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Purpose: Study purpose was to describe the child safety injury experiences, injury prevention behaviors and educational needs of immigrant Vietnamese women on Jeju Island, and to explore associations among those factors., Methods: A descriptive correlational study was conducted using structured questionnaires to collect data from immigrant Vietnamese women who visited a multicultural centers on Jeju Island from January to April, 2017., Results: Data from 60 women were analyzed. They were 28.2±5.5 years old, had resided in Korea for 40.6±31.1 months, and had 1.5±0.6 children on average. In total, 51.7% had previous injury prevention education, 68.2% had experienced child safety injuries, and 95.0% wanted to receive education on how to prevent child safety injuries. The mean total score of child injury prevention behaviors was 27.33±17.79, and that variable was associated with a longer duration of formal education (t=2.41, p =.021) and with women's experiences of child safety injury (t=5.97, p <.001)., Conclusion: Immigrant Vietnamese women experienced a higher frequency of child safety injuries and needed educational opportunities to prevent these injuries. Further research is necessary to develop the essential content and effective methods for education on child safety injury prevention among this unique multicultural population., Competing Interests: No existing or potential conflict of interest relevant to this article was reported., (Copyright © 2019 Korean Academy of Child Health Nursing. All rights reserved.)

This study investigated the effects of negative air ions (NAIs) on cognitive function in young male adults, specifically examined whether NAIs could influence the behavioral and neuroelectrical indices of inhibition. Thirty-nine young adults participated in the NAI and the control sessions in a counterbalanced order. A computerized Stroop color-word test was administrated, and N2 of the event-related potential was recorded and then analyzed. The results revealed that participants in the NAI session demonstrated shorter reaction times and higher accuracy for both Stroop congruent and incongruent trials. Larger N2 amplitudes were also observed in the NAI session than in the control session, whereas no alterations in the latencies were found. These findings suggest that NAIs resulted in a general improvement in both basic information processing and inhibition. This facilitation may be related to an enhanced neuronal processing or alertness status reflected by larger amplitudes of the N2 component.

Aims: The hypoxia-stimulated response of the endocrine system depends on the kind and duration of hypoxia. Hypoxia has been reported to stimulate testosterone (T) production in rats, but the mechanisms remain to be investigated., Materials and Methods: Male rats were divided into two groups. The rats exposed to chronic intermittent hypoxia (CIH) at 8 h/day were housed in a hypoxic chamber (12% O 2 ) for 14 days. Normoxic rats were used as control animals. T was measured after challenging the rat Leydig cells (LCs) with different stimulators, including hCG (0.01 IU/ml), forskolin (10 - 5  M), 8-bromo-cAMP (10 - 4  M), A23187 (10 - 5  M), cyclopiazonic acid (10 - 4  M), and androstenedione (10 - 8  M). Meanwhile, the LCs were incubated with trilostane (10 - 5  M) and/or 25-OH-hydroxycholesterol (10 - 5  M); thereafter the media were collected for pregnenolone assay., Key Findings: In the CIH group, plasma T levels were increased, but the serum luteinizing hormone (LH) was decreased. Furthermore, at several time intervals after hCG injection, plasma T levels were higher in the CIH group. The evoked-release of T and pregnenolone were significantly increased in the CIH group. Compared with the normoxic group, the CIH group had higher mRNA and protein expression levels of the LH receptor and CYP11A1 but not StAR. The plasma and testicular microvasculature VEGF levels were increased in the CIH group. The testicular vessel distribution was more obvious in CIH rats., Significance: CIH-induced T secretion might be partially mediated by mechanisms involving the induction of LH receptor expression, testicular angiogenesis, CYP11A1 activity, 17β-HSD activity, and calcium-related pathway., (Copyright © 2019 Elsevier Inc. All rights reserved.)

An 8-year-old girl with masticatory movement disorder received botulinum toxin-A (BTX-A) injection and orthodontic treatment. She showed facial asymmetry with right masseter muscle hyperplasia. After BTX-A injection combined with orthodontic treatment, the transverse discrepancy between right and left maxillary dentition completely corrected. Cone-beam computed tomography images revealed that the height of the left mandibular ramus had increased by 2.3 mm, considerably more than on the right side, the discrepancy in mandibular ramus height between the left and the right decreased dramatically. In a short period, BTX-A injection combined with orthodontic treatment corrected a mandibular movement disorder with asymmetric mandibular growth in a growing patient.

Purpose: Monogenic diabetes is a specific type of diabetes in which precision medicine could be applied. In this study, we used targeted panel sequencing to investigate pathogenic variants in Korean patients with clinically suspected monogenic diabetes., Methods: The eligibility criteria for inclusion were patients with nontype 1 diabetes with age at onset ≤30 years and body mass index (BMI) ≤30 kg/m2. Among the 2090 patients with nontype 1 diabetes, 109 had suspected monogenic diabetes and underwent genetic testing. We analyzed 30 monogenic diabetes genes using targeted panel sequencing. The pathogenicity of the genetic variants was evaluated according to the American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines., Results: Among the 109 patients with suspected monogenic diabetes, 23 patients (21.1%) harbored pathogenic/likely pathogenic variants. A total of 14 pathogenic/likely pathogenic variants of common maturity-onset diabetes of the young (MODY) genes were identified in GCK, HNF1A, HNF4A, and HNF1B. Other pathogenic/likely pathogenic variants were identified in WFS1, INS, ABCC8, and FOXP3. The mitochondrial DNA 3243A>G variant was identified in five participants. Patients with pathogenic/likely pathogenic variants had a significantly higher MODY probability, a lower BMI, and a lower C-peptide level than those without pathogenic/likely pathogenic variants (P = 0.007, P = 0.001, and P = 0.012, respectively)., Conclusions: Using targeted panel sequencing followed by pathogenicity evaluation, we were able to make molecular genetic diagnoses for 23 patients (21.1%) with suspected monogenic diabetes. Lower BMI, higher MODY probability, and lower C-peptide level were characteristics of these participants., (Copyright © 2019 Endocrine Society.)

Background: The objective of this study was to examine the relationship between employee work schedule and failure in smoking cessation., Methods: Logistic regression was used to estimate the association between work schedule and failed smoking cessation rate among 4927 male workers who had attempted smoking cessation. The data was obtained from the annual Korean National Health and Nutrition Examination Survey from 2007 to 2015 (excluding data from 2013). An adjusted model, including demographic and occupational variables, was constructed after stratifying the data into two subgroups by age (the 19- to 40-year-old group and the 41- to 60-year-old group)., Results: The percentage of smoking-cessation failure varied according to work schedule and age. The failure rate in the 19- to 40-year-old group was generally higher for all work schedule categories than in the 41- to 60-year-old group. In particular, the highest percentage (90.9%) of smoking-cessation failure was in the fixed overnight work group. After adjusting for demographic characteristics and work organization variables, the odds ratio for failed smoking cessation across all ages was 3.30 (95%CI 2.23-4.86) among the fixed overnight workers compared to the daytime workers. Both of the age-stratified subgroups maintained this relationship, with a notably higher OR in the 19- to 40-year-old group (OR 3.74, 95% CI 1.80-7.77)., Conclusions: Fixed overnight work is likely to negatively affect smoking cessation compared to other work schedules. Tailored anti-smoking intervention programs are required based on work schedule., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Background: We aimed to investigate the effectiveness and safety of adding basal insulin to initiating dipeptidyl peptidase-4 (DPP-4) inhibitor and metformin and/or sulfonylurea (SU) in achieving the target glycosylated hemoglobin (HbA1c) in patients with type 2 diabetes mellitus (T2DM)., Methods: This was a single-arm, multicenter, 24-week, open-label, phase 4 study in patients with inadequately controlled (HbA1c ≥7.5%) T2DM despite the use of DPP-4 inhibitor and metformin. A total of 108 patients received insulin glargine while continuing oral antidiabetic drugs (OADs). The primary efficacy endpoint was the percentage of subjects achieving HbA1c ≤7.0%. Other glycemic profiles were also evaluated, and the safety endpoints were adverse events (AEs) and hypoglycemia., Results: The median HbA1c at baseline (8.9%; range, 7.5% to 11.1%) decreased to 7.6% (5.5% to 11.7%) at 24 weeks. Overall, 31.7% subjects ( n =33) achieved the target HbA1c level of ≤7.0%. The mean differences in body weight and fasting plasma glucose were 1.2±3.4 kg and 56.0±49.8 mg/dL, respectively. Hypoglycemia was reported in 36 subjects (33.3%, 112 episodes), all of which were fully recovered. There was no serious AE attributed to insulin glargine. Body weight change was significantly different between SU users and nonusers (1.5±2.5 kg vs. -0.9±6.0 kg, P =0.011)., Conclusion: The combination add-on therapy of insulin glargine, on metformin and DPP-4 inhibitors with or without SU was safe and efficient in reducing HbA1c levels and thus, is a preferable option in managing T2DM patients exhibiting dysglycemia despite the use of OADs., Competing Interests: Sponsorship for this study and article processing charges was funded by Sanofi-Aventis Korea. Dol Mi Kim is an employee at Sanofi-Aventis Korea. No potential conflict of interest relevant to this article was reported except for her., (Copyright © 2019 Korean Diabetes Association.)

