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Introduction: We evaluated whether preoperative carbohydrate drink would be able to decrease postoperative nausea and vomiting (PONV) and improve the quality of recovery (QoR) in diabetic patients undergoing total knee arthroplasty (TKA)., Methods: Eighty-two patients were randomized to either the intravenous (IV) Dextrose group (n = 41) or Oral carbohydrate (CHO) group (n = 41). The IV Dextrose group received dextrose solution mixed with insulin while fasting, and the Oral CHO group received carbohydrate drinks preoperatively. PONV was assessed up to postoperative 36 hours, and QoR was assessed before surgery and on postoperative day (POD) 1. Blood glucose was measured from the morning of surgery until POD 1., Results: PONV scores were not different between the groups. Postoperative QoR scores were significantly higher in the Oral CHO group (median [interquartile range]; 160 [153 to 167]) than the IV Dextrose group (155 [147 to 159]) (P = 0.009), but the difference did not meet the minimal clinically important difference. Blood glucose was comparable between the groups., Discussion: Preoperative CHO drink did not reduce PONV in diabetic patients after total knee arthroplasty. A statistically significant but clinically questionable improvement in the QoR was seen in the Oral CHO group. However, preoperative CHO drink did not increase hyperglycemia, which suggests that it may be a safe component of perioperative care in diabetic patients., (Copyright © 2020 by the American Academy of Orthopaedic Surgeons.)

Computerized registration between maxillofacial cone-beam computed tomography (CT) images and a scanned dental model is an essential prerequisite for surgical planning for dental implants or orthognathic surgery. We propose a novel method that performs fully automatic registration between a cone-beam CT image and an optically scanned model. To build a robust and automatic initial registration method, deep pose regression neural networks are applied in a reduced domain (i.e., two-dimensional image). Subsequently, fine registration is performed using optimal clusters. A majority voting system achieves globally optimal transformations while each cluster attempts to optimize local transformation parameters. The coherency of clusters determines their candidacy for the optimal cluster set. The outlying regions in the iso-surface are effectively removed based on the consensus among the optimal clusters. The accuracy of registration is evaluated based on the Euclidean distance of 10 landmarks on a scanned model, which have been annotated by experts in the field. The experiments show that the registration accuracy of the proposed method, measured based on the landmark distance, outperforms the best performing existing method by 33.09%. In addition to achieving high accuracy, our proposed method neither requires human interactions nor priors (e.g., iso-surface extraction). The primary significance of our study is twofold: 1) the employment of lightweight neural networks, which indicates the applicability of neural networks in extracting pose cues that can be easily obtained and 2) the introduction of an optimal cluster-based registration method that can avoid metal artifacts during the matching procedures.

Many technologies have been developed for breast reconstruction after lumpectomy. Although the technologies achieved promising success in clinical, there are still many shortages hanging over and trouble the researchers. Tissue engineering technology was introduced to plastic surgery that gave a light to lumpectomy patients in breast reconstruction. The unexpected absorption rate, resulting from limited vascularization and low cell survival rate, is a major factor that leads to unsatisfactory results for the previous studies in our lab. In the study, the laminin-modified alginate synthesized by a new method of low concertation of sodium periodate would be mixed with ADSCs and Rg1 in the medium; and then sprayed into a calcium chloride (CaCl 2 ) solution to prepare into microsphere (abbreviated as ADSC-G-LAMS) by bio-electrospray with a power syringe for the mass production and smaller bead size. The developed ADSC-G-LAMS microspheres had the diameter of 232 ± 42 μm. Sustained-release of the Rg1 retained its biological activity. WST-1, live/dead staining, and chromosome aberration assay were evaluated to confirm the safety of the microspheres. In in vivo study, ADSC-G-LAMS microspheres combined with autologous adipocytes were transplanted into the dorsum of rats by subcutaneous injection. The efficacy was investigated by H&E and immunofluorescence staining. The results showed that the bioactive ADSC-G-LAMS microspheres could integrate well into the host adipose tissue with an adequate rate of angiogenesis by constantly releasing Rg1 to enhance the ADSC or adipocyte survival rate to join tissue growth and repair with adipogenesis for breast reconstruction after lumpectomy., (© 2020 The Authors. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Objective: To investigate the dental phenotypes and treatment modalities (Tx- Mod) in Korean patients with Parry-Romberg syndrome (PRS) using longitudinal data., Methods: The samples consisted of 10 PRS patients, who were treated and/or followed-up at Seoul National University Dental Hospital between 1998 and 2019. Using a novel PRS severity index based on the numbers of the atrophy-involved area and asymmetry-involved item, we classified them into mild (n = 3), moderate (n = 2), and severe (n = 5). Dental phenotypes, including congenitally missing tooth (Con-Missing-Tooth), microdontia, tooth with short root (Short-Root), tooth with dilacerated root, and delayed eruption/impacted tooth, were investigated along with Tx-Mod., Results: The side of occurrence of all dental phenotypes showed 100% concordance with the side of PRS involvement. The most two common dental phenotypes were Con-Missing- Tooth and Short-Root (n = 29 and n = 17 in six patients). The sums of the average number of Con-Missing-Tooth and Short-Root increased from mild PRS to moderate PRS and severe PRS cases (1.0, 6.0, and 6.2). In terms of Tx- Mod, growth observation due to mild atrophy, fixed orthodontic treatment, and grafting were used for mild PRS cases. Tx-Mod for moderate PRS cases involved growth observation for surgery due to an early age at the initial visit. For severe PRS cases, diverse Tx-Mod combinations including unilateral functional appliance, fixed orthodontic treatment, growth observation, grafting, and orthognathic surgery were used., Conclusions: The novel PRS severity index may be useful to provide primary data for individualized diagnosis and treatment planning for PRS patients.

Objective: To investigate the distribution, side involvement, phenotype, and associated anomalies of Korean patients with craniofacial clefts (CFC)., Methods: The samples consisted of 38 CFC patients, who were treated at Seoul National University Dental Hospital during 1998-2018. The Tessier cleft type, sex, side involvement, phenotype, and associated anomalies were investigated using nonparametric statistical analysis., Results: The three most common types were #7 cleft, followed by #0 cleft and #14 cleft. There was no difference between the frequency of male and female. Patients with #0 cleft exhibited nasal deformity, bony defect, and missing teeth in the premaxilla, midline cleft lip, and eye problems. A patient with #3 cleft (unilateral type) exhibited bilateral cleft lip and alveolus. All patients with #4 cleft were the bilateral type, including a combination of #3 and #4 clefts, and had multiple missing teeth. A patient with #5 cleft (unilateral type) had a posterior openbite. In patients with #7 cleft, the unilateral type was more prevalent than the bilateral type (87.0% vs. 13.0%, p < 0.001). Sixteen patients showed hemifacial microsomia (HFM), Goldenhar syndrome, and unilateral cleft lip and palate (UCLP). There was a significant match in the side involvement of #7 cleft and HFM (87.5%, p < 0.01). Patients with #14 cleft had plagiocephaly, UCLP, or hyperterorbitism. A patient with #30 cleft exhibited tongue tie and missing tooth., Conclusions: Due to the diverse associated craniofacial anomalies in patients with CFC, a multidisciplinary approach involving a well-experienced cooperative team is mandatory for these patients.

Recently, 3D concrete printing has progressed rapidly in the construction industry. However, this technique still contains several factors that influence the buildability and mechanical properties of the printed concrete. Therefore, this study investigated the effects of the nozzle speed, the interlayer interval time, the rotations per minute (RPMs) of the screw in the 3D printing device, and the presence of lateral supports on the buildability of 3D concrete printing. In addition, this paper presents the results of the mechanical properties, including the compressive, splitting tensile, and flexural tensile strengths of 3D printed concrete. The buildability of 3D printed structures was improved with an extended interlayer interval time of up to 300 s. The printing processes were interrupted because of tearing of concrete filaments, which was related to excessive RPMs of the mixing screw. The test results also showed that a lateral support with a wide contact surface could improve the resistance to buckling failure for 3D printed structures. The test results of the mechanical properties of the 3D printed concrete specimens indicated that the compressive, splitting tensile, and flexural tensile strengths significantly depended on the bonding behavior at the interlayers of the printed specimens. In addition, although metal laths were expected to improve the tensile strength of the printed specimens, they adversely affected the tensile performance due to weak bonding between the reinforcements and concrete filaments.

