considerably higher levels of within-population genetic diversities (e.g. haplotype/allelic richness, heterozygosities) than C. koreanus. In contrast, the fluvial sculpin exhibited noticeably more spatial population structure than did the amphidromous sculpin, as suggested by pairwise F ST statistics. The finding that C. hangiongensis individuals comprised a single random mating population across the east-flowing river basins in the Korean Peninsula, whereas C. koreanus individuals comprised genetically discrete individual populations, was further supported by an individual-based Bayesian population assignment and also factorial correspondence analyses., Conclusions: The higher genetic diversity, but lower population structure, of the amphidromous sculpin relative to the fluvial sculpin may have resulted from its greater larval dispersal and also possibly, higher fecundity accompanied by an amphidromous life history. Hence, we conclude that contrasting early life histories - including the presence or absence of the pelagic larval phase - may have led to divergent patterns of within-population genetic diversities and spatial population structure between the sister Cottus species following speciation from a common ancestor of marine sculpin.

Background: This study aimed to evaluate clinical implications of single vessel coronary spasm provoked by intracoronary ergonovine provocation test in Korean population., Method: A total of 1248 patients who presented with single vessel coronary artery spasm induced by intracoronary ergonovine provocation test, excluding 1712 with negative spasms, multiple and mixed coronary artery spasms and missing data among 2960 patients in the VA-KOREA (Vasospastic Angina in Korea) registry, were classified into diffuse (n=705) and focal (n=543) groups., Results: The 24-month incidences of a composite primary endpoints (cardiac death, new-onset arrhythmia, and acute coronary syndrome) were determined. Over a median follow-up of 30months, the composite primary end point occurred more frequently in the focal type patients than in the diffuse type patients (primary endpoint: adjusted hazard ratio [aHR], 1.658; 95% confidence interval [CI] 1.272 to 2.162, P<0.001). Especially, unstable angina in ACS components played a major role in this effect (hazard ratio [HR], 2.365; 95% confidence interval [CI] 1.100 to 5.087, P=0.028)., Conclusion: Focal type of single vessel coronary artery spasm in vasospastic angina (VSA) patients is found to be associated with worse clinical outcomes. It is thought that the effect is stemmed from unstable angina among ACS rather than the other components of primary endpoint. Therefore, focal type of single vessel coronary artery spasm in patients with VSA should be more carefully assessed and managed with appropriate medication., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In recent years, various van der Waals (vdW) materials have been used in implementing high-performance photodetectors with high photoresponsivity over a wide detection range. However, in most studies reported so far, photodetection in the infrared (IR) region has not been achieved successfully. Although several vdW materials with narrow bandgaps have been proposed for IR detection, the devices based on these materials exhibit notably low photoresponsivity under IR light illumination. Here, highly efficient near-infrared (NIR) photodetection based on the interlayer optical transition phenomenon in a vdW heterojunction structure consisting of ReS 2 and ReSe 2 is demonstrated. In addition, by applying the gate-control function to the two-terminal vdW heterojunction photodetector, the photoresponsivity is enhanced to 3.64 × 10 5 A W -1 at λ = 980 nm and 1.58 × 10 5 A W -1 at λ = 1310 nm. Compared to the values reported for previous vdW photodetectors, these results are the highest levels of photoresponsivity in the NIR range. The study offers a novel device platform for achieving high-performance IR photodetectors.

It is necessary for molecular breeders to overcome the difficulties in applying abundant genomic information to crop breeding. Candidate orthologs would be discovered more efficiently in less-studied crops if the information gained from studies of related crops were used. We developed a comparative analysis tool and web-based genome viewer to identify orthologous genes based synteny as well as sequence similarity between tomato, pepper and potato. The tool has a step-by-step interface with multiple viewing levels to support the easy and accurate exploration of functional orthologs. Furthermore, it provides access to single nucleotide-polymorphism markers from the massive genetic resource pool in order to accelerate the development of molecular markers for candidate orthologs in the Solanaceae. This tool provides a bridge between genome data and breeding by supporting effective marker development, data utilization and communication.Database URL: http://tgsol.seeders.co.kr/scomp/.

