Three-dimensional body composition parameters using automatic volumetric segmentation allow accurate prediction of colorectal cancer outcomes.

BACKGROUND: Parameters obtained from two-dimensional (2D) cross-sectional images have been used to determine body composition. However, data from three-dimensional (3D) volumetric body images reflect real body composition more accurately and may be better predictors of patient outcomes in cancer. This study aimed to assess the 3D parameters and determine the best predictive factors for patient prognosis. METHODS: Patients who underwent surgery for colorectal cancer (CRC) between 2010 and 2016 were included in this study. Preoperative computed tomography images were analysed using an automatic segmentation program. Body composition parameters for muscle, muscle adiposity, subcutaneous fat (SF) and abdominal visceral fat (AVF) were assessed using 2D images at the third lumbar (L3) level and 3D images of the abdominal waist (L1-L5). The cut-off points for each parameter were determined using X-tile software. A Cox proportional hazards regression model was used to identify the association between the parameters and the treatment outcomes, and the relative influence of each parameter was compared using a gradient boosting model. RESULTS: Overall, 499 patients were included in the study. At a median follow-up of 59 months, higher 3D parameters of the abdominal muscles and SF from the abdominal waist were found to be associated with longer overall survival (OS) and disease-free survival (all P < 0.001). Although the 3D parameters of AVF were not related to survival outcomes, patients with a high AVF volume and mass experienced higher rate of postoperative complications than those with low AVF volume (27.4% vs. 18.7%, P = 0.021, for mass; 27.1% vs. 19.0%, P = 0.028, for volume). Low muscle mass and volume (hazard ratio [HR] 1.959, P = 0.016; HR 2.093, P = 0.036, respectively) and low SF mass and volume (HR 1.968, P = 0.008; HR 2.561, P = 0.003, respectively), both in the abdominal waist, were identified as independent prognostic factors for worse OS. Along with muscle mass and volume, SF mass and volume in the abdominal waist were negatively correlated with mortality (all P < 0.001). Both AVF mass and volume in the abdominal waist were positively correlated with postoperative complications (P < 0.05); 3D muscle volume and SF at the abdominal waist were the most influential factors for OS. CONCLUSIONS: 3D volumetric parameters generated using an automatic segmentation program showed higher correlations with the short- and long-term outcomes of patients with CRC than conventional 2D parameters.

Gut microbiome associated with low anterior resection syndrome after rectal cancer surgery.

This study aimed to assess the likely association of gut microbiome with low anterior resection syndrome (LARS) symptoms. Postoperative stool samples from patients with minor or major LARS after sphincter-preserving surgery (SPS) for rectal cancer were collected and analyzed using 16S ribosomal RNA sequencing method. The symptom patterns of LARS were classified into two groups (PC1LARS, PC2LARS) using principal component analysis. The dichotomized sum of questionnaire items (sub1LARS, sub2LARS) was used to group patients according to the main symptoms. According to microbial diversity, enterotype, and taxa, PC1LARS and sub1LARS were associated with frequency-dominant LARS symptoms and patients, while PC2LARS and sub2LARS were grouped as incontinence-dominant LARS symptoms and patients. Butyricicoccus levels decreased while overall LARS scores increased. The α-diversity richness index Chao1 showed a significantly negative correlation in sub1LARS and a positive correlation in sub2LARS. In sub1LARS, the severe group showed a lower Prevotellaceae enterotype and higher Bacteroidaceae enterotype than the mild group. Subdoligranulum and Flavonifractor showed a negative and a positive correlation with PC1LARS, respectively, while showing a negative relationship with PC2LARS. Lactobacillus and Bifidobacterium were negatively correlated to PC1LARS. Frequency-dominant LARS had decreased diversity of gut microbiome and showed lower levels of lactic acid-producing bacteria.

The Association between Dental Implant Treatment Experience and Socioeconomic Factors in Korean Adults: A Cross-Sectional Survey Data Analysis.

