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This study analyzed the association between autoantibody types and salivary gland hypofunction in patients with primary Sjögren's syndrome (pSS).A retrospective analysis was performed on patients who visited the Department of Orofacial Pain and Oral Medicine at Yonsei University Dental Hospital from January 1, 2010 to May 31, 2021, and who were diagnosed with pSS. Out of 191 patients who fulfilled the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria, 50 were positive for both anti-Ro/SSA and anti-La/SSB, whereas 97 had anti-Ro/SSA but not anti-La/SSB antibodies. Forty-four patients for whom neither anti-Ro/SSA nor anti-La/SSB antibodies were found were diagnosed with Sjögren's syndrome by minor salivary gland biopsy.The anti-Ro/SSA antibody-positive group showed higher rheumatoid factor (RF) levels than the anti-Ro/SSA antibody-negative group. The anti-La/SSB antibody-positive group showed lower unstimulated whole saliva (UWS), stimulated whole saliva (SWS), higher erythrocyte sedimentation rate and RF level than the anti-La/SSB antibody-negative group. In addition, the group with both anti-Ro/SSA and anti-La/SSB antibodies showed lower UWS than the group with only anti-Ro/SSA antibodies. However, there were no significant differences in UWS or SWS after taking pilocarpine, and C-reactive protein.UWS and SWS were lower when a patient was positive for anti-La/SSB, showing that anti-La/SSB is more likely to be involved in salivary gland hypofunction than anti-Ro/SSA in patients with pSS. Therefore, performing laboratory tests, including anti-La/SSB, helps predict the prognosis of salivary gland function in patients with suspected pSS.

Chemotherapy-induced cognitive impairment (CICI) is often reported as a neurotoxic side effect of chemotherapy. Although CICI has emerged as a significant medical problem, meaningful treatments are not currently available due to a lack of mechanistic understanding underlying CICI pathophysiology. Using the platinum-based chemotherapy cisplatin as a model for CICI, we show here that cisplatin suppresses nicotinamide adenine dinucleotide (NAD+) levels in the adult female mouse brain in vivo and in human cortical neurons derived from induced pluripotent stem cells in vitro. Increasing NAD+ levels through nicotinamide mononucleotide (NMN) administration prevented cisplatin-induced abnormalities in neural progenitor proliferation, neuronal morphogenesis, and cognitive function without affecting tumor growth and antitumor efficacy of cisplatin. Mechanistically, cisplatin inhibited expression of the NAD+ biosynthesis rate-limiting enzyme nicotinamide phosphoribosyl transferase (Nampt). Selective restoration of Nampt expression in adult-born neurons was sufficient to prevent cisplatin-induced defects in dendrite morphogenesis and memory function. Taken together, our findings suggest that aberrant Nampt-mediated NAD+ metabolic pathways may be a key contributor in cisplatin-induced neurogenic impairments, thus causally leading to memory dysfunction. Therefore, increasing NAD+ levels could represent a promising and safe therapeutic strategy for cisplatin-related neurotoxicity. Significance: Increasing NAD+ through NMN supplementation offers a potential therapeutic strategy to safely prevent cisplatin-induced cognitive impairments, thus providing hope for improved quality of life in cancer survivors.

Purpose The criteria for discontinuing antiepileptic drugs (AEDs) in children with well-controlled epilepsy remain unclear. This study sought to identify the recurrence rate of epilepsy after the discontinuation of AEDs and the risk factors associated with recurrence. Methods We retrospectively reviewed the records of 441 children who discontinued AEDs at our department of pediatrics from August 2007 to July 2017. AED tapering was performed in patients who were seizure-free for more than 2 years after taking AEDs, and patients were monitored for 1 year after the discontinuation of AEDs. Results We found that 87 patients (87/441, 19.7%) experienced seizure recurrence within 1 year after the discontinuation of AEDs. Among them, 38 patients (38/87, 43.7%) experienced recurrence during AED tapering. The recurrence of seizures was related to the patient’s age at AED onset and when seizures were controlled, a history of seizure recurrence after previous discontinuation of AEDs or a seizure episode during AED administration, and no improvement of electroencephalographic (EEG) findings. Conclusion The recurrence rate within 1 year after the discontinuation of AEDs was almost 20%, and nearly half of the recurrences took place during the tapering period. We recommend caution when considering whether to discontinue AEDs in patients with a history of seizure recurrence after AED discontinuation, a seizure episode during AED administration, or no (or slight) improvement of EEG findings.