Nitidine chloride (NC) was recently reported to exhibit a wide range of pharmacological properties for several diseases, including cancer. Here we report for the first time that NC is a potential therapeutic agent for mucoepidermoid carcinoma (MEC) occurring in the head and neck because it suppresses X chromosome-linked inhibitor of apoptosis protein (XIAP) in human MEC in vitro and in vivo. The antitumor effects of NC were evaluated by trypan blue exclusion assay, western blotting, live/dead assay, 4',6-diamidino-2-phenylindole (DAPI) staining, human apoptosis antibody array, immunofluorescence staining, immunohistochemistry, small interfering RNA assay, transient transfection of XIAP overexpression vector, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and histopathological examination of organs. NC inhibited cell viability and induced caspase-dependent apoptosis in vitro. A human apoptosis antibody array assay showed that XIAP is suppressed by NC treatment. XIAP was overexpressed in oral squamous cell carcinoma (OSCC) tissues that arose from the head and neck, and high XIAP expression was correlated with poor prognosis in OSCC patients. XIAP depletion significantly increased apoptosis, and ectopic XIAP overexpression attenuated the apoptosis induced by NC treatment. NC suppressed tumor growth in vivo at a dosage of 5 mg/kg/day. The number of TUNEL-positive cells increased and the protein expression of XIAP was consistently downregulated in NC-treated tumor tissues. In addition, NC caused no histopathological changes in the liver or kidney. These findings provide new insights into the mechanism of action underlying the anticancer effects of NC and demonstrate that NC is a promising therapeutic agent for the treatment of human MEC of the head and neck. KEY MESSAGES: • Nitidine chloride induces caspase-dependent apoptosis in MEC of the head and neck. • High XIAP expression correlates with poor prognosis of OSCC patients. • Nitidine chloride suppresses tumor growth in vivo without any systemic toxicities. • Targeting XIAP is a novel chemotherapeutic strategy for MEC of the head and neck.

Objective: To investigate the treatment modalities (Tx-Mods) for patients with unilateral hemifacial microsomia (UHFM) according to Pruzansky-Kaban types and growth stages., Methods: The samples consisted of 82 Korean UHFM patients. Tx-Mods were defined as follows: Tx-Mod-1, growth observation due to mild facial asymmetry; Tx-Mod-2, unilateral functional appliance; Tx- Mod-3, fixed orthodontic treatment; Tx-Mod-4, growth observation due to a definite need for surgical intervention; Tx-Mod-5, unilateral mandibular or bimaxillary distraction osteogenesis (DO); Tx-Mod-6, maxillary fixation using LeFort I osteotomy and mandibular DO/sagittal split ramus osteotomy; Tx- Mod-7, orthognathic surgery; and Tx-Mod-8, costochondral grafting. The type and frequency of Tx-Mod, the number of patients who underwent surgical procedures, and the number of surgeries that each patient underwent, were investigated., Results: The degree of invasiveness and complexity of Tx-Mod increased, with an increase in treatment stage and Pruzansky-Kaban type (initial < final; [I, IIa] < [IIb, III], all p < 0.001). The percentage of patients who underwent surgical procedures increased up to 4.2 times, with an increase in the Pruzansky-Kaban type (I, 24.1%; IIa, 47.1%; IIb, 84.4%; III, 100%; p < 0.001). However, the mean number of surgical procedures that each patient underwent showed a tendency of increase according to the Pruzansky-Kaban types (I, n = 1.1; IIa, n = 1.5; IIb, n = 1.6; III, n = 2.3; p > 0.05)., Conclusions: These findings might be used as basic guidelines for successful treatment planning and prognosis prediction in UHFM patients.

Background: Despite being one of the leading cancer types in the world, the diagnosis of oral cancer and its suitable therapeutic options remain limited. This study aims to investigate the single and chemosensitizing effects of TW-37, a BH3 mimetic in oral cancer, on human oral cancer cell lines., Methods: We assessed the single and chemosensitizing effects of TW-37 in vitro using trypan blue exclusion assay, Western blotting, DAPI staining, Annexin V-FITC/PI double staining, and quantitative real-time PCR. Mcl-1 overexpression models were established by transforming vector and transient transfection was performed to test for apoptosis., Results: TW-37 enhanced the cytotoxicity of human oral cancer cell lines by inducing caspase-dependent apoptosis, which correlates with the reduction of the myeloid cell leukemia-1 (Mcl-1) expression via transcriptional and post-translational regulation. The ectopic expression of Mcl-1 partially attenuated the apoptosis-inducing capacity of TW-37 in human oral cancer cell lines. Besides, TW-37 decreased the phosphorylation of signal transducer and activator of transcription 3 (STAT3) at Tyr 705 and nuclear translocation in human oral cancer cell lines at the early time points. Furthermore, TW-37 potentiated chemosusceptibility of cryptotanshinone in human oral cancer cell lines by suppressing STAT3-Mcl-1 signaling compared with either TW-37 or cryptotanshinone alone, resulting in potent apoptosis., Conclusions: This study not only unravels the single and chemosensitizing effects of TW-37 for treatment of human oral cancer but also highlights the likelihood of TW-37 as a good therapeutic strategy to enhance the prognosis of patients with oral cancer in the future., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Background: Although several factors exacerbate osteonecrosis of the femoral head (ONFH), little is known about whether pelvic sagittal parameters are associated with a greater risk of ONFH progression., Questions/purposes: The purpose of this study was to investigate the association between pelvic sagittal parameters and disease progression (collapse of the femoral head) in patients with nontraumatic ONFH., Methods: From March 2010 through December 2016, we saw 401 patients with unilateral ONFH diagnosed at an outpatient clinic using plain radiography and MRI that were retrospectively reviewed. Of those, 276 patients met our inclusion criteria: Association Research Circulation Osseous (ARCO) Stage I or II nontraumatic unilateral ONFH without femoral head collapse, older than 18 years, and no prior surgical treatment. In all, 74% (203 of 276) of hips had complete follow-up (clinical and radiographic) at a minimum of 2 years. The pelvic sagittal parameters (pelvic incidence, pelvic tilt, and sacral slope) of all patients were measured with standing radiographs by two observers. Progression of disease and potential collapse of the femoral head of all patients (ARCO Stage ≥ III) was examined using radiography every 2 to 3 months after the first outpatient clinic visit. If patients with intractable pain associated with collapse of the femoral head did not respond to nonoperative treatment, THA was performed during the follow-up period. The patients were divided into two groups for comparison: those whose femoral head collapsed within 12 months (rapid progression group) and those whose femoral head did not collapse (nonrapid progression group). The rapid progression group consisted of 49 men and 55 women with a mean age of 55 years; the nonrapid progression group consisted of 60 men and 39 women with a mean age of 56 years. Factors such as age, sex, BMI, size of necrotic lesions, location of necrosis, necrosis risk factor associated with the rapid progression of disease were analyzed using an exploratory univariate analysis followed by a multivariate analysis., Results: Pelvic incidence (53° ± 9° versus 49° ± 7°; p < 0.01) and sacral slope (38° ± 9° versus 33° ± 7°; p < 0.01) were greater in the rapid progression group than in the non-rapid progression group. After accounting for potentially confounding variables like age, sex, BMI, size of necrotic lesions, location of necrosis, and necrosis risk factors, the only variable we found that was independently associated with more rapid disease progression was high (> 55°) pelvic incidence (odds ratio, 0.95 [95% CI 0.91 to 0.99]; p = 0.03)., Conclusions: After controlling for potential confounders such as age, sex, BMI, size of necrotic lesions, location of necrosis, and necrosis risk factors, we found that a high pelvic incidence was associated with a greater likelihood of femoral head collapse in patients with nontraumatic ONFH. Assessing pelvic sagittal parameters in patients with early nontraumatic ONFH may help anticipate which patients are at risk for femoral head collapse, but future prospective studies are needed to confirm these findings., Level of Evidence: Level III, therapeutic study.

