A multi-layered network model identifies Akt1 as a common modulator of neurodegeneration.

The accumulation of misfolded and aggregated proteins is a hallmark of neurodegenerative proteinopathies. Although multiple genetic loci have been associated with specific neurodegenerative diseases (NDs), molecular mechanisms that may have a broader relevance for most or all proteinopathies remain poorly resolved. In this study, we developed a multi-layered network expansion (MLnet) model to predict protein modifiers that are common to a group of diseases and, therefore, may have broader pathophysiological relevance for that group. When applied to the four NDs Alzheimer's disease (AD), Huntington's disease, and spinocerebellar ataxia types 1 and 3, we predicted multiple members of the insulin pathway, including PDK1, Akt1, InR, and sgg (GSK-3ß), as common modifiers. We validated these modifiers with the help of four Drosophila ND models. Further evaluation of Akt1 in human cell-based ND models revealed that activation of Akt1 signaling by the small molecule SC79 increased cell viability in all models. Moreover, treatment of AD model mice with SC79 enhanced their long-term memory and ameliorated dysregulated anxiety levels, which are commonly affected in AD patients. These findings validate MLnet as a valuable tool to uncover molecular pathways and proteins involved in the pathophysiology of entire disease groups and identify potential therapeutic targets that have relevance across disease boundaries. MLnet can be used for any group of diseases and is available as a web tool at http://ssbio.cau.ac.kr/software/mlnet.

Comparison of the Triglyceride Glucose Index and Modified Triglyceride Glucose Indices to Predict Nonalcoholic Fatty Liver Disease in Youths.

OBJECTIVE: To assess the associations between the triglyceride glucose (TyG) index and modified TyG indices with nonalcoholic fatty liver disease (NAFLD) and evaluate their ability as predictors of NAFLD in youths. STUDY DESIGN: We analyzed the cross-sectional data of 3728 individuals aged 10-19 years using the Korea National Health and Nutrition Examination Survey, a nationally representative survey. Logistic regression analysis was performed, and ORs and 95% CIs of tertiles 2 and 3 for each variable for predicting NAFLD were calculated and compared with those of tertile 1 as the reference. Receiver operating characteristic (ROC) curves were plotted to evaluate the ability of each variable for NAFLD prediction. RESULTS: All TyG and modified TyG indices exhibited progressively increased ORs and 95% CIs for NAFLD across all tertiles (all P < .001). In addition, all TyG and modified TyG indices significantly predicted NAFLD through ROC curves. All modified TyG indices were superior to the TyG index for predicting NAFLD in all subjects and in males. Among females, the TyG-waist-to-height ratio was superior to the TyG index, TyG-body mass index (BMI), and TyG-waist circumference (WC), and the TyG-BMI SDS and TyG-WC were superior to the TyG index. CONCLUSIONS: The TyG and modified TyG indices are markers for NAFLD prediction in youths, and the modified TyG indices are superior to the TyG index. Modified TyG indices have the potential to be simple and cost-effective markers in screening for NAFLD in youths.

Structural characteristics of sediment humins from South Korean lakes and their phenanthrene binding compared to other carbon sources.

Sediment humins are extremely important for binding hydrophobic organic contaminants in rivers and lakes. Nonetheless, little is known about their structure and binding. We, therefore, examined the structure and phenanthrene sorption affinity of sediment humin samples upstream, midstream, and downstream from two artificial lakes in South Korea by using the elemental 13C-NMR analysis, Freundlich model, and Langmuir model. The characteristics and phenanthrene sorption affinity of sediment humins were also compared with those of sediment humic acids from similar origins as well as soil humins/humic acids in South Korea from previous studies by using principal component analysis. In both lakes, downstream sediment humins exhibited lower N/C, O/C, and (N + O)/C ratios, lower internal oxidation, and higher aliphaticity due to the presence of long-chain aliphatic compounds generated during anaerobic decomposition. The principal component analysis results also showed that C,H-alkyl, O-alkyl, and polar organic carbon contents were significantly different when comparing the up-mid stream and downstream sediment samples in Daecheong Lake. In addition, midstream sediment humin in Andong Lake presented higher C,H-alkyl and lower polar organic carbon contents compared to those of up-downstream samples. In both lakes, the sorption coefficient and adsorption isotherm linearity were positively correlated with the C,H-alkyl content and negatively correlated with the O-aryl content. Similar to C,H-alkyl and POC, C,H-alkyl, and (N + O)/C had an extremely high correlation coefficient when predicting the sorption coefficient (Freundlich model) and the maximum adsorption capacity (Langmuir model) of sediment humins. Sediment humins had higher C,H-alkyl contents and lower sorption coefficients than those of sediment humic acids and soil humins/humic acids. These findings provide key information for monitoring water quality and polycyclic aromatic hydrocarbon contamination in South Korean lake sediments.