Background: We examined the Korean adults' experience with dental implants and analyzed its association with various socioeconomic factors. Methods: This study was based on the participants enrolled in the 2013-2015 KNHANES. Using the variables associated with dental implant treatment experience and other socioeconomic factors, we evaluated the statistical significance and potential associations between the dental implant treatment experience and its related factors. The final analysis in this study was performed on adults aged 20 yr and over. It comprised 4,893 subjects in the year 2013, 4,431 subjects in 2014, and 4,430 subjects in 2015. Results: An increasing number of individuals had reported undergoing dental implant treatment. An older age was associated with a higher likelihood of undergoing dental implant treatment, particularly in adults aged ≥40 years. Additionally, the likelihood was higher in individuals with a greater income level, low-level of educational background, and married status. Factors that were observed to influence dental implant treatment experience included age, education level, income level, marital status. Conclusion: Our analysis confirmed the growing accessibility to dental implants among Korean adults and an association between dental implant treatment experience and socioeconomic factors. We recommend a healthcare policy on dental implants that considers relevant socioeconomic factors, in order to provide dental implant treatment to individuals who are in absolute need of treatment.

Effects of Problem-Based Learning on the Problem-Solving Ability and Self-Efficacy of Students Majoring in Dental Hygiene.

This study developed a problem-based learning (PBL) module to improve integrated thinking and problem-solving ability in students of dental hygiene. After applying PBL, the study tested the improvement in the problem-solving ability and self-efficacy of students. The subjects were 31 fourth-year students of the Department of Dental Hygiene at G University. The PBL process was applied to three topics for 15 weeks, and the tools for evaluating problem-solving ability and self-efficacy were reconstructed and used before and after the application to examine the effects of the module. The result indicates that the mean of problem-solving ability (32 detailed items) increased from 3.37 to 3.65 (an increase of 0.28) after classes (p < 0.001). Alternatively, the average for self-efficacy (22 detailed questions) increased from 0.21 to 2.89 (p < 0.05; an increase of 2.67). The study also confirmed the correlation between problem-solving ability and the total posttest score for self-efficacy (p < 0.001). Thus, the problem-solving ability and self-efficacy of learners were improved in the class to which PBL was applied. These improvements exerted a significant effect on the improvement of problem-solving ability. This finding confirmed the effect of the PBL method on dental hygiene education.

Has the Health Insurance Coverage of Scaling Contributed Positively to Periodontal Health in Korea?

This study aimed to evaluate the effectiveness of the health insurance coverage of dental scaling (introduced in 2013) using the Community Periodontal Index of Treatment Needs parameter among Korean adults aged 20 years or older. We used the Korea National Health and Nutrition Examination Survey data from before and after 2013 to analyze the statistical significance and associations of the covariates with the prevalence of healthy periodontal tissues, prevalence of people in need of scaling, and prevalence of periodontal diseases. The results showed that the prevalence of healthy periodontal tissues increased by 4.9% (from 34.2% to 39.1%), the number of people in need of scaling decreased by 5% (from 65.9% to 60.9%), and the prevalence of periodontal diseases increased by 7.2% (from 23.4% to 30.6%). Moreover, after the scaling coverage policy, the odds ratio of the prevalence of healthy periodontal tissues was 1.10 times higher, the prevalence of the need for scaling was 1.5 times higher, and the prevalence of periodontal diseases was 0.90 times lower. Therefore, the state should formulate policies that provide dental biofilm management through a disclosing agent, impart education about oral hygiene, and develop a health management system that enables the concurrent management of periodontal diseases and systemic diseases.

The Impact of Expanded National Health Insurance Coverage of Dentures and Dental Implants on Dental Care Utilization among Older Adults in South Korea: A Study Based on the Korean Health Panel Survey.

In South Korea, the National Health Insurance Service (NHIS) began its coverage of dentures and dental implants for older people in 2012 and 2014, respectively. This study aimed to investigate the impact of these policies on dental care utilization among people aged 65 years or older according to their sociodemographic characteristics. Data were collected from the Korea Health Panel Survey (KHP; years 2012 and 2015). The statistical significance of the relationships between sociodemographic characteristics and the use of outpatient dental care, denture, and dental implant were analyzed. Results showed an increase of 5.7%, 1.4%, and 2.8% in the use of outpatient dental care, denture, and dental implant, respectively, over the course of three years. Including dentures increased its use by 2.5-3.7 times among people aged 70 years or older. Including dental implants alleviated the disparities among older adults based on age groups and duration of education, except those among uneducated people; however, it caused inequity according to household income. Some Korean older adults remain neglected from the benefits of the expanded NHIS. Therefore, older adults' access to dental care should be enhanced by the implementation of policies to promote oral health care utilization, dental prosthetic services, and older adults' insurance coverage.

Changes in oral health indicators due to implementation of the National Health Insurance Services coverage for first molar dental sealant for children and adolescents in South Korea.

