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The effect of microthreads at the implant neck on the amount of marginal bone resorption is controversial. This multicenter retrospective study compared the implant survival rate and amount of marginal bone resorption between two platform-switching internal connection implant systems with or without microthreads. Patient-related (age and sex), surgery-related (implant installation site, type, diameter, and length), and prosthesis-related (prosthesis type) data were collected from patient charts from the implant placement surgery to the final recall visit. A total of 1780 implants, including 1379 with microthreads and 401 without microthreads, were placed in 804 patients. For implants with and without microthreads, the longest follow-up period after prosthesis delivery was 15 and 6 years, respectively. Twenty implants failed during the 15-year follow-up period (98.8% survival rate) due to failed osseointegration, peri-implantitis, implant fractures, and non-functioning implants. The mean marginal bone loss was < 0.1 mm for both implant systems at the 1-year follow-up and 0.18 mm and 0.09 mm at the 4-year follow-up for implants with and without microthreads, respectively, without statistical significance. Microthreads did not significantly affect the amount of marginal bone loss or the implant survival rate for implants with an internal connection with a platform-switching design.

The conventional method of fabricating implant-retained overdentures involves multiple steps and patient visits. However, the duplication of existing complete dentures could decrease the number of visits and increase patient satisfaction. An existing maxillary implant-retained overdenture was replaced for a 78-year-old man; the existing implant-retained overdenture and his face were scanned at the first visit. The scanned intaglio image was inverted to obtain a virtual maxillary cast and used to fabricate the metal framework of the replacement implant-retained overdenture. Prefabricated artificial teeth were arranged on a 3-dimensional trial denture created from the scan data of the existing implant-retained overdenture. The replacement implant-retained overdenture was fabricated on the metal framework by using the injection molding technique. By using these digital techniques, a stable and esthetic implant-retained overdenture was delivered in 2 visits.

Mitochondrial and oxidative stress play critical roles in the pathogenic mechanisms of carbon monoxide (CO)-induced toxicity. This study was designed to evaluate whether the serum levels of specific stress biomarkers might reflect brain injury and act as prognostic markers for the development of neurocognitive sequelae following CO poisoning. We analyzed the data from 51 adult patients admitted with acute CO poisoning and measured the serum level expression of growth differentiation factor 15 (GDF15) and fibroblast growth factor 21 (FGF21), indicators of mitochondrial stress, and 8-Oxo-2′-deoxyguanosine (8-OHdG) and malondialdehyde (MDA), indicators of oxidative stress. Serum was collected upon arrival at the hospital, at 24 h post treatment, and within 7 days of HBO2 therapy. Global Deterioration Scale scores were measured 1 month post incident and used to place the patients in either favorable or poor outcome groups. Initial serum GDF15 and 8-OHdG concentrations were significantly increased in the poor-outcome group and all four biomarkers decreased at 24 h post HBO2 therapy, and were then maintained or further decreased at the 1-week mark. Notably, the degree of change in these biomarkers between baseline and 24 h post HBO2 were significantly larger in the poor-outcome group, reflecting greater CO-associated stress, confirming that post-CO poisoning serum biomarker levels and their response to HBO2 were proportional to the initial stress. We suggest that these biomarkers accurately reflect neuronal toxicity in response to CO poisoning, which is consistent with their activity in other pathologies.

Lack of adequate retention, support, and stability in the complete denture can be attributed to a poor fit or incorrect shape of the polished surfaces. This article presents a case using the neutral zone technique effectively with the fabrication of computer-aided design and computer-aided manufacturing (CAD-CAM) record bases in an edentulous patient with severely resorbed alveolar ridges and discusses the overall treatment steps and clinical implications of this technique. A stable neutral zone and an accurate jaw relation were recorded using CAD-CAM record bases and stability of complete denture was optimized by arranging denture teeth and reforming polishing surfaces in the neutral zone. A new complete denture was fabricated for a patient with atrophic alveolar ridges by a technique utilizing the neutral zone with CAD-CAM record bases.

