BACKGROUND/OBJECTIVES: Oxidative stress is caused by reactive oxygen species and free radicals that accelerate inflammatory responses and exacerbate fatigue. Tormentic acid (TA) has antioxidant and anti-inflammatory properties. Thus, the aim of present study is to determine the fatigue-regulatory effects of TA in H2O2 -stimulated myoblast cell line, C2C12 cells and treadmill stress test (TST) and forced swimming test (FST) animal models.MATERIALS/METHODS: In the in vitro study, C2C12 cells were pretreated with TA before stimulation with H2O2 . Then, malondialdehyde (MDA), lactate dehydrogenase (LDH), creatine kinase (CK) activity, tumor necrosis factor (TNF)-α, interleukin (IL)-6, superoxide dismutase (SOD), catalase (CAT), glycogen, and cell viability were analyzed. In the in vivo study, the ICR male mice were administered TA or distilled water orally daily for 28 days. FST and TST were then performed on the last day. In addition, biochemical analysis of the serum, muscle, and liver was performed. RESULTS: TA dose-dependently alleviated the levels of MDA, LDH, CK activity, TNF-α, and IL-6 in H2O2 -stimulated C2C12 cells without affecting the cytotoxicity. TA increased the SOD and CAT activities and the glycogen levels in H2O2 -stimulated C2C12 cells. In TST and FST animal models, TA decreased the FST immobility time significantly while increasing the TST exhaustion time without weight fluctuations. The in vivo studies showed that the levels of SOD, CAT, citrate synthase, glycogen, and free fatty acid were increased by TA administration, whereas TA significantly reduced the levels of glucose, MDA, LDH, lactate, CK, inflammatory cytokines, alanine transaminase, aspartate transaminase, blood urea nitrogen, and cortisol compared to the control group. CONCLUSIONS TA improves fatigue by modulating oxidative stress and energy metabolism in C2C12 cells and animal models. Therefore, we suggest that TA can be a powerful substance in healthy functional foods and therapeutics to improve fatigue.

Background: Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy. Methods: This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years. Conclusion The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.

Background and Objectives: Fine needle aspiration cytology (FNAC) combined with washout thyroglobulin (Tg) measurement is the gold standard for the evaluation of metastatic lymph nodes (LNs) in thyroid cancer. However, few studies have assessed the clinical outcomes of discordant results between FNAC and washout Tg based on surgery status and follow-up imaging in real-world practice. Materials and Methods: A total of 707 LNs in 512 patients who underwent FNAC and washout Tg measurements from 2015 to 2017 were analyzed. The final LN outcomes were confirmed through postoperative histology, or through metastatic FNAC findings combined with high washout Tg level, follow-up imaging studies, or repeat FNA, if LNs were not dissected. Results: The cut-off values of washout Tg for indicating LN metastasis in preoperative and postoperative LNs were 9.6 ng/mL and 2.1 ng/mL. The diagnostic accuracy was improved by applying washout Tg according to surgery status and the results of discordant rate was reduced, Discordant between results of FNAC with washout Tg and final outcome were 9.2% (27/295) of preoperative LNs and 8.7% (36/412) of postoperative LNs. Due to inconclusive results, unnecessary neck dissection can occur in 13.9% (36/259 dissected cases). Conclusion To improve diagnostic accuracy, cut-off values of washout Tg should be applied depending on surgery status. New biomarkers in washout fluid is necessary to resolve discordant findings.

Background: Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy. Methods: This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years. Conclusion The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.

Background and Objectives: Fine needle aspiration cytology (FNAC) combined with washout thyroglobulin (Tg) measurement is the gold standard for the evaluation of metastatic lymph nodes (LNs) in thyroid cancer. However, few studies have assessed the clinical outcomes of discordant results between FNAC and washout Tg based on surgery status and follow-up imaging in real-world practice. Materials and Methods: A total of 707 LNs in 512 patients who underwent FNAC and washout Tg measurements from 2015 to 2017 were analyzed. The final LN outcomes were confirmed through postoperative histology, or through metastatic FNAC findings combined with high washout Tg level, follow-up imaging studies, or repeat FNA, if LNs were not dissected. Results: The cut-off values of washout Tg for indicating LN metastasis in preoperative and postoperative LNs were 9.6 ng/mL and 2.1 ng/mL. The diagnostic accuracy was improved by applying washout Tg according to surgery status and the results of discordant rate was reduced, Discordant between results of FNAC with washout Tg and final outcome were 9.2% (27/295) of preoperative LNs and 8.7% (36/412) of postoperative LNs. Due to inconclusive results, unnecessary neck dissection can occur in 13.9% (36/259 dissected cases). Conclusion To improve diagnostic accuracy, cut-off values of washout Tg should be applied depending on surgery status. New biomarkers in washout fluid is necessary to resolve discordant findings.

