Novel Organoid Culture System for Improved Safety Assessment of Nanomaterials.

Over the past few decades, the increased application of nanomaterials has raised questions regarding their safety and possible toxic effects. Organoids have been suggested as promising tools, offering efficient assays for nanomaterial-induced toxicity evaluation. However, organoid systems have some limitations, such as size heterogeneity and poor penetration of nanoparticles because of the extracellular matrix, which is necessary for organoid culture. Here, we developed a novel system for the improved safety assessment of nanomaterials by establishing a 3D floating organoid paradigm. In addition to overcoming the limitations of two-dimensional systems including the lack of in vitro-in vivo cross-talk, our method provides multiple benefits as compared with conventional organoid systems that rely on an extracellular matrix for culture. Organoids cultured using our method exhibited relatively uniform sizing and structural integrity and were more conducive to the internalization of nanoparticles. Our floating culture system will accelerate the research and development of safe nanomaterials.

Automatic and robust estimation of sex and chronological age from panoramic radiographs using a multi-task deep learning network: a study on a South Korean population.

Sex and chronological age estimation are crucial in forensic investigations and research on individual identification. Although manual methods for sex and age estimation have been proposed, these processes are labor-intensive, time-consuming, and error-prone. The purpose of this study was to estimate sex and chronological age from panoramic radiographs automatically and robustly using a multi-task deep learning network (ForensicNet). ForensicNet consists of a backbone and both sex and age attention branches to learn anatomical context features of sex and chronological age from panoramic radiographs and enables the multi-task estimation of sex and chronological age in an end-to-end manner. To mitigate bias in the data distribution, our dataset was built using 13,200 images with 100 images for each sex and age range of 15-80 years. The ForensicNet with EfficientNet-B3 exhibited superior estimation performance with mean absolute errors of 2.93 ± 2.61 years and a coefficient of determination of 0.957 for chronological age, and achieved accuracy, specificity, and sensitivity values of 0.992, 0.993, and 0.990, respectively, for sex prediction. The network demonstrated that the proposed sex and age attention branches with a convolutional block attention module significantly improved the estimation performance for both sex and chronological age from panoramic radiographs of elderly patients. Consequently, we expect that ForensicNet will contribute to the automatic and accurate estimation of both sex and chronological age from panoramic radiographs.

The landscape of PBMC methylome in canine mammary tumors reveals the epigenetic regulation of immune marker genes and its potential application in predicting tumor malignancy.

BACKGROUND: Genome-wide dysregulation of CpG methylation accompanies tumor progression and characteristic states of cancer cells, prompting a rationale for biomarker development. Understanding how the archetypic epigenetic modification determines systemic contributions of immune cell types is the key to further clinical benefits. RESULTS: In this study, we characterized the differential DNA methylome landscapes of peripheral blood mononuclear cells (PBMCs) from 76 canines using methylated CpG-binding domain sequencing (MBD-seq). Through gene set enrichment analysis, we discovered that genes involved in the growth and differentiation of T- and B-cells are highly methylated in tumor PBMCs. We also revealed the increased methylation at single CpG resolution and reversed expression in representative marker genes regulating immune cell proliferation (BACH2, SH2D1A, TXK, UHRF1). Furthermore, we utilized the PBMC methylome to effectively differentiate between benign and malignant tumors and the presence of mammary gland tumors through a machine-learning approach. CONCLUSIONS: This research contributes to a better knowledge of the comprehensive epigenetic regulation of circulating immune cells responding to tumors and suggests a new framework for identifying benign and malignant cancers using genome-wide methylome.

Naturally occurring substitution in one amino acid in VHSV phosphoprotein enhances viral virulence in flounder.