Objectives: Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent metabolic disease. Muscle is known to influence NAFLD development. Therefore, this study aimed to determine the relationships among low muscle mass, NAFLD, and hepatic fibrosis using various definitions of low muscle mass and NAFLD diagnostic methods, including magnetic resonance imaging-based proton density fat fraction (MRI-PDFF).Methods: This cross-sectional study included 320 participants (107 males, 213 females) from the Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in the Korean General Population cohort. Muscle mass was assessed using whole-body dual-energy X-ray absorptiometry and adjusted for the height squared, body weight, and body mass index (BMI). NAFLD was diagnosed using ultrasonography (US), MRI-PDFF, and the comprehensive NAFLD score (CNS). Hepatic fibrosis was assessed using magnetic resonance elastography. Multivariable logistic and linear regression analyses were performed to determine the aforementioned associations.Results: According to US, 183 participants (57.2%) had NAFLD. Muscle mass adjusted for body weight was associated with NAFLD diagnosed using US (odds ratio [OR], 3.00; 95% confidence interval [CI], 1.70 to 5.31), MRI-PDFF (OR, 2.00; 95% CI, 1.13 to 3.53), and CNS (OR, 3.39; 95% CI, 1.73 to 6.65) and hepatic fibrosis (males: β=-0.070, p

PURPOSE/OBJECTIVE(S) In patients with a limited oligometastatic tumor burden, emerging evidence suggests that the treatment of all visible metastatic sites with locally ablative therapies (LAT) can improve oncologic outcomes. Appropriate identification of the oligometastatic patient requires comprehensive evaluation medical images. In this context, this study aims to evaluate the clinical utility of computer-aided detection (CAD) in the identification of lung nodules in pulmonary oligo-metastases. MATERIALS/METHODS From the database of 1395 patients who were diagnosed with lung metastasis of colorectal cancer from March 2006 to November 2018, chest CT scans of randomly selected three-hundred five patients were collected. CAD counted suspicious lung nodules from chest CT scans of all 305 patients while the radiologist counted nodules of 50 randomly selected patients among them. For those 50 patients, respective percentage of patients with oligo-nodules (< 5), false-positive and false-negative rate of CAD against the radiologist were calculated. With the results from 305 patients, metastatic burden quantification ability of CAD was indirectly evaluated by comparing survival outcomes of these patients according to the number of detected nodules. The nomogram was generated by multiple factors related to the prognosis of colorectal cancer. RESULTS In per patient analysis for the first cohort with 50 patients, the percentage of patients who were defined to have oligometastatic state was 70% (35/50) by CAD and 64% (32/50) by the radiologist, respectively (P = 0.377). Respective false-positive and false-negative rate of CAD in determining oligometastatic state compared to the radiologist were 11.4% and 6.7%. The sensitivity of CAD was 96.9% (95% confidence interval (CI), 82.0-99.8) and the specificity of CAD was 77.8% (95% CI, 51.9-92.6). In per lesion analysis among these patients, sensitivity of CAD was 81.6% (95% CI, 74.3-87.2) for nodules equal to or bigger than 3 mm. Respective 5-year survival rates and mean overall survival in the expanded cohort with 305 patients according to the number of nodules were as follows: 75.2%, 106.9 months (95% CI, 89.0-124.8) for patients with a single nodule, 52.9%, 96.1 months (95% CI, 71.5-120.8) for patients with two nodules, 45.7%, 86.9 months (95% CI, 62.4-111.4) for patients with three nodules, 29.1%, 51.2 months (95% CI, 32.4-70.0) for patients with four nodules, and 22.7%, 36.5 months (95% CI, 29.9-43.0) for patients with equal to or more than five nodules. Internal validation of the nomogram based on the data of expanded cohort showed good discrimination with the median time-dependent area under curve at 5-year of 0.830 (Interquartile range, 0.813-0.828). CONCLUSION Proper identification of oligo-metastatic state for local ablative therapy with acceptable quantification of metastatic burden was achievable by utilizing CAD.