A number of cell culture approaches have been described for maintenance of primary hepatocytes. Forming hepatocytes into three-dimensional (3-D) spheroids is one well-accepted method for extending epithelial phenotype of these cells. Our laboratory has previously observed enhanced function of two-dimensional (2-D, monolayer) hepatocyte cultures in microfluidic devices due to increased production of several hepato-inductive growth factors, including hepatocyte growth factor (HGF). In the present study, we wanted to test a hypothesis that culturing hepatocyte spheroids (3-D) in microfluidic devices will also result in enhanced phenotype and function. To test this hypothesis, we fabricated devices with small and large volumes. Both types of devices included a microstructured floor containing arrays of pyramidal wells to promote assembly of hepatocytes into spheroids with individual diameters of ~100 µm. The hepatocyte spheroids were found to be more functional, as evidenced by higher level of albumin synthesis, bile acid production, and hepatic enzyme expression, in low-volume compared with large-volume devices. Importantly, high functionality of spheroid cultures correlated with elevated levels of HGF secretion. Although decay of hepatic function (albumin secretion) was observed over the course 3 wk, this behavior could be abrogated by inhibiting TGF-β1 signaling. With TGF-β1 inhibitor, microfluidic hepatocyte spheroid cultures maintained high and stable levels of albumin synthesis over the course of 4 wk. To further highlight utility of this culture platform for liver disease modeling, we carried out alcohol injury experiments in microfluidic devices and tested protective effects of interleukin-22: a potential therapy for alcoholic hepatitis.

Three-dimensional (3D) printing technology is highly regarded in the field of dentistry. Three-dimensional printed resin restorations must undergo a washing process to remove residual resin on the surface after they have been manufactured. However, the effect of the use of different washing solutions and washing times on the biocompatibility of the resulting resin restorations is unclear. Therefore, we prepared 3D-printed denture teeth and crown and bridge resin, and then washed them with two washing solutions (isopropyl alcohol and tripropylene glycol monomethyl ether) using different time points (3, 5, 10, 15, 30, 60, and 90 min). After this, the cell viability, cytotoxicity, and status of human gingival fibroblasts were evaluated using confocal laser scanning. We also analyzed the flexural strength, flexural modulus, and surface SEM imaging. Increasing the washing time increased the cell viability and decreased the cytotoxicity (p < 0.001). Confocal laser scanning showed distinct differences in the morphology and number of fibroblasts. Increasing the washing time did not significantly affect the flexural strength and surface, but the flexural modulus of the 90 min washing group was 1.01 ± 0.21 GPa (mean ± standard deviation), which was lower than that of all the other groups and decreased as the washing time increased. This study confirmed that the washing time affected the biocompatibility and mechanical properties of 3D printed dental resins.

The receptor activator of nuclear factor-kappa B ligand (RANKL) mediates osteoclast differentiation and functions by inducing Ca2+ oscillations, activating mitogen-activated protein kinases (MAPKs), and activating nuclear factor of activated T-cells type c1 (NFATc1) via the RANK and tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) interaction. Reactive oxygen species (ROS) also plays an important role during osteoclastogenesis and Sestrin2, an antioxidant, maintains cellular homeostasis upon stress injury via regulation of ROS, autophagy, and inflammation. However, the role of Sestrin2 in osteoclastogenesis remains unknown. In this study, we investigated the role of Sestrin2 in the RANKL-RANK-TRAF6 signaling pathway during osteoclast differentiation. Deletion of Sestrin2 (Sesn2) increased bone mass and reduced the number of multinucleated osteoclasts on bone surfaces. RANKL-induced osteoclast differentiation and function decreased in Sesn2 knockout (KO) bone marrow-derived monocytes/macrophages (BMMs) due to inhibition of NFATc1 expression, but osteoblastogenesis was not affected. mRNA expression of RANKL-induced specific osteoclastogenic genes and MAPK protein expression were lower in Sesn2 KO BMMs than wild-type (WT) BMMs after RANKL treatment. However, the Sesn2 deletion did not affect ROS generation or intracellular Ca2+ oscillations during osteoclastogenesis. In contrast, the interaction between TRAF6 and p62 was reduced during osteoclasts differentiation in Sesn2 KO BMMs. The reduction in the TRAF6/p62 interaction and TRAP activity in osteoclastogenesis in Sesn2 KO BMMs was recovered to the WT level upon expression of Flag-Sesn2 in Sesn2 KO BMMs. These results suggest that Sestrin2 has a novel role in bone homeostasis and osteoclasts differentiation through regulation of NFATc1 and the TRAF6/p62 interaction.

Cancer is a second leading cause of death and current treatments which are applicable to cancers are still confined to chemotherapeutics followed by surgical debulking. Currently, image-guided drug delivery system (IGDDS) has strong satisfaction for its request and there has been intensively researched to develop innovative IGDDS by using nanoparticles including organic or inorganic theranostic systems. Among them, liposomes, polymeric micelles, dendrimers, and carbon nanotubes represent major organic systems while gold nanoparticles, iron oxide nanoparticles, quantum dots, and silica nanoparticles are major inorganic systems. Bae et al. built pH-sensitive PEG-b-PHis polymeric micelles displaying the sensitivity to tumor tissues of slightly acidic pH. However, one limitation holds on this well-designed work that the originally nonfluorescent polymeric micelles will dissociate by high dilution into unimers at a concentration below the CMC, which initiates premature emission prior to reaching the pathological location. The double hydrophilic and amphiphilic pH-sensitive block copolymers are mainly discussed below.

