Internal structural analysis of the nasomaxillary complex in patients with skeletal class III asymmetry: A study on asymmetry patterns.

OBJECTIVES: To investigate the internal structure of the nasomaxillary complex, including the maxillary sinus, nasal cavity and nasal septum according to the facial asymmetry pattern and to evaluate its correlation with external maxillomandibular asymmetry in Class III patients based on cone-beam computerized tomography (CBCT) images. MATERIALS AND METHODS: Facial asymmetry was analysed in a total of 100 Class III patients aged 16 years or older using CBCT scans. Patients were categorized into subgroups based on asymmetry pattern. Measurements of the nasomaxillary complex were obtained from the CBCT scans, including the volume and width of the maxillary sinuses and nasal cavities on deviated and non-deviated sides, as well as the displacement of the nasal septum. Statistical analysis was performed to compare the internal nasomaxillary variables within and between groups, and regression analysis was conducted to evaluate the correlation between facial asymmetry and the internal nasomaxillary variables. RESULTS: Group comparisons showed that there were no significant differences in the volume of the maxillary sinus and nasal cavity. However, the direction and extent of nasal septum deviation, as well as the width of the nasal cavity, varied depending on the maxillary asymmetry pattern. Regression analysis indicated a correlation between nasal septum deviation and the difference in maxillary height, while the difference in nasal cavity width was correlated with the difference in maxillary width. CONCLUSION: A comprehensive evaluation of the internal nasal anatomy is vital for understanding the intricate relationship between nasal structure and maxillary growth.

Antioxidant Iron Oxide Nanoparticles: Their Biocompatibility and Bioactive Properties.

A lot of nanomaterials have been applied to various nano-biotechnological fields, such as contrast agents, drug or gene delivery systems, cosmetics, and so on. Despite the expanding usage of nanomaterials, concerns persist regarding their potential toxicity. To address this issue, many scientists have tried to develop biocompatible nanomaterials containing phytochemicals as a promising solution. In this study, we synthesized biocompatible nanomaterials by using gallic acid (GA), which is a phytochemical, and coating it onto the surface of iron oxide nanoparticles (IONPs). Importantly, the GA-modified iron oxide nanoparticles (GA-IONPs) were successfully prepared through environmentally friendly methods, avoiding the use of harmful reagents and extreme conditions. The presence of GA on the surface of IONPs improved their stability and bioactive properties. In addition, cell viability assays proved that GA-IONPs possessed excellent biocompatibility in human dermal papilla cells (HDPCs). Additionally, GA-IONPs showed antioxidant activity, which reduced intracellular reactive oxygen species (ROS) levels in an oxidative stress model induced by hydrogen peroxide (H2O2). To investigate the impact of GA-IONPs on exosome secretions from oxidative stress-induced cells, we analyzed the number and characteristics of exosomes in the culture media of HDPCs after H2O2 stimulation or GA-IONP treatment. Our analysis revealed that both the number and proportions of tetraspanins (CD9, CD81, and CD63) in exosomes were similar in the control group and the GA-IONP-treated groups. In contrast, exosome secretion was increased, and the proportion of tetraspanin was changed in the H2O2-treated group compared to the control group. It demonstrated that treatment with GA-IONPs effectively attenuated exosome secretion induced by H2O2-induced oxidative stress. Therefore, this GA-IONP exhibited outstanding promise for applications in the field of nanobiotechnology.

Genomic characteristics of invasive mucinous adenocarcinoma of the lung with multiple pulmonary sites of involvement.