PURPOSE/OBJECTIVE(S) Radiation-induced cardiac toxicity is an importantissue of breast RT. Although a relationship between mean heart dose and acute coronary event (ACE) risk was reported in previous study, the specific relationships between doses to cardiac structures or their sub-regions and subsequent toxicity have not been well defined. In this study, we studied the effect of radiation on specific heart segments on subsequent cardiac toxicity. MATERIALS/METHODS From the 1294 patients with breast cancer where previously demonstrated a relationship between mean heart dose and ACE, 21 patients who developed HF following breast RT and 39 with ACE were identified after an independent review by cardiologists. The study included 21 and 39 controls for respective toxicity who were matched according to age, comorbidities, and physical activity. For each patient who received radiotherapy, substructures were manually drawn, and then dose-distribution parameters of heart and substructures (Mean, Maximum (Max) dose, Relative volume at least given dose from 5-50 Gy in 5 Gy increments) were collected from CT planning data. To specify most critical regions for developing ACE, analysis using High-dimensional Cox regression model (SNet) was performed to reveal the effect of radiation on specific heart segments on subsequent cardiac toxicity. RESULTS In HF (n = 42) and ACE (n = 78) cohorts, characteristics between case and control were well matched. Mean time to develop heart failure, acute coronary events were 40.0 months and 42.2 months, respectively. In HF cohort, there was no significant difference not only in the mean heart dose (3.7 Gy vs 3.1 Gy, P = 0.652), but also in the mean left ventricle (LV) (5.0 Gy vs 4.1 Gy, P = 0.587), mean right ventricle (RV) (4.8 Gy vs 3.6 Gy, P = 0.473). On the other hand, in ACE cohort, there was significant difference in mean dose of heart (2.9 Gy vs 1.3 Gy, P = 0.015), left atrium (LA) (1.0 Gy vs 0.5 Gy, P = 0.008), LV (3.7 Gy vs 1.5 Gy, P = 0.028), left anterior descending artery (LAD) (6.6 Gy vs 2.4 Gy, P = 0.028) and right atrium (RA) (1.5 Gy vs 0.9 Gy, P = 0.025). In univariate analysis, mean dose of heart, LA, LV, LAD and RA was significant factors for acute coronary event free survival. ((Heart; P = 0.006, Hazard ratio (HR) 1.139, 95% Confidence Interval (CI) 1.035-1.253) (LA; P = 0.002, HR 1.735, 95% CI 1.209-2.490), (LV; P = 0.018, HR 1.079, 95% CI 1.012-1.150), (LAD; P = 0.031, HR 1.032, 95% CI 1.002-1.064), (RA; P = 0.008, HR = 1.307, 95% CI 1.068-1.598)). For predicting ACE risk for breast cancer patients, SNet model suggested nomogram based on mean and max LA dose, LAD V10, 15, 20, mean heart dose, mean RA dose and RV V35 in the order of higher predicted point variation. Based on this risk stratification model, event free survival significantly showed difference (P = 0.013). CONCLUSION There was significant difference between cardiac substructure dose parameters in ACE cohort, but not in HF cohort. Further analysis using convolution neural network will be performed to specify most critical region to be spared.

Metabolic syndrome (MetS) pathogenesis involves oxidative stress associated with mitochondrial dysfunction, which triggers integrated stress responses via various compensatory metabolic modulators like mitokines and hepatokines. However, the regulatory mechanisms underlying the exercise-derived benefits with respect to mitokines and hepatokines (potential MetS biomarkers) are unknown. Thus, we investigated the effects of exercise training on MetS biomarkers and their associations with clinical parameters. In this single-center trial, 30 women with MetS were randomly assigned to 12-week supervised exercise or control groups (1:1) and compared with 12 age-matched healthy volunteers. All participants completed the study except one subject in the control group. Expectedly, serum levels of the mitokines, fibroblast growth factor-21 (FGF21), growth differentiation factor-15 (GDF15), and the hepatokine, angiopoietin-like 6 (ANGPTL6), were higher in MetS patients than in healthy volunteers. Moreover, their levels were markedly attenuated in the exercise group. Further, exercise-mediated changes in serum FGF21 and GDF15 correlated with changes in the homeostasis model of assessment of insulin resistance (HOMA-IR) and appendicular lean mass (ALM), respectively. Additionally, changes in serum triglycerides and ANGPTL6 were correlated with changes in leptin. Aberrant mitokine and hepatokine levels can be rectified by relieving metabolic stress burden. Therefore, exercise training may reduce the need for the compensatory upregulation of MetS metabolic modulators by improving gluco-lipid metabolism.

This study investigated whether T1 values in native T1 mapping of 3T magnetic resonance imaging (MRI) of the liver were affected by the fatty component.This prospective study involved 340 participants from a population-based cohort study between May 8, 2018 and August 8, 2019. Data obtained included: (1) hepatic stiffness according to magnetic resonance elastography (MRE); (2) T1 value according to T1 mapping; (3) fat fraction and iron concentration from multi-echo Dixon; and (4) clinical indices of hepatic steatosis including body mass index, waist circumference, history of diabetes, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, and triglycerides. The correlations between T1 value and fat fraction, and between T1 value and liver stiffness were assessed using Pearson's correlation coefficient. The independent two-sample t-test was used to evaluate the differences in T1 values according to the presence or absence of hepatic steatosis, and the one-way analysis of variance was used to evaluate the difference in T1 value by grading of hepatic steatosis according to MRI-based proton density fat fraction (PDFF). In addition, univariate and multivariate linear regression analyses were performed to determine whether other variables influenced the T1 value.T1 value showed a positive correlation with the fat fraction obtained from PDFF (r = 0.615, P 0.001) and with the liver stiffness obtained from MRE (r = 0.370, P 0.001). Regardless of the evaluation method, the T1 value was significantly increased in subjects with hepatic steatosis (P 0.001). When comparing hepatic steatosis grades based on MRI-PDFF, the mean T1 values were significantly different in all grades, and the T1 value tended to increase as the grade increased (P 0.001, P for trend0.001). On multiple linear regression analysis, the T1 value was influenced by MRI-PDFF, calculated liver iron concentration, liver stiffness, and serum aspartate aminotransferase level.The T1 value obtained by current T1 mapping of 3T MRI was affected by the liver fat component and several other factors such as liver stiffness, iron concentration, and inflammation.