Oncothermia, a special form of hyperthermia for oncological purposes, has been widely shown to be an effective mode of cancer therapy. However, its adoption among standard therapeutic practices has been limited by constraints in delivering sufficient thermal energy to tumor targets. To overcome these unique challenges in delivery presented by oncothermic therapeutics, we engineered a novel universal platform for hyperthermia cancer therapy utilizing versatile biocompatible materials. Herein, we show that Gold particle-in-particle (PIP), in which gold nanoparticles are physically confined within PLGA-PEG nanoparticles, significantly enhances thermal energy production by red-shifting the gold nanoparticle's absorption spectra via a mechanism in which we call nanoconfinement-induced therapeutic enhancement (NITE). NITE mediated Gold PIPs significantly suppress breast, skin, and multidrug resistant tumors and result in a multifold increase of heat shock protein expressed by cancer cells

Plasma damage of indium-gallium-zinc-oxide (IGZO) thin film transistor (TFT) was investigated. The IGZO TFT was fabricated and the performance was measured before and after BCl3 and/or Cl2 plasma treatment to evaluate the IGZO damage. The BCl3 and/or Cl2 plasma deteriorated the IGZO TFT performance significantly even after a short exposure time in the plasma. We propose a new wet etching process to remove a source/drain metal without damaging the underlying IGZO layer. The wet etching process can be utilized for the fabrication of IGZO TFT array using a roll-to-roll process via a self-aligned imprint lithography technique.

In this study, we described an "all-in-one" polymer-lipid conjugate (PEG2k-ppTAT-PEG1k-PE) that could self-assemble to matrix metalloproteinase 2 (MMP2)-sensitive multifunctional micelles. The assembled micelles had several key features, including a protective long chain poly(ethylene glycol) (PEG2k) (the outer shell), an MMP2-sensitive peptide linker (pp) (the tumor-targeting middle layer), a trans-activating transcriptional activator (TAT) peptide (the cell-penetrating middle layer), and a stable PEG1k-PE micelle for drug loading (the inner core). In the absence of MMP2, the PEG2k-ppTAT-PEG1k-PE micelles were intact and showed low bioactivity due to the surface-anchored PEG2k, whereas in the presence of MMP2, the pp was cleaved, resulting in the PEG2k deshielding and exposure of the previously hidden TAT for enhanced intracellular drug delivery. Even if completely cleaved by MMP2, the remaining PEG1k-PE micelles were stable and the micelles' particle size and drug release were not significantly influenced. The paclitaxel (PTX)-loaded PEG2k-ppTAT-PEG1k-PE micelles showed significant MMP2-dependent cellular uptake, tumor penetration, and anticancer activity in various cancer cells and three-dimensional multicellular spheroids. Because of the enhanced intracellular drug accumulation, these multifunctional micelles were able to sensitize the drug-resistant cancer cells and their spheroids to PTX treatments. Furthermore, in vivo tumor uptake and retention data indicated that the PEG2k-ppTAT-PEG1k-PE micelles could dramatically increase the residence time of their payloads in the tumor.

The ability to detect multiple analytes in a small sample volume has significance for numerous areas of research, including organs-on-chip, small animal experiments, and neonatology. The objective of this study was to develop an automated microfluidics platform for multiplexed detection of analytes in microliter sample volumes. This platform employed computer-controlled microvalves to create laminar co-flows of sample and assay reagent solutions. It also contained valve-regulated cross-junction for discretizing sample/reagent mixtures into water-in-oil droplets. Microfluidic automation allowed us to control parameters related to frequency of droplet generation and the number of droplets of the same composition, as well as the size of droplets. Each droplet represented an individual enzymatic assay carried out in a sub-nanoliter (0.8 nL) volume reactor. An enzymatic reaction involving target analyte and assay reagents produced colorimetric or fluorescent signals in droplets. Importantly, intensity of optical signal was proportional to the concentration of analyte in question. This microfluidic bioanalysis platform was used in conjunction with commercial "mix-detect" assays for glucose, total bile acids, and lactate dehydrogenase (LDH). After characterizing these assays individually, we demonstrated sensitive multiplexed detection of three analytes from as little as 3 μL. In fact, this volume was sufficient to generate multiple repeat droplets for each of the three biochemical assays as well as positive control droplets, confirming the quality of assay reagents and negative control droplets to help with background subtraction. One potential application for this microfluidic bioanalysis platform involves sampling cell-conditioned media in organ-on-chip devices. To highlight this application, hepatocyte spheroids were established in microfluidic devices, injured on-chip by exposure to lipotoxic agent (palmitate), and then connected to the bioanalysis module for daily monitoring of changes in cytotoxicity (LDH), energy metabolism (glucose), and liver function (total bile acids). Microfluidic in-droplet assays revealed increased levels of LDH as well as reduction in bile acid synthesis-results that were consistent with hepatic injury. Importantly, these experiments highlighted the fact that in-droplet assays were sufficiently sensitive to detect changes in functional output of a relatively small (∼100) number of hepatocyte spheroids cultured in a microfluidic device. Moving forward, we foresee increasing the multiplexing capability of this technology and applying this platform to other biological/medical scenarios where detection of multiple analytes from a small sample volume is desired.