Viral hemorrhagic septicemia virus (VHSV) is a rhabdovirus that causes high mortality in cultured flounder. Naturally occurring VHSV strains vary greatly in virulence. Until now, little has been known about genetic alterations that affect the virulence of VHSV in flounder. We recently reported the full-genome sequences of 18 VHSV strains. In this study, we determined the virulence of these 18 VHSV strains in flounder and then the assessed relationships between differences in the amino acid sequences of the 18 VHSV strains and their virulence to flounder. We identified one amino acid substitution in the phosphoprotein (P) (Pro55-to-Leu substitution in the P protein; PP55L) that is specific to highly virulent strains. This PP55L substitution was maintained stably after 30 cell passages. To investigate the effects of the PP55L substitution on VHSV virulence in flounder, we generated a recombinant VHSV carrying PP55L (rVHSV-P) from rVHSV carrying P55 in the P protein (rVHSV-wild). The rVHSV-P produced high level of viral RNA in cells and showed increased growth in cultured cells and virulence in flounder compared to the rVHSV-wild. In addition, rVHSV-P significantly inhibited the induction of the IFN1 gene in both cells and fish at 6 h post-infection. An RNA-seq analysis confirmed that rVHSV-P infection blocked the induction of several IFN-related genes in virus-infected cells at 6 h post-infection compared to rVHSV-wild. Ectopic expression of PP55L protein resulted in a decrease in IFN induction and an increase in viral RNA synthesis in rVHSV-wild-infected cells. Taken together, our results are the first to identify that the P55L substitution in the P protein enhances VHSV virulence in flounder. The data from this study add to the knowledge of VHSV virulence in flounder and could benefit VHSV surveillance efforts and the generation of a VHSV vaccine.

Comparison of 2D, 2.5D, and 3D segmentation networks for maxillary sinuses and lesions in CBCT images.

BACKGROUND: The purpose of this study was to compare the segmentation performances of the 2D, 2.5D, and 3D networks for maxillary sinuses (MSs) and lesions inside the maxillary sinus (MSL) with variations in sizes, shapes, and locations in cone beam CT (CBCT) images under the same constraint of memory capacity. METHODS: The 2D, 2.5D, and 3D networks were compared comprehensively for the segmentation of the MS and MSL in CBCT images under the same constraint of memory capacity. MSLs were obtained by subtracting the prediction of the air region of the maxillary sinus (MSA) from that of the MS. RESULTS: The 2.5D network showed the highest segmentation performances for the MS and MSA compared to the 2D and 3D networks. The performances of the Jaccard coefficient, Dice similarity coefficient, precision, and recall by the 2.5D network of U-net + + reached 0.947, 0.973, 0.974, and 0.971 for the MS, respectively, and 0.787, 0.875, 0.897, and 0.858 for the MSL, respectively. CONCLUSIONS: The 2.5D segmentation network demonstrated superior segmentation performance for various MSLs with an ensemble learning approach of combining the predictions from three orthogonal planes.

Automatic classification of 3D positional relationship between mandibular third molar and inferior alveolar canal using a distance-aware network.

The purpose of this study was to automatically classify the three-dimensional (3D) positional relationship between an impacted mandibular third molar (M3) and the inferior alveolar canal (MC) using a distance-aware network in cone-beam CT (CBCT) images. We developed a network consisting of cascaded stages of segmentation and classification for the buccal-lingual relationship between the M3 and the MC. The M3 and the MC were simultaneously segmented using Dense121 U-Net in the segmentation stage, and their buccal-lingual relationship was automatically classified using a 3D distance-aware network with the multichannel inputs of the original CBCT image and the signed distance map (SDM) generated from the segmentation in the classification stage. The Dense121 U-Net achieved the highest average precision of 0.87, 0.96, and 0.94 in the segmentation of the M3, the MC, and both together, respectively. The 3D distance-aware classification network of the Dense121 U-Net with the input of both the CBCT image and the SDM showed the highest performance of accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve, each of which had a value of 1.00. The SDM generated from the segmentation mask significantly contributed to increasing the accuracy of the classification network. The proposed distance-aware network demonstrated high accuracy in the automatic classification of the 3D positional relationship between the M3 and the MC by learning anatomical and geometrical information from the CBCT images.

Association between Condylar Bone Density and Disk Displacement in the Temporomandibular Joint.