Trends of Dyslipidemia in Korean Youth According to Sex and Body Mass Index: Based on the Korea National Health and Nutrition Examination Survey (2007-2018).

OBJECTIVE: To assess trends of dyslipidemia among youth, we investigated secular trends in serum lipid levels from 2007 to 2018 and the current prevalence of dyslipidemia in Korean children and adolescents. STUDY DESIGN: This cross-sectional study investigated lipid profiles of 10 734 youths aged 10-18 years using data from phases IV-VII of the Korea National Health and Nutritional Examination Survey. We assessed age-, sex-, and body mass index (BMI)-adjusted mean levels of lipids at each survey. RESULTS: Mean levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) levels increased from phase IV to VII. Among boys, the prevalence of acceptable levels of total cholesterol, LDL-C, and non-HDL-C decreased significantly (P = .005, P = .001, and P < .001, respectively). In girls, the prevalence of acceptable levels of total cholesterol, LDL-C, HDL-C, and non-HDL-C decreased significantly (P = .003, P = .005, P = .008, and P = .013, respectively). In BMI- and age-specific analyses, worsening trends in total cholesterol, LDL-C, and non-HDL levels were more apparent in youths with a normal BMI and young age. CONCLUSIONS: Dyslipidemia trends are worsening in Korean youth, even in those with a normal BMI and young age. Thus, future cardiovascular disease risk may increase and comprehensive management plans are required for youth with overweight or obesity and those with a normal BMI and young age.

Tannylated Calcium Carbonate Materials with Antacid, Anti-Inflammatory, and Antioxidant Effects.

Calcium carbonate (CaCO3)-based materials have received notable attention for biomedical applications owing to their safety and beneficial characteristics, such as pH sensitivity, carbon dioxide (CO2) gas generation, and antacid properties. Herein, to additionally incorporate antioxidant and anti-inflammatory functions, we prepared tannylated CaCO3 (TA-CaCO3) materials using a simple reaction between tannic acid (TA), calcium (Ca2+), and carbonate (CO32-) ions. TA-CaCO3 synthesized at a molar ratio of 1:75 (TA:calcium chloride (CaCl2)/sodium carbonate (Na2CO3)) showed 3-6 µm particles, comprising small nanoparticles in a size range of 17-41 nm. The TA-CaCO3 materials could efficiently neutralize the acid solution and scavenge free radicals. In addition, these materials could significantly reduce the mRNA levels of pro-inflammatory factors and intracellular reactive oxygen species, and protect chondrocytes from toxic hydrogen peroxide conditions. Thus, in addition to their antacid property, the prepared TA-CaCO3 materials exert excellent antioxidant and anti-inflammatory effects through the introduction of TA molecules. Therefore, TA-CaCO3 materials can potentially be used to treat inflammatory cells or diseases.

Competitive adsorption of heavy metals onto modified biochars: Comparison of biochar properties and modification methods.

Various biochars (BCs) have been developed to remove heavy metals contained in road runoff; however, there is insufficient information regarding the competitive adsorption efficiency of modified BC with regard to heavy metals due to a lack of comparative evaluation based on BC properties and modification methods. In this study, three different types of BC (RBC: rice husk, WBC: wood chip, MBC: mixture) were modified following five different methods: acidic, alkaline, oxidic, and manganese oxide (MnOx) and iron oxide (FeOx) impregnation. The changes in the physicochemical and morphological properties of the modified BC were investigated, and the adsorption characteristics of three heavy metals (Cd, Pb, and Zn) under single and mixed conditions were compared and evaluated. The improvements in the BC properties varied for different BC types and modification methods; in particular, alkaline and manganese modification caused substantial the changes in the surface area and functional groups (such as aromatic ring, -OH, and Mn-O groups). The BC prepared by manganese oxide impregnation absorbed a high amount of heavy metals (>9.15 mg/g) even under mixed conditions through cation exchange and surface complexation. The distribution coefficient (Kd) of heavy metals was high in the order of Pb > Cd > Zn; thus, the adsorption of Pb replaced that of Zn in competitive adsorption due to the difference in their affinity to BC. Therefore, the results suggest that BC prepared by manganese oxide impregnation is suitable for removing heavy metals from road runoff, as it maintained high heavy metals adsorption regardless of the BC material, even under competitive conditions.

