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Background and Aims: Diabetes and/or hypertension are the most common conditions in older people, and also related to higher cardiovascular disease (CVD) incidence and mortality. This study aims to explore the risk of CVD incidence and mortality among older people with diabetes and/or hypertension over a 16 years follow-up period and investigates the role of depression and obesity in these relationships., Methods: 6,855 participants aged 50+ from the English Longitudinal Study of Ageing (ELSA). The main exposure is having diabetes and/or hypertension at baseline (2002/2003) compared to not having, but excluded those with coronary heart disease (CHD) and/or stroke (CVD). Survival models are used for CVD incidence and mortality up to 2018, adjusted for socio-demographic, health, health behaviours, cognitive function, and physical function characteristics., Results: 39.3% of people at baseline had diabetes and/or hypertension. The risk of CVD incidence was 1.7 (95%CI: 1.5; 1.9) higher among people with diabetes and/or hypertension compared to those without and was independent of covariates adjustment. People with diabetes and/or hypertension were also 1.3 (95%CI: 1.1; 1.8) times more likely to die from CVD than those without. We did not find evidence for an elevated risk of CVD incidence and mortality among people with obesity nor among those with depression., Conclusions: In order to effectively reduce the risk of CVD incidence and mortality among older people, treatment as well as management of hypertension and diabetes should be routinely considered for older people with diabetes and/or hypertension., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zaninotto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Many of the college students expressed experiencing moderate or severe psychological distress. In their emergence as adults, college students encounter significant periods of drastic change. Family functions play a crucial role in determining individuals' mental health status., Objectives: The first objective of this study was to investigate whether family communication mediates the relationships between family dysfunctions and perceived mental health status among under/graduate students. The second objective was to investigate whether the mediation effects of family communication on the relationships between family dysfunctions and perceived mental health status differ by gender., Methods: The current study applied Minuchin's Structural Family Theory with under/graduate students (N = 348) in Ohio. Structural Equation Modeling was conducted to examine the effects of family dysfunctions and communication on perceived mental health status among under/graduate students., Results: Disengaged family function significantly influenced family communication, which, in turn, significantly impacted perceived mental health (mediation effect). Enmeshed family function did not show a significant relationship with family communication, whereas family communication had a significant impact on perceived mental health (no mediation effect). The model comparison test indicated that there were differences between males and females: the structural weights of the current path models were consistent with the full models, and there was a significant difference in the effect of parents' marital status on perceived mental health, with males being significantly impacted in both models., Conclusions: Practitioners should recognize that improving positive communication skills within the family unit can be a realistic approach to supporting the perceived mental health of under/graduate students. Colleges/universities should offer regular education programs to promote an understanding of the relationship between family communication strategies and the mental health of under/graduate students., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shon, Lee. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Previous studies have reported inconsistent results regarding the advantages or disadvantages of spironolactone use in patients undergoing hemodialysis (HD). This study aimed to evaluate survival according to the use of spironolactone in a large sample of patients undergoing maintenance HD., Methods: This retrospective study used laboratory and clinical data from the national HD Quality Assessment Program and claims data. The participants of the quality assessment program were patients who had been undergoing maintenance HD for ≥ 3 months, patients undergoing HD at least twice a week. Patients with no spironolactone prescription during the assessment periods were designated as the control group. Patients with one or more prescriptions of spironolactone during the assessment periods were assigned to the SPR group., Results: The number of patients in the control and SPR groups were 54,588 and 315, respectively. The 5-year survival rates were 69.1% and 59.1% in the control and SPR groups, respectively (P < 0.001). Cox regression analyses showed that the hazard ratio in the SPR group was 1.34 (P < 0.001) in univariate analysis and 1.13 (P = 0.249) in multivariable analysis. Univariate Cox-regression analysis showed a better patient survival rate in the control group than in the SPR group; however, multivariable analyses showed similar patient survival rates between the two groups., Conclusion: This study showed no difference in survival between patients undergoing HD with and without spironolactone use., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Emerging evidence has demonstrated that PIWI-interacting RNAs (piRNAs) play important roles in various physiological processes and contribute to cancer progression. Moreover, piRNAs and PIWI protein levels are associated with the prognosis and chemoresistance of various cancers. The limitations of biomarkers challenge early detection and monitoring of chemoresistance and cancer relapse., Methods: To evaluate the potential of piRNA as a diagnostic biomarker in oncology, we systematically reviewed previous studies on the subject. PubMed, Embase, and Cochrane databases were searched to evaluate the diagnostic relevance of piRNAs in cancer. Eighteen studies (2,352 patients) were included. The quality of each study was evaluated with AMSTAR and QUADAS-2 tool., Results & Conclusions: The area under the curve (AUC) values of 26 piRNAs in patients with cancer ranged from 0.624 to 0.978, with piR-9491 showing the highest value (0.978). The sensitivity of the total of 21 piRNAs in cancer patients was between 42.86 and 100, with piR-9491 showing the highest sensitivity (100). The specificity of these 21 piRNAs ranged from 60.10 to 96.67 (with piR-018569 showing the highest specificity (96.67)). Their odds ratios were between 1.61 and 44.67, and piR-12488 showed the highest odds ratio (44.67). Generally, the piRNAs in this review showed better sensitivity and AUC values than current clinical diagnostic biomarkers, although current biomarkers appear to be more specific. Reviewed piRNAs showed better diagnostic performance than currently used clinical biomarkers. Notably, piR-823 showed a significant diagnostic performance in four types of cancer (colorectal, esophageal, gastric, and renal cell cancer). However, all 18 studies included in this review were a case-control study. So, further prospective studies are required for their validation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Sohn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The prevalence of multiple chronic conditions (MCC), defined as several coexisting chronic conditions, has increased with the aging of society. MCC is associated with poor outcomes, but most comorbid diseases in asthma patients have been evaluated as asthma-associated diseases. We investigated the morbidity of coexisting chronic diseases in asthma patients and their medical burdens., Methods: We analyzed data from the National Health Insurance Service-National Sample Cohort for 2002-2013. We defined MCC with asthma as a group of one or more chronic diseases in addition to asthma. We analyzed 20 chronic conditions, including asthma. Age was categorized into groups 1-5 (< 10, 10-29, 30-44, 45-64, and ≥ 65 years, respectively). The frequency of medical system use and associated costs were analyzed to determine the asthma-related medical burden in patients with MCC., Results: The prevalence of asthma was 13.01%, and the prevalence of MCC in asthmatic patients was 36.55%. The prevalence of MCC with asthma was higher in females than males and increased with age. The significant comorbidities were hypertension, dyslipidemia, arthritis, and diabetes. Dyslipidemia, arthritis, depression, and osteoporosis were more common in females than males. Hypertension, diabetes, COPD, coronary artery disease, cancer, and hepatitis were more prevalent in males than females. According to age, the most prevalent chronic condition in groups 1 and 2 was depression, dyslipidemia in group 3, and hypertension in groups 4 and 5. Older age, low income, and severe disability were independent risk factors for MCC in patients with asthma. The frequency of asthma-related medical system use and asthma-associated costs increased with increasing numbers of coexisting chronic diseases., Conclusion: Comorbid chronic diseases in asthma patients differed according to age and sex. The asthma-related-medical burdens were highest in patients with five or more chronic conditions and groups 1 and 5., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Jo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Arterial cannulation in elderly patients is difficult because of age-related morphological changes. Applying dynamic needle tip positioning (DNTP) that guides the catheter to position inside the vessel sufficiently may aid in successful cannulation., Methods: This prospective study enrolled patients aged over 70 years, who were scheduled for elective surgery under general anaesthesia with arterial cannulation. The patients were randomly assigned to the DNTP (group D, n = 76) or the conventional short-axis view(group C, n = 75) group. The arterial depth, diameter, and arterial conditions(calcification, segmental stenosis, and tortuosity) were evaluated using ultrasound, before puncture. We recorded the first attempt success, cannulation time, the number of attempts, and cannulation-related complications., Results: A total of 151 patients were enrolled in this study. The first attempt success rate in group D was significantly higher than that in group C (89% versus 72%; P = 0.0168). The median cannulation time per last attempt in group D versus group C was 25 versus 30 sec(P = 0.0001), and the overall cannulation time was 25 versus 35 sec(P = 0.0001), respectively. Arterial cannulation per last attempt and overall cannulation time were shorter in group D. The number of attempts was higher in group C (P = 0.0038). The occurrence rate of hematoma was significantly lower in group D (16% versus 47%, relative risk = 3.0, P = 0.0001)., Conclusions: The DNTP method may improve the first attempt success rate of arterial cannulation and reduce complications in elderly patients over 70 years of age., Competing Interests: The authors have declared that no competing interests exist.