Measuring bone density (BD) is a common method of determining bone quality; however, the relationship between condylar BD and the occurrence of temporomandibular joint (TMJ) disorders has not been investigated. To address this knowledge gap, we aimed to investigate condylar BD in terms of TMJ disk displacement (TMJ DD) using computed tomography (CT) and magnetic resonance imaging (MRI). We classified TMJ MRI results according to the position of the disk: normal disk position (Normal), anterior disk displacement with reduction (ADDR), and anterior disk displacement without reduction (ADDNR). After retrospectively evaluating 86 female condyles, we determined the total, cortical, and trabecular BD in the upper-joint portion of the condyle and the whole condyle using CT data. To standardize condylar BD, we calculated the BD ratios by dividing the condylar BD by the cervical axis BD. The Kruskal-Wallis test analyzed the differences in BD measurements in the TMJ DD patient groups and showed significant between-group differences in condylar BD. The total and trabecular BD was significantly higher in ADDNR condyles than in Normal or ADDR condyles (Normal = ADDR < ADDNR). However, there was no significant difference in the cortical BD among the three TMJ DD groups. The BD ratios showed a similar tendency with condylar BD. These results suggest that increased condylar BD - specifically total and trabecular BD - may be significantly associated with ADDNR condyles. Our findings will help clinicians determine the course of treatment for patients with disk-related TMJ disorders.

Older adult psychopathology: international comparisons of self-reports, collateral reports, and cross-informant agreement.

OBJECTIVES: To conduct international comparisons of self-reports, collateral reports, and cross-informant agreement regarding older adult psychopathology. PARTICIPANTS: We compared self-ratings of problems (e.g. I cry a lot) and personal strengths (e.g. I like to help others) for 10,686 adults aged 60-102 years from 19 societies and collateral ratings for 7,065 of these adults from 12 societies. MEASUREMENTS: Data were obtained via the Older Adult Self-Report (OASR) and the Older Adult Behavior Checklist (OABCL; Achenbach et al., ). RESULTS: Cronbach's alphas were .76 (OASR) and .80 (OABCL) averaged across societies. Across societies, 27 of the 30 problem items with the highest mean ratings and 28 of the 30 items with the lowest mean ratings were the same on the OASR and the OABCL. Q correlations between the means of the 0-1-2 ratings for the 113 problem items averaged across all pairs of societies yielded means of .77 (OASR) and .78 (OABCL). For the OASR and OABCL, respectively, analyses of variance (ANOVAs) yielded effect sizes (ESs) for society of 15% and 18% for Total Problems and 42% and 31% for Personal Strengths, respectively. For 5,584 cross-informant dyads in 12 societies, cross-informant correlations averaged across societies were .68 for Total Problems and .58 for Personal Strengths. Mixed-model ANOVAs yielded large effects for society on both Total Problems (ES = 17%) and Personal Strengths (ES = 36%). CONCLUSIONS: The OASR and OABCL are efficient, low-cost, easily administered mental health assessments that can be used internationally to screen for many problems and strengths.

Dual-Stage Deeply Supervised Attention-Based Convolutional Neural Networks for Mandibular Canal Segmentation in CBCT Scans.

Accurate segmentation of mandibular canals in lower jaws is important in dental implantology. Medical experts manually determine the implant position and dimensions from 3D CT images to avoid damaging the mandibular nerve inside the canal. In this paper, we propose a novel dual-stage deep learning-based scheme for the automatic segmentation of the mandibular canal. In particular, we first enhance the CBCT scans by employing the novel histogram-based dynamic windowing scheme, which improves the visibility of mandibular canals. After enhancement, we designed 3D deeply supervised attention UNet architecture for localizing the Volumes Of Interest (VOIs), which contain the mandibular canals (i.e., left and right canals). Finally, we employed the Multi-Scale input Residual UNet (MSiR-UNet) architecture to segment the mandibular canals using VOIs accurately. The proposed method has been rigorously evaluated on 500 and 15 CBCT scans from our dataset and from the public dataset, respectively. The results demonstrate that our technique improves the existing performance of mandibular canal segmentation to a clinically acceptable range. Moreover, it is robust against the types of CBCT scans in terms of field of view.