Endovascular thrombectomy revolutionized the treatment of acute ischemic stroke. Nevertheless, access to endovascular thrombectomy is limited in many parts of the world. Asia holds 60% of the world's population and its countries carry some of the highest stroke disease burden. To understand the availability of endovascular thrombectomy and intravenous thrombolysis in this region, we interviewed stroke neurologists and neuro-interventionists of 19 Asian countries, and found a large disparity in access to endovascular thrombectomy and intravenous thrombolysis between high- and low-income countries. Lack of neuro-interventionists, comprehensive stroke units, stroke triage systems and high treatment cost are the major obstacles to wider accessibility of endovascular thrombectomy, especially among developing countries. The potential solutions to provide equitable access to stroke revascularization therapy are discussed.

Oridonin, an active diterpenoid isolated from Rabdosia rubescens, has been reported to exhibit anticancer activities in several tumors. The aim of the present study was to investigate the anticancer effects and molecular mechanisms of oridonin in mucoepidermoid carcinoma (MEC). Treatment with oridonin induced the apoptosis of MC‑3 and YD‑15 cell and inhibited the expression of myeloid cell leukemia‑1 (MCL‑1) through the regulation of the protein level through post‑translational regulation in these cell lines. Oridonin significantly increased the expression level of truncated Bid (t‑Bid) as a downstream target of MCL‑1 and subsequently decreased the mitochondrial membrane potential. The ectopic expression of MCL‑1 protein was sufficient to reverse the induction of apoptosis and the increased t‑Bid expression induced by oridonin in both cell lines. Taken together, these results suggest that oridonin exerts an apoptotic effect through the modulation of MCL‑1 and t‑Bid in human MEC cell lines and may thus be a potential anticancer drug candidate for the treatment of human MEC.

Despite the improvement in clinical outcome with 13-cis-retinoic acid (13-cisRA) + anti-GD2 antibody + cytokine immunotherapy given in first response ~40% of high-risk neuroblastoma patients die of recurrent disease. MYCN genomic amplification is a biomarker of aggressive tumors in the childhood cancer neuroblastoma. MYCN expression is downregulated by 13-cisRA, a differentiating agent that is a component of neuroblastoma therapy. Although MYC amplification is rare in neuroblastoma at diagnosis, we report transcriptional activation of MYC medicated by the transcription factor OCT4, functionally replacing MYCN in 13-cisRA-resistant progressive disease neuroblastoma in large panels of patient-derived cell lines and xenograft models. We identified novel OCT4-binding sites in the MYC promoter/enhancer region that regulated MYC expression via phosphorylation by MAPKAPK2 (MK2). OCT4 phosphorylation at the S111 residue by MK2 was upstream of MYC transcriptional activation. Expression of OCT4, MK2, and c-MYC was higher in progressive disease relative to pre-therapy neuroblastomas and was associated with inferior patient survival. OCT4 or MK2 knockdown decreased c-MYC expression and restored the sensitivity to 13-cisRA. In conclusion, we demonstrated that high c-MYC expression independent of genomic amplification is associated with disease progression in neuroblastoma. MK2-mediated OCT4 transcriptional activation is a novel mechanism for activating the MYC oncogene in progressive disease neuroblastoma that provides a therapeutic target.

Ultrahigh-performance concrete (UHPC) and high-strength concrete (HSC) are currently widely used because of their distinct superior properties. Thus, a comprehensive comparison of the flexural behavior of UHPC and HSC beams is presented in this study. Nine UHPC beams and three HSC beams were subjected to pure bending tests to investigate the effect of various reinforcement ratios and steel fiber volume contents on the cracking and failure patterns, load-deflection behavior, ductility, and flexural toughness of these beams. The addition of steel fibers in the UHPC improved the energy absorption capacity of the beams, causing the UHPC beams to fail via rebar fracture. The deflection and curvature ductility indices were determined and compared in this study. The ductility indices of the HSC beam tended to decrease sharply as the rebar ratio increased, whereas those of the UHPC beam did not show a clear trend with respect to the rebar ratio. In addition, a comparison between the results in this study and the results from previous studies was performed. In this study, the addition of steel fiber contents up to 1.5% in UHPC increased the load capacity, ductility, and flexural toughness of the UHPC beams, whereas the addition of a steel fiber content of 2.0% did not significantly increase the ductility or flexural toughness of the UHPC beams.

A single-beam acoustic trapping technique has been shown to be very useful for determining the invasiveness of suspended breast cancer cells in an acoustic trap with a manual calcium analysis method. However, for the rapid translation of the technology into the clinic, the development of an efficient/accurate analytical method is needed. We, therefore, develop a fully-automatic deep learning-based calcium image analysis algorithm for determining the invasiveness of suspended breast cancer cells using a single-beam acoustic trapping system. The algorithm allows to segment cells, find trapped cells, and quantify their calcium changes over time. For better segmentation of calcium fluorescent cells even with vague boundaries, a novel deep learning architecture with multi-scale/multi-channel convolution operations (MM-Net) is devised and constructed by a target inversion training method. The MM-Net outperforms other deep learning models in the cell segmentation. Also, a detection/quantification algorithm is developed and implemented to automatically determine the invasiveness of a trapped cell. For the evaluation of the algorithm, it is applied to quantify the invasiveness of breast cancer cells. The results show that the algorithm offers similar performance to the manual calcium analysis method for determining the invasiveness of cancer cells, suggesting that it may serve as a novel tool to automatically determine the invasiveness of cancer cells with high-efficiency., Competing Interests: The authors declare that there are no conflicts of interest related to this article., (© 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

Background: The relationship between smoking and osteoarthritis (OA) has not been investigated in a large-scale study. The aim of this study was to examine the relationship between smoking and knee OA in the elderly., Methods: This study included 5117 subjects aged >60 years who responded to questionnaires on their history of smoking and knee OA diagnosed by a physician taken from the Korean National Health and Nutritional Examination Survey (KNHANES-VI) 2013-2015. We classified all 5117 subjects into 2 groups (the OA group and non-OA group) and compared the demographics and characteristics between the 2 groups. A multivariate logistic regression analysis was conducted to investigate the possible association between knee OA and smoking., Results: The prevalence of current smoking in the OA group (5.1%) was significantly lower than in the non-OA group (14.6%; p < 0.001). Furthermore, the proportion of moderate smokers who smoked >10 cigarettes per day or heavy smokers who smoked >20 cigarettes per day was significantly higher in the non-OA group. In the multivariate analysis, current smoking history was a preventative factor for the prevalence of OA in a multivariate model that included age, sex, body mass index, waist circumference (OR: 0.752, 95% CI: 0.571-0.989, p = 0.042)., Conclusions: This large-scale national study highlights an inverse association between smoking and the prevalence of knee OA in the general Korean elder adult population, primarily in males. Further investigation of this relationship between smoking and knee OA is needed to determine smoking's specific mechanism of protection against knee OA., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Individual tooth segmentation from cone beam computed tomography (CBCT) images is an essential prerequisite for an anatomical understanding of orthodontic structures in several applications, such as tooth reformation planning and implant guide simulations. However, the presence of severe metal artifacts in CBCT images hinders the accurate segmentation of each individual tooth. In this study, we propose a neural network for pixel-wise labeling to exploit an instance segmentation framework that is robust to metal artifacts. Our method comprises of three steps: 1) image cropping and realignment by pose regressions, 2) metal-robust individual tooth detection, and 3) segmentation. We first extract the alignment information of the patient by pose regression neural networks to attain a volume-of-interest (VOI) region and realign the input image, which reduces the inter-overlapping area between tooth bounding boxes. Then, individual tooth regions are localized within a VOI realigned image using a convolutional detector. We improved the accuracy of the detector by employing non-maximum suppression and multiclass classification metrics in the region proposal network. Finally, we apply a convolutional neural network (CNN) to perform individual tooth segmentation by converting the pixel-wise labeling task to a distance regression task. Metal-intensive image augmentation is also employed for a robust segmentation of metal artifacts. The result shows that our proposed method outperforms other state-of-the-art methods, especially for teeth with metal artifacts. Our method demonstrated 5.68% and 30.30% better accuracy in the F1 score and aggregated Jaccard index, respectively, when compared to the best performing state-of-the-art algorithms. The major implication of the proposed method is two-fold: 1) an introduction of pose-aware VOI realignment followed by a robust tooth detection and 2) a metal-robust CNN framework for accurate tooth segmentation., Competing Interests: Declaration of competing interest None Declared., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: Coverage of the anterior spinal artery (ASA) ostia is a source of considerable consternation regarding flow diversion (FD) in vertebral artery (VA) aneurysms due to cord supply. The authors sought to assess the association between coverage of the ASA, posterior spinal artery (PSA), or lateral spinal artery (LSA) ostia when placing flow diverters in distal VAs and clinical outcomes, with emphasis on cord infarction., Methods: A multicenter retrospective study of 7 institutions in which VA aneurysms were treated with FD between 2011 and 2019 was performed. The authors evaluated the risk of ASA and PSA/LSA occlusion, associated thromboembolic complication, complications overall, aneurysm occlusion status, and functional outcome., Results: Sixty patients with 63 VA and posterior inferior cerebellar artery aneurysms treated with FD were identified. The median aneurysm diameter was 7 mm and fusiform type was the commonest morphology (42.9%). During a procedure, 1 (61.7%) or 2 (33.3%) flow diverters were placed. Complete occlusion was achieved in 71.9%. Symptomatic thromboembolic complications occurred in 7.4% of cases and intracranial hemorrhage in 10.0% of cases. The ASA and PSA/LSA were identified in 51 (80.9%) and 35 (55.6%) complications and covered by the flow diverter in 29 (56.9%) and 13 (37.1%) of the procedures, respectively. Patency after flow diverter coverage on last follow-up was 89.2% for ASA and 100% for PSA/LSA, not significantly different between covered and noncovered groups (p = 0.5 and p > 0.99, respectively). No complications arose from coverage., Conclusions: FD aneurysm treatment in the posterior circulation with coverage of ASA or PSA/LSA was not associated with higher rates of occlusion of these branches or any instances of cord infarction.