Combined dual-size foam glass media filtration process with micro-flocculation for simultaneous removal of particulate and dissolved contaminants in urban road runoff.

In this study, a combined media filtration process with micro-flocculation (CMF) was developed, to simultaneously treat particulate and dissolved contaminants in urban road runoff. Dual-size foam glass media with stone and sand layers were applied and the efficiency of road runoff treatment was investigated according to filtration and micro-flocculation under various experimental conditions (stone/sand layer ratio, linear velocity, and coagulant types). Moreover, the removal efficiencies of suspended solids (SS), phosphorus, organic carbon, and heavy metals (Zn, Cu, Pb, Cd) by CMF were evaluated. The removal rate of SS was maintained to be above 84.1% for 1 h filtration by the dual-size foam glass, regardless of increasing pressure. The removal of phosphorus by micro-flocculation was more suitable in alum than ferric due to a higher initial floc growth rate and an increased particle size. The performance of the CMF was significantly improved over media filtration only process (MF) in removing both particulate and dissolved contaminants. The removal efficiency of all particulate pollutants by CMF was found to be more than 90%, and notably, the dissolved phosphorus, which was mostly not removed by MF, was also removed by 97.4%. Meanwhile, the backwash efficiency of CMF was half that of MF. Physical removal mechanisms, such as internal diffusion, dominated MF, whereas chemical removal mechanisms, such as adsorption and surface precipitation, dominated CMF. These results show the potential of the CMF process for the treatment of urban road runoff and identify the removal mechanisms of the filtration process that use micro-flocculation with dual-size foam glass.

Cardioprotective effects of genetically engineered cardiac stem cells by spheroid formation on ischemic cardiomyocytes.

BACKGROUND: Sca-1+ cardiac stem cells and their limited proliferative potential were major limiting factors for use in various studies. METHODS: Therefore, the effects of sphere genetically engineered cardiac stem cells (S-GECS) inserted with telomerase reverse transcriptase (TERT) were investigated to examine cardiomyocyte survival under hypoxic conditions. GECS was obtained from hTERT-immortalized Sca-1+ cardiac stem cell (CSC) lines, and S-GECS were generated using poly-HEMA. RESULTS: The optimal conditions for S-GECS was determined to be 1052 GECS cells/mm2 and a 48 h culture period to produce spheroids. Compared to adherent-GECS (A-GECS) and S-GECS showed significantly higher mRNA expression of SDF-1α and CXCR4. S-GECS conditioned medium (CM) significantly reduced the proportion of early and late apoptotic cardiomyoblasts during CoCl2-induced hypoxic injury; however, gene silencing via CXCR4 siRNA deteriorated the protective effects of S-GECS against hypoxic injury. As downstream pathways of SDF-1α/CXCR4, the Erk and Akt signaling pathways were stimulated in the presence of S-GECS CM. S-GECS transplantation into a rat acute myocardial infarction model improved cardiac function and reduced the fibrotic area. These cardioprotective effects were confirmed to be related with the SDF-1α/CXCR4 pathway. CONCLUSIONS: Our findings suggest that paracrine factors secreted from transplanted cells may protect host cardiomyoblasts in the infarcted myocardium, contributing to beneficial left ventricle (LV) remodeling after acute myocardial infarction (AMI).

Skullcapflavone II inhibits osteoclastogenesis by regulating reactive oxygen species and attenuates the survival and resorption function of osteoclasts by modulating integrin signaling.

