Tooth caries classification with quantitative light-induced fluorescence (QLF) images using convolutional neural network for permanent teeth in vivo.

BACKGROUND: Owing to the remarkable advancements of artificial intelligence (AI) applications, AI-based detection of dental caries is continuously improving. We evaluated the efficacy of the detection of dental caries with quantitative light-induced fluorescence (QLF) images using a convolutional neural network (CNN) model. METHODS: Overall, 2814 QLF intraoral images were obtained from 606 participants at a dental clinic using Qraypen C® (QC, AIOBIO, Seoul, Republic of Korea) from October 2020 to October 2022. These images included all the types of permanent teeth of which surfaces were smooth or occlusal. Dataset were randomly assigned to the training (56.0%), validation (14.0%), and test (30.0%) subsets of the dataset for caries classification. Moreover, masked images for teeth area were manually prepared to evaluate the segmentation efficacy. To compare diagnostic performance for caries classification according to the types of teeth, the dataset was further classified into the premolar (1,143 images) and molar (1,441 images) groups. As the CNN model, Xception was applied. RESULTS: Using the original QLF images, the performance of the classification algorithm was relatively good showing 83.2% of accuracy, 85.6% of precision, and 86.9% of sensitivity. After applying the segmentation process for the tooth area, all the performance indics including 85.6% of accuracy, 88.9% of precision, and 86.9% of sensitivity were improved. However, the performance indices of each type of teeth (both premolar and molar) were similar to those for all teeth. CONCLUSION: The application of AI to QLF images for caries classification demonstrated a good performance regardless of teeth type among posterior teeth. Additionally, tooth area segmentation through background elimination from QLF images exhibited a better performance.

Association between periodontal disease and hypertriglyceridemia: Propensity score matching analysis using the 7th Korea National Health and Nutrition Examination Survey.

The prevalence of periodontitis and dyslipidemia continues to increase, and several studies have reported an association between the 2. Therefore, we assessed the relationship between periodontitis and hypertriglyceridemia using propensity score matching to efficiently address confounding factors, as well as complex sample analysis with data from Korea National Health and Nutrition Examination Survey VII (2016-2018). To match the 1:1 ratio between the groups with and without periodontitis, the propensity scores of covariates, such as age, sex, education, income, smoking, drinking, obesity, and diabetes mellitus, were calculated using logistic regression. Both results of logistic regression analysis using complex sample design for whole and matched sample after propensity score matching demonstrated a significant association between hypertriglyceridemia and periodontitis, of which the adjusted odds ratio was 1.28 (95% confidence interval = 1.10-1.50) and 1.29 (95% confidence interval = 1.09-1.52), respectively. Our findings suggest that dental healthcare workers can help raise awareness among patients with periodontitis regarding the association between periodontitis and hypertriglyceridemia, which may help them manage the condition and receive treatment.

Silibinin induces oral cancer cell apoptosis and reactive oxygen species generation by activating the JNK/c-Jun pathway.

Background: Oral cancer is one of the most prevalent malignant tumors worldwide. Silibinin has been reported to exert therapeutic effects in various cancer models. However, its mechanism of action in oral cancer remains unclear. We aimed to examine the molecular processes underlying the effects of silibinin in oral cancer in vitro and in vivo as well as its potential anticancer effects. Next, we investigated the molecular processes underlying both in vitro and in vivo outcomes of silibinin treatment on oral cancer. Methods: To investigate the effects of silibinin on the growth of oral cancer cells, cell proliferation and anchorage-independent colony formation tests were conducted on YD10B and Ca9-22 oral cancer cells. The effects of silibinin on the migration and invasion of oral cancer cells were evaluated using transwell assays. Flow cytometry was used to examine apoptosis, cell cycle distribution, and accumulation of reactive oxygen species (ROS). The molecular mechanism underlying the anticancer effects of silibinin was explored using immunoblotting. The in vivo effects of silibinin were evaluated using a Ca9-22 xenograft mouse model. Results: Silibinin effectively suppressed YD10B and Ca9-22 cell proliferation and colony formation in a dose-dependent manner. Moreover, it induced cell cycle arrest in the G0/G1 phase, apoptosis, and ROS generation in these cells. Furthermore, silibinin inhibited the migration and invasion abilities of YD10B and Ca9-22 cells by regulating the expression of proteins involved in the epithelial-mesenchymal transition. Western blotting revealed that silibinin downregulated SOD1 and SOD2 and triggered the JNK/c-Jun pathway in oral cancer cells. Silibinin significantly inhibited xenograft tumor growth in nude mice, with no obvious toxicity. Conclusions: Silibinin considerably reduced the development of oral cancer cells by inducing apoptosis, G0/G1 arrest, ROS generation, and activation of the JNK/c-Jun pathway. Importantly, silibinin effectively suppressed xenograft tumor growth in nude mice. Our findings indicate that silibinin may be a promising option for the prevention or treatment of oral cancer.

