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Graphene oxide (GO) nanosheets were utilized as a selective layer on a highly porous polyvinyl alcohol (PVA) nanofiber support via a pressure-assisted self-assembly technique to synthesize composite nanofiltration membranes. The GO layer was rendered stable by cross-linking the nanosheets (GO-to-GO) and by linking them onto the support surface (GO-to-PVA) using glutaraldehyde (GA). The amounts of GO and GA deposited on the PVA substrate were varied to determine the optimum nanofiltration membrane both in terms of water flux and salt rejection performances. The successful GA cross-linking of GO interlayers and GO-PVA via acetalization was confirmed by FTIR and XPS analyses, which corroborated with other characterization results from contact angle and zeta potential measurements. Morphologies of the most effective membrane (CGOPVA-50) featured a defect-free GA cross-linked GO layer with a thickness of ~67 nm. The best solute rejections of the CGOPVA-50 membrane were 91.01% for Na2SO4 (20 mM), 98.12% for Eosin Y (10 mg/L), 76.92% for Methylene blue (10 mg/L), and 49.62% for NaCl (20 mM). These findings may provide one of the promising approaches in synthesizing mechanically stable GO-based thin-film composite membranes that are effective for solute separation via nanofiltration.

O-linked-N-acetylglucosaminylation (O-GlcNAcylation) performed by O-GlcNAc transferase (OGT) is a nutrient-responsive post-translational modification (PTM) via the hexosamine biosynthetic pathway (HBP). Various transcription factors (TFs) are O-GlcNAcylated, affecting their activities and significantly contributing to cellular processes ranging from survival to cellular differentiation. Given the pleiotropic functions of O-GlcNAc modification, it has been studied in various fields; however, the role of O-GlcNAcylation during osteoclast differentiation remains to be explored. Kinetic transcriptome analysis during receptor activator of nuclear factor-kappaB (NF-κB) ligand (RANKL)-mediated osteoclast differentiation revealed that the nexus of major nutrient metabolism, HBP was critical for this process. We observed that the critical genes related to HBP activation, including Nagk, Gfpt1, and Ogt, were upregulated, while the global O-GlcNAcylation was increased concomitantly during osteoclast differentiation. The O-GlcNAcylation inhibition by the small-molecule inhibitor OSMI-1 reduced osteoclast differentiation in vitro and in vivo by disrupting the translocation of NF-κB p65 and nuclear factor of activated T cells c1 (NFATc1) into the nucleus by controlling their PTM O-GlcNAcylation. Furthermore, OSMI-1 had a synergistic effect with bone target therapy on osteoclastogenesis. Lastly, knocking down Ogt with shRNA (shOgt) mimicked OSMI-1’s effect on osteoclastogenesis. Targeting O-GlcNAcylation during osteoclast differentiation may be a valuable therapeutic approach for osteoclast-activated bone diseases.

Abstract Recently, the roles of FAM83H in tumorigenesis have been interested and increased expression of FAM83H and MYC in hepatocellular carcinoma (HCC) have been reported. Therefore, we investigated the expression and role of FAM83H in 163 human HCCs and further investigated the relationship between FAM83H and oncogene MYC. The expression of FAM83H is elevated in liver cancer cells, and nuclear expression of FAM83H predicted shorter survival of HCC patients. In HLE and HepG2 HCC cells, knock-down of FAM83H inhibited proliferation and invasive activity of HCC cells. FAM83H induced expression of cyclin-D1, cyclin-E1, snail and MMP2 and inhibited the expression of P53 and P27. In hepatic tumor cells derived from Tet-O-MYC mice, the expression of mRNA and protein of FAM83H were dependent on MYC expression. Moreover, a chromatin immunoprecipitation assay demonstrated that MYC binds to the promotor of FAM83H and that MYC promotes the transcription of FAM83H, which was supported by the results of a dual-luciferase reporter assay. In conclusion, we present an oncogenic role of FAM83H in liver cancer, which is closely associated with the oncogene MYC. In addition, our results suggest FAM83H expression as a poor prognostic indicator of HCC patients.

We report a noble coherent optical frequency domain reflectometry (OFDR) system that simply enables measurement range enhancement up to full coherence length of a laser source. The proposed technique is based on bidirectional determination of Rayleigh backscattered signal along a fiber. To do this, complex OFDR signals are acquired with the help of $\pi / 2$ phase-shifting interferometry in a detection part and an additional delay fiber in a reference arm. Through a bidirectional determination process using the complex OFDR signals, mirrored signals appearing at both sides of the spatial domain were completely discriminated, so that ambiguity arising due to a positional origin can be removed. Bidirectional distributed strain and temperature sensing is successfully performed for the first time. Spectral shifts by applying strain to and heating of the test fiber were found to be independent on both sides of the reference position, indicating that twofold enhancement of the measurement range can be obtained compared to previous systems.

Investigates the effects of diabetes and hypertension on glomerular transforming growth factor-beta (TGF-beta) receptor expression. Influence of hemodynamic and metabolic factors on glomerular TGF-beta receptor; Characterization of diabetic nephropathy; Expression of TGF-beta receptor in glomeruli.