Hyperbaric oxygen therapy (HBOT) has been used to provide oxygen to underperfused organs following ischemia or carbon monoxide intoxication. Various beneficial consequences of HBOT have been reported, including wound healing, anti-inflammatory action, and cell survival, however, the molecular mechanisms underlying these effects have not been elucidated yet. We applied a single HBOT program consisting of administration of 2.8 atmospheres absolute (ATA) for 45 min, followed by 2.0 ATA for 55 min, to 10 male volunteers without any metabolic disease. Within 1 week of HBOT, there was no alteration in serum biochemical variables, except for an increase in triglyceride content. As a mitochondrial stress indicator, the serum concentration of growth differentiation factor 15 was reduced by HBOT. The circulating level of &gamma, &ndash, glutamyltransferase was also decreased by HBOT, suggesting an attenuation of oxidative stress. HBOT increased adiponectin and reduced leptin levels in the serum, leading to an elevated adiponectin/leptin ratio. This is the first study to investigate the effect of HBOT on serum levels of metabolic stress-related biomarkers. We suggest that HBOT attenuates mitochondrial and oxidative stresses, and relieves metabolic burdens, indicating its potential for use in therapeutic applications to metabolic diseases.

Insulin resistance is associated with increased risk for and recurrence of breast cancer. Recently, Wnt1-inducible signaling pathway protein-1 (WISP-1) was reported to impair glucose metabolism and insulin sensitivity. In various cancer tissues, Wnt signaling is upregulated and induces further oncogenic and metastatic activity. However, the effects of exercise on serum levels of WISP-1 and its upstream β-catenin have not been studied in cancer patients. We investigated the effects of exercise training on Wnt signaling and insulin sensitivity in breast cancer survivors (BCS). This single-center trial randomized 46 BCS into either 12-week exercise or control groups (1:1), and included an additional 12 age-matched healthy women. Kinanthropometric parameters, serum Wnt signaling markers, and gluco-lipid profiles were evaluated before and after the intervention. Serum β-catenin and WISP-1 concentrations were significantly higher in BCS than in healthy subjects. There was a positive correlation between β-catenin and WISP-1 levels. Exercise training in BCS significantly reduced body fat and waist circumference and enhanced aerobic and muscular fitness. Exercise decreased β-catenin and WISP-1 levels and improved gluco-lipid profiles. There was a notable correlation between changes in HOMA-IR indexes and serum WISP-1, but not with β-catenin during the exercise intervention. In conclusion, a 12-week community-based exercise intervention resulted in significant reductions in serum β-catenin and WISP-1 levels, accompanied by favorable improvements in body composition, physical fitness, and biochemical parameters in BCS. We also highlight that this is the first report concerning effects of exercise on circulating β-catenin and WISP-1 levels and correlations between WISP-1 and insulin sensitivity, which could be important for determining prognoses for BCS.

With‐no‐lysine 1 (WNK1) kinase is a substrate of the insulin receptor/Akt pathway. Impaired insulin signaling in skeletal muscle disturbs glucose transporter 4 (GLUT4) translocation associated with the onset of type 2 diabetes (T2D). WNK1 is highly expressed in skeletal muscle. However, it is currently unknown how insulin signaling targeting WNK1 regulates GLUT4 trafficking in skeletal muscle, and whether this regulation is perturbed in T2D. Hereby, we show that insulin phosphorylates WNK1 at its activating site via a phosphatidylinositol 3‐kinase‐dependent mechanism. WNK1 promotes the cell surface abundance of GLUT4 via regulating TBC1D4. Of note, we observed insulin resistance and decreased WNK1 phosphorylation in T2D db/db mice as compared to the control mice. These results provide a new perspective on WNK1 function in the pathogenesis of hyperglycemia in T2D.

