Search

Background Hemodialysis (HD) patients have an increased risk of thrombosis. Endothelial progenitor cells (EPCs), which function in vascular repair, are deficient in HD patients. Nonetheless, the relationship between EPC deficiency and thrombosis in HD patients is unknown. Methods From January 2010 to December 2012, circulating levels of EPCs that were positive for CD34 and kinase insert domain receptor (KDR) were measured in 269 HD patients. Patients received prospective follow-ups at 6-month intervals until May 2015. The primary outcome was the composite of HD access thrombosis and systemic vascular thrombosis. Results There were 141 thrombotic events, 50 systemic vascular thrombotic events and 116 HD access thrombotic events. We found significantly negative associations between CD34 + KDR + tertile and overall thrombotic events (low: 61%; middle: 56%; high: 40%; P = 0.02), systemic vascular thrombotic events (low: 27%; middle: 18%; high: 10%; P = 0.03) and HD access thrombotic events (low: 52%; middle: 46%; high: 36%; P = 0.02). Univariate analysis indicated that systemic vascular thrombotic events were positively associated with age, diabetes, dyslipidemia, vascular disease history, urea clearance, albumin and C-reactive protein (CRP), and negatively associated with CD34 + KDR + cell count. HD access thrombosis was positively associated with vascular disease history and CRP, and negatively associated with CD34 + KDR + cell count. Multivariate analysis indicated that a low CD34 + KDR + cell count was an independent risk factor for both types of thrombosis. Conclusions Our study of a population of HD patients showed that a low level of circulating EPCs is associated with thrombosis.

Excessive accumulation of cadmium is known to cause nephrotoxicity by targeting renal proximal tubular epithelial cells. Studies showed an essential role of autophagy in cadmium-induced nephrotoxicity; however, its underlying mechanisms accompanied by autophagy are incompletely understood. Using an HK-2 human renal proximal tubular epithelial cell line as a study model, sustained exposure of cadmium chloride (CdCl2) was shown to cause cell viability loss, which was alleviated by inhibitors of autophagy but not apoptosis. Data from molecular and biochemical studies revealed an induction of autophagy proteins, intracellular acidic vesicles, and autophagic flux in CdCl2-treated cells. However, there was little sign of apoptosis-related changes. Pharmacological and genetic studies indicated an elevation of Endoplasmic Reticulum (ER) stress, Forkhead Box Class O (FoxO3a), Bcl-2 Interacting Protein 3 (Bnip3), and Beclin1, as well as their involvement in cadmium-induced autophagy and autophagic cell death. Renal injury, histological changes, and molecular marker of ER stress, FoxO3a, Bnip3, and autophagy were observed in the kidney cortex of CdCl2-exposed Sprague-Dawley rats. These observations indicate that ER stress, FoxO3a, Bnip3, and autophagy signaling were actively involved in cadmium-induced nephrotoxicity. Additionally, FoxO3a may act as a linking molecule to convey ER stress signals to Bnip3 and autophagy machinery upon cadmium exposure.

Beyond nutrition effect, quercetin is applied as a complement or an alternative for promoting human health and treating diseases. However, its complicated neuroprotective mechanisms have not yet been fully elucidated. This study provides evidence of an alternative target for quercetin, and sheds light on the mechanisms of its neuroprotection against cerebral ischemia/reperfusion (I/R) injury in Sprague-Dawley rats. Oral pretreatment using quercetin has alleviated cerebral I/R-induced neurological deficits, brain infarction, blood-brain barrier disruption, oxidative stress, TNF-α and IL-1β mRNA expression, along with apoptotic caspase 3 activity. The neuroprotective, anti-oxidative, anti-inflammatory, and anti-apoptotic effects of quercetin were replicated in rat hippocampal slice cultures and neuron/glia cultures which suffered from oxygen-glucose deprivation and reoxygenation (OGDR). Biochemical studies revealed a reduction of extracellular signal-regulated kinase (ERK) and Akt phosphorylation, along with an increase in protein tyrosine and serine/threonine phosphatase activity in cerebral I/R rat cortical tissues and OGDR hippocampal slice and neuron/glia cultures. Quercetin alleviated the changes in ERK/Akt phosphorylation and protein phosphatase activities. Inhibition of ERK or Akt alone was enough to cause apoptotic cell death and cytotoxicity in hippocampal slice cultures and neuron/glia cultures, while activators of ERK or Akt alleviated OGDR-induced cytotoxicity. Taken together, our results demonstrate that quercetin alleviated the increment of protein tyrosine and serine/threonine phosphatase activity, along with the reduction of ERK and Akt phosphorylation, which may play pivotal roles in the expansion of brain injury after cerebral I/R.

Contains fulltext : 215333.pdf (Publisher’s version ) (Closed access) BACKGROUND: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. METHODS: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). FINDINGS: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3.3 years (IQR 2.8-3.8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7.3%] of 5558 vs 480 [8.6%] of 5596; HR 0.85 [95% CI 0.74-0.97], p=0.013). The same effect was not observed in patients without PCI (p=0.76, pinteraction=0.16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3.1%] with ticagrelor vs 183 (3.3%) with placebo; HR 0.96 [95% CI 0.78-1.18], p=0.68), as well as all-cause death (282 [5.1%] vs 323 [5.8%]; 0.88 [0.75-1.03], p=0.11). TIMI major bleeding occurred in 111 (2.0%) of 5536 patients receiving ticagrelor and 62 (1.1%) of 5564 patients receiving placebo (HR 2.03 [95% CI 1.48-2.76], p

