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Background Reducing the duration of intraoperative hypoxemia in pediatric patients by means of rapid detection and early intervention is considered crucial by clinicians. We aimed to develop and validate a machine learning model that can predict intraoperative hypoxemia events 1 min ahead in children undergoing general anesthesia. Methods This retrospective study used prospectively collected intraoperative vital signs and parameters from the anesthesia ventilator machine extracted every 2 s in pediatric patients undergoing surgery under general anesthesia between January 2019 and October 2020 in a tertiary academic hospital. Intraoperative hypoxemia was defined as oxygen saturation Results In total, 1,540 (11.73%) patients with intraoperative hypoxemia out of 13,130 patients’ records with 2,367 episodes were included for developing the model dataset. After model development, 200 (13.25%) of the 1,510 patients’ records with 289 episodes were used for holdout validation. Among the models developed, the GBM had the highest AUROC of 0.904 (95% confidence interval [CI] 0.902 to 0.906), which was significantly higher than that of the LSTM (0.843, 95% CI 0.840 to 0.846 P < .001) and the transformer model (0.885, 95% CI, 0.882–0.887, P < .001). In holdout validation, GBM also demonstrated best performance with an AUROC of 0.939 (95% CI 0.936 to 0.941) which was better than LSTM (0.904, 95% CI 0.900 to 0.907, P < .001) and the transformer model (0.929, 95% CI 0.926 to 0.932, P < .001). Conclusions Machine learning models can be used to predict upcoming intraoperative hypoxemia in real-time based on the biosignals acquired by patient monitors, which can be useful for clinicians for prediction and proactive treatment of hypoxemia in an intraoperative setting.

Background There is currently no validated risk prediction model for recurrent events among patients with acute ischemic stroke (AIS) and atrial fibrillation (AF). Considering that the application of conventional risk scores has contextual limitations, new strategies are needed to develop such a model. Here, we set out to develop and validate a comprehensive risk prediction model for stroke recurrence in AIS patients with AF. Methods AIS patients with AF were collected from multicenter registries in South Korea and Japan. A developmental dataset was constructed with 5648 registered cases from both countries for the period 2011‒2014. An external validation dataset was also created, consisting of Korean AIS subjects with AF registered between 2015 and 2018. Event outcomes were collected during 1 year after the index stroke. A multivariable prediction model was developed using the Fine–Gray subdistribution hazard model with non-stroke mortality as a competing risk. The model incorporated 21 clinical variables and was further validated, calibrated, and revised using the external validation dataset. Results The developmental dataset consisted of 4483 Korean and 1165 Japanese patients (mean age, 74.3 ± 10.2 years; male 53%); 338 patients (6%) had recurrent stroke and 903 (16%) died. The clinical profiles of the external validation set (n = 3668) were comparable to those of the developmental dataset. The c-statistics of the final model was 0.68 (95% confidence interval, 0.66 ‒0.71). The developed prediction model did not show better discriminative ability for predicting stroke recurrence than the conventional risk prediction tools (CHADS2, CHA2DS2-VASc, and ATRIA). Conclusions Neither conventional risk stratification tools nor our newly developed comprehensive prediction model using available clinical factors seemed to be suitable for identifying patients at high risk of recurrent ischemic stroke among AIS patients with AF in this modern direct oral anticoagulant era. Detailed individual information, including imaging, may be warranted to build a more robust and precise risk prediction model for stroke survivors with AF.

Purpose Endothelin-1 (ET-1) is a potent vasoconstrictor which seems to be involved in the pathogenesis of diabetic retinopathy (DR). However, studies on intraocular ET-1 in DR have been limited. Thus, we investigated aqueous ET-1 levels in patients with DR. Methods A total 85 subjects were included in this prospective study. Those were classified into three groups: advanced DR group included those with severe nonproliferative DR or proliferative DR, whereas early DR group included those with mild nonproliferative DR or moderative nonproliferative DR. Those who underwent cataract surgery and had no concomitant ocular disease were included in the control group. Aqueous humor levels of ET-1 were obtained before intravitreal bevacizumab injection (IVB) and after 1 month for the DR patients, and at the time of cataract surgery for the control group. Results Advanced DR group included 40 eyes (47.1%), whereas early DR group did 19 eyes (22.4%), and control group (26 eyes, 30.5%). Mean aqueous ET-1 level was 10.1±4.1 pg/mL (6.0–21.0 pg/mL) in advanced DR group, 1.9±0.7 pg/mL (0.6–2.8 pg/mL) in early DR group, and 2.1±1.0 pg/mL (0.7–3.9 pg/mL) in control group (P < 0.001). Advanced DR group was further subdivided into severe nonproliferative DR (15 eyes, 12.8%) and proliferative DR (25 eyes, 34.3%). Mean aqueous ET-1 level was 10.1±4.3 pg/mL (6.0–20.1 pg/mL) in patients with severe nonproliferative DR, and 10.0±4.0 pg/mL (6.0–21.0 pg/mL) in those with proliferative DR (P = 0.928) at baseline. Mean ET-1 level at 1 month after intravitreal injection was 2.5±1.0 pg/mL (0.3–4.8 pg/mL) in patients with severe proliferative DR and 2.9±1.7 pg/mL (1.0–7.0 pg/mL) in those with proliferative DR (P = 0.443). Mean aqueous ET-1 level was significantly reduced in both groups (P < 0.001, respectively). Conclusion The mean aqueous ET-1 level was significantly higher in the eyes with advanced DR than those with early DR and the control group. The mean aqueous ET-1 level was significantly reduced after intravitreal injections in the advanced DR group. Based on our results, future studies on the exact role of ET-1 in the pathogenesis of DR and future implication for intervention would be helpful for managing DR.

To develop deep learning models for predicting Interoperative hypotension (IOH) using waveforms from arterial blood pressure (ABP), electrocardiogram (ECG), and electroencephalogram (EEG), and to determine whether combination ABP with EEG or CG improves model performance. Data were retrieved from VitalDB, a public data repository of vital signs taken during surgeries in 10 operating rooms at Seoul National University Hospital from January 6, 2005, to March 1, 2014. Retrospective data from 14,140 adult patients undergoing non-cardiac surgery with general anaesthesia were used. The predictive performances of models trained with different combinations of waveforms were evaluated and compared at time points at 3, 5, 10, 15 minutes before the event. The performance was calculated by area under the receiver operating characteristic (AUROC), area under the precision-recall curve (AUPRC), sensitivity and specificity. The model performance was better in the model using both ABP and EEG waveforms than in all other models at all time points (3, 5, 10, and 15 minutes before an event) Using high-fidelity ABP and EEG waveforms, the model predicted IOH with a AUROC and AUPRC of 0.935 [0.932 to 0.938] and 0.882 [0.876 to 0.887] at 5 minutes before an IOH event. The output of both ABP and EEG was more calibrated than that using other combinations or ABP alone. The results demonstrate that a predictive deep neural network can be trained using ABP, ECG, and EEG waveforms, and the combination of ABP and EEG improves model performance and calibration.

Purpose We sought to evaluate changes of mean peripapillary choroidal thickness (PCT) and subfoveal choroidal thickness (SFCT) over 12 months in patients with unilateral central retinal vein occlusion (CRVO). Methods Our retrospective, observational study included 19 patients with treatment-naïve, unilateral CRVO who completed at least 12 months of follow-up period. Mean PCT and mean SFCT in CRVO-affected eyes and unaffected contralateral eyes were measured at each follow-up visit, and then compared. Differences between baseline and 12 months (ΔSFCT and ΔPCT) and percentage changes (ΔSFCT or ΔPCT/baseline×100%) were determined. We also investigated the predictive factors for visual outcome in the CRVO-affected eyes. Results In the CRVO-affected eyes, mean PCT was 146.7±41.9 μm at baseline, and 106.5±24.2 μm at 12 months (P < 0.001). Mean PCT of the contralateral eyes was 129.8±42.6 μm at baseline and 124.6±39.7 μm at 12 months (P = 0.089). Mean SFCT of CRVO-affected eyes was 225.8±77.9 μm at baseline, and 199.4±66.6 μm at 12 months (P = 0.009). Mean SFCT of the contralateral eyes was 218.4±83.0 μm at baseline, and 208.4±78.1 μm at 12 months (P = 0.089). Δ PCT was -41.6±25.3 μm in the CRVO-affected eyes, and -5.2±5.8 μm in the contralateral eyes (P Conclusion Both peripapillary and subfoveal choroidal thickness reduced significantly over 12 months in the CRVO-affected eyes, but not in the contralateral eyes. In addition, the absolute reduction amount and reduction ratio of PCT and SFCT were significantly greater in the CRVO-affected eyes than the contralateral eyes.