Invasive mucinous adenocarcinoma (IMA) of the lung frequently presents with diffuse pneumonic-type features or multifocal lesions, which are regarded as a pattern of intrapulmonary metastases. However, the genomics of multifocal IMAs have not been well studied. We performed whole exome sequencing on samples taken from 2 to 5 regions in seven patients with synchronous multifocal IMAs of the lung (24 regions total). Early initiating driver events, such as KRAS, NKX2-1, TP53, or ARID1A mutations, are clonal mutations and were present in all multifocal IMAs in each patient. The tumor mutational burden of multifocal IMAs was low (mean: 1.13/mega base), but further analyses suggested intra-tumor heterogeneity. The mutational signature analysis found that IMAs were predominantly associated with endogenous mutational process (signature 1), APOBEC activity (signatures 2 and 13), and defective DNA mismatch repair (signature 6), but not related to smoking signature. IMAs synchronously located in the bilateral lower lobes of two patients with background usual interstitial pneumonia had different mutation types, suggesting that they were double primaries. In conclusion, genomic evidence found in this study indicated the clonal intrapulmonary spread of diffuse pneumonic-type or multifocal IMAs, although they can occur in multicentric origins in the background of usual interstitial pneumonia. IMAs exhibited a heterogeneous genomic landscape despite the low somatic mutation burden. Further studies are warranted to determine the clinical significance of the genomic characteristics of IMAs in expanded cohorts.

Genetic effect of single nucleotide polymorphisms in growth hormone receptor gene on the risk of non-syndromic mandibular prognathism in the Korean population.

OBJECTIVES: To evaluate the association of three single-nucleotide polymorphisms (SNPs) of growth hormone receptor (GHR) gene with mandibular prognathism (MP) and relationships between mandibular morphology and GHR gene SNPs in the Korean population. MATERIALS AND METHODS: A total of 325 subjects were divided into two groups based on sagittal maxillomandibular relationship by the lateral cephalography: the MP and control groups. From the SNPs in the GHR gene, three SNPs (rs6180, rs6182 and rs6184) were selected. SNP genotyping was performed using direct sequencing. The craniofacial measurements of lateral cephalography were analysed. RESULTS: We found a lack of association between GHR and MP. However, in the analysis according to the values of cephalometric measurements, rs6180 was significantly associated with ANB, SNB, effective mandibular length and SNMP in females. Additionally, rs6182 and rs6184 were significantly associated with ramal height in males. CONCLUSION: Growth hormone receptor SNPs may affect not only the sagittal development of mandible but also the vertical development of ramal height, and GHR SNPs may gender-differently influence mandibular morphology. This finding supports that the GHR might be susceptible on mandibular morphogenesis in the Korean population.

Accuracy of convolutional neural networks-based automatic segmentation of pharyngeal airway sections according to craniofacial skeletal pattern.

INTRODUCTION: This study aimed to evaluate a 3-dimensional (3D) U-Net-based convolutional neural networks model for the fully automatic segmentation of regional pharyngeal volume of interests (VOIs) in cone-beam computed tomography scans to compare the accuracy of the model performance across different skeletal patterns presenting with various pharyngeal dimensions. METHODS: Two-hundred sixteen cone-beam computed tomography scans of adult patients were randomly divided into training (n = 100), validation (n = 16), and test (n = 100) datasets. We trained the 3D U-Net model for fully automatic segmentation of pharyngeal VOIs and their measurements: nasopharyngeal, velopharyngeal, glossopharyngeal, and hypopharyngeal sections as well as total pharyngeal airway space (PAS). The test datasets were subdivided according to the sagittal and vertical skeletal patterns. The segmentation performance was assessed by dice similarity coefficient, volumetric similarity, precision, and recall values, compared with the ground truth created by 1 expert's manual processing using semiautomatic software. RESULTS: The proposed model achieved highly accurate performance, showing a mean dice similarity coefficient of 0.928 ± 0.023, the volumetric similarity of 0.928 ± 0.023, precision of 0.925 ± 0.030, and recall of 0.921 ± 0.029 for total PAS segmentation. The performance showed region-specific differences, revealing lower accuracy in the glossopharyngeal and hypopharyngeal sections than in the upper sections (P <0.001). However, the accuracy of model performance at each pharyngeal VOI showed no significant difference according to sagittal or vertical skeletal patterns. CONCLUSIONS: The 3D-convolutional neural network performance for region-specific PAS analysis is promising to substitute for laborious and time-consuming manual analysis in every skeletal and pharyngeal pattern.