Background Parenteral anticoagulants and vitamin K antagonists (VKAs) have constituted the cornerstone of venous thromboembolism (VTE) treatment. Meanwhile, direct oral anticoagulants (DOACs) provide physicians with an alternative. The Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE observes real-world treatment practices. Objectives Describe initial anticoagulation (AC) treatment patterns in VTE patients who received parenteral AC, VKAs, and/or DOACs within ±30 days of diagnosis. Methods VTE patients were categorized into parenteral AC only, parenteral AC with transition to VKA, VKA only, parenteral AC with transition to DOAC, and DOAC only. Results A total of 9647 patients were initiated on AC treatment alone. 4781 (49.6%) patients received DOACs ± parenteral ACs; 3187 (33.0%), VKA ± parenteral ACs; and 1679 (17.4%) parenteral ACs alone. Rivaroxaban was the most frequently used DOAC (79.4%). DOACs were more frequently used in North America/Australia (58.1%), Europe (52.2%), and Asia (47.6%) than in Latin America (29.7%) and the Middle East/South Africa (32.5%). In patients with suspected VTE, most received parenteral AC monotherapy (67.7%). Patients with deep vein thrombosis were more likely to receive DOACs alone than those with pulmonary embolism with or without deep vein thrombosis (36.2% vs 25.9%). Active cancer patients received parenteral AC alone (58.9%), with 25.5% receiving DOAC ± parenteral AC and 12.8% parenteral AC and VKA. A total of 46.5% of pregnant patients received parenteral AC monotherapy, 34.0% were treated with VKA ± parenteral AC, and 19.5% received a DOAC (± parenteral AC). Conclusion AC treatment patterns vary by patient population, geographic region and site of VTE. Guidelines for AC therapy are not always adhered to.

Renal ischemia/reperfusion (I/R) is an alternation of renal hemodynamics, which results in diverse postischemic responses and eventually acute kidney injury. Although renal ischemic preconditioning (IPC) is known to protect the kidney from I/R injury, the precise renoprotective mechanisms are not completely understood. The multiple renoprotective effects of IPC underscore the importance in understanding molecular mechanisms and the targets of action involved. This study aimed to identify the biochemical changes in renal I/R injury and investigate the renoprotective mechanisms of IPC. Herein, renal I/R was produced in adult male Sprague-Dawley rats through the bilateral ligation of renal pedicles for 45 min, followed by reperfusion for 24 h. For the IPC group, rats were subjected to three cycles of 2-min ischemia, followed by a 5-min reperfusion, 15 min prior to renal I/R. Our data confirmed the beneficial effects that IPC has on renal I/R injury. IPC-mediated renoprotection was associated with the resolution of oxidative stress, inflammation, apoptosis, and hyperglycemia. Among the numerous signaling molecules involved in the renoprotective mechanisms of IPC, an elevated protein expression of Nrf2, HO-1, LC3 II conversion, along with Atg12 and protein phosphorylation of AMPK, as well as a decreased protein phosphorylation of ERK, p38 MAPK, and Akt and NF-κB DNA binding activity were identified. Importantly, the post renal I/R overproduction of counter-regulatory hormones, impaired hepatic insulin action, and augmented hepatic gluconeogenesis were improved through IPC. As counter-regulatory hormones have been implicated in the induction of oxidative stress, inflammation, apoptosis, impaired insulin action, hyperglycemia, and tissue destruction, our findings suggest that counter-regulatory hormones may well be valuable targets of IPC for combatting renal I/R injury. © 2018 IUBMB Life, 71(3):321-329, 2019.

Background and objectives There is increasing evidence that microRNAs (miRNAs) play crucial roles in the regulation of neointima formation. However, the translational evidence of the role of miRNAs in dialysis vascular access is limited. Design, setting, participants, & measurements miRNA expression in tissues was assessed by using venous tissues harvested from ten patients on dialysis who received revision or removal surgery, and ten patients who were predialysis and received creation surgery of arteriovenous fistulas served as controls. To extend these findings, 60 patients who received angioplasty of dialysis access were enrolled and the levels of circulating miRNAs were determined before and 2 days after angioplasty. Clinical follow-up was continued monthly for 6 months. The primary outcome of angioplasty cohort was target lesion restenosis within 6 months after angioplasty. Results In the surgery cohort, the expressions of miR-21, miR-130a, and miR-221 were upregulated in stenotic tissues, whereas those of miR-133 and miR-145 were downregulated. In situ hybridization revealed similar expression patterns of these miRNAs, localized predominantly in the neointima region. Twenty eight patients in the angioplasty cohort developed restenosis within 6 months. The levels of circulating miR-21, miR-130a, miR-221, miR-133, and miR-145 significantly increased 2 days after angioplasty. Kaplan–Meier plots showed that patients with an increase of miR-21 expression level >0.35 have a higher risk of patency loss (hazard ratio, 4.45; 95% confidence interval, 1.68 to 11.7). In a multivariable analysis, postangioplasty increase of miR-21 expression was independently associated with restenosis (hazard ratio, 1.20; 95% confidence interval, 1.07 to 1.35 per one unit increase of miR-21 expression level; P=0.001). Conclusions Certain miRNAs are differentially expressed in the stenotic venous segments of dialysis accesses. An increase in blood miR-21 level with angioplasty is associated with a higher risk of restenosis.

Autophagy and apoptosis represent important cellular processes involved in cancer cell killing mechanisms. Epidermal growth factor receptor inhibitor gefitinib and valproic acid have been implicated in the treatment of malignancies including glioma involving autophagic and apoptotic mechanisms. Therefore, it is interesting to investigate whether a combination of gefitinib and valproic acid shows better cancer cell killing effect on human glioma cells. We found that a nontoxic concentration of valproic acid sensitized U87 and T98G glioma cells to gefitinib cytotoxicity by inhibiting cell growth and long-term clonogenic survival. The augmented consequences were accompanied by the formation of autophagic vacuoles, conversion of microtubule-associated protein-1 light chain 3-II (LC3-II), and degradation of p62. Autophagy inhibitor 3-methyladenosine and chloroquine and genetic silencing of LC3 but not broad-spectrum caspase inhibitor attenuated gefitinib/valproic acid-induced growth inhibition. Gefitinib/valproic acid-induced autophagy was accompanied by the activation of liver kinase-B1 (LKB1)/AMP-activated protein kinase (AMPK)/ULK1. Silencing of AMPK and ULK1 suppressed gefitinib/valproic acid-induced autophagy and growth inhibition. Mechanistic studies showed that gefitinib/valproic acid increased intracellular reactive oxygen species generation and N-acetyl cysteine attenuated gefitinib/valproic acid-caused autophagy and growth inhibition. In addition to demonstrating the autophagic mechanisms of gefitinib/valproic acid, the results of this study further suggest that intracellular oxidative stress and the LKB1/AMPK signaling might be a potential target for the development of therapeutic strategy against glioma.