A highly efficient synthetic route was successfully developed to prepare crystallized and well dispersed Cu, Cu2O, and CuO nanoparticles (NPs) on reduced graphene oxide (rGO) by controlling the impregnation condition of a copper-precursor (Cu(NO3)2·3H2O) on graphene oxide (GO) and subsequent thermal treatments. The morphological and chemical structures of the nanocomposites were systemically evaluated by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), X-ray absorption fine structure (XAFS), and transmission electron microscopy (TEM). The rGO based CuOx nanocomposites exhibited a much higher catalytic activity than bare CuOx NPs toward the decomposition reaction of dye molecules under visible light illumination. Among the CuOx/rGO nanocomposites, CuO/rGO showed excellent photocatalytic efficiency and recyclability without significant loss of activity. Based on the XPS, XRD, XAFS, and TEM results, the high photocatalytic efficiency of the CuO/rGO can be attributed to the synergistic combination of dye adsorptivity and electron acceptability of the rGO, the surface hydroxyl species in the CuO/rGO, and the narrow band gap and smaller size of the CuO NPs. This work could be applied to the removal and water treatment of waste dye.

Numb chin syndrome, or mental neuropathy is a rare sensory neuropathy characterized by abnormal sensation such as hypoesthesia, paresthesia, or dysesthesia in the chin and lower lip innervated by the mental nerve. Sensory neuropathy of mental nerve is somewhat familiar to dentists because it can occur following nerve damage by trauma or dental treatment such as implant surgery or third molar extraction. It can also result from dental causes including abscess or osteomyelitis. However, it can be the first sign of the systemic disease or malignancy if it is not related to dental causes. In this study, we present the case of a patient who present with hypoesthesia and pain in chin area without other symptoms and is later diagnosed with diffuse large B-cell lymphoma.

Lichen planus is a chronic disease characterized by bilateral and multiple lesions on the skin or oral mucosa. Lichen planus is caused by immune mediated degeneration along the border between epithelium and connective tissue. The incidence of oral squamous cell carcinoma in patients diagnosed with oral lichen planus (OLP) is reported to be between 0.4%-5.6% in different studies and the World Health Organization has categorized lichen planus as “a potentially malignant disorder”. However, the correlation between OLP and oral cancer still remains controversial as some reported that the reason for increased incidence of squamous cell carcinoma in OLP patient is misdiagnosis of dysplastic lesion as OLP. This report aims to discuss the correlation between OLP and oral cancer through a case of middle aged woman diagnosed with OLP who was successfully treated but developed squamous cell carcinoma 8 years later.

Nanoparticle-based imaging and therapy are of interest for theranostic nanomedicine. In particular, superparamagnetic iron oxide (SPIO) nanoparticles (NPs) have attracted much attention in cancer imaging, diagnostics, and treatment because of their superior imagability and biocompatibility (approved by the Food and Drug Administration). Here, we developed SPIO nanoparticles (NPs) that self-assembled into magnetic nanoclusters (SAMNs) in aqueous environments as a theranostic nano-system. To generate multi-functional SPIO NPs, we covalently conjugated β-cyclodextrin (β-CD) to SPIO NPs using metal-adhesive dopamine groups. Polyethylene glycol (PEG) and paclitaxel (PTX) were hosted in the β-CD cavity through high affinity complexation. The core-shell structure of the magnetic nanoclusters was elucidated based on the condensed SPIO core and a PEG shell using electron microscopy and the composition was analyzed by thermogravimetric analysis (TGA). Our results indicate that nanocluster size could be readily controlled by changing the SPIO/PEG ratio in the assemblies. Interestingly, we observed a significant enhancement in magnetic resonance contrast due to the large cluster size and dense iron oxide core. In addition, tethering a tumor-targeting peptide to the SAMNs enhanced their uptake into tumor cells. PTX was efficiently loaded into β-CDs and released in a controlled manner when exposed to competitive guest molecules. These results strongly indicate that the SAMNs developed in this study possess great potential for application in image-guided cancer chemotherapy. Statement of Significance In this study, we developed multi-functional SPIO NPs that self-assembled into magnetic nanoclusters (SAMNs) in aqueous conditions as a theranostic nano-system. The beta-cyclodextrin (β-CD) was immobilized on the surfaces of SPIO NPs and RGD-conjugated polyethylene glycol (PEG) and paclitaxel (PTX) were hosted in the β-CD cavity through high affinity complexation. We found that nanocluster size could be readily controlled by varying the SPIO/PEG ratio in the assemblies, and also demonstrated significant improvement of the functional nanoparticles for theranostic systems; enhanced magnetic resonance, improved cellular uptake, and efficient PTX loading and sustained release at the desired time point. These results strongly indicate that the SAMNs developed in this study possess great potential for application in image-guided cancer chemotherapy.