Purpose To investigate aqueous humor concentrations of endothelin-1 (ET-1) in patients with central retinal vein occlusion (CRVO) compared with patients with branch retinal vein occlusion (BRVO) and a normal control group. Methods A total 80 subjects were included in this prospective study, including 15 patients with CRVO, 20 patients with BRVO, and 45 patients who underwent cataract surgery and had no concomitant ocular disease. Aqueous humor levels of ET-1 were obtained before intravitreal bevacizumab injection (IVB) and after 1 month. Results At baseline, the mean aqueous ET-1 level was 12.7±3.6 pg/mL in the CRVO group, 8.0±2.3 pg/mL in the BRVO group, and 2.0±0.9 pg/mL in the control group (P Conclusion The mean aqueous humor ET-1 level was significant higher in the patients with CRVO than those with BRVO and in the control group. After IVB, the mean level was significantly reduced in both the patients with CRVO and those with BRVO.

Background Statins have been recommended for use in atherosclerotic cardio-cerebrovascular disease (CCVD). The purpose of this study was to investigate the efficacy of five different types of statin in the secondary prevention of CCVD in patients. Methods This study has a retrospective design and utilised data from the Korean National Health Insurance Service-National Health Screening Cohort. Participants aged 40 to 69 years at baseline were categorized into five statin groups (atorvastatin, rosuvastatin, pitavastatin, simvastatin, and pravastatin). The primary composite outcome was defined as recurrence of CCVD or all causes of death. Cox proportional hazard regression models were adopted after stepwise adjustments for confounders to investigate the difference in efficacy among the different statins. Results Of the 755 final study participants (485: atorvastatin, 34: pitavastatin, 8: pravastatin, 96: rosuvastatin, and 132: simvastatin group), 48 patients experienced primary composite outcomes. The median follow-up duration was 12.4 years across all groups. After stepwise adjustments, the hazard ratios (95% confidence intervals) for primary composite outcomes of atorvastatin, pitavastatin, and rosuvastatin groups were 0.956 (0.456–2.005), 1.347 (0.354–5.116), and 0.943 (0.317–2.803), respectively, when compared with the simvastatin group. Conclusions There were no significant differences between the statins in their efficacy for preventing recurrence of CCVD events and/or death in CCVD patients. However, further large-scale clinical trials are required to confirm these results.

PurposeTo investigate the association between daily sunlight exposure duration and diabetic retinopathy in Korean adults with diabetes.MethodsThis study used data from the 2008-2011 Korea National Health and Nutrition Examination Survey. Overall, 1,089 patients with diabetes aged >40 years were included. The duration of daily sunlight exposure was assessed via health interviews. Comprehensive ophthalmic evaluations, including standard retinal fundus photography after pupil dilation, were conducted. Diabetic retinopathy was graded using the modified Airlie House Classification. Multivariate logistic regression analysis was performed to analyze the association between daily sunlight exposure duration and the diagnosis of diabetic retinopathy and non-proliferative diabetic retinopathy.ResultsThe risk of diabetic retinopathy was 2.66 times higher in the group with ≥5 h of daily sunlight exposure than in the group with less exposure after adjusting for risk factors such as duration of diabetes, serum hemoglobin A1c level, hypertension, and dyslipidemia (P = 0.023). Furthermore, the risk of non-proliferative diabetic retinopathy was 3.13 times higher in the group with ≥5 h of daily sunlight exposure than in the group with less exposure (P = 0.009). In patients with diabetes for ConclusionsThis study revealed that sunlight exposure for ≥5 h a day was significantly associated with an increased risk of diabetic retinopathy and non-proliferative diabetic retinopathy in Korean patients with diabetes. The risks were significantly higher in patients with diabetes for

Anesthesia with desflurane and remifentanil can be maintained with either fixed or titrated desflurane concentration. We hypothesized that the fixed-gas concentration (FG) method would reduce the number of anesthetic titrations without hypnotic and hemodynamic instability compared to the bispectral index (BIS)-guided (BG) method. Forty-eight patients were randomly allocated to the FG or BG groups. In the FG group, desflurane vaporizer setting was fixed at 1 age-corrected minimum alveolar concentration (MAC). In the BG group, desflurane was titrated to target a BIS level at 50. Remifentanil was titrated to maintain a systolic arterial pressure (SAP) of 120 mmHg in both groups. Our primary endpoint was the hypnotic stability measured by the wobble of BIS in performance analysis, and the secondary endpoints included the wobble of SAP, mean BIS value during surgery, and the number of anesthetic titrations. The BIS in the FG group showed significantly less wobble (3.9 ± 1.1% vs 5.5 ± 1.5%, P vs 46 ± 7, P vs 5.2 (4.2–8.3)%, P = 0.557]. The numbers of anesthetic titrations in the FG group were significantly lower than the BG group (0 ± 0 vs 8 ± 5, Pvs 22 ± 17, P = 0.047 for remifentanil). Less wobble in BIS and reduced anesthetic titration without hemodynamic instability during the FG technique may be practical in balanced anesthesia using desflurane and remifentanil anesthesia. Clinical trial: This study was registered at ClinicalTrials.gov (NCT02283866).

In order to improve treatment selection for high grade neuroendocrine carcinomas of the cervix (NECC), we performed a comparative genomic analysis between this rare tumor type and other cervical cancer types, as well as extra-cervical neuroendocrine small cell carcinomas of the lung and bladder. We performed whole exome sequencing on fresh-frozen tissue from 15 NECCs and matched normal tissue. We then identified mutations and copy number variants using standard analysis pipelines. Published mutation tables from cervical cancers and extra-cervical small cell carcinomas were used for comparative analysis. Descriptive statistical methods were used and a two-sided threshold of P < .05 was used for significance. In the NECC cohort, we detected a median of 1.7 somatic mutations per megabase (range 1.0–20.9). PIK3CA p.E545K mutations were the most frequency observed oncogenic mutation (4/15 tumors, 27%). Activating MAPK pathway mutations in KRAS (p.G12D) and GNAS (p.R201C) co-occurred in two tumors (13%). In total we identified PI3-kinase or MAPK pathway activating mutations in 67% of NECC. When compared to NECC, lung and bladder small cell carcinomas exhibited a statistically significant higher rate of coding mutations (P < .001 for lung; P = .001 for bladder). Mutation of TP53 was uncommon in NECC (13%) and was more frequent in both lung (103 of 110 tumors [94%], P < .001) and bladder (18 of 19 tumors [95%], P < .001) small cell carcinoma. These comparative genomics data suggest that NECC may be genetically more similar to common cervical cancer subtypes than to extra-cervical small cell neuroendocrine carcinomas of the lung and bladder. These results may have implications for the selection of cytotoxic and targeted therapy regimens for this rare disease.