Recently, Hou and others introduced a (2, n) block-based progressive visual cryptographic scheme (BPVCS) in which image blocks can be gradually recovered step by step. In Hou and others' (2, n)-BPVCS, a secret image is subdivided into n non-overlapping image blocks. When t () participants stack their shadow images, all the image blocks associated with these t participants will be recovered. However, Hou and others' scheme is only a simple 2-out-of-n case. In this paper, we discuss a general (k, n)-BPVCS for any k and n. Our main contribution is to give two constructions (Construction 1 and Construction 2) of this general (k, n)-BPVCS. Also, we theoretically prove that both constructions satisfy a threshold property and progressive recovery of the proposed (k, n)-BPVCS. For k = 2, Construction 1 is reduced to Hou and others' (2, n)-BPVCS.

Objective To explore the point-specific clinical effect of 2 Hz electroacupuncture (EA) in treating postoperative pain in patients undergoing total knee arthroplasty (TKA), Methods In a randomised, partially single-blinded preliminary study, 47patients with TKA were randomly divided into three groups: control group (CG, n=17) using only patient-controlled analgesia (PCA); EA group (EAG, n=16) with 2 Hz EA applied at ST36 ( Zusanli) and GB34 ( Yanglingquan) contralateral to the operated leg for 30 min on the first two postoperative days, also receiving PCA; and non-point group (NPG, n=14), with EA identical to the EAG except given 1 cm lateral to both ST36 and GB34. The Mann–Whitney test was used to show the difference between two groups and the Kruskal–Wallis test to show the difference between the three groups. Results The time until patients first required PCA in the CG was 34.1±22.0 min, which was significantly shorter than the 92.0±82.7 min in the EAG (p0.05). The total dosage of PCA solution given was 4.6±0.9 mL/kg body weight in the CG, 4.2±1.0 mL/kg in the EAG and 4.5±1.0 mL/kg in the NPG; there were no significant differences (p>0.05) among the three groups. Conclusions In this small preliminary study, EA retarded the first demand for PCA in comparison with no EA. No effect was seen on the total dosage of PCA required and no point-specific effect was seen.

Blood-brain barrier (BBB) characteristics are induced and maintained by crosstalk between brain microvascular endothelial cells and neighboring cells. Using in vitro cell models, we previously found that a bystander effect was a cause for Japanese encephalitis-associated endothelial barrier disruption. Brain astrocytes, which neighbor BBB endothelial cells, play roles in the maintenance of BBB integrity. By extending the scope of relevant studies, a potential mechanism has been shown that the activation of neighboring astrocytes could be a cause of disruption of endothelial barrier integrity during the course of Japanese encephalitis viral (JEV) infection. JEV-infected astrocytes were found to release biologically active molecules that activated ubiquitin proteasome, degraded zonula occludens-1 (ZO-1) and claudin-5, and disrupted endothelial barrier integrity in cultured brain microvascular endothelial cells. JEV infection caused astrocytes to release vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and matrix metalloproteinases (MMP-2/MMP-9). Our data demonstrated that VEGF and IL-6 released by JEV-infected astrocytes were critical for the proteasomal degradation of ZO-1 and the accompanying disruption of endothelial barrier integrity through the activation of Janus kinase-2 (Jak2)/signal transducer and activator of transcription-3 (STAT3) signaling as well as the induction of ubiquitin-protein ligase E3 component, n-recognin-1 (Ubr 1) in endothelial cells. MMP-induced endothelial barrier disruption was accompanied by MMP-mediated proteolytic degradation of claudin-5 and ubiquitin proteasome-mediated degradation of ZO-1 via extracellular VEGF release. Collectively, these data suggest that JEV infection could activate astrocytes and cause release of VEGF, IL-6, and MMP-2/MMP-9, thereby contributing, in a concerted action, to the induction of Japanese encephalitis-associated BBB breakdown. GLIA 2015;63:1915-1932.

Background: No randomized controlled trials evaluating metformin therapy efficacy in patients with type 2 diabetes mellitus (DM) and acute coronary syndrome (ACS) have been reported. Well-designed retrospective studies controlling for imbalance in baseline patient characteristics are scarce. We aimed to examine the mortality benefit of metformin therapy in patients with type 2 DM and ACS, compared with non-metformin anti-diabetes agent users. Method: Data were extracted from the prospective nationwide ACS-DM Taiwan Society of Cardiology registry. Propensity score (PS) matching on baseline characteristics and treatment measures was performed for metformin versus non-metformin users. Cox proportional hazard models were used to compare mortality outcomes among the PS-matched cohort as a primary analysis. Traditional Cox proportional hazard models adjusting for all pre-determined covariates and quintiles of the PS among the overall population were performed as a secondary analysis. Findings: Of 1157 patients with type 2 DM and ACS receiving anti-diabetes agents, 78 patients (6.7%) died over the 2-year follow-up period. After PS matching, 318 metformin users were matched with 318 non-metformin users. Metformin users had a lower all-cause mortality rate (adjusted hazard ratio [aHR] 0·50, 95% confidence interval [CI] 0·26-0·95) in the primary analysis. The survival benefit of metformin therapy was consistent in the secondary analyses (aHR 0·30, 95% CI 0·17-0·54 while adjusting for all pre-determined covariates, and aHR 0·34, 95% CI 0·19-0·59 while adjusting for quintiles of the PS). Interpretation: Among patients with type 2 DM and ACS, metformin was associated with lower all-cause mortality. Funding Statement: This work was supported with grants from the Hsin-Chu branch of the National Taiwan University Hospital (HCH-106036). The funding source also provided technical help (Biotechnology R&D Center) with data analysis and interpretation of the findings. Declaration of Interest: All authors report no relationships that could be construed as a conflict of interest. Ethics Approval Statement: Patients are treated according to international or local guidelines and evidence-based strategies. The protocol and consent forms used in this study were consistent with the Declaration of Helsinki and relevant regulations. The ethics committees of each participating hospital approved the study, and all enrolled patients provided written informed consent.