Background and Objectives: Lilly insulin glargine (LY IGlar; Basaglar ® ) and the reference insulin glargine product (IGlar; Lantus ® ) are basal insulin glargine analogs with identical amino acid sequence and similar pharmacological profiles. ELEMENT 5, a Phase 3, prospective, randomized, multinational, two-arm, active-controlled, open-label, parallel-design study in type 2 diabetes mellitus (T2DM) patients (N = 493) showed similar efficacy and safety profiles with LY IGlar and IGlar. This study reports results from India (N = 100) and East Asia (N = 134) subpopulations., Methods: Patients from India and East Asia (Korea and Taiwan) with T2DM who were insulin naïve (glycated hemoglobin (HbA1c) ≥ 7.0% and ≤ 11.0%) or on basal insulin (HbA1c ≤ 11.0%) were randomized to receive LY IGlar or IGlar along with oral antihyperglycemic medications (OAMs) for 24 weeks. Patients were instructed to self-titrate from the starting dose by 1 unit/day until fasting blood glucose (FBG) ≤ 5.6 mmol/L (100 mg/dL) was achieved. The key outcome was HbA1c change from baseline to Week 24., Results: Within-group least-squares mean (LSM) decrease (baseline to Week 24) in HbA1c was similar between treatments. The upper limit of confidence interval (CI) for treatment difference was below the defined 0.4% noninferiority margin in India (LY IGlar: - 0.83%; IGlar: - 0.62%; difference [95% CI] - 0.21 [- 0.70, 0.28]) and East Asia (LY IGlar: - 1.28%; IGlar: - 1.26%; difference [95% CI] - 0.02 [- 0.34, 0.30]) subpopulations. Results of other efficacy and safety endpoints at Week 24 were similar between treatments in both subpopulations. LSM self-monitored FBG levels were similar between treatments at all visits in both subpopulations except at Week 24 in the India subpopulation (LY IGlar: 5.65 [0.10] mmol/L or 101.8 [1.86] mg/dL; IGlar: 5.18 [0.10] mmol/L or 93.3 [1.75] mg/dL; p = 0.002)., Conclusion: Efficacy and safety profiles of LY IGlar and IGlar, in combination with OAMs, were similar in India and East Asia subpopulations. This was consistent with the ELEMENT 5 total population., Clinical Trial Registration: NCT02302716.

Background: Ileal transposition (IT) is an experimental surgery to investigate the role of the distal ileum in Roux-en-Y gastric bypass (RYGB) surgery. To systematically investigate the dynamic adaptation process of the ileum after IT, we performed transcriptome analyses of the transposed ileum compared with the ileum in situ at different postoperative time points., Methods: Sprague-Dawley rats fed a chow diet underwent IT or sham surgery. One and 4 weeks after IT or sham surgery, total RNA was extracted from the ileal tissue and subjected to transcriptome analyses using microarray., Results: Principal component analysis showed that the difference between weeks 1 and 4 was the largest, and the differences between the IT and sham groups were larger in week 4 than in week 1. We identified 1792 differentially expressed genes (DEGs) between IT and sham ileal tissues, including 659 and 1133 DEGs in weeks 1 and 4, respectively. Interestingly, only 45 and 24 DEGs were commonly up- or downregulated in weeks 1 and 4, indicating a marked transition during the adaptation process. Functional enrichment and network analyses showed that structural adaptation predominantly occurred in week 1, while metabolic and immune adaptations predominantly occurred in week 4. These analyses further revealed potential components that modulate structural adaptation (e.g., extracellular matrix) in week 1 and metabolic (e.g., glucose transporter) and immune (e.g., Th17 cells) adaptations in week 4., Conclusions: The transposed distal ileum underwent dynamic adaptation processes that may help explain the metabolic changes after RYGB.

MoEDAL is designed to identify new physics in the form of stable or pseudostable highly ionizing particles produced in high-energy Large Hadron Collider (LHC) collisions. Here we update our previous search for magnetic monopoles in Run 2 using the full trapping detector with almost four times more material and almost twice more integrated luminosity. For the first time at the LHC, the data were interpreted in terms of photon-fusion monopole direct production in addition to the Drell-Yan-like mechanism. The MoEDAL trapping detector, consisting of 794 kg of aluminum samples installed in the forward and lateral regions, was exposed to 4.0  fb^{-1} of 13 TeV proton-proton collisions at the LHCb interaction point and analyzed by searching for induced persistent currents after passage through a superconducting magnetometer. Magnetic charges equal to or above the Dirac charge are excluded in all samples. Monopole spins 0, ½, and 1 are considered and both velocity-independent and-dependent couplings are assumed. This search provides the best current laboratory constraints for monopoles with magnetic charges ranging from two to five times the Dirac charge.

Purpose: Transglutaminase type 2 (TG2) is an extracellular matrix crosslinking enzyme with a pivotal role in kidney fibrosis. We tested whether quantification of urinary TG2 may represent a noninvasive method to estimate the severity of kidney allograft fibrosis., Methods: We prospectively collected urine specimens from 18 deceased donor kidney transplant recipients at 1-day, 7-day, 1-month, 3-month, and 6-month posttransplant. In addition, kidney allograft tissue specimens at 0-day and 6-month posttransplant were sampled to analyze the correlation of urinary TG2 and kidney allograft fibrosis., Results: Thirteen recipients had increased interstitial fibrosis and tubular atrophy (IFTA) scores at the 6-month protocol biopsy (IFTA group). The mean level of urinary TG2 in the IFTA group was higher compared to that of 5 other recipients without IFTA (no IFTA group). Conversely, the mean level of urinary syndecan-4 in the IFTA group was lower than levels in patients without IFTA. In the IFTA group, double immunofluorescent staining revealed that TG2 intensity was significantly upregulated and colocalizations of TG2/heparin sulfate proteoglycan and nuclear syndecan-4 were prominent, usually around tubular structures., Conclusion: Urinary TG2 in early posttransplant periods is a potent biomarker for kidney allograft inflammation or fibrosis., Competing Interests: CONFLICTS OF INTEREST: No potential conflict of interest relevant to this article was reported.

Film-type thermoelectric generator (TEG) utilizing Bi-Te based paste has been highly considered as advanced power sources for the wearable electronic devices due to its light, thin and flexible characteristics when producing electricity from certain thermal resources such as human body heat. However, the application of the film-typed TEG has been often limited due to its low TE conversion efficiency caused by low electrical conductivity resulting from severe porosity. Thus, it is crucial to increase electrical properties via densification of the TE film. Here, we synthesized silver nanoparticle (AgNP)-dispersed (Bi,Sb)₂Te₃ (BSbT) powders to fabricate AgNP-BSbT pastes by adding organic binder. The synthesized AgNP-BSbT pastes were printed through a hand-painting process and were consolidated into Ag-doped BSbT (Ag-BSbT) thick film with a few hundreds μ m with controlled 2-step heat treatment. The microstructures of Ag-BSbT films show abnormally elongated grains but also the amount of porosities in the film significantly decreased by addition of AgNP. As a result, it is confirmed that the 0.072 at% Ag-BSbT thick film exhibits power factor of 2.93 × 10 -3 W/mK² at room temperature, which is comparable to that of practically utilized bulk materials. It is elucidated that the increase in power factor originates from the modulation between electrical conductivity and Seebeck coefficients due to increased hole carrier density at room temperature.