FAM83H is primarily known for its role in amelogenesis; however, recent reports suggest FAM83H might be involved in tumorigenesis. Although the studies of FAM83H in kidney cancer are limited, a search of the public database shows a significant association between FAM83H and pannexin-2 (PANX2) in clear cell renal cell carcinomas (CCRCCs). Therefore, we evaluated the clinicopathological significance of the immunohistochemical expression of FAM83H and PANX2 in 199 CCRCC patients. The expression of FAM83H and PANX2 were significantly associated with each other. In univariate analysis, individual, and co-expression pattern of FAM83H and PANX2 was significantly associated with shorter overall survival (OS) and relapse-free survival (RFS) of CCRCC patients: nuclear expression of FAM83H (OS; P < 0.001, RFS; P < 0.001), cytoplasmic expression of FAM83H (OS; P < 0.001, RFS; P < 0.001), nuclear expression of PANX2 (OS; P < 0.001, RFS; P < 0.001), cytoplasmic expression of PANX2 (OS; P < 0.001, RFS; P < 0.001), co-expression pattern of nuclear FAM83H and nuclear PANX2 (OS; P < 0.001, RFS; P < 0.001). In multivariate analysis, nuclear expression of FAM83H (OS; P < 0.001, RFS; P = 0.003) and the co-expression pattern of nuclear FAM83H and PANX2 (OS; P < 0.001, RFS; P < 0.001) were independent indicators of shorter survival of CCRCC patients. Cytoplasmic expression of FAM83H was associated with shorter RFS (P = 0.030) in multivariate analysis. In Caki-1 and Caki-2 CCRCC cells, knock-down of FAM83H decreased PANX2 expression and cell proliferation, and overexpression of FAM83H increased PANX2 expression and cell proliferation. These results suggest that FAM83H and PANX2 might be involved in the progression of CCRCC in a co-operative manner, and their expression might be used as novel prognostic indicators for CCRCC patients.

Finasteride is commonly used for treatment of alopecia. Because finasteride is a cause of gynecomastia, there is concern regarding the continuation of finasteride therapy after mastectomy. No studies have been performed to determine whether finasteride should be continued after mastectomy when gynecomastia occurs in patients taking finasteride for the treatment of alopecia. The researchers studied the effects of finasteride on gynecomastia recurrence after mastectomy in men with gynecomastia taking finasteride for alopecia. The researchers retrospectively evaluated 1,673 patients with gynecomastia who underwent subcutaneous mastectomy with liposuction at Damsoyu Hospital from January 2014 to December 2016. In total, 52 of the patients were taking finasteride for alopecia before surgery and continued to use it in the same manner after mastectomy. Ultrasonography was performed 1 year after mastectomy. The patients’ median age was 26.5 (24.75–30) years. All 52 patients had bilateral gynecomastia. The median duration of finasteride therapy before and after surgery was 12 (5–25.75) and 33 (27.5–40.5) months, respectively. There were no statistically significant differences between the groups with and without the use of finasteride in relation to postoperative complications and recurrence rates. Taking finasteride seems to have little effect on recurrence in patients with alopecia who have undergone surgical treatment of gynecomastia. Surgeons may recommend continuous finasteride therapy in patients with alopecia who wish to take finasteride after mastectomy.

[This corrects the article DOI: 10.1371/journal.pone.0137589.].

SCRIB is a polarity protein important in maintaining cell junctions. However, recent reports have raised the possibility that SCRIB might have a role in human cancers. Thus, this study evaluated the roles of SCRIB in ovarian cancers. In 102 human ovarian carcinomas, nuclear expression of SCRIB predicted shorter survival of ovarian carcinoma patients, especially in the patients who received post-operative chemotherapy. In SKOV3 and SNU119 ovarian cancer cells, overexpression of SCRIB stimulated the proliferation and invasion of cells. Knockout of SCRIB inhibited in vivo tumor growth of SKOV3 cells and overexpression of SCRIB promoted tumor growth. Overexpression of SCRIB stimulated epithelial-to-mesenchymal transition by increasing the expression of N-cadherin, snail, TGF-β1, and smad2/3, and decreasing the expression of E-cadherin; the converse was observed with inhibition of SCRIB. In conclusion, this study presents the nuclear expression of SCRIB as a prognostic marker of ovarian carcinomas and suggests that SCRIB is involved in the progression of ovarian carcinomas by stimulating proliferation and epithelial-to-mesenchymal transition-related invasiveness.

The incorporation of permeation enhancers in topical preparations has been recognized as a simple and valuable approach to improve the penetration of antifungal agents into toenails. In this study, to improve the toenail delivery of efinaconazole (EFN), a triazole derivative for onychomycosis treatment, topical solutions containing different penetration enhancers were designed, and the permeation profiles were evaluated using bovine hoof models. In an in vitro permeation study in a Franz diffusion cell, hydroalcoholic solutions (HSs) containing lipophilic enhancers, particularly prepared with propylene glycol dicaprylocaprate (Labrafac PG), had 41% higher penetration than the HS base. Moreover, the combination of hydroxypropyl-β-cyclodextrin with Labrafac PG further facilitated the penetration of EFN across the hoof membrane. In addition, this novel topical solution prepared with both lipophilic and hydrophilic enhancers was physicochemically stable, with no drug degradation under ambient conditions (25 °C, for 10 months). Therefore, this HS system can be a promising tool for enhancing the toenail permeability and therapeutic efficacy of EFN.

With the increasing demand for renewable energy power generation systems, high-power DC transmission technology is drawing considerable attention. As a result, stability issues associated with high power DC transmission have been highlighted. One of these problems is the fault current that appears when a fault occurs in the transmission line. If the fault current flows in the transmission line, it has a serious adverse effect on the rectifier stage, inverter stage and transmission line load. This makes the transmission technology less reliable and can lead to secondary problems such as fire. Therefore, fault current must be managed safely. DC circuit breaker technology has been proposed to solve this problem. However, conventional technologies generally do not take into account the effects of fault current on the transmission line, and their efficiency is relatively low. The purpose of this study is to introduce an improved DC circuit breaker that uses a blocking inductor to minimize the effect of fault current on the transmission line. It also uses a ground inductor to efficiently manage the LC resonant current and dissipate residual current. DC circuit breakers minimize adverse effects on external elements and transmission lines because the use of elements placed on each is distinct. All of these processes are precisely verified by conducting simulation under 200 MVA (±100 kV) conditions based on the VSC-based HVDC transmission link. In addition, the mechanism was explained by analyzing the simulation results to increase the reliability of the circuit in this paper.