BACKGROUND: In South Korea, dental sealant was included in the National Health Insurance Services (NHIS) coverage for the first molar for ages 6-14 in December 2009. The second molar was included in 2012, and the age of insurance coverage was extended to under 18 in 2013. This study aimed to verify the effectiveness of an NHIS dental sealant coverage policy for children and adolescents by comparing the changes in first molar oral health indicators before and after policy implementation. METHODS: The Korea National Health and Nutrition Examination Survey data were analyzed; the fourth period (2007-2009) provided data for before and the sixth period (2013-2015) provided data for after policy implementation. The proportion of individuals with first-molar sealant, decay-missing-filled first molar permanent teeth, and single crowns in the group aged 11-20 years were calculated. Data were analyzed using chi-square for complex samples and the complex samples general linear model. In addition, complex-sample logistic regression analysis was performed to confirm the association between factors. RESULTS: Compared with non-beneficiaries, among policy beneficiaries, sealant ownership increased by 7.7% (from 27.8 to 35.5, P < 0.001), and the number of permanent teeth with sealant per capita increased by approximately 0.4 to 0.8 (P < 0.001). The proportion of individuals with decay-missing-filled permanent teeth decreased by 9.1% (from 68.4 to 59.3, P < 0.001), and the average decay-missing-filled permanent teeth index per person decreased by approximately 2.0 to 1.5 (P < 0.001). The rate of single-crown holders decreased by 2.7% (from 8.7 to 6.0, P > 0.05), and the average single-crown index decreased by approximately 0.11 to 0.08 per person(P > 0.05). The number of sealants increased with age and household income (P < 0.001). The mother's education level affected sealant experience (P < 0.05). The caries rate was higher in females and older respondents (P < 0.001). CONCLUSIONS: The sealant covered by NHIS contributed to decreasing dental caries in Korea. However, policies that can reduce oral health inequality should also be considered, and a follow-up study is required for long-term sealant maintenance in Korea.

The impact of national health insurance coverage on pit and fissure sealing experience.

INTRODUCTION: The purpose of this study was to review the change of supplied amount of oral pit and fissure sealing (PFS) in urban and rural areas of South Korea after including PFS into the list of treatments covered by the National Health Insurance (NHI), and to check whether there is a difference in supplied amount in areas where the dental treatment accessibility is different based on the data of the Korean National Health and Nutritional Examination Survey (KNHANES). METHODS: The KNHANES data year used for 'before coverage' was 2007, and that of 'after coverage' was 2012. Data analysis was done using STATA software. RESULTS: Areas were classified as urban or rural. Reduction of out-of-pocket expenses, according to the NHI coverage PFS experience of children aged 6-14 years, increased from 28.7% before coverage to 34.9% after coverage. PFS experience of children aged 6-14 years in the urban area was increased from 29.2% before coverage to 35.6% after coverage. The increase in rural areas was from 27.2% before coverage to 31.5% after coverage. CONCLUSIONS: Although PFS supplying was increased after inclusion in NHI coverage, it is still insufficient to reduce the decayed, missing, filled teeth index effectively. To reduce inequality, supply of PFS in rural area by community oral health program should be strengthened. And also, waiving out-of-pocket money for PFS in NHI should be considered.

Association of meal frequency with metabolic syndrome in Korean adults: from the Korea National Health and Nutrition Examination Survey (KNHANES).

BACKGROUND: Although previous studies have established a close relationship between caloric intake and metabolic syndrome, there is limited research exploring the impact of meal frequency adjusted by caloric intake on metabolic syndrome (MetS). OBJECTIVE: To evaluate the association of meal frequency and MetS after adjusting for confounding factors including caloric intake in Korean men and women. METHODS: We analyzed the national representative data of a total 12,389 adults (5171 men, 7218 women) from the Korean National Health and Nutrition Examination Survey (KNHANES) 2010-2012. Subjects were categorized as eating 3 meals/day (MF3) or 2 or fewer meals/day (MF ≤ 2). Daily caloric intake was calculated using CAN-Pro 4.0 (The Korean Nutrition Society, Seoul, Korea). RESULTS: The prevalence of components of MetS differed significantly according to meal frequency in both men and women. In an unadjusted analysis, the prevalence of MetS in women was significantly higher in the MF3 group than the MF ≤ 2 group (27.5% vs. 17.8%, P < 0.001), whereas the prevalence of MetS in men did not differ between the MF3 and MF ≤ 2 groups (24.6% vs. 22.7%, P = 0.281). However, after adjusting for age, caloric intake, smoking status, alcohol consumption, physical activity, income, and education level, men in the MF ≤ 2 group had an increased risk of metabolic syndrome compared to men in the MF3 group (OR = 1.37, 95%, CI = 1.12-1.67). On the other hand, meal frequency did not affect the risk of metabolic syndrome in women after adjusting for confounding factors including caloric intake (OR = 1.09, 95%, CI = 0.90-1.31). CONCLUSIONS: This study suggests that lower meal frequency adjusted for caloric intake, physical activity, age, smoking, alcohol, income, and education may be associated with increased risk of MetS in Korean men.