COVID-19 has had a substantial national impact in South Korea, causing negative psychological responses including sleep-related problems. Literature indicates sleep problems among the general population have been reported to be as high as around 35.7% during the first 8 months of COVID-19. Therefore, the aim of this study was to investigate the impact of COVID-19 pandemic on sleep problems among the general population using relative search volume (RSV) data, and whether there are any differences by age and time periods spanning before and during the pandemic. RSV data was collected from the most commonly used search engine in South Korea, NAVER. Search terms were grouped into 4 categories: insomnia, other sleep disorders, sleeping pills, and sleeping pill side effects. Time points were divided into 4 periods, each 7 months long: 7 months before COVID-19 (T0), first confirmed COVID-19 case to 7 months after (T1), 7 to 14 months (T2), and 14 to 21 months (T3). A 2x4 factorial Analysis of Variance was conducted to investigate main effects and interactions between age and time periods. Main effects and interaction effects of age and time periods were significant for all search term groups. For all search terms, both age groups showed dramatic increase from T0 to T1. In age group 60 or above, RSV continued to increase for other sleep disorders and sleeping pill. Insomnia and sleeping pill side effects showed decreasing trend at T3. In general, sudden increase in RSV after occurrence of COVID-19 followed by slow decline were observed. However, for age group 60 or above, RSV values of other sleep disorders and sleeping pills continued to increase, suggesting slower recovery of psychological impact with increasing age. Overall, the results underscore the importance of implementing preventive measures for monitoring sleep problems during the pandemic, especially in the elderly., Competing Interests: The authors have declared that no competing interests exist.

We sought to assess the impact of sex on in-hospital mortality of patients with COVID-19 infection in South Korea. The study recruited 5,628 prospective consecutive patients who were hospitalized in South Korea with COVID-19 infection, and enrolled in the Korea Centers for Disease Control and Prevention (KCDC) dataset between January 20, 2020, and April 30, 2020. The primary endpoint was in-hospital death from COVID-19. The cohort comprised of 3,308 women (59%) and 2,320 men (41%). In-hospital death was significantly lower in women than men (3.5% vs. 5.5%, hazard ratio (HR): 0.61; 95% confidence interval (CI): 0.47 to 0.79, p <0.001). Results were consistent after multivariable regression (HR: 0.59; 95% CI: 0.41 to 0.85, p = 0.023) and propensity score matching (HR: 0.51; 95% CI: 0.30 to 0.86, p = 0.012). In South Korea, women had a significantly lower risk of in-hospital death amongst those patients hospitalized with COVID-19 infection., Competing Interests: The authors have declared that no competing interests exist.

Background and Aims: Fibrosis progression is the most important prognostic factor, and insulin resistance is one of the main mechanisms associated with fibrosis progression in patients with nonalcoholic fatty liver disease (NAFLD). We evaluate the association between baseline insulin resistance and future fibrosis progression in patients with NAFLD without diabetes., Approach and Results: This retrospective longitudinal study with 8-year follow-up period included 32,606 (men, 83%) participants aged >20 years (average age, 38.0 years) without diabetes at baseline who completed at least two comprehensive health checkups from January 1, 2010 to December 31, 2018. NAFLD was diagnosed based on ultrasonography. The homeostasis model assessment of insulin resistance (HOMA-IR) was used to evaluate baseline insulin resistance. Fibrosis progression was assessed using the aspartate aminotransferase to platelet ratio index (APRI). The advanced liver fibrosis with an APRI value above the intermediate fibrosis probability (≥0.5) developed in a total of 2,897 participants during 136,108 person-years. 114 participants progressed to a high fibrosis probability stage (APRI >1.5) during 141,064 person-years. Using the lowest baseline HOMA-IR quartile group (Q1) as a reference, the multivariate-adjusted hazard ratio (HR) for development of advanced liver fibrosis (APRI ≥0.5) in the highest baseline HOMA-IR quartile group (Q4) was 1.95 (95% confidence interval [CI] 1.74-2.19; Model 4). And the HR for development of advanced liver fibrosis with high fibrosis probability was 1.95 (95% CI 1.10-3.46; Model 4). The positive association was maintained throughout the entire follow-up period. The baseline HOMA-IR model was superior to the baseline body mass index (BMI) model in predicting the progression of fibrosis probability., Conclusions: In this longitudinal study, we found that the degree of baseline insulin resistance, assessed by HOMA-IR values, was positively associated with future fibrosis progression in patients with NAFLD without diabetes., Competing Interests: The authors have declared that no competing interests exist.

Objectives: There do not appear to be many studies which have examined the socio-economic burden and medical factors influencing the mortality and hospital costs incurred by patients with cardiac arrest in South Korea. We analyzed the differences in characteristics, medical factors, mortality, and costs between patients with national health insurance and those on a medical aid program., Methods: We selected patients (≥20 years old) who experienced their first episode of cardiac arrest from 2004 to 2015 using data from the National Health Insurance Service database. We analyzed demographic characteristics, insurance type, urbanization of residential area, comorbidities, treatments, hospital costs, and mortality within 30 days and one year for each group. A multiple regression analysis was used to identify an association between insurance type and outcomes., Results: Among the 487,442 patients with cardiac arrest, the medical aid group (13.3% of the total) had a higher proportion of females, rural residents, and patients treated in low-level hospitals. The patients in the medical aid group also reported a higher rate of non-shockable conditions; a high Charlson Comorbidity Index; and pre-existing comorbidities, such as hypertension, diabetes mellitus, and renal failure with a lower rate of providing a coronary angiography. The national health insurance group reported a lower one-year mortality rate (91.2%), compared to the medical aid group (94%), and a negative association with one-year mortality (Adjusted OR 0.74, 95% CI 0.71-0.76). While there was no significant difference in short-term costs between the two groups, the medical aid group reported lower long-term costs, despite a higher rate of readmission., Conclusions: Medical aid coverage was an associated factor for one-year mortality, and may be the result of an insufficient delivery of long-term services as reflected by the lower long-term costs and higher readmission rates. There were differences of characteristics, comorbidities, medical and hospital factors and treatments in two groups. These differences in medical and hospital factors may display discrepancies by type of insurance in the delivery of services, especially in chronic healthcare services., Competing Interests: The authors have declared that no competing interests exist.

Background: Thoracotomy is an invasive surgical procedure that produces intense postoperative pain. Electroacupuncture has been used to induce analgesia in various situations, including after surgery. The aim of the following systematic review and meta-analysis was to evaluate the effect of electroacupuncture on post-thoracotomy pain., Methods: The studies for the systematic review were searched using the following 9 databases: PubMed, Cochrane Library, EMBASE, MEDLINE Complete, Google Scholar, China National Knowledge Infrastructure (CNKI), Korean Medical Database (KMBASE), Koreanstudies Information Service System (KISS), and OASIS, without language restriction. Randomized controlled trials (RCTs) that met the inclusion criteria were selected. The quality assessment was performed using the Cochrane risk-of-bias tool, and RevMan 5.3 was used for meta-analysis. The review protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42019142157., Results: Eleven randomized controlled trials were included in the systematic review. The meta-analysis was performed for two outcome measures: pain score 24 hours after surgery and total dose of opioid analgesics. A subgroup analysis was performed according to the control group: sham acupuncture and conventional analgesia group. Pain score 24 hours after surgery of electroacupuncture group showed a standard mean difference of -0.98 (95% CI: -1.62 to -0.35) compared to sham acupuncture. The standard mean difference was -0.94 (95% CI: -1.33 to -0.55) compared to conventional analgesia. The total dose of opioid analgesics of electroacupuncture group showed a standard mean difference values of -0.95 (95% CI: -1.42 to -0.47) compared to sham acupuncture. The standard mean difference was -1.96 (95% CI: -2.82 to -1.10) compared to conventional analgesia., Conclusion: Current evidence suggests that electroacupuncture might provide useful pain relieving effect on post-thoracotomy patients. However, due to low quality and high heterogeneity of existing data, further rigorously designed studies should be performed to confirm the safety and efficacy., Competing Interests: The authors have declared that no competing interests exist.

Visual social media platforms can function as both facilitators and intervenors of concerning behaviors. This study focused on one of the health concerns worldwide, a leading cause of death related to mental health-suicide-in the context of a dominant visual social media platform, YouTube. This study employed content analysis method to identify the factors predicting viewer responses to suicide-themed content from the perspectives of who's, what's, and how's of suicide-themed videos. The results of the hierarchical multiple regression showed that the characteristics of content provider and content expression were more significant predictors of viewer engagement than were the characteristics of the message. These findings have implications for not only platform service providers but also diverse groups of individuals who participate in online discussions on suicide. YouTube has the potential to function as a locus for open discussion, education, collective coping, and even the diagnosis of suicidal ideation., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Wound healing after Ahmed glaucoma valve (AGV) implantation often entails fibrosis as a foreign body reaction to the silicone plate. Poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) forms an antifouling surface that inhibits fibrosis during wound healing. In this study, we aimed to compare the effects of the implantation of AGV coated with PMPC (wPMPC) versus AGV without PMPC (woPMPC) in rabbits., Methods: Six New Zealand White rabbit does underwent AGV implantation in both eyes. For each rabbit, one eye was randomly selected for implantation of AGV wPMPC and a conventional AGV (woPMPC) was implanted in the contralateral eye. Gross conjunctival vascularity was compared between the two groups at the first, second, and fourth weeks after surgery. The eyes were enucleated in four weeks and subjected to staining with hematoxylin and eosin and Masson's trichrome stain. The fibrosis and inflammation status among the eye samples were compared by measuring the thickness of the fibrotic walls and counting the number of chronic inflammatory cells around the AGV. Counting of inflammatory cells and measuring fibrotic wall thickness were done in a blinded method to eliminate observer bias. Statistical analysis was performed using the Mann-Whitney U test., Results: Gross and histological examinations revealed no toxic effects of PMPC. There were no apparent differences in overall conjunctival vascularity between the two groups at weeks 1, 2, and 4 after surgery. The average inflammatory cell counts were 14.3 ± 5.8 per slide and 27.3 ± 8.6 per slide in the wPMPC and woPMPC groups, respectively (p = 0.037). The average thicknesses of the fibrotic wall were 57.9 ± 11.3 μm and 81.5 ± 21.3 μm in the wPMPC and woPMPC groups, respectively (p = 0.025)., Conclusion: Compared to the woPMPC group, the number of inflammatory cells and fibrosis were significantly decreased in the wPMPC group., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To investigate the association between peripheral vasospasm and the visual field (VF) progression rate in patients with normal-tension glaucoma (NTG) with low-teen intraocular pressure (IOP)., Methods: The finger temperature of 113 NTG patients was measured before and after exposure to ice water using a Temperature gun (cold pressor test). These patients had confirmed VF progression, despite a low-teen IOP during a follow-up period of >5 years. VF progression rates were calculated as the slope of the visual field index (VFI) and mean deviation (MD) over time. Demographic, systemic, and ocular factors and VF progression rates were compared, based on the cold pressor test results. A regression analysis was used to investigate the factors affecting VF progression rates., Results: Mean age, initial IOP, mean IOP during the follow-up period, and initial VF MD were 57.1 years, 15.8 mmHg, 12.0 mmHg, and -5.2 dB, respectively. When patients were divided into two groups (less vasospasm and more vasospasm) according to changes in temperature after exposure to ice water, the VF progression rate was significantly faster in the group with more vasospasm. In a multiple regression analysis, older age, worse initial VF MD, and greater decrease in finger temperature after ice water exposure were significantly associated with faster VF progression rates., Conclusion: An excessive drop in finger temperature after exposure to ice water was significantly associated with faster VF progression in patients with low-teen NTG. This suggests that the blood flow in the optic nerve head may also be disturbed by peripheral vasospasm, accelerating glaucomatous damage regardless of IOP., Competing Interests: The authors have declared that no competing interests exist.

