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Purpose: Programmed cell death protein 1 (PD-1) and ligand programmed death ligand 1 (PD-L1) are important immune-suppressive regulators in the tumor microenvironment. A vaccine-induced immune effect on tumor cells is blunted by the immunosuppressive tumor microenvironment. Therefore, we hypothesized that a dendritic cell (DC) vaccine combined with anti-PD-1 (αPD-1) antibodies could elicit a synergistic anti-tumor immunity in bladder cancer. Materials and Methods: We produced a model of subcutaneous transplantation in C3H/HeJ mice by transplanting murine MBT-2 bladder cancer cells. DCs were isolated from normal C3H/HeJ mice, followed by stimulation against MBT-2 lysate before injection. Two weeks later of MBT-2 inoculation, αPD-1 and stimulated DCs were injected two times at one-week interval intraperitoneally and intravenously, respectively. Tumor-infiltrating immune cells and splenocytes were analyzed using flow cytometry. T-cell-mediated anti-tumor responses were measured by interferon (IFN)-γ ELISPOT and lactate dehydrogenase assays. Results: The mice treated with DC+α PD-1 showed a significant decrease in tumor volume compared to the DC-treated mice and IgG-treated group. Survival of the DC+α PD-1–treated group was improved compared with that of the IgG-treated mice. IFN-γ secretion from splenocytes against tumor cells was significantly increased in the DC+α PD-1 group compared with that of αPD-1– treated mice. The frequency of CD8+ and CD4+ T-cells in spleens was statistically increased in the DC+αPD-1–treated mice compared to those receiving monotherapy (DC- or αPD-1–treated group). Conclusions: Our results support the hypothesis that the combination therapy of a DC vaccine and αPD-1 antibodies could enhance the anti-tumor immune response against bladder cancer. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to identify the effects of psychological insulin resistance, diabetes distress, and diabetes self-efficacy of patients and their spouses on insulin therapy adherence of patients with type 2 diabetes. Methods: A path analysis based on the actor-partner interdependence model, a couple analysis method, was used to identify the actor and partner effects of psychological insulin resistance, diabetes distress, diabetes self-efficacy on the insulin therapy adherence of patients with type 2 diabetes. Data were collected between February 25 and May 1, 2019, from 200 patients with type 2 diabetes and their spouses. Results: The psychological insulin resistance of the patient had an actor effect on the diabetes self-efficacy of the patient and a partner effect on the diabetes self-efficacy of the spouse, and the patient's diabetes distress had a partner effect on the diabetes self-efficacy of the spouse. The psychological insulin resistance of the spouse had an actor effect on the diabetes self-efficacy of the spouse, and the diabetes self-efficacy of the patient and spouse were found to affect the insulin therapy adherence of the patient directly. Conclusion: This study provided basic data for the development of programs that can enhance insulin therapy adherence in patients with type 2 diabetes, focusing on the perspectives of both the patient and spouse. [ABSTRACT FROM AUTHOR]

Background: Adipose tissue-derived mesenchymal stem cells (AT-MSCs) offer potential as a therapeutic option for chronic discogenic low back pain (LBP) because of their immunomodulatory functions and capacity for cartilage differentiation. The goal of this study was to assess the safety and tolerability of a single intradiscal implantation of combined AT-MSCs and hyaluronic acid (HA) derivative in patients with chronic discogenic LBP. Methods: We performed a single-arm phase I clinical trial with a 12-month follow-up and enrolled 10 eligible chronic LBP patients. Chronic LBP had lasted for more than 3 months with a minimum intensity of 4/10 on a visual analogue scale (VAS) and disability level ≥ 30% on the Oswestry Disability Index (ODI). The 10 patients underwent a single intradiscal injection of combined HA derivative and AT-MSCs at a dose of 2 × 107 cells/disc (n=5) or 4×107 cells/disc (n=5). Safety and treatment outcomes were evaluated by assessing VAS, ODI, Short Form-36 (SF-36), and imaging (lumbar spine X-ray imaging and MRI) at regular intervals over 1 year. Results: No patients were lost at any point during the 1-year clinical study. We observed no procedure or stem cell-related adverse events or serious adverse events during the 1-year follow-up period. VAS, ODI, and SF-36 scores significantly improved in both groups receiving both low (cases 2, 4, and 5) and high (cases 7, 8, and 9) cell doses, and did not differ significantly between the two groups. Among six patients who achieved significant improvement in VAS, ODI, and SF-36, three patients (cases 4, 8, and 9) were determined to have increased water content based on an increased apparent diffusion coefficient on diffusion MRI. Conclusions: Combined implantation of AT-MSCs and HA derivative in chronic discogenic LBP is safe and tolerable. However, the efficacy of combined AT-MSCs and HA should be investigated in a randomized controlled trial in a larger population. [ABSTRACT FROM AUTHOR]