PCB19, a 2,2',6-trichlorinated biphenyl, is one of many non-dioxin-like polychlorinated biphenyls (NDL-PCBs), which are ubiquitous pollutants. NDL-PCBs affect cytosolic Ca 2+ signaling by promoting Ca 2+ release from ryanodine receptor-sensitive Ca 2+ pools and inhibiting store-operated Ca 2+ entry (SOCE) from the extracellular space. However, NDL-PCB-mediated SOCE inhibition has only been demonstrated in PC12 cells, in which SOCE is thought to be mainly mediated by TRPC family channels. Here, we investigated the effect of PCB19 on SOCE using human embryonic kidney 293 (HEK293) cells, human leukemia T cell line Jurkat-T cells and human promyelocytoma HL-60 cells which are the cell lines that are previously demonstrated to mediate the most common form of SOCE solely by the intrinsic Orai channels. PCB19 reduced thapsigargin-induced Ca 2+ influx after Ca 2+ pool depletion in HEK293 cells. SOCEs in HEK293, Jurkat T, HL-60 and PC12 cells showed distinct sensitivities to SOCE inhibitors such as Gd 3+ and ML-9; however, PCB19 also showed a common effect of inhibiting SOCEs in all cell lines. PCB19-mediated SOCE inhibition was confirmed by demonstrating the ability of PCB19 to inhibit the SOCE current but not the TRPM7 current. These results imply that PCB19 inhibits not only TRPC-mediated SOCE as in PC12 cells but also Orai-mediated SOCE as in many other cells including HEK293, Jurkat T and HL-60 cells.

Variovorax paradoxus KB5, isolated from the inside of Arabidopsis thaliana leaves, showed antibacterial activity against the phytopathogen Pseudomonas syringae pv. tomato DC3000. Here, we report a draft genome sequence of V. paradoxus KB5, which contains a delftibactin-like nonribosomal peptide biosynthetic gene cluster., (Copyright © 2017 Hong et al.)

The prevalence of heart failure (HF) is skyrocketing worldwide, and is closely associated with serious morbidity and mortality. In particular, HF is one of the main causes for the hospitalization and mortality in elderly individuals. Korea also has these epidemiological problems, and HF is responsible for huge socioeconomic burden. However, there has been no clinical guideline for HF management in Korea. 
The present guideline provides the first set of practical guidelines for the management of HF in Korea and was developed using the guideline adaptation process while including as many data from Korean studies as possible. The scope of the present guideline includes the definition, diagnosis, and treatment of chronic HF with reduced/preserved ejection fraction of various etiologies., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest.

Cancer-associated fibroblasts (CAFs) are important for tumor initiation and promotion. CSL, a transcriptional repressor and Notch mediator, suppresses CAF activation. Like CSL, ATF3, a stress-responsive transcriptional repressor, is down-modulated in skin cancer stromal cells, and Atf3 knockout mice develop aggressive chemically induced skin tumors with enhanced CAF activation. Even at low basal levels, ATF3 converges with CSL in global chromatin control, binding to few genomic sites at a large distance from target genes. Consistent with this mode of regulation, deletion of one such site 2 Mb upstream of IL6 induces expression of the gene. Observed changes are of translational significance, as bromodomain and extra-terminal (BET) inhibitors, unlinking activated chromatin from basic transcription, counteract the effects of ATF3 or CSL loss on global gene expression and suppress CAF tumor-promoting properties in an in vivo model of squamous cancer-stromal cell expansion. Thus, ATF3 converges with CSL in negative control of CAF activation with epigenetic changes amenable to cancer- and stroma-focused intervention., (© 2017 Kim et al.)

Lactobacillus fermentum strain JDFM216, isolated from a Korean infant feces sample, possesses the ability to enhance the longevity and immune response of a Caenorhabditis elegans host. To explore the characteristics of strain JDFM216 at the genetic level, we performed whole-genome sequencing using the PacBio system. The circular draft genome has a total length of 2,076,427 bp and a total of 2,682 encoding sequences were identified. Five phylogenetically featured genes possibly related to the longevity and immune response of the host were identified in L. fermentum strain JDFM216. These genes encode UDP- N -acetylglucosamine 1-carboxyvinyltransferase (E.C. 2.5.1.7), ErfK/YbiS/YcfS/YnhG family protein, site-specific recombinase XerD, homocysteine S-methyltransferase (E.C. 2.1.1.10), and aspartate-ammonia ligase (E.C. 6.3.1.1), which are involved in peptidoglycan synthesis and amino acid metabolism in the gut environment. Our findings on the genetic background of L. fermentum strain JDFM216 and its potential candidate genes for host longevity and immune response provide new insight for the application of this strain in the food industry as newly isolated functional probiotic.