Disease progression (DP) in interstitial lung disease (ILD) is variable and difficult to predict. In previous reports, serum Krebs von den Lungen-6 (KL-6) was suggested to be useful in diagnosing and predicting survival in ILD. The aim of our study was to investigate the usefulness of serum KL-6 as a predictor of DP in ILD. Clinical data of 199 patients with ILD (idiopathic pulmonary fibrosis: 22.8%) were prospectively collected and serum KL-6 levels were measured. DP was defined as a relative decline in forced vital capacity (FVC) ≥ 10%, acute exacerbation, or death during follow-up. The median follow-up period was 11.1 months. The mean age of the subjects was 62.2 years, and 59.8% were male. DP occurred in 21.6% of patients. The progressed group showed lower FVC, lower diffusing capacity for carbon monoxide, lower the minimum oxygen saturation during the 6-minute walk test, higher fibrosis scores on high-resolution computed tomography, and higher KL-6 levels (826.3 vs. 629.0 U/mL; p < 0.001) than those of the non-progressed group. In receiver operating characteristic curve analysis, serum KL-6 levels were a significant predictor of DP in ILD (area under the curve = 0.629, p = 0.009, and the optimal cut-off level was 811 U/mL). In multivariable Cox analysis, high serum KL-6 levels (≥ 800 U/mL) were only independently associated with DP in ILD (HR 2.689, 95% CI 1.445-5.004, P = 0.002). Serum KL-6 levels might be useful to predict DP in patients with ILD., Competing Interests: The authors have declared that no competing interests exist.

Objective: To evaluate the changes of vaginal microbiota during cervical carcinogenesis in women with high-risk human papillomavirus infection., Materials and Methods: Vaginal microbiota was analyzed using next-generation sequencing in women with normal, cervical intraepithelial neoplasia (CIN), or cervical cancer., Results: A marked decrease of Lactobacillus crispatus was found in the CIN/cancer groups compared with that in the normal group. The diversity of microorganisms increased in patients with CIN or cervical cancer with HPV infection. Atopobium vaginae (OR 4.33, 95% CI 1.15-16.32), Dialister invisus (OR 4.89, 95% CI 1.20-19.94), Finegoldia magna (OR 6.00, 95% CI 1.08-33.27), Gardnerella vaginalis (OR 7.43, 95% CI 1.78-31.04), Prevotella buccalis (OR 11.00, 95% CI 2.00-60.57), and Prevotella timonensis (OR 6.00, 95% CI 1.46-24.69) were significantly associated with the risk of CIN 2/3 or cervical cancer., Conclusion: Women with the CIN and cervical cancer showed a high diversity in vaginal microbiota. Depletion of Lactobacillus crispatus and increased abundance of anaerobic bacteria were detected in women with cervical disease., Competing Interests: The authors have declared that no competing interests exist.

Xylose, the second most abundant sugar in lignocellulosic biomass hydrolysates, can be fermented by Saccharomyces cerevisiae expressing one of two heterologous xylose pathways: a xylose oxidoreductase pathway and a xylose isomerase pathway. Depending on the type of the pathway, its optimization strategies and the fermentation efficiencies vary significantly. In the present study, we constructed two isogenic strains expressing either the oxidoreductase pathway (XYL123) or the isomerase pathway (XI-XYL3), and delved into simple and reproducible ways to improve the resulting strains. First, the strains were subjected to the deletion of PHO13, overexpression of TAL1, and adaptive evolution, but those individual approaches were only effective in the XYL123 strain but not in the XI-XYL3 strain. Among other optimization strategies of the XI-XYL3 strain, we found that increasing the copy number of the xylose isomerase gene (xylA) is the most promising but yet preliminary strategy for the improvement. These results suggest that the oxidoreductase pathway might provide a simpler metabolic engineering strategy than the isomerase pathway for the development of efficient xylose-fermenting strains under the conditions tested in the present study., Competing Interests: The authors have declared that no competing interests exist.

Smoking cessation reduces the cardiovascular risk but increases body weight. We investigated the risk of subsequent myocardial infarction and ischemic stroke according to weight gain after smoking cessation, using a nationwide population based cohort. We enrolled 3,797,572 Korean adults aged over 40 years who participated in national health screenings between 2009 and 2010. Subjects who quit smoking were classified into three subgroups according to the weight change between baseline and 4 years prior. Myocardial infarctions and ischemic strokes were followed until the end of 2015. We compared the hazard ratios among smoking cessation subgroups, non-smokers, and current smokers. The mean changes in weight (1.5 ± 3.9 kg) of the smoking cessation group were higher than those of the other groups (p < 0.0001). A total of 31,277 and 46,811 subjects were newly diagnosed with myocardial infarction and ischemic stroke, respectively. Regardless of weight change, all subgroups of smoking cessation had significantly less risk than current smokers. The subgroup of smoking cessation with weight gain over 4kg showed the lowest risk for myocardial infarctions (hazard ratio 0.646, 95% confidence interval 0.583-0.714, p < 0.0001) and ischemic strokes (hazard ratio 0.648, 95% confidence interval 0.591-0.71, p < 0.0001) after multivariable adjustment. In conclusion, weight gain after smoking cessation did not adversely affect the cardiovascular protective effect., Competing Interests: The authors have declared that no competing interests exist.

Background: We evaluated whether a simulation-based training with a vessel phantom improves the basic skills of a novice required for ultrasound-guided radial artery cannulation in real patients. In addition, we analysed whether repeated simulation training sets with an inter-training interval would accelerate the learning curve., Methods: From March 2019 to July 2019, twenty-one anesthesiology residents were randomized into either a simulation group (n = 11) or control group (n = 10). Residents performed a total of 84 ultrasound-guided radial artery cannulations in real patients. The simulation group participated in two sets of simulation training on a vessel phantom (10 sessions per set) with a one-month inter-training interval. Trainee's performance proficiency was scored using a developed checklist, and a learning curve for each training set was constructed. To evaluate the effectiveness of our training curriculum in skill transfer, each resident performed four ultrasound-guided radial artery cannulations in real patients. The primary outcome was first attempt success rate and the secondary outcome was dynamic needle-tip positioning ability in real patients., Results: The first attempt success rate and dynamic needle-tip positioning ability by ultrasound transducer were significantly higher in the simulation group than the control group (81.8% vs. 50%, P = 0.002 and 68.2% vs. 7.5%, P < 0.001, respectively). A reduced number of sessions was required to reach a plateau score on the learning curve in the repeated training set compared in the first-set (7 (5-8) vs. 3 (2-4), P = 0.003, respectively)., Conclusions: Simulation-based training using a vessel phantom effectively improved the first attempt success rate for ultrasound-guided radial artery cannulation in real patients and the dynamic needle-tip positioning ability by ultrasound transducer in novice anesthesiology residents. In addition, repeated training curriculum accelerated the learning curve for recall skill proficiency and reduced inter-individual variability for skill acquisition., Clinical Trial Registration: Clinical Research Information Service (KCT0003471, Principle investigator: Jeong Jin Min, Date of registration: 06/March/2019)., Competing Interests: NO authors have competing interests.