Background: Oral semaglutide is the first oral formulation of a glucagon-like peptide-1 (GLP-1) receptor agonist developed for the treatment of type 2 diabetes. We aimed to compare the efficacy and safety of flexible dose adjustments of oral semaglutide with sitagliptin 100 mg., Methods: In this 52-week, multicentre, randomised, open-label, phase 3a trial, we recruited patients with type 2 diabetes from 81 sites in ten countries. Patients were eligible if they were aged 18 years or older (19 years or older in South Korea), had type 2 diabetes (diagnosed ≥90 days before screening), HbA 1c of 7·5-9·5% (58-80 mmol/mol), and were inadequately controlled on stable daily doses of one or two oral glucose-lowering drugs (for 90 days or more before screening). Participants were randomly assigned (1:1) by use of an interactive web-response system, stratified by background glucose-lowering medication at screening, to oral semaglutide with flexible dose adjustments to 3, 7, or 14 mg once daily or sitagliptin 100 mg once daily. To approximate treatment individualisation in clinical practice, oral semaglutide dose could be adjusted on the basis of prespecified HbA 1c and tolerability criteria. Two efficacy-related estimands were prespecified: treatment policy (regardless of treatment discontinuation or use of rescue medication) and trial product (on treatment and without use of rescue medication) for participants randomly assigned to treatment. The primary endpoint was achievement of HbA 1c of less than 7% (53 mmol/mol) at week 52 and the confirmatory secondary efficacy endpoint was change in bodyweight from baseline to week 52. Safety was assessed in all participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT02849080, and European Clinical Trials Database, EudraCT number 2015-005593-38, and an open-label extension is ongoing., Findings: Between Sept 20, 2016, and Feb 7, 2017, of 804 patients assessed for eligibility, 504 were eligible and randomly assigned to oral semaglutide (n=253) or sitagliptin (n=251). Most participants were male (285 [57%] of 504) with a mean age of 57·4 years (SD 9·9). All participants were given at least one dose of their allocated study drug except for one participant in the sitagliptin group. From a mean baseline HbA 1c of 8·3% (SD 0·6%; 67 mmol/mol [SD 6·4]), a greater proportion of participants achieved an HbA 1c of less than 7% with oral semaglutide than did with sitagliptin (treatment policy estimand: 58% [134 of 230] vs 25% [60 of 238]; and trial product estimand: 63% [123 of 196] vs 28% [52 of 184]). The odds of achieving an HbA 1c of less than 7% was significantly better with oral semaglutide than sitagliptin (treatment policy estimand: odds ratio [OR] 4·40, 95% CI 2·89-6·70, p<0·0001; and trial product estimand: 5·54, 3·54-8·68, p<0·0001). The odds of decreasing mean bodyweight from baseline to week 52 were higher with oral semaglutide than with sitagliptin (estimated mean change in bodyweight, treatment policy estimand: -2·6 kg [SE 0·3] vs -0·7 kg [SE 0·2], estimated treatment difference [ETD] -1·9 kg, 95% CI -2·6 to -1·2; p<0·0001; and trial product estimand: -2·9 kg [SE 0·3] vs -0·8 kg [SE 0·3], ETD -2·2 kg, -2·9 to -1·5; p<0·0001). Adverse events occurred in 197 (78%) of 253 participants in the oral semaglutide group versus 172 (69%) of 250 in the sitagliptin group, and nausea was the most common adverse event with oral semaglutide (53 [21%]). Two deaths occurred in the sitagliptin group during the trial., Interpretation: Oral semaglutide, with flexible dose adjustment, based on efficacy and tolerability, provided superior glycaemic control and weight loss compared with sitagliptin, and with a safety profile consistent with subcutaneous GLP-1 receptor agonists., Funding: Novo Nordisk A/S., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Hexyl acetate (CAS No. 142-92-7) is a naturally occurring ester compound that has a fruity odor. Despite its frequent use as a nature-identical flavoring agent, there are limited repeated dose toxicity data for hexyl acetate. Here we performed a 13-week subchronic toxicity study of hexyl acetate in male and female Crl:CD(SD) rats under GLP regulations. Hexyl acetate was given orally by gavage at doses of 0, 100, 300, or 1,000 mg/kg/day using corn oil as the vehicle. No significant toxicological changes in general condition, body weights, food intake, ophthalmology, hematology, organ weights, and histopathological findings were observed in any groups. Urinalysis revealed occult blood in two male animals treated with 1,000 mg/kg/day hexyl acetate, and one showed red blood cells in the urine sediment. Furthermore, blood biochemistry showed a significant increase in inorganic phosphorus levels in males treated with 1,000 mg/kg/day hexyl acetate. These results indicated that the no-observed-adverse-effect level (NOAEL) of hexyl acetate was 300 mg/kg/day for males and more than 1,000 mg/kg/day for females.

Phosphorylated histone H2AX (γ-H2AX) has been demonstrated as a DNA damage marker both in vitro and in vivo. We previously reported the effects of genotoxic carcinogens in the urinary bladder of rats by immunohistochemical analysis of γ-H2AX using samples from 28-day repeated-dose tests. To evaluate the application of γ-H2AX as a biomarker of carcinogenicity in the bladder, we examined species differences in γ-H2AX formation in the urinary bladder of mice. Six-week-old male B6C3F 1 mice were treated orally with 12 chemicals for 4 weeks. Immunohistochemical analysis demonstrated that N-butyl-N-(4-hydroxybutyl)nitrosamine, p-cresidine and 2-acetylaminofluorene (2-AAF), classified as genotoxic bladder carcinogens, induced significant increases in γ-H2AX levels in the bladder urothelium. In contrast, genotoxic (2-nitroanisole, glycidol, N-nitrosodiethylamine and acrylamide) and non-genotoxic (dimethylarsinic acid and melamine) non-bladder carcinogens did not upregulate γ-H2AX. Importantly, 2-nitroanisole, a potent genotoxic bladder carcinogen in rats, significantly increased the proportion of γ-H2AX-positive cells in rats only, reflecting differences in carcinogenicity in the urinary bladder between rats and mice. Significant upregulation of γ-H2AX was also induced by uracil, a non-genotoxic bladder carcinogen that may be associated with cell proliferation, as demonstrated by increased Ki67 expression. 2-AAF caused γ-H2AX formation mainly in the superficial layer, together with reduced and disorganized expression of uroplakin III, unlike in rats, suggesting the mouse-specific cytotoxicity of 2-AAF in umbrella cells. These results suggest γ-H2AX is a useful biomarker reflecting species differences in carcinogenicity in the urinary bladder., (© 2019 John Wiley & Sons, Ltd.)

Tyrosine kinase inhibitors (TKIs) are widely accepted as treatment for metastatic clear cell renal cell carcinoma (ccRCC). However, most patients eventually experience disease progression despite TKI treatment, even if the initial response is favorable. To define the underlying mechanism of TKI resistance, 10 TKI-treated metastatic ccRCC cases in which tumor samples were harvested before treatment and immediately after disease progression were examined. Gene expression profiles and copy number variations of matched pre- and post-treatment tumor samples were investigated. Altered biologic characteristics were confirmed in sunitinib-resistant ccRCC cell lines, which were generated by long-term treatment with sunitinib-containing media. Gene transcript levels related to the cell cycle and epithelial-mesenchymal transition (EMT) were significantly upregulated in the treated tumor samples compared with the pre-treatment samples. The mitotic count and sarcomatoid component were significantly increased in treated tumor samples. Alteration of EMT-related genes was also demonstrated in a sunitinib-resistant ccRCC cell line that showed enhanced migration and invasion compared to the parent cell line. siRNA-induced inhibition of EMT-related gene expression significantly suppressed the migration and invasion capacity of TKI-resistant cell lines. The present study shows that both ccRCC cases that progressed after TKI treatment and sunitinib-resistant ccRCC cell lines demonstrated alteration of EMT-related gene expression and enhancement of EMT-related behavior. These results suggest that EMT may explain the aggressive behavior of TKI-resistant ccRCC.