The aim of this study was to evaluate whether a new method using quantitative light-induced fluorescence-digital (QLF-D) was appropriate for the diagnosis of oral malodor by quantifying the fluorescence of tongue coating.This study examined 103 healthy subjects who have an oral malodor as a main complaint. The levels of oral malodor were measured by organoleptic scores (OLS) and volatile sulfur compound (VSC) levels. The fluorescent tongue coating images captured by QLF-D were quantified as the integrated fluorescence score (IF score) by multiplying the intensity and area of fluorescence. The correlations between the fluorescence parameters and OLS as well as VSC levels and the diagnostic accuracy of the IF score were evaluated.The IF score of tongue coating showed a significant positive correlation with the OLS (r=0.54, p0.01) and the VSC levels (r=0.49, p0.01). This score was significantly differed with the level of oral malodor (p0.001), and its AUC was 0.72 in identifying the patient with definite oral malodor (≥OLS 2).A new method quantifying tongue coating fluorescence detected by QLF-D can be used to diagnose oral malodor and assess its severity in the clinical practice.

Infantile hepatic hemangioma (IHH) is the most common type of benign hepatic vascular tumor that presents in infancy. IHH presents as abdominal mass, cutaneous hemangiomas, and unexplained jaundice. Children with asymptomatic lesions generally undergo spontaneous regression within a year, but it may become symptomatic and be associated with life-threatening complications including congestive heart failure, consumptive coagulopathy and hepatic rupture. Treatment options are divided into medical treatment, interventional therapy including embolization, and surgical resection. The steroid has been considered as first-line medical treatment, but it has a low therapeutic effect and may be associated with significant side effects. Since propranolol has been recently used successfully to treat cutaneous infantile hemangiomas, we decided to use it in a patient who presented with hepatic hemangioma and skin hemangiomatosis. In our case, regression of both skin and hepatic lesions was noted without any adverse effects. We think propranolol can be considered as a potential first-line therapy in patients with symptomatic hepatic hemangioma.

Objective: This study was conducted to assess the clinical usability of the zero-echo time (ZTE) technique of MRI for evaluating bone changes of the temporomandibular joint (TMJ) in comparison with CBCT. Methods: Twenty patients with TMJ disorder who underwent both CBCT and MRI were randomly selected. CBCT images were obtained with an Alphard 3030 device (Asahi Roentgen Ind., Co. Ltd, Kyoto, Japan). MRIs were obtained using a 3.0 T scanner (Pioneer; GE Healthcare, Waukesha, WI, USA) and a 21-channel head coil. An isotropic three-dimensional proton-density-weighted ZTE sequence was acquired. Two radiologists evaluated 40 joints of 20 patients for the presence of the following osseous changes: flattening, erosion, osteophyte and sclerosis of the condyle; and flattening, erosion and sclerosis of the articular fossa. CBCT and ZTE-MRI assessments were performed at a 2-month interval. The prevalence-adjusted and bias-adjusted κ statistic was used to analyse interexaminer and intraexaminer agreement and the agreement between ZTE-MRI and CBCT. Results: Intraexaminer and interexaminer agreement analyses of ZTE-MRI showed high reproducibility (κ>0.80), which was comparable to that of CBCT. Flattening, osteophyte and sclerosis of the condyle and all types of bone changes in the mandibular fossa showed nearly perfect agreement between CBCT and ZTE-MRI (κ = 0.80–0.90). Erosion of the condyle showed substantial agreement between both sets of images (κ = 0.65–0.70). Conclusions: It is suggested that ZTE-MRI provides clinically reliable images for bone assessment in TMJ disorder. MRI may become a beneficial diagnostic tool for patients with both TMJ disc and bone pathology, with advantages involving medical costs and radiation dose.

The difference in autofluorescence between enamel and dentine layer has prompted recommendations to use the quantitative light-induced fluorescence (QLF) method for quantifying tooth wear (TW). This study investigated the potential of QLF for distinguishing the severity of occlusal TW based on differences in the autofluorescence intensity.In total, 106 extracted permanent molars and premolars having suspected wear without pulp exposure were used. The severity of wear was determined by visually examining all teeth using the tooth wear index (TWI) of Smith and Knight. QLF images were captured and converted into 8-bit grayscale images. The difference in the fluorescence intensity (ΔG) was calculated by comparing mean grayscale levels between sound and worn areas. Finally, histological examination was conducted by stereomicroscope to confirm the presence of dentine exposure.100 teeth were included in the final analysis without six teeth having enamel cracks around worn area. The ΔG values increased with the severity of TW as quantified using conventional TWI codes, and differed significantly between the sound and enamel- and dentine-wear teeth (P 0.001). The histology indicated that enamel remained on 57 teeth, while 43 teeth had dentine-exposed wear and showed significant differences in ΔG compared with enamel-remained teeth.The fluorescence intensity differed significantly depending on the presence of dentine exposure. ΔG could be used to distinguish between sound and enamel- and dentine-wear teeth with a significant correlation. These findings indicate that QLF could be useful for determining the severity of TW of occlusal surfaces noninvasively.