Objective: To determine the association of radiological and symptomatic osteoarthritis with sleep duration in a representative sample of the Korean population., Methods: Using data from the national cross-sectional fifth Korea National Health and Nutrition Examination Survey 2010-2012. Of the 16,528 participants in KNHANES-V, 8,918 were adults aged≥ 50 years who had completed the survey questions on sleep duration and osteoarthritis, and had diagnostic X-ray results. We evaluated the association between sleep duration as the primary predictor for osteoarthritis involving the hip, knee, and spinal joints. A complex sample logistic regression analysis was performed to adjust for the covariates., Results: Proportions of participants with total daily sleep duration of ≤6 hours, 7-8 hours, and ≥9 hours were 47.1%, 45.2, and 7.7%, respectively. The rate of osteoarthritis diagnoses in the ≤6 hours, 7-8 hours, and ≥9 hours of sleep duration groups was 24.1%, 17.6%, and 21.8%, respectively (p <0.0001). The odds ratios (OR) were significantly higher in the ≤6 hours of sleep group than in the 7-8 hours of sleep group (OR, 1.20; 95% confidence interval [CI], 1.03-1.39; p = 0.02), but no significant difference in the ≥9 hours of sleep group was found after adjusting the confounding variables. When we compared knee joint pain (Numeric Rating Scale 0 versus 1-10) in participants with grade 2-4 Kellgren-Lawrence (KL) classification after adjusting these same confounding variables, the ≤6 hours of sleep group (OR, 1.32; 95% CI, 1.10-1.58) and the ≥9 hours of sleep group (OR, 1.41; 95% CI, 1.03-1.95) showed significantly higher ORs., Conclusion: This study confirmed the significant association between sleep duration and osteoarthritis in adults aged ≥50 years. Participants' positive for both radiological (KL grade ≥2) and symptomatic osteoarthritis showed a strong association between knee joint pain and not enough sleep duration., Competing Interests: The authors have declared that no competing interests exist.

Background: Breast cancer is the most common cancer among Asian women in the U.S. The first objective was to investigate predictors (including ethnicity) of never having a mammogram in middle-aged and older Chinese, Vietnamese, and Korean immigrant women (main effects). The second objective was to explore whether relationships between predictors and never having a mammogram varied across the three groups (moderation effects of ethnicity)., Methods: Merged (2005-2007-2009-2011) California Health Interview Survey data were utilized. Unweighted sample was 3,710 Asian women ages 40 years and older (Chinese = 1,389; Vietnamese = 1,094; Korean = 1,227). Replicate weighted total sample size was 1,710,233 (Chinese = 940,000; Vietnamese = 410,000; Korean = 360,000). Replicate-weighted multivariate logistic regression was applied. Interaction effects (moderator role of ethnicity) were also examined, using multivariate logistic regression, for the second objective., Results: For the first objective, odds of never having a mammogram were higher for women who were Korean (Ref = Vietnamese), unmarried, or a non-U.S. citizen. Odds were lower in women ages 50-59 or 60-69 (Ref = 70-85). Regarding the second objective, only for Chinese women, odds of never having a mammogram were lower as the number of physician visits got higher., Conclusion: Culturally-sensitive outreach and services should be developed to target higher-risk groups. Patient-centered healthcare strategies tailored for the three groups could be effective. For Chinese women, in particular, regular information sessions or education programs could be provided for enhancing their physician visits., Competing Interests: The authors have declared that no competing interests exist.

Muscle development and lipid accumulation in muscle critically affect meat quality of livestock. However, the genetic factors underlying myofiber-type specification and intramuscular fat (IMF) accumulation remain to be elucidated. Using two independent intercrosses between Western commercial breeds and Korean native pigs (KNPs) and a joint linkage-linkage disequilibrium analysis, we identified a 488.1-kb region on porcine chromosome 12 that affects both reddish meat color (a*) and IMF. In this critical region, only the MYH3 gene, encoding myosin heavy chain 3, was found to be preferentially overexpressed in the skeletal muscle of KNPs. Subsequently, MYH3-transgenic mice demonstrated that this gene controls both myofiber-type specification and adipogenesis in skeletal muscle. We discovered a structural variant in the promotor/regulatory region of MYH3 for which Q allele carriers exhibited significantly higher values of a* and IMF than q allele carriers. Furthermore, chromatin immunoprecipitation and cotransfection assays showed that the structural variant in the 5'-flanking region of MYH3 abrogated the binding of the myogenic regulatory factors (MYF5, MYOD, MYOG, and MRF4). The allele distribution of MYH3 among pig populations worldwide indicated that the MYH3 Q allele is of Asian origin and likely predates domestication. In conclusion, we identified a functional regulatory sequence variant in porcine MYH3 that provides novel insights into the genetic basis of the regulation of myofiber type ratios and associated changes in IMF in pigs. The MYH3 variant can play an important role in improving pork quality in current breeding programs., Competing Interests: We registered a patent in the Republic of Korea using the results generated in this study to protect any potential intellectual property derived from this research: Patent registration number: 1019293830000. Title: Genetic marker for determining meat quality traits of pigs and use thereof. Applicant: Rural Development Administration of the republic of Korea, Korea Research Institute of Bioscience and Biotechnology, and Jeju National University. Registration date: 2018-12-10. We also made provisional patent applications to EU (17200547.2), China (201711106017.5), Japan (2017-214510), Canada (2,984,938) and USA (20180135123) using the same materials used for the Korean patent.

Background: This study investigated the time to appropriate treatment and factors affecting late treatment initiation in patients with multidrug-resistant tuberculosis (MDR-TB) in South Korea., Methods: Data from patients with culture-confirmed pulmonary MDR-TB who received treatment at Pusan National University Hospital (PNUH) between January 2010 and July 2018 were reviewed retrospectively. Patients were divided into two groups according to the first institution they visited [patients who were transferred to PNUH after diagnosis of MDR-TB (Group A) and patients who were initially diagnosed with TB at PNUH (Group B)]., Results: A total of 100 patients were included (53 in Group A and 47 in Group B). The percentage of patients in whom line probe assays (LPAs) for isoniazid and rifampin or Xpert MTB/RIF assays were performed was higher in Group B than in Group A [20.8 vs. 57.4% (P < 0.001) and 17.0 vs. 46.8% (P = 0.001), respectively]. The median time from the first visit to appropriate treatment initiation was longer in Group A (102.0 vs. 77.0 days, P = 0.002). However, a subgroup analysis of patients with pre-extensively or extensively drug-resistant TB (pre-XDR- or XDR-TB) revealed that the time to appropriate treatment did not differ between Groups A and B. Although the time to appropriate treatment decreased during the study period in both Groups A and B, this trend was not evident in patients with pre-XDR- or XDR-TB in Group B. Based on multivariate analyses, performance of LPAs for isoniazid and rifampin, performance of Xpert MTB/RIF assays, and the presence of uncomplicated MDR-TB were protective against delays in appropriate treatment initiation., Conclusions: The time to appropriate treatment in patients with MDR-TB in South Korea was not acceptable, particularly for patients diagnosed outside of PNUH and for patients with pre-XDR- or XDR-TB. The use of rapid molecular drug susceptibility tests in various healthcare settings and introduction of second-line LPAs are required., Competing Interests: The authors have declared that no competing interests exist.

Objective: We analyzed the impact of rapid lactate clearance as an indicator of hemodynamic optimization on the outcome of out-of-hospital cardiac arrest (OHCA) during early post-cardiac arrest care (PCAC)., Methods: This retrospective analysis was based on a prospective cohort. We selected adult patients with OHCA who achieved a survival event between May 2006 and December 2017. Serum lactate levels were measured at 0 and 6 h after a survival event. The lactate clearance rate was calculated as (lactate at 0 h-lactate at 6 h)/lactate at 0 h. The threshold lactate clearance value for predicting survival to discharge was determined by receiver operating characteristic (ROC) curve analysis. Rapid lactate clearance was defined as the lactate clearance above the threshold value or normalization of serum lactate level (<2.0 mmol/L) at 6 h after a survival event. The primary outcome was survival to discharge. Multivariate logistic regression was used to predict survival to discharge., Results: We enrolled 335 patients. 145 patients (43.3%) survived at discharge. The threshold value of lactate clearance was ≥34% to predict survival to discharge. After adjustment for confounders, the adjusted odds ratios for no hypotension at both 0 and 6 hours and for the presence of rapid lactate clearance for survival to discharge were 8.018 (95% confidence interval [CI] 2.802-22.947) and 2.193 (95% CI 1.263-3.808), respectively. Among patients with early recovery from initial hypotension or with no hypotension events at both 0 and 6 hours, the survival rates were significantly higher in the rapid lactate clearance group than in the non-rapid lactate clearance group., Conclusions: During the early PCAC period, a rapid decrease in serum lactate level was an indicator of good outcome. Hemodynamic optimization including not only prevention and immediate correction of hypotension but also rapid lactate clearance should be considered in OHCA patients., Competing Interests: The authors have declared that no competing interests exist.

Purpose: This study investigated the significance of change in neutrophil-to-lymphocyte ratio (NLR) during preoperative chemoradiotherapy (preop-CRT) in patients with non-metastatic rectal cancer using a propensity score matching method (PSM)., Methods: Patients who underwent surgery after completion of preop-CRT for non-metastatic rectal cancers from Jan 2004 to Dec 2013 were retrospectively enrolled. NLRs were obtained before commencement of CRT (pre-NLR) and between completion of CRT and surgery (post-NLR). Using Cox regression hazards models, the association of NLRs with survival after PSM was examined., Results: A total of 131 patients were grouped as follows: group A, pre-NLR < 3 & post-NLR < 3 (n = 47); group B, pre-NLR < 3 & post-NLR ≥ 3 (n = 45); group C, pre-NLR ≥ 3 & post-NLR < 3 (n = 5); group D, pre-NLR ≥ 3 & post-NLR ≥ 3 (n = 34). There was no difference in disease-free survival (DFS) or overall survival (OS) rate according to group. When dichotomized into group A versus groups B-D, DFS was higher in group A (84.7%) than groups B-D (67.5%, p = 0.021). After PSM (n = 94), multivariable analysis identified persistent lower NLR as an independent favorable prognosticator of DFS (HR 0.37, 95% CI 0.15-0.92, p = 0.033)., Conclusions: Persistent non-inflammatory state measured by NLR may be an indicator of decreased risk of recurrence in patients with locally advanced rectal cancer treated with preop-CRT., Competing Interests: The authors have declared that no competing interests exist.