Effects of professional toothbrushing among patients with gingivitis.

OBJECTIVES: This study aimed to evaluate the biological and clinical effect of professional toothbrushing on the periodontal health of patients with gingivitis. METHODS: We enrolled 21 university students with gingivitis in Jinju City in this study between April 24 and October 28, 2014. A dental hygienist performed a professional toothbrushing routine on the participants twice, once at baseline and after 3 months. Oral examinations were performed at baseline, 3, and 6 months to assess the periodontal health. The patient hygiene performance index, gingival bleeding rate, periodontal pocket depth, amount of gingival sulcus fluid, and number of bacterial colonies in the gingival sulcus (CFU/mL) were evaluated during the oral examination. RESULTS: The patient hygiene performance index, gingival bleeding rate, pocket depth, amount of gingival sulcus fluid, and CFU/mL within the gingival sulcus significantly decreased after professional toothbrushing (p < 0.05), indicating an improvement in the periodontal health. The patient hygiene performance index, gingival bleeding rate, pocket depth, amount of gingival sulcus fluid, and CFU/mL within the gingival sulcus decreased more among those whose pocket depth was 4-5 mm than among those whose PD was ≤3 mm (p < 0.05). CONCLUSIONS: Professional toothbrushing improved the periodontal health in patients with gingivitis in respect of both biological and clinical results.

Association between dental amalgam restoration and urine mercury concentrations among young women: a cross-sectional study.

BACKGROUND: The association between dental amalgam fillings and urine mercury concentrations was investigated in this study to assess the health risks associated with dental amalgams. METHODS: This cross-sectional study included 99 women in their 20s who visited the dental clinic in Daegu, Korea. The 99 participants were composed of 68 subjects who had dental amalgam fillings (exposure group) and 31 subjects who did not have dental amalgam fillings (nonexposure group). Oral examinations were conducted by a single dental hygienist, sociodemographic features were investigated as confounding variables, and urine mercury concentrations were measured using an automatic mercury analyzer. RESULTS: The mean±standard deviation of the urine mercury concentrations of the exposure and nonexposure groups were 1.50±1.78 µg/g creatinine and 0.53±0.63 µg/g creatinine, respectively. The exposure group showed significantly higher levels than the nonexposure group (p<0.01). The urine mercury concentration significantly increased with an increase in the number of teeth filled with amalgam, cavity surfaces involved, and number of defective amalgam fillings, and according to the latest exposure time (p<0.001). In the multiple regression analysis of amalgam-related factors and urine mercury concentrations after correction for confounding factors, the urine mercury concentration in the group with six or more amalgam-filled teeth, 11 or more cavity surfaces, and two or more defective amalgams was significantly higher than that in the nonexposure group (p<0.001). CONCLUSION: According to this study, exposure to dental amalgams was confirmed to significantly affect urine mercury concentrations.

Three-dimensional printing of temporary crowns with polylactic acid polymer using the fused deposition modeling technique: a case series.