Craniofacial treatment protocol for a pediatric patient with obstructive sleep apnea and skeletal Class III malocclusion: A 13-year follow-up.

This report aimed to describe the long-term effects of craniofacial growth modification treatment on sleep and breathing functions in a 7-year-old girl diagnosed with skeletal Class III malocclusion and sleep-disordered breathing. Based on the flowchart of orthodontic intervention protocol that we proposed for phenotype-based patient selection and skeletal target-based treatment selection for pediatric patients with sleep-disordered breathing, a 2-phase treatment targeting the nasomaxillary complex was performed. Posttreatment 3-dimensional changes in the skeletal structure and upper airway were evaluated in association with functional assessment using a validated pediatric sleep questionnaire and home sleep test. Esthetic improvement and obstructive sleep apnea cure were achieved without skeletal surgery. The 2-year retention records showed stable occlusion and improved facial profile with normal breathing and sleep.

Fully automated identification of cephalometric landmarks for upper airway assessment using cascaded convolutional neural networks.

OBJECTIVES: The aim of the study was to evaluate the accuracy of a cascaded two-stage convolutional neural network (CNN) model in detecting upper airway (UA) soft tissue landmarks in comparison with the skeletal landmarks on the lateral cephalometric images. MATERIALS AND METHODS: The dataset contained 600 lateral cephalograms of adult orthodontic patients, and the ground-truth positions of 16 landmarks (7 skeletal and 9 UA landmarks) were obtained from 500 learning dataset. We trained a UNet with EfficientNetB0 model through the region of interest-centred circular segmentation labelling process. Mean distance errors (MDEs, mm) of the CNN algorithm was compared with those from human examiners. Successful detection rates (SDRs, per cent) assessed within 1-4 mm precision ranges were compared between skeletal and UA landmarks. RESULTS: The proposed model achieved MDEs of 0.80 ± 0.55 mm for skeletal landmarks and 1.78 ± 1.21 mm for UA landmarks. The mean SDRs for UA landmarks were 72.22 per cent for 2 mm range, and 92.78 per cent for 4 mm range, contrasted with those for skeletal landmarks amounting to 93.43 and 98.71 per cent, respectively. As compared with mean interexaminer difference, however, this model showed higher detection accuracies for geometrically constructed UA landmarks on the nasopharynx (AD2 and Ss), while lower accuracies for anatomically located UA landmarks on the tongue (Td) and soft palate (Sb and St). CONCLUSION: The proposed CNN model suggests the availability of an automated cephalometric UA assessment to be integrated with dentoskeletal and facial analysis.

Efficacy of entecavir versus tenofovir in preventing hepatocellular carcinoma in patients with chronic hepatitis B with maintained virologic response.

BACKGROUND & AIMS: Several studies suggested that efficacy of tenofovir in reducing the risk of the development of hepatocellular carcinoma (HCC) might be better than that of entecavir. It remains unknown whether a change in therapy can further reduce the risk of HCC in patients receiving entecavir therapy and achieved goal of antiviral therapy, a maintained undetectable hepatitis B virus (HBV) DNA level in the serum. METHODS: A total of 1336 treatment-naïve chronic HBV mono-infected adult patients, who started entecavir or tenofovir treatment and achieved a maintained virologic response during follow-up were analysed. RESULTS: During a median 4.4 years of follow-up (range, 1.0-7.4 years) after achieving virologic response, 99 patients developed HCC. The 5-year cumulative HCC incidence rate was 7.3% and 6.3% for the entecavir and tenofovir groups, respectively, with similar risk of HCC between the two groups (adjusted HR, 0.82; 95% CI, 0.52-1.29; p = 0.3). The risk of HCC was similar in the propensity score-matched cohort (HR, 1.02; 95% CI, 0.68-1.52; p = 0.94) and inverse probability treatment weighting analysis (HR, 1.11; 95% CI, 0.74-1.66; p = 0.62). In the subgroup analysis, HCC risk was similar between the two drugs in both patients with and without cirrhosis. DISCUSSION: In patients showing maintained virologic response, no difference in the risk of HCC between entecavir and tenofovir was observed. This indicates entecavir might be as effective as tenofovir in the prevention of HCC among those patients and suggest that a change in therapy in anticipation of further reducing the risk of HCC might not be necessary for patients receiving entecavir and showing virologic response.