Background: Radial probe endobronchial ultrasound using a guide sheath (EBUS-GS) is used to diagnose peripheral lung cancer. The aim was to identify the accuracy of molecular analysis that were performed with EBUS-GS specimens in patients with non-small cell lung cancer (NSCLC)., Method: From December 2015 to September 2017, we retrospectively studied 91 patients with peripheral NSCLC who underwent surgery after EBUS-GS. Epidermal growth factor receptor (EGFR) mutational and anaplastic lymphoma kinase (ALK) translocation status obtained from surgical specimens served as the references., Results: Compared to the reference data, EGFR mutational testing of EBUS-GS specimens was in 97% agreement, and the κ coefficient was 0.931 (P< 0.001). In addition, on ALK translocation testing, the results of all 91 patients were in agreement with the reference data (concordance rate of 100%, κ coefficient 1.000; P< 0.001)., Conclusion: We found that EBUS-GS could be used for molecular diagnosis, such as EGFR mutational and ALK translocation status, in patients with peripheral NSCLC., Competing Interests: The authors have declared that no competing interests exist.

Attenuated live infectious laryngotracheitis (ILT) virus (ILTV) vaccines have been used to prevent and control the outbreak of ILT worldwide. Recent studies using high-throughput sequencing technology have increased the number of complete genome sequences of ILTVs, enabling comparative genome analysis. Although 37 complete genome sequences of ILTV, including vaccine strains, have been reported, the complete genome sequence of any field strain of ILTV in South Korea is yet to be published. In this study, we determined and analyzed the complete genome sequences of three virulent Korean field strains of ILTV (40798/10/Ko, 0206/14/Ko, and 30678/14/Ko). Two of the Korean field strains (40798/10/Ko and 0206/14/Ko) displayed fewer non-synonymous single nucleotide polymorphisms than those of the Serva vaccine strain, indicating that these Korean field strains of ILTV most likely originated from the vaccine strain. The third ILTV strain, 307678/14/Ko, had two regions in the genome showing recombination between the Serva vaccine-like strain and the Australian A20 vaccine-like strain. Comparative genome analysis of ILTV using the Korean field strains with variable virulence can shed light on the recent trend of the emergence of virulent ILTV strains in the field. A few amino acid changes in the genome of ILTV vaccines could enhance the virulence in the vaccine strain, and natural recombination should be considered one of the major risks for the generation of revertant strains of ILTV under field conditions., Competing Interests: The authors have declared that no competing interests exist.

Background: Overweight is known as a risk factor for ischemic stroke. However, the effect of weight change on the development of ischemic stroke remains controversial. We investigated the relationship between weight change and the risk of ischemic stroke using a nationwide population-based cohort., Methods: Our study enrolled 11,084,683 participants (Mean age 49.7±13.5 years, range 20-114 years) in the Korean National Health Screening Program from 2009 to 2012. Weight change was calculated using the difference between the baseline weight and the weight at health screening four years prior to the baseline. The occurrence of newly-diagnosed ischemic stroke was observed until the end of 2015. We categorized the study population according to weight change and performed multivariable analysis to compare the risk., Results: Ischemic stroke was newly diagnosed in 113,591 subjects. The crude incidence rates of ischemic stroke per 1000 person-years according to the change in body weight were 3.059, 1.906, and 1.491 in the <-5%, ±5%, and ≥+5% groups, respectively. After adjusting all variables, the hazard ratio (HR) of ischemic stroke was higher in subjects who underwent weight loss (HR 1.152) or weight gain (HR 1.087) than in those who maintained their weight. When analyzed by eight groups of 5% intervals, the risk showed a U-shaped curve with those who maintained their weight showing the lowest risk., Conclusions: The risk of ischemic stroke was gradually increased in those who lost or gained more than 5% of their weight over four years, after adjusting for confounders. We should be aware of the increased risk of ischemic stroke in people who undergo weight change and should identify and manage the cause of weight change., Competing Interests: The authors have declared that no competing interests exist.

Background: Anastomotic leakage can be classified by free and contained leakage according to clinical manifestations. The risk factors and their comparison between these leakage subtypes are uncertain. This study aims to evaluate anastomotic leakage patterns and to compare clinical features between free and contained leakages after low anterior resection for rectal cancer., Materials and Methods: Between January 2005 and December 2012, a total of 2035 consecutive patients who underwent low anterior resection for primary rectal cancer were evaluated retrospectively at two-tertiary referral centers. The primary end points of this study were to assess detailed clinical features among leakage subtypes. The secondary end point was to compare risk factors between free and contained leakages., Results: Patients were subdivided into a no leakage group (n = 1890), free leakage group (n = 73), and contained leakage group (n = 72). Free leakage occurred more frequently in laparoscopic and robotic surgeries than open surgery (p = 0.015). On the other hand, contained leakage was developed in a higher rate of patients who received preoperative chemoradiotherapy (p<0.001). The mean development time was 4.6 days in the free leakage group, and 23.6 days in the contained leakage group. Patients with free leakage had a lower rate of a defunctioning stoma than contained leakage (5.5% vs. 29.2%, p<0.001). Risk factors for free leakage were smoking, tumor location, and laparoscopic surgery. However, tumor location and preoperative chemoradiotherapy increased the risk for contained leakage., Conclusions: Contained leakage in rectal cancer surgery showed different clinical manifestations and risk factors compared to free leakage. It is necessary to pay more attention to patients with particular risk factors for anastomotic leakage subtypes., Competing Interests: The authors have declared that no competing interests exist.

Background: The Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines recommend intra-access flow (Qa) measurement as the preferred vascular access surveillance method over static intra-access pressure ratio (SIAPR). Recently, it has become possible to perform Qa measurement during hemodialysis using thermodilution method called blood temperature monitoring (BTM) with the Twister device. The aim of this study was to investigate the correlation between Qa by BTM and SIAPR and to compare the performance of two tests in prediction of vascular access stenosis., Methods: The study was performed from January 2016 to November 2017 and included 97 patients with arteriovenous fistulas (AVF). Qa by BTM and SIAPR were simultaneously measured every 1~3 months with a total of 449 measurements during study period., Results: In our study population, mean age was 59.9±10.0 years and 61.9% were diabetes. The mean Qa obtained by BTM was 1186±588 mL/min. There was no correlation between Qa by BTM and venous SIAPR (r = 0.061, P = 0.196). Angiography identified 36 stenotic AVFs (37.1%) among the study subjects. They included 13 cases with only inflow stenosis, 6 with only outflow stenosis, and 17 with stenosis on both sides. Receiver-operating characteristic (ROC) curve analysis showed that Qa by BTM had higher discriminative ability to diagnose vascular access stenosis compared to SIAPR (P <0.001). The Qa less than 583 mL/min showed the highest diagnostic accuracy in vascular stenosis prediction., Conclusion: Intradialytic measurement of Qa by BTM showed better diagnostic power over venous SIAPR in prediction of vascular access stenosis., Competing Interests: The authors have declared that no competing interests exist.

Objective: The purpose of this study was to investigate the risk factors that influence depression among single mothers., Methods: Participants were 195 single mothers and 357 married mothers living in an urban community in South Korea. All subjects completed self-report questionnaires that included the following self-rating scales: the Global Assessment of Recent Stress, the Center for Epidemiologic Studies-Depression scale, and the Korean version of the Alcohol Use Disorder Identification Test. Multiple logistic regression analysis was performed to examine independent factors affecting single mothers' depression., Results: The prevalence of depression differed notably between the single mothers and the control group, at 33% and 8%, respectively. In the single mothers, young age, low income, residential instability, high stress, and high alcohol-related problems were determined to be associated with depression. Furthermore, after adjusting for covariates, living in rental housing (OR = 11.46, 95% CI 1.72-76.46) was found to be an independent risk factor of depression in the single mothers, while stress (OR = 1.16, 95% CI 1.09-1.24) was found to have this effect on the married mothers., Conclusions: Practical services concerning economic stability and parenting support should be provided for single mothers to reduce depression among this demographic., Competing Interests: The authors have declared that no competing interests exist.

Background: Diabetic patients are susceptible to renal ischemia-reperfusion injury, which leads to perioperative complications. Activation of NOD-like receptor protein 3 (NLRP3) inflammasome participates in the development of diabetes, and contributes to renal ischemia-reperfusion injury. Dexmedetomidine (DEX), a highly selective α2-adrenoreceptor agonist, shows renoprotective effects against ischemia-reperfusion injury. We aimed to elucidate the effects, underlying mechanisms, and optimal timing of DEX treatment in diabetic rats., Methods: Male Sprague-Dawley rats (n = 12 per group) were randomly divided into normal-sham, diabetes-sham, diabetes-ischemia-reperfusion-control, diabetes-ischemia-reperfusion-DEX-pre-treatment, and diabetes-ischemia-reperfusion-DEX-post-treatment groups. Renal ischemia-reperfusion injury was induced in diabetic rats by occlusion of both renal arteries for 45 min, followed by reperfusion for 24 h. DEX (10 μg/kg) was administered intraperitoneally 1 h before ischemia (pre-treatment) or upon reperfusion (post-treatment). After reperfusion, renal tissue was biochemically and histopathologically evaluated., Results: DEX treatment attenuated ischemia reperfusion-induced increase in NLRP3, caspase-1, IL-1β, phospho-AKT, and phospho-ERK signaling. Moreover, oxidative stress injury, inflammatory reactions, apoptosis, and renal tubular damage were favorably modulated by DEX treatment. Furthermore, post-reperfusion treatment with DEX was significantly more effective than pre-treatment in modulating NLRP3 inflammasome, AKT and ERK signaling, and oxidative stress., Conclusions: This study shows that the protective effects of DEX in renal ischemia-reperfusion injury are preserved in diabetic conditions and may potentially provide a basis for the use of DEX in clinical treatment of renal ischemia-reperfusion injury., Competing Interests: The authors have declared that no competing interests exist.