To develop accurate quantitation methods for two major permanent gases, N 2 and O 2 , a series of calibration experiments were carried out using a gas chromatograph (GC)/barrier discharge ionization detector (BID) equipped with a large-volume injection (LVI) system. To this end, gaseous working standards (WSs) diluted with helium gas were prepared at ten different concentration levels representing three different concentration ranges (in ppm) in 1-L polyester aluminum (PEA) bags ((1) low, 209~2090 (O 2 ) and 791~7910 (N 2 ); (2) moderate, 2090 ~ 20,900 (O 2 ) and 7910~79,100 (N 2 ); and (3) high, 20,900~209,000 (O 2 ) and 79,100~791,000 (N 2 )). Cross-calibration experiments for each individual WS were carried out using the loop injection system with four different capacities (0.01, 0.5, 1, and 10 mL). The calibration results were then evaluated with respect to key variables including loop capacity, concentration, and mass quantity. Accordingly, we observed the optimal performance of the BID in terms of sensitivity and linearity (R 2  > 0.98) when the WS of the moderate concentration range was analyzed with the small loop (0.01 and 0.5 mL). The method detection limit (MDL) values of the four loop sizes (between 0.01 and 10 mL) were 7~500 ng for O 2 (38.4~557 ppm) and 24~2230 ng for N 2 (195~2105 ppm).

Background: Takotsubo cardiomyopathy (TC) is acute, but completely reversible in the absence of significant coronary artery disease. This study aims to assess the functional recovery of regional myocardial deformation in patients with TC using 2-dimensional (2D) speckle tracking echocardiography., Methods: Thirty-three patients diagnosed with TC (mean age 63 years, 26 female) prospectively underwent serial 2D echocardiography on day 1 (initial presentation), day 4 [the middle, interquartile range (IQR), 2-5 days], and day 21 (recovery, IQR 13-32 days). Twenty-one (64%) patients showed classical type of TC with akinesis of mid-left ventricular (LV) and apical segments and 12 (36%) of patients presented with mid-LV variant with apical sparing. Myocardial deformations were serially assessed using 2D strain analysis. All echocardiographic values on day 21 were compared with the corresponding values from 30 controls of similar age and gender., Results: LV ejection fraction (EF) gradually improved at follow-up (32±8% on day 1 vs. 62±4% on day 21, p<0.001). Despite no difference in LVEF between the patients with complete recovery (LVEF >60% on day 21) and controls, the patients showed significantly lower global longitudinal strain than controls. On regional analysis of the mid-LV segments, both longitudinal and circumferential strains of patients with TC were similarly diminished on day 1. During recovery, longitudinal strain showed more delayed recovery than circumferential strain compared to the values of controls. In LV apex of controls, circumferential strain normally presented higher value than longitudinal strain. In LV apex of patients with classical TC, the reduced circumferential strain on day 1 rapidly increased with a wide variation to maintain augmented circumferential shortening., Conclusions: Quantifying LV myocardial deformation in patients with TC is informative in the detection of persistent subtle LV dysfunction and improves our understanding of regional myocardial mechanics during recovery., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Multivalued logic (MVL) devices/circuits have received considerable attention because the binary logic used in current Si complementary metal-oxide-semiconductor (CMOS) technology cannot handle the predicted information throughputs and energy demands of the future. To realize MVL, the conventional transistor platform needs to be redesigned to have two or more distinctive threshold voltages (V TH s). Here, we report a finding: the photoinduced drain current in graphene/WSe 2 heterojunction transistors unusually decreases with increasing gate voltage under illumination, which we refer to as the light-induced negative differential transconductance (L-NDT) phenomenon. We also prove that such L-NDT phenomenon in specific bias ranges originates from a variable potential barrier at a graphene/WSe 2 junction due to a gate-controllable graphene electrode. This finding allows us to conceive graphene/WSe 2 -based MVL logic circuits by using the I D -V G characteristics with two distinctive V TH s. Based on this finding, we further demonstrate a light-triggered ternary inverter circuit with three stable logical states (ΔV out of each state <0.05 V). Our study offers the pathway to substantialize MVL systems.