Roots of Lithospermum erythrorhizon promotes retinal cell survival in optic nerve crush-induced retinal degeneration.

Lithospermum erythrorhizon (L. erythrorhizon), used in traditional medicine, is a potent wound healing, anti-inflammatory and antioxidant plant. However, the effects of L. erythrorhizon on retinal degenerative diseases remain unknown. Here, we explored the protective effects of L. erythrorhizon in in vitro and in vivo retinal degeneration. We found that ethanol extract of L. erythrorhizon (EELE) and the dichloromethane fraction of L. erythrorhizon (MCLE) significantly increased cell viability under glutamate/BSO-induced excitotoxicity/oxidative stress in R28 cells. Treatment with EELE and MCLE reduced the intracellular reactive oxygen species (ROS) and the levels of apoptotic proteins, such as cleaved PARP and cleaved caspase-3. Furthermore, oral administration of EELE and MCLE in an in vivo optic nerve crush mouse model decreased RGC cell death and increased retinal thickness. The major compound between EELE and MCLE was found to be lithospermic acid A (LAA), which has been shown to prevent the elevation of ROS in R28. Therefore, EELE and MCLE have protective effects against the death of retinal cells in vitro and in vivo, and the major compound, LAA, has an antioxidant effect on retinal cells, suggesting that EELE and MCLE could be beneficial agents for retinal degenerative diseases, including glaucoma.

Multi-perspective clustering of obstructive sleep apnea towards precision therapeutic decision including craniofacial intervention.

PURPOSE: Previous studies focusing on phenotyping obstructive sleep apnea (OSA) have outlined its heterogeneity in clinical symptoms, comorbidities, and polysomnographic features. However, the role of anatomical or pathophysiological causality including craniofacial skeletal deformity has not been studied. We aimed to identify and characterize phenotypes of OSA based on multi-perspective clustering by incorporating craniofacial risks with obesity, apnea severity, arousability, symptom, and comorbidity. METHODS: A total of 421 Korean patients with OSA (apnea-hypopnea index, AHI ≥ 5; age ≥ 20 years old) were recruited. A K-means cluster analysis was performed following principal component analysis with sagittal and vertical skeletal variables (ANB and mandibular plane angle), AHI, body mass index, and Epworth sleepiness scale. Inter-cluster comparison was conducted using demographic, cephalometric, and polysomnographic variables in addition to presence of diabetes and hypertension. Risk factors contributing to OSA severity were evaluated in each cluster using multivariable regression analysis with adjustment for age and gender. RESULTS: Three phenotypic clusters were identified and characterized as follows: Cluster-1 (noncraniofacial phenotype, 39%), non-obese moderate-to-severe OSA with no skeletal discrepancy representing low arousal threshold (ArTh), little sleepiness, and low comorbidity; Cluster-2 (craniofacial skeletal phenotype, 33%), non-obese moderate OSA with definite skeletal discrepancy showing low ArTh, mild sleepiness, and low comorbidity; and Cluster-3 (complicated phenotype, 28%), obese severe OSA with skeletal discrepancy exhibiting high ArTh, excessive daytime sleepiness, and high incidence of hypertension. CONCLUSIONS: The three OSA phenotypes from multi-perspective clustering may provide a basis for precise therapeutic decision-making including craniofacial skeletal intervention beyond usual characterization of OSA subgroups.

Critical issues concerning biocreative strategy in contemporary temporary skeletal anchorage device orthodontics: A narrative review.