BACKGROUND/OBJECTIVES: Evidence-based customized nutritional interventions are required for effective treatment of moderate to severe obese children and adolescents. SUBJECTS/METHODS: Sixty six (64.1% of 103) of the eligible participants who joined the usual care or physical activity group in the clinic were involved in 16-week intervention. Customized nutritional intervention was implemented for each participant based on a nutrition care process (NCP) model. Sociodemographic assessment, anthropometrics data, health- and dietary-related behaviors, and dietary intake of the study subjects were assessed at baseline and follow-up. All participants engaged in 30-minute nutritional sessions on a monthly basis. RESULTS: After 16 weeks, there were significant improvements in body composition [BMI (−0.8 ± 0.9, P < 0.05), BMI z-score (−0.3 ± 0.2, P < 0.001), body fat (kg) (−1.3 ± 2.1, P < 0.05), and body fat (%)(−1.5 ± 1.9, P < 0.05)] as well as macronutrient intake [total energy intake (kcal) (−563.7 ± 656.8, P < 0.05), energy (%) (−26.5 ± 30.0, P < 0.05) and fat (g) (−28.3 ± 40.6, P < 0.05)] in the adherent group than the non-adherent group. The SOC was higher in both groups after the intervention (P < 0.001). CONCLUSIONS Our results highlight the positive effects of an evidence-based approach as a multidisciplinary intervention for people-centered nutritional care and weight management.

Background: Estrogen controls the pubertal growth spurt, growth plate closure, and accretion of bone mineral density (BMD) of long bones after biding estrogen receptor (ER).There are two subtypes of ER, ERα and ERβ. If each ER subtype has different effects, we may control those actions by manipulating the estrogen binding intensity to each ER subtype and increase the final adult height without markedly reducing BMD or impairing reproductive functions. The purpose of our study was to compare these effects of ERα and ERβ on long bones in ovariectomized rats. Methods: Thirty female rats were ovariectomized and randomly divided into 3 groups. The control, propylpyrazole triol (PPT), and 2,3-bis (4-hydroxyphenyl) propionitrile (DPN) groups were subcutaneously injected for 5 weeks with sesame oil, PPT as an ERα agonist, and DPN as an ERβ agonist, respectively. The crown-lump length and body weight were measured weekly.BMD, serum levels of growth hormone (GH) and estradiol were checked before and after 5 weeks of injections. Pituitary GH1 expression levels were determined with quantitative realtime polymerase chain reaction, the proximal tibias were dissected, decalcified and stained with hematoxylin-eosin, and the thicknesses of epiphyseal plates including proliferative and hypertrophic zones were measured in 20-evenly divided sites after 5 weeks of injections. Comparisons for auxological data, serum hormone and pituitary GH1 expression levels, BMD, and epiphyseal plate thicknesses among 3 groups before and after injections were conducted. Results: There was no significant difference in body lengths among 3 groups. The body weights were significantly lower, but, serum GH, pituitary GH1 expression levels, and BMDs were higher in PPT group than the other 2 groups after 5 weeks of injections. There was no significant difference in the thicknesses of the total epiphyseal plate, proliferative, and hypertrophic zone among 3 groups. Conclusion ERα is more involved in pituitary GH secretion and bone mineral deposition than ERβ. Weight gain might be prevented with the ERα agonist.