Background and Objectives: The harmonization of recovery of consciousness and muscular function is important in emergence from anesthesia. Even if muscular function is recovered, tracheal extubation without adequate recovery of consciousness may increase the risk of respiratory complications. In particular, upper airway obstruction is one of the common respiratory complications and can sometimes be fatal. However, the association between the timing of sugammadex administration and the upper airway obstruction that can occur during awakening from anesthesia has rarely been studied. Materials and Methods: The medical records of 456 patients who had surgery under general endotracheal anesthesia (GETA) at the Haeundae Paik Hospital between October 2017 and July 2018 and who received intravenous sugammadex to reverse rocuronium-induced neuromuscular blockade were analyzed. The correlations between bispectral index (BIS) and minimum alveolar concentration (MAC) at the time of sugammadex administration, the incidence of complications, and the time to tracheal extubation were analyzed to investigate how different timings of sugammadex administration affected upper airway obstruction after tracheal extubation. Conclusions: The effect of BIS and the duration from anesthetic discontinuation to sugammadex administration on upper airway obstruction was not statistically significant. However, the odds ratio of complication rates with MAC < 0.3 compared with MAC ≥ 0.3 was 0.40 (95% confidence interval 0.20 to 0.81, p = 0.011), showing a statistically significant increase in risk with MAC ≥ 0.3 for upper airway obstruction.

PurposeThis study aimed to identify prognostic factors of neurological outcomes, including developmental delay, cerebral palsy and epilepsy in late-preterm and term infants with perinatal asphyxia.MethodsAll late-preterm and term infants with perinatal asphyxia or hypoxic-ischemic insults who admitted the neonatal intensive care unit of Inje University Sanggye Paik Hospital between 2006 and 2014 and were followed up for at least 2 years were included in this retrospective study. Abnormal neurological outcomes were defined as cerebral palsy, developmental delay and epilepsy.ResultsOf the 114 infants with perinatal asphyxia, 31 were lost to follow-up. Of the remaining 83 infants, 10 died, 56 had normal outcomes, and 17 had abnormal outcomes: 14 epilepsy (82.4%), 13 cerebral palsy (76.5%), 16 developmental delay (94.1%). Abnormal outcomes were significantly more frequent in infants with later onset seizure, clinical seizure, poor electroencephalography (EEG) background activity, lower Apgar score at 1 and 5 minutes and abnormal brain imaging (P

Purpose Acute care surgery (ACS) models have evolved worldwide over the last decade. However, South Korea has an established trauma system and does not consider the ACS model. This study compares the management and outcome of emergency cholecystectomy in the ACS model to those of traditional on-call attending surgeon model for emergency surgery. Methods Retrospectively collected data for patients who underwent emergency cholecystectomy from May 2013 to January 2015 was analyzed to compare data from a traditional on-call system (OCS) and ACS. Results One hundred and twenty-four patients were enrolled in the study (62 patients ACS vs. 62 patients OCS). Hospital stay (days) (ACS=4.29±2.49 vs. OCS=4.82±4.48, p=0.46) and stay in emergency room (minutes) (ACS=213.10±113.99 vs. OCS=241.10±150.73, p=0.20) did not differ significantly between groups. Operation time (minutes) was significantly shorter in the ACS than OCS group (389.97±215.21 vs. 566.35±290.14, p

A 76-year-old man with no notable medical history was scheduled for a robot-assisted radical prostatectomy. After the operation, he was given sugammadex. Two minutes later, ventricular premature contraction bigeminy began, followed by cardiac arrest. Cardiac arrest occurred three times and cardiopulmonary resuscitation was done. The patient recovered after the third cardiopulmonary resuscitation and was transferred to the intensive care unit. Coronary angiography was done on postoperative day 1. The patient was diagnosed with variant angina and discharged uneventfully on postoperative day 8.

Objectives. To evaluate the factors that limit post-cochlear implantation (CI) speech perception in prelingually deaf children. Methods. Patients with CI were divided into two groups according to Category of Auditory Performance (CAP) scores 3 years post-CI: the poor performance group (poor performance group, CAP scores≤4, n=41) and the good performance group (good performance group, CAP scores≥5, n=85). The distribution and contribution of the potential limiting factors related to post-CI speech perception was compared. Results. Perinatal problems, inner ear anomalies, narrow bony cochlear nerve canal (BCNC), and intraoperative problems was significantly higher in the poor performance group than the good performance group (P=0.010, P=0.003, P=0.001, and P=0.045, respectively). The mean number of limiting factors was significantly higher in the poor performance group (1.98±1.04) than the good performance group (1.25±1.11, P=0.001). The odds ratios for perinatal problems and narrow bony cochlear nerve canal in the poor performance group in comparison with the good performance group were 4.878 (95% confidence interval, 0.067 to 0.625; P=0.005) and 4.785 (95% confidence interval, 0.045 to 0.972; P=0.046). Conclusion. This study highlights the comprehensive prediction of speech perception after CI and provides otologic surgeons with useful information for individualized preoperative counseling of CI candidates.