The current standard care for acute mesenteric ischemia (AMEI) involves urgent revascularization and resection of the necrotic bowel. Since 2012, we have used an AMEI protocol of our own design, which focused on early treatment and allowed interventional cardiologists to become involved when interventional radiologist was not available. A total of 8 patients were treated, and two interventional cardiologists performed all the stenting procedures. The procedure success rate was 100% in patients with non-calcified lesions (6/8). The 30-day survival rate was 100% in patients with angiographic success, and was 0% in patients with failed procedure. In two patients with total occlusion of the superior mesenteric artery, laparotomy was avoided when interventions were successful and completed within six hours of protocol activation. Four surviving patients were discharged after short intensive care unit stays (less than 48 hours); these patients returned to and remained at home throughout their 90-day follow-up. The overall procedure success rate and 30-day survival rate were both 75%. There was no access site or intervention-related complications. Using our protocol, we believe that primary endovascular treatment for AMEI is feasible. In geographic regions where healthcare resources are lacking, a time-efficient strategy adopted by interventional cardiologists should be considered for the purpose of saving lives and possibly even avoiding open laparotomy.

Background and aims MicroRNA (miR)-10a is a shear-regulated miR with the lowest expression in vascular endothelial cells (ECs) in athero-susceptible regions with oscillatory shear stress (OS). The aim of this study is to elucidate the relationship between EC miR-10a and atherosclerosis and develop a hemodynamics-based strategy for atherosclerosis treatment. Methods A combination of in vitro flow system and in vivo experimental animals was used to examine the functional roles of EC miR-10a and its clinical applications in atherosclerosis. Results En face staining showed that EC miR-10a is down-regulated in the inner curvature (OS region) of aortic arch in rats. Co-administration with retinoic acid receptor-α (RARα)- and retinoid X receptor-α (RXRα)-specific agonists rescued EC miR-10a expression in this OS region. These effects of OS and RARα/RXRα-specific agonists on EC miR-10a expression were confirmed by the in vitro flow system, and were modulated by the RARα-histone deacetylases complex, with the consequent modulation in the downstream GATA6/vascular cell adhesion molecule (VCAM)-1 signaling cascade. Animal studies showed that miR-10a levels are decreased in both aortic endothelium of atherosclerotic lesions and blood plasma from apolipoprotein E-deficient (ApoE−/−) mice. In vivo induction of EC miR-10a by administration of RARα/RXRα-specific agonists protects ApoE−/− mice from atherosclerosis through inhibition of GATA6/VCAM-1 signaling and inflammatory cell infiltration. Conclusions Our findings indicate that down-regulation of miR-10a in aortic endothelium and blood serum is associated with atherosclerosis, and miR-10a has potential to be developed as diagnostic molecule for atherosclerosis. Moreover, EC miR-10a induction by RARα/RXRα-specific agonists is a potential hemodynamics-based strategy for atherosclerosis treatment.

// I-Chun Chen 1 , Chin-Sung Kuo 1, 2 , Chih-Cheng Wu 3, 4, 5, 6 , Hsiao-Ya Tsai 1 , Chih-Pei Lin 7, 8 , Szu-Yuan Li 1, 9 , Ruey-Hsing Chou 1, 3, 10 , Po-Hsun Huang 1, 3, 10 , Jaw-Wen Chen 3, 10, 11, 12 and Shing-Jong Lin 1, 3, 10, 11, 13 1 Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan 2 Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan 3 Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan 4 National Tsing-Hua University, Institute of Biomedical Engineering, Hsinchu, Taiwan 5 National Taiwan University Hospital, College of Medicine, Taipei, Taiwan 6 Cardiovascular Center, National Taiwan University Hospital, Hsinchu Branch, Hsinchu, Taiwan 7 Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan 8 Department of Biotechnology and Laboratory Science in Medicine and Institute of Biotechnology in Medicine, National Yang-Ming University, Taipei, Taiwan 9 Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan 10 Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan 11 Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan 12 Institute and Department of Pharmacology, National Yang-Ming University, Taipei, Taiwan 13 Taipei Medical University, Taipei, Taiwan Correspondence to: Po-Hsun Huang, email: huangbsvgh@gmail.com Chih-Cheng Wu, email: chihchengwumd@gmail.com Chin-Sung Kuo, email: cskuo241@yahoo.com.tw Keywords: hyperuricemia; endothelial progenitor cell; ischemia; neovascularization Received: August 14, 2017 Accepted: January 02, 2018 Published: January 22, 2018 ABSTRACT Objective: Chronic hyperuricemia is associated with cardiovascular disease, but its impact on endothelial progenitor cells (EPC) and ischemia-induced neovascularization remains unclear. Herein we investigated whether chronic hyperuricemia could impede blood flow recovery in response to tissue ischemia by suppression of EPC. Methods: Human EPC were isolated and cultured in a high-level uric acid medium for functional testing. Cell proliferation, nitric oxide (NO) production and apoptosis assay were examined. A chronic hyperuricemia mouse model was established by potassium oxonate treatment and/or a high-level uric acid diet to evaluate the actions of chronic hyperuricemia on ischemia-induced blood flow recovery. After 4 weeks of drug treatment, hindlimb ischemia surgery was performed in the control and hyperuricemia mice. Blood flow recovery was followed up every week before and after ischemic surgery using a laser Doppler Perfusion Imager System. The circulating EPC number in the peripheral blood was determined by flow cytometry (Sca-1 + /Flk-1 + ). Results: Incubation with a high-level uric acid medium (10 mg/dL) significantly suppressed EPC proliferation, reduced NO production, and lessened phosphorylation of Akt and eNOS. Moreover, EPC treated with high-level uric acid increased reactive oxygen species production, promoted cellular apoptosis and senescence, and also inhibited EPC tube formation. Four weeks after hindlimb ischemia surgery, the chronic hyperuricemia mice had significantly reduced tissue reperfusion, EPC mobilization, and impaired neovascularization in the ischemic hindlimbs compared with the control mice. Conclusions: Chronic hyperuricemia impaired blood flow recovery and EPC mobilization in response to tissue ischemia, and these effects could have occurred through suppression of EPC.