Purpose To investigate long-term treatment response after intravitreal bevacizumab injections (IVBIs) for central serous chorioretinopathy (CSC). Methods This retrospective, interventional study investigated the medical records of 45 eyes of 44 patients with CSC who underwent IBVIs and completed at least 2-year follow-up period. Complete resolution (CR) was defined as complete resolution of subretinal fluid at least 3 months after the last IVBI. Thick-choroid CSC was defined as mean subfoveal choroidal thickness more than 300.0 μm. The main outcome measure was long-term treatment outcome after IVBIs in patients with CSC. Results Thirty-five patients (79.5%) were male, and their mean age was 45.5 ± 9.6 years. The mean follow-up period was 35.1 ± 11.5 months. Twenty-two eyes (48.9%) had acute CSC, and 40 eyes (88.9%) achieved CR. Twenty eyes (50.0%) developed recurrence, the mean number of IVBIs to achieve the first CR was not significantly different between eyes with and without recurrences (2.6 ± 1.6 vs. 2.9 ± 1.9; P = 0.658). Thick-choroid CSC was significantly difference between the eyes with and without recurrence (17 eyes, 85.0% vs. eyes, 50.0%; P = 0.020). Among the baseline characteristics, serous pigment epithelial detachment (B = - 2.580, P = 0.032) and thick-choroid (B = 1.980, P = 0.019) were significantly associated with recurrence. Conclusion Eyes with CSC treated with IVBI and achieving complete resolution of subretinal fluid have 50% chance of recurrence in the long term. Thinner choroid and serous pigment epithelial detachment appear protective for recurrences.

Purpose To investigate the prevalence of focal lamina cribrosa (LC) defects in patients with unilateral branch retinal vein occlusion (BRVO) and to compare ocular characteristics between eyes with and without focal LC defect and those eyes with normal-tension glaucoma (NTG). Methods This retrospective, cross-sectional study included 121 patients. Thirty-nine patients had unilateral BRVO (BRVO group), 36 patients had NTG (NTG group), and 36 patients had vitreous floaters, but no other ocular diseases (control group). In addition to baseline characteristics such as age, sex, refractive errors, the ocular characteristics such as peripapillary choroidal thickness (PCT), retinal nerve fiber layer thickness, and subfoveal choroidal thickness were retrospectively analyzed. Results Focal LC defects were detected in 20 eyes of 14 patients (38.9%) in the BRVO group, 24 eyes of 15 patients (41.7%) in the NTG group, and none in the control group (P

Objective To investigate the association between relative grip strength and the prevalence of type 2 diabetes mellitus (T2DM) independently and in combination with body mass index (BMI) in Korean adults. Methods The cross-sectional study includes 2,811 men and women (age 40 to 92 years old) with no history of heart disease, stroke, or cancer. Relative grip strength was measured by a handheld dynamometer and calculated by dividing absolute grip strength by body weight. Logistic regression analysis was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of T2DM by sex-specific quintiles of relative grip strength. In a joint analysis, participants were classified into 4 groups: “weak (lowest 20% quintile one) and normal weight (BMI 2)”, “weak and overweight/obese (BMI ≥25.0 kg/m2)”, “strong (upper 80% four quintiles) and normal weight” or “strong and overweight/obese”. Results Among the 2,811 participants, 371 were identified as having T2DM. Compared with the lowest quintile of relative grip strength (weakest), the ORs (95% CIs) of T2DM were 0.73 (0.53–1.02), 0.68 (0.48–0.97), 0.72 (0.50–1.03), and 0.48 (0.32–0.74) in upper quintiles two, three, four, and five, respectively, after adjusting for BMI and other potential confounders. In the joint analysis, compared with the “weak and overweight/obese” reference group, the odds of T2DM [ORs (95% CIs)] was lower in the “strong and overweight/obese” group [0.65 (0.46–0.92)] and the “strong and normal weight” group [0.49 (0.35–0.67)], after adjusting for potential confounders. Conclusion In this cross-sectional study, greater relative grip strength was associated with a lower prevalence of T2DM independent of BMI in Korean adults. Additional prospective studies are needed to determine whether a causal association exists between relative grip strength and T2DM prevalence considering BMI.

Purpose To evaluated the changes in choroidal vasculature in patients with ocular ischemic syndrome (OIS) and in the ipsilateral eyes of patients with symptomatic carotid artery stenosis (CAS) Method A total of 50 patients (15 patients with OIS, 10 patients with symptomatic CAS, 25 patients of age-and sex-matched control group) were included, and the medical records were retrospectively reviewed. The mean subfoveal choroidal thickness (SFCT) of each eye was measured, and binary images of the choroid were evaluated to compare the mean choroidal area and the luminal area. Results The mean SFCT was 170.5±75.3 μm in the eyes with OIS, 154.8±62.9 μm in the ipsilateral eyes with symptomatic CAS, and 277.5±73.2 μm in the right eyes of the control group patients (P

Among a variety of comorbidities of ankylosing spondylitis (AS), the association between dementia and AS by using an extensive dataset from the Korean National Health Insurance System was evaluated in this study. We extracted 15,547 newly diagnosed AS subjects among the entire Korean population and excluded wash-out patients (n = 162) and patients that were inappropriate for cohort match (n = 1192). Finally, 14,193 subjects were chosen as the AS group, and through 1:5 age- and sex-stratified matching, 70,965 subjects were chosen as the control group. We evaluated patient demographics, household incomes, and comorbidities, including hypertension, diabetes, and dyslipidemia. The prevalence of overall dementia (1.37%) and Alzheimer's dementia (AD) (0.99%) in the AS group was significantly higher than in the control group (0.87% and 0.63%), respectively. The adjusted hazard ratio of the AS group for overall dementia (1.758) and AD (1.782) showed statistical significance also. On the other hand, the prevalence of vascular dementia did not differ significantly between the two groups. Subgroup analyses revealed the following risk factors for dementia in the AS group: male gender, greater than 65 years in age, fair income (household income greater than 20% of the median), urban residency, no diabetes, and no hypertension. From the nationwide, population-based, retrospective, longitudinal cohort study, AS patients showed a significantly higher prevalence of overall dementia and Alzheimer's dementia. Comprehensive patient assessment using our subgroup analysis could help to prevent dementia in patients suffering from AS.

Although exercise has well-documented health benefits on cardiovascular disease (CVD), the benefit of combination exercise on CVD risk factors in individuals with elevated risk has not been fully elucidated. We compared the effects of aerobic, resistance, and a combination of both aerobic and resistance training on CVD risk factors including peripheral and central BP, cardiorespiratory fitness (CRF), muscular strength, body composition, blood glucose and lipids. Sixty-nine adults (58±7 years) with an elevated blood pressure or hypertension, overweight/obesity, and sedentary lifestyle were randomized to one of the three 8-week exercise programs or a non-exercise control group. Participants in all three exercise groups had an equal total exercise time, 3 days/week (aerobic: 60 minutes/session vs. resistance: 60 minutes/session vs. combination: aerobic 30 minutes/session plus resistance 30 minutes/session). Combined training provided significant reductions in peripheral (-4 mmHg) and central diastolic BP (-4 mmHg), increase in CRF (4.9 ml/kg/min), increase in upper (4 kg) and lower (11 kg) body strength, and increase in lean body mass (0.8 kg) (p 0.05). Furthermore, a composite score of CVD risk factors indicated a greater reduction with combination training compared to the control group. In conclusion, among individuals at an increased risk for CVD, as little as 8-weeks of combined training may provide more comprehensive CVD benefits compared to time-matched aerobic or resistance training alone.

PurposeTo investigate long-term treatment response after intravitreal bevacizumab injections (IVBIs) for central serous chorioretinopathy (CSC).MethodsThis retrospective, interventional study investigated the medical records of 45 eyes of 44 patients with CSC who underwent IBVIs and completed at least 2-year follow-up period. Complete resolution (CR) was defined as complete resolution of subretinal fluid at least 3 months after the last IVBI. Thick-choroid CSC was defined as mean subfoveal choroidal thickness more than 300.0 μm. The main outcome measure was long-term treatment outcome after IVBIs in patients with CSC.ResultsThirty-five patients (79.5%) were male, and their mean age was 45.5 ± 9.6 years. The mean follow-up period was 35.1 ± 11.5 months. Twenty-two eyes (48.9%) had acute CSC, and 40 eyes (88.9%) achieved CR. Twenty eyes (50.0%) developed recurrence, the mean number of IVBIs to achieve the first CR was not significantly different between eyes with and without recurrences (2.6 ± 1.6 vs. 2.9 ± 1.9; P = 0.658). Thick-choroid CSC was significantly difference between the eyes with and without recurrence (17 eyes, 85.0% vs. eyes, 50.0%; P = 0.020). Among the baseline characteristics, serous pigment epithelial detachment (B = - 2.580, P = 0.032) and thick-choroid (B = 1.980, P = 0.019) were significantly associated with recurrence.ConclusionEyes with CSC treated with IVBI and achieving complete resolution of subretinal fluid have 50% chance of recurrence in the long term. Thinner choroid and serous pigment epithelial detachment appear protective for recurrences.