The aim of this study was to assess the oral health knowledge, attitude and behavior among geriatric care workers in long-term care facilities. A self-administered questionnaire was obtained from 212 geriatric care workers attending a professional education program of 2014 dementia pilot project. The questionnaire consisted of 4 parts of the training experience (2 items), knowledge (16 items), attitude (13 items), and behavior (4 items) on oral health care. Collected data were analyzed by frequency analysis, independent t-test, and one-way ANOVA using SPSS Statistics ver. 20.0. The percentage of educational experience on oral care was 27.9% and most respondents answered that they have received the education about denture cleaning (98.3%) and brushing method (91.4%). The average knowledge score was , and respondents showed high-level agreement in 8 of the 10 items in attitude questions. They revealed difficulties in providing oral care to the elderly people because of their lack of knowledge. The deficiencies of knowledge about oral care would have a decisive effect on not only oral and general health, but also quality of life of the elderly people. Therefore, it is required to develop professional oral care training programs for geriatric care workers and support systems should be legalized.

Liposomes containing nanogels (liponanogels) were fabricated by sonicating heparin-Pluronic (HP) nanogels with pegylated lipids for ribonuclease (RNase) delivery. Liponanogels with an average diameter of 316 nm were obtained and their spherical morphology was elucidated by atomic force microscopy (AFM). Confocal laser scanning microscopy (CLSM) revealed the core-shell structure of the liponanogels using two different fluorescent dyes, showing that HP nanogels were localized in the core of the liposomes. Interestingly, the hybridization of these two systems remedies the drawbacks of each system while they hold their strengths called “WIN-WIN effect”. When HP nanogels were used to encapsulate RNase in liponanogels, the loading of RNase was almost doubled as compared with the loading in liposomes without nanogels. Due to the presence of a lipid bilayer on the nanogels, the release of RNase was prolonged over 4 days whereas it was much faster (82% after 21 h) for bare HP nanogels. The cytotoxicity of the RNase-loaded liponanogels was much higher than that of free RNase because of the endocytic cellular uptake of the particles. We believe that these hybrid liponanogel systems can potentially be utilized for the hereditary diseases and targeted cancer therapy since they can efficiently load RNases and sustainly release in target cells. Open image in new window

To improve tumor targetability and drug efficacy and decrease drug resistance of dasatinib (DSB), the multifunctional micellar nanoparticles that combined the matrix metalloproteinase 2 (MMP2)-sensitive tumor (site) targeting with folate receptor-mediated tumor (cell) targeting were developed. Two major functional polymers, polyethylene glycol (5000 Da)-MMP2-sensitive peptide-phosphoethanolamine (PEG5k-pp-PE) and folic acid-polyethylene glycol (2000 Da)-phosphoethanolamine (FA-PEG2k-PE), were synthesized to construct the dual-targeted micellar nanoparticles (MMP/FR micelles). In the absence of MMP2, the FA was shielded by PEG5k and the MMP/FR micelles showed low bioactivity. In the presence of MMP2, the nanoparticulate structure, stability, and cargo release profile of the MMP/FR micelles were not significantly affected, however, the MMP2-mediated PEG5k deshielding and FA exposure remarkably increased the cellular uptake and anticancer activity of the micelles in the MMP2 and FR expressing (MMP2+/FR+) cells, including multidrug resistant (MDR) cancer cells, rather than the MMP2- and FR- cells. In the 3D MDR tumor spheroids, the significant MMP2-dependent tissue penetration, uptake and cytotoxicity of the MMP/FR micelles were also observed. Furthermore, in the in vivo biodistribution study, the MMP2 and FR dual targeting strategy could significantly prolong the systemic circulation, decrease the nonspecific distribution in nontumor tissues, and increase the tumor accumulation of the polymeric micelles in a melanoma xenograft mouse model. The MMP2-sensitive FR-targeted micelles might have great potential as a tumor-targeted platform for delivery of molecular targeted therapeutics.

This paper presents a scheduling problem for a high-density robotic workcell using multi-objective genetic algorithm. We propose a new algorithm based on NSGA-II(Non-dominated Sorting Algorithm-II) which is the most popular algorithm to solve multi-objective optimization problems. To solve the problem efficiently, the proposed algorithm divides the problem into two processes: clustering and scheduling. In clustering process, we focus on multi-robot positions because they are fixed in manufacturing system and have a great effect on task distribution. We test the algorithm by changing multi-robot positions and compare it to previous work. Test results shows that the proposed algorithm is effective under various conditions.