The thermal conductivity of concrete is a key factor for efficient energy consumption in concrete buildings because thermal conductivity plays a significant role in heat transfer through concrete walls. This study investigated the effects of replacing fine aggregates with coal bottom ash (CBA) and the influence of curing age on the thermal properties of high-strength concrete with a compressive strength exceeding 60 MPa. The different CBA aggregate contents included 25%, 50%, 75%, and 100%, and different curing ages included 28 and 56 days. For concrete containing CBA fine aggregate, the thermal and mechanical properties, including the unit weight, thermal conductivity, compressive strength, and ultrasonic velocity, were measured. The experimental results reveal that the unit weight and thermal conductivity of the CBA concrete were highly dependent on the CBA content. The unit weight, thermal conductivity, and compressive strength of the concrete decreased as the CBA content increased. Relationships between the thermal conductivity and the unit weight, thermal conductivity and compressive strength of the CBA concrete were proposed in the form of exponential functions. The equations proposed in this study provided predictions that were in good agreement with the test results. In addition, the test results show that there was an approximately linear relationship between the thermal conductivity and ultrasonic velocity of the CBA concrete., Competing Interests: The authors declare that they have no conflicts of interest regarding the publication of this manuscript.

Fibroblast-like transformation of retinal pigment epithelial (RPE) cells is a pathological feature of proliferative vitreoretinopathy (PVR) that may cause blindness. The effect of oxidative stress alone or together with transforming growth factor-beta 2 (TGF-β2) on epithelial-mesenchymal transformation (EMT) is not fully understood in RPE. TGF-β2 induced the upregulation EMT markers including α-smooth muscle actin (α-SMA), Snail, and Slug and downregulation of E-cadherin (E-cad) in ARPE-19 cells. Hydrogen peroxide (H 2 O 2 ) not only upregulated α-SMA but also enhanced the effect of TGF-β2 on the expression of Snail and Slug. The CXCL family of cytokines could be the mediators of EMT induced by H 2 O 2 and TGF-β2. H 2 O 2 induced CXCL1, that upregulated α-SMA and fibronectin. Both SB225002, an inhibitor of CXCR2, and antioxidant N-acetylcysteine suppressed the TGF-β2-induced EMT in ARPE-19 cells. Taken together, the results suggest that oxidative stress enhanced TGF-β2-induced EMT through the possible autocrine effect of CXCL1 on CXCR2 in ARPE-19 cells.

Objective: To investigate the distribution and phenotypes of hemifacial microsomia (HFM) and its association with other anomalies., Methods: This study included 249 Korean patients with HFM, whose charts, photographs, radiographs, and/or computed tomography scans acquired during 1998-2018 were available from Seoul National University Hospital and Dental Hospital. Prevalence according to sex, side involvement, degree of mandibular deformity, compensatory growth of the mandibular body, and Angle's classification, and its association with other anomalies were statistically analyzed., Results: Prevalence was not different between male and female patients (55.0% vs. 45.0%, p > 0.05). Unilateral HFM (UHFM) was more prevalent than bilateral HFM (BHFM) (86.3% vs. 13.7%, p < 0.001). Although distribution of the Pruzansky-Kaban types differed significantly in patients with UHFM (I, 53.0%; IIa, 18.6%; IIb, 24.7%; III, 3.7%; p < 0.001), no difference was observed in occurrence between the right and left sides (52.6% vs. 47.4%, p > 0.05). Among patients with BHFM, prevalence of different Pruzansky-Kaban types on the right and left sides was greater than that of the same type on both sides (67.6% vs. 32.4%, p < 0.05). Despite hypoplasia of the condyle/ramus complex, compensatory growth of the mandibular body on the ipsilateral side occurred in 35 patients (14.1%). Class I and II molar relationships were more prevalent than Class III molar relationships (93.2% vs. 6.8%, p < 0.001). Forty-eight patients (19.3%) had other anomalies, with 50.0% and 14.4% in the BHFM and UHFM groups ( p < 0.001)., Conclusions: Patients with HFM require individualized diagnosis and treatment planning because of diverse phenotypes and associations with other anomalies., Competing Interests: CONFLICTS OF INTEREST: No potential conflict of interest relevant to this article was reported., (© 2020 The Korean Association of Orthodontists.)

Microelectronic gas-sensor devices were developed for the detection of carbon monoxide (CO), nitrogen dioxides (NO 2 ), ammonia (NH 3 ) and formaldehyde (HCHO), and their gas-sensing characteristics in six different binary gas systems were examined using pattern-recognition methods. Four nanosized gas-sensing materials for these target gases, i.e., Pd-SnO 2 for CO, In 2 O 3 for NO X , Ru-WO 3 for NH 3 , and SnO 2 -ZnO for HCHO, were synthesized using a sol-gel method, and sensor devices were fabricated using a microsensor platform. Principal component analysis of the experimental data from the microelectromechanical systems gas-sensor arrays under exposure to single gases and their mixtures indicated that identification of each individual gas in the mixture was successful. Additionally, the gas-sensing behavior toward the mixed gas indicated that the traditional adsorption and desorption mechanism of the n-type metal oxide semiconductor (MOS) governs the sensing mechanism of the mixed gas systems.

Background: The aim of this study was to compare the clinical and radiologic outcomes of robot-assisted unicompartmental knee arthroplasty (UKA) to those of conventional UKA in Asian patients., Methods: Fifty-five patients underwent robot-assisted UKA and 57 patients underwent conventional UKA were assessed in this study. Preoperative and postoperative range of motion (ROM), American Knee Society (AKS) score, Western Ontario McMaster University Osteoarthritis Index scale score (WOMAC), and patellofemoral (PF) score values were compared between the two groups. The mechanical femorotibial angle (mFTA) and Kennedy zone were also measured. Coronal alignments of the femoral and tibial components and posterior slopes of the tibial component were compared. Additionally, polyethylene (PE) liner thicknesses were compared., Results: There was no significant difference between the two groups regarding postoperative ROM, AKS, WOMAC and PF score. Robot group showed fewer radiologic outliers in terms of mFTA and coronal alignment of tibial and femoral components (p = 0.022, 0.037, 0.003). The two groups showed significantly different PE liner thicknesses (8.4 ± 0.8 versus 8.8 ± 0.9, p = 0.035). Robot group was the only influencing factor for reducing radiologic outlier (postoperative mFTA) in multivariate model (odds ratio: 2.833, p = 0.037)., Conclusion: In this study, robot-assisted UKA had many advantages over conventional UKA, such as its ability to achieve precise implant insertion and reduce radiologic outliers. Although the clinical outcomes of robot-assisted UKA over a short-term follow-up period were not significantly different compared to those of conventional UKA, longer follow-up period is needed to determine whether the improved radiologic accuracy of the components in robotic-assisted UKA will lead to better clinical outcomes and improved long-term survival., Competing Interests: The authors have declared that no competing interests exist.