PURPOSE/OBJECTIVE(S) Although radiation-induced cardiac toxicity is an important issue in breast radiation therapy (RT), the dose relationship between cardiac structures and its toxicity has not been fully elucidated, partially because many centers do not routinely administer intravenous (IV) contrast for breast RT, which preclude substructure delineation and detection of potential correlations. In this study, we attempted to generate the synthetic contrast-enhanced CT (CECTsyn) from the non-contrast CT (NCTreal) using deep convolutional neural network (DCNN) and to investigate whether CECTsyn can take a supportive role in case the studies for the cardiac toxicity induced by radiation is needed for the patient whose CECTreal cannot be obtained. MATERIALS/METHODS For this study, 22 NCTreal-CECTreal cardiac scan-pairs have been prepared of which the volume size was ∼512 × 512 × 400 and the resolution was ∼0.75 × 0.75 × 1 mm3 on average. Of the 22 datasets, 13/2/7 were used for training, validation, and testing, respectively. After matching the structure of paired scans using the deformable image registration (DIR), the area near the heart was cropped and used for training the deep learning model. We adopted the modified 2D fully convolution DenseNet (FC-DenseNet) as our backbone and trained it in the conditional generative adversarial network (cGAN) framework. The similarity between CECTsyn and CECTreal was evaluated first, and all NCTreal,CECTsyn, and CECTreal were applied to pre-trained cardiac auto-segmentation models to obtain the substructures of the heart, which is used for dose assessments in each of them. Finally, dose evaluations were conducted on CECTsyn and CECTreal with the dose distributions which are from clinical treatment plans and the manually modified contours of cardiac substructures. RESULTS Firstly, the peak signal-to-noise ratio (PSNR) and the structural similarity index measure (SSIM) between CECTsyn and CECTreal were 23.96 and 0.772, whereas those of NCTreal and CECTreal were 22.25and 0.748, respectively. Secondly, the results of applying the pre-trained cardiac auto-segmentation model were obtained, and the dice similarity coefficient (DSC) of CECTsyn was 0.762 on average which is superior to 0.267 of NCTreal and comparable to 0.843 of CECTreal. We could distinguish the L/R ventricles, L/R atriums, left anterior descending artery (LAD), and right coronary artery (RCA) clearly on CECTsyn. Finally, the dose differences between CECTsyn and CECTreal were on average 0.4/2.0 Gy in Dmean and Dmax, and 2.1/1.3/0.6/0.4/0.3/0.1/0.0% in V5 Gy, V10 Gy, V20 Gy, V30 Gy, V40 Gy, V50 Gy, and V60 Gy, respectively. CONCLUSION DCNN model proposed here showed the feasibility of CECTsyn generation from NCTreal and potential for cardiac substructure delineation such as ventricles, atriums, LAD, and RCA on NCTreal for breast RT. Furthermore, it is shown that CECTsyn can play a supportive role when the studies for the radiation-induced cardiac toxicity is needed.

Purpose/Objective(s) There is a paucity of data studying the significance of neutrophil-to-lymphocyte ratio (NLR) in peripheral blood of patients with locally advanced rectal cancer (LARC) planning to undergo preoperative RT. We aimed to investigate the prognostic impact of NLR in patients with LARC and whether there are modifiable factors in RT which influencing the level of NLR. Materials/Methods We studied 1366 patients treated with neoadjuvant RT with concurrent or sequential chemotherapy for LARC from 2006 to 2019. Most (97.8%) were treated with long-course RT (50-50.4 Gy in 25-28 fractions) with 3DCRT (n = 851) or helical tomotherapy (n = 504). Short-course RT (25 Gy in 5 fractions, followed by 6-week XELOX) was used in 30 cases (NCT03676517). The absolute neutrophil and lymphocyte counts were obtained from the sample collected at the time of initial diagnosis, before and during the course of preoperative RT and before surgery. The primary endpoint was distant metastasis-free survival (DMFS). Results With the median follow-up time of 61.3 months (4.1-173.7 months), the 5-year DMFS was 80.1%. 5-year DMFS was significantly associated with the level of NLR after RT, but not with the level of NLR before RT. In Cox multivariate model, post-RT NLR greater than 4 was independently correlated with worse DMFS (HR 1.37, 95% CI, 1.08-1.73), along with higher icT stage, ypT stage and ypN stage. The 5-year OS of patients with post-RT NLR > 4.0 was 83.2%, compared to 94.4% in post-RT NLR ≤ 4 patients (P 4.0) was more frequently developed after long-course RT (OR, 2.77, P = 0.032) or helical tomotherapy (OR, 1.29, P .05). Conclusion Elevation of NLR after neoadjuvant RT is associated with increased risk of DM development and poor OS in LARC. Development of high NLR following RT is directly related to RT fractionation and delivery modality, and tumor characteristics. Incorporation of SCRT with 3D-CRT or active bone marrow sparing-IMRT may be a modifiable factor that can indirectly affect DMFS by means of attenuating NLR in LARC patients, which needs further investigations.