The urgency with which salvage of thrombosed vascular accesses for dialysis should be attempted remains unknown. We examined the effect of a timely thrombectomy approach on vascular access outcomes for dialysis.A before-and-after study was conducted with patients on hemodialysis who had undergone endovascular thrombectomy. A timely thrombectomy initiative (ie, salvage within 24 hours of thrombosis diagnosis) was started in July 2015 at our institution. Data about thrombectomy procedures, performed within 1 year before and after the initiative was introduced, were abstracted from an electronic database. Immediate outcomes and patency outcomes were compared between the preinitiative (control) and postinitiative (intervention) groups.During the study period, 329 patients were enrolled, including 165 cases before and 164 cases after the initiative. The intervention group had more thrombectomy procedures performed within 24 hours (93% vs 55%; P .01) and within 48 hours (97% vs 79%; P .01) than the control group. No between-group differences in procedural success or clinical success rates were found. At 3 months, the intervention group had a higher postintervention primary patency rate than the control group, although this did not reach statistical significance (58% vs 48%; P = .06). After stratification into native or graft accesses, the patency benefit was observed in the native access group (68% vs 50%; P = .03) but not in the graft access group (50% vs 46%; P = .65). After adjusting for potential confounders, timely thrombectomy remained an independent predictor of postintervention primary patency (hazard ratio, 0.449; 95% confidence interval, 0.224-0.900; P = .02) for native dialysis accesses.Our results suggest that a timely thrombectomy approach, in which salvage is attempted within 24 hours of thrombosis diagnosis, improves postintervention primary patency of native but not graft accesses for dialysis.

Heart failure (HF) is a global health problem. The Taiwan Society of Cardiology-Heart Failure with reduced Ejection Fraction (TSOC-HFrEF) registry was a multicenter, observational survey of patients admitted with HFrEF in Taiwan. The aim of this study was to report the one-year outcome in this large-cohort of hospitalized patients presenting with acute decompensated HFrEF.Patients hospitalized for acute HFrEF were recruited in 21 hospitals in Taiwan. A total of 1509 patients were enrolled into the registry by the end of October 2014. Clinical status, readmission rates and dispensed medications were collected and analyzed 1 year after patient index hospitalization.Our study indicated that re-hospitalization rates after HFrEF were 31.9% and 38.5% at 6 and 12 months after index hospitalization, respectively. Of these patients, 9.7% of them were readmitted more than once. At 6 and 12 months after hospital discharge, all-cause mortality rates were 9.5% and 15.9%, respectively, and cardiovascular mortality rates were 6.8% and 10.5%, respectively. Twenty-three patients (1.5%) underwent heart transplantation. During a follow-up period of 1 year, 46.4% of patients were free from mortality, HF re-hospitalization, left ventricular assist device use and heart transplantation. At the conclusion of follow-up, 57.5% of patients were prescribed either with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers; also, 66.3% were prescribed with beta-blockers and 40.8% were prescribed with mineralocorticoid receptor antagonists.The TSOC-HFrEF registry showed evidence of suboptimal practice of guideline-directed medical therapy and high HF re-hospitalization rate in Taiwan. The one-year mortality rate of the TSOC-HFrEF registry remained high. Ultimately, our data indicated a need for further improvement in HF care.

Epidermal growth factor receptor tyrosine kinase inhibitors, including gefitinib, have been evaluated in patients with malignant gliomas. However, the molecular mechanisms involved in gefitinib-mediated anticancer effects against glioma are incompletely understood. In the present study, the cytostatic potential of gefitinib was demonstrated by the inhibition of glioma cell growth, long-term clonogenic survival, and xenograft tumor growth. The cytostatic consequences were accompanied by autophagy, as evidenced by monodansylcadaverine staining of acidic vesicle formation, conversion of microtubule-associated protein-1 light chain 3-II (LC3-II), degradation of p62, punctate pattern of GFP-LC3, and conversion of GFP-LC3 to cleaved-GFP. Autophagy inhibitor 3-methyladenosine and chloroquine and genetic silencing of LC3 or Beclin 1 attenuated gefitinib-induced growth inhibition. Gefitinib-induced autophagy was not accompanied by the disruption of the Akt/mammalian target of rapamycin signaling. Instead, the activation of liver kinase-B1/AMP-activated protein kinase (AMPK) signaling correlated well with the induction of autophagy and growth inhibition caused by gefitinib. Silencing of AMPK suppressed gefitinib-induced autophagy and growth inhibition. The crucial role of AMPK activation in inducing glioma autophagy and growth inhibition was further supported by the actions of AMP mimetic AICAR. Gefitinib was shown to be capable of reducing the proliferation of glioma cells, presumably by autophagic mechanisms involving AMPK activation.

Background and aim Atrial fibrillation (AF) is an important cardiovascular disease in the elderly. The association between hyperuricemia and AF is unclear. Therefore, we aimed to investigate the prospective relationship between uric acid and development of AF in a nationally representative cohort of elderly people. Methods and results A total of 1485 elderly people (age ≥ 65 yrs) from the Elderly Nutrition and Health Survey in Taiwan (1999–2000) were without AF on “electrocardiography” at baseline. Incident AF events (International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM: 427.31) were identified using data from the National Health Insurance Dataset. Hyperuricemia was defined as levels of uric acid >7.0 mg/dL in men and 6.0 mg/dL in women. A Cox proportional hazards model was used to evaluate the association between hyperuricemia and incident AF. The follow-up period was from 1999 to 2000 to 2008. During the follow-up period (median: 9.16 yrs), 90 AF events occurred (44 in men and 46 in women). Older age, elevated systolic blood pressure, being an ex-smoker, and high uric acid were positively associated with incident AF. Hyperuricemia was positively associated with incident AF in normotensive (age-adjusted hazard ratio (HR): 2.65 and 95% confidence intervals: 1.05–6.69), but not in (1.20:0.74–1.94) hypertensive individuals (systolic blood pressure ≥130 or diastolic blood pressure ≥85 or using hypertensive medicine). A significant association between hyperuricemia and AF (3.78; 1.24–11.59) remained after adjusting for other potential confounders among normotensive older persons. Conclusion Hyperuricemia is associated with the development of AF in elderly people with normal blood pressure.