Repeated exposure to traumatic experiences may put professional firefighters at increased risk of developing posttraumatic stress disorder (PTSD). To date, however, the rate of PTSD symptoms, unmet need for mental health treatment, and barriers to treatment have only been investigated in subsamples rather than the total population of firefighters. We conducted a nationwide, total population-based survey of all currently employed South Korean firefighters (n = 39,562). The overall response rate was 93.8% (n = 37,093), with 68.0% (n = 26,887) complete responses for all variables. The rate of current probable PTSD was estimated as 5.4%. Among those with current probable PTSD (n = 1,995), only a small proportion (9.7%) had received mental health treatment during the past month. For those who had not received treatment, perceived barriers of accessibility to treatment (29.3%) and concerns about potential stigma (33.8%) were reasons for not receiving treatment. Although those with higher PTSD symptom severity and functional impairment were more likely to seek treatment, greater symptom severity and functional impairment were most strongly associated with increased concerns about potential stigma. This nationwide study points to the need for new approaches to promote access to mental health treatment in professional firefighters.

Type 1 diabetes with periodontitis shows elevated TNF-α expression. Tumor necrosis factor (TNF)-α stimulates the expression of receptor activator of nuclear factor-κB ligand (RANKL) and sclerostin. The objective of this study was to determine the effect of TNF-α expression of osteocytic RANKL and sclerostin in type 1 diabetes rats with periodontitis using infliximab (IFX), a TNF-α antagonist. Rats were divided into two timepoint groups: day 3 and day 20. Each timepoint group was then divided into four subgroups: 1) control (C, n = 6 for each time point); 2) periodontitis (P, n = 6 for each time point); 3) diabetes with periodontitis (DP, n = 8 for each time point); and 4) diabetes with periodontitis treated with IFX (DP+IFX, n = 8 for each time point). To induce type 1 diabetes, rats were injected with streptozotocin (50 mg/kg dissolved in 0.1 M citrate buffer). Periodontitis was then induced by ligature of the mandibular first molars at day 7 after STZ injection (day 0). IFX was administered once for the 3 day group (on day 0) and twice for the 20 day group (on days 7 and 14). The DP group showed greater alveolar bone loss than the P group on day 20 (P = 0.020). On day 3, higher osteoclast formation and RANKL-positive osteocytes in P group (P = 0.000 and P = 0.011, respectively) and DP group (P = 0.006 and P = 0.017, respectively) than those in C group were observed. However, there was no significant difference in osteoclast formation or RANKL-positive osteocytes between P and DP groups. The DP+IFX group exhibited lower alveolar bone loss (P = 0.041), osteoclast formation (P = 0.019), and RANKL-positive osteocytes (P = 0.009) than that of the DP group. On day 20, DP group showed a lower osteoid area (P = 0.001) and more sclerostin-positive osteocytes (P = 0.000) than P group. On days 3 and 20, the DP+IFX group showed more osteoid area (P = 0.048 and 0.040, respectively) but lower sclerostin-positive osteocytes (both P = 0.000) than DP group. Taken together, these results suggest that TNF-α antagonist can diminish osteocytic RANKL/sclerostin expression and osteoclast formation, eventually recovering osteoid formation. Therefore, TNF-α might mediate alveolar bone loss via inducing expression of osteocytic RANKL and sclerostin in type 1 diabetes rats with periodontitis.

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.

Purpose: To identify ocular parameters corresponding to asymmetric visual field (VF) loss in normal tension glaucoma (NTG) through intereye comparisons., Patients and Methods: Medical records of NTG patients with asymmetric and symmetric VF losses were retrospectively reviewed. The criterion for asymmetry in VF was 6 dB difference of mean deviation. Refractive error, intraocular pressure (IOP), central corneal thickness, ovality index, and peripapillary atrophy (PPA)/disc area ratio were obtained from each patient. Intereye comparison was performed for asymmetric group, symmetric group, and myopic and nonmyopic asymmetric subgroups., Results: We included 155 patients; 110 patients in asymmetric group and 45 patients in symmetric group. In intereye comparison for total asymmetric group, refractive error (P = 0.006), initial IOP (P = 0.001), ovality index (P = 0.008), and PPA (P < 0.001) were significantly asymmetric. For myopic subgroup, refractive error (P = 0.004), ovality index (P = 0.001), and PPA (P = 0.003) were significant factors. For nonmyopic subgroup, initial IOP (P = 0.003) and PPA (P = 0.007) were significant factors. Symmetric group showed no significant difference between the eyes. Multivariate analysis demonstrated that refractive error (P = 0.002) and PPA (P = 0.028) were significant factors in myopic subgroup, and initial IOP (P = 0.022) and PPA (P = 0.002) were significant factors in nonmyopic subgroup., Conclusions: In this intereye comparison, the more myopic eye in myopic NTG patient, and the more pressured eye in nonmyopic NTG patient demonstrated more severe VF loss. Myopic and nonmyopic patients may follow different pathophysiologic processes. Discriminative attentions should be paid to NTG patients by subtypes.

Background: Vascular calcification is common and may affect cardiac function in patients with end-stage renal disease (ESRD). However, little is known about the effect of residual renal function on vascular calcification and cardiac function in patients on hemodialysis., Methods: This study was conducted between January 2014 and January 2017. One hundred six patients with residual renal function on maintenance hemodialysis for 3 months were recruited. We used residual renal urea clearance (KRU) to measure residual renal function. First, abdominal aortic calcification score (AACS) and brachial-ankle pulse wave velocity (baPWV) were measured in patients on hemodialysis. Second, we performed echocardiography and investigated new cardiovascular events after study enrollment., Results: The median KRU was 0.9 (0.3-2.5) mL/min/1.73m2. AACS (4.0 [1.0-10.0] vs. 3.0 [0.0-8.0], p = 0.05) and baPWV (1836.1 ± 250.4 vs. 1676.8 ± 311.0 cm/s, p = 0.01) were significantly higher in patients with a KRU < 0.9 mL/min/1.73m2 than a KRU ≥ 0.9 mL/min/1.73m2. Log-KRU significantly negatively correlated with log-AACS (ß = -0.29, p = 0.002) and baPWV (ß = -0.19, P = 0.05) after factor adjustment. The proportion of left ventricular diastolic dysfunction was significantly higher in patients with a KRU < 0.9 mL/min/1.73m2 than with a KRU ≥ 0.9 mL/min/1.73m2 (67.9% vs. 49.1%, p = 0.05). Patients with a KRU < 0.9 mL/min/1.73m2 showed a higher tendency of cumulative cardiovascular events compared to those with a KRU ≥ 0.9 ml/min/1.73m2 (P = 0.08)., Conclusions: Residual renal function was significantly associated with vascular calcification and left ventricular diastolic dysfunction in patients on hemodialysis.

Purpose: To determine peripapillary vessel density in eyes with perimetric glaucoma (PG) or preperimetric glaucoma (PPG) compared to normal controls using optical coherence tomography-angiography (OCT-A)., Methods: We recruited 13 patients with unilateral perimetric normal-tension glaucoma (NTG) and fellow preperimetric NTG showing only inferotemporal retinal nerve fiber layer (RNFL) defect in red-free RNFL photography in both eyes. We also enrolled 9 healthy controls. Using OCT-A, radial peripapillary capillary densities at inferotemporal and superotemporal regions were evaluated. Paired comparison of peripapillary vessel density was performed for PG eye, PPG eye, and normal eye., Results: A total of 26 eyes of the 13 patients with unilateral PG and fellow PPG eyes and 18 eyes of 9 normal controls were analyzed. Vessel densities at the whole peripapillary region and inferotemporal region in PG eyes were significantly lower than those in PPG eyes (P = 0.001, P<0.001, respectively). Comparison between PPG and normal eyes showed no significant difference in the whole peripapillary region or the inferotemporal region (P = 0.654, P = 0.174, respectively). There was no significant (P = 0.288) difference in vessel density at superotemporal region among the three types of eyes (PG eye, PPG eye, and normal eye)., Conclusion: PPG eyes and normal eyes were found to have the similar densities of peripapillary microvasculature at the area with nerve fiber layer defect, whereas in PG eye, there was a significant decrease in vessel density at the area of RNFL thinning. This provides evidence that microvascular compromise in the retina might be a secondary change to nerve fiber layer degeneration in the pathogenesis of NTG.