In situ-forming hydrogels are an attractive class of implantable biomaterials that are used for biomedical applications. These injectable hydrogels are versatile and provide a convenient platform for delivering cells and drugs via minimally invasive surgery. Although several crosslinking methods for preparing in situ forming hydrogels have been developed over the past two decades, most hydrogels are not sufficiently versatile for use in a wide variety of tissue-engineering applications. In recent years, enzyme-catalysed crosslinking approaches have been emerged as a new approach for developing in situ-forming hydrogels. In particular, the horseradish peroxidase (HRP)-catalysed crosslinking approach has received increasing interest, due to its highly improved and tunable capacity to obtain hydrogels with desirable properties. The HRP-catalysed crosslinking reaction immediately occurs upon mixing phenol-rich polymers with HRP and hydrogen peroxide (H2O2) in aqueous media. Based on this unique gel-forming feature, recent studies have shown that various properties of formed hydrogels, such as gelation time, stiffness and degradation rate, can be easily manipulated by varying the concentrations of HRP and H2O2. In this review, we outline the versatile properties of HRP-catalysed in situ-forming hydrogels, with a brief introduction to the crosslinking mechanisms involved. In addition, the recent biomedical applications of HRP-catalysed in situ-forming hydrogels for tissue regeneration are described.

Many women around the world are suffering from urinary incontinence, defined as the unintentional leakage of urine by external abnormal pressure. Although various kinds of materials have been utilized to treat this disease, therapies that are more effective are still needed for the treatment of urinary incontinence. Here, we present a macro/nanogel composed of in situ forming gelatin-based macrogels and self-assembled heparin-based nanogels, which can serve as an injectable and bioactive bulking material for the treatment of urinary incontinence. The hybrid hydrogels were prepared via enzymatic reaction in the presence of horseradish peroxidase and hydrogen peroxide. Incorporating a growth factor (GF)-loaded heparin nanogel into a gelatin gel matrix enabled the hybrid gel matrix to release GF continuously up to 28 days. Moreover, we demonstrated that the hydrogel composites stimulated the regeneration of the urethral muscle tissue surrounding the urethral wall and promoted the recovery of their biological function when injected in vivo. Thus, the macro/nanohydrogels may provide an advanced therapeutic technique for the treatment of urinary incontinence as well as an application for regenerative medicine.

Synovial chondromatosis (SC) in temporomandibular joint is a rare benign disorder characterized by cartilaginous metaplasia of the mesenchymal remnants of the synovial tissue. The etiology of the disease is unclear but may be associated with trauma, overuse, local infection, and embryologic disturbance. SC does not spontaneously resolve and respond to nonsurgical treatment. SC should be differentially diagnosed with other temporomandibular joint disorders such as arthralgia or osteoarthritis because surgery should be done for managing it. However, primary diagnosis of SC is not easy because of nonspecific symptoms and signs. For the patients with unsuccessful conservative treatment response, especially accompanied by crepitus, preauricular swelling or posterior open bite, computed tomography/cone-beam computed tomography or magnetic resonance imaging should to be performed to exclude SC. We discussed the importance of the early diagnosis and surgical treatment of SC from this case.

Oral hairy leukoplakia occurs on the lateral surface of the tongue that clinically as an asymptomatic white lesion. It is mainly found in patient with human immunodeficiency virus infection. However, it rarely outbreak immunosuppressed patients after organ transplantation, or the patients taking steroids or immunosuppressants. It is the result of proliferating Epstein-Barr virus in the oral epithelium. Most of human immunodeficiency virus infected patients with oral hairy leukoplakia are highly contagious and possible to progress acquired immunodeficiency syndrome. Therefore, the early diagnosis of oral hairy leukoplakia is very important. Taking a thorough history and human immunodeficiency virus screening test is highly recommended in case oral hairy leukoplakia is detected. In this case, a 29-year-old man presented with whitish lesion on lateral border of tongue is diagnosed as oral hairy leukoplakia and human immunodeficiency virus infection.

In situ formation of horseradish peroxidase (HRP)-free gelatin hydrogels was achieved via ferromagnetic microbead-assisted enzymatic cross-linking. Gelation time and mechanical stiffness of the hydrogels can be tuned in situ, which makes HRP-free gelatin hydrogels suitable for injectable cell delivery.