An interstitial, apparently-balanced chromosomal insertion in the etiology of Langer-Giedion syndrome in an Asian family.

Langer-Giedion syndrome (LGS; MIM 150230), also called trichorhinophalangeal syndrome type II (TRPS2), is a contiguous gene syndrome caused by a one-copy deletion in the chromosome 8q23-q24 region, spanning the genes TRPS1 and EXT1. We identified an LGS family with two affected and two unaffected siblings from unaffected parents. To investigate the etiology of recurrence of LGS in this family, array CGH was performed on all family members. We identified a 7.29 Mb interstitial deletion at chromosome region 8q23-q24 in the two affected siblings, but no such deletion in the unaffected family members. However, the mother and one of the two unaffected siblings carried a 1.29 Mb deletion at chromosome region 8q24.1, sharing the distal breakpoint with the larger deleted segment found in the affected siblings. Another unaffected sibling had a 6.0 Mb duplication, sharing the proximal breakpoint of the deletion in the affected siblings. Karyotypic and FISH analyses in the unaffected mother revealed an insertional translocation of 8q23-q24 genomic material into chromosome 13: 46,XX,ins(13;8)(q33;q23q24). This insertional translocation in the mother results in the recurrence of LGS in this family, highlighting the importance of submicroscopic rearrangements in the genetic counseling for LGS.

Identification of fused bicyclic heterocycles as potent and selective 5-HT(2A) receptor antagonists for the treatment of insomnia.

A series of fused bicyclic heterocycles was identified as potent and selective 5-HT(2A) receptor antagonists. Optimization of the series resulted in compounds that had improved PK properties, favorable CNS partitioning, good pharmacokinetic properties, and significant improvements on deep sleep (delta power) and sleep consolidation.

Effect on Glycemic, Blood Pressure, and Lipid Control according to Education Types.

BACKGROUND: Diabetes self-management education and reinforcement are important for effective management of the disease. We investigated the effectiveness of interactive small-group education on glycemic, blood pressure, and lipid levels. METHODS: For this study, 207 type 2 diabetes patients with suboptimal glycemic control (HbA1c levels >6.5%) were enrolled. The conventional education group received an existing education program from April to November in 2006, and the interactive education group received a new small-group education program from December 2006 to July 2007. The two groups were comparatively analyzed for changes in blood sugar, glycated hemoglobin, lipid, and blood pressure at baseline, 3, 6, and 12 months and the proportion of patients achieving target goals at 12 months. RESULTS: After 12 months of follow-up, HbA1c levels in the interactive education group were significantly lower than in the conventional education group (6.7% vs. 6.4%, P<0.001). Fasting and 2 hour postprandial glucose concentrations, total cholesterol, and low density lipoprotein cholesterol were significantly lower in the interactive education group than in the conventional education group. The proportion of patients that achieved target goals was significantly higher in the interactive education group. CONCLUSION: The small-group educational method improved and re-established the existing group educational method. This finding suggests that the importance of education appears to be related to the method by which it is received rather than the education itself. Thus, the use of small-group educational methods to supplement existing educational methods established for diverse age levels should be considered in the future.

Synthesis and in vivo evaluation of phenethylpiperazine amides: selective 5-hydroxytryptamine(2A) receptor antagonists for the treatment of insomnia.

Recent developments in sleep research suggest that antagonism of the serotonin 5-HT(2A) receptor may improve sleep maintenance insomnia. We herein report the discovery of a series of potent and selective serotonin 5-HT(2A) receptor antagonists based on a phenethylpiperazine amide core structure. When tested in a rat sleep pharmacology model, these compounds increased both sleep consolidation and deep sleep. Within this series of compounds, an improvement in the metabolic stability of early leads was achieved by introducing a carbonyl group into the phenethylpiperazine linker. Of note, compounds 14 and 27 exhibited potent 5-HT(2A) receptor binding affinity, high selectivity over the 5-HT(2C) receptor, favorable CNS partitioning, and good pharmacokinetic and early safety profiles. In vivo, these two compounds showed dose-dependent, statistically significant improvements on deep sleep (delta power) and sleep consolidation at doses as low as 0.1 mg/kg.