Objectives: To assess the impact of conversion from histologically positive to negative soft tissue margins at the apex and bladder neck on biochemical recurrence-free survival (BCRFS) and distant metastasis-free survival (DMFS) after radical prostatectomy (RP) for prostate cancer., Materials and Methods: The records of 2 013 patients who underwent RP and intra-operative frozen section (IFS) analysis between July 2007 and June 2016 were reviewed. IFS analysis of the urethra and bladder neck was performed, and if malignant or atypical cells remained, further resection with the aim of achieving histological negativity was carried out. Patients were divided into three groups according to the findings: those with a negative surgical margin (NSM), a positive surgical margin converted to negative (NCSM) and a persistent positive surgical margin (PSM)., Results: Among the 2 013 patients, rates of NSMs, NCSMs and PSMs were 75.1%, 4.9%, and 20.0%, respectively. The 5-year BCRFS rates of patients with NSMs, NCSMs and PSMs were 89.6%, 85.1% and 57.1%, respectively (P < 0.001). In both pathological (p)T2 and pT3 cancers, the 5-year BCRFS rate for patients with NCSMs was similar to that for patients with NSMs, and higher than for patients with PSMs. The 7-year DMFS rates of patients with NSMs, NCSMs and PSMs were 97.8%, 99.1% and 89.4%, respectively (P < 0.001). Among patients with pT3 cancers, the 7-year DMFS rate was significantly higher in the NCSM group than in the PSM group (98.0% vs 86.7%; P = 0.023), but not among those with pT2 cancers (100% vs 96.9%; P = 0.616). The 5-year BCRFS rate for the NCSM group was not significantly different from that of the NSM group among the patients with low- (96.3% vs 95.8%) and intermediate-risk disease (91.1% vs 82.8%), but was lower than that of the NSM group among patients in the high-risk group (73.2% vs 54.7%)., Conclusions: Conversion of the soft tissue margin at the prostate apex and bladder neck from histologically positive to negative improved the BCRFS and DMFS after RP for prostate cancer; however, the benefit of conversion was not apparent in patients in the high-risk group., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Background: Many factors influence bone metastases of lung cancer, and several studies report about survival of skeletal metastasis. However, few studies have focused on identifying the prognostic factors for skeletal metastasis of lung cancer, especially following orthopedic surgery. We conducted a retrospective analysis of the clinical characteristics of skeletal metastasis from lung cancer and discuss the prognostic factors., Methods: We performed a medical record review of 202 patients who were diagnosed with skeletal metastasis from lung cancer. Adenocarcinoma was found in 116 patients (57.4%), squamous cell carcinoma in 29 (14.4%), small-cell lung cancer (SCLC) in 37 (18.7%), and large-cell carcinoma and other types of cancer in 20 patients (9.9%). Orthopedic surgery for skeletal metastasis was performed in 41 patients (20.3%)., Results: Lung cancer survival was 12.1 months. After diagnosis of lung cancer, skeletal metastasis was found at a mean of 2.5 months, and skeletal metastasis survival was 9.8 months. Lung cancer survival in patients younger than 60 years was 13.8 months, and lung cancer survival in patients 60 years or older was 10.8 months (p = 0.009). Skeletal metastasis survival in patients younger than 60 years was 11.0 months, and skeletal metastasis survival in patients 60 years or older was 8.8 months (p = 0.002). Mean skeletal metastasis survival with surgery was 12.6 months and without surgery was 9.1 months (p < 0.000). In the multivariate analysis of lung cancer survival, age under 60 years [HR (95% CI) 1.549 (1.122-2.139), p = 0.008], non-small cell lung cancer pathology type [HR (95% CI) 1.711 (1.157-2.532), p = 0.008], chemotherapy for skeletal metastasis [HR (95% CI) 8.064 (3.981-16.332), p < 0.000], and radiation therapy for skeletal metastasis [HR (95% CI) 1.791 (1.170-2.742), p = 0.007] were significant, independent, good prognostic factors. In the multivariate analysis of skeletal metastasis survival, age under 60 years [HR (95% CI) 1.549 (1.124-2.134), p = 0.007], non-small cell lung cancer pathology type [HR (95% CI) 2.045 (1.373-3.047), p < 0.000], chemotherapy for skeletal metastasis [HR (95% CI) 7.121 (3.542-14.317), p < 0.000], and orthopedic surgical treatment for skeletal metastasis [HR (95% CI) 1.710 (1.148-2.547), p = 0.008] were significant, independent, good prognostic factors., Conclusions: Patients who survived longer were less than 60 years old, received chemotherapy as treatment for skeletal metastasis, had NSCLC rather than SCLC, and underwent orthopedic surgery for skeletal metastasis.

Urban-use pesticides are of increasing concern as they are widely used and have been linked to toxicity of aquatic organisms. To assess the occurrence and treatment of these pesticides in stormwater runoff, an approach combining field sampling and watershed-scale modeling was employed. Stormwater samples were collected at four locations in the lower San Diego River watershed during a storm event and analyzed for fipronil, three of its degradation products, and eight pyrethroids. All 12 compounds were detected with frequency ranging from 50 to 100%. Field results indicate pesticide pollution is ubiquitous at levels above toxicity benchmarks and that runoff may be a major pollutant source to urban surface waters. A watershed-scale stormwater model was developed, calibrated using collected data, and evaluated for pesticide storm load and concentrations under several management scenarios. Modeling results show that enhanced stormwater control measures, such as biochar-amended biofilters, reduce both pesticide storm load and toxicity benchmark exceedances, while conventional biofilters reduce the storm load but provide minimal toxicity benchmark exceedance reduction. Consequently, biochar amendment has the potential to broadly improve water quality at the watershed scale, particularly when meeting concentration-based metrics such as toxicity benchmarks. This research motivates future work to demonstrate the reliability of full-scale enhanced stormwater control measures to treat pollutants of emerging concern.

Arsenic is a known human carcinogen, inducing tumors of the lung, urinary bladder, skin, liver and prostate. However, there are no reports of prostate tumors induced by arsenicals in in vivo animal models. In a previous study, we found that HMGB2 expression was a predictive marker for prostate carcinogens in the rat 4-week repeated dose test. In this study, six-week-old male F344 rats were orally treated with a total of six chemicals (2-acetylaminofluorene (2-AAF), p-cresidine, dimethylarsinic acid (DMA), glycidol, N-nitrosodiethylamine and acrylamide) for four weeks. Animals were sacrificed at the end of the study, and HMGB2 and Ki-67 immunohistochemistry was performed. The numbers of HMGB2- and Ki-67- positive cells in all prostate lobes were significantly increased by DMA, one of the arsenicals, compared with the controls. Meanwhile, the number of Ki-67-positive cells in lateral and dorsal prostate lobes was significantly decreased by 2-AAF with the reduction of body weight, but HMGB2 expression was not. The other chemicals did not change HMGB2 and Ki-67 expression. These data indicate that DMA may have an ability to enhance prostate carcinogenesis.

Isoeugenyl methyl ether (CAS No. 93-16-3) is a food additive used as a nature identical flavoring agent. To determine the toxicity profile and the no-observed-adverse-effect level (NOAEL), we performed a subchronic toxicity test in male and female F344/DuCrj rats by intragastric administration of isoeugenyl methyl ether at doses of 8, 40, and 200 mg/kg body weight (BW)/day for 13 weeks. In this study, BW gain in the male 200 mg/kg BW/day group was decreased from week 9. In serum biochemistry, decreased triglycerides were observed in the male 200 mg/kg BW/day group. In organ weights, increases in both absolute and relative liver weights were observed in both sexes in the 200 mg/kg BW/day group. In histopathological examination, hepatocyte hypertrophy was observed in the male 200 mg/kg BW/day group. Based on these results, we concluded that the main target organ of isoeugenyl methyl ether was the liver and that the NOAEL of isoeugenyl methyl ether for both male and female F344/DuCrj rats was estimated to be 40 mg/kg BW/day., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: This study evaluated the efficacy of a smartphone-based, patient-centered diabetes care system (mDiabetes) for type 2 diabetes that contains comprehensive modules for glucose monitoring, diet, physical activity, and a clinical decision support system., Research Design and Methods: We conducted a 24-week, multicenter, randomized controlled trial with adult patients with inadequately controlled type 2 diabetes. The patients were randomly assigned to the mDiabetes group or the paper logbook (pLogbook) group. The primary end point was the difference of the change in HbA 1c from baseline between the two groups., Results: HbA 1c reduction from baseline was greater in the mDiabetes group (-0.40 ± 0.09%, n = 90) than in the pLogbook group (-0.06 ± 0.10%, n = 82). The difference of adjusted mean changes was 0.35% (95% CI 0.14-0.55, P = 0.001). The proportion of patients whose HbA 1c fell below 7.0% (53 mmol/mol) was 41.1% for the mDiabetes group and 20.7% for the pLogbook group (odds ratio [OR] 2.01, 95% CI 1.24-3.25, P = 0.003). The percentage of patients who attained HbA 1c levels below 7.0% (53 mmol/mol) without hypoglycemia was 31.1% in the mDiabetes group and 17.1% in the pLogbook group (OR 1.82, 95% CI 1.03-3.21, P = 0.024). There was no difference in the event numbers of severe hyperglycemia and hypoglycemia between the two groups., Conclusions: The implementation of the mDiabetes for patients with inadequately controlled type 2 diabetes resulted in a significant reduction in HbA 1c levels, with tolerable safety profiles., (© 2018 by the American Diabetes Association.)