Abstract Background This study investigated whether the prevalence, awareness, treatment, and control of hypertension and diabetes differed by residential areas. In addition, the rate of good hypertension or diabetes control was examined separately in men and women, and in urban and rural areas. Methods This study used Korea National Health and Nutrition Examination V (2010–2012) data, a nationwide cross-sectional survey of general South Korean population. Residential areas were categorized into urban and rural areas. To examine differences between the residential areas in terms of prevalence, awareness, treatment, and control of hypertension and diabetes we performed a multivariate logistic regression adjusting for age, body mass index, physical activity, alcohol use, smoking, marital status, monthly income, and educational level. To investigate control of hypertension or diabetes within each residential area, we performed a subgroup analysis in both urban and rural areas. Results The prevalence of hypertension is higher among men in urban areas than among those in rural areas (OR = 0.80; 95 % CI = 0.67–0.96, reference group = urban areas). However, the subgroups did not differ in terms of diabetes prevalence, awareness, treatment, and control. Regardless of both sex and residential area, participants in good control of their hypertension and diabetes were younger. Inequality in good control of hypertension was observed in men who lived in urban (≤Elementary school, OR 0.74, 95 % CI 0.60–0.92) and rural areas (≤Elementary school, OR 0.67, 95 % CI 0.46–0.99). Inequality in health status was found in women who resided in urban areas (≤Elementary school, OR 0.53, 95 % CI 0.37–0.75). Good control of diabetes also showed inequalities in health status for both men (≤Elementary school, OR 0.61, 95 % CI 0.40–0.94; Middle/High school, OR 0.69, 95 % CI 0.49–0.96) and women in urban areas (≤1 million won, OR 0.56, 95 % CI 0.33–0.93) (Reference group = ‘≥College’ for education and ‘>3 million’ Korean won for income). Conclusions After correction for individual socioeconomic status, differences by residential area were not observed. However, when the participants with good disease control were divided by region, inequality was confirmed in urban residents. Therefore, differentiated health policies to resolve individual and regional health inequalities are necessary.

There have been tremendous interests about the single molecule analysis using a sold-state nanopore. The solid-state nanopore can be fabricated either by drilling technique, or diffusion technique by using electron beam irradiations. The solid-state SiN nanopore device with electrical detection technique recently fabricated, however, the solid-state Au nanopore with optical detection technique can be better utilized as the next generation single molecule sensor. In this report, the nanometer size openings with its size less than 10 nm on the diffused membrane on the 200 nm Au pyramid were fabricated by using field emission scanning electron microscopy (FESEM) electron beam irradiations, transmission electron microscopy (TEM), etc. After the sample was being kept under a room environment for several months, several Au (111) clusters with ~6 nm diameter formed via Ostwald ripening are observed using a high resolution TEM imaging. The nanopore with Au nanoclusters on the diffused membrane can be utilized as an optical nanopore device. Keywords: Electron beam irradiation, Surface diffusion, Carbon contamination, Au cluster, Ostwald ripening

Background: Increasing evidence has shown that tumor initiation and growth are nourished by a small subpopulation of cancer stem cells (CSCs) within the tumor mass. CSCs are posited to be responsible for tumor maintenance, growth, distant metastasis, and relapse after curative operation. We examined the expression of CSC markers in paraffin-embedded tissue sections of hepatocellular carcinoma (HCC) and correlated the results with clinicopathologic characteristics. Methods: Immunohistochemical staining for the markers believed to be expressed in the CSCs, including epithelial cell adhesion molecule (EpCAM), keratin 19 (K19), CD133, and CD56, was performed in 82 HCC specimens. Results: EpCAM expression was observed in 56% of the HCCs (46/82) and K19 in 6% (5/82). EpCAM expression in HCC significantly correlated with elevated α-fetoprotein level, microvessel invasion of tumor cells, and high histologic grade. In addition, EpCAM expression significantly correlated with K19 expression. The overall survival and relapsefree survival rates in patients with EpCAM-expressing HCC were relatively lower than those in patients with EpCAM-negative HCC. All but two of the 82 HCCs were negative for CD133 and CD56, respectively. Conclusions: Our results suggest that HCCs expressing EpCAM are associated with unfavorable prognostic factors and have a more aggressive clinical course than those not expressing EpCAM. Further, the expression of either CD133 or CD56 in paraffin-embedded HCC tissues appears to be rare.

BackgroundType 2 diabetes is one of the most common diseases with devastating complications. However, genetic susceptibility of diabetic complications has not been clarified. The vitamin D endocrine system is related with calcification and lipolysis, insulin secretion, and may be associated with many complicated disease including diabetes and cardiovascular disease. Recent studies reported that single nucleotide polymorphisms of vitamin D receptor (VDR) gene were associated with diabetic complications.MethodsIn present study, we evaluated the association of BsmI polymorphism of VDR with diabetic complications in Korean diabetes patients. Total of 537 type 2 diabetic subjects from the Endocrinology Clinic of Chungbuk National University Hospital were investigated. Polymerase chain reaction-restriction fragment length polymorphism was used to test the genotype and allele frequency of BsmI (rs1544410; BB, Bb, bb) polymorphisms.ResultsMean age was 62.44±10.64 years and mean disease duration was 13.65±7.39 years. Patients with B allele (BB or Bb) was significantly associated with lower risk of diabetic retinopathy (severe non-proliferative diabetic retinopathy or proliferative retinopathy; 7.4%, 5/68) compared with patients without B allele (bb; 17.3%, 81/469; P=0.035). This association was also significant after adjusting for hemoglobin A1c level, body mass index, age, sex, and diabetes mellitus duration, concurrent dyslipidemia and hypertension (odds ratio, 2.99; 95% confidence interval, 1.08 to 8.29; P=0.035) in logistic regression analysis.ConclusionOur findings suggest that B allele of Bsm1 polymorphism in VDR gene is associated with lower risk of diabetic retinopathy in type 2 diabetic patients. Bsm1 genotype could be used as a susceptibility marker to predict the risk of diabetes complication.