RNA-seq transcriptome analysis in flounder cells to compare innate immune responses to low- and high-virulence viral hemorrhagic septicemia virus.

Viral hemorrhagic septicemia virus (VHSV) is a rhabdovirus that causes high mortality in cultured flounder. Viral growth and virulence rely on the ability to inhibit the cellular innate immune response. In this study, we investigated differences in the modulation of innate immune responses of HINAE flounder cells infected with low- and high-virulence VHSV strains at a multiplicity of infection of 1 for 12 h and 24 h and performed RNA sequencing (RNA-seq)-based transcriptome analysis. A total of 193 and 170 innate immune response genes were differentially expressed by the two VHSV strains at 12 and 24 h postinfection (hpi), respectively. Of these, 73 and 77 genes showed more than a twofold change in their expression at 12 and 24 hpi, respectively. Of the genes with more than twofold changes, 22 and 11 genes showed high-virulence VHSV specificity at 12 and 24 hpi, respectively. In particular, IL-16 levels were more than two time higher and CCL20a.3, CCR6b, CCL36.1, Casp8L2, CCR7, and Trim46 levels were more than two times lower in high-virulence-VHSV-infected cells than in low-virulence-VHSV-infected cells at both 12 and 24 hpi. Quantitative PCR (qRT-PCR) confirmed the changes in expression of the ten mRNAs with the most significantly altered expression. This is the first study describing the genome-wide analysis of the innate immune response in VHSV-infected flounder cells, and we have identified innate immune response genes that are specific to a high-virulence VHSV strain. The data from this study can contribute to a greater understanding of the molecular basis of VHSV virulence in flounder.

Toxicity of orally administered food-grade titanium dioxide nanoparticles.

This year, France banned the application of titanium dioxide nanoparticles as a food additive (hereafter, E171) based on the insufficient oral toxicity data. Here, we investigated the subchronic toxic responses of E171 (0, 10, 100, and 1,000 mg/kg) and tried to elucidate the possible toxic mechanism using AGS cells, a human stomach epithelial cell line. There were no dose-related changes in the Organisation for Economic Cooperation and Development test guideline-related endpoints. Meanwhile, E171 deeply penetrated cells lining the stomach tissues of rats, and the IgM and granulocyte-macrophage colony-stimulating factor levels were significantly lower in the blood from rats exposed to E171 compared with the control. The colonic antioxidant protein level decreased with increasing Ti accumulation. Additionally, after 24-h exposure, E171 located in the perinuclear region of AGS cells and affected expression of endoplasmic reticulum stress-related proteins. However, cell death was not observed up to the used maximum concentration. A gene profile analysis also showed that immune response-related microRNAs were most strongly affected by E171 exposure. Collectively, we concluded that the NOAEL of E171 for 90 days repeated oral administration is between 100 and 1,000 mg/kg for both male and female rats. Additionally, further study is needed to clarify the possible carcinogenesis following the chronic accumulation in the colon.

The generalizability of Older Adult Self-Report (OASR) syndromes of psychopathology across 20 societies.

OBJECTIVES: As the world population ages, psychiatrists will increasingly need instruments for measuring constructs of psychopathology that are generalizable to diverse elders. The study tested whether syndromes of co-occurring problems derived from self-ratings of psychopathology by US elders would fit self-ratings by elders in 19 other societies. METHODS/DESIGN: The Older Adult Self-Report (OASR) was completed by 12 826 adults who were 60 to 102 years old in 19 societies from North and South America, Asia, and Eastern, Northern, Southern, and Western Europe, plus the United States. Individual and multigroup confirmatory factor analyses (CFAs) tested the fit of the seven-syndrome OASR model, consisting of the Anxious/Depressed, Worries, Somatic Complaints, Functional Impairment, Memory/Cognition Problems, Thought Problems, and Irritable/Disinhibited syndromes. RESULTS: In individual CFAs, the primary model fit index showed good fit for all societies, while the secondary model fit indices showed acceptable to good fit. The items loaded strongly on their respective factors, with a median item loading of .63 across 20 societies, and 98.7% of the loadings were statistically significant. In multigroup CFAs, 98% of items demonstrated approximate or full metric invariance. Fifteen percent of items demonstrated approximate or full scalar invariance, and another 59% demonstrated scalar invariance across more than half of societies. CONCLUSIONS: The findings supported the generalizability of OASR syndromes across societies. The seven syndromes offer empirically based clinical constructs that are relevant for elders of different backgrounds. They can be used to assess diverse elders and as a taxonomic framework to facilitate communication, services, research, and training in geriatric psychiatry.