Nitidine chloride (NC), a natural, bioactive, phytochemical alkaloid derived from the roots of Zanthoxylum nitidum , has been reported to exhibit anti-tumor activity against various types of cancer. However, the potential therapeutic role of NC in human cervical cancer has not yet been studied. We are the first to report that NC acts as a potential apoptosis-inducing agent for human cervical cancer in vitro . NC treatment of human cervical cancer cell lines induced caspase-mediated apoptosis, thereby reducing cell viability. Phospho-kinase proteome profiling using a human phospho-kinase array revealed that NC treatment phosphorylated Checkpoint kinase 2 (Chk2) at Thr68, which activates Chk2 in both cell lines. We also found that NC significantly affected the p53/Bim signaling axis, which was accompanied by mitochondrial membrane depolarization and cytochrome c release from the mitochondria into the cytosol. In addition, NC profoundly increased phosphorylation of the histone variant H2AX at Ser139, a typical marker of DNA damage. Taken together, these results provide in vitro evidence that NC can increase Chk2 activation, thereby acting as an attractive cell death inducer for treatment of human cervical cancer., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2019 JCBN.)

Pseudolaric Acid B (PAB), diterpenoid isolated from the root bark of Pseudolarix kaempferi Gordon tree (Pinaceae), exhibits an anti-proliferative and apoptotic activity in various cancer cell lines but to date, the effects of PAB on head and neck cancer (HNC) cell lines remain to be elucidated. In this study, we showed that PAB significantly inhibited the viability and caspase-dependent apoptosis in HN22 cell line. PAB-induced apoptosis is through inducing death receptor 5 (DR5) together with the increase in the expression of cleaved caspase-8. It also inhibited the proliferations and induced apoptosis through DR5 in other three HNC cell lines (HSC3, Ca9.22, and HSC4). Extending our in vitro findings, we found that ethanol extract of Pseudolarix kaempferi (2.5 mg/kg/day) reduced tumor growth in a xenograft model bearing HN22 cell line without any change in body weight. DR5 were also found to be increased in tumors tissue of PAB-treated mice without any apparent histopathological changes in liver or kidney tissues. Taken together, PAB may be a potential lead compound for chemotherapeutic agents against head and neck cancer.

Diagnosis and treatment planning are the most important steps in the orthognathic surgery for the successful treatment. The purpose of this study was to develop a new artificial intelligent model for surgery/non-surgery decision and extraction determination, and to evaluate the performance of this model. The sample used in this study consisted of 316 patients in total. Of the total sample, 160 were planned with surgical treatment and 156 were planned with non-surgical treatment. The input values of artificial neural network were obtained from 12 measurement values of the lateral cephalogram and 6 additional indexes. The artificial intelligent model of machine learning consisted of 2-layer neural network with one hidden layer. The learning was carried out in 3 stages, and 4 best performing models were adopted. Using these models, decision-making success rates of surgery/non-surgery, surgery type, and extraction/non-extraction were calculated. The final diagnosis success rate was calculated by comparing the actual diagnosis with the diagnosis obtained by the artificial intelligent model. The success rate of the model showed 96% for the diagnosis of surgery/non-surgery decision, and showed 91% for the detailed diagnosis of surgery type and extraction decision. This study suggests the artificial intelligent model using neural network machine learning could be applied for the diagnosis of orthognathic surgery cases.

Electrical stimulation has been playing a significant role in revealing various functions and mechanisms of the nervous system. It is no different for myelination, a process in which oligodendrocytes in the central nervous system (CNS) or Schwann Cells in the peripheral nerve system (PNS) wrap around axons to provide an insulating layer in vitro and in vivo . It has been widely recognized that the myelin sheath accelerates axon signal conduction and provides neuroprotection. Recent studies have begun to reveal its role in plasticity. The major mechanism that enables this process is activity-dependent myelination - the phenomenon where neuronal activity supports oligodendrocyte maturation and myelin sheath formation. In light of recent discoveries, a better understanding of this phenomenon has a potential to provide therapeutic targets for not only demyelinating diseases, but also psychiatric disorders. There is a growing need for experimental platforms capable of dissecting the effect of neural activity on myelination in health and disease. The effect of neural activity is commonly studied by comparing the myelination levels in cultures with neurons of low and high activity. Electrical stimulation is particularly well suited as a method of inducing neural activity in these systems. In this review, we describe in vitro platforms for studying activity-dependent myelination, which utilize neuron stimulation via electrical field. We also discuss stimulation profiles, as well as the alternatives to electrical stimulation in the context of regular, compartmentalized, and organotypic co-cultures.

Distal intracranial occlusions can sometimes cause significant neurological deficits. Endovascular thrombectomy in these vessels may improve outcome but carry a higher risk of haemorrhagic complications due to the small calibre and tortuosity of the target vessel. We report two cases of isolated M2/3 artery occlusion causing dense hemiplegia that was successfully treated with stent retrieval thrombectomy. A "semi-deployment technique" of a 3 mm stentriever was employed at the M2/3 bifurcation of the middle cerebral artery. Partial stent unsheathing allowed adequate clot engagement while avoiding excessive tension by the stent metal struts along the tortuous course of a distal vessel. Complete revascularization was achieved after firstpass of the stent retriever without complication, resulting in good clinical outcome in both cases. The described semi-deployment technique reduces the radial and tractional force exerted by the stentreiver on small branches, and may reduce the risk of vessel laceration or dissection in distal vessel thrombectomy.

Background: The aim of this study was to investigate the relationship between estimated glomerular filtration rate (eGFR) and outcomes of bipolar hemiarthroplasty for femoral neck fracture in elderly patients, and to compare postoperative complications and mortality among groups according to eGFR., Methods: A total of 181 patients who underwent bipolar hemiarthroplasty for displaced femoral neck fracture were divided into three groups according to eGFR. Data were retrospectively analyzed. Group 1 had 96 patients with eGFR greater than or equal to 60 mL/min/1.73 m 2 ; Group 2 had 54 patients with eGFR greater than or equal to 30&nbsp;mL/min/1.73&nbsp;m 2 and lower than 60 mL/min/1.73 m 2 ; and Group 3 had 31 patients with eGFR lower than 30 mL/min/1.73 m 2 . Postoperative complications and mortality were compared between groups at a minimum 2-year follow-up., Results: Patients in Group 3 had the longest hospital stay of the three groups ( p = 0.001). The rates of medical complications did not differ significantly among groups. However, Group 2 and 3 had higher rates of surgical complications ( p = 0.001) and mortality ( p = 0.043) than Group 1. Severe renal impairment was associated with increased risk of postoperative complications compared to mild renal impairment (odds ratio (95% confidence interval)&nbsp;= 4.33 (1.32-13.19), p = 0.015)., Conclusion: Patients with moderate or severe decreased eGFR associated with chronic kidney disease (CKD) could have higher postoperative complications and mortality after bipolar hemiarthroplasty compared to patients with CKD stage 1 or 2., Competing Interests: The authors declare no conflict of interest