BACKGROUND: Rapid and accurate diagnosis of acute myocardial infarction (AMI) is critical for initiating effective treatment and achieving better prognosis. We investigated the performance of copeptin for early diagnosis of AMI, in comparison with creatine kinase myocardial band (CK-MB) and troponin I (TnI). METHODS: We prospectively enrolled 271 patients presenting with chest pain (within six hours of onset), suggestive of acute coronary syndrome, at an emergency department (ED). Serum CK-MB, TnI, and copeptin levels were measured. The diagnostic performance of CK-MB, TnI, and copeptin, alone and in combination, for AMI was assessed by ROC curve analysis by comparing the area under the curve (AUC). Sensitivity, specificity, negative predictive value, and positive predictive value of each marker were obtained, and the characteristics of each marker were analyzed. RESULTS: The patients were diagnosed as having ST elevation myocardial infarction (STEMI; N=43), non-ST elevation myocardial infarction (NSTEMI; N=25), unstable angina (N=78), or other diseases (N=125). AUC comparisons showed copeptin had significantly better diagnostic performance than TnI in patients with chest pain within two hours of onset (AMI: P=0.022, ≤1 hour; STEMI: P=0.017, ≤1 hour and P=0.010, ≤2 hours). In addition, TnI and copeptin in combination exhibited significantly better diagnostic performance than CK-MB plus TnI in AMI and STEMI patients. CONCLUSIONS The combination of TnI and copeptin improves AMI diagnostic performance in patients with early-onset chest pain in an ED setting.

Purpose: Targeted next-generation sequencing (NGS) panels for solid tumors have been useful in clinical framework for accurate tumor diagnosis and identifying essential molecular aberrations. However, most cancer panels have been designed to address a wide spectrum of pan-cancer models, lacking integral prognostic markers that are highly specific to gliomas. Materials and Methods: To address such challenges, we have developed a glioma-specific NGS panel, termed “GliomaSCAN,” that is capable of capturing single nucleotide variations and insertion/deletion, copy number variation, and selected promoter mutations and structural variations that cover a subset of intron regions in 232 essential glioma-associated genes. We confirmed clinical concordance rate using pairwise comparison of the identified variants from whole exome sequencing (WES), immunohistochemical analysis, and fluorescence in situ hybridization. Results: Our panel demonstrated high sensitivity in detecting potential genomic variants that were present in the standard materials. To ensure the accuracy of our targeted sequencing panel, we compared our targeted panel to WES. The comparison results demonstrated a high correlation. Furthermore, we evaluated clinical utility of our panel in 46 glioma patients to assess the detection capacity of potential actionable mutations. Thirty-two patients harbored at least one recurrent somatic mutation in clinically actionable gene. Conclusion We have established a glioma-specific cancer panel. GliomaSCAN highly excelled in capturing somatic variations in terms of both sensitivity and specificity and provided potential clinical implication in facilitating genome-based clinical trials. Our results could provide conceptual advance towards improving the response of genomically guided molecularly targeted therapy in glioma patients.

BACKGROUND: This study aimed to investigate the association between physical fitness and cardiometabolic health of Korean children and adolescents. METHODS: In total, 168 participants (89 boys and 79 girls) aged 10–16 years were recruited for the Intervention for Childhood and Adolescent Obesity via Activity and Nutrition Study in 2016. The subjects were categorized into two groups using the definition of metabolic syndrome by the International Diabetes Federation: metabolically unhealthy (with at least two of the five criteria) and healthy groups (with less than one criterion). Correlation analysis of the participants' general characteristics was performed. Odds ratios (ORs) of physical fitness for cardiometabolic risk were evaluated via logistic regression. RESULTS: Metabolically unhealthy children showed greater weight, height, and body mass index, higher Children's Depression Inventory score, and longer screen time than did the metabolically healthy children. Metabolically healthy children showed greater upper and lower extremity muscular strength than did the metabolically unhealthy children (P=0.04 and P<0.001, respectively). In the multiple logistic regression analysis, lower extremity muscle strength was inversely related to the clustered cardiometabolic risk of the children and adolescents with or without adjustment for confounders (OR, 4.32; 95% confidence interval [CI], 1.87–9.97; OR, 7.64; 95% CI, 1.55–37.74, respectively). CONCLUSION: Physical fitness, especially lower extremity muscle strength, is significantly inversely associated with individual and clustered cardiometabolic risks in Korean children and adolescents.
Adolescent ; Body Mass Index ; Child ; Depression ; Humans ; Korea ; Logistic Models ; Lower Extremity ; Muscle Strength ; Odds Ratio ; Pediatric Obesity ; Physical Fitness