Blue light is an important environmental factor that induces mushroom growth and morphological changes. In this study, after confirming the morphological difference between Lentinula edodes (LE) under blue light condition (BL) and lightless condition (LL), the increase and decrease in LE protein and the expression of RNA of each protein were confirmed under each condition. LE specimens grown in BL and LL were identified by 253 spots in BL through 2D electrophoresis and LC-MSMS analysis, and 22 types of proteins were identified. It was confirmed that 14 types of proteins showed reduced expression in BL compared to LL. On the other hand, eight kinds of proteins with increased expression in blue light compared to LL were identified. As a result of confirming the difference from the expression pattern in 2D electrophoresis through Quantitative Real-Time PCR, it was confirmed that the expression pattern of the two proteins showed a difference. Therefore, this study will be a key study on the changes in mushroom morphology induced by blue light and the proteins that induce it.

Switch/sucrose non-fermentable (SWI/SNF)-related matrix-associated actin-dependent regulator of chromatin (SMARC) subfamily B member 1 (SMARCB1) is a core subunit of the switch/sucrose non-fermentable (SWI/SNF) complex, one of the adenosine triphosphate (ATP)-dependent chromatin remodeler complexes. The unique role of SMARCB1 has been reported in various cellular contexts. Here, we focused on the general role of the ubiquitous expression of SMARCB1 in a normal cell state. We selected ARPE19 (human primary retinal pigment epithelium) and IMR90 (from human fetal lung fibroblasts) cell lines as they have completely different contexts. Furthermore, although these cell lines have been immortalized, they are relatively close to normal human cells. The loss of SMARCB1 in ARPE19 and IMR90 cells reduced cell cycle progression via the upregulation of P21. Transcriptome analysis followed by SMARCB1 knockdown in both cell lines revealed that SMARCB1 was not only involved in cell maintenance but also conferred immunomodulation. Of note, SMARCB1 bound to interleukin (IL) 6 promoter in a steady state and dissociated in an active immune response state, suggesting that SMARCB1 was a direct repressor of IL6, which was further confirmed via loss- and gain-of-function studies. Taken together, we demonstrated that SMARCB1 is a critical gatekeeper molecule of the cell cycle and immune response.

In this work, we have investigated the role of high-energy ball milling (HEBM) on the evolution of microstructure, thermal, and wetting properties of an Sn-0.7Cu alloy. We ball-milled the constituent Sn and Cu powders in eutectic composition for 45 h. The microstructural studies were carried out using optical and scanning electron microscopy. The melting behavior of the powder was examined using differential scanning calorimetry (DSC). We observed a considerable depression in the melting point of the Sn-0.7Cu alloy (≈7 °C) as compared to standard cast Sn-0.7Cu alloys. The resultant crystallite size and lattice strain of the ball-milled Sn-0.7Cu alloy were 76 nm and 1.87%, respectively. The solderability of the Sn-0.7Cu alloy was also improved with the milling time, due to the basic processes occurring during the HEBM.

SIRT6 is involved in various cellular signaling pathways including those involved in tumorigenesis in association with β-catenin. However, the role of SIRT6 in tumorigenesis has been controversially reported and the studies on the role of SIRT6 in ovarian cancers is limited. In this study, we evaluated the expression and roles of SIRT6 in conjunction with the expression of active β-catenin in 104 human ovarian carcinomas and ovarian cancer cells. In human ovarian carcinomas, the expressions of SIRT6 and active β-catenin were associated with higher tumor stage, higher histologic grade, and platinum-resistance. Moreover, nuclear expression of SIRT6 (104 ovarian carcinomas; P = 0.010, 63 high-grade serous carcinomas; P = 0.040), and activated β-catenin (104 ovarian carcinomas; P = 0.013, 63 high-grade serous carcinomas; P = 0.005) were independent indicators of shorter overall survival of ovarian carcinoma patients in multivariate analysis. In OVCAR3 and OVCAR5 ovarian cancer cells, knock-down of SIRT6 significantly inhibited the migration and invasion of cells, but did not inhibit the proliferation of cells. SIRT6-mediated invasiveness of ovarian cancer cells was associated with the expression of epithelial-to-mesenchymal transition-related signaling molecules such as snail, vimentin, N-cadherin, E-cadherin, and activated β-catenin. Especially, SIRT6-mediated increase of invasiveness and activation of epithelial-to-mesenchymal transition signaling was attenuated by knock-down of β-catenin. In conclusion, this study suggests that SIRT6-β-catenin signaling is involved in the epithelial-to-mesenchymal transition of ovarian cancer cells, and the expression of SIRT6 and active β-catenin might be used as indicators of poor prognosis of ovarian carcinoma patients. In addition, our results suggest that SIRT6-β-catenin signaling might be a new therapeutic target of ovarian carcinomas.

A novel nanocrystal system of montelukast (MTK) was designed to improve the transdermal delivery, while ensuring chemical stability of the labile compound. MTK nanocrystal suspension was fabricated using acid-base neutralization and ultra-sonication technique and was characterized as follows: approximately 100 nm in size, globular shape, and amorphous state. The embedding of MTK nanocrystals into xanthan gum-based hydrogel caused little changes in the size, shape, and crystalline state of the nanocrystal. The in vitro drug release profile from the nanocrystal hydrogel was comparable to that of the conventional hydrogel because of the rapid dissolution pattern of the drug nanocrystals. The drug degradation under visible exposure (400−800 nm, 600,000 lux·h) was markedly reduced in case of nanocrystal hydrogel, yielding only 30% and 50% amount of cis-isomer and sulfoxide as the major degradation products, as compared to those of drug alkaline solution. Moreover, there was no marked pharmacokinetic difference between the nanocrystal and the conventional hydrogels, exhibiting equivalent extent and rate of drug absorption after topical administration in rats. Therefore, this novel nanocrystal system can be a potent tool for transdermal delivery of MTK in the treatment of chronic asthma or seasonal allergies, with better patient compliance, especially in children and elderly.