The Gotjawal areas of Jeju Island, Korea, are comprised of unmanaged forests growing on volcanic soils. They support unique assemblages of vascular plants from both northern and southern hemispheres, but are threatened by human disturbance. The health and ecosystem function of these assemblages likely depends in part on the diversity and community structure of soil microbial communities, about which little is known. To assess the diversity of Gotjawal soil microbial communities, twenty samples were collected in November 2010 from 4 representatives of Gotjawal forests. While soil properties and microbial communities measured by 16S rRNA gene sequence data were marginally distinct among sites by PERMANOVA (p = 0.017-0.191), GeoChip data showed significant differences among sites (p

BackgroundThis study investigated the association of central macular thickness (CMT) and macular volume (MV) with severity of Behçet uveitis in the absence of macular edema (ME).MethodsThis retrospective, interventional study included a total 131 treatment-naïve Behçet patients with varying degree of uveitis in the absence of ME. The mean CMT and MV were obtained by spectral domain optical coherence tomography (SD ODT). The patients were classified according to the anatomical classification of Behçet uveitis. The main outcome measure was comparison of mean CMT and MV with the types of Behçet uveitis.ResultsSixty patients (45.8%) with no uveitis, 41 patients (31.3%) with anterior uveitis, 18 patients (13.7%) with posterior uveitis, and 12 patients (9.2%) with panuveitis. The mean CMT were 261.6±22.2 μm in no uveitis, 268.1±17.8 μm in anterior uveitis, 306.4±32.9 μm in posterior uveitis, and 300.4±44.0 μm in panuveitis (P < 0.001). The mean MV was 8.7±0.3 mm3 in those without uveitis, 8.8±0.3 mm3 in anterior uveitis, 9.9±1.1 mm3 in those with posterior uveitis, and 9.7±0.4 mm3 in panuveitis (P < 0.001). Types of Behçet uveitis was the only significant factor correlated with the mean CMT (B = 18.170, β = 0.408, P < 0.001) and the mean MV (B = 0.328, β = 0.652, P < 0.001).ConclusionsThe mean CMT and MV were significantly thicker in the Behçet uveitis with posterior involvement. SD OCT can be used for an adjunctive tool for screening Behçet uveitis, especially for the presence of posterior involvement.

Introduction This study evaluates whether a health club membership is associated with meeting the US physical activity (PA) guidelines and/or favorable cardiovascular health. Methods Using cross-sectional data of health club members (n = 204) and non-members (n = 201) from April to August 2013, this is the first study to our knowledge to examine a health club membership in relation to objectively measured cardiovascular health indicators including resting blood pressure, resting heart rate, body mass index, waist circumference, and cardiorespiratory fitness based on a non-exercise test algorithm. To determine the total PA and sedentary time, this study used a comprehensive PA questionnaire about both aerobic and resistance activities at the health club, as well as lifestyle activities in other settings, which was developed based on the International Physical Activity Questionnaire (IPAQ). Results The odds ratios (95% confidence interval) of meeting either the aerobic, resistance, or both aerobic and resistance PA guidelines for members compared to non-members were 16.5 (9.8–27.6), 10.1 (6.2–16.3), and 13.8 (8.5–22.4), respectively. Significant associations of health club membership with more favorable cardiovascular health outcomes and sedentary behavior were observed for resting heart rate (B: -4.8 b/min, p1 year had more favorable health outcomes, with a smaller waist circumference (men, B: -4.0 cm, p = 0.04; women, B: -3.4 cm, p = 0.06), compared to non-members. Conclusions Health club membership is associated with significantly increased aerobic and resistance physical activity levels and more favorable cardiovascular health outcomes compared to non-members. However, longitudinal, randomized controlled trials would be clearly warranted as cross-sectional data prohibits causal inferences.

Clostridium difficile is one of the main etiological agents causing antibiotic-associated diarrhea. This study investigated the genetic diversity of 70 toxigenic C. difficile isolates from two Korean hospitals by employing toxinotyping, ribotyping, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). Toxin gene amplification resulted in 68 A(+)B(+) and two A(-)B(+) isolates. Most isolates (95.7-100%) were susceptible to daptomycin, metronidazole, and vancomycin. Seventy C. difficile isolates were classified into five toxinotypes, 19 ribotypes, 16 sequence types (STs), and 33 arbitrary pulsotypes. All C. difficile isolates of ribotype 018 (n = 38) were classified into ST17, which was the most prevalent ST in both hospitals. However, C. difficile isolates of ST17 (ribotype 018) exhibited pulsotypes that differed by hospital. ST2 (ribotype 014/020), 8 (ribotypes 002), 17 (ribotype 018), and 35 (ribotypes 015) were detected in both hospitals, whereas other STs were unique to each hospital. Statistical comparison of the different typing methods revealed that ribotyping and PFGE were highly predictive of STs. In conclusion, our epidemiological study indicates that C. difficile infections in both hospitals are associated with the persistence of endemic clones coupled with the emergence of many unique clones. A combination of MLST with PFGE or ribotyping could be useful for monitoring epidemic C. difficile strains and the emergence of new clones in hospitals.

Placing the tunnels in the anatomic positions is important for successful restoration of knee function after anterior cruciate ligament reconstruction (ACLR). It has been shown that it is difficult to place the tunnels in the anatomic position using the transtibial technique. The purpose of this study was to evaluate the effect of each step of our modified transtibial technique (mTT) on the positioning of the femoral tunnel so as to assess whether the mTT could achieve anatomic placements of the tunnels without tibial tunnel expansion. Ten fresh-frozen cadaveric knees were used. First, the tibial tunnel was created in the center of ACL footprint. Then, a pin was inserted through the tibial tunnel using a femoral guide by four stepwise techniques: transtibial technique, additional anterior drawer force applied to the proximal tibia, another additional varus force applied to the tibia and finally, additional external rotation of the tibia and the femoral guide (mTT). Then, tibial tunnel was re-reamed using mTT with 10mm-diameter reamer. The pin positions in each technique on the femur were evaluated by the quadrant method and shapes of the tibial tunnel apertures were evaluated. Femoral pin positions in the four techniques were 23.6±4.5%, 28.4±3.4%, 30.1±3.8%, 33.2±4.5% in the superior-inferior position, and 23.9±4.3%, 26.2±3.7%, 32.0±4.3%, 36.9±4.8% in the anterior-posterior position, respectively. Pin position shifted to more inferior and posterior position with each step of mTT (all p values comparing superior-inferior and anterior-posterior positions of each step with positions of previous step were 0.008 or less). Using mTT, tibial tunnel aperture was 10.5±0.3mm wide and 12.9±1.1mm long. In conclusion, anatomic placements of femoral tunnels in ACLR without excessive tibial tunnel expansion could be achieved using the mTT.

The discrepancy between spatial orientations of an endoscopic image and a physician's working environment can make it difficult to interpret endoscopic images. In this study, we developed and evaluated a device that corrects the endoscopic image orientation using an accelerometer and gyrosensor. The acceleration of gravity and angular velocity were retrieved from the accelerometer and gyrosensor attached to the handle of the endoscope. The rotational angle of the endoscope handle was calculated using a Kalman filter with transmission delay compensation. Technical evaluation of the orientation correction system was performed using a camera by comparing the optical rotational angle from the captured image with the rotational angle calculated from the sensor outputs. For the clinical utility test, fifteen anesthesiology residents performed a video endoscopic examination of an airway model with and without using the orientation correction system. The participants reported numbers written on papers placed at the left main, right main, and right upper bronchi of the airway model. The correctness and the total time it took participants to report the numbers were recorded. During the technical evaluation, errors in the calculated rotational angle were less than 5 degrees. In the clinical utility test, there was a significant time reduction when using the orientation correction system compared with not using the system (median, 52 vs. 76 seconds; P = .012). In this study, we developed a real-time endoscopic image orientation correction system, which significantly improved physician performance during a video endoscopic exam.