Biocreative Orthodontic Strategy (BOS) is designed to establish a physiologically stable occlusion in harmony with masticatory and TMJ function and healthy supporting tissues with strategic use of temporary skeletal anchorage devices (TSADs). This narrative review surveys current research that demonstrates how BOS with TSADs uses a target approach to overcome the limitations experienced with conventional orthodontic treatment. A narrative review article including research on TSADs orthodontics in the permanent dentition. This review is a brief survey of five BOS principles for contemporary TSAD orthodontics: elegant selection of TSADs, bracket prescription to enhance TSAD orthodontics, antero-posterior dimension control, transverse dimension control and airway control issues. Severe malocclusion and craniofacial dysmorphology can be treated with Biocreative Orthodontic Strategy with a minimum number of TSADs. In order to achieve successful treatment outcome using TSADs, it is critical to understand the key diagnosis and treatment principles of BOS and how to develop a target approach for the tooth and bone movement.

Force Distribution of a Novel Core-Reinforced Multilayered Mandibular Advancement Device.

A mandibular advancement device (MAD) is a commonly used treatment modality for patients with mild-to-moderate obstructive sleep apnea. Although MADs have excellent therapeutic efficacy, dental side effects were observed with long-term use of MADs. The aim of this study was to analyze the force distribution on the entire dentition according to the materials and design of the MADs. Three types of MADs were applied: model 1 (single layer of polyethylene terephthalate glycol (PETG)), model 2 (double layer of PETG + thermoplastic polyurethane (TPU)), and model 3 (core-reinforced multilayer). In the maxilla, regardless of the model, the incisors showed the lowest force distribution. In most tooth positions, the force distribution was lower in models 2 and 3 than in model 1. In the mandible, the mandibular second molar showed a significantly lower force in all models. The mandibular incisors, canines, and molars showed the highest force values in model 1 and the lowest values in model 3. Depending on the material and design of the device, the biomechanical effect on the dentition varies, and the core-reinforced multilayered MAD can reduce the force delivered to the dentition more effectively than the conventional single- or double-layer devices.

Computerized Assessment of Occlusion and Muscle Activity during Use of a Multilayer Clear Retainer: A Preliminary Study.

The aim of this preliminary study was to evaluate the short-term changes of occlusal contacts and muscle activity after orthodontic treatment during the use of a multi-layer clear retainer. Evaluation was done with the T-scan and BioEMG systems. A total of 18 subjects were included, who were evaluated at three time intervals-T0 at debonding, T1 at one month after retainer delivery, and T2 at four months after retainer delivery. The T-scan and electromyography (EMG) data were recorded simultaneously. The T-scan system recorded the occlusion time, disclusion time and force distribution. The EMG waves were quantified by calculating the asymmetry index and activity index. The time variables changed but not significantly. Occlusal force decreased in the anterior dentition and increased in the posterior dentition during T0-T2. There was no clear evidence of a relationship between unbalanced occlusal forces and muscle activity. In most subjects, the temporalis anterior muscle was more dominant than the masseter muscle. From this preliminary computerized study, there were no significant changes in the state of the occlusion or muscle activity during the short-term retention period.

Expression of V-set immunoregulatory receptor in malignant mesothelioma.