Background: To evaluate the clinical outcome of revision of primary shoulder replacement by using reverse total shoulder arthroplasty (RTSA)., Methods: Seven patients underwent revision RTSA with a mean follow-up of 22.1 months (range, 12 to 54 months). Their mean age at the time of operation was 75.5 years (range, 70 to 80 years). Assessments were performed on the preoperative and postoperative visual analogue scale (VAS) score, muscle strength, range of motion, University of California at Los Angeles (UCLA) score, Constant score, subjective satisfaction and the anteroposterior and axillary views of the glenohumeral joint. The primary operation was hemiarthroplasty in 5 patients, total shoulder replacement in 1 patient, and reverse shoulder arthroplasty in 1 patient. The cause of revision surgery was infection in 2 patients, humeral stem loosening in 2 patients, glenoid arthropathy in 2 patients, and glenoid loosening in 1 patient. The mean duration from primary operation to revision surgery was 52 months (range, 27 to 120 months)., Results: The VAS score for pain during motion was improved from 7.3 preoperatively to 2.1 postoperatively ( p = 0.03). There were increases in the mean active forward flexion (from 62.1° to 92.8°), abduction (from 70° to 87.1°), external rotation (from 44.2° to 47.4°), and internal rotation (from L5 to L4; p > 0.05) postoperatively. Performance in activities of daily living improved ( p > 0.05), except for lifting 10 lb above the shoulder (from 1.2 to 1.1; p = 0.434). Overall, 5 of 7 patients were satisfied with the results of revision surgery. The mean Constant score improved from 44.8 preoperatively to 57.1 postoperatively ( p = 0.018). The mean UCLA score improved from 12.8 preoperatively to 22.8 postoperatively ( p = 0.027). In the postoperative radiological evaluation, no radiolucency was observed around the base plate or humeral stem., Conclusions: Pain could be reduced after revision RTSA, but improvements in range of motion and function were difficult to achieve. We think that the patients' satisfaction was relatively high despite the low function score due to the preoperative severe pain and marked limitation of range of motion., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported.

Endoplasmic reticulum (ER)-stress-mediated apoptosis is a host defense mechanism against Mycobacterium tuberculosis (Mtb) infection. Calreticulin (CRT) is the major calcium-binding chaperone protein. Previous reports have suggested a close relationship between the cell-surface expression of CRT and apoptosis. In this study, the role of CRT during Mtb infection was examined. The results showed that Mtb infection induces CRT production by macrophages and that CRT levels are correlated with the degree of apoptotic cell death. The enhanced production of CRT was associated with the ER stress induced by Mtb infection. A significant increase in CRT translocation from the cytosol to the plasma membrane after 24 h of infection suggested the importance of CRT localization in the induction of apoptosis during Mtb infection. An investigation of the factors associated with CRT translocation and the ability of ectopically expressed CRT to induce apoptosis showed that pretreatment with a reactive oxygen species scavenger decreased Mtb-induced CRT expression, leading to the reduction of CHOP and caspase-3 activation. The intracellular survival of Mtb was significantly higher in macrophages transfected with a CRT-specific small interfering RNA than in control cells. The key role of CRT in inducing apoptosis included its interaction with CXCR1 and TNFR1 in Mtb-infected macrophages. The CRT/CXCR1/TNFR1 complex was shown to induce the extrinsic apoptotic pathway during Mtb infection. Together, these results demonstrate that CRT is critical for the intracellular survival of Mtb, via ER-stress-induced apoptosis, as well as the importance of ER stress-mediated CRT localization in the pathogenesis of tuberculosis., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

The adsorption properties of various sorbent materials were investigated to assess the factors affecting biases in the sorbent tube (ST) sampling of airborne phthalates. The recovery of phthalates was assessed critically in relation to four key sampling parameters: (1) three types of sorbent materials (quartz wool (QW), glass wool (GW), and quartz wool plus Tenax TA (QWTN)), (2) the concentration level of phthalate standards, (3) purge flow rate, and (4) purge volume for analysis based on a 'sorbent tube-thermal desorption-gas chromatography-mass spectrometry (ST-TD-GC-MS)' system. Among these parameters, the type of ST was the most influential in determining the recovery of phthalates. For a given ST type, the recovery of phthalates tends to improve with increases in the concentration level of standards. In case of QW and QWTN tubes, the breakthrough of phthalates was not observed up to the maximum purge volume (100 L) tested in this work; however, in case of GW, the recovery decreased drastically to 60% even at a purge volume of 1 L for low molecular weight phthalates. The results of our study demonstrate that accurate analysis of airborne phthalates can be achieved through proper control of key sampling parameters, particularly the choice of sorbent material.