To investigate the chemopreventive mechanisms of 4-Methylthio-3-butenyl isothiocyanate (MTBITC), we analyzed cell viability, cell cycle distribution, and expression levels for cell cycle and apoptosis-related proteins in MTBITC-treated malignant esophageal KYSE510 cells, with and without the reactive oxygen species (ROS) scavenger N-acethyl-L-Cysteine (NAC). MTBITC dose-dependently reduced cell viability and Bcl2 protein expression, while it induced cleavages of caspase-3, caspase-9, and PARP-1, suggesting that reduced cell viability occurred through the mitochondrial apoptotic pathway in KYSE510 cells. In cell cycle distribution analysis, MTBITC (20-40 µM) induced cell cycle arrest at G2/M phase. Furthermore, MTBITC induced Chk1 and Akt phosphorylations and decreased p27 protein expression. Both apoptotic- and cell cycle-related changes induced by MTBITC treatment were abolished by NAC. These results suggest that MTBITC has chemopreventive potential for esophageal carcinogenesis by elimination of cancer cells via induction of mitochondrial apoptotic cell death, G2/M cell cycle arrest, and ROS production.

Introduction: Uterine-conservative surgery via laparoscopy is a challengeable and high risk because of heavy intra-operative bleeding events in reproductive women with highly vascular uterine benign disease. There are three reported cases of women with highly vascular uterine benign diseases and high risk of intra-operative heavy bleeding, but were treated successfully to control intra-operative heavy bleeding risk by transient occlusion of the uterine artery (TOUA) through laparoscopy and resulted in safe conservation of the uterus., Case Presentation: The cases of women with high risk of heavy bleeding during therapeutic procedure included cesarean scar pregnancy, hydatid form mole on cesarean scar, and cervical pregnancy. All these women had the strong desire to presere their fertility and uterus. In all the three cases, we used the method of TOUA and performed therapeutic surgeries successfully, with less bleeding and safe conservation of the uterus through laparoscopy., Conclusion: Laparoscopic TOUA could be a therapeutic option to manage heavy intra-operative bleeding during conservative uterine surgeries associated with the risk of heavy bleeding., Competing Interests: Conflicts of Interest: All authors declare no conflict of interest regarding the publication of this article.

Fibroadenoma (FA) is a common mammary fibroepithelial tumor. The tumor size of the FA is increased by estrogen, progesterone, prolactin, and pregnancy, whereas it decreases after menopause. These observations in humans indicate that FA is hormone dependent. In rats, the most common mammary neoplasm is also FA. Expression levels of Twist1, a transcriptional regulator of epithelial-mesenchymal transition, were examined in paraffin-embedded tissue sections of an experimental rat breast model to find physiological alternations coincident with reproductive hormonal changes. Twenty-three Fischer 344/Brown Norway F1 hybrid rats were used as 14- to 16-week-old adolescent rats (n=3), pregnant rats (n=4), and lactating rats (n=6) in addition to rats over 100-weeks-old that exhibited aging (n=3) and FA (n=7). Seventy-six cases of chemically induced breast carcinoma and two cases of FA in Sprague Dawley rats were also examined. Using tissue sections, we observed that Twist1-positive mesenchymal cells were predominantly located in the periductal region in adolescent and pregnant rats and in the terminal duct lobular unit in pregnant and elderly rats. Twist1 was also expressed diffusely in the mesenchymal cells of FA rats. Twist1-positive cancer-associated mesenchymal cells were found more frequently in the invasive components of breast carcinomas than in intraductal components. The expressions of Twist1 in mesenchymal cells were induced by physiological and pathological stimuli, suggesting the biological role of Twist1 in tissue structure. Further study may reveal the role of Twist1 in mesenchymal cells of mammary glands in rats.

Vascular endothelial growth factor receptor (VEGFR)-targeted therapy improved the outcome of metastatic renal cell carcinoma (mRCC) patients. However, a prediction of the response to VEGFR-tyrosine kinase inhibitor (TKI) remains to be elucidated. We aimed to develop a classifier for VEGFR-TKI responsiveness in mRCC patients. Among 101 mRCC patients, ones with complete response, partial response, or ≥24 weeks stable disease in response to VEGFR-TKI treatment were defined as clinical benefit group, whereas patients with <24 weeks stable disease or progressive disease were classified as clinical non-benefit group. Clinicolaboratory-histopathological data, 41 gene mutations, 20 protein expression levels and 1733 miRNA expression levels were compared between clinical benefit and non-benefit groups. The classifier was built using support vector machine (SVM). Seventy-three patients were clinical benefit group, and 28 patients were clinical non-benefit group. Significantly different features between the groups were as follows: age, time from diagnosis to TKI initiation, thrombocytosis, tumor size, pT stage, ISUP grade, sarcomatoid change, necrosis, lymph node metastasis and expression of pAKT, PD-L1, PD-L2, FGFR2, pS6, PDGFRβ, HIF-1α, IL-8, CA9 and miR-421 (all, P < 0.05). A classifier including necrosis, sarcomatoid component and HIF-1α was built with 0.87 accuracy using SVM. When the classifier was checked against all patients, the apparent accuracy was 0.875 (95% CI, 0.782-0.938). The classifier can be presented as a simple decision tree for clinical use. We developed a VEGFR-TKI response classifier based on comprehensive inclusion of clinicolaboratory-histopathological, immunohistochemical, mutation and miRNA features that may help to guide appropriate treatment in mRCC patients.

Safety issues regarding consumer products contaminated with trace amounts of chemicals are of great concern to consumers, with the degree of concern occasionally escalating to the psychological syndrome, chemophobia, i.e., the fear of chemicals. Hazardous substances frequently implicated in safety concerns include heavy metals (arsenic, mercury, cadmium, and lead), volatile organic compounds (VOC) such as benzene and o-toluidine, pesticides, carcinogens, radioactive substances, and endocrine disrupting chemicals (EDC) such as bisphenol A and phthalates. To improve communication of risk to society, members of academia, government, consumer organizations, and industry participated in this workshop to discuss and exchange perspectives on trace chemical safety. From the perspective of academia, integrated risk assessments need to be implemented to encompass various exposure sources and routes. The identification and investigation of new exposure-related biomarkers are also recommended to verify direct causal relationships between specific chemical exposure and effects on human health. As for regulation, governments need to establish and maintain acceptable limits for trace chemicals in products. In addition, harmonized efforts need to be undertaken among government agencies to share regulatory limits and effectively control trace chemicals in consumer products. Manufacturers need to faithfully abide by Good Manufacturing Practice (GMP) guidelines, monitor sources of contamination, and minimize these for consumer safety. To effectively resolve safety issues arising from trace chemicals exposure, collaborative efforts are needed involving academia, government, consumer organizations, and industry. Further, scientific evidence-based risk assessment is a critical approach to effectively manage trace chemical safety issues.

5-Hexenyl isothiocyanate (5-HeITC) is a naturally derived flavoring substance from Wasabia japonica. To clarify the toxicological profile of 5-HeITC, we performed a subchronic toxicity study of 5-HeITC with intragastric administration at daily doses of 0, 3, 12, or 48 mg/kg body weight (BW) to 6-week-old male and female F344/DuCrj rats for 13 weeks. Body weight gain was decreased in the male 48 mg/kg BW group. Decreased triglycerides were observed in the male over 12 mg/kg BW and female 48 mg/kg BW groups. Decreased total cholesterol was observed in the male 48 mg/kg BW group. Increases in relative liver weights were observed in the male 48 mg/kg BW and female over 12 mg/kg BW groups. Increases in absolute and relative heart weights were observed in the female over 12 mg/kg BW groups. Simple hyperplasia in the urinary bladder was found in the male and female 12 mg/kg BW groups, and nodular hyperplasia was found in the female 48 mg/kg BW group. Based on these findings, the target organs of 5-HeITC were determined to be the urinary bladder, heart, and liver. The no-observed-adverse-effect level of 5-HeITC for both sexes was estimated to be 3 mg/kg BW., (Copyright © 2018. Published by Elsevier Ltd.)

Objectives: The project Seoul Atopy ∙ Asthma-friendly School investigated the current status of childhood asthma to enable formulation of a preventative policy. We evaluated the current prevalence of childhood asthma in Seoul and its trends and related factors., Methods: The project was conducted annually from 2011 to 2016 and involved around 35 000 children aged 1-13 years. Based on the International Study of Asthma and Allergies in Childhood guidelines, the survey involved parents. The associations of the particulate matter (PM10) concentration, and the number of days on which the daily air quality guidance level was exceeded in the 25 districts of Seoul, with the prevalence of asthma were assessed., Results: The age-standardized asthma prevalence in 2011 and 2016 was 6.74 and 4.02%, respectively. The prevalence of lifetime asthma treatment and treatment during the last 12 months tended to decrease from 2011 to 2016. Asthma treatment was significantly correlated with the number of days on which the daily air quality guidance level was exceeded, but not with the PM10 concentration., Conclusions: This study reports the prevalence of asthma among children in Seoul and confirmed the relationship between childhood asthma and known risk factors in a large-scale survey.