Background: Tonsillectomy is themost common type of surgical procedure performed in preschool children. Due to short period of hospitalization, mothers are expected tomanage their children's care at home. However, they are rarely provided with sufficient information about postoperative management. This study aims to determine the effectiveness of providing caregivers with information on tonsillectomy care by smartphone textmessaging in increasing their mothers' knowledge, reducing the anxiety, and improving the sick-role behavior of pediatric tonsillectomy patients. Materials andMethods:Asample of61 pediatric patients and their mothers was recruited. Participants were randomly assigned into either the experimental group (n = 27) or the control group (n = 34). The control group was given information about the tonsillectomy by conventional textual and verbal means, whereas the experimental group received the same information in the form of 10 textmessages during the period from hospitalization to their first follow-up visits. Results: Results of mixed design, two-way analysis of variance indicated significant interaction effects between time points and groups for mothers' knowledge (F = 4.26, p = 0.043) and children's anxiety (F = 3.32; p = 0.037). Thus, the results do support the effectiveness of tonsillectomy education using smartphone text messaging in increasing mothers' knowledge and reducing children's anxiety. Conclusions: These results can be applied to preoperative and postoperative interventions for children not only for tonsillectomy but also for many other operations. The development of various educational programs using smartphone text messaging for postoperative patient management would also be valuable. [ABSTRACT FROM AUTHOR]

Background: Epithelial-myoepithelial carcinoma is an extremely rare disease that usually occurs in the parotid gland but can occur in a variety of sites such as the nasal cavity, paranasal sinus, and base of the tongue.Case Presentation: We report a rare case of epithelial-myoepithelial carcinoma, which developed in the subglottic region. A 78-year-old Korean woman visited our hospital complaining of hoarseness, which had developed 1 month previously. Flexible laryngoscopy showed a round mass that blocked approximately 80 % of the tracheal diameter. Complete excision of the mass was carried out under general anesthesia, using a transoral approach. Epithelial-myoepithelial carcinoma was diagnosed following immunohistochemical analysis.Conclusions: We report a rare case of epithelial-myoepithelial carcinoma that occurred in the subglottic region. To the best of our knowledge, only one other case has been reported since this disease was first identified approximately 40 years ago. [ABSTRACT FROM AUTHOR]

Introduction: Despite the success of interventional processes such as drug-eluting stents, complete prevention of restenosis is still hindered by impaired or delayed endothelialization or both. Here, we report that 1H-pyrrole-2,5-dione-based small molecule-generated mesenchymal stem cell-derived functional endothelial cells (MDFECs) facilitated rapid transmural coverage of injured blood vessels. Methods: Small molecules that induced CD31 expression were screened by principal component analysis (PCA). Rat mesenchymal stem cells (MSCs) were treated with selected small molecules for up to 16 days, and the expression levels of CD90 and CD31 were examined by immunocytochemistry. In vitro functional assays of MDFECs, including tube formation assays and nitric oxide production assays, were performed. After MDFECs (intravenous, 3×106 cells per animal) were injected into balloon-injured rats, neointima formation was monitored for up to 21 days. The endothelial coverage of denuded blood vessels was evaluated by Evans Blue staining. The functionality of repaired blood vessels was evaluated by measuring vasorelaxation and hemodynamic changes. Additionally, derivatives of the selected small molecules were examined for their ability to induce endothelial markers. Results: PCA indicated that 3-(2,4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione effectively induced MDFECs. MDFECs inhibited the neointima formation of denuded blood vessels by facilitating more rapid endothelialization. Further examination indicated that derivatives with a 1H-pyrrole-2,5-dione moiety are important for initiating the endothelial cell differentiation of MSCs. Conclusions: Small molecules with 1H-pyrrole-2,5-dione as a core structure have great potential to improve the efficacy of MSC-based cell therapy for vascular diseases, such as atherosclerosis and restenosis. [ABSTRACT FROM AUTHOR]