Oral toxicity of titanium dioxide P25 at repeated dose 28-day and 90-day in rats.

BACKGROUND: Nanotechnology is indispensable to many different applications. Although nanoparticles have been widely used in, for example, cosmetics, sunscreen, food packaging, and medications, they may pose human safety risks associated with nanotoxicity. Thus, toxicity testing of nanoparticles is essential to assess the relative health risks associated with consumer exposure. METHODS: In this study, we identified the NOAEL (no observed adverse effect level) of the agglomerated/aggregated TiO2 P25 (approximately 180 nm) administered at repeated doses to Sprague-Dawley (SD) rats for 28 and 90 days. Ten of the 15 animals were necropsied for toxicity evaluation after the repeated-dose 90-day study, and the remaining five animals were allowed to recover for 28 days. The agglomerated/aggregated TiO2 P25 dose levels used included 250 mg kg- 1 d- 1 (low), 500 mg kg- 1 d- 1 (medium), and 1000 mg kg- 1 d- 1 (high), and their effects were compared with those of the vehicle control. During the treatment period, the animals were observed for mortality, clinical signs (detailed daily and weekly clinical observations), functional observation battery, weekly body weight, and food and water consumption and were also subjected to ophthalmological examination and urinalysis. After termination of the repeated-dose 28-day, 90-day, and recovery studies, clinical pathology (hematology, blood coagulation time, and serum biochemistry), necropsy (organ weights and gross findings), and histopathological examinations were performed. RESULTS: No systemic toxicological effects were associated with the agglomerated/aggregated TiO2 P25 during the repeated-dose 28-day, 90-day, and recovery studies in SD rats. Therefore, the NOAEL of the agglomerated/aggregated TiO2 P25 was identified as 1000 mg kg- 1 d- 1, and the substance was not detected in the target organs. CONCLUSION: Subacute and subchronic oral administration of the agglomerated/aggregated TiO2 P25 was unlikely to cause side effects or toxic reactions in rats.

Developing evidence-based clinical imaging guidelines of justification for radiographic examination after dental implant installation.

BACKGROUND: This study aimed to develop evidence-based clinical imaging guidelines to assess the proper implant location following implant surgery and identify potential complications during follow-up. METHODS: The guideline development process employed an adaptation methodology in accordance with the Korean clinical imaging guidelines (K-CIG). Core (Ovid-Medline, Ovid-Embase, National Guideline Clearinghouse, and Guideline International Network) and domestic databases (KoreaMed, KMbase, and KoMGI) were searched used to retrieve guidelines, and two reviewers analyzed the retrieved articles. The articles were included in this review using well-established inclusion criteria. RESULTS: Our online search identified 66 articles, of which 3 were selected for the development of the guidelines. Consequently, based on these three guidelines, we formulated distinct recommendations regarding the appropriate imaging modalities that should be used following implant placement. CONCLUSIONS: Conventional imaging (e.g., periapical or panoramic radiography) should be the first choice for assessing the implant following its placement and osseointegration. The metal artifacts in Cone Beam Computed Tomography (CBCT) should be considered. However, CBCT is recommended for patients with sensory abnormalities following dental implant surgery to evaluate and identify the underlying cause of implant complications and to determine the appropriate treatment.

Correlation between spatial resolution and ball distortion rate of panoramic radiography.