The characteristics of malodor released from piggery excreta samples were investigated by measuring their emission concentrations both before and after such treatments as composting or aeration from field sites. These samples were then collected from field sites and brought into the lab for analysis with the aid of the dynamic flux chamber method. The dominating compounds in the emissions were reduced sulfur compounds, phenol, and indole. The results were examined in terms of two key odor indices: odor intensity (OI) and odor activity values (OAVs), after being grouped by some criteria. When the odor contribution in the composting facility was assessed by the OAV value, methanethiol (53.1%), trimethylamine (TMA) (25.5%), and skatole (10.1%) were dominant in the pretreatment facilities, while skatole (64.7%) and p-cresol (27.9%) in the post-treatment specimens. Likewise, in the liquid treatment facility, hydrogen sulfide (47.4%), p-cresol (26.9%), and skatole (20.2%) were dominant in the pretreatment, while only p-cresol (73.6%) in the post-treatment. In comparison to the composting facility, the liquid treatment facility proved to be more efficient in the treatment of diverse hog-barn-related odorants.

Bradykinin is an important peptide modulator that affects the function of neurons and immune cells. However, there is no evidence of the bradykinin receptors and their functions in human salivary glands. Here we have identified and characterized bradykinin receptors on human submandibular gland cells. Both bradykinin B1 and B2 receptors are expressed on human submandibular gland cells, A253 cells, and HSG cells. Bradykinin increased the intracellular Ca 2+ concentration ([Ca 2+ ] i ) in a concentration-dependent manner. Interestingly, a specific agonist of the B1 receptor did not have any effect on [Ca 2+ ] i in HSG cells, whereas specific agonists of the B2 receptor had a Ca 2+ mobilizing effect. Furthermore, application of the B1 receptor antagonist, R715, did not alter the bradykinin-mediated increase in cytosolic Ca 2+ , whereas the B2 receptor antagonist, HOE140, showed a strong inhibitory effect, which implies that bradykinin B2 receptors are functional in modulating the concentration of cytosolic Ca 2+ . Bradykinin did not affect a carbachol-induced rise of [Ca 2+ ] i and did not modulate translocation of aquaporin-5. However, bradykinin did promote the expression of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), implying the role of bradykinin in salivary gland inflammation. These data suggest that bradykinin receptors are involved in Ca 2+ signaling in human submandibular gland cells and serve a unique role, which is separate from that of other salivary gland G protein-coupled receptors., (© 2016 Eur J Oral Sci.)

Objective: To investigate the effect of intravenous infusion of peripheral blood mononuclear cells (mPBMC) mobilized by granulocyte-colony stimulating factor (G-CSF) on upper extremity function in children with cerebral palsy (CP)., Methods: Fifty-seven children with CP were enrolled. Ten patients were excluded due to follow-up loss. In total, 47 patients (30 males and 17 females) were analyzed. All patients' parents provided signed consent before the start of the study. After administration of G-CSF for 5 days, mPBMC was collected and cryopreserved. Patients were randomized into two groups 1 month later. Twenty-two patients were administered mPBMC and 25 patients received normal saline as placebo. Six months later, the two groups were switched, and administered mPBMC and placebo, respectively. Quality of Upper Extremity Skills Test (QUEST) and the Manual Ability Classification System (MACS) were used to evaluate upper motor function., Results: All subdomain and total scores of QUEST were significantly improved after mPBMC and placebo infusion, without significant differences between mPBMC and placebo groups. A month after G-CSF, all subdomain and total scores of QUEST were improved. The level of MACS remained unchanged in both mPBMC and placebo groups., Conclusion: In this study, intravenously infused mPBMC showed no significant effect on upper extremity function in children with CP, as compared to placebo. The effect of mPBMC was likely masked by the effect of G-CSF, which was used in both groups and/or G-CSF itself might have other neurotrophic potentials in children with CP., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported.