Introduction: Despite the success of interventional processes such as drug-eluting stents, complete prevention of restenosis is still hindered by impaired or delayed endothelialization or both. Here, we report that 1H-pyrrole-2,5-dione-based small molecule-generated mesenchymal stem cell-derived functional endothelial cells (MDFECs) facilitated rapid transmural coverage of injured blood vessels. Methods: Small molecules that induced CD31 expression were screened by principal component analysis (PCA). Rat mesenchymal stem cells (MSCs) were treated with selected small molecules for up to 16 days, and the expression levels of CD90 and CD31 were examined by immunocytochemistry. In vitro functional assays of MDFECs, including tube formation assays and nitric oxide production assays, were performed. After MDFECs (intravenous, 3×106 cells per animal) were injected into balloon-injured rats, neointima formation was monitored for up to 21 days. The endothelial coverage of denuded blood vessels was evaluated by Evans Blue staining. The functionality of repaired blood vessels was evaluated by measuring vasorelaxation and hemodynamic changes. Additionally, derivatives of the selected small molecules were examined for their ability to induce endothelial markers. Results: PCA indicated that 3-(2,4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione effectively induced MDFECs. MDFECs inhibited the neointima formation of denuded blood vessels by facilitating more rapid endothelialization. Further examination indicated that derivatives with a 1H-pyrrole-2,5-dione moiety are important for initiating the endothelial cell differentiation of MSCs. Conclusions: Small molecules with 1H-pyrrole-2,5-dione as a core structure have great potential to improve the efficacy of MSC-based cell therapy for vascular diseases, such as atherosclerosis and restenosis. [ABSTRACT FROM AUTHOR]

Introduction: Mesenchymal stem cells (MSCs) have therapeutic potential for the repair of myocardial injury. The efficacy of MSC therapy for myocardial regeneration mainly depends on the survival of cells after transplantation into the infarcted heart. In the transplanted regions, reactive oxygen species (ROS) can cause cell death, and this process depends on caspase activation and autophagosome formation. Methods: A Software TargetScan was utilized to search for microRNAs (miRNAs) that target caspase-3 mRNA. Six candidate miRNAs including let-7b were selected and transfected into human MSCs in vitro. Expression of MEK-EKR signal pathways and autophagy-related genes were detected. Using ischemia/reperfusion model (I/R), the effect of MSCs enriched with let-7b was determined after transplantation into infarcted heart area. Miller catheter was used to evaluate cardiac function. Results: Here, we report that let-7b targets caspase-3 to regulate apoptosis and autophagy in MSCs exposed to ROS. Let-7b-transfected MSCs (let-7b-MSCs) showed high expression of survival-related proteins, including p-MEK, p-ERK and Bcl-2, leading to a decrease in Annexin V/PI- and TUNEL-positive cells under ROS-rich conditions. Moreover, autophagy-related genes, including Atg5, Atg7, Atg12 and beclin-1, were significantly downregulated in let-7b-MSCs. Using a rat model of acute myocardial infarction, we found that intramyocardial injection of let-7b-MSCs markedly enhanced left ventricular (LV) function and microvessel density, in accordance with a reduced infarct size and the expression of caspase-3. Conclusions: Taken together, these data indicate that let-7b may protect MSCs implanted into infarcted myocardium from apoptosis and autophagy by directly targeting caspase-3 signaling. [ABSTRACT FROM AUTHOR]