Understanding the biology behind the epidemicity and persistence of Acinetobacter baumannii in the hospital environment is critical to control outbreaks of infection. This study investigated the contributing factors to the epidemicity of carbapenem-resistant A. baumannii (CRAB) sequence type (ST) 191 by comparing the differences in biofilm formation, expression of biofilm-associated genes, and resistance to desiccation between major epidemic (n = 16), minor epidemic (n = 12), and sporadic (n = 12) clones. Biofilm mass was significantly greater in the major epidemic than the minor epidemic and sporadic clones. Major and minor epidemic clones expressed biofilm-associated genes, abaI, bap, pgaABCD, and csuA/BABCDE, higher than the sporadic clones in sessile conditions. The csuC, csuD, and csuE genes were more highly expressed in the major epidemic than minor epidemic clones. Interestingly, minor epidemic clones expressed more biofilm-associated genes than the major epidemic clone under planktonic conditions. Major epidemic clones were more resistant to desiccation than minor epidemic and sporadic clones on day 21. In conclusion, the epidemic CRAB ST191 clones exhibit a higher capacity to form biofilms, express the biofilm-associated genes under sessile conditions, and resist desiccation than sporadic clones. These phenotypic and genotypic characteristics of CRAB ST191 may account for the epidemicity of specific CRAB ST191 clones in the hospital.

BACKGROUND:The purpose of this study was to examine the impact of combined cardiorespiratory fitness and waist-to-height ratio in the form of a fit-fat index on incident diabetes risk. Additionally, the independent predictive performance of cardiorespiratory fitness, waist-to-height ratio, and body mass index also were estimated and compared. METHODS:This was a prospective cohort study of 10,381 men who had a normal electrocardiogram and no history of major chronic disease at baseline from 1979 to 2005. Random survival forest models and traditional Cox proportional hazards models were used to predict diabetes at 5-, 10-, and 15-year incidence horizons. RESULTS:Overall, 4.8% of the participants developed diabetes. Receiver operating characteristic curve analyses for incidence risk demonstrated good discrimination using random survival forest models across fitness and fatness measures; Cox models were poor to fair. The differences between fitness and fatness measures across horizons were clinically negligible. Smoothed random survival forest estimates demonstrated the impact of each fitness and fatness measure on incident diabetes was intuitive and graded. CONCLUSIONS:Although fitness and fatness measures showed a similar discriminative ability in predicting incident diabetes, unique to the study was the ability of the fit-fat index to demonstrate a better indication of incident risk when compared to fitness or fatness alone. A single index combining cardiorespiratory fitness and waist-to-height ratio may be more useful because it can indicate improvements in either or both of the measures.

Objective This study investigated the associations between physical activity and the prevalence of obesity determined by waist-to-height ratio (WHtR) and body mass index (BMI). Methods This is the first study to our knowledge on physical activity and obesity using a nationally representative sample of South Korean population from The Korea National Health and Nutrition Examination Survey. We categorized individuals into either non-obese or obese defined by WHtR and BMI. Levels of moderate-to-vigorous physical activity were classified as ‘Inactive’, ‘Active’, and ‘Very active’ groups based on the World Health Organization physical activity guidelines. Multivariable logistic regression was used to examine the associations between physical activity and the prevalence of obesity. Results Physical activity was significantly associated with a lower prevalence of obesity using both WHtR and BMI. Compared to inactive men, odds ratios (ORs) (95% confidence intervals [CIs]) for obesity by WHtR ≥0.50 were 0.69 (0.53–0.89) in active men and 0.76 (0.63–0.91) in very active men (p for trend = 0.007). The ORs (95% CIs) for obesity by BMI ≥25 kg/m2 were 0.78 (0.59–1.03) in active men and 0.82 (0.67–0.99) in very active men (p for trend = 0.060). The ORs (95% CIs) for obesity by BMI ≥30 kg/m2 were 0.40 (0.15–0.98) in active men and 0.90 (0.52–1.56) in very active men (p for trend = 0.978). Compared to inactive women, the ORs (95% CIs) for obesity by WHtR ≥0.50 were 0.94 (0.75–1.18) in active women and 0.84 (0.71–0.998) in very active women (p for trend = 0.046). However, no significant associations were found between physical activity and obesity by BMI in women. Conclusions We found more significant associations between physical activity and obesity defined by WHtR than BMI. However, intervention studies are warranted to investigate and compare causal associations between physical activity and different obesity measures in various populations.

The widespread use of remifentanil during total intravenous anesthesia (TIVA) has raised concerns about the risk of postoperative remifentanil-associated pain. Although a recent meta-analysis suggests that remifentanil-associated pain is unlikely to occur in patients with TIVA because of the protective effect of co-administered propofol, the evidence is not conclusive. We retrospectively assessed 635 patients who received robotic thyroid surgery under TIVA to evaluate the risk of remifentanil-associated pain. Postoperative pain was evaluated using 11-point numeric rating scale (NRS). Time dependent Cox proportional hazards regression analysis was used to determine the risk factors of treatment-requiring pain (NRS > 4) during the first 48 postoperative hours. Postoperative pain rapidly decreased, and treatment-requiring pain remained in 12.8% (81 out of 635) of patients at 48 hours postoperatively. After adjusting for the time-dependent analgesic consumption, intraoperative use of remifentanil > 0.2 mcg/kg/min was a positive predictor of postoperative pain with a hazard ratio of 1.296 (95% C.I., 1.014–1.656, P = 0.039) during 48 hours after surgery. In conclusion, excessive use of remifentanil during TIVA was associated with increased risk of pain after robotic thyroid surgery. Prospective trials are required to confirm these results and determine whether decreasing remifentanil consumption below the threshold can reduce postoperative pain.

Background Understanding the epidemiological characteristics of anaphylaxis-associated out-of-hospital cardiac arrest (OHCA) is the first step toward developing preventative strategies and optimizing care systems. We aimed to describe and compare epidemiological features and clinical outcomes among patients with anaphylaxis-associated OHCAs according to causative agent groups. Methods We identified emergency medical service (EMS)-treated anaphylaxis-associated OHCA patients from a nationwide OHCA registry between 2008 and 2015. We compared epidemiological characteristics and outcomes according to causal agents (a natural agents group and an iatrogenic agents group) and evaluated temporal variability in incidence. Multivariate logistic regression analysis was performed to compare survival to discharge between causative agent groups. Results During the study period (8 years), the total number of anaphylaxis-associated OHCAs was 233. A total of 224 eligible cases were included in the analysis. There were 192 patients (85.6%) in the natural agents group and 32 patients (14.3%) in the iatrogenic agents group. There was significant diurnal and seasonal variability in the frequency of anaphylaxis-associated OHCAs (p values

[This corrects the article DOI: 10.1371/journal.pone.0128720.].