Background and Objective: Pulsatile tinnitus (PT) can be debilitating and lead to significant morbidity. Cerebral venous sinus lesions, such as venous sinus stenosis, diverticula, and high-riding jugular bulb, are uncommon causes of PT, for which there is no standard treatment. Endovascular interventions have shown promising results for PT secondary to idiopathic intracranial hypertension, and may be a valid therapeutic option for isolated venous PT., Methods: We conducted a systematic literature review on the outcome and safety of endovascular treatment for patients with isolated, debilitating venous PT. The venous lesion characteristics, endovascular techniques, complications, and clinical outcomes were assessed. In addition, an illustrative case of endovascular stenting for PT caused by venous sinus stenosis was included., Results: A total of 41 patients (90.2% female) from 26 papers were included. The median age was 46 years (IQR 23; range 25-72 years). Focal venous sinus stenosis (20 patients) and sinus diverticula (14 patients) were the most common culprit lesions. Endovascular treatment included venous sinus stenting in 35 patients, 11 of whom had adjuvant coil embolization, and coil embolization alone in six patients. Complete resolution of the tinnitus was achieved in 95.1% of patients. There was one complication of cerebellar infarct, and no procedure-related mortality., Conclusions: In patients with debilitating PT secondary to venous sinus lesions, endovascular treatment by stenting and/or coil embolization appears to be safe and effective. Prospective randomized studies with objective outcome assessments are needed to confirm the treatment benefits., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Graves' orbitopathy (GO) is an autoimmune inflammatory disease affecting the orbit. Orbital fibroblasts are a key component in GO pathogenesis, which includes inflammation, adipogenesis, hyaluronic acid (HA) secretion, and fibrosis. Macrophages are thought to participate in the immunological stage of GO, but whether they can directly affect the fibroblasts phenotype and modulate disease progression is unknown. We previously showed that GO adipogenic and fibrotic phenotypes could be modelled in a pseudo-physiological 3D environment in vitro. Here, we introduced macrophages in this 3D culture model to investigate role for macrophages in modulating adipogenesis, HA production, and contractility in orbital fibroblasts. Macrophages had a minimal effect on lipid droplet formation in fibroblasts, but significantly increased HA production and cell contractility, suggesting that they may promote the fibrotic phenotype. This effect was found to be mediated at least in part through phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) activation and linked to an increase in actin polymerization and protrusive activity in fibroblasts. Overall our work shows for the first time a direct role for macrophages in modulating the fibroblasts' phenotype in GO, supporting a role for macrophages in the progression of the fibrotic phenotype through induction of HA production and stimulation of the contractile phenotype in orbital fibroblasts.

Cargo transport along axons, a physiological process mediated by motor proteins, is essential for neuronal function and survival. A current limitation in the study of axonal transport is the lack of a robust imaging technique with a high spatiotemporal resolution to visualize and quantify the movement of motor proteins in real-time and in different depth planes. Herein, we present a dynamic imaging technique that fully exploits the characteristics of upconversion nanoparticles. This technique can be used as a microscopic probe for the quantitative in situ tracking of retrograde transport neurons with single-particle resolution in multilayered cultures. This study may provide a powerful tool to reveal dynamic neuronal activity and intra-axonal transport function as well as any associated neurodegenerative diseases resulting from mutation or impairment in the axonal transport machinery., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: This study evaluated whether blunted autonomic activity as measured by heart rate recovery (HRR) was associated with increased arterial stiffness, especially increased exercise-induced arterial stiffness, in normotensive patients without overt atherosclerosis., Methods: One hundred fifty-four normotensive patients without overt atherosclerosis who had undergone a treadmill exercise test were consecutively enrolled. HRR was measured at one minute after exercise. Brachial-ankle pulse wave velocity (baPWV) at rest was measured, and carotid arterial stiffness indices at rest (CSI at rest) and after exercise (CSI after exercise) were assessed., Results: Patients with slow HRR were older and tended to be male, and they had diabetes, higher resting and peak systolic blood pressures, higher resting heart rate, lower peak heart rate, lower metabolic equivalents, increased baPWV, and increased CSIs at rest and after exercise. HRR was inversely associated with baPWV and CSI after exercise when established cardiovascular risk factors were adjusted as confounding factors, and HRR was associated with CSI after exercise when resting systolic blood pressure and metabolic equivalent of tasks on cardiovascular risk factors were added as confounding factors., Conclusions: Sympathovagal imbalance demonstrated by slow HRR was associated with increased arterial stiffness and, above all, was closely associated with exercise-induced arterial stiffness in normotensive patients without overt atherosclerosis. This phenomenon might have been observed because blunt carotid arterial vasomotion following exercise results from autonomic dysfunction as well as vascular endothelial dysfunction., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2019 Korean Society of Echocardiography.)

Purpose: ABT-263 is a potent BH3 mimetic that possesses anticancer potential against various types of cancer. In general, this potential is due to its high binding affinity to anti-apoptotic proteins in the Bcl-2 family that disrupt sequestration of pro-apoptotic proteins. In the present study, we sought to identify an alternative regulatory mechanism responsible for ABT-263-mediated anticancer activity in human oral cancer., Methods: We investigated the in vitro anti-cancer effects of ABT-263 using a trypan blue exclusion assay, Western blotting, DAPI staining, immunofluorescence staining, a live/dead assay, microarray-based expression profiling, and quantitative real-time PCR. In vivo anti-tumorigenic effects of ABT-263 were examined using a nude mouse tumor xenograft model, a TUNEL assay, and immunohistochemistry., Results: We found that ABT-263 suppressed viability and induced apoptosis in human oral cancer-derived cell lines HSC-3 and HSC-4. Subsequent microarray-based gene expression profiling revealed 55 differentially expressed genes in the ABT-263-treatead group, including 12 genes associated with "endoplasmic reticulum stress and apoptosis." Consistent with the microarray results, the mRNA expression levels of the top four genes (CHOP, TRB3, ASNS, and STC2) were found to be significantly increased. In addition, we found that ABT-263 considerably enhanced the expression levels of the C/EBP-homologous protein (CHOP) and its mRNA, resulting in apoptosis induction in four other human oral cancer-derived cell lines (MC-3, YD-15, HN22, and Ca9.22). Extending our in vitro findings, we found that ABT-263 reduced the growth of HSC-4 cells in vivo at a dosage of 100 mg/kg/day without any change in body weight. TUNEL-positive cells were also found to be increased in tumors of ABT-263-treated mice without any apparent histopathological changes in liver or kidney tissues., Conclusions: These results provide evidence that ABT-263 may serve as an effective therapeutic agent for the treatment of human oral cancer.

Background and Purpose- Intracranial atherosclerosis (ICAS) is an important cause of large vessel occlusion and poses unique challenges for emergent endovascular thrombectomy. The risk factor profile and therapeutic outcomes of patients with ICAS-related occlusions (ICAS-O) are unclear. We performed a systematic review and meta-analysis of studies reporting the clinical features and thrombectomy outcomes of large vessel occlusion stroke secondary to underlying ICAS (ICAS-O) versus those of other causes (non-ICAS-O). Methods- A literature search on thrombectomy for ICAS-O was performed. Random-effect meta-analysis was used to analyze the prevalence of stroke risk factors and outcomes of thrombectomy between ICAS-O and non-ICAS-O groups. Results- A total of 1967 patients (496 ICAS-O and 1471 non-ICAS-O) were included. The ICAS-O group had significantly higher prevalence of hypertension (odds ratio [OR] 1.46; 95% CI, 1.10-1.93), diabetes mellitus (OR, 1.68; 95% CI, 1.29-2.20), dyslipidemia (OR, 1.94; 95% CI, 1.04-3.62), smoking history (OR, 2.11; 95% CI, 1.40-3.17) but less atrial fibrillation (OR, 0.20; 95% CI, 0.13-0.31) than the non-ICAS-O group. About thrombectomy outcomes, ICAS-O had higher intraprocedural reocclusion rate (OR, 23.7; 95% CI, 6.96-80.7), need for rescue balloon angioplasty (OR, 9.49; 95% CI, 4.11-21.9), rescue intracranial stenting (OR, 14.9; 95% CI, 7.64-29.2), and longer puncture-to-reperfusion time (80.8 versus 55.5 minutes, mean difference 21.3; 95% CI, 11.3-31.3). There was no statistical difference in the rate of final recanalization (modified Thrombolysis in Cerebral Infarction score of 2b/3; OR, 0.67; 95% CI, 0.36-1.27), symptomatic intracerebral hemorrhage (OR, 0.79; 95% CI, 0.50-1.24), good functional outcome (modified Rankin Scale score of 0-2; OR, 1.16; 95% CI, 0.85-1.58), and mortality (OR, 0.94; 95% CI, 0.64-1.39) between ICAS-O and non-ICAS-O. Conclusions- Patients with ICAS-O display a unique risk factor profile and technical challenges for endovascular reperfusion therapy. Intraprocedural reocclusion occurs in one-third of patients with ICAS-O. Intraarterial glycoprotein IIb/IIIa inhibitors infusion, balloon angioplasty, and intracranial stenting may be viable rescue treatment to achieve revascularization, resulting in comparable outcomes to non-ICAS-O.