Rationale: Stellate Ganglion Block (SGB) provides a blockade of sympathetic signals from the sympathetic chain and appears to be a promising method of controlling refractory ventricular arrhythmias, but there are scanty data in the literature. Patient concerns: Herein, we describe a 59-year-old male patient with a history of non-ischemic cardiomyopathy and suffering from frequent VT episodes, who received ICD implantation and regular amiodarone medication control. Diagnoses: Monomorphic VT refractory to standard medication control and focal extensive catheter ablation. Interventions: Left Stellate Ganglion Block (LSGB) was performed under ultrasound-assisted injection at the C6 level using a 10 ml solution of 0.4% lidocaine and 0.5% bupivacaine. Outcomes: In our case, refractory VT subsided and sinus rhythm was retained immediately after LSGB. There were no VT episodes for at least 3 hours during the inter-hospital transfer, which did not involve any specific complications. Lessons: LSGB may provide effective VT control and play an important role in rescue and bridge therapy before catheter ablation.

Arteriovenous graft (AVG) dysfunction is mainly caused by neointimal hyperplasia. Endovascular intervention can salvage the stenosis. But the long-term patent rate doesn’t improve due to repeated restenosis. Paclitaxel-coated balloon (PCB) is used to reduce neointimal hyperplasia in patients with

Patient initials or identifier number 607300 ### Relevant clinical history and physical exam A 33-year-old man came for a 12-hour history of totally occluded arteriovenous fistula (AVF). Past history: polycystic kidney disease with regular hemodialysis since childhood and active smoker.

Patient initials or identifier number CSC ### Relevant clinical history and physical exam A 52 y/o man with hyperlipidemia presented with exertional chest tightness and dyspnea for 1 year. He had received PCI with a BMS implanted in LAD one year ago in a local hospital; however, his chest

We report the novel use of a Sengstaken-Blakemore tube in an 82-year-old man with severe upper gastrointestinal bleeding and subsequent hypovolemic shock. When exploratory laparotomy failed to locate the source of the bleeding, a Sengstaken-Blakemore tube was placed retrograde to the gastroesophageal junction using a previously inserted nasogastric tube for guidance. The bleeding stopped immediately after mechanical compression by the inflated gastric and esophageal balloons. Hemodynamic stability permitted a thorough evaluation of the surgical field. The balloons were deflated intermittently to allow the surgeon to address the major and other smaller bleeding vessels in a stepwise manner. The intraoperative insertion of a Sengstaken-Blakemore tube can be used to control disastrous upper gastrointestinal bleeding located at or above the gastroesophagealjunction. It helps to achieve hemodynamic stability with less transfusion required and results in fewer complications. However, the lack of experience with the direct placement of a Sengstaken-Blakemore tube and the need for the equipment-dependent confirmation of the SengstakenBlakemore tube position reduces its clinical usage. The retrograde Sengstaken-Blakemore tube insertion strategy does not require assistance by ultrasonography or endoscopy and avoids most procedure-related complications.

Chronic kidney disease (CKD) is now clearly recognized as a public health problem worldwide. Patients with CKD display a substantial increase in end‐stage renal disease (ESRD) and cardiovascular disease (CVD).[1][1] Moreover, the prognosis of CVD in CKD is extremely poor.[2][2] Understanding the

The deficiency of endothelial progenitor cells has been demonstrated to be associated with cardiovascular events in patients undergoing dialysis. However, their correlation with dialysis graft outcomes remains unknown. The objective of this study was to investigate the relationship between circulating endothelial progenitor cells and dialysis graft outcomes.After excluding 14 patients with acute coronary syndrome, decompensated heart failure or graft thrombosis in the prior three months, a total of 120 patients undergoing dialysis who underwent endovascular therapy of dysfunctional dialysis grafts were prospectively enrolled. Blood was sampled from study subjects in the morning of a mid-week non-dialysis day. Surface makers of CD34, KDR, and CD133 were used in combination to determine the number of circulating endothelial progenitor cells. All participants were prospectively followed until June 2013.The median follow-up duration was 13 months, within which 62 patients experienced at least one episode of graft thrombosis. Patients with graft thrombosis had lower CD34Our study demonstrated an independent association between low circulating endothelial progenitor cell counts and dialysis graft thrombosis.

Ethnopharmacological relevance In traditional Chinese medicine, Glechoma hederacea is frequently prescribed to patients with cholelithiasis, dropsy, abscess, diabetes, inflammation, and jaundice. Polyphenolic compounds are main bioactive components of Glechoma hederacea. Aim of the study This study was aimed to investigate the hepatoprotective potential of hot water extract of Glechoma hederacea against cholestatic liver injury in rats. Materials and methods Cholestatic liver injury was produced by ligating common bile ducts in Sprague-Dawley rats. Saline and hot water extract of Glechoma hederacea were orally administrated using gastric gavages. Liver tissues and bloods were collected and subjected to evaluation using histological, molecular, and biochemical approaches. Results Using a rat model of cholestasis caused by bile duct ligation (BDL), daily oral administration of Glechoma hederacea hot water extracts showed protective effects against cholestatic liver injury, as evidenced by the improvement of serum biochemicals, ductular reaction, oxidative stress, inflammation, and fibrosis. Glechoma hederacea extracts alleviated BDL-induced transforming growth factor beta-1 (TGF-β1), connective tissue growth factor, and collagen expression, and the anti-fibrotic effects were accompanied by reductions in α-smooth muscle actin-positive matrix-producing cells and Smad2/3 activity. Glechoma hederacea extracts attenuated BDL-induced inflammatory cell infiltration/accumulation, NF-κB and AP-1 activation, and inflammatory cytokine production. Further studies demonstrated an inhibitory effect of Glechoma hederacea extracts on the axis of high mobility group box-1 (HMGB1)/toll-like receptor-4 (TLR4) intracellular signaling pathways. Conclusions The hepatoprotective, anti-oxidative, anti-inflammatory, and anti-fibrotic effects of Glechoma hederacea extracts seem to be multifactorial. The beneficial effects of daily Glechoma hederacea extracts supplementation were associated with anti-oxidative, anti-inflammatory, and anti-fibrotic potential, as well as down-regulation of NF-κB, AP-1, and TGF-β/Smad signaling, probably via interference with the HMGB1/TLR4 axis.