BACKGROUND: Poly(ADP-ribose) polymerase 1 (PARP1), γH2AX, BRCA1, and BRCA2 are conventional molecular indicators of DNA damage in cells and are often overexpressed in various cancers. In this study, we aimed, using immunohistochemical detection, whether the co-expression of PARP1, γH2AX, BRCA1, and BRCA2 in breast carcinoma (BCA) tissue can provide more reliable prediction of survival of BCA patients. MATERIALS AND METHODS: We investigated immunohistochemical expression and prognostic significance of the expression of PARP1, γH2AX, BRCA1, and BRCA2 in 192 cases of BCAs. RESULTS: The expression of these four molecules predicted earlier distant metastatic relapse, shorter overall survival (OS), and relapse-free survival (RFS) by univariate analysis. Multivariate analysis revealed the expression of PARP1, γH2AX, and BRCA2 as independent poor prognostic indicators of OS and RFS. In addition, the combined expressional pattern of BRCA1, BRCA2, PARP1, and γH2AX (CSbbph) was an additional independent prognostic predictor for OS (P < .001) and RFS (P < .001). The 10-year OS rate was 95% in the CSbbph-low (CSbbph scores 0 and 1) subgroup, but that was only 35% in the CSbbph-high (CSbbph score 4) subgroup. CONCLUSION: This study has demonstrated that the individual and combined expression patterns of PARP1, γH2AX, BRCA1, and BRCA2 could be helpful in determining an accurate prognosis for BCA patients and for the selection of BCA patients who could potentially benefit from anti-PARP1 therapy with a combination of genotoxic chemotherapeutic agents.

Purpose: The aim of this study is to investigate the clinical characteristics and epidemiology of stab wound in a single center for 5 years. Methods: Eighty-seven patients visited the emergency room with stab wounds between March 2008 and October 2013. Patient demographics, location of the wound, injured internal organ, and clinical parameters were reviewed. Results: Among eighty seven patients, 59 were male, and the mean age was 45.6 years old (range, 18∼85 years old). The most common age group was fifth and sixth decades. The most common cause of stab injury was self-infliction (32 cases), followed by violence (31 cases) and accident (23 cases). Self-infliction injuries were associated with underlying psychological problems in 20 patients. The most common injured sites were abdomen (48 cases), followed by thorax (20 cases) and neck (12 cases). Emergent exploration was required in 37 patients. Four patients (4.6%) were dead due to hypovolemic shock after injury of the thorax (lung) or neck (transection of carotid artery and transection of trachea). The length of hospital stay was 3 days (0∼6.5 days) and the injury severity score (ISS) was 4 points (1∼9 points). ISS was associated with the length of hospital stay (p

AIM:To assess the safety and cosmetic efficacy of a new multiple noncontinuous transepithelial puncture technique for tattooing a decompensated cornea.METHODS:It was anon-comparative clinical case series study.The study examines 33 eyes in 33 patients with total corneal opacity due to corneal decompensation, which developed following intraocular surgery.Corneal tattooing was performed using the multiple noncontinuous transepithelial puncture technique (i.e. pointage). The safety of this new surgical strategy was assessed by occurrence of adverse events for the follow-up period. The cosmetic efficacy was determined by the patient’s cosmetic satisfaction and independent observer’s opinion about patient appearance.RESULTS:Seven women and 26 men were included in the study. The mean age was 46.4±17.5y (range:7-67). In total, 30 of 33 patients (91%) reported cosmetic satisfaction within the follow-up period. Only 3 patients (9%) required additional tattooing due to cosmetic unsatisfaction. Cosmetic outcomes were analyzed and classified as excellent or good in 13 (39%) and 17 (52%) patients, respectively. No serious adverse events developed, except delayed epithelial healing in 3 cases.CONCLUSION:The cosmetic outcomes of the multiple noncontinuous transepithelial puncture technique for corneal tattooing were good. The safety of this method is higher than conventional procedures. This new procedure also provides improved cost-effectiveness and safety over current corneal tattooing techniques.

Global energy consumption has been highly dependent on fossil fuels which cause severe climate change and, therefore, the exploration of new technologies to produce effective renewable energy plays an important role in the world. Pressure-retarded osmosis (PRO) is one of the promising candidates to reduce the reliance on fossil fuels by harnessing energy from the salinity gradient between seawater and fresh water. In PRO, water is transported though a semi-permeable membrane from a low-concentrated feed solution to a high-concentrated draw solution. The increased volumetric water flow then runs a hydro-turbine to generate power. PRO technology has rapidly improved in recent years; however, the commercial-scale PRO plant is yet to be developed. In this context, recent developments on the PRO process are reviewed in terms of mathematical models, membrane modules, process designs, numerical works, and fouling and cleaning. In addition, the research requirements to accelerate PRO commercialization are discussed. It is expected that this article can help comprehensively understand the PRO process and thereby provide essential information to activate further research and development.

Senescence secretome was recently reported to promote liver cancer in an obese mouse model. Steatohepatitic hepatocellular carcinoma (SH-HCC), a new variant of HCC, has been found in metabolic syndrome patients, and pericellular fibrosis, a characteristic feature of SH-HCC, suggests that alteration of the tumor stroma might play an important role in SH-HCC development. Clinicopathological characteristics and tumor stroma showing senescence and senescence-associated secretory phenotype (SASP) were investigated in 21 SH-HCCs and 34 conventional HCCs (C-HCCs). The expression of α-smooth muscle actin (α-SMA), p21Waf1/Cif1, γ-H2AX, and IL-6 was investigated by immunohistochemistry or immunofluorescence. SH-HCCs were associated with older age, higher body mass index, and a higher incidence of metabolic syndrome, compared to C-HCC (P