With recent developments in digital dentistry, research on techniques and materials for three-dimensional (3D) printing is actively underway. We report the clinical applications and outcomes of 3D printing of temporary crowns fabricated with polylactic acid (PLA) using a fused deposition modeling (FDM) printer. Five participants were recruited from among patients scheduled to be treated with a single full-coverage crown at a dental clinic in a university medical center from June to August 2022. We used 3D-printed crowns fabricated with PLA using an FDM printer as temporary crowns and were assessed for discomfort, fracture, and dislodging. The 3D-printed temporary crowns were maintained without fracture, dislodging, or discomfort until the permanent prosthesis was ready. The average time required for printing the temporary crowns was approximately 7 minutes. The 3D printing of temporary crowns with PLA using an FDM printer is a convenient process for dentists. However, these crowns have some limitations, such as rough surface texture and translucency; therefore, the 3D printing process should be improved to produce better prostheses.

Effects of Hydrogen-rich Water on Cariogenic Bacteria.

Context: Some kinds of electrolysed water have been reported to exhibit antioxidant and bactericidal activity. However, studies on the effect of electrolysed hydrogen-rich water (EHW) with a neutral pH on cariogenic bacteria are limited. Aim: This study aimed to evaluate the feasibility of using EHW as a mouthwash by examining its various effects on cariogenic bacteria. Materials and Methods: To test the bactericidal and anti-biofilm formation effects of EHW on Streptococcus mutans and Streptococcus sobrinus, bacterial growth curves, colony-forming unit (CFU) counts, and crystal violet staining of biofilms were examined after exposing the bacterial pellets to EHW or tap water as a control for one minute. In addition, the expressions of glucosyltransferase and glucan-binding proteins encoding genes were examined using real-time PCR. Results: Bacterial growth and biofilm formation were inhibited, and the number of CFUs was significantly reduced in the EHW group compared to the control group. The expression of genes encoding glucosyltransferases (gtfB, gtfC, and gtfI) and glucan-binding proteins (gbpC and dblB) were also decreased in the EHW group compared to the control. Conclusions: Exposing cariogenic bacteria to EHW at neutral pH for one minute can effectively inhibit bacterial growth and biofilm formation in vitro, suggesting that EHW is a promising mouthwash.

Caries detection with tooth surface segmentation on intraoral photographic images using deep learning.

BACKGROUND: Intraoral photographic images are helpful in the clinical diagnosis of caries. Moreover, the application of artificial intelligence to these images has been attempted consistently. This study aimed to evaluate a deep learning algorithm for caries detection through the segmentation of the tooth surface using these images. METHODS: In this prospective study, 2348 in-house intraoral photographic images were collected from 445 participants using a professional intraoral camera at a dental clinic in a university medical centre from October 2020 to December 2021. Images were randomly assigned to training (1638), validation (410), and test (300) datasets. For image segmentation of the tooth surface, classification, and localisation of caries, convolutional neural networks (CNN), namely U-Net, ResNet-18, and Faster R-CNN, were applied. RESULTS: For the classification algorithm for caries images, the accuracy and area under the receiver operating characteristic curve were improved to 0.813 and 0.837 from 0.758 to 0.731, respectively, through segmentation of the tooth surface using CNN. Localisation algorithm for carious lesions after segmentation of the tooth area also showed improved performance. For example, sensitivity and average precision improved from 0.890 to 0.889 to 0.865 and 0.868, respectively. CONCLUSION: The deep learning model with segmentation of the tooth surface is promising for caries detection on photographic images from an intraoral camera. This may be an aided diagnostic method for caries with the advantages of being time and cost-saving.

Association between periodontal disease and diabetes using propensity score matching: The seventh Korea National Health and Nutrition Examination Survey.