Japanese encephalitis is a mosquito-borne disease caused by Japanese encephalitis virus (JEV) infection. Although JEV infects and replicates in cells with multiple tissue origins, neurons are the preferential cells for JEV infection. Currently, the identities of JEV cell tropism are largely unclear. To gain better insight into the underlying identities of JEV cell tropism, this study was designed to compare the JEV cell tropism with naïve or differentiated PC12 cells. Through nerve growth factor-differentiated PC12 cells, we discovered that JEV efficiently replicated in differentiated PC12 cells rather than naïve cells. Mechanistic studies revealed that viral adsorption/attachment seemed not to be a crucial factor. Supporting data showed that antagonizing postreceptor intracellular signaling of interferons, along with the activation of suppressor of cytokine signaling-3 (SOCS3) expression and protein tyrosine phosphatase activity, were apparent in differentiated PC12 cells after JEV infection. Independent of differentiating inducing agents, the upregulation of SOCS3 expression and protein tyrosine phosphatase activity, as well as preferential JEV tropism, were common in JEV-infected differentiated PC12 cells. Using cultured primary neurons, JEV efficiently replicated in embryonic neurons rather than adult neurons, and the preference was accompanied by higher SOCS3 expression and protein tyrosine phosphatase activity. Given that both SOCS3 and protein tyrosine phosphatases have been implicated in the process of neuronal differentiation, JEV infection seems to not only create an antagonizing strategy to escape host's interferon antiviral response but also takes advantage of cellular machinery to favor its replication. Taken together, current findings imply that dynamic changes within cellular regulators of antiviral machinery could be accompanied by events of neuronal differentiation, thus concurrently playing roles in the control of JEV cell tropism and replication. © 2017 IUBMB Life, 69(2):79-87, 2017.

Right heart catheterization is an important diagnostic tool but carries risks of adverse events. Little is known about the feasibility and safety of using dialysis arteriovenous (AV) shunts. We aim to evaluate the feasibility and safety of using dialysis AV shunts for access in right heart catheterization.Hemodialysis patients who required right heart catheterization were prospectively enrolled. A 7 Fr sheath was inserted and a balloon-tipped pulmonary artery catheter was advanced for right heart catheterization. Patients were followed for 1 month, and technical success, procedure details, and complications were recorded.Thirteen patients received right heart catheterization via AV shunts. Three patients were evaluated for heart failure, and 10 were examined for pulmonary hypertension. Median patient age was 69 years (interquartile range [IQR], 58-77 years), and median shunt age was 50 months (IQR, 32-75 months). Five shunts were located in the upper arm, 2 were in the right arm, and 5 were native fistulas. All AV shunt punctures were successful on the first attempt. All right heart catheterizations were completed via AV shunts, and the technical success rate was 100%. Median fluoroscopy time was 6.9 minutes. No venous access complications or right heart catheterization-related complications occurred immediately after the procedure or during the 1-month follow-up period.AV dialysis shunts can be used for venous access for right heart catheterization with acceptable feasibility and patient tolerability. Further randomized studies are needed to confirm the benefits of this approach compared with other approaches.

Background: Arteriovenous fistula (AVF) thrombosis is a relevant cause of morbidity in hemodialysis (HD) patients. The number of circulating endothelial progenitor cells (EPCs) has been identified as a surrogate marker for vascular repair and health. Deficiency of EPCs has been demonstrated in dialysis patients to be associated with vascular events. Nonetheless, their role in thrombosis of AVFs remains unknown. Methods: From January 2010 to May 2013, 147 HD patients with dysfunctional AVFs were enrolled. Surface makers including CD34, KDR and CD133 were used in combination to determine the number of circulating EPCs. All participants were prospectively followed at 6-month interval until December 2015. The primary outcome was thrombosis of dialysis AVFs. Results: The median follow-up was 47 months, within which 42 patients experienced at least one episode of AVF thrombosis. Patients with AVF thrombosis had lower CD34+KDR+ cell counts compared with patients without thrombosis (median 5 vs. 13 per 150,000 mononuclear cells, p < 0.001). Kaplan-Meier analysis demonstrated an inverse relationship between CD34+KDR+ cell count tertiles and thrombosis-free patency (59, 69 and 86% for low, middle and high tertiles; p = 0.02). Using Cox regression analysis, AVF thrombosis was predicted by baseline CD34+KDR+ cell counts (hazards ratio (HR) 0.963, 95% CI 0.928-1.000, p = 0.05) and tertiles (high vs. low, HR 3.266, 95% CI 1.380-7.728, p < 0.01). In multivariate analysis, only CD34+KDR+ cell tertiles, C-reactive protein and lesion length remained independent predictors for thrombosis. Conclusion: Our study demonstrated an independently reverse association between circulating EPCs and thrombosis of dialysis AVFs. Further studies are warranted to ascertain whether EPCs serve as a marker or a therapeutic target for AVF thrombosis.