The functional role of Langerhans cells (LCs) in ocular surface inflammation and nerve damage in dry eye (DE) disease has yet to be determined. This study was performed to investigate this relationship through both clinical study on DE patients and in vivo mouse models with induced DE disease. In a cross-sectional case-control study (54 eyes of DE patients; 34 eyes of control patients), average cell density, area, and process length of LCs were measured using confocal microscopy. Data were analyzed to determine whether changes in LCs are correlated with subbasal nerve plexus (SNP) parameters (nerve density, beading, and tortuosity). In DE patients, SNP density marginally decreased and nerve beading and tortuosity were significantly increased compared to the control group. The total number of LCs significantly increased in DE patients, and some LCs with elongated processes were found to be attached to nerve fibers. Interestingly, nerve loss and deformation were correlated with inactivation of LCs. In an in vivo experiment to elucidate the role of LCs in ocular surface inflammation and corneal nerve loss, we used a genetically modified mouse model (CD207-DTR) that reduced the population of CD207 (Langerin) expressing cells by injection of diphtheria toxin. In CD207-depleted mice with DE disease (CD207-dDTR+DE), corneal nerves in the central region were significantly decreased, an effect that was not observed in wild-type (WT)+DE mice. In CD207-dDTR+DE mice, infiltration of CD4+, CD19+, CD45+, and CD11b+ cells into the ocular surface was increased, as confirmed by flow cytometry. Increased IL-17 and IFN-γ mRNA levels, and decreased expression of neurotrophic factors and neurotransmitters, were also found in the CD207-dDTR+DE mice. These data support a functional role for LCs in negatively regulating ocular surface inflammation and exhibiting a neuroprotective function in DE disease.

Background: Roles of immune reaction and toll-like receptor-4 (TLR-4) have widely been established in the pathogenesis of alcoholic liver disease (ALD). Methods: We evaluated the biologic efficacy of Korean Red Ginseng (KRG), urushiol, and probiotics (Lactobacillus rhamnosus R0011 and Lactobacillus acidophilus R0052) in mouse models of ALD. Sixty C57BL/6 mice were equally divided into six feeding groups for 10 weeks: normal diet, alcohol, control, alcohol + KRG, alcohol + urushiol, and alcohol + probiotics. Alcohol was administered via a Lieber–DeCarli liquid diet containing 10% alcohol. TLR-4 expression, proinflammatory cytokines, and histology, as well as the results of liver function tests were evaluated and compared. Results: No between-group differences were observed with regard to liver function. TLR-4 levels were significantly lower in the KRG, urushiol, and probiotics groups than in the alcohol group (0.37 ± 0.06 ng/mL, 0.39 ± 0.12 ng/mL, and 0.33 ± 0.07 ng/mL, respectively, vs. 0.88 ± 0.31 ng/mL; p

A novel polymeric microsphere (MS) containing micronized triamcinolone acetonide (TA) in a crystalline state was structured to provide extended drug retention in joints after intra-articular (IA) injection. Microcrystals with a median diameter of 1.7 μm were prepared by ultra-sonication method, and incorporated into poly(lactic-co-glycolic acid)/poly(lactic acid) (PLGA/PLA) MSs using spray-drying technique. Cross-sectional observation and X-ray diffraction analysis showed that drug microcrystals were evenly embedded in the MSs, with a distinctive crystalline nature of TA. In vitro drug release from the novel MSs was markedly decelerated compared to those from the marketed crystalline suspension (Triam inj.®), or even 7.2 μm-sized TA crystals-loaded MSs. The novel system offered prolonged drug retention in rat joints, providing quantifiable TA remains over 28 days. Whereas, over 95% of IA TA was removed from joints within seven days, after injection of the marketed product. Systemic exposure of the steroidal compound was drastically decreased with the MSs, with

We have observed the high-temperature (T=300 K) photoluminescence (PL) spectra from free to Mn-related acceptor pair transitions in Ga1-xMnxN layers (where x≈0.2%–0.6%) grown on sapphire (0001) substrates using the plasma-enhanced molecular-beam epitaxy technique. Luminescence from an Mn acceptor level in Ga1-xMnxN layer with a low Mn content was observed at around E=3.08 eV in the PL spectra. When compared to the PL from undoped GaN, the excitation, temperature-dependent PL at E=3.08 eV provides convincing evidence for a neutral Mn acceptor-bound hole character. The binding energy of the Mn acceptor-bound holes of E=330 meV is in good agreement with an ionization energy of E=402 meV obtained using effective mass theory of shallow impurity states for the hydrogen model. In addition, analysis of the PL intensities of an acceptor-bound hole in a Ga1-xMnxN layer with x≈0.6% gave an activation energy of E=310 meV, which indicates that the acceptor-bound hole with a binding energy of E=310 meV was dissociated due to thermal quenching. [ABSTRACT FROM AUTHOR]

AIM: To compare the effect of topically administered and subconjunctivally injected bevacizumab on experimental corneal neovascularization in rats for two weeks after treatment.METHODS: Twenty-eight Sprague-Dawley rats were divided into four groups of 7 animals. Each corneal center of right eye was cauterized with silver/potassium nitrate for 8s. After corneal burning, bevacizumab (12.5mg/mL) was topically administered three times per day (TB group) for two weeks or subconjunctivally injected on days 2 and 4 after cauterization (0.02mL; SB group). As negative controls, rats received 0.9% saline topically three times per day (TS group) or subconjunctivally on days 2 and 4 (0.02mL; SS group). Digital photographs of the cornea were taken 1 and 2 weeks after treatment and analyzed to determine the area of cornea covered by neovascularization as the percentage of corneal neovascularization.RESULTS: One week after treatment, the percentage of corneal neovascularization was significantly lower in the TB and SB groups than in the TS and SS groups (all PPPCONCLUSION: Topically administered bevacizumab has longer standing anti-angiogenic effect than subconjunctivally injected bevacizumab in corneal neovascularization following chemical injury in rats.