Norcantharidin (NCTD), a demethylated derivative of cantharidin, has been reported to exhibit activity against various types of cancers. However, the anti-invasive effects of NCTD and its molecular mechanism in human mucoepidermoid carcinoma (MEC) remain incompletely elucidated. Clonogenic, wound healing, invasion, zymography, western blotting and immunocytochemistry assays were performed in YD-15 cells to investigate the anti-invasive effect of NCTD and its molecular mechanism of action. The inhibitory effects of NCTD on invasiveness were compared with those of a novel focal adhesion kinase (FAK) kinase inhibitor, PF-562271. NCTD markedly suppressed the colony formation, migration, and invasion of YD-15 cells as well as the activities of MMP-2 and MMP-9. It disrupted F-actin reorganization through suppressing the FAK/Paxillin axis. Moreover, NCTD exhibited a powerful anti-invasive effect compared with that of PF-562271 in YD-15 cells. Collectively, these results suggest that NCTD has a potential anti-invasive activity against YD-15 cells. This study may clarify the impact of NCTD on migration and invasion of human MEC cells.

TW-37 is a small-molecule inhibitor of Bcl-2 family proteins, which can induce anti-cancer activities in various types of cancer. In the current study, we investigated the potential molecular mechanism underlying the differential response to TW-37-induced apoptosis in two human mucoepidermoid carcinoma (MEC) cell lines. The differential response and underlying molecular mechanism of human MEC cells to TW-37 was evaluated by trypan blue exclusion assay, western blotting, 4', 6-diamidino-2-phenylindole staining, annexin V/propidium iodide double staining, analysis of the sub-G1 population, human apoptosis array, and measurements of intracellular reactive oxygen species (ROS). TW-37 decreased cell viability and induced apoptosis in YD-15 cells, but not in MC3 cells. Proteome profiling using a human apoptosis array revealed four candidate proteins and of these, heme oxygenase-1 (HO-1) was mainly related to the differential response to TW-37 of YD-15 and MC3 cells. TW-37 also led to a significant increase in intracellular levels of ROS in YD-15 cells, which is associated with apoptosis induction. The ectopic expression of HO-1 recovered YD-15 cells from TW-37-induced apoptosis by reducing intracellular levels of ROS. The expression of HO-1 was reduced through both transcriptional and post-translational modification during TW-37-mediated apoptosis. We conclude that HO-1 is a potential indicator to estimate response to TW37-induced apoptosis in human MEC.

Ability to direct neuronal growth not only carries great potential for treating neural conditions-for example, bridging traumatically shattered connections-but would also be an exquisite tool for bionic applications that require a physical interface between neurons and electronics. A testing platform is needed to better understand axonal guidance in the context of a specific in vivo application. Versatility of 3D printing technology allows tailoring to researcher needs, both in vitro and in vivo. In this paper, we establish a fibro-neuronal co-culture inspired by our neural interface research and demonstrate axon alignment on a textured substrate fabricated with a common, versatile 3D-printing set-up.

A noncontact single-beam acoustic trapping technique has proven to be a promising tool for cell manipulation and characterization that provide essential knowledge for a variety of biomedical applications. Here, we investigated cell characteristics as to whether the calcium responses of suspended breast cancer cells to different acoustic trapping forces are related to their invasiveness. For this, we combined a single-beam acoustic trapping system with a 30-MHz press-focused lithium niobate ultrasound transducer and an epifluorescence microscope. Using the system, intracellular calcium changes of suspended MDA-MB-231 (highly invasive) and MCF-7 (weakly invasive) cells were monitored while trapping the cells at different acoustic pressures. The results showed that a single suspended breast cancer cell isolated by the acoustic microbeam behaved differently on the calcium elevation in response to changes in acoustic trapping force, depending on its invasiveness. In particular, the MDA-MB-231 cells exhibited higher calcium elevation than MCF-7 cells when each cell was trapped at low acoustic pressure. Based on these results, we believe that the single-beam acoustic trapping technique has high potential as an alternative tool for determining the degree of invasiveness of suspended breast cancer cells.

Purpose: The aim of this study was to investigate the effects of relaxin (RLN) expression on fibrosis inhibition in synovial fibroblasts., Materials and Methods: Tissue cells from patients with knee osteoarthritis and >30° flexion contractures were utilised. Synovial fibroblasts were activated by TGF-β1 (two nanograms per millilitre) and then exposed to Ad-RLN as a therapeutic gene, adenovirus-lacZ construct as a marker gene, and SB505124 as an inhibitor for TGF-β1 signal for 48 h. The mRNA expression levels of collagens and MMPs were analysed by reverse transcription-polymerase chain reaction. Also, fibronectin, phosphorylation of Smad2 and ERK1/2, alpha smooth muscle actin, TIMP-1, TIMP-2, MMP-1 and MMP-13 levels were estimated using western blotting, and the total collagen synthesis was assayed., Results: Ad-RLN-transduced synovial fibroblasts demonstrated 17%, 13%, and 48% reduction in collagen I, III and IV mRNA expression levels, respectively, and a 40% decrease in MMP-3, MMP-8, 20% decrease in MMP-9, MMP-13 mRNA expression, compared to non-Ad-RLN-transduced cells. In protein expression, Ad-RLN-transduced synovial fibroblasts demonstrated 46% increase in MMP-1, 5% decrease in MMP-2, 51% increase in MMP-9, and 22% increase in MMP-13, compared to non-Ad-RLN-transduced cells. Ad-RLN-transduced synovial fibroblasts showed a 25% decrease in TIMP-1 and 65% decrease in TIMP-2 protein expression at 48h, compared to non-Ad-RLN-transduced cells. Ad-RLN-transduced synovial fibroblasts demonstrated a 45% inhibition of fibronectin in protein expression level and 38% decrease in total collagen synthesis at 48h, compared to non-Ad-RLN-transduced cells., Conclusion: Relaxin expression exerted anti-fibrogenic effects on synovial fibroblasts from patients with knee osteoarthritis and flexion contractures. Therefore, relaxin could be an alternative therapeutic agent during the initial stage of osteoarthritis with flexion contracture by exerting its anti-fibrogenic effects., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: The purpose of this study was to compare the static (SFF) and kinetic frictional forces (KFF) of a computer-aided design and computer-aided manufacturing lingual bracket (CAD/CAM-LB) with those of conventional LB (Con-LB) and Con-LB with narrow bracket width (Con-LB-NBW) under 3 tooth displacement conditions., Methods: The samples were divided into 9 groups according to combinations of 3 LB types (CAD/CAM-LB [Incognito], Con-LB [7th Generation, 7G], and Con-LB-NBW [STb]) with 3 displacement conditions (no displacement [control], maxillary right lateral incisor with 1-mm palatal displacement [MXLI-PD], and maxillary right canine with 1-mm gingival displacement [MXC-GD]; n = 6/group). While drawing a 0.016-inch copper or super-elastic nickel-titanium archwire with 0.5 mm/min for 5 minutes in a chamber maintained at 36.5℃, SFF and KFF were measured. The Kruskal-Wallis method with Bonferroni correction was performed., Results: The Incognito group demonstrated the highest SFF, followed by the 7G and STb groups ([STb-control, STb-MXLI-PD, Stb-MXC-GD] < [7G-MXC-GD, 7G-MXLI-PD, 7G-control] < [Incognito-MXLI-PD, Incognito-control, Incognito-MXC-GD]; p < 0.001). However, there were no significant differences in SFF among the 3 displacement conditions within each bracket group. Within each displacement condition, the Incognito group demonstrated the highest KFF, followed by the 7G and STb groups ([STb-control, STb-MXLI-PD] < Stb-MXC-GD < 7G-MXLI-PD < [7G-control, 7G-MXC-GD] < [7G-MXC-GD, Incognito-MXLI-PD, Incognito-control] < [Incognito-control, Incognito-MXC-GD]; p < 0.001). MXC-GD exhibited higher KFFs than MXLI-PD in the same bracket group., Conclusions: The slot design and ligation method of the CAD/CAM-LB system should be modified to reduce SFF and KFF during the leveling/alignment stage., Competing Interests: CONFLICTS OF INTEREST: No potential conflict of interest relevant to this article was reported.