Many bone diseases, such as osteoporosis and rheumatoid arthritis, are attributed to an increase in osteoclast number or activity; therefore, control of osteoclasts has significant clinical implications. This study shows how skullcapflavone II (SFII), a flavonoid with anti-inflammatory activity, regulates osteoclast differentiation, survival, and function. SFII inhibited osteoclastogenesis with decreased activation of MAPKs, Src, and cAMP response element-binding protein (CREB), which have been known to be redox sensitive. SFII decreased reactive oxygen species by scavenging them or activating nuclear factor-erythroid 2-related factor 2 (Nrf2), and its effects were partially reversed by hydrogen peroxide cotreatment or Nrf2 deficiency. In addition, SFII attenuated survival, migration, and bone resorption, with a decrease in the expression of integrin ß3, Src, and p130 Crk-associated substrate, and the activation of RhoA and Rac1 in differentiated osteoclasts. Furthermore, SFII inhibited osteoclast formation and bone loss in an inflammation- or ovariectomy-induced osteolytic mouse model. These findings suggest that SFII inhibits osteoclastogenesis through redox regulation of MAPKs, Src, and CREB and attenuates the survival and resorption function by modulating the integrin pathway in osteoclasts. SFII has therapeutic potential in the treatment and prevention of bone diseases caused by excessive osteoclast activity.-Lee, J., Son, H. S., Lee, H. I., Lee, G.-R., Jo, Y.-J., Hong, S.-E., Kim, N., Kwon, M., Kim, N. Y., Kim, H. J., Lee, Y. J., Seo, E. K., Jeong, W. Skullcapflavone II inhibits osteoclastogenesis by regulating reactive oxygen species and attenuates the survival and resorption function of osteoclasts by modulating integrin signaling.

Adolescents with thyroid nodules: retrospective analysis of factors predicting malignancy.

Thyroid nodules are less common in children than in adults. However, pediatric thyroid nodules have a higher rate of malignancy compared to those in adults, and increased risk of metastasis and recurrence. In the present study, we analyzed the clinical features as well as laboratory and thyroid ultrasound (US) findings of children and adolescents with thyroid nodules to identify predictive factors of thyroid cancer. We retrospectively analyzed 275 patients with thyroid nodules under 18 years of age who visited Severance Children's Hospital between January 2005 and May 2017. Among them, 141 patients who underwent ultrasonography-guided fine needle aspiration biopsy (FNAB), and four patients without FNAB who underwent surgical resection, were included in this study. The remaining 125 patients without FNAB and five patients with follow-up loss after FNAB were excluded. Clinical, laboratory, and US data were evaluated in 145 patients to establish the potential predictive factors of thyroid cancer. Thyroid malignancies were observed in 101 patients. Grade 2 goiters were seen more often in benign nodule group. Hypoechoic nodules, nodules with microcalcifications, abnormal lymph nodes, and irregular margins were findings significantly associated with thyroid cancer. The findings of hypoechoic nodule, nodule with microcalcifications, and abnormal lymph nodes showed statistical significance in predicting thyroid cancer.Conclusion: Hypoechoic nodules, nodules with microcalcifications, and abnormal lymph nodes are predictive factors for thyroid cancer in children. Therefore, further diagnostic evaluations, including FNAB, should be considered in patients with such findings.What is Known:• Thyroid nodules are less common in children than in adults, but pediatric thyroid nodules have a higher rate of malignancy, and also have increased risk of metastasis and recurrence.• Research on ways to predict thyroid cancer have mostly been accomplished in adult patients, and the application of risk stratification system has not been fully satisfactory in children, which requires further studies in pediatric thyroid nodules.What is New:• Hypoechoic nodules, nodules with microcalcifications, and abnormal lymph nodes are predictive factors for thyroid cancer in Korean children.

Savior in Desperate Situation: Successful TAVI for Critically Ill Patient with Severe Aortic Stenosis and Concomitant Constrictive Pericarditis Accompanied by Radiation Dermatitis, Complicated by Cold Abscess in Anterior Chest Wall.