BACKGROUND: The purpose of this study was to analyze the correlation between spatial resolution and ball distortion rate of panoramic radiography and to elucidate the minimum criterion for ball distortion rate, which is very relevant to clinical readability. METHODS: Horizontal and vertical spatial resolution and ball distortion rates were calculated in the same position, such as the incisor, premolar, molar, and temporomandibular joint area with various object depths corresponding to 48 mm. Three devices were evaluated. A region showing spatial resolution above the reference standard was selected, and the ball distortion rate corresponding to the same region was divided into horizontal and vertical phantom groups. The mean and standard deviation of the obtained ball distortion rates were calculated. Student's t-test was used to statistically analyze the mean difference in ball distortion rates between vertical and horizontal phantom groups. RESULTS: In all devices, the horizontal line pair phantom, but not the vertical line pair phantom, was readable in all areas measured at the line pair value of at least 1.88 lp/mm. The line pair value tended to be higher toward the center and lower toward the outside. The ball distortion rate tended to decrease closer to the center and increased further away. In addition, ball distortion rates could not be measured at some areas as they were not recognized as balls due to the high degree of distortion at the outermost and innermost sides. The number of balls satisfying the reference value using the horizontal line pair phantom was 102 (mean of ball distortion rates, 20.98; standard deviation, 15.25). The number of balls satisfying the reference value using the vertical line pair phantom was 49 (mean of ball distortion rates, 16.33; standard deviation, 14.25). However, mean ball distortion rate was not significantly different between the two groups. CONCLUSIONS: Image layer of panoramic radiography could be evaluated by the spatial resolution using horizontal and vertical line pair phantoms and by assessing ball distortion rates through a ball-type panorama phantom. A ball distortion rate of 20% could be used as a threshold to evaluate the image layer of panoramic radiography.

Quantitative Augmented Reality-Assisted Free-Hand Orthognathic Surgery Using Electromagnetic Tracking and Skin-Attached Dynamic Reference.

The purpose of this study was to develop a quantitative AR-assisted free-hand orthognathic surgery method using electromagnetic (EM) tracking and skin-attached dynamic reference. The authors proposed a novel, simplified, and convenient workflow for augmented reality (AR)-assisted orthognathic surgery based on optical marker-less tracking, a comfortable display, and a non-invasive, skin-attached dynamic reference frame. The 2 registrations between the physical (EM tracking) and CT image spaces and between the physical and AR camera spaces, essential processes in AR-assisted surgery, were pre-operatively performed using the registration body complex and 3D depth camera. The intraoperative model of the maxillary bone segment (MBS) was superimposed on the real patient image with the simulated goal model on a flat-panel display, and the MBS was freely handled for repositioning with respect to the skin-attached dynamic reference tool (SRT) with quantitative visualization of landmarks of interest using only EM tracking. To evaluate the accuracy of AR-assisted Le Fort I surgery, the MBS of the phantom was simulated and repositioned by 6 translational and three rotational movements. The mean absolute deviations (MADs) between the simulation and post-operative positions of MBS landmarks by the SRT were 0.20, 0.34, 0.29, and 0.55 mm in x- (left lateral, right lateral), y- (setback, advance), and z- (impaction, elongation) directions, and RMS, respectively, while those by the BRT were 0.23, 0.37, 0.30, and 0.60 mm. There were no significant differences between the translation and rotation surgeries or among surgeries in the x-, y-, and z-axes for the SRT. The MADs in the x-, y-, and z-axes exhibited no significant differences between the SRT and BRT. The developed method showed high accuracy and reliability in free-hand orthognathic surgery using EM tracking and skin-attached dynamic reference.

Perphenazine Attenuates the Pro-Inflammatory Responses in Mouse Models of Th2-Type Allergic Dermatitis.

Developing dermatitis therapeutics has been faced with challenges including adverse effects of topical steroid and high cost of new developing drugs. Here, we found the expression levels of dopamine receptor D2 is higher in skin biopsies of dermatitis patients and an oxazolone-induced animal model of dermatitis. We used perphenazine, an FDA-approved dopamine receptor antagonist to determine the therapeutic effect. Two different animal models including 12-o-tetradecanoylphorbol-13-acetate (TPA) and oxazolone (OXA)-induced dermatitis were employed. TPA and OXA-mediated ear swelling was attenuated by perphenazine. Moreover, perphenazine inhibited infiltrated mast cells into lesion area. We found levels of serum IgE, histamine and cytokines are decreased in mice cotreated with perphenazine and OXA compared to OXA-treated mice. Overall, this is a first study showing that the FDA-approved, anti-psychotic drug, perphenazine, alleviates animal models of dermatitis.