Central venous catheterization (CVC) can be difficult, especially with pediatric patients in critical care. Accessing the subclavian vein (SCV) can cause serious complications, including pneumothorax, arterial puncture, and hemothorax. Recently, the ultrasonographic (USG) technique has gained popularity, but its efficiency is not yet confirmed. Subclavian venous catheterization (SCVC) through the supraclavicular approach (SCA) with USG or accessing the brachiocephalic vein through the infraclavicular approach (ICA) has been reported in the past. A useful technique is reported that involves the use of a 40 mm probe rather than the usual 25 mm probe in order to confirm the location of the needle while successfully performing subclavian venous catheterization in pediatric patients weighing 1.1 kg to 15.0 kg.

To compare a modified phacoemulsification tip with the established micro tip, in terms of temperature at the corneal wound, efficiency, and chatter events, using the Centurion® Vision system.Eighty porcine eyes were randomized into 4 groups: 1)sleeveless conventional 45D MiniFlared ABS® Kelman tip (1.1-mm incision); 2)sleeveless new modified 45D ABS® INTREPID® balanced tip(1.1-mm incision); 3) Kelman tip with own sleeve (2.2-mm incision); 4)Balanced tip with modified 4-rib sleeve (2.2-mm incision). Measurements were taken with 2 settings: longitudinal(power 40% and 70%) and torsional mode (power 40% and 100%). Peak temperatures were measured 0, 10, 30, and 60 seconds after continuous ultrasound power. For the efficiency test, porcine lens nuclei were formalin soaked and cut into 2.0 mm3 cubes. Efficiency and chatter were examined.In all longitudinal settings, the sleeveless groups(1 and 2) showed lower temperatures than the sleeved groups(3 and 4) (P = 0.003). In 100% torsional mode, groups 3 and 4 produced significantly different temperatures(37.13 ± 1.44 and 35.14 ± 0.54, respectively; P = 0.007).The efficiency, in a 100% power torsional setting, was13.52 ± 2.60 sec for group 4, and 44.45± 14.75 sec for group 3 (P

To differentiate smoking-related interstitial fibrosis (SRIF) from usual interstitial pneumonia (UIP) with emphysema on CT in combined pulmonary fibrosis and emphysema (CPFE) patients.This study was approved by the institutional review board and informed consent was waived. We included 65 patients who underwent lung biopsy under the suspicion of UIP pattern on HRCT, and after radiologic-pathologic correlation, they were divided into three groups: UIP without emphysema (n = 30), UIP with emphysema (n = 26), and SRIF (n = 9). The quantitative extent of emphysema in the entire lung was visually assessed and fibrotic patterns were qualitatively analyzed based on six characteristics (asymmetry, juxta-subpleural sparing, emphysema beside the honeycombing area, absence of ground grass attenuation/reticulation in honeycombing area, inhomogeneous honeycombing, and absence of honeycombing in the upper lobes). Kaplan-Meier analysis was used for survival analysis, and logistic regression with a receiver operating characteristic curve was used to predict the possibility of SRIF.In qualitative analysis of fibrotic patterns, SRIF tended to exhibit more than three of six fibrotic features, whereas UIP with emphysema demonstrated about two of these characteristics (p = 0.035). In addition, SRIF had a higher extent of emphysema than UIP with emphysema when they have same amount of fibrosis (p = 0.014). In patients with SRIF, 5-year survival rate was 85.7%, while it was 40.7% in UIP with emphysema patients (p = 0.035).Fibrotic CT patterns and survival rate differed between SRIF and UIP with emphysema among CPFE patients, which explains the variable prognosis of CPFE.

Purpose. To assess the effect of three-dimensional (3D) printed personalized moisture chamber spectacles (PMCS) on the periocular humidity. Methods. Facial computed tomography (CT) scanning was conducted on 10 normal subjects. PMCS was designed based on volume rendered CT images and produced using a 3D printer. Periocular humidity of PMCS and commercially available uniformed moisture chamber spectacles (UMCS) were measured for 30 minutes via microhydrometer. Results. The mean ambient humidity was 15.76±1.18%. The mean periocular humidity was 52.14±3.00% in PMCS and 37.67±8.97% in UMCS. The difference was significant (P

Fiber optic interferometers to sense various physical parameters including temperature, strain, pressure, and refractive index have been widely investigated. They can be categorized into four types: Fabry-Perot, Mach-Zehnder, Michelson, and Sagnac. In this paper, each type of interferometric sensor is reviewed in terms of operating principles, fabrication methods, and application fields. Some specific examples of recently reported interferometeric sensor technologies are presented in detail to show their large potential in practical applications. Some of the simple to fabricate but exceedingly effective Fabry-Perot interferometers, implemented in both extrinsic and intrinsic structures, are discussed. Also, a wide variety of Mach-Zehnder and Michelson interferometric sensors based on photonic crystal fibers are introduced along with their remarkable sensing performances. Finally, the simultaneous multi-parameter sensing capability of a pair of long period fiber grating (LPG) is presented in two types of structures; one is the Mach-Zehnder interferometer formed in a double cladding fiber and the other is the highly sensitive Sagnac interferometer cascaded with an LPG pair.

Hypertensive nephrosclerosis is usually associated with chronic hypertension, which increases the risk of progressive renal disease. Among the causes of malignant hypertension, thrombotic microangiopathy is complicated and is associated with renal dysfunction at the time of diagnosis. In this case, a young man with hypertension presented with renal failure and thrombocytopenia in the emergency department. This case emphasizes the importance of early recognition of renal failure and thrombocytopenia among patients with uncontrolled hypertension.