Objective: The purpose of this study was to determine whether a CT interpretation with imaging pattern analysis differentiates Kikuchi disease (KD) from the two more frequently encountered differential lymph nodes diagnoses of tuberculous lymphadenopathy (TL) and reactive hyperplasia (RH)., Materials and Methods: Between January 2012 and July 2015, 20 patients with KD (6 men, 14 women; mean age, 27.80 years), 36 patients with RH (10 men, 26 women; mean age, 33.08 years) and 34 patients with TL (17 men, 17 women; mean age, 39.82 years) were pathologically diagnosed using US-guided fine needle aspiration biopsy, core needle biopsy, or surgical excisional biopsy. We recorded the total number, location, and size of the affected cervical lymph nodes, and two radiologists reviewed the characteristic imaging findings, including the presence of necrosis, cortical enhancement pattern, perinodal infiltration, conglomeration and nodal calcification, to form a consensus. In addition, we compared two attenuation indices on the nonnecrotic portion of the affected lymph nodes, nodal cortical attenuation (NCA) and the ratio of NCA to the adjacent muscle (NCA/M)., Results: Conglomeration, enhancement pattern and NCA/M values were independent predictive CT features to distinguish KD from RH. Age and enhancement pattern discriminated KD from TL. Only the mean NCA/M value was a statistically significant CT feature (p = .008) in differentiating KD from both RH+TL. The mean NCA/M of KD (1.67 ± 0.20) was significantly higher than that of RH (1.49 ± 0.20) or TL (1.47 ± 0.21)., Conclusion: Our results indicate that in case of nonnecrotic lymphadenopathy, a higher NCA/M index can differentiate KD from RH and TL. In addition, the enhancement pattern according to the degree of necrosis discriminated between KD and TL in the case of necrotic lymphadenopathy.

Background: Recent studies have suggested the importance of non-alcoholic fatty liver disease (NAFLD) and systemic inflammation in the development of atherosclerosis. The aim of this study was to compare the risk for coronary artery calcification (CAC) development according to the status of NAFLD and inflammation over four years of follow-up in subjects without baseline CAC., Methods: A total of 1,575 participants in a health screening program were divided into four groups according to baseline NAFLD state and high-sensitivity C-reactive protein (hs-CRP) (median 0.06 mg/L) levels as follows: no NAFLD and hs-CRP <0.06 mg/L, no NAFLD and hs-CRP ≥0.06 mg/L, NAFLD and hs-CRP <0.06 mg/L, and NAFLD and hs-CRP ≥0.06 mg/L. Coronary artery calcium score (CACS) was repeatedly measured by multi-detector computed tomography at four-year intervals and CAC development during those intervals was monitored in subjects with baseline CACS = 0., Results: Over four years, 148 subjects (9.4%) developed CAC. The proportion of subjects who developed CAC was significantly higher in subjects with NAFLD at baseline compared with those without NAFLD at baseline (6.8 vs. 12.4%, p<0.01), and it was also higher in subjects with hs-CRP ≥0.06 mg/L compared with those with hs-CRP <0.06 mg/L (7.2 vs. 11.5%, p<0.01). In addition, the proportion of subjects who developed CAC was highest in subjects with NAFLD and hs-CRP ≥0.06 mg/dL, followed by subjects with NAFLD, subjects without NAFLD and hs-CRP ≥0.06 mg/L, and subjects without NALFD and hs-CRP <0.05 mg/L at baseline, in that order (13.7, 10.0, 8.3, and 5.8%, respectively; p for trend<0.01). The odds ratio for CAC development was highest in subjects with NAFLD and hs-CRP ≥0.06 mg/L (1.67, 95% CI 1.01-2.77), though it was attenuated after adjustment for body mass index., Conclusions: The concomitant presence of NAFLD and systemic inflammation as assessed by hs-CRP increases the risk of CAC development over four years.

Background: Recent studies suggest a role for hyperlipidemia in the development of diabetes. The aim of this study is to analyze the relationship between variations of total cholesterol (TC) levels and the risk for type 2 diabetes development from a Korean nationwide population-based database., Materials and Methods: We examined the General Health Check-up sub-dataset of the Korean National Health Insurance Service (NHIS) of 2,827,950 participants who had at least three health check-ups between 2002 and 2007, and were not reported to have diabetes during that time. The variations of TC levels between the examinations were calculated as follows: [Formula: see text]. The examinees were divided into 10 groups according to TC variation, and the hazard ratio for diabetes development from 2007 to 2013, were analyzed., Results: During the follow-up period, 3.4% of the participants had developed diabetes. The hazard ratio (HR) for diabetes development relative to the overall risk in the whole study population started to be higher than 1.0 from eighth decile of TC variation. The highest decile group showed an increased HR for diabetes development after adjustment for confounding variables (1.139; 95% confidence interval 1.116~1.163). These results were similar regardless of the use of anti-hyperlipidemic medication and baseline TC levels., Conclusions: The participants with a large variation in TC levels showed an increased risk for diabetes development, independent of the use of anti-hyperlipidemic medications. These results suggest a relationship between fluctuations in lipid levels and the development of type 2 diabetes.

Background: Recent studies suggest an association between Lipoprotein(a) [Lp(a)] and the development of diabetes mellitus. We analyzed the association between baseline Lp(a) levels and diabetes development after 4 years of follow-up, in a population of apparently healthy Korean subjects., Methods: A total of 2,536 non-diabetic participants (mean age: 41 years, men: 92%) of a health checkup program were included in the study. Diabetes development was defined by fasting blood glucose ≥126 mg/dL, HbA1c ≥6.5%, and self-reported treatment of diabetes. Homeostasis model assessment (HOMA) indices were used to assess insulin resistance (IR) and insulin secretion (IS). Presence of IR and impaired IS was defined by being in the highest quartile of HOMA-IR and in the lowest quartile HOMA-IS., Results: After four years, 3.4% of the participants developed diabetes. The odds ratio (OR) of developing diabetes was lowest in the 4th quartile group of baseline Lp(a) (0.323 [95% CI 0.153-0.685])with the 1st quartile group as the reference. The subjects with both IR & impaired IS plus baseline Lp(a)<50 mg/dL showed the higher OR for diabetes development compared with those without IR and normal IS as the reference (67.277 [20.218-223.871], and those with IR plus Lp(a)<50 mg/dL showed higher OR for diabetes than in those with impaired IS and Lp(a)<50 mg/dL (3.811 [1.938-7.495] vs. 3.452 [1.620-7.353])., Conclusions: The subjects with low baseline Lp(a) level showed higher risk for development of diabetes compared with high baseline Lp(a) level, and this was prominent in those with IR than in those with impaired IS.

Increased glycemic exposure, even below the diagnostic criteria for diabetes mellitus, is crucial in the pathogenesis of diabetic microvascular complications represented by microalbuminuria. Nonetheless, there is limited evidence regarding which single nucleotide polymorphisms (SNPs) are associated with prediabetes and whether genetic predisposition to prediabetes is related to microalbuminuria, especially in the general population. Our objective was to answer these questions. We conducted a genomewide association study (GWAS) separately on two population-based cohorts, Ansung and Ansan, in the Korean Genome and Epidemiology Study (KoGES). The initial GWAS was carried out on the Ansung cohort, followed by a replication study on the Ansan cohort. A total of 5682 native Korean participants without a significant medical illness were classified into either control group (n = 3153) or prediabetic group (n = 2529). In the GWAS, we identified two susceptibility loci associated with prediabetes, one at 17p15.3-p15.1 in the GCK gene and another at 7p15.1 in YKT6. When variations in GCK and YKT6 were used as a model of prediabetes, this genetically determined prediabetes increased microalbuminuria. Multiple logistic regression analyses revealed that fasting glucose concentration in plasma and SNP rs2908289 in GCK were associated with microalbuminuria, and adjustment for age, gender, smoking history, systolic blood pressure, waist circumference, and serum triglyceride levels did not attenuate this association. Our results suggest that prediabetes and the associated SNPs may predispose to microalbuminuria before the diagnosis of diabetes mellitus. Further studies are needed to explore the details of the physiological and molecular mechanisms underlying this genetic association., Competing Interests: The authors have declared that no competing interests exist.

Hyperglycemia, which reduces the efficacy of treatments and worsens clinical outcomes, is common in stroke. Ability of pregabalin to reduce neuroexcitotoxicity may provide protection against stroke, even under hyperglycemia. We investigated its protective effect against hyperglycemic stroke and its possible molecular mechanisms. Male Wistar rats administered dextrose to cause hyperglycemia, underwent middle cerebral artery occlusion for 1 h and subsequent reperfusion. Rats were treated with an intraperitoneal injection of 30 mg/kg pregabalin or an equal amount of normal saline at the onset of reperfusion (n = 16 per group). At 24 h after reperfusion, neurological deficit, infarct volume, and apoptotic cell count were assessed. Western blot analysis was performed to determine protein expression of high-mobility group box 1 (HMGB1), toll-like receptor-4 (TLR-4), phosphorylated nuclear factor-kappa B (p-NF-κB), interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), phosphorylated inducible and endothelial nitric oxide synthase (p-iNOS, p-eNOS), Bcl-2, Bax, Cytochrome C, and caspase-3 in the brain. Pregabalin-treated rats showed significantly improved neurological function (31% decrease in score), reduced infarct size (by 33%), fewer apoptotic cells (by 63%), and lower expression levels of HMGB1, TLR4, p-NF-κB, IL-1β, and TNF- α, compared with control rats. Decreased p-iNOS and increased p-eNOS expressions were also observed. Expression of Bax, Cytochrome C, and cleaved caspase-3/caspase3 was significantly downregulated, while Bcl-2 expression was increased by pregabalin treatment. Pregabalin administration upon reperfusion decreased neuronal death and improved neurological function in hyperglycemic stroke rats. Cogent mechanisms would include attenuation of HMGB1/TLR-4-mediated inflammation and favorable modulation of the NOS., Competing Interests: Pfizer Inc. (New York, NY, USA) have provided pregabalin via their compound transfer program. This does not alter adherence to PLOS ONE policies on sharing data and materials.