The association between periodontitis and diabetes have been assessed by many cross-sectional studies, in which controlling confounding factors is important. Propensity score matching (PSM) may help address this issue. Therefore, we evaluated this relationship in a (PSM) analysis of individuals representing the general Korean population. Periodontitis was significantly associated with diabetes before PSM (odds ratio [OR] = 1.53; 95 % confidence interval (CI) = 1.31-1.80) and after PSM (OR = 1.52; 95 % CI = 1.28-1.80). This study showed the association between periodontitis and diabetes using PSM, suggesting that periodontitis may be positively related with diabetes. We included 9508 adults who were aged ≥ 19 years from the Korea National Health and Nutrition Examination Survey VII (2016-2018) and performed logistic regression analyses before and after PSM. The PSM was based on periodontal disease (yes or no) using a 1:1 match ratio and included 5858 individuals (2929 per group). Confounding variables, such as age, sex, marital status, occupation, education, income, smoking and drinking habits, obesity, hypertension, hypercholesterolemia, and hypertriglyceridemia, were matched and adjusted in the logistic regression analysis.

Incidence of edentulism among older adults using the Korean National Health Insurance Service database, 2013-2018.

OBJECTIVES: Population aging is rapidly accelerating worldwide. Oral diseases related to aging are also on the rise. This study examined trends in the incidence of edentulism among the older Korean population using data from the Korean National Health Insurance Service (KNHIS). METHODS: Data on older adults, aged ≥75 years of age, were obtained from the KNHIS for the period 2013-2018. Edentulism was defined as a treatment history of complete dentures in the KNHIS database. The exclusion criteria consisted of both disease codes and treatment codes related to conservative dental treatment, including periodontal and extraction treatment afterward. Crude incidence rates (CIRs) and age-standardized incidence rates (AIRs) with 95% confidence intervals were calculated and reported per 100,000 person-years by the direct method. Trends were tested by Cochrane Armitage models. RESULTS: Statistically significant increasing trends in both CIRs and AIRs were found among the older Korean population registered in the KNHIS (CIRs, 707.92 to 895.92; AIRs, 705.11 to 889.68; p<0.01). The incidence tended to increase in both genders (p<0.01). Both CIRs and AIRs in specific regions also showed slight but significant annual increases except for Jeju Island (p<0.01 or <0.05). The incidence showed increasing trends (p<0.01) in all income quintiles apart from the highest quintile. The edentulism incidence was highest in the lowest income group (the first quintile). CONCLUSIONS: Our data showed that the incidence of edentulism among the elderly showed an increasing trend from 2013 to 2018. This result provides a basis for future epidemiological studies on the incidence of edentulism in the older Korean population.

Influence of Chewing Ability on Elderly Adults' Cognitive Functioning: The Mediating Effects of the Ability to Perform Daily Life Activities and Nutritional Status.

Chewing ability is also related to activities of daily living (ADLs) and nutritional status; however, these associations have not been firmly established. We examined chewing ability as a predictor variable and explored its relationship with cognitive functioning as mediated by ADLs and nutritional status data were collected by face-to-face interviews. Patients were receiving home healthcare service in Mun-gyeong city, Gyung-buk, Korea. Participants comprised 295 patients aged 81.35 ± 6.70 years. Structural equation modeling (SEM) was performed using AMOS 18.0 (SPSS Inc., Chicago, IL, USA). The model fit was based on absolute fit index and incremental fit index. Data were collected to assess cognitive functioning (using the Korean version of the Mini-Mental Status Examination for dementia screening (MMSE-DS)), ADL, a mini-nutritional assessment (MNA) questionnaire, and a chewing ability test. Participants with better chewing ability had significantly better cognitive functioning, ADLs, and nutritional status (p < 0.001). Chewing ability directly affected cognitive functioning and indirectly affected how ADLs and MNA affected MMSE-DS. Chewing ability is an important factor influencing the cognitive functioning of elderly adults in Korea, both directly and indirectly through mediating variables such as nutritional status and ADLs. Efforts to help older adults maintain their chewing ability are necessary for preventing cognitive impairment.

[6]-Gingerol Suppresses Oral Cancer Cell Growth by Inducing the Activation of AMPK and Suppressing the AKT/mTOR Signaling Pathway.