Malignant mesothelioma is a highly lethal cancer. V-set immunoregulatory receptor (VSIR, also known as V-domain Ig suppressor T-cell activation, VISTA), a negative immune checkpoint regulator, was reported to be expressed in malignant mesothelioma; however, its detailed expression pattern and clinicopathological significance have not been elucidated. We examined the expression of VSIR and CD274 and CD8+ tumor-infiltrating lymphocytes in a total of 124 samples from 66 patients with malignant mesothelioma and analyzed the clinicopathological characteristics and their relationship with the immunohistochemical findings. A total of 553 non-small cell lung carcinomas were also evaluated for VSIR expression. VSIR expression was higher in epithelioid type mesothelioma (p < 0.001), whereas CD274 expression was higher in sarcomatoid type (p < 0.001). CD8+ tumor-infiltrating lymphocytes were more abundant in sarcomatoid mesotheliomas (p < 0.001), VSIR-low tumors (p = 0.045), and CD274-high tumors (p < 0.001). VSIR and CD274 were differentially expressed in each histological component of the biphasic type. VSIR expression was associated with favorable survival (p = 0.008). Two patients with VSIR-high tumors had received pembrolizumab; however, they showed progressive disease. No VSIR expression was observed in tumor cells of non-small cell lung carcinomas. In conclusion, VSIR expression may define a unique class of mesothelioma, characterized by predominantly epithelioid type and favorable prognosis. VSIR expression may be used as an immunohistochemical diagnostic marker for epithelioid mesothelioma. CD274 expression was associated with sarcomatoid mesothelioma and high infiltration of CD8+ lymphocytes. Because VSIR is a negative immune regulator and expressed in malignant mesothelioma, further study is warranted to investigate the therapeutic significance of VSIR blockade in this deadly cancer.

Pre-screening of patient-reported symptoms using the Edmonton Symptom Assessment System in outpatient palliative cancer care.

OBJECTIVES: Although early palliative care is associated with a better quality of life and improved outcomes in end-of-life cancer care, the criteria of palliative care referral are still elusive. METHODS: We collected patient-reported symptoms using the Edmonton Symptom Assessment System (ESAS) at the baseline, first and second follow-up visits. A total of 71 patients were evaluable, with a median age of 65 years, male (62%) and Eastern Cooperative Oncology Group (ECOG) performance status distribution of 1/2/3 (28%/39%/33%) respectively. RESULTS: Twenty (28%) patients had moderate/severe symptom burden with the mean ESAS ≥ 5. Interestingly, most of the patients with moderate/severe symptom burdens (ESAS ≥ 5) had globally elevated symptom expression. While the mean ESAS score was maintained in patients with mild symptom burden (ESAS < 5; 2.7 at the baseline; 3.4 at the first follow-up; 3.0 at the second follow-up; p = .117), there was significant symptom improvement in patients with moderate/severe symptom burden (ESAS ≥ 5; 6.5 at the baseline; 4.5 at the first follow-up; 3.6 at the second follow-up; p < .001). CONCLUSIONS: In conclusion, advanced cancer patients with ESAS ≥ 5 may benefit from outpatient palliative cancer care. Pre-screening of patient-reported symptoms using ESAS can be useful for identifying unmet palliative care needs in advanced cancer patients.

Asymmetric nasomaxillary expansion induced by tooth-bone-borne expander producing differential craniofacial changes.

OBJECTIVES: To evaluate three-dimensional (3D) craniofacial changes induced by a non-surgical tooth-bone-borne rapid palatal expander (TBB-RPE) according to the symmetrical pattern of expansion, to investigate the 3D changes between the sides in patients with asymmetric expansion, and to identify the related factors of asymmetric expansion. SETTING AND SAMPLE POPULATION: Sixty-six patients (mean age: 19.3 ± 5.7 years) treated with TBB-RPE were divided into a symmetric expansion group (Group S, n = 46) or asymmetric expansion group (Group A, n = 20). Group S was subdivided into Group Ss (n = 27), with bilateral frontomaxillary suture (FMS) split, and Group Sn (n = 19), with no FMS split. MATERIALS AND METHODS: Pre- and post-expansion cone-beam computed tomography images were superimposed, and the common coordinated system was set. All landmarks were designated as coordinate pairs, and treatment changes were automatically calculated. Analysis of variance was conducted for intergroup comparison of craniofacial changes, and logistic regression analysis was performed to identify the related factors of asymmetric expansion. RESULTS: The frequency of asymmetric expansion was 30.3%. Group A with unilateral FMS split showed less craniofacial changes than Group Ss and more changes than Group Sn. Group A exhibited different nasomaxillary displacement between the two halves, showing greater changes in the FMS-split side. Among the tested six variables (age, gender, Angle's classification, unilateral crossbite, maxillary cant and chin deviation), chin deviation was uniquely associated with asymmetric expansion. CONCLUSIONS: Tooth-bone-borne rapid palatal expander had a risk of asymmetric expansion, especially in facial asymmetric patients with chin deviation, producing different craniofacial changes from symmetric expansion.