Metformin ameliorates animal models of dermatitis.

Metformin, a potent AMPK activator is the most commonly used drug for diabetes. According to recent reports, metformin lowers the risk of diabetic complications and inflammatory diseases. We found the expression levels of AMPK subunits including PRKAA1, PRKAA2, PRKAB1 and PRKAB2 are decreased in skin biopsies of dermatitis patients from multiple datasets. Interestingly, metformin treatment ameliorates dermatitis symptom in animal model of dermatitis using O-tetradecanoylphorbol-13-acetate (TPA). Especially, the levels of epidermis and dermis thickness were decreased by metformin. We found NFκB activity as well as of gene expression associated with collagen synthesis are attenuated by metformin treatment. These results suggest that metformin treatment alleviates animal model of dermatitis.

Therapeutic effect of intraductal saline irrigation in chronic obstructive sialadenitis.

BACKGROUND: The aim of the present study was to evaluate the effectiveness of intraductal irrigation using normal saline in chronic obstructive sialadenitis. METHODS: Patients who had one of the following symptoms were recruited: pain, swelling, stiffness, and dry mouth. A total of 58 salivary glands in 33 patients were diagnosed as having sialadenitis using sialography and ultrasonography. The patients were divided into two groups (swelling group and dry mouth group), according to the major complaint. Repeated intraductal irrigation was performed on each gland. Difference of symptom severity evaluated using numerical rating scale (NRS), and ductal width measured using ultrasonography were compared between the two groups. RESULTS: The average NRS score was significantly decreased from 6.0 to 3.3 after 3-5 visits of intraductal irrigation (P < 0.05). The reduction in NRS was greater in the swelling group than in the dry mouth group, although the difference between the groups was not statistically significant. There was no change of ductal width before and after the irrigation. CONCLUSIONS: Intraductal irrigation according to this study method using normal saline is a simple treatment for the patients with chronic obstructive sialadenitis. It provides a conservative treatment option reducing the subjective symptoms.

Vitamin D-conjugated gold nanoparticles as functional carriers to enhancing osteogenic differentiation.

In an aging society, bone disorders such as osteopenia, osteoporosis, and degenerative arthritis cause serious public health problems. In order to solve these problems, researchers continue to develop therapeutic agents, increase the efficacy of developed therapeutic agents, and reduce side effects. Gold nanoparticles (GNPs) are widely used in tissue engineering applications as biosensors, drug delivery carriers, and bioactive materials. Their special surface property enables easy conjugation with ligands including functional groups such as thiols, phosphines, and amines. This creates an attractive advantage to GNPs for use in the bone tissue engineering field. However, GNPs alone are limited in their biological effects. In this study, we used thiol-PEG-vitamin D (SPVD) to conjugate vitamin D, an essential nutrient critical for maintaining normal skeletal homeostasis, to GNPs. To characterize vitamin D-conjugated GNPs (VGNPs), field emission transmission electron microscopy, energy dispersive X-ray spectroscopy, dynamic light scattering, and ultraviolet/visible absorption analysis were carried out. The developed VGNPs were well bound through the thiol groups between GNPs and vitamin D, and were fabricated in size of 60 nm. Moreover, to demonstrate VGNPs osteogenic differentiation effect, various assays were carried out through cell viability test, alkaline phosphatase assay, calcium deposition assay, real-time polymerase chain reaction, and immunofluorescence staining. As a result, the fabricated VGNPs were found to effectively enhance osteogenic differentiation of human adipose-derived stem cells (hADSCs) in vitro. Based on these results, VGNPs can be utilized as functional nanomaterials for bone regeneration in the tissue engineering field.