BACKGROUND/AIM: [6]-Gingerol, a compound extracted from ginger, has been studied for its therapeutic potential in various types of cancers. However, its effects on oral cancer remain largely unknown. Here, we aimed to investigate the potential anticancer activity and underlying mechanisms of [6]-gingerol in oral cancer cells. MATERIALS AND METHODS: We analyzed the antigrowth effects of [6]-gingerol in oral cancer cell lines by cell proliferation, colony formation, migration, and invasion assays. We detected cell cycle and apoptosis with flow cytometry and further explored the mechanisms of action by immunoblotting. RESULTS: [6]-Gingerol significantly inhibited oral cancer cell growth by inducing apoptosis and cell cycle G2/M phase arrest. [6]-Gingerol also inhibited oral cancer cell migration and invasion by up-regulating E-cadherin and down-regulating N-cadherin and vimentin. Moreover, [6]-gingerol induced the activation of AMPK and suppressed the AKT/mTOR signaling pathway in YD10B and Ca9-22 cells. CONCLUSION: [6]-Gingerol exerts anticancer activity by activating AMPK and suppressing the AKT/mTOR signaling pathway in oral cancer cells. Our findings highlight the potential of [6]-gingerol as a therapeutic drug for oral cancer treatment.

Costunolide Induces Apoptosis via the Reactive Oxygen Species and Protein Kinase B Pathway in Oral Cancer Cells.

Oral cancer (OC) has been attracted research attention in recent years as result of its high morbidity and mortality. Costunolide (CTD) possesses potential anticancer and bioactive abilities that have been confirmed in several types of cancers. However, its effects on oral cancer remain unclear. This study investigated the potential anticancer ability and underlying mechanisms of CTD in OC in vivo and in vitro. Cell viability and anchorage-independent colony formation assays were performed to examine the antigrowth effects of CTD on OC cells; assessments for migration and invasion of OC cells were conducted by transwell; Cell cycle and apoptosis were investigated by flow cytometry and verified by immunoblotting. The results revealed that CTD suppressed the proliferation, migration and invasion of oral cancer cells effectively and induced cell cycle arrest and apoptosis; regarding the mechanism, CTD bound to AKT directly by binding assay and repressed AKT activities through kinase assay, which thereby downregulating the downstream of AKT. Furthermore, CTD remarkably promotes the generation of reactive oxygen species by flow cytometry assay, leading to cell apoptosis. Notably, CTD strongly suppresses cell-derived xenograft OC tumor growth in an in vivo mouse model. In conclusion, our results suggested that costunolide might prevent progression of OC and promise to be a novel AKT inhibitor.

20(S)-Ginsenoside Rh2 Suppresses Oral Cancer Cell Growth by Inhibiting the Src-Raf-ERK Signaling Pathway.

BACKGROUND: 20(S)-Ginsenoside Rh2 (G-Rh2) has demonstrated therapeutic effects in many types of cancers. We aimed to investigate the potential anticancer activity and underlying mechanisms of G-Rh2 in oral cancer cells. MATERIALS AND METHODS: The antigrowth effect of G-Rh2 in oral cancer cells was stimulated by cell proliferation, soft agar colony formation, and migration and invasion assay. The cell cycle and apoptosis were detected by flow cytometry. The underlying mechanism of G-Rh2 in oral cancer cells was explored by immunoblotting. RESULTS: G-Rh2 significantly inhibited oral cancer cell growth by inducing apoptosis and cell cycle G0/G1-phase arrest. G-Rh2 inhibited oral cancer cell migration and invasion through regulation of epithelial-mesenchymal transition (EMT)-related proteins. G-Rh2 inhibited the Src/Raf/ERK signaling pathway in YD10B and Ca9-22 cells. CONCLUSION: G-Rh2 exerted anticancer activity in vitro by inhibiting the Src/Raf/ERK signaling pathway in oral cancer. G-Rh2 is a potential therapeutic drug for oral cancer treatment.

Association between Periodontal Health and Stroke: Results from the 2013-2015 Korea National Health and Nutrition Examination Survey (KNHANES).