Purpose/Objective(s) A large inter-physician variation can be seen when delineating organ-at-risks (OARs) for breast radiotherapy. This study aimed to externally validate the performance of deep learning-based auto-contouring system (ACS) for breast radiotherapy. Materials/Methods Eleven experts from two institutions were asked to delineate 9 OARs of 10 cases of breast radiotherapy. Then, auto-contours were provided to the experts for correction. To compare the performance of auto-, corrected-auto-, and experts’ manual contours, Dice similarity coefficient (DSC) and Hausdorff distance (HD) between each contour and the best manual contour were used, where higher DSC and lower HD means better geometric overlap. Results Total mean time for 9 OARs was 37 ± 20 min for manual and 6 ± 5 min for corrected-auto-contours. Among the DSC of experts’ manual contours and an auto-contour, DSC of an auto-contour ranked the second place and HD ranked the first place. Better performance was shown in corrected-auto-contours than in manual contours (median DSC: 0.90 vs. 0.88; median HD: 4.5 vs. 6.5 mm). The inter-physician variations among experts were reduced in corrected-auto-contours, compared with manual contours (DSC range: 0.86–0.90 vs. 0.89–0.90; HD range: 5.1–9.1 mm vs. 4.3–5.7 mm). Among manual OARs, breast contours had the largest variations, which were most significantly improved with an aid of ACS. Conclusion ACS showed at least similar performance in OARs compared with experts’ manual contouring, which anticipates further applications of ACS to target volumes. ACS can be a valuable tool for improving the quality of breast radiotherapy and reducing inter-physician variability in clinical practice.

Background Exercise has been identified as a beneficial intervention to enhance quality of life in breast cancer survivors. In addition, there has been a noteworthy increase in studies emphasizing the benefits of exercise in cancer. We sought to summarize the empirical literature concerning the effects of exercise on physical fitness and biomarker levels in breast cancer survivors according to the type of exercise. Methods We searched PubMed and PubMed Central for studies on the association of exercise with the levels of various biomarkers and physical fitness in breast cancer survivors. We investigated the effects of different types of exercise (aerobic, resistance, or combined) on breast cancer survivors, with changes in physical fitness and biomarker levels as the primary outcomes. Results In total, 118 research papers published from 2012 to July 2016 were retrieved from PubMed and PubMed Central. Of these, 24 papers met our inclusion criteria. All types of exercise were found to improve physical fitness in breast cancer survivors. However, the results with regard to biomarkers were controversial. Conclusion The findings of this review suggest that combined exercise is associated with better outcomes than aerobic or resistance exercise alone in breast cancer survivors.

Aim Myokines are peptides released by the skeletal muscle, and have gained popularity as potential biomarkers for sarcopenia. Irisin is a recently identified myokine, but its role in pathological sarcopenia remains unclear. We investigated the validity and accuracy of circulating irisin levels as a potential biomarker for sarcopenia. Methods We evaluated the anthropometrics, body composition, sarcopenia-related parameters and serum irisin levels of 715 community-dwelling Koreans. Sarcopenia was determined on the basis of the clinical diagnostic criteria of muscle atrophy and weakness, which were proposed by the Asian Working Group for Sarcopenia. Results Circulating irisin levels were correlated with appendicular lean mass/height2 (rmen = 0.275; rwomen = 0.321) and handgrip strength (rmen = 0.219; rwomen = 0.312) in both sexes (all P < 0.01). Furthermore, the mean circulating irisin levels were lower in the sarcopenia group than in the normal group (all P < 0.05). In the logistic regression models, the association between serum irisin concentration and incident sarcopenia persisted even after adjusting for potential confounders, such as sex, age and fat indices (odds ratio 0.20, 95% CI 0.07–0.60; P for trend

This study introduces a personalized automated exercise guidance system for the efficient reduction of obesity. The proposed system was composed of wearable biometric devices and exercise-machine control systems connected with the integrated database server. It was designed for providing customized exercise prescription (intensity, repetition, frequency, etc.) according to ACSM guidelines for obesity based on real-time biosignals feedback and an individual’s exercise capacity. Nineteen subjects participated in evaluating the proposed system, and we found that the risk factors (body composition, hemodynamics, blood enzymes, and exercise variables) related to obesity were statistically significantly improved. Other exercise prescriptions for chronic diseases and symptoms will be able to adapt to the proposed system so that we believe it would be substantially helpful to improve geriatric diseases and symptoms by using technology-driven exercise.