Introduction: Mesenchymal stem cells (MSCs) have therapeutic potential for the repair of myocardial injury. The efficacy of MSC therapy for myocardial regeneration mainly depends on the survival of cells after transplantation into the infarcted heart. In the transplanted regions, reactive oxygen species (ROS) can cause cell death, and this process depends on caspase activation and autophagosome formation. Methods: A Software TargetScan was utilized to search for microRNAs (miRNAs) that target caspase-3 mRNA. Six candidate miRNAs including let-7b were selected and transfected into human MSCs in vitro. Expression of MEK-EKR signal pathways and autophagy-related genes were detected. Using ischemia/reperfusion model (I/R), the effect of MSCs enriched with let-7b was determined after transplantation into infarcted heart area. Miller catheter was used to evaluate cardiac function. Results: Here, we report that let-7b targets caspase-3 to regulate apoptosis and autophagy in MSCs exposed to ROS. Let-7b-transfected MSCs (let-7b-MSCs) showed high expression of survival-related proteins, including p-MEK, p-ERK and Bcl-2, leading to a decrease in Annexin V/PI- and TUNEL-positive cells under ROS-rich conditions. Moreover, autophagy-related genes, including Atg5, Atg7, Atg12 and beclin-1, were significantly downregulated in let-7b-MSCs. Using a rat model of acute myocardial infarction, we found that intramyocardial injection of let-7b-MSCs markedly enhanced left ventricular (LV) function and microvessel density, in accordance with a reduced infarct size and the expression of caspase-3. Conclusions: Taken together, these data indicate that let-7b may protect MSCs implanted into infarcted myocardium from apoptosis and autophagy by directly targeting caspase-3 signaling. [ABSTRACT FROM AUTHOR]

We demonstrate a continuous-wave 460-nm compact visible laser module having a footprint of 75 mm × 25 mm × 25 mm. This blue light source is achieved through single-pass second harmonic generation with a distributed Bragg reflector tapered diode laser as a single-frequency pump source at ~920 nm in a periodically poled MgO-doped lithium niobate crystal with a planar waveguide. The compact blue laser module reached an optical output power of 286 mW with the highest optical conversion efficiency of 11.6% at room temperature. The power stability of the blue light from the laser module is measured at an output power of 268 mW with a variation of ±3.5% during a period of 1 h. [ABSTRACT FROM PUBLISHER]

Objective : The aim of this study is to evaluate the clinical course of intracranial aneurysm in patients aged 65 years and older and the immediate outcome after its aggressive management. Materials and Methods : We performed a retrospective analysis using the medical records of 159 elderly patients managed at our institute from September 2008 to December 2013. Obtained clinical information included age, sex, Hunt and Hess grade (HHG), aneurysm location, Fisher grade (FG) and the treatment modality. Concomitant clinical data aside from cerebrovascular condition (hypertension, diabetes, previous medication) were evaluated to determine risk factors that might affect the functional outcomes. Results : A total of 108 patients (67.9%) presented with subarachnoid hemorrhage (SAH), and 51 (32.1%) with unruptured intracranial aneurysms (UIAs). Coiling was performed in 101 patients and 58 patients underwent clipping. In the SAH population, 62 patients (57.4%) showed favorable outcomes, with a mortality rate of 11.3% (n = 18). In the UIAs population, 50 (98%) patients achieved 'excellent' and one (2%) achieved 'good' outcome. Factors including high-grade HHG (p < 0.001), advanced age (p = 0.014), and the presence of intraventricular hematoma (IVH) (p = 0.017) were significant predictors of poor outcome. Conclusion : SAH patients with high grade HHG and IVH are associated with poor outcome with statistical significance, all the more prominent the older the patient is. Therefore, the indication for aggressive therapy should be considered more carefully in these patients. However, as the outcomes for elderly patients with UIAs were excellent regardless of the treatment modality, aggressive treatment could always be considered in UIAs cases. [ABSTRACT FROM AUTHOR]

Background: Otolaryngologists encounter cases of various foreign bodies in the oral and pharyngeal regions. One commonly found foreign body is a fish bone, ingested in most cases by carelessness or an accident. These foreign materials are removed by endoscopy or through a simple procedure. However, hypopharyngeal damage is rarely caused by a foreign body in the pharynx following the swallowing of a toothbrush. Case presentation: A 44-year-old Asian male visited the emergency room with chief complaints of intraoral pain and dysphagia that had started on the same day. The patient had paranoid-type schizophrenia that began 10 years ago; he had been hospitalized and was being treated at another clinic, and was transferred to the emergency room by the medical staff after swallowing a toothbrush. We successfully removed a toothbrush located within the pharynx of a patient with a history of a psychologic disorder via surgery and conservative treatment. Conclusion: The case with this patient, and a rapid diagnosis as well as treatment is imperative. The presence and state of a foreign body must be determined through a careful physical examination and imaging, followed by the immediate removal of the foreign body, all while keeping in mind the possibility of accompanying damage to nearby tissues. [ABSTRACT FROM AUTHOR]