BACKGROUND: Constrictive pericarditis (CP) can coexist with severe aortic stenosis (AS), especially in patients with previous mediastinal radiation. Because impaired diastolic filling by CP may aggravate hemodynamic abnormalities from severe AS, leading to very low cardiac output, concomitant AS and CP result in a critical debilitating condition and pose a challenge to therapy. CASE REPORT: A 79-year-old woman was brought to our hospital with New York Heart Association class IV dyspnea and severe frailty (clinical frailty scale 8). She had a history of chronic constrictive pericarditis, severe aortic stenosis with reduced left ventricular systolic function (ejection fraction 40%), paroxysmal atrial fibrillation, diabetes mellitus, and radiation dermatitis complicated by a cold abscess in the anterior chest wall from previous mediastinal radiation. She continually complained of dizziness, general weakness, and dyspnea despite optimal medical treatment, and her symptoms worsened recently while bedridden. Although simultaneous surgical pericardiectomy and aortic valve replacement is curative treatment, and the surgical risk was not high (Society of Thoracic Surgery score 4.745), her other comorbidities (radiation dermatitis, cold abscess, and severe frailty) eliminated the possibility of surgical treatment. Therefore, we decided on palliative treatment for CP after performing transcatheter aortic valve implantation (TAVI) for severe AS. We could not predict how she would recover from these conditions and were concerned about the high procedural risk associated with TAVI. Indeed, the patient had cardiac arrest during the TAVI procedure, and we implanted a 31-mm CoreValve while performing cardiac massage. After the patient recovered from cardiac arrest, we safely completed the TAVI procedure with a temporary pacemaker because of complete atrioventricular block. She recovered remarkably after TAVI with permanent pacemaker implantation, and is now able to walk without support. CONCLUSION: Reduced diastolic filling by chronic CP aggravates hemodynamic deterioration through severe AS, leading to a very serious debilitating condition including severe frailty and decompensated heart failure. Although surgical pericardiectomy and aortic valve replacement are recommended as optimal therapy, TAVI alone can be an alternative therapeutic option if surgery is not possible.

Enhancing the total organic carbon measurement efficiency for water samples containing suspended solids using alkaline and ultrasonic pretreatment methods.

In this study, we investigated the effect of sample pretreatments (ultrasonication and alkaline extraction) on total organic carbon (TOC) measurements for water samples containing suspended solids (SS) of four different origins (algae, soil, sewage sludge, and leaf litter) to more clearly assess the impact of particulate organic carbon (POC) in water. The effects each of ultrasonication (power, pulse, etc.) and alkaline extraction condition (concentration, time, etc.) on the TOC recovery and precision were investigated, and the results were compared with those of a new sample pretreatment method combining both methods. Alkaline treatment (0.01 mol/L NaOH) showed higher precision than ultrasonication (100/5 on/off pulse), and notably, the differences among the measured TOC values in samples of different origins were also further reduced in the alkaline treatment. This suggests that the ultrasonic pretreatment results can be mainly attributed to the increase in POC recovery through particle size reduction, whereas the alkaline treatment results are achieved through the enhancement of POC solubilization. It is also particularly noteworthy that a higher TOC recovery of 87.6% ± 7.4% with a higher precision of 8.4% could be obtained using the combined method, compared to each treatment (ultrasonic: TOC recovery 34.7%, relative standard deviation 63.1%; alkaline: 49.6% and 23.0%, respectively). Thus, simultaneous pretreatment with ultrasonication and alkaline extraction is expected to increase the oxidation rate of organic matter and the homogeneity of the samples, minimizing the loss of POC measurement values, and thereby improving the reliability of the TOC measurements of water samples containing SS.

Fimasartan reduces neointimal formation and inflammation after carotid arterial injury in apolipoprotein E knockout mice.

BACKGROUND: The beneficial effects of angiotensin II type 1 receptor blockers (ARBs) on atherosclerosis have been demonstrated in numerous studies. We investigated the effects of fimasartan on reducing neointimal formation and systemic inflammation after carotid artery (CA) injury in Apolipoprotein E knockout (ApoE KO) mice. METHODS: ApoE KO mice were randomly allocated to Group I (without CA injury), Group II (without CA injury + Fimasartan), Group III (CA injury), and Group IV (CA injury + Fimasartan). Fimasartan was orally administered everyday starting 3 days before iatrogenic left CA injury. RESULTS: At 28 days, neointimal hyperplasia and the inflammatory cytokines including TNFα, IL-6, ICAM, and MMP-9 in the peripheral blood were significantly reduced in Groups II and IV compared to Groups I and III, respectively. All fimasartan-administered groups revealed significant increases of CD4+CD25+Foxp3+ regulatory T (Treg) cells with increased plasma levels of IL-10 and TGFß. In addition, increased CD8+ T cells by fimasartan were correlated with reduced smooth muscle cell (SMC) proliferation in the neointima in Groups II and IV. Furthermore, the populations of Treg and CD8+ T cells in total splenocytes were increased in Groups II and IV compared to Groups I and III, respectively. The enlargement of spleens due to CA injury in the Group III was attenuated by fimasartan, as shown in the Group IV. These data indicate that fimasartan significantly reduced SMC proliferation in neointima and increased Treg cells in ApoE KO CA injury mice. CONCLUSIONS: This study suggests fimasartan could be an efficient strategy for reduction of atherosclerotic progression, with a decrease in immune response and systemic inflammation.