Irisin is a myokine secreted mainly from skeletal muscle that is known for having beneficial metabolic effects via enhancement of energy expenditure and insulin sensitivity. Studies show that irisin also acts as an autocrine/paracrine to promote myogenesis and muscle growth. However, the protective role of irisin against muscular wasting remains unclear. We confirmed that irisin secretion was upregulated by electrical pulse stimulation an in vitro exercise mimetic model. Next, we tested if irisin exerted an anti-atrophic effect on cultured C2C12 myotubes treated with dexamethasone (DEX), a representative inducer of muscular atrophy. Treatment of cultured myotubes with DEX reduced myotube size and increased proteasome activity, which were attenuated by irisin. Also, irisin effectively prevented dephosphorylation of forkhead box O (FoxO) 3α and upregulation of muscle-specific ubiquitin ligases in DEX-treated myotubes. The protective effect of irisin on DEX-mediated myotube atrophy was partially regulated by insulin-like growth factor-1-dependent signaling. These results suggested that irisin may prevent glucocorticoid-induced muscle atrophy by inhibiting FoxO-mediated ubiquitin-proteasome overactivity. Electronic supplementary material The online version of this article (10.1007/s00424-020-02367-4) contains supplementary material, which is available to authorized users.

Objective Problematic online gaming (POG) and problematic Internet use (PIU) have become a serious public mental health problem, with Internet gaming disorder (IGD) included in “Conditions for further study” section of DSM-5. Although higher immersive tendency is observed in people affected by POG, little is known about the simultaneous effect of immersive tendency and its highly comorbid mental disorder, attention deficit/hyperactivity disorder (ADHD). This study aimed to assess the relationship between immersive tendency, ADHD, and IGD.Methods Cross-sectional interview study was conducted in Seoul, Korea with 51 male undergraduate students; 23 active gamers and 28 controls.Results Current ADHD symptoms showed partial mediation effect on the path of immersive tendency on POG and PIU. The mediation model with inattention explained variance in both POG and PIU better than other current ADHD symptom models (R2=69.2 in POG; 69.3 in PIU). Childhood ADHD symptoms models demonstrated mediation effect on both POG and PIU which explained less variance than current ADHD symptom models (R2=53.7 in POG; 52.1 in PIU). Current ADHD symptoms, especially inattention, appear to mediate the effect of immersive tendency on POG/PIU.Conclusion Immersive tendencies may entail greater susceptibility to IGD, and comorbidity with ADHD may mediate the effect of immersive tendency on IGD.

PURPOSE The design and surface features of dental implants substantially affect the healing and remodeling of adjacent bones. This study aimed to investigate the impact of design and surface on bone regeneration using implants of two different pitches, each with three different surface features. MATERIALS AND METHODS Custom-manufactured titanium implants (length, 10 mm; diameter, 3.5 mm) were divided along the major axis into two sections: one with 0.6-mm pitch and the other with 0.4-mm pitch. They were processed by turned, blasting and etching, and anodic oxidation surface treatments and implanted into rabbit tibia. The upper 4 mm of the inserted implants was exposed, and bone regeneration was induced around the exposed area using a titanium chamber (height: 4 mm) containing particulate autogenous and bovine bone. After a 12-week healing period, the quantity and quality of bone regeneration around the implants were evaluated. Thirty specimens-10 specimens each from the turned, blasting and etching, and anodic oxidation surface groups with 0.6- and 0.4-mm pitch sizes- were evaluated by histomophometric analysis. RESULTS The vertical height and width of regenerated bone around blasting and etching and anodic oxidation surfaces were significantly greater than those around turned implants (P < .05); the vertical heights of regenerated bone around the 0.4-mm-pitch sections of blasting and etching and anodic oxidation surfaces were significantly greater than those around the 0.6-mm-pitch sections (P < .05). Both blasting and etching and anodic oxidation surfaces exhibited significantly greater bone-to-implant contact and bone volume at the implant thread than turned implants (P < .05). However, there was no significant difference between the 0.6- and 0.4-mm-pitch sections. CONCLUSION The findings of this study indicate that blasting and etching and anodic oxidation surfaces with a 0.4-mm-pitch design result in greater vertical ingrowth of regenerated bone than those with a 0.6-mm-pitch design.