Accurate measurement of knee range of motion (ROM) is critical to predict the outcomes of knee surgery and prognosis. We investigated the reliability of knee ROM measurements by goniometer compared with robotic system. Fifty-three patients with medial osteoarthritis who were planning to undergo unicompartmental knee arthroplasty (UKA) with robotic UKA were prospectively enrolled. During the operation, knee ROM measurement was performed in both flexion and extension before and after insertion of the implant using both a goniometer and robotic system. The intraclass correlation coefficient (ICC) of extension measured by the goniometer and robotic system showed good agreement; however, the ICC of flexion did not show good agreement. During passive flexion, the mean values measured before insertion of the implant were significantly lower by goniometer (134.6 ± 6.43) than by robot (145.4 ± 6.80; p  = 0.017); likewise, the mean values after insertion of the implant were significantly lower by goniometer (138.6 ± 6.07) than by robotic system (147.0 ± 6.60; p  = 0.045). A goniometer can underestimate knee ROM measurements compared with robotic system, especially in flexion. Orthopaedic surgeons should be cautious when measuring the flexion angle with a goniometer., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Fisetin was reported to have an anti-proliferative and apoptotic activity as a novel anti-cancer agent in various cancer cell lines. However, the possible molecular targets for the anti-cancer effect of fisetin in human head and neck cancer (HNCC) have not yet been clarified. In this study, the influence of fisetin on the growth and apoptosis of HNCCs were examined. In HSC3 cells, fisetin treatment reduced the viability and induced apoptosis. Through the results from the screening of the expression profile of apoptosis-related genes, sestrin 2 (SESN2) was functionally involved in fisetin-mediated apoptosis showing the knockdown of SESN2 by siRNA clearly restored fisetin-induced apoptosis. In addition, fisetin reduced the protein expression levels of phospho-mTOR (p-mTOR) and Mcl-1, which are the downstream molecules of SESN2. It also induced PARP cleavage by inducing an increase in the expression levels of SESN2 together with reducing mTOR and Mcl-1 proteins in other three HNCCs (MC3, Ca9.22, and HN22). Taken together, our findings suggest that the anti-cancer effect of fisetin on HNCCs is associated with SESN2/mTOR/Mcl-1 signaling axis., Competing Interests: No potential conflicts of interest were disclosed.

An acoustic field flow fractionation (FFF) device was developed to fractionate a micro-particle mixture on the basis of the particle diameter using an acoustic force field in a carrier liquid flow. In the acoustic FFF channel used in the device, ultrasound waves generated from piezoelectric transducers driven by a sinusoidal signal of 2.02 Mhz propagated into the carrier liquid flow and built up a quarter-wavelength ultrasound standing wave field across the channel height. It was experimentally demonstrated that the acoustic field with a pressure node plane at the bottom surface of the channel reduced the thickness of the particle diffusion layer in a stagnant liquid proportional to the applied voltage driving the piezoelectric transducer. In the size-dependent particle separation, the particle mixture flowing through the acoustic FFF channel experienced an acoustic radiation force in the gravitational direction. As a result, suppressing the diffusion of small particles, particles were transported along the bottom surface of the channel with the local velocity of the carrier liquid at the particle center. The developed acoustic FFF device successfully fractionated a fluorescent micro-particle mixture (1, 3, 5, and 10 μm diameter), whereas the 3 and 5 μm particles were not fractionated in the FFF device using only the gravitational force field due to the diffusion of 3 μm particles., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Sodium butyrate (NaBu) is a histone deacetylase inhibitor that possesses an apoptotic ability. However, the molecular mechanism by which NaBu induces apoptosis in human oral mucoepidermoid carcinoma (MEC), a type of salivary gland tumor, remains unclear., Materials and Methods: The anticancer effects of NaBu and its related molecular mechanisms were determined by trypan blue exclusion assay, 4'-6-diamidino-2-phenylindole staining, live/dead assay, human apoptosis array, RT-PCR, western blotting, immunocytochemistry, preparation of nuclear fractions, and nude mice tumor xenograft., Results: In this study, we found that NaBu inhibited growth and induced apoptosis in the human oral MEC cell lines MC3 and YD15 with acetylation of histone proteins H2A and H3. NaBu apparently down-regulated survivin protein, as evidenced by the results of the human apoptosis antibody array, and modulated it at the post-translational process. Interestingly, NaBu caused nuclear translocation of survivin protein in both cell lines. NaBu also resulted in decreased expression levels of Bcl-xL mRNA and protein, leading to induction of caspase-dependent apoptosis in human oral MEC cell lines. In addition, NaBu administration inhibited tumor growth in vivo at a dosage of 500 mg/kg/day, but it did not cause any hepatic or renal toxicity., Conclusion: This study provides new insights into the molecular mechanism of apoptotic actions by NaBu in human oral MEC and the basis of its clinical application for the treatment of human oral MEC., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: This study aimed to evaluate the efficacy of simultaneous computed tomography (CT) and quantitative CT (QCT) in patients with osteoporotic hip fracture (OHF) by analyzing the osteoporosis detection rate and physician prescription rate in comparison with those of conventional dual-energy X-ray absorptiometry (DXA)., Materials and Methods: This study included consecutive patients older than 65 years who underwent internal fixation or hip arthroplasty for OHF between February and May 2015. The patients were assigned to either the QCT (47 patients) or DXA group (51 patients). The patients in the QCT group underwent QCT with hip CT, whereas those in the DXA group underwent DXA after surgery, before discharge, or in the outpatient clinic. In both groups, the patients received osteoporosis medication according to their QCT or DXA results. The osteoporosis evaluation rate and prescription rate were determined at discharge, postoperative (PO) day 2, PO day 6, and PO week 12 during an outpatient clinic visit., Results: The osteoporosis evaluation rate at PO week 12 was 70.6% (36 of 51 patients) in the DXA group and 100% in the QCT group ( P <0.01). The prescription rates of osteoporosis medication at discharge were 70.2% and 29.4% ( P <0.001) and the cumulative prescription rates at PO week 12 were 87.2% and 60.8% ( P =0.003) in the QCT and DXA groups, respectively., Conclusion: Simultaneous CT and QCT significantly increased the evaluation and prescription rates in patients with OHF and may enable appropriate and consistent prescription of osteoporosis medication, which may eventually lead to patients' medication compliance., Competing Interests: CONFLICT OF INTEREST: The authors declare that there is no potential conflict of interest relevant to this article.

Purpose: Ischiofemoral impingement (IFI)-primarily diagnosed by magnetic resonance imaging (MRI)-is an easily overlooked disease due to its low incidence. The purpose of this study was to evaluate the usefulness of false profile view as a screening test for IFI., Materials and Methods: Fifty-eight patients diagnosed with IFI between June 2013 and July 2017 were enrolled in this retrospective study. A control group (n=58) with matching propensity scores (age, gender, and body mass index) were also included. Ischiofemoral space (IFS) was measured as the shortest distance between the lateral cortex of the ischium and the medial cortex of lesser trochanter in weight bearing hip anteroposterior (AP) view and false profile view. MRI was used to measure IFS and quadratus femoris space (QFS). The receiver operating characteristics (ROC), area under the ROC curve (AUC) and cutoff point of the IFS were measured by false profile images, and the correlation between the IFS and QFS was analyzed using the MRI scans., Results: In the false profile view and hip AP view, patients with IFI had significantly decreased IFS ( P <0.01). In the false profile view, ROC AUC (0.967) was higher than in the hip AP view (0.841). Cutoff value for differential diagnosis of IFI in the false profile view was 10.3 mm (sensitivity, 88.2%; specificity, 88.4%). IFS correlated with IFS (r=0.744) QFS (0.740) in MRI and IFS (0.621) in hip AP view ( P <0.01)., Conclusion: IFS on false profile view can be used as a screening tool for potential IFI., Competing Interests: CONFLICT OF INTEREST: The authors declare that there is no potential conflict of interest relevant to this article.