Incidence of new-onset diabetes with 1 mg versus 4 mg pitavastatin in patients at high risk of developing diabetes during a 3-year follow-up.

BACKGROUND: Statin therapy reduces the risk of cardiovascular events across a broad spectrum of patients; however, it increases the risk of new-onset diabetes (NOD). Although the highest dose pitavastatin is considered to not be associated with NOD, there are limited data regarding the impact of long-term highest dose pitavastatin use on the development of NOD in patients at high risk of developing diabetes. Therefore, we prospectively compared the differences in the development of NOD between the lowest and the highest dose of pitavastatin in patients at high risk of developing diabetes during a 3-year follow-up. METHODS: This post hoc analysis of a prospective, single-blinded, randomized study compared the risk of NOD between the highest dose of pitavastatin (4 mg) and the lowest dose of pitavastatin (1 mg) over a 3-year follow-up in patients with acute coronary syndrome. Among 1044 patients of the original study, 667 patients at high risk of developing type 2 diabetes mellitus were in the subgroup analysis. The primary endpoint was a comparison of the differences in the cumulative incidence of NOD in the pitavastatin 1 mg and 4 mg groups during a 3-year follow-up. RESULTS: With propensity score matching, there were no significant differences in baseline demographic characteristics between the 2 groups. Incidence of NOD was similar between the pitavastatin 1 mg and 4 mg groups [12 of 289 patients (4.2%) and 8 of 289 patients (2.8%), respectively; p = 0.36]. In a prespecified analysis, there were no significant differences in NOD events according to sex, age, diagnosis, body mass index, glucose intolerance, or dyslipidemia. CONCLUSIONS: Administration of highest-dose pitavastatin did not increase the risk of NOD in patients at high risk of developing diabetes during the 3-year follow-up. Moreover, various risk factors for NOD such as metabolic syndrome components, glucose intolerance, dyslipidemia, obesity, or hypertension did not affect the development of NOD during pitavastatin administration. Thus, the highest dose pitavastatin can be safely used in patients with metabolic syndrome who are at high risk of developing diabetes. Trial registration Clinical Trial registration information. URL: https://clinicaltrials.gov/ct2/show/NCT02545231. Unique identifier: NCT02545231.

Effects of lowest-dose vs. highest-dose pitavastatin on coronary neointimal hyperplasia at 12-month follow-up in type 2 diabetic patients with non-ST elevation acute coronary syndrome: an optical coherence tomography analysis.

Current ACC/AHA guidelines recommend high-dose statin therapy after coronary stenting, especially in diabetic patients; however, pitavastatin 4 mg or pitavastatin 1 mg are frequently used after coronary stenting in Asia, even in patients with acute coronary syndrome. We compared the effects of highest-dose and lowest-dose pitavastatin therapy on coronary neointimal hyperplasia at 12-month follow-up in diabetic patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) using optical coherence tomography. A total of 72 diabetic patients with NSTE-ACS were randomized to lowest-dose pitavastatin [1 mg (n = 36)] or highest-dose pitavastatin [4 mg (n = 36)] after everolimus-eluting stent implantation. The primary endpoint was to compare the normalized neointimal volume at 12-month follow-up. Normalized neointimal volume was significantly lower in the pitavastatin 4 mg group (4.00 ± 2.80 vs. 8.24 ± 2.83 mm3/mm, p < 0.01) at 12-month follow-up. There was also significant difference in neointimal area between the pitavastatin 4 mg group and pitavastatin 1 mg group (0.41 ± 0.28 vs. 0.74 ± 0.23 mm2, p < 0.01). Improvement of brachial artery flow-mediated dilation (baFMD) was significantly higher in the pitavastatin 4 mg group than in pitavastatin 1 mg group (0.15 ± 0.15 vs. - 0.03 ± 0.19 mm, p < 0.001). In addition, the improvement of adiponectin levels was significantly greater in the pitavastatin 4 mg group than in the pitavastatin 1 mg group (2.97 ± 3.98 vs. 0.59 ± 2.80 µg/mL, p < 0.05). Pitavastatin 4 mg significantly improved inflammatory cytokines and lipid profiles compared to pitavastatin 1 mg during the 12-month follow-up, contributing to the reduction of neointimal hyperplasia and to the improvement of baFMD in diabetic patients with NSTE-ACS requiring coronary stenting. Thus, the administration of pitavastatin 4 mg can be safely and effectively used in high-risk patients requiring coronary stenting. Trial registration NCT02545231 (Clinical Trial registration information: https://clinicaltrials.gov/ct2/show/NCT02545231 ).