Objective: As smartphone penetration increases and the technology advances, various mobile services have reached the market. mHealth Applications are specifically highlighted for phenomena such as global aging & well-being, but the technology-driven mHealth services have not been successful in the market because consumer needs have not been reflected in the services properly. This study developed a research model consisting of context/contents values to explain the intention of consumers over the age of 40 in using mHealth Applications., Method: To carry out this research, an online survey was conducted of mHealth Application users and recognizers in South Korea who are over 40 years old. 313 respondents gave usable data; those data were analyzed via a structural equation model., Results: Context values (health stress, epistemic) produce an effect on contents values and contents values (convenience, usefulness), excepting reassurance and enjoyment, positively affect the intention to use mHealth Applications. The findings indicate that people who are stressed out about their health and are interested in new ways to control their health think that mHealth Applications are very convenient and useful because people can manage their health at home or at the office, even when they cannot go to a hospital. However, they feel that the current level of service does not provide reassurance. The level of service is behind people's expectations. Hence, a market-oriented approach that can determine user needs, specifically in terms of the reassurance value in the mHealth service field, is needed to develop mHealth Applications., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The parallel artificial membrane permeability assay (PAMPA) is widely used in early-stage drug discovery to discriminate compounds by intestinal permeability. The purpose of the current study was to establish a cassette (n-in-1) PAMPA to enable permeability screening of lipophilic compounds. A double-sink PAMPA consisting of a pH gradient (i.e., pH 6.5 and 7.4 for the donor and receiver compartments, respectively) and a lipophilic sink (i.e., a surfactant in the receiver solution) was utilized with cassette incubation of 10 reference compounds. Sample analysis was conducted using selected reaction monitoring (SRM) with a triple quadrupole LC-MS/MS system. Correlation between PAMPA permeability and human intestinal absorption (HIA) of the reference compounds yielded two false negatives, namely propranolol (PPN) and verapamil (VER); these two compounds showed a substantially lower recovery (ca. 10%) than other reference compounds (>69%). This cassette PAMPA was repeated subsequently with polysorbate 80 added to the donor compartments, which resulted in a significant increase in both the recovery and the permeability of the false negatives. Accordingly, the permeability class of all reference compounds could be unambiguously differentiated using this cassette PAMPA. Also, a strong linear correlation (r=0.9845) was observed between the cassette and discrete permeability of all reference compounds.

Lipid profiling in nine bacterial species has been accomplished by laser desorption ionization mass spectrometry (LDI-MS) using amorphous silicon (a-Si) thin film with 100 nm thickness. Lipid ions could be generated by LDI on a-Si regardless of ion acquisition modes because of a thermal property of a-Si to govern laser-induced surface heating. In a comparative study of lipid profiling in Bacillus lichemiformis by LDI-MS and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), LDI-MS on a-Si shows a higher efficiency in lipid and lipopeptide detection than MALDI-MS. A total of 53 peaks of lipid ions generated by LDI on a-Si in both acquisition modes for m/z 400-1200 was 1.6 times more than that detected by MALDI-MS using three organic matrices-2,5-dihydroxybenzoic acid, 1,5-diaminonaphthalene, and 2,4,6-trihydroxyacetophenone monohydrate. Also, the authors demonstrate by mass spectrometry imaging (MSI) that LDI-MS provides high detection coverage through whole sample area. MSI results show the detection yield in LDI on a-Si is 94.8% calculated by counting the number of points detected in the analyte ion signal in a whole spot. It means that reproducible detection of lipid ions by LDI-MS is possible even if laser is randomly irradiated at any position within the bacterial sample area applied on a-Si. Lipid profiling by LDI-MS on a-Si was applied to bacterial differentiation of nine bacterial species conducted by performing principal component analysis. Nine bacterial species are successfully distinguishable from each other by LDI-MS lipid profiling.