Recording an accurate maxillomandibular relationship by adding vertical stops to the occlusal rims.

Complete denture fabrication includes accurate recording of the maxillomandibular relationship to ensure the functional requirements of occlusion and minimize the traumatic effects on the residual alveolar ridges. However, errors may occur when the occlusal rims have uneven and nonuniform occlusal contacts. The technique described is a straightforward method for recording an accurate silicone centric relationship record with dome-shaped baseplate wax added as vertical stops on the occlusal surface of the mandibular occlusal rim.

Maxillary Corticotomies With Bone-to-Bone Retraction and Mandibular Segmental Osteotomy for Correcting an Anterior Double Protrusion.

BACKGROUNDS: This article presents maxillary corticotomies with bone-to-bone retraction and anterior segmental osteotomy (ASO) as an alternative to 2-jaw orthognathics in the bimaxilary protrusion patient with partially anchylosed maxillary anterior tooth. METHODS: The 18-year-old male, complaining of anterior protrusion, with a trauma history to the maxillary central incisor, and requesting rapid treatment, was treated with maxillary corticotomies in 2 stages and ASO in the mandible. The mandibular ASO and palatal corticotomy were done under local anesthesia and 2 weeks later, labial corticotomy followed. The anterior segment was retracted bodily using buccal C-tubes and a combination of the C-lingual retractor and palatal C-plate. RESULTS: Due to a concern about ankylosis of the maxillary right central incisor, retraction of the anterior bone/tooth segment was chosen over any attempt to move teeth through the bone. After bone-to-bone retraction, the remaining extraction space was closed by protraction of posteriors. The total treatment period was 18 months. There was good retraction of the anterior segment and retrusion of the lips. CONCLUSIONS: A combination of maxillary corticotomies with skeletal anchorage for bone-to-bone retraction and a mandibular ASO under local anesthesia might be an alternative treatment option for excellent profile change in a short treatment period.

The leaves of Diospyros kaki exert beneficial effects on a benzalkonium chloride-induced murine dry eye model.

PURPOSE: In this study, the beneficial effects of the oral administration of ethanol extract of Diospyros kaki (EEDK) were tested on a mouse dry eye model induced by benzalkonium chloride (BAC). METHODS: A solution of 0.2% BAC was administered topically to mouse eyes for 14 days, twice daily, to induce dry eye. Various concentrations of EEDK were administrated daily by oral gavage for 14 days after BAC treatment. Preservative-free eye drops were instilled in the positive-control group. The tear secretion volume (Schirmer's test), tear break-up time (BUT), and fluorescein score were measured on the ocular surface. BAC-induced corneal damage was tested with hematoxylin-eosin staining. Moreover, apoptotic cell death in the corneal epithelial layer was investigated with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. The protein expression level of interleukin-1alpha (IL-1α), IL-1ß, IL-6, tumor necrosis factor- alpha (TNF-α), and monocyte chemotactic protein-1 (MCP-1) was determined with western blot analysis. Furthermore, squamous metaplasia in the corneal epithelial layer was detected with immunofluorescent staining for cytokeratine-10. The cellular proliferation in the cornea was examined with immunohistochemical staining for Ki-67. RESULTS: EEDK treatment resulted in prolonged BUT, decreased fluorescein score, increased tear volume, and smoother epithelial cells compared with BAC treatment alone in the cornea. Moreover, EEDK treatment inhibited the inflammatory response and corneal epithelial cell death in a BAC-induced murine dry eye model, and changes in squamous cells were inhibited. Proliferative activity in the corneal epithelium cells was improved with EEDK. CONCLUSIONS: EEDK could be a potential therapeutic agent in the clinical treatment of dry eye.