BACKGROUND/PURPOSE: As the population ages, the prevalence of stroke increases, and as such there has been increasing interest in the risk factors associated with stroke. Although an association between periodontitis and stroke has been suggested, there has been no study of this association among the Korean population. Therefore, we investigated the association between periodontal health and stroke among Korean adults. MATERIALS AND METHODS: A total of 9497 adults aged ≥40 years representing the Korean population were included in this cross-sectional study from the Korea National Health and Nutrition Examination Survey (KNHANES) VI (2013-2015). Periodontitis was diagnosed by dentists based on the Community Periodontal Index (CPI). Also, participants filled out a questionnaire regarding their experience of doctor-diagnosed stroke. Hypertension, diabetes, body mass index (BMI), and oral hygiene behavior covariates were adjusted in logistic regression analysis. RESULTS: The mean age of the study population was 55.71 ±â€¯0.17 years and 52.7% of them were female. Also, 248 people had a history of having a stroke. Results of the logistic regression analysis after adjusting for age and sex showed a significant relationship between oral health behavior, periodontal health, and stroke even after adjusting for age, sex, education, household income, national health insurance, employment status, alcohol, smoking, diabetes, hypertension, BMI, and oral health behaviors (odds ratio [OR], 1.71; 95% confidence interval [CI] = 1.03-2.85). CONCLUSION: Our findings suggest that periodontitis is associated with stroke in Korean adults.

Effects of the professional oral care management program on patients with head and neck cancer after radiotherapy: A 12-month follow-up.

BACKGROUND/PURPOSE: Because oral health of patients with head & neck cancer is prone to disease after radiotherapy, effective and long-lasting oral care program is necessary. We aimed to evaluate the effects of the oral care management program, which lasted up to 12 months after radiotherapy for patients with head and neck cancer. MATERIALS AND METHODS: Sixty-eight patients who visited a dental clinic prior to the initiation of radiotherapy were recruited and categorized into either a "healthy" or a "vulnerable" group. The vulnerable group was made of patients with dental caries or periodontal attachment loss. Professional oral hygiene care, including tooth brushing instructions, professional mechanical tooth cleaning, and fluoride varnish application, was conducted once every week for a month during radiotherapy and once every 3 months after radiotherapy. Oral health, including dental caries, plaques, gingival index, and periodontal attachment loss, was examined at baseline, 6 months, and 12 months after radiotherapy. RESULTS: ; Twenty-nine and 16 patients were followed up at 6 and 12 months after radiotherapy, respectively. Oral health indices, such as the number of decayed teeth, amount of plaque, and gingival index, did not significantly change in either group. However, the periodontal pocket depth significantly decreased in both groups at 6 months after baseline, and this decrease continued in the vulnerable group up to 12 months after baseline. CONCLUSION: Periodic dental visits and professional oral hygiene care during and after radiotherapy were effective in maintaining oral health for over 12 months after radiotherapy in patients with head and neck cancer.

Evaluation of craniofacial morphology in short-statured children: growth hormone deficiency versus idiopathic short stature.

BACKGROUND: Short stature is defined as a height below the 3rd percentile or more than two standard deviations below the mean for a given age, sex, and population. There have been inconsistent results regarding craniofacial morphology in short-statured children. This study aimed to analyze the differences between short-statured children with growth hormone deficiency, idiopathic short-statured children, and normal children. METHODS: Thirty-one short-statured children with growth hormone deficiency, 32 idiopathic short-statured children, and 32 healthy children were enrolled in this study. The measurements of their craniofacial structures from lateral cephalograms were evaluated. RESULTS: There were statistically significant differences among the three groups seven variables (anterior cranial base length, posterior cranial base length, total cranial base length, upper posterior facial height, posterior total facial height, mandibular ramus length, and overall mandibular length) in the linear measurement and five variables (saddle angle, gonial angle, mandibular plane angle, position of mandible, and maxilla versus mandible) in the angular measurement. CONCLUSION: Compared to the control group, many linear and angular measurements of the craniofacial structures were significantly different in the two short-statured groups (p<0.05). Treatment plans by orthodontists should include these craniofacial structure characteristics.

Comparison of the removal torque and a histomorphometric evaluation of the RBM treated implants with the RBM followed by laser treated implants: an experimental study in rabbits.