Purpose: To evaluate the blood pressure (BP) lowering efficacy and safety of CKD-828, a fixed-dose combination of S-amlodipine (the more active isomer of amlodipine besylate, which is calcium channel blocker) and telmisartan (long acting angiotensin receptor blocker), in patients with hypertension inadequately controlled with S-amlodipine monotherapy., Patients and Methods: Eligible patients (N=187) who failed to respond after 4-week S-amlodipine 2.5 mg monotherapy (sitting diastolic blood pressure [sitDBP] ≥90 mmHg) to receive CKD-828 2.5/40 mg (n=63), CKD-828 2.5/80 mg (n=63), or S-amlodipine 2.5 mg (n=61) for 8 weeks. The primary efficacy endpoint, mean sitDBP change from baseline to Week 8, was compared between the combination (CKD-828 2.5/40 mg and CKD-828 2.5/80 mg) and S-amlodipine monotherapy groups. The safety was assessed based on adverse events, vital signs, and physical examination findings., Results: After the 8-week treatment, changes in sitDBP/systolic BP (SBP) were -9.67±6.50/-12.89±11.78, -10.72±6.19/-13.79±9.41, and -4.93±7.26/-4.55±11.27 mmHg in the CKD-828 2.5/40 mg ( P <0.0001/ P <0.0001), CKD-828 2.5/80 mg ( P <0.0001/ P <0.0001), and S-amlodipine 2.5 mg ( P <0.0001/ P =0.0027) groups, respectively, which were all significant BP reductions. At Week 8, the CKD-828 2.5/40 mg (sitDBP/SBP: P =0.0002/ P <0.0001) and CKD-828 2.5/80 mg (sitDBP/SBP: P =0.0001/ P <0.0001) showed superior BP-lowering effects to S-amlodipine 2.5 mg ( P <0.001). At Week 4, all groups showed significant antihypertensive effects but both CKD-828 combinations (CKD-828 2.5/40 mg and CKD-828 2.5/80 mg) exhibited superior BP-lowering effects to that of S-amlodipine 2.5 mg (sitDBP/SBP: P =0.0028/ P =0.0001 and P <0.0001/ P =0.0012, respectively). The adverse event incidence was significantly lower in the CKD-828 2.5/40 mg (9.52%, P =0.0086) than in the S-amlodipine 2.5 mg group (27.87%) and increasing the telmisartan dose induced no unexpected adverse events, suggesting the safety of CKD-828., Conclusion: CKD-828 is an effective and safe option for patients with inadequate responses to S-amlodipine monotherapy., Competing Interests: The authors report no conflicts of interest in this work.

Alteration of macrophage function has an important regulatory impact on the survival of intracellular mycobacteria. We found that macrophages infected with attenuated Mycobacterium tuberculosis (Mtb) strain H37Ra had elevated expression of M1-related molecules, whereas the M2 phenotype was dominant in macrophages infected with virulent Mtb H37Rv. Further, the TLR signalling pathway played an important role in modulating macrophage polarization against Mtb infection. Interestingly, endoplasmic reticulum (ER) stress was significantly increased in M1 polarized macrophages and these macrophages effectively removed intracellular Mtb, indicating that ER stress may be an important component of the host immune response to Mtb in M1 macrophages. This improved understanding of the mechanisms that regulate macrophage polarization could provide new therapeutic strategies for tuberculosis.

In this study, a novel quantitation method was developed to facilitate the simple and effective sampling and analysis of phthalates in air based on a sorbent tube-thermal desorption-gas chromatography-mass spectrometry system combination. The performance of the thermal desorption-based analysis was assessed using three different sorbent combinations [1]: quartz wool (QW) [2], glass wool (GW), and [3] quartz wool plus Tenax TA (QWTN) in terms of relative recovery in reference to a direct injection method. There was no significant difference in the average recovery rate for seven target phthalates based on sorbent tube type (QW, 70.2 ± 4.28; GW, 73.2 ± 8.8; and QWTN, 72.5 ± 5.02%). However, the recovery rate of phthalates in each sorbent tube type was distingusihed by physicochemical properties of the target compound (e.g., molecular weight and boiling point). The recovery rate of the QW tube was high for dimethyl phthalate and diethyl phthalate compared to other sorbent tubes, while that of the GW tube exhibited greater values for dibutyl phthalate, benzyl butyl phthalate, di(2-ethylhexyl) adipate, di(2-ethylhexyl) phthalate, and di-n-octyl phthalate. The simple sorbent tube-thermal desorption approach is feasible for the quantitation of seven phthalates present at 0.45-24.5 ng m -3 levels in actual air samples (20 L)., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Recently, negative differential resistance devices have attracted considerable attention due to their folded current-voltage characteristic, which presents multiple threshold voltage values. Because of this remarkable property, studies associated with the negative differential resistance devices have been explored for realizing multi-valued logic applications. Here we demonstrate a negative differential resistance device based on a phosphorene/rhenium disulfide (BP/ReS 2 ) heterojunction that is formed by type-III broken-gap band alignment, showing high peak-to-valley current ratio values of 4.2 and 6.9 at room temperature and 180 K, respectively. Also, the carrier transport mechanism of the BP/ReS 2 negative differential resistance device is investigated in detail by analysing the tunnelling and diffusion currents at various temperatures with the proposed analytic negative differential resistance device model. Finally, we demonstrate a ternary inverter as a multi-valued logic application. This study of a two-dimensional material heterojunction is a step forward toward future multi-valued logic device research.