Background: Recently there has been dramatic increase in the use of mobile technologies for health (m-Health) in both high and low- and middle-income countries (LMICs). However, little is known whether m-Health interventions in LMICs are based on relevant theories critical for effective implementation of such interventions. This review aimed to systematically identify m-Health studies on health behavioral changes in LMICs and to examine how each study applied behavior change theories., Materials and Methods: A systematic review was conducted using the standard method from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. By searching electronic databases (MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials [CENTRAL]), we identified eligible studies published in English from inception to June 30, 2017. For the identified m-Health studies in LMICs, we examined their theoretical bases, use of behavior change techniques (BCTs), and modes of delivery., Results: A total of 14 m-Health studies on behavioral changes were identified and, among them, only 5 studies adopted behavior change theory. The most frequently cited theory was the health belief model, which was adopted in three studies. Likewise, studies have applied only a limited number of BCTs. Among the seven BCTs identified, the most frequently used one was the social support (practical) technique for medication reminder and medical appointment. m-Health studies in LMICs most commonly used short messaging services and phone calls as modes of delivery for behavior change interventions., Conclusions: m-Health studies in LMICs are suboptimally based on behavior change theory yet. To maximize effectiveness of m-Health, rigorous delivery methods as well as theory-based intervention designs will be needed.

Background: Confluent and reticulated papillomatosis (CRP) is an uncommon dermatosis characterized by hyperpigmented scaly macules or papillomatous papules coalescing into confluent patches or plaques centrally with a reticular pattern peripherally. Few studies regarding this have been reported in the literature., Objective: The purpose of this study was to investigate the clinical and histologic characteristics of CRP in Korean patients according to anatomic site and age., Methods: We retrospectively reviewed the medical records, clinical photographs, and 40 histopathologic slides of 29 patients diagnosed with CRP., Results: Sixteen adults and 13 adolescents were included. The predominantly involved anatomic sites were the trunk (89.7%) and axillae (27.6%); flexural area involvement was mainly found in the adolescent group. The mean disease duration was 2.3 times longer in the adult group than in the adolescent group. The histopathologic features included hyperkeratosis (95.0%), acanthosis (87.5%), and papillomatosis (77.5%) in the epidermis. In the adult group, only 10 specimens (52.6%) showed mild to moderate papillomatosis. There was no relationship between the histologic findings and disease duration; however, the former was associated with the anatomic site., Conclusion: The present study is the first to present the clinical and histologic features of CRP according to age and anatomic site in Korean patients. The patients in this study more frequently had fungal infections (31%) than patients in a previous study (12.8%). Histologic changes were more prominent in the adolescent group than in the adult group and in the flexural area than in the non-flexural area., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose., (Copyright © 2018 The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)

This study aimed to determine the dose-response relationship between exercise duration and task switching in older adults. Acute moderate intensity aerobic exercise for 20 min resulted in shorter response times than control and 10-min sessions in the heterogeneous, non-switch, and switch conditions, but not in the homogeneous condition. Additionally, linear and cubic trends between exercise duration and global switching performance as well as local switching performance were revealed with faster times being predicted by longer duration exercise; however, the cubic relationship resulted in performance following the 45-min session being not significantly different from the other three sessions. Acute aerobic moderate intensity exercise for 20 min is an effective duration to improve task switching. Although a longer duration of exercise is not optimal for benefiting task switching, it does not harm task switching in older adults and hence may be of value for other health-related reasons.

We investigated ethnicity-specific exonic variants of type 2 diabetes (T2D) and its related clinical phenotypes in an East Asian population. We performed whole-exome sequencing in 917 T2D case and control subjects, and the findings were validated by exome array genotyping in 3,026 participants. In silico replication was conducted for seven nonsynonymous variants in an additional 13,122 participants. Single-variant and gene-based association tests for T2D were analyzed. A total of 728,838 variants were identified by whole-exome sequencing. Among nonsynonymous variants, PAX4 Arg192His increased risk of T2D and GLP1R Arg131Gln decreased risk of T2D in genome-wide significance (odds ratio [OR] 1.48, P = 4.47 × 10 -16 and OR 0.84, P = 3.55 × 10 -8 , respectively). Another variant at PAX4 192 codon Arg192Ser was nominally associated with T2D (OR 1.62, P = 5.18 × 10 -4 ). In T2D patients, PAX4 Arg192His was associated with earlier age at diagnosis, and GLP1R Arg131Gln was associated with decreased risk of cardiovascular disease. In control subjects without diabetes, the PAX4 Arg192His was associated with higher fasting glucose and GLP1R Arg131Gln was associated with lower fasting glucose and HbA 1c level. Gene-based analysis revealed that SLC30A8 was most significantly associated with decreased risk of T2D ( P = 1.0 × 10 -4 ). In summary, we have identified nonsynonymous variants associated with risk of T2D and related phenotypes in Koreans., (© 2018 by the American Diabetes Association.)

Objective: To investigate the effect of depressive symptoms on ill-health retirement (IHR)., Methods: Data were collected from the Korean Longitudinal Study of Ageing which conducted biennially from 2006 to 2014. IHR were defined as those who retired due to their health problems. The short-form Center for Epidemiological Studies-Depression scale served as outcome measure for definition of depressive symptoms. Hazard ratios of IHR were estimated by Cox regression., Results: We observed that depressive symptoms significantly increased risk of IHR during 8-year follow-up period. Compared with those without depressive symptoms, depressed worker had 1.27-fold elevated risk for IHR. Subgroup analysis showed that the association between depressive symptoms and IHR is greater in the elders, women, and lower income group than the others., Conclusion: Depressive symptoms independently predicted IHR. Moreover, age, sex, and socioeconomic status modified these effects.

Aims/introduction: Protein preload improves postprandial glycemia by stimulating secretion of insulin and incretin hormones. However, it requires a large dose of protein to produce a significant effect. The present study was carried out to investigate the postprandial glucose-lowering effect of a premeal protein-enriched, dietary fiber-fortified bar (PFB), which contains moderate amounts of protein, in individuals with type 2 diabetes mellitus or normal glucose tolerance (NGT)., Materials and Methods: The participants (15 type 2 diabetes mellitus and 15 NGT) were randomly assigned to either a premeal or postmeal PFB group and underwent two mixed meal tolerance tests, 1 week apart in reverse order. Plasma levels of glucose, insulin, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide were measured., Results: During the mixed meal tolerance tests, the incremental area under the curve from 0 to 180 min of plasma glucose levels was lower with premeal PFB than with postmeal PFB in the type 2 diabetes mellitus (14,723 ± 1,310 mg min/dL vs 19,642 ± 1,367 mg min/dL; P = 0.0002) and NGT participants (3,943 ± 416 mg min/dL vs 4,827 ± 520 mg min/dL, P = 0.0296). In the type 2 diabetes mellitus participants, insulinogenic index and the incremental area under the curve from 0 to 180 min of plasma total glucagon-like peptide-1 levels were higher with premeal PFB than with postmeal PFB, but not in the NGT participants. There was no difference in postprandial glucose-dependent insulinotropic polypeptide levels between premeal and postmeal PFB in both groups., Conclusions: Acute administration of premeal PFB decreased postprandial glucose excursion in both type 2 diabetes mellitus and NGT participants. In the type 2 diabetes mellitus participants, premeal PFB augmented the early-phase insulin secretion, possibly through enhancing glucagon-like peptide-1 secretion., (© 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Aims: To compare the efficacy and safety of once-weekly glucagon-like peptide-1 receptor agonist dulaglutide 1.5 and 0.75 mg with glimepiride in East-Asian patients with type 2 diabetes (T2D)., Materials and Methods: In this phase III, multinational, multicentre, double-blind, randomized, parallel-arm, 26-week study, patients with inadequate glycaemic control were randomized 1:1:1 to once-weekly dulaglutide 1.5 or 0.75 mg or daily glimepiride (1-3 mg/d). The primary endpoint was assessment of the non-inferiority of dulaglutide (1.5 mg), as measured by change in glycated haemoglobin (HbA1c), compared with glimepiride using a 0.4% non-inferiority margin., Results: A total of 737 patients were randomized (dulaglutide 1.5 mg, n = 244; dulaglutide 0.75 mg, n = 248; glimepiride, n = 245). At week 26, both doses of dulaglutide were non-inferior and also superior to glimepiride for HbA1c reduction from baseline with a least squares mean difference of -6.34 mmol/mol (95% confidence interval [CI] -8.31, -4.26) or -0.58% (95% CI -0.76, -0.39) for dulaglutide 1.5 mg and -3.50 mmol/mol (95% CI -5.47, -1.42) or -0.32% (95% CI -0.50, -0.13) for dulaglutide 0.75 mg (P < .001). A greater proportion of patients in the dulaglutide 1.5 mg group achieved the HbA1c target of <53 mmol/mol (<7.0%) compared with the glimepiride group (74.1% vs 57.4%; P < .001). The mean body weight decreased (P < .005) and total hypoglycaemia rates were lower (P < .001) in the dulaglutide groups compared with the glimepiride group. The most common drug-related adverse events in both dulaglutide groups (≥5% of patients) included diarrhoea, nausea, increased lipase, decreased appetite, abdominal distension and vomiting., Conclusions: Dulaglutide (both doses) demonstrated superior glycaemic control vs glimepiride, with a favourable tolerability and safety profile in East-Asian patients with T2D., (© 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