The analysis of endocrine disruptors in patients with central precocious puberty.

BACKGROUND: A few studies have reported a positive association between phthalate exposure and pubertal timing, but several conflicting reports exist. The main objective of the study was to determine whether phthalate exposure was associated with central precocious puberty in girls. METHODS: This was a multicenter case-control study wherein 47 girls with central precocious puberty (CPP) and 47 controls (26 pre-pubertal girls and 21 pubertal girls) were enrolled. No obese girls were included. Five phthalate metabolites (creatinine adjusted) and bisphenol A (BPA) were measured in the first spot urine samples of these 94 girls in the early morning. RESULTS: The median values of monobenzyl phthalate (MBzP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), and mono-n-butyl phthalate (MnBP) were 3.1, 29.3, 18.0, 15.4, and 25.2 µg/g creatinine in the CPP group, 4.3, 53.7, 35.7, 29.1, and 66.0 µg/g creatinine in the pre-pubertal control group, and 1.7, 28.7, 21.4, 12.1, and 33.3 µg/g creatinine in the pubertal control group, respectively. The urinary concentration of the five phthalates was significantly lower in the CPP group than in the pre-pubertal control group (P < 0.001). Conversely, there was no significant difference in the urinary concentration of the five phthalates between the CPP and pubertal control groups (P values: 0.077 for MBzP, 0.733 for MECPP, 0.762 for MEHHP, 0.405 for MEOHP, and 0.981 for MnBP). In addition, the BPA level was not significantly different between the CPP and pubertal control groups (BPA median values: 0.63 µg/g creatinine, the CPP group; 1.7 µg/g creatinine, the pubertal control group; P value = 0.092). CONCLUSIONS: Our study showed that there was no significant difference in the urinary phthalate levels between the CPP and pubertal control groups. Moreover, phthalate metabolites were significantly lower in the CPP group than in the pre-pubertal control group. Further investigation about endocrine disruptors and pubertal progression is needed.

Rosacea and its association with enteral microbiota in Korean females.

Rosacea is a chronic inflammatory dermatosis affecting the face and eyes. An association between systemic comorbidities and rosacea has been reported, but the link to enteral microbiota is uncertain. We aimed to investigate the link between rosacea and enteral microbiota. A cross-sectional study was performed in a sample of Korean women who participated in a health check-up programme at the Kangbuk Samsung Hospital Health Screening Center between 23 June 2014 and 5 September 2014. The gut microbiome was evaluated by 16S rRNA gene and metagenome sequence analyses. A total of 12 rosacea patients and 251 controls were enrolled. We identified links between rosacea and several changes in gut microbiota: reduced abundance of Peptococcaceae family unknown genus, Methanobrevibacter (genus), Slackia (genus), Coprobacillus (genus), Citrobacter (genus), and Desulfovibrio (genus), and increased abundance of Acidaminococcus (genus), Megasphaera (genus), and Lactobacillales order unknown family unknown genus. A link between rosacea and enteral microbiota was observed in this metagenomic study. A large and elaborate study is needed to confirm these findings and to elucidate the mechanisms involved.

Endovascular Versus Open Surgical Intervention in Patients with Takayasu's Arteritis: A Meta-analysis.