Background: In the osseointegration of dental implants, the implant surface properties have been reported to be some of the most important critical factors. The effect of implant's surfaces created by resorbable blast media (RBM) followed by laser ablation on bone tissue reactions was examined using the removal torque test and histomorphometric analysis. Methods: Two types of dental implants, RBM-laser implants (experimental group) and RBM implants (control group) (CSM implant system, Daegu, Korea; L=6 mm, diameter=3.75 mm) were placed into the right and left distal femoral metaphysis of 17 adult rabbits. Six weeks after placement, removal torque was measured and histomorphometric analysis was performed. Results: The mean removal torque was 24.0±10.2 Ncm and 46.6±16.4 Ncm for the control and test specimens, respectively. The experimental RBM-laser implants had significantly higher removal torque values than the control RBM implants (p=0.013). The mean values of total and cortical bone to implant contact (BIC) were respectively 46.3±10.8% and 65.3±12.5% for the experimental group, and 41.9±18.5% and 57.6±10.6% for the control group. The experimental RBM-laser implants showed a higher degree of total and cortical BIC compared with RBM implants, but there was no statistical significance (p=0.482, 0.225). Conclusion: The removal torque and BIC of the test group were higher than those of the control group. In this study, the surface treatment created by RBM treatment followed by laser ablation appears to have a potential in improving bone tissue reactions of dental implants.

Design and Synthesis of a Novel and Selective Kappa Opioid Receptor (KOR) Antagonist (BTRX-335140).

κ opioid receptor (KOR) antagonists are potential pharmacotherapies for the treatment of migraine and stress-related mood disorders including depression, anxiety, and drug abuse, thus the development of novel KOR antagonists with an improved potency/selectivity profile and medication-like duration of action has attracted the interest of the medicinal chemistry community. In this paper, we describe the discovery of 1-(6-ethyl-8-fluoro-4-methyl-3-(3-methyl-1,2,4-oxadiazol-5-yl)quinolin-2-yl)- N-(tetrahydro-2 H-pyran-4-yl)piperidin-4 amine (CYM-53093, BTRX-335140) as a potent and selective KOR antagonist, endowed with favorable in vitro ADMET and in vivo pharmacokinetic profiles and medication-like duration of action in rat pharmacodynamic experiments. Orally administered CYM-53093 showed robust efficacy in antagonizing KOR agonist-induced prolactin secretion and in tail-flick analgesia in mice. CYM-53093 exhibited a broad selectivity over a panel of off-target proteins. This compound is in phase 1 clinical trials for the treatment of neuropsychiatric disorders wherein dynorphin is thought to contribute to the underlying pathophysiology.

Subjective chewing ability and health-related quality of life among the elderly.

OBJECTIVE: Chewing ability may reflect the overall oral health, which affects the general health of the elderly. Therefore, we assessed the association between subjective chewing ability and health-related quality of life (HRQOL) among the elderly. METHODS: We analysed the data of 3034 elderly people aged ≥65 years from the Korean National Health and Nutrition Examination Survey that was conducted by the Korean government from 2013 to 2015 (KNHANES-VI). Subjective chewing ability was evaluated using a questionnaire, and HRQOL was assessed using EuroQol 5-dimension (EQ-5D) instrument by trained examiners. Covariates, such as socio-demographic, oral health-related and general health-related variables, were investigated. RESULTS: Logistic regression analysis showed that chewing ability was significantly associated with HRQOL in both crude and adjusted model for covariates such as age, gender, economic activity, residence, education, smoking, alcohol, hypertension, diabetes, remaining teeth, denture, CPI, tooth brushing and oral hygiene (crude OR, 2.67; 95% CI, 2.23-3.20) (adjusted OR, 2.36; 95% CI, 1.95-2.86). Chewing ability was also significantly associated with most dimensions of EQ-5D, such as motor ability, self-care, daily activities, pain and discomfort, and anxiety and depression (P < 0.05). CONCLUSION: Chewing ability was significantly associated with HRQOL, suggesting that elderly people with low chewing ability are more likely to have poor health-related quality of life.