The peroxisome proliferator-activated receptor-γ (PPARγ) improves whole-body insulin sensitivity by regulating the adipogenic and metabolic functions of mature adipocytes. We have previously demonstrated that an active splice variant of X-box binding protein 1 (XBP1s) enhances PPARγ expression during adipogenesis. In this study, we investigated the role of XBP1s, particularly with respect to PPARγ, in the mechanisms underlying insulin sensitivity in mature adipocytes. Insulin was able to stimulate XBP1s generation by activating inositol-requiring enzyme 1 (IRE1) α and was also able to increase its transcriptional activity by inducing nuclear translocation. XBP1s also upregulated the levels of phosphorylated IRS1 and AKT, demonstrating a positive feedback regulatory mechanism linking insulin and XBP1s. XBP1s enhanced the expression of fibroblast growth factor 21 and, in turn, increased PPARγ activity, translocation of GLUT4 to the cell surface, and glucose uptake rate in adipocytes. In addition, XBP1s abolished palmitate-induced insulin resistance in adipocytes by increasing adiponectin secretion, repressing the secretion of pro-inflammatory adipokines such as leptin, monocyte chemoattractant protein 1, and tumor necrosis factor α, and decreasing fatty acid release. These findings provide a novel mechanism by which XBP1s stimulate insulin sensitivity in adipocytes through fibroblast growth factor 21 induction and PPARγ activation.

We evaluated bioturbation as a facilitator for in situ treatment with a thin layer of activated carbon to treat dichlorodiphenyltrichloroethane (DDT)-contaminated sediment and contaminant influx by sediment deposition. Using the freshwater worm Lumbriculus variegatus as a bioturbator, microcosm time-series studies were conducted for 4 mo and monitored for DDT flux and porewater concentration profiles by polyethylene passive samplers. With bioturbators present, the thin-layer activated carbon amendment reduced DDT flux by >90% compared with the same simulated scenario without activated carbon amendment. In contrast, a clean sediment cap without activated carbon was ineffective in reducing flux when bioturbation was present. In simulated scenarios with contaminant influx through deposition of contaminated sediment, bioturbation facilitated in situ activated carbon treatment, reducing 4-mo DDT flux by 77% compared with the same scenario without bioturbation. Porewater concentration profiles and activated carbon dose profiles confirmed effective mixing of activated carbon particles down to 1-cm depth. A mass transfer model was developed to predict flux with consideration of bioturbation and sediment deposition processes. Predicted flux values were consistent with experimental results and confirm that bioturbation activity helps reduce DDT sediment-to-water fluxes in activated carbon-treated sediment with recontamination by contaminated sediment deposition. To our knowledge, this is the first study to combine experimental and modeling results showing how bioturbation enhances activated carbon amendment effectiveness against ongoing contaminant influx by sediment deposition. Environ Toxicol Chem 2018;37:2013-2021. © 2018 SETAC., (© 2018 SETAC.)

Aim: To study the effects of angiotensin receptor blockers (ARBs) on insulin secretion in hypertensive patients with type 2 diabetes., Materials and Methods: A total of 41 patients were enrolled in this open-label, active comparator-controlled, crossover study. After a 2-week run-in period with amlodipine, the participants were assigned to receive either fimasartan (60-120 mg daily) or amlodipine (5-10 mg daily) for 16 weeks. Thereafter, they were treated with the other drug for another 16 weeks. Physical examinations and laboratory tests were performed before and after each treatment., Results: Blood pressure, glycated haemoglobin and oral glucose tolerance test (OGTT) values were similar with each treatment. Fimasartan treatment significantly increased median (range) homeostatic assessment of β-cell function values (49.9 [22.5-174.4] vs 46.9 [15.6-148.0]), area under the curve of insulin during OGTT (27 284 [9501-94 525] vs 26 818 [8112-76 704] pmol/L × min), insulinogenic index at 60 minutes (19.7 [3.0-131.2] vs 15.0 [2.4-103.8] pmol/mmol) and at 120 minutes (19.1 [1.9-85.5] vs 12.6 [-4.3-178.8] pmol/mmol) compared with those with amlodipine (all P < .05); however, acute insulin response and insulin resistance indices were similar for both agents., Conclusions: Compared with amlodipine, fimasartan increased late-phase glucose-stimulated insulin secretion in patients with type 2 diabetes and hypertension. This finding suggests that ARBs would be more beneficial in such patients compared with other classes of anti-hypertensives., (© 2018 John Wiley & Sons Ltd.)

Aims/introduction: The combination of dipeptidyl peptidase-4 (DPP4) inhibitors and α-glucosidase inhibitors (AGIs) might provide an additive or synergistic glucose-lowering effect, as they have a complementary mode of action. In the present study, we examined the efficacy and safety of the addition of a DPP4 inhibitor to patients with type 2 diabetes inadequately controlled with an AGI., Materials and Methods: We carried out an electronic search of MEDLINE, EMBASE, the Cochrane Library and Clinicaltrials.gov through October 2016. Randomized controlled trials written in English that compared DPP4 inhibitors plus AGI (DPP4i/AGI) and placebo plus AGI (PCB/AGI) in patients with type 2 diabetes were selected. Data on the study characteristics, efficacy and safety outcomes were extracted, and the risk of potential biases was assessed. The efficacy and safety of DPP4i/AGI and PCB/AGI were compared., Results: Of 756 potentially relevant published articles and 40 registered trials, five studies including 845 patients randomized to DPP4i/AGI and 832 patients randomized to PCB/AGI were included for meta-analysis. Compared with PCB/AGI, DPP4i/AGI showed a greater reduction in glycated hemoglobin (weighted mean difference -1.2%, 95% confidence interval -1.6 to -0.8), fasting plasma glucose and 2-h postprandial plasma glucose levels, with no increase in bodyweight. The risks of hypoglycemia and gastrointestinal adverse events were similar between DPP4i/AGI and PCB/AGI., Conclusions: The addition of a DPP4 inhibitor to patients with type 2 diabetes inadequately controlled with an AGI achieved better glycemic control without further increasing the risk of weight gain and hypoglycemia., (© 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Objectives: Population aging has increased the burden of chronic diseases globally. mHealth is often cited as a viable solution to enhance the management of chronic conditions. In this study, we conducted a systematic review of mHealth interventions for the self-management of chronic diseases in Korea, a highly-connected country with a high chronic care burden., Methods: Five databases were searched for relevant empirical studies that employed randomized controlled trial (RCT) or quasi-experimental methods published in English or Korean from the years 2008 to 2018. The selected studies were reviewed according to the PRISMA guidelines. The selected studies were classified using the Individual and Family Self-Management Theory conceptual framework., Results: Sixteen studies met the inclusion criteria, 9 of which were targeted towards diabetes management, and 7 of which were RCTs. Other target diseases included hypertension, stroke, asthma, and others. mHealth interventions were primarily delivered through smartphone applications, mobile phones connected to a monitoring device, and short message services (SMS). Various self-management processes were applied, including providing social influence and support, and facilitating self-monitoring and goal setting. Eleven studies showed mHealth interventions to be effective in improving self-management behaviors, biomarkers, or patient-reported outcome measures associated with chronic diseases., Conclusions: While the number of identified studies was not large, none reported negative impacts of mHealth on selected outcomes. Future studies on mHealth should design interventions with a greater variety of targeted functions and should adopt more rigorous methodologies to strengthen the evidence for its effectiveness in chronic disease management., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported.