OBJECTIVE/BACKGROUND: Although medical treatment has advanced, surgical treatment is needed to control symptoms of Takayasu's arteritis (TA), such as angina, stroke, hypertension, or claudication. Endovascular or open surgical intervention is performed; however, there are few comparative studies on these methods. This meta-analysis and systematic review aimed to examine the outcome of surgical treatment of TA. METHODS: A meta-analysis comparing outcomes of endovascular and open surgical intervention was performed using MEDLINE and Embase. This meta-analysis included only observational studies, and the evidence level was low to moderate. Data were pooled and analysed using a fixed or random effects model with the I2 statistic. RESULTS: The included studies involved a total of 770 patients and 1363 lesions, with 389 patients treated endovascularly and 420 treated by surgical revascularization. Restenosis was more common with endovascular than open surgical intervention (odds ratio [OR] 5.18, 95% confidence interval [CI] 2.78-9.62; p < .001). In subgroup analysis according to the involved lesions, endovascular intervention patients showed more restenosis than open surgical intervention patients in the coronary artery, supra-aortic branches, and renal artery. In both the active and inactive stages, restenosis was more common in those treated endovascularly than in those treated by open surgery. However, stroke occurred less often with endovascular intervention than with open surgical intervention (OR 0.33, 95% CI 0.12-0.90; p = .003). Mortality and complications other than stroke and mortality did not differ between endovascular and open surgical intervention. CONCLUSION: This meta-analysis has shown a lower risk of restenosis with open surgical intervention than with endovascular intervention. Stroke was generally more common with open surgical intervention than with endovascular intervention. However, there were differences according to the location of the lesion, and the risk of stroke in open surgery is higher when the supra-aortic branches are involved rather than the renal arteries.

Impact of hyperuricemia on clinical outcomes after percutaneous coronary intervention for in-stent restenosis.

BACKGROUND: There have been limited data on the impact of hyperuricemia on long-term clinical outcomes after percutaneous coronary intervention (PCI) for in-stent restenosis (ISR). METHODS: From January 2009 to July 2015, 317 patients who underwent repeat PCI for ISR were divided into two groups: patients with normal serum uric acid (UA) levels (normal UA group) and patients with higher serum UA levels (higher UA group). The higher UA group included patients with serum UA levels > 6.8 mg/dL or patients who were taking anti-hyperuricemic medication. RESULTS: During a median follow-up period of 1088 days, the cumulative incidence rates of major adverse event (MAE), including a composite of all-cause death, non-fatal myocardial infarction, and any revascularization, were similar between the two groups (higher UA 36.4% vs. normal UA 29.9%, p = 0.389, log-rank p = 0.367). Follow-up angiographic data showed similar outcomes of late lumen loss (0.8 ± 0.9 mm vs. 0.8 ± 1.1 mm, p = 0.895) and binary restenosis rate (28.1% vs. 34.7%, p = 0.622). Multivariate Cox regression analysis indicated higher levels of low-density lipoprotein cholesterol (hazard ratio [HR] 1.011, 95% confidence interval [CI] 1.003-1.019, p = 0.006) and lower left ventricular ejection fraction (HR 0.972, 95% CI 0.948-0.996, p = 0.022), but not UA levels, to be the independent risk predictors of MAE. CONCLUSION: Hyperuricemia is not associated with poor clinical outcomes after repeat PCI for ISR lesions.

Expression and antigenicity of recombinant human respiratory syncytial virus glycoproteins having different affinity tags.

Human respiratory syncytial virus (HRSV) is a main cause of lower respiratory tract infections in infants and the elderly. Glycoprotein (G) is major antigen on the viral surface, and plays a key role for virus entry. Therefore, purification of the glycoprotein of HRSV is critical for the development of HRSV vaccine and serological diagnosis. In this study, we report the design and characterization of glycoprotein engineered rationally to enhance the protein solubility and to facilitate efficient purification. We permuted HRSV glycoproteins with two tags: (i) an immunoglobulin (Ig) M signal peptide and a protein A B domain tag to render HRSV glycoprotein secret into the culture media and (ii) a foldon and 6 × histidine tag with or without transmembrane domain. Three recombinant baculoviruses were constructed: (i) transmembrane-truncated HRSV glycoprotein (amino acid positions 66-298) inserted with the N-terminal IgM signal peptide and protein A B domain (MG-GΔTM), (ii) truncated HRSV glycoprotein (amino acid positions 66-298) fused with a C-terminal foldon and 6 × histidine tag (GΔTM-FH), and (iii) full-length HRSV glycoprotein (amino acid positions 1-298) fused with a C-terminal foldon and 6 × histidine tag (G-FH). Highly soluble recombinant MG-GΔTM protein was clearly purified using one-step affinity chromatography with IgG-sepharose resin, whereas the recombinant G-FH protein and truncated GΔTM-FH were purified partially using nickel-resin. Although, the antigenicity of GΔTM-FH was stronger than highly mannose-rich MG-GΔTM protein, MG-GΔTM induced neutralizing antibodies efficiently in the mice to protect from infectious HRSV.