Angiopoietin-like 6 (ANGPTL6) is a hepatokine that antagonizes obesity and insulin resistance by increasing energy expenditure. Despite its beneficial effects on metabolism, human studies have shown a paradoxical increase in ANGPTL6 level in the serum of patients with metabolic diseases, which has been interpreted as a compensatory upregulation. However, the regulatory mechanism of ANGPTL6 remains unclear. Since upregulation of ANGPTL6 is induced on metabolic stress, we investigated the hepatic expression of ANGPTL6 by leptin, a representative adipokine of obesity. Mice on a high-fat diet showed increased serum leptin levels and hepatic Angptl6 expression, which were attenuated by exercise training. A single leptin injection also induced hepatic ANGPTL6 expression and increased serum ANGPTL6 levels. In an in vitro model using primary hepatocytes, leptin treatment significantly upregulated ANGPTL6 expression at the mRNA and protein levels, as well as the amount of secreted ANGPTL6 protein in conditioned media. Similarly, exercise training on human participants also showed diminished serum levels of leptin and ANGPTL6. Altogether, these results strongly indicated that hepatic ANGPTL6 expression was determined by leptin.

Aim The present cross-sectional study was carried out among community-dwelling Koreans to determine the validity of various muscle mass indices and to propose more clinically relevant diagnostic criteria. Methods This study measured the anthropometrics, body composition and physical capability of 415 older Koreans. Skeletal muscle indices were calculated by dividing appendicular lean mass by height or weight. Apart from this, we adjusted appendicular lean mass for body mass index, body surface area or waist-to-height ratio, which we then named the qualitative muscle mass index. Skeletal muscle function deficit was defined as a combination of weakness and slowness. Results Qualitative muscle indices were closely associated with physical capabilities. Receiver operating characteristic and logistic analyses showed that qualitative muscle indices had significantly greater discriminatory powers regarding low muscle function than did the height-adjusted index in both men and women, and even showed higher discriminatory potentials than the weight-adjusted index in men (all P

Background Insulin-like growth factor (IGF-1) is associated with chronic diseases such as diabetes, cardiovascular disease, and hypertension, as well as muscle dysfunction. Previous studies of exercise interventions yield controversial results regarding plasma IGF-1, IGFBP3, and IGF-1/IGFBP3 ratio. In this study, we examined whether 100 km walking exercise affects serum levels of IGF-1 and IGFBP3 and IGF-1/IGFBP3 ratio. We also investigated several metabolic-related blood parameters before and after walking. Methods Participants were 14 healthy middle aged men (41.0 ± 6.78 years of age). We assessed body composition and measured metabolic-related blood indicators, such as such as lipid profiles, glucose, renal and hepatic metabolic bio-markers before and after a 100 km walking race. Blood samples from all participants were taken before and immediately after the walkathon. We also analyzed serum levels of IGF-1 and IGFBP3, and calculated the IGF-1/IGFBP3 ratio. Results After participants completed a 100 km walking race, some of their metabolic profiles were markedly changed. Serum levels of IGF-1 and IGFBP3 were significantly decreased, and therefore the IGF-1/IGFBP3 ratio also decreased before and after 100 km of walking. Conclusion Our results indicate that intense walking exercise affects serum levels of IGF-1 and IGFBP3 as well as metabolic bio-markers including high density cholesterol, glucose and triglycerides.

Seasonality is one of the key features in subjects with mood disorders and is involved in the multi-faceted nature of the clinical course. However, few studies have explored the clinical implications of seasonality in bipolar disorders. We examined the differential effects of seasonality on clinical variables between bipolar I and II disorder (BD I and II). Seasonality was assessed using the Seasonal Pattern Assessment Questionnaire (SPAQ) in 204 subjects with BD I and 308 with BD II. Following the comparisons between BD I and II groups, clinical characteristics related to seasonality were explored. Next, to predict the presence of seasonality, a logistic regression model was applied. The global seasonality score on the SPAQ was significantly higher in the BD II group than in the BD I group. In the BD I group, seasonality was associated with suicide attempt history. In the BD II group, on the other hand, seasonality was associated with female gender, depressive predominance, and premenstrual dysphoric disorder (PMDD). In the regression models, the presence of PMDD and female gender was significantly associated with seasonality in the BD II group. Our findings suggest that high seasonality tendency, a vulnerability maker for cyclic worsening, may contribute to a differential pattern of clinical characteristics in BD II.