Objective: To verify the clinical outcomes of posterior C2-C3 fixation for unstable Hangman's fracture compared with posterior C1-C3 fixation. Methods: Twenty four patients for unstable Hangman's fracture were enrolled between July 2007 and June 2010 in this study. Thirteen patients underwent posterior C2-C3 fusion and 11 patients underwent posterior C1-C3 fusion. Clinical outcomes were evaluated using Neck Disability Index (NDI) scores and Visual Analogue Scale (VAS) scores during preoperative and postoperative follow up period. Plain radiographs were obtained on postoperative 1 day, 1 week, and then at 1, 2, 6, and 12 months. CT was done at postoperative 12 months in all patients for evaluation of bone fusion. The mean period of clinical follow-up was 15 months. Results: The mean ages were 43.3 years in C2-C3 group and 50.0 years in C1-C3 group. Mean follow-up period was 17.2 months in C2-C3 group and 16.3 months in C1-C3 group. VAS scores and NDI scores in C2-C3 group were much less than those in C1-C3 group at each follow-up period. The differences of VAS score and NDI scores between C2-C3 and C1-C3 groups at each follow-up period were statistically significant (p<0.001) by paired T-test. Solid Bone fusion was confirmed in all cases at the final follow-up. Conclusion: C2-C3 group showed better clinical and biomechanical results than C1-C3 group in terms of axial pain and disability of neck. [ABSTRACT FROM AUTHOR]

The use of synovial fluid-derived mesenchymal stem cells (SFMSCs) obtained from patients with degenerative arthropathy may serve as an alternative therapeutic strategy in osteoarthritis (OA) and rheumatoid arthritis (RA). For treatment of OA and RA patients, autologous transplantation of differentiated MSCs has several beneficial effects for cartilage regeneration including immunomodulatory activity. In this study, we induced chondrogenic differentiation of SFMSCs by inhibiting protein kinase A (PKA) with a small molecule and microRNA (miRNA). Chondrogenic differentiation was confirmed by PCR and immunocytochemistry using probes specific for aggrecan, the major cartilaginous proteoglycan gene. Absorbance of alcian blue stain to detect chondrogenic differentiation was increased in H-89 and/or miRNA-23btransfected cells. Furthermore, expression of matrix metalloproteinase (MMP)-9 and MMP-2 was decreased in treated cells. Therefore, differentiation of SFMSCs into chondrocytes through inhibition of PKA signaling may be a therapeutic option for OA or RA patients. [ABSTRACT FROM AUTHOR]

Home appliance manufacturers have recently been trying to provide smart products capable of various Internet services. For example, one health care manufacturer provides a Wi-Fi-capable scale. Once users register their information with the manufacturer's server, their weight and body fat records are automatically uploaded to the server whenever they measure their weight. The users can then watch and check their weight log easily using a smart device, such as a smartphone or tablet. One of the biggest problems, however, is that the initial configuration of the appliances and the user registration process may be quite complicated to typical users who are unfamiliar with such IT devices. This paper proposes an autoconfiguration system structure and protocol for Internet-capable home appliances, which supports the initial configuration and remote maintenance service of the device with only little user effort. Manufacturers can develop their own information appliances and provide differentiated services using the proposed system and protocol. [ABSTRACT FROM AUTHOR]

As an isotropic conductive adhesive, that is, a hybrid Cu paste composed of Cu powder, solder powder, and a fluxing resin system, has been quantitatively characterized. The mechanism of an electrical connection based on a novel concept of electrical conduction is experimentally characterized using an analysis of a differential scanning calorimeter and scanning electron microscope energy-dispersive X-ray spectroscopy. The oxide on the metal surface is sufficiently removed with an increase in temperature, and intermetallic compounds between the Cu and melted solder are simultaneously generated, leading to an electrical connection. The reliability of the hybrid Cu paste is experimentally identified and compared with existing Ag paste. As an example of a practical application, the hybrid Cu paste is used for LED packaging, and its electrical and thermal performances are compared with the commercialized Ag paste. In the present research, it is proved that, except the optical function, the electrical and thermal performances are similar to pre-existing Ag paste. The hybrid Cu paste could be used as an isotropic conductive adhesive due to its low production cost. [ABSTRACT FROM AUTHOR]