Summary This study examined changes in masticatory function after botulinum toxin type A (BTX-A) injection using objective and subjective tests during 12 weeks. Also, we compared differences in masticatory function between group in which only masseter muscle (M group) was injected and group in which masseter and temporal muscle (M-T group) were injected. Forty subjects were assigned into two groups; M group (n = 20) and the M-T group (n = 20). The Meditoxin® was used as BTX-A injection. The mixing ability index (MAI) was used as the objective indicator, and visual analogue scale (VAS) and food intake ability (FIA) index were used as subjective indicators. Overall, the masticatory function drastically declined after 4 weeks and gradually recovered with time. Compared with the pre-injection state, the masticatory function decreased by 89·2% (MAI), 12·2% (FIA) and 32·2% (VAS) 4 weeks after the injection (P

Bioreducible are described here, cross-linked Pluronic micelles carrying doxorubicin (DOX) for folate-mediated cancer targeting. The amine-terminated Pluronic® F-127 was functionalized by grafting acrylic acid (AA) to the hydrophobic block (AA-Pluronic-NH2). Folic acid (FA), hydrazine (H), and cystamine (C) were sequentially conjugated to AA-Pluronic-NH2, followed by DOX conjugation via an acid-labile hydrazone bond (FA-Pluronic-C/H-DOX). The DOX content was approximately 143 µg/mg of polymer. We prepared bioreducible cross-linked micelles using FA-Pluronic-C/H-DOX, which had a diameter of 156.1 nm. After incubation for 24 h with 10 mM of dithiothreitol, the micelle size decreased dramatically to 87.6 nm with a broad distribution, indicating that disulfide bonds in the micelle core were reductively cleaved. In vitro release data showed that the conjugated DOX was released slowly from the FA-Pluronic C/H-DOX micelles at pH 7.4, whereas there was a rapid DOX release at pH 5.2. Confocal images of HeLa cells showed enhanced cellular uptake of FA-Pluronic-C/H-DOX micelles as compared to nontargeted Pluronic-C/H-DOX micelles. The FA-Pluronic-C/H-DOX micelles killed more cells than the nontargeted micelles, but the cytotoxic effect was not as significant as free DOX. Additionally, micelles without DOX were not cytotoxic. On the basis of these results, pH- and redox potential–responsive FA-Pluronic-C/H-DOX micelles could potentially function as cancer-targeted and controlled DOX delivery systems.

This study was aimed to evaluate the masticatory efficiency after botulinum toxin type A (BTX-A) injection during 12 weeks using objective and subjective test. Also, we compared the difference of masticatory efficiency between group that injected into the masseter muscle only (M-group) and group that injected into the masseter and temporalis muscle (M-T group). The mixing ability index (MAI) was used as the objective indicator, and visual analogue scale (VAS) and food intake ability (FIA) index were used as the subjective indicators. It was concluded that masticatory efficiency was significantly lowered after a BTX-A injection into the masticatory muscle, but it gradually recovered in a predictable pattern by the 12 weeks. The disturbance of subjective masticatory efficiency was lasted longer than objective masticatory efficiency. The masticatory efficiency was lower in M-T group than M group. It was statistically significant in the VAS and FIA at 4 weeks, but the MAI showed no significancy. After 4weeks, there was rapid recovery of muscle function in M-T group, and the difference between two groups was not significant. It could be concluded that there will be no serious disturbance of mastication compared to injection is done only into the masseter muscle, even if injection is done into the masseter and temporalis muscle in dose of this study. According to the food properties, it was confirmed that people feel more discomfort on taking hard and tough foods after BTX-A injection and not only hard foods, but also intake of soft and runny foods were influenced by botulinum toxin injection.

We describe a facile and effective poly(ethylene glycol) (PEG) coating method that has not been used previously for decoration of nanogels. Layer-by-layer (LbL) assembly was the technique of choice to introduce PEG onto the surface of multi-layered nanogels (MLNGs). Pegylated MLNGs were prepared simply by sequentially dispersing nanogels in solutions of cationic polymer, anionic polymer, and modified PEGs, and each coating step was validated by measuring changes in size and surface charge. Particularly, a peptide linker that is cleavable by matrix metalloproteinase-2 (MMP-2) in the tumor microenvironment was introduced between PEG layer and nanogels because it is known that PEG reduces the uptake of nanoparticles in tumor cells due to its high mobility. In vitro cell studies demonstrated that MLNGs with MMP-cleavable PEGs enhanced the particle uptake up to 3 times in tumor cells due to unmasking of PEG brushes as compared to pegylated MLNGs without MMP-sensitive peptide linkers.

Combination chemotherapy using more than two therapeutic agents with different modes of action is a promising strategy that can be used to enhance the therapeutic efficacy of cancer treatment, even though it is a complicated treatment modality. The aim of this study was to investigate how a novel multidrug nanocarrier is effective for combination chemotherapy in vitro and, more specifically, whether combined agents with different modes of action and physicochemical properties show synergistic cytotoxicity with the use of this nanocarrier. A heparin-Pluronic (Hep-Pr) nanogel encapsulating both paclitaxel and DNase was shown to be efficient for intracellular delivery with respect to size, encapsulation efficiency, and intracellular uptake/fates. As a result of these properties, a Hep-Pr nanogel combined with paclitaxel and DNase exhibited a dose-dependent synergistic cytotoxicity compared to single drug and free-drug treatments, whose combination indices were 0.93 and 0.45 at higher concentrations (250 and 500 μg/mL). Therefore, Hep-Pr nanogels have the potential to deliver multitherapeutic agents with different characteristics and thereby enhance the therapeutic efficacy of combination cancer chemotherapy.