Overexpression of p53 is the most frequent genetic alteration in breast cancer. Recently, many studies have shown that the expression of mutant p53 differs for each subtype of breast cancer and is associated with different prognoses. In this study, we aimed to determine the suitable cut-off value to predict the clinical outcome of p53 overexpression and its usefulness as a prognostic factor in each subtype of breast cancer, especially in luminal A breast cancer. Approval was granted by the Institutional Review Board of Samsung Medical Center. We analyzed a total of 7,739 patients who were surgically treated for invasive breast cancer at Samsung Medical Center between Dec 1995 and Apr 2013. Luminal A subtype was defined as ER&PR + and HER2- and was further subclassified according to Ki-67 and p53 expression as follows: luminal A (Ki-67-,p53-), luminal A (Ki-67+, p53-), luminal A (Ki-67 -, p53+) and luminal A (Ki-67+, p53+). Low-risk luminal A subtype was defined as negative for both Ki-67 and p53 (luminal A [ki-67-, p53-]), and others subtypes were considered to be high-risk luminal A breast cancer. A cut-off value of 10% for p53 was a good predictor of clinical outcome in all patients and luminal A breast cancer patients. The prognostic role of p53 overexpression for OS and DFS was only significant in luminal A subtype. The combination of p53 and Ki-67 has been shown to have the best predictive power as calculated by the area under curve (AUC), especially for long-term overall survival. In this study, we have shown that overexpression of p53 and Ki-67 could be used to discriminate low-risk luminal A subtype in breast cancer. Therefore, using the combination of p53 and Ki-67 expression in discriminating low-risk luminal A breast cancer may improve the prognostic power and provide the greatest clinical utility.

The aim of this study was to investigate the association of central and abdominal obesity with the prevalence of cataracts in a middle-aged Korean population. This retrospective cross-sectional study was based on the data collected from the Korea National Health and Nutrition Examination Survey 2008-2009, in which 4,914 subjects were examined. Ophthalmological examinations were performed to determine the presence of a nuclear, cortical, or posterior subcapsular cataract. Both general obesity (a body mass index >= 25 kg/m(2)) and abdominal obesity (a waist circumference >= 90 cm for men and >= 80 cm for women) were significantly associated with the occurrence of cataracts among middle-aged women [adjusted odds ratio (aOR), 1.32; 95% confidence interval (CI), 1.03-1.69; and aOR, 1.40; 95% CI, 1.06-1.85, respectively], while abdominal obesity was significantly inversely associated with the occurrence of cataracts among middle-aged men (aOR, 0.76; 95% CI, 0.58-1.01; and aOR, 0.66; 95% CI, 0.49-0.89, respectively). We report a difference in the association between obesity and the prevalence of cataracts based on gender.

Consumption of a typical Western diet is a risk factor for several disorders. Metabolic syndrome is the most common disease associated with intake of excess fat. However, the incidence of inflammatory bowel disease is also greater in subjects consuming a Western diet, although the mechanism of this phenomenon is not clearly understood. We examined the morphological and functional changes of the intestine, the first site contacting dietary fat, in mice fed a high-fat diet (HFD) inducing obesity. Paneth cell area and production of antimicrobial peptides by Paneth cells were decreased in HFD-fed mice. Goblet cell number and secretion of mucin by goblet cells were also decreased, while intestinal permeability was increased in HFD-fed mice. HFD-fed mice were more susceptible to experimental colitis, and exhibited severe colonic inflammation, accompanied by the expansion of selected pathobionts such as Atopobium sp. and Proteobacteria. Fecal microbiota transplantation transferred the susceptibility to DSS-colitis, and antibiotic treatment abrogated colitis progression. These data suggest that an experimental HFD-induced Paneth cell dysfunction and subsequent intestinal dysbiosis characterized by pathobiont expansion can be predisposing factors to the development of inflammatory bowel disease.

Angiogenic peptides have therapeutic potential for the treatment of chronic ischemic diseases. Periostin, an extracellular matrix protein expressed in injured tissues, promotes angiogenesis and tissue repair. We previously reported that in vivo administration of both recombinant full-length protein and the first FAS I domain of periostin alleviated peripheral artery occlusive disease by stimulating the migration of humane endothelial colony forming cells (ECFCs) and subsequent angiogenesis. In the present study, we ascertained the peptide sequence responsible for the periostin-induced angiogenesis. By serial deletion mapping of the first FAS I domain, we identified a peptide sequence (amino acids 142-151) of periostin for stimulation of chemotactic migration, adhesion, proliferation and endothelial tube formation of human ECFCs in vitro. Chemotactic migration of ECFCs induced by the periostin peptide was blocked by pre-incubation with an anti-β5 integrin neutralizing antibody. Treatment of ECFCs with the periostin peptide led to phosphorylation of both AKT and ERK, and pretreatment of ECFCs with the MEK-ERK pathway inhibitor U0126 or the PI3K-AKT pathway inhibitors, LY294002 or Wortmannin, blocked the periostin peptide-stimulated migration of ECFCs. These results suggest that the synthetic periostin peptide can be applied for stimulating angiogenic and therapeutic potentials of ECFCs.

Choroidal neovascularization (CNV) is a major cause of severe visual loss in patients with age-related macular degeneration (AMD). Recently, itraconazole has shown potent and dose-dependent inhibition of tumor-associated angiogenesis. We evaluated the anti-angiogenic effect of itraconazole in a rat model of laser-induced CNV. After laser photocoagulation in each eye to cause CNV, right eyes were administered intravitreal injections of itraconazole; left eyes received balanced salt solution (BSS) as controls. On day 14 after laser induction, fluorescein angiography (FA) was used to assess abnormal vascular leakage. Flattened retinal pigment epithelium (RPE)-choroid tissue complex was stained with Alexa Fluor 594-conjugated isolectin B4 to measure the CNV area and volume. Vascular endothelial growth factor receptor 2 (VEGFR2) mRNA and protein expression was determined 1, 4, 7, and 14 days after intravitreal injection by quantitative RT-PCR or Western blot. VEGF levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Intravitreal itraconazole significantly reduced leakage from CNV as assessed by FA and CNV area and volume on flat mounts compared with intravitreal BSS (p = 0.002 for CNV leakage, p

Objectives Among a variety of relevant factors of osteoporosis, the association between alcohol intake and postmenopausal women’s bone mineral density (BMD) by using data from the Korean National Health and Nutrition Examination Survey was evaluated in this study. Materials and methods Among a total of 31,596 subjects, males, premenopausal women, participants without BMD data were excluded. Finally, a total number of subjects in the study was 3,312. The frequency and amount of alcohol intake were determined by self-reported questionnaires, and BMD was measured by dual-energy x-ray absorptiometry. Results Mean femoral BMD for light drinkers was statistically significantly greater than that for heavy drinkers and non-drinkers. We observed the characteristic trends for BMD by drinking frequency; the mean BMD gradually increased from non-drinkers to the participants who drank 2–3 times per week; these participants exhibited the highest BMD. Participants who drank alcohol greater than 4 times per week showed a lower BMD. In the risk factor analysis, the adjusted odds ratio for osteoporosis (at femoral neck) was 1.68 in non-drinkers and 1.70 in heavy drinkers compared with light drinkers. Conclusions Light alcohol intake (2–3 times per week and 1–2 or 5–6 glasses per occasion) in South Korean postmenopausal women was related to high femoral BMD. Non-drinkers and heavy drinkers had approximately a 1.7-times greater risk for osteoporosis than light drinkers.

Background The association between preoperative aspirin use and postoperative acute kidney injury (AKI) in cardiovascular surgery is unclear. We sought to evaluate the effect of preoperative aspirin use on postoperative AKI in cardiac surgery. Methods A total of 770 patients who underwent cardiovascular surgery under cardiopulmonary bypass were reviewed. Perioperative clinical parameters including preoperative aspirin administration were retrieved. We matched 108 patients who took preoperative aspirin continuously with patients who stopped aspirin more than 7 days or did not take aspirin for the month before surgery. The parameters used in the matching included variables related to surgery type, patient’s demographics, underlying medical conditions and preoperative medications. Results In the first seven postoperative days, 399 patients (51.8%) developed AKI, as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria and 128 patients (16.6%) required hemodialysis. Most patients took aspirin 100 mg once daily (n = 195, 96.5%) and the remaining 75 mg once daily. Multivariable analysis showed that preoperative maintenance of aspirin was independently associated with decreased incidence of postoperative AKI (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.21–0.98, P = 0.048; after propensity score matching: OR 0.39, 95% CI 0.22–0.67, P = 0.001). Preoperative maintenance of aspirin was associated with less incidence of AKI defined by KDIGO both in the entire and matched cohort (n = 44 [40.7%] vs. 69 [63.9%] in aspirin and non-aspirin group, respectively in matched sample, relative risk [RR] 0.64, 95% CI 0.49, 0.83, P = 0.001). Preoperative aspirin was associated with decreased postoperative hospital stay after matching (12 [9–18] days vs. 16 [10–25] in aspirin and non-aspirin group, respectively, P = 0.038). Intraoperative estimated or calculated blood loss using hematocrit difference and estimated total blood volume showed no difference according to aspirin administration in both entire and matched cohort. Conclusions Preoperative low dose aspirin administration without discontinuation was protective against postoperative AKI defined by KDIGO criteria independently in both entire and matched cohort. Preoperative aspirin was also associated with decreased hemodialysis requirements and decreased postoperative hospital stay without increasing bleeding. However, differences in AKI and hospital stay were not associated with in-hospital mortality.