Background: The number of pneumonia patients increased suddenly in Korean military hospitals in late December 2014, indicating the urgent need for an epidemic outbreak investigation., Methods: We conducted a prospective study of pneumonia etiology among immunocompetent young adults admitted to Daejeon Armed Forces hospital. Patient blood and sputum samples were subjected to conventional culture, serology, and polymerase chain reaction tests for respiratory viruses and atypical pathogens., Results: From January to May 2015, we enrolled 191 (189 male) adults with pneumonia; the mean age was 20.1 ± 1.3 years. Five patients had severe pneumonia, and one died. Pathogenic human adenoviruses were most common (HAdV, 153/191 [80.1%]), indicating a HAdV pneumonia outbreak. Genotyping of 35 isolates indicated that 34 matched HAdV-55 and one matched HAdV-2. HAdV pneumonia infected recruit trainees most frequently. High and prolonged fever, nasal congestion, sore throat, and pharyngeal inflammation were significantly more common in the HAdV pneumonia group, compared to patients with other or unknown causes of pneumonia. Only 12% of HAdV pneumonia patients displayed leukocytosis, whereas febrile leukopenia (62.7%) and thrombocytopenia (41%) were commonly observed. HAdV pneumonia patient chest CT scans displayed ground glass opacity (with or without septal thickness) with consolidation in 50.0% of patients., Conclusions: An outbreak of HAdV respiratory infection occurred at the Korean military training center. HAdV pneumonia exhibited specific laboratory and clinical features, and although most patients were cured without complication, some progressed to respiratory failure and fatality. Therefore, HAdV vaccine should be provided to military trainees in Korea., Competing Interests: The authors have declared that no competing interests exist.

Background: In hemodialysis patients, fluid overload and malnutrition are accompanied by extracellular fluid (ECF) expansion and intracellular fluid (ICF) depletion, respectively. We investigated the relationship between ECF/ICF ratio (as an integrated marker reflecting both fluid overload and malnutrition) and survival and cardiovascular disease (CVD) in the context of malnutrition-inflammation-arteriosclerosis (MIA) complex., Methods: Seventy-seven patients from a single hemodialysis unit were prospectively enrolled. The ECF/ICF volume was measured by segmental multi-frequency bioimpedance analysis. MIA and volume status were measured by serum albumin, C-reactive protein (CRP), pulse wave velocity (PWV) and plasma B-type natriuretic peptide (BNP), respectively., Results: The mean ECF/ICF ratio was 0.56±0.06 and the cut-off value for maximum discrimination of survival was 0.57. Compared with the low ECF/ICF group, the high ECF/ICF group (ratio≥0.57, 42%) had higher all-cause mortality, CVD, CRP, PWV, and BNP, but lower serum albumin. During the 5-year follow-up, 24 all-cause mortality and 38 CVD occurred (18 and 24, respectively, in the high ECF/ICF group versus 6 and 14 respectively in the low ECF/ICF group, P<0.001). In the adjusted Cox analysis, the ECF/ICF ratio nullifies the effects of the MIA and volume status on survival and CVD and was an independent predictor of all-cause mortality and CVD: hazard ratio (95% confidence interval); 1.12 (1.01-1.25) and 1.09 (1.01-1.18) for a 0.01 increase in the ECF/ICF ratio. The degree of malnutrition (albumin), inflammation (CRP), arteriosclerosis (PWV), and fluid overload (BNP) were correlated well with the ECF/ICF ratio., Conclusions: Hemodialysis patients with high ECF/ICF ratio are not only fluid overloaded, but malnourished and have stiff artery with more inflammation. The ECF/ICF ratio is highly related to the MIA complex, and is a major risk indicator for all-cause mortality and CVD., Competing Interests: The authors have declared that no competing interests exist.

Periodontitis is a very common oral inflammatory disease that results in the destruction of supporting connective and osseous tissues of the teeth. Although the exact etiology is still unclear, Gram-negative bacteria, especially Porphyromonas gingivalis in subgingival pockets are thought to be one of the major etiologic agents of periodontitis. Endothelin (ET) is a family of three 21-amino acid peptides, ET-1, -2, and -3, that activate G protein-coupled receptors, ETA and ETB. Endothelin is involved in the occurrence and progression of various inflammatory diseases. Previous reports have shown that ET-1 and its receptors, ETA and ETB are expressed in the periodontal tissues and, that ET-1 levels in gingival crevicular fluid are increased in periodontitis patients. Moreover, P. gingivalis infection has been shown to induce the production of ET-1 along with other inflammatory cytokines. Despite these studies, however, the functional significance of endothelin in periodontitis is still largely unknown. In this study, we explored the cellular and molecular mechanisms of ET-1 action in periodontitis using human gingival epithelial cells (HGECs). ET-1 and ETA, but not ETB, were abundantly expressed in HGECs. Stimulation of HGECs with P. gingivalis or P. gingivalis lipopolysaccharide increased the expression of ET-1 and ETA suggesting the activation of the endothelin signaling pathway. Production of inflammatory cytokines, IL-1β, TNFα, and IL-6, was significantly enhanced by exogenous ET-1 treatment, and this effect depended on the mitogen-activated protein kinases via intracellular Ca2+ increase, which resulted from the activation of the phospholipase C/inositol 1,4,5-trisphosphate pathway. The inhibition of the endothelin receptor-mediated signaling pathway with the dual receptor inhibitor, bosentan, partially ameliorated alveolar bone loss and immune cell infiltration. These results suggest that endothelin plays an important role in P. gingivalis-mediated periodontitis. Thus, endothelin antagonism may be a potential therapeutic approach for periodontitis treatment., Competing Interests: The authors have declared that no competing interests exist.

The aim of this study is to investigate whether the beneficial effect of exendin-4 on hepatic steatosis is mediated by β-catenin signaling. After the HepG2 human hepatoma cells were treated with PA for 24 hours, total triglycerides levels were increased in a dose-dependent manner, and the expression levels of perilipin family members were upregulated in cells treated with 400 μM PA. For our in vitro model of hepatic steatosis, HepG2 cells were treated with 400 μM palmitic acid (PA) in the presence or absence of 100 nM exendin-4 for 24 hours. PA increased the expression of lipogenic genes, such as sterol regulatory element-binding protein 1c (SREBP-1c), peroxisome proliferator-activated receptor gamma (PPARγ), stearoyl-CoA desaturase 1 (SCD1), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) and triglyceride synthesis-involved genes, such as diacylglycerol acyltransferase 1 (DGAT1) and diacylglycerol acyltransferase 2 (DGAT2) in HepG2 cells, whereas exendin-4 treatment significantly prevented the upregulation of SREBP-1c, PPARγ, SCD1, FAS, ACC, DGAT1 and DGAT2. Moreover, exendin-4 treatment increased the expression of phosphorylated glycogen synthase kinase-3 beta (GSK-3β) in the cytosolic fraction and the expression of β-catenin and transcription factor 4 (TCF4) in the nuclear fraction. In addition, siRNA-mediated inhibition of β-catenin upregulated the expression of lipogenic transcription factors. The protective effects of exendin-4 on intracellular triglyceride content and total triglyceride levels were not observed in cells treated with the β-catenin inhibitor IWR-1. These data suggest that exendin-4 treatment improves hepatic steatosis by inhibiting lipogenesis via activation of Wnt/β-catenin signaling., Competing Interests: The authors have declared that no competing interests exist.

Transplantation of ovarian tissue (OT) is currently the only clinical option to restore fertility with cryopreserved OT. However, follicle loss caused by ischemia and slow revascularization occurs in transplanted OT. To shorten the ischemic period and promote angiogenesis, some angiogenic factors have been used. Angiopoietin-2 (Ang2) is one of the major angiogenic factors and has been reported to promote blood vessels and increase vascular permeability in ischemic and/or hypoxic environment. This study was performed to investigate the effects of Ang2 on follicle integrity and revascularization of transplanted mouse OT. Five-week-old B6D2F1 female mice were divided into a control group and two Ang2 groups, followed by ovary collection and vitrification. After warming, the ovaries were autotransplanted into kidney capsules with/without Ang2 injection (50 or 500 ng/kg), and then the mice were sacrificed at days 2, 7, 21, and 42 after transplantation. A total 2,437 follicles in OT grafts were assessed for follicular density, integrity, and classification by using hematoxylin and eosin staining. Apoptosis and revascularization were evaluated by using TUNEL assay and CD31 immunohistochemistry, respectively. Serum follicle-stimulating hormone (FSH) levels were measured by using enzyme-linked immunosorbent assay. Both Ang2 groups showed remarkable increase in morphologically intact follicle ratio across all grafting durations except D21. The numbers of CD31(+) vessels were significantly increased in both Ang2 groups compared with the control group at all durations, except in the 50 ng Ang2 group at D42. However, the mean numbers of follicles of the grafts, apoptosis ratios, and serum FSH levels showed no significant differences among the groups. Our results show that Ang2 treatment significantly increased the intact follicle ratios and the number of blood vessels of the mouse OT grafts. However, further studies performed with large animal or human OT are necessary before clinical application for fertility preservation in cancer patients, and the reliability of the systemic effects of Ang2 should be verified., Competing Interests: The authors have declared that no competing interests exist.