Despite the safety and feasibility of mesenchymal stem cell (MSC) therapy, an optimal cell type has not yet emerged in terms of electromechanical integration in infarcted myocardium. We found that poor to moderate survival benefits of MSC-implanted rats were caused by incomplete electromechanical integration induced by tissue heterogeneity between myocytes and engrafted MSCs in the infarcted myocardium. Here, we report the development of cardiogenic cells from rat MSCs activated by phorbol myristate acetate, a PKC activator, that exhibited high expressions of cardiac-specific markers and Ca2+ homeostasis-related proteins and showed adrenergic receptor signaling by norepinephrine. Histological analysis showed high connexin 43 coupling, few inflammatory cells, and low fibrotic markers in myocardium implanted with these phorbol myristate acetate-activated MSCs. Infarct hearts implanted with these cells exhibited restoration of conduction velocity through ciacreased tissue heterogeneity and improved myocardial contractility. These findings have major implications for the development of better cell types for electromechanical integration of cell-based treatment for infarcted myocardium. [ABSTRACT FROM AUTHOR]

Various home network middleware such as HAVi, LnCP, LonWorks, and UPnP have been designed. They coexist because one middleware cannot support diverse requests of services and devices. This circumstance creates an interoperability problem among devices based on various types of home network middleware. The Universal Middleware Bridge system is designed and implemented to solve this interoperability problem using a device conversion mechanism and a message translation mechanism among the middleware. These conversion mechanisms make it possible for devices to distinguish and control other devices connected to different middleware networks in the Universal Middleware Bridge system. These mechanisms also easily support new device and middleware by adding some XML files. [ABSTRACT FROM AUTHOR]

Background:Fine-needle aspiration diagnosis of follicular carcinoma presents a dilemma because malignancy is confirmed when vascular or capsular invasion is present. Completion thyroidectomy may be necessary when the diagnosis of follicular carcinoma is made following hemithyroidectomy. Ablation of the remaining lobe with radioactive iodine has been used as an alternative to completion thyroidectomy. Here we report an unusual apparent complication of this treatment.Patient Findings:A 51-year-old woman presented in September 24, 2009 with a stony, hard calcification of left thyroid gland. She complained of recent progressive hoarsening of her voice. Her medical history was positive for a subtotal thyroidectomy on September 6, 1993. Histologic analysis identified follicular carcinoma. Two months postoperatively, the remaining tissue was ablated with 131I (150 mCi) as an alternative to completion thyroidectomy. We performed computed tomography of the neck, which demonstrated 1.6 × 1.9 × 2.2 cm dense speculated calcification of the entire left residual thyroid gland. The calcification infiltrated the trachea wall. Completion thyroidectomy, including resection of the calcification, was performed. Histologic examination revealed dystrophic calcification.Conclusion:We report an unusual replacement of the thyroid remnant with calcification that developed over a period of 16 years following radioactive iodine lobe ablation as an alternative to completion thyroidectomy for thyroid follicular carcinoma. To our knowledge, this is the first such case in the English language literature. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented on Ala57Val as a novel mutation underlying severe congenital neutropenia.

We report on spatial mode behavior of the second harmonic (SH) generated by nonlinear interaction in the a z-cut Mg-doped periodically poled LiNbO3 (MgO:PPLN) ridge-type waveguide. Specific SH modes were selectively generated by mode mixing of the fundamental harmonic (FH) waves. In addition, high-order SH modes TM10 and TM01 were simultaneously generated under similar phase-matching conditions in a quasi-phase matching (QPM) grating structure. The interfered mode profiles of high-order SH modes demonstrated specific mode distribution to have a diagonal angle and the Laguerre–Gaussian (LG) mode at a certain phase-matching condition obtained by temperature control. [ABSTRACT FROM AUTHOR]