Discovery and structure-activity relationship of 3-methoxy-N-(3-(1-methyl-1H-pyrazol-5-yl)-4-(2-morpholinoethoxy)phenyl)benzamide (APD791): a highly selective 5-hydroxytryptamine2A receptor inverse agonist for the treatment of arterial thrombosis.

Serotonin, which is stored in platelets and is released during thrombosis, activates platelets via the 5-HT(2A) receptor. 5-HT(2A) receptor inverse agonists thus represent a potential new class of antithrombotic agents. Our medicinal program began with known compounds that displayed binding affinity for the recombinant 5-HT(2A) receptor, but which had poor activity when tested in human plasma platelet inhibition assays. We herein describe a series of phenyl pyrazole inverse agonists optimized for selectivity, aqueous solubility, antiplatelet activity, low hERG activity, and good pharmacokinetic properties, resulting in the discovery of 10k (APD791). 10k inhibited serotonin-amplified human platelet aggregation with an IC(50) = 8.7 nM and had negligible binding affinity for the closely related 5-HT(2B) and 5-HT(2C) receptors. 10k was orally bioavailable in rats, dogs, and monkeys and had an acceptable safety profile. As a result, 10k was selected further evaluation and advanced into clinical development as a potential treatment for arterial thrombosis.

Activation of autophagy during glutamate-induced HT22 cell death.

Recent evidence suggests that autophagy plays a role in oxidative injury-induced cell death. Here we examined whether glutamate-mediated oxidative toxicity induces autophagy in murine hippocampal HT22 cells and if autophagy induction affects the molecular events associated with cell death. Markers for autophagy induction including LC3 conversion, suppression of mTOR pathway, and GFP-LC3 dot formation were enhanced by glutamate treatment. By contrast, autophagy inhibition blocked glutamate-induced LC3 conversion and consequently reduced cell death. Activation of ERK1/2, a hallmark of glutamate-induced cytotoxicity, was also decreased by autophagy inhibition. Interestingly, autophagy inhibition also affected the expression of chaperones including Hsp60 and Hsp70, which are differentially regulated during HT22 cell death. Conversely, knock-down of Hsp60 greatly decreased LC3 conversion. Together these results suggest that glutamate-induced cytotoxicity involves autophagic cell death and chaperones may play a role in this process.

Reflection minimization at two-dimensional photonic crystal interfaces.

We propose a method to design antireflection structures to minimize the reflection of light beams at the interfaces between a two-dimensional photonic crystal and a homogeneous dielectric. The design parameters of the optimal structure to give zero reflection can be obtained from the one-dimensional antireflection coating theory and the finite-difference time-domain simulations. We examine the performance of a Mach-Zehnder interferometer utilizing the self-collimated beams in two-dimensional photonic crystals with and without the optimal antireflection structure introduced. It is shown that the optimal antireflection structure significantly improves the performance of the device.

Co-chaperone CHIP associates with mutant Cu/Zn-superoxide dismutase proteins linked to familial amyotrophic lateral sclerosis and promotes their degradation by proteasomes.

Although the ubiquitin-proteasome system and the molecular chaperones are implicated to play an important role in pathogenesis of familial amyotrophic lateral sclerosis (FALS) caused by mutations in Cu/Zn-superoxide dismutase (SOD1), the mechanism underlying the causes of this fatal disease is still poorly understood. Here we found that co-chaperone CHIP (carboxyl terminus of Hsc70-interacting protein), together with molecular chaperones Hsc70/Hsp70 and Hsp90, associates with FALS-linked mutant SOD1 proteins in cultured human cells. S5a subunit of 26S proteasomes, which recognizes polyubiquitylated proteins, also interacts with mutant SOD1 proteins. Over-expression of CHIP leads to the reduction in cellular levels of mutant SOD1 as well as the suppression of cytotoxicity induced by mutant SOD1. Unusually, rather than increasing the level of poly-ubiquitylated SOD1, over-expressed CHIP alters the ubiquitylation pattern of mutant SOD1 proteins. Both down-regulation and ubiquitylation of mutant SOD1 are greatly reduced by a mutant CHIP protein lacking U-box domain. Taken together, these results suggest that co-chaperone CHIP, possibly with another E3 ligase(s), modulates the ubiquitylation of mutant SOD1 and renders them more susceptible for proteasomal degradation.