BACKGROUND AND PURPOSE: The time of hospital arrival may have an effect on prognosis of various vascular diseases. We examined whether off-hour admission would affect the 3-month functional outcome in acute ischemic stroke patients admitted to tertiary hospitals. METHODS: We analyzed the 'off-hour effect' in consecutive patients with acute ischemic stroke using multi-center prospective stroke registry. Work-hour admission was defined as when the patient arrived at the emergency department between 8 AM and 6 PM from Monday to Friday and between 8 AM and 1 PM on Saturday. Off-hour admission was defined as the rest of the work-hours and statutory holidays. Multivariable logistic regression was used to analyze the association between off-hour admission and 3-month unfavorable functional outcome defined as modified Rankin Scale (mRS) 3-6. Multivariable model included age, sex, risk factors, prehospital delay time, intravenous thrombolysis, stroke subtypes and severity as covariates. RESULTS: A total of 7075 patients with acute ischemic stroke were included in this analysis: mean age, 67.5 (±13.0) years; male, 58.6%. In multivariable analysis, off-hour admission was not associated with unfavorable functional outcome (OR, 0.89; 95% CI, 0.72-1.09) and mortality (OR, 1.09; 95% CI, 0.77-1.54) at 3 months. Moreover, off-hour admission did not affect a statistically significant shift of 3-month mRS distributions (OR, 0.90; 95% CI, 0.78-1.05). CONCLUSIONS: 'Off-hour' admission is not associated with an unfavorable 3-month functional outcome in acute ischemic stroke patients admitted to tertiary hospitals in Korea. This finding indicates that the off-hour effects could be overcome with well-organized stroke management strategies.

Background: Glycated albumin (GA) has been increasingly used as a reliable index for short-term glycemic monitoring, and is inversely associated with beta-cell function. Because the pathophysiologic nature of type 2 diabetes (T2D) is characterized by progressive decline in insulin secretion, the aim was to determine whether GA levels were affected by diabetes duration in subjects with T2D. Methods: To minimize the effect of glucose variability on GA, subjects with stably maintained HbA(1c) levels of 1 year (n = 781) were recruited and categorized as New-T2D and Old-T2D, respectively. Biochemical, glycemic, and C-peptide parameters were measured. Results: GA levels were significantly elevated in HbA(1c)-matched Old-T2D subjects compared to New-T2D subjects. Duration of diabetes was positively correlated with GA, whereas a negative relationship was found with C-peptide increment (Delta C-peptide). Among insulin secretory indices, dynamic parameters such as Delta C-peptide were inversely related to GA (r = -0.42, p < 0.001). Multiple linear regression analyses showed that duration of diabetes was associated with GA (standardized beta coefficient [STD beta] = 0.05, p < 0.001), but not with HbA(1c) (STD beta = 0.04, p < 0.095). This association disappeared after additional adjustment with Delta C-peptide (STD beta = 0.02, p = 0.372), suggesting that beta-cell function might be a linking factor of close relationship between duration of diabetes and GA values. Conclusions: The present study showed that GA levels were significantly increased in subjects with longer duration T2D and with decreased insulin secretory function. Additional caution should be taken when interpreting GA values to assess glycemic control status in these individuals.

Repeat proteins have recently attracted much attention as alternative scaffolds to immunoglobulin antibodies due to their unique structural and biophysical features. In particular, repeat proteins show high stability against temperature and chaotic agents. Despite many studies, structural features for the stability of repeat proteins remain poorly understood. Here we present an interesting result from in silico analyses pursuing the factors which affect the stability of repeat proteins. Previously developed repebody structure based on variable lymphocytes receptors (VLRs) which consists of leucine-rich repeat (LRR) modules was used as initial structure for the present study. We constructed extra six repebody structures with varying numbers of repeat modules and those structures were used for molecular dynamics simulations. For the structures, the intramolecular interactions including backbone H-bonds, van der Waals energy, and hydrophobicity were investigated and then the radius of gyration, solvent-accessible surface area, ratio of secondary structure, and hydration free energy were also calculated to find out the relationship between the number of LRR modules and stability of the protein. Our results show that the intramolecular interactions lead to more compact structure and smaller surface area of the repebodies, which are critical for the stability of repeat proteins. The other features were also well compatible with the experimental results. Based on our observations, the repebody-5 was proposed as the best structure from the all repebodies in structure optimization process. The present study successfully demonstrated that our computer-based molecular modeling approach can significantly contribute to the experiment-based protein engineering challenge.

BackgroundObesity is a known risk factor for colorectal cancer (CRC), and emerging data suggest that this association is mediated by visceral fat rather than total body fat. However, there is a lack of studies evaluating the association between visceral fat area and the prevalence of CRC.MethodsTo investigate the relationship between visceral adiposity and prevalence of CRC, data of 497 women diagnosed with CRC and 318 apparently healthy women were analysed and data of well-balanced 191 pairs of women with CRC and healthy women matched based on propensity scores were additionally analysed. Diagnosis of CRC was confirmed by colonoscopy and histology. Metabolic parameters were assessed, along with body composition, using computed tomography.ResultsThe median visceral fat area was significantly higher in the CRC group compared with the control group before and after matching. The prevalence of CRC increased significantly with increasing visceral fat tertiles after matching (p for trend ConclusionThus, we conclude that visceral fat area is positively associated with the prevalence of CRC. Although we could not determine the causality, visceral adiposity may be associated with the risk of CRC. Further prospective studies are required to determine the benefits of controlling visceral obesity for reducing CRC risk.

Because human mesenchymal stem cells (hMSC) have profound immunomodulatory effects, many attempts have been made to use hMSCs in preclinical and clinical trials. For hMSCs to be used in therapy, a large population of hMSCs must be generated by in vitro expansion. However, the immunomodulatory changes following the in vitro expansion of hMSCs have not been elucidated. In this study, we evaluated the effect of replicative senescence on the immunomodulatory ability of hMSCs in vitro and in vivo. Late-passage hMSCs showed impaired suppressive effect on mitogen-induced mononuclear cell proliferation. Strikingly, late-passage hMSCs had a significantly compromised protective effect against mouse experimental colitis, which was confirmed by gross and histologic examination. Among the anti-inflammatory cytokines, the production of prostaglandin E-2 (PGE(2)) and the expression of its primary enzyme, cyclooxygenase-2 (COX-2), were profoundly increased by pre-stimulation with interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha), and this response was significantly decreased with consecutive passages. We demonstrated that the impaired phosphorylation activity of p38 MAP kinase (p38 MAPK) in late-passage hMSCs led to a compromised immunomodulatory ability through the regulation of COX-2. In conclusion, our data indicate that the immunomodulatory ability of hMSCs gradually declines with consecutive passages via a p38-mediated alteration of COX-2 and PGE(2) levels.