Background: To examine the effect and mechanism of Roux-en-Y gastric bypass (RYGB) on the improvement of diabetes according to the length of anastomosis and the gastric pouch volume in an animal model., Methods: Glucose intolerance was induced with a high-fat diet for 3 months in Sprague-Dawley rats. The animals were subjected to conventional RYGB (cRYGB; 5% gastric pouch with 15-cm Roux limb, 40-cm biliopancreatic limb; n = 9), short-limb RYGB (sRYGB; 5%, 8, 4 cm; n = 9), fundus-sparing RYGB (fRYGB; 30%, 8, 4 cm; n = 9), or sham operation (n = 9). After 6 weeks, oral glucose tolerance tests (OGTTs) were performed, and gut hormones including insulin, total GLP-1, GIP, and ghrelin were analyzed., Results: The cRYGB group showed significantly decreased food intake, body weight, and random glucose (p < 0.05). sRYGB resulted in a similar change of body weight loss to that of cRYGB, but with no improvement of hyperglycemia. The fRYGB group showed similar changes of body weight and random glucose to those of the sham group. In cRYGB and sRYGB, the level of insulin steeply increased until 30 min during OGTT. GLP-1 was higher at 30 min in cRYGB than in other groups, without significance. The fRYGB group showed a slowly increasing pattern in OGTT and GLP-1, and the lowest peak point in insulin and GIP., Conclusion: cRYGB with 95% gastric resection was needed to achieve not only weight loss but also diabetes improvement, which could be related to the increase in GLP-1.

Artificial selection has been demonstrated to have a rapid and significant effect on the phenotype and genome of an organism. However, most previous studies on artificial selection have focused solely on genomic sequences modified by artificial selection or genomic sequences associated with a specific trait. In this study, we generated whole genome sequencing data of 126 cattle under artificial selection, and 24,973,862 single nucleotide variants to investigate the relationship among artificial selection, genomic sequences and trait. Using runs of homozygosity detected by the variants, we showed increase of inbreeding for decades, and at the same time demonstrated a little influence of recent inbreeding on body weight. Also, we could identify ~0.2 Mb runs of homozygosity segment which may be created by recent artificial selection. This approach may aid in development of genetic markers directly influenced by artificial selection, and provide insight into the process of artificial selection.

Sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors have complementary mode of action. For the meta-analysis comparing the efficacy and safety between SGLT2 inhibitor plus DPP4 inhibitor (SGLT2i/DPP4i) and placebo plus DPP4 inhibitor (PCB/DPP4i) in patients with type 2 diabetes mellitus (T2DM), we selected randomized controlled trials from electronic databases by predefined criteria. The primary outcome of interest was the change in glycated hemoglobin A1c (HbA1c) from baseline. Of 605 potentially relevant studies, 7 eligible RCTs comprising 2,082 patients were included.SGLT2i/DPP4i showed a greater reduction in HbA1c (weighted mean difference -0.6%, 95% CI -0.7 to -0.5%), fasting plasma glucose, 2 h postprandial plasma glucose, and body weight compared to PCB/DPP4i. The risk of hypoglycemia increased in SGLT2i/DPP4i compared to that in PCB/DPP4i only when insulin or sulfonylureas were included as a background therapy. The risk of urinary tract infection was not increased in SGLT2i/DPP4i; however, the risk of genital infection increased upon adding SGLT2 inhibitors to pre-existing DPP4 inhibitors. In conclusion, compared to PCB/DPP4i, SGLT2i/DPP4i achieved better glycemic control and greater weight reduction without increasing the risk of hypoglycemia and urinary tract infection in patients with inadequately controlled T2DM.

We aimed to evaluate the comparative efficacy and safety of dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose co-transporter 2 inhibitors (SGLT2i), or thiazolidinedione (TZD) as an adjunctive treatment in patients with poorly controlled type 2 diabetes mellitus (T2DM) on insulin therapy. We searched Medline, Embase, the Cochrane Library, and ClinicalTrials.gov through April 2016. Bayesian network meta-analyses were performed with covariate adjustment. The primary outcome was the change in glycated hemoglobin A1c (HbA1c) from baseline. Fifty randomized controlled trials covering 15,494 patients were included. GLP-1RA showed the greatest HbA1c-lowering effect compared to the control (-0.84%; 95% credible interval, -1.00% to -0.69%), followed by TZD (-0.73%; -0.93 to -0.52%), SGLT2i (-0.66%; -0.84% to -0.48%), and DPP4i (-0.54%; -0.68% to -0.39%). SGLT2i showed the greatest fasting plasma glucose reduction. GLP-1RA and SGLT2i showed greater body weight reduction, whereas TZD increased body weight. TZD was ranked the highest in terms of insulin dose reduction. The risk of hypoglycemia was increased with TZD or GLP-1RA. The study provides the best available evidence on the comparative efficacy and safety of non-insulin anti-diabetic agents on top of pre-existing insulin therapy for inadequately controlled T2DM patients.

Agrimonia eupatoria L. has been shown to protect against liver injury due to its lipid lowering and antioxidant activities. The aim of this research was to evaluate the effect of A. eupatoria L. aqueous extract (AEE) on 80 subjects with elevated alanine transaminase (ALT) levels in a randomized, double-blind, placebo-controlled, 8-week study. This trial was conducted between January 2013 and July 2013 at the Oriental Medical Hospital (Jecheon) of Semyung University. The trial included subjects aged 20 years or older who were diagnosed with mildly to moderately elevated ALT levels (between 45 and 135 IU/L). Subjects received two capsules of placebo or AEE twice a day for 8 weeks. Adverse events were recorded. Eighty subjects were randomized to placebo or AEE groups who had similar baseline characteristics. During the 8 weeks of treatment, 11 subjects were excluded from the analysis for protocol violation or consent withdrawal; efficacy of treatment was, therefore, evaluated in 69 subjects (placebo = 35, AEE = 34). The AEE group showed a significant reduction in ALT and serum triglyceride (TG) at 8 weeks compared with the placebo group (ALT P = .044, TG P = .020). Significant group and time interactions were found in ALT (P = .038), aspartate aminotransferase (P = .040), and TG (P = .010). Alkaline phosphatase, total bilirubin, and gamma-glutamyl transferase levels were not different between the two groups. There were no reported severe adverse events during this study, and total protein, albumin, blood urea nitrogen, creatine, and total cholesterol levels were normal in both groups. AEE consumption was safe and generally well tolerated without severe adverse events.

Until now microsatellite (MS) have been a popular choice of markers for parentage verification. Recently many countries have moved or are in process of moving from MS markers to single nucleotide polymorphism (SNP) markers for parentage testing. FAO-ISAG has also come up with a panel of 200 SNPs to replace the use of MS markers in parentage verification. However, in many countries most of the animals were genotyped by MS markers till now and the sudden shift to SNP markers will render the data of those animals useless. As National Institute of Animal Science in South Korea plans to move from standard ISAG recommended MS markers to SNPs, it faces the dilemma of exclusion of old animals that were genotyped by MS markers. Thus to facilitate this shift from MS to SNPs, such that the existing animals with MS data could still be used for parentage verification, this study was performed. In the current study we performed imputation of MS markers from the SNPs in the 500-kb region of the MS marker on either side. This method will provide an easy option for the labs to combine the data from the old and the current set of animals. It will be a cost efficient replacement of genotyping with the additional markers. We used 1,480 Hanwoo animals with both the MS data and SNP data to impute in the validation animals. We also compared the imputation accuracy between BovineSNP50 and BovineHD BeadChip. In our study the genotype concordance of 40% and 43% was observed in the BovineSNP50 and BovineHD BeadChip respectively.

Background: This study aimed investigate the effect of the level of invasion into fibromuscular band (FMB) of prostate on the positive surgical margin (PSM) and biochemical recurrence (BCR) after radical prostatectomy (RP) in patients with organ-confined (pT2) prostate cancer., Methods: The clinical and pathological data of 461 consecutive patients with pT2 prostate cancer were evaluated regarding the level of invasion into FMB. The relationship between levels of invasion into FMB and PSM / BCR was assessed., Results: The rate of PSM at an FMB level of at 2 was 18.8%, which was significantly greater than the rates at levels 0 (5.4%) and 1 (7.8%). The level of FMB (p = 0.007) and percentage of tumor volume (p = 0.012) were identified as independent factors predictive of a positive surgical margin in a multivariate analysis. The 5-year BCR-free survival rates for a level 0-1 FMB with negative surgical margin, level 0-1 FMB with positive surgical margin, level 2 FMB with negative surgical margin, and level 2 FMB with positive surgical margin were 96.6%, 86.4%, 85.6%, and 72.9%, respectively (p <  0.001). A level 2 FMB (p = 0.050), positive surgical margin (p = 0.001), and surgical Gleason score (p = 0.001) were identified as independent predictors of a BCR of pT2 prostate cancer., Conclusions: Among patients with negative surgical margins, the surgical Gleason score and level of FMB independently affected the incidence of a BCR of pT2 prostate cancer. The level of FMB was an independent predictor of both a positive surgical margin and a BCR of pT2 disease. Accordingly, the level of FMB might help to further stratify the prognosis of patients with pT2 disease.