The activities and side effects of 5-lipoxygenase (5-LO) inhibitors can be predicted by identifying their redox mechanisms. In this study, we developed a fluorescence-based method to measure the redox potential of 5-LO inhibitors and compared it to the conventional, absorbance-based method. After the pseudo-peroxidase reaction, the amount of remaining lipid peroxide was quantified using the H2DCFDA (2′,7′-dichlorodihydrofluorescein diacetate) fluorescence dye. Our method showed large signal windows and provided comparable redox potential values. Importantly, the redox mechanisms of known inhibitors were accurately measured with the fluorescence assay, whereas the conventional, absorbance-based method showed contradictory results. Our findings suggest that our developed method is a better alternative for classifying the redox potential of 5-LO inhibitors, and the fluorescence assay can be effectively used to study the mechanisms of action that are related to redox cycling.

BACKGROUND: Obesity, especially visceral obesity, is known to be an important correlate for cardiovascular disease and increased mortality. On the other hand, high cardiorespiratory fitness is suggested to be an effective contributor for reducing this risk. This study was conducted to determine the combined impact of cardiorespiratory fitness and visceral adiposity, otherwise known as fitness and fatness, on metabolic syndrome in overweight and obese adults. METHODS: A total of 232 overweight and obese individuals were grouped into four subtypes according to their fitness level. This was measured by recovery heart rate from a step test in addition to visceral adiposity defined as the visceral adipose tissue area to subcutaneous adipose tissue area ratio (VAT/SAT ratio). Associations of fitness and visceral fatness were analyzed in comparison with the prevalence of metabolic syndrome. RESULTS: The high visceral fat and low fitness group had the highest prevalence of metabolic syndrome [Odds Ratio (OR) 5.02; 95% Confidence Interval (CI) 1.85-13.61] compared with the reference group, which was the low visceral adiposity and high fitness group, after adjustments for confounding factors. Viscerally lean but unfit subjects were associated with a higher prevalence of metabolic syndrome than more viscerally obese but fit subjects (OR 3.42; 95% CI 1.27-9.19, and OR 2.70; 95% CI 1.01-7.25, respectively). CONCLUSIONS: Our study shows that visceral obesity and fitness levels are cumulatively associated with a higher prevalence of metabolic syndrome in healthy overweight and obese adults. This suggests that cardiorespiratory fitness is a significant modifier in the relation of visceral adiposity to adverse metabolic outcomes in overweight and obese individuals.

BackgroundAdipose tissue, mainly composed of adipocytes, plays an important role in metabolism by regulating energy homeostasis. Obesity is primarily caused by an abundance of adipose tissue. Therefore, specific targeting of adipose tissue is critical during the treatment of obesity, and plays a major role in overcoming it. However, the knowledge of cell-surface markers specific to adipocytes is limited.Methods and resultsWe applied the CELL SELEX (Systematic Evolution of Ligands by EXponential enrichment) method using flow cytometry to isolate molecular probes for specific recognition of adipocytes. The aptamer library, a mixture of FITC-tagged single-stranded random DNAs, is used as a source for acquiring molecular probes. With the increasing number of selection cycles, there was a steady increase in the fluorescence intensity toward mature adipocytes. Through 12 rounds of SELEX, enriched aptamers showing specific recognition toward mature 3T3-L1 adipocyte cells were isolated. Among these, two aptamers (MA-33 and 91) were able to selectively bind to mature adipocytes with an equilibrium dissociation constant (Kd) in the nanomolar range. These aptamers did not bind to preadipocytes or other cell lines (such as HeLa, HEK-293, or C2C12 cells). Additionally, it was confirmed that MA-33 and 91 can distinguish between mature primary white and primary brown adipocytes.ConclusionsThese selected aptamers have the potential to be applied as markers for detecting mature white adipocytes and monitoring adipogenesis, and could emerge as an important tool in the treatment of obesity.

BACKGROUND: Blood pressure (BP) is directly and causally associated with body size in the general population. Whether muscle mass is an important factor that determines BP remains unclear. OBJECTIVE: To investigate whether sarcopenia is associated with hypertension in older Koreans. PARTICIPANTS: We surveyed 2,099 males and 2,747 females aged 60 years or older. MEASUREMENTS: Sarcopenia was defined as an appendicular skeletal muscle mass divided by body weight (ASM/Wt) that was

Background Lithospermic acid B (LAB), an active component isolated from Salvia miltiorrhiza radix, has been reported to have antioxidant effects. We examined the effects of LAB on the prevention of diabetic retinopathy in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. Methods and Findings LAB (10 or 20 mg/kg) or normal saline were given orally once daily to 24-week-old male OLETF rats for 52 weeks. At the end of treatment, fundoscopic findings, vascular endothelial growth factor (VEGF) expression in the eyeball, VEGF levels in the ocular fluid, and any structural abnormalities in the retina were assessed. Glucose metabolism, serum levels of high-sensitivity C-reactive protein (hsCRP), monocyte chemotactic protein-1 (MCP1), and tumor necrosis factor-alpha (TNFα) and urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels were also measured. Treatment with LAB prevented vascular leakage and basement membrane thickening in retinal capillaries in a dose-dependent manner. Insulin resistance and glucose intolerance were significantly improved by LAB treatment. The levels of serum hsCRP, MCP1, TNFα, and urinary 8-OHdG were lower in the LAB-treated OLETF rats than in the controls. Conclusions Treatment with LAB had a preventive effect on the development of diabetic retinopathy in this animal model, probably because of its antioxidative effects and anti-inflammatory effects.

Stroke is the second leading cause of death. Experimental animal models of cerebral ischemia are widely used for researching mechanisms of ischemic damage and developing new drugs for the prevention and treatment of stroke. The present study aimed to comparatively investigate neuroprotective effects of aspirin (ASA), decursinol (DA) and new synthetic aspirin-decursinol adduct (ASA-DA) against transient focal and global cerebral ischemic damage. We found that treatment with 20 mg/kg, not 10 mg/kg, ASA-DA protected against ischemia-induced neuronal death after transient focal and global ischemic damage, and its neuroprotective effect was much better than that of ASA or DA alone. In addition, 20 mg/kg ASA-DA treatment reduced the ischemia-induced gliosis and maintained antioxidants levels in the corresponding injury regions. In brief, ASA-DA, a new synthetic drug, dramatically protected neurons from ischemic damage, and neuroprotective effects of ASA-DA may be closely related to the attenuation of ischemia-induced gliosis and maintenance of antioxidants.

Recent advance in sequencing technology has enabled comprehensive profiling of genetic alterations in cancer. We have established a targeted sequencing platform using next-generation sequencing (NGS) technology for clinical use, which can provide mutation and copy number variation data. NGS was performed with paired-end library enriched with exons of 183 cancer-related genes. Normal and tumor tissue pairs of 60 colorectal adenocarcinomas were used to test feasibility. Somatic mutation and copy number alteration were analyzed. A total of 526 somatic non-synonymous sequence variations were found in 113 genes. Among these, 278 single nucleotide variations were 232 different somatic point mutations. 216 SNV were 79 known single nucleotide polymorphisms in the dbSNP. 32 indels were 28 different indel mutations. Median number of mutated gene per tumor was 4 (range 0-23). Copy number gain (>X2 fold) was found in 65 genes in 40 patients, whereas copy number loss (

This study was undertaken to elucidate detailed event of early embryogenesis in chicken embryos using a noninvasive egg retrieval technique before oviposition. White Leghorn intrauterine eggs were retrieved from 95 cyclic hens aged up to 54-56 weeks and morphogenetic observation was made under both bright field and fluorescent image in a time course manner. Differing from mammals, asymmetric cleavage to yield preblastodermal cells was observed throughout early embryogenesis. The first two divisions occurred synchronously and four polarized preblastodermal cells resulted after cruciform cleavage. Then, asynchronous cleavage continued in a radial manner and overall cell size in the initial cleavage region was smaller than that in the distal area. Numerous sperms were visible, regardless of zygotic nuclei formation. Condensed sperm heads were present mainly in the perivitelline space and cytoplasm, and rarely in the yolk region, while decondensed sperm heads were only visible in the yolk. In conclusion, apparent differences in sperm dynamics and early cleavage events compared with mammalian embryos were detected in chick embryo development, which demonstrated polarized cleavage with penetrating supernumerary sperm into multiple regions.