Traditionally, a radial or brachial arterial approach is unadvisable in hemodialysis patients. Consequently, coronary angiography or angioplasty is usually performed via a femoral artery approach in these patients, who carry a higher risk of vascular access complications. In hemodialysis patients, arteriovenous grafts (AVG) are created for repeated punctures; however, the feasibility and safety of a trans-AVG approach for coronary angiography or angioplasty remains unclear.In our institution, cardiac catheterizations were attempted via AV grafts in hemodialysis patients with a U-shaped forearm AVG. We retrospectively identified coronary angiography or angioplasty procedures in hemodialysis patients from a computer-based database in our hospital. The procedure details and outcomes were obtained from review of the clinical, angiographic and hemodialysis records.From 2008 to 2013, 167 procedures in hemodialysis patients were identified from 2866 diagnostic or interventional coronary procedures in our institution. Out of these, 24 procedures in 17 patients were performed via a trans-AVG approach. In all AVG procedures, a 6F 16-cm or 7F 10-cm sheath was placed from the AVG into the brachial artery. All diagnostic procedures were successfully performed. In 14 procedures, the patients also underwent angioplasty and all of the angioplasty procedures were successful. There was no arterial spasm, arterial dissection, puncture site hematoma, or acute thrombosis of the AVG during or after the procedures.A trans-AVG approach appears to be a feasible and safe route for coronary angiography or angioplasty in hemodialysis patients with a U-shaped forearm AVG. However, further studies with a larger patient number are necessary.Arteriovenous graft; Hemodialysis; Percutaneous coronary intervention.

To investigate the efficacy, safety, and patency following treatment of wall-adherent thrombus in hemodialysis vascular access with a wall-contact device, the Arrow-Trerotola percutaneous thrombolytic device (PTD).We retrospectively reviewed an existing database of procedures fulfilling the following criteria: thrombosed hemodialysis access, wall-adherent thrombus, and use of PTD for mechanical thrombectomy. Data on immediate success, complications, and patency were collected from medical records, dialysis records, and angiographic reports.Ninety-three patients with 108 episodes of vascular access thrombosis were included in the study. Fifty-three of the procedures were performed on native fistulas, and 55 were on synthetic grafts. Anatomical and clinical success was achieved in 97% and 96% of the procedures, respectively. The average procedure time was 52 ± 23 minutes. Complications occurred in three of the procedures (2.7%), but none of these complications were device-related. The primary patency rates in the native fistula group were 57% and 42% at three and six months, respectively. The primary patency rates in the synthetic graft group were 40% at three months, and 27% at six months. The secondary patency rates at six months were 91% in the native fistula group, and 93% in the synthetic graft group.Our results show that a wall-contact mechanical device, PTD, is effective and safe for endovascular removal of wall-adherent thrombi in hemodialysis vascular access in both native fistulas and synthetic grafts.Adherent; Angioplasty; Endovascular; Hemodialysis; Thrombectomy; Vascular access.

Inflammation is relevant in restenosis of atherosclerotic vascular diseases, but its role in dialysis arteriovenous fistula remains unknown. In animal studies, upregulation of monocyte chemoattractant protein-1 has been shown in venous segments of arteriovenous fistula. We, therefore, aimed to investigate serial changes in circulating monocyte chemoattractant protein-1 after percutaneous transluminal angioplasty of dialysis arteriovenous fistulas and its relation to restenosis.Fifty-nine patients with dysfunctional arteriovenous fistulas that were referred for percutaneous transluminal angioplasty were enrolled prospectively between January of 2010 and July of 2012. Three of them were excluded due to percutaneous transluminal angioplasty failure or acute infection. Blood was sampled from arteriovenous fistulas at baseline, 2 days, 2 weeks, and 3 months after percutaneous transluminal angioplasty. Clinical follow-up was continued monthly for 3 months. Angiographic follow-up was arranged at the end of 3 months. Seventeen patients without significant stenosis were enrolled as the control group.Fifty-six patients completed clinical follow-up. Significant increases in monocyte chemoattractant protein-1 were observed at 2 days and 2 weeks (both P0.001) after percutaneous transluminal angioplasty. Twenty-three (41%) patients had symptomatic restenosis. The restenosis group had a higher percentage change in monocyte chemoattractant protein-1 levels at 2 days (median =47%; interquartile range, 27%-65% versus median =17%; interquartile range, 10%-25%; P0.001) after percutaneous transluminal angioplasty compared with the patent group. Fifty-two patients completed angiographic follow-up. A positive correlation between relative luminal loss and monocyte chemoattractant protein-1 increase at 2 days after percutaneous transluminal angioplasty was found (r=0.53; P0.001). In multivariate analysis, postangioplasty monocyte chemoattractant protein-1 increase at 2 days was an independent predictor of restenosis. Using receiver operator characteristic analysis,25% postangioplasty increase of monocyte chemoattractant protein-1 was significantly associated with restenosis after percutaneous transluminal angioplasty (hazard ratio, 5.36; 95% confidence interval, 1.81 to 15.8).Circulating monocyte chemoattractant protein-1 levels were elevated 2 days and 2 weeks after percutaneous transluminal angioplasty. Early postangioplasty increase of monocyte chemoattractant protein-1 level was associated with restenosis of arteriovenous fistulas.

To evaluate the usefulness of an approach through the radial artery distal to the arteriovenous anastomosis for salvaging nonmaturing radiocephalic arteriovenous fistulas. Procedures that fulfilled the following criteria were retrospectively reviewed: (1) autogenous radiocephalic fistulas, (2) fistulas less than 3 months old, (3) distal radial artery approach for salvage. From 2005 to 2011, a total of 51 patients fulfilling the above criteria were enrolled. Outcome variables were obtained from angiographic, clinical and hemodialysis records, including the success, complication, and primary and secondary patency rates. The overall anatomical and clinical success rates for the distal radial artery approach were 96 and 94 %, respectively. The average procedure time was 36 ± 19 min. Six patients (12 %) experienced minor complications as a result of extravasations. No arterial complication or puncture site complication was noted. The postinterventional 6-month primary patency rate was 51 %, and the 6-month secondary patency rate was 90 %. When the patients were divided into a stenosed group (20 patients) and an occluded group (31 patients), there were no differences in the success rate, complication rate, or primary and secondary patency rates. An approach through the radial artery distal to the arteriovenous anastomosis is an effective and safe alternative for the salvage of nonmaturing radiocephalic arteriovenous fistulas, even for occluded fistulas.

Recently, Rey proposed an efficient (2, n) matrix- based secret image sharing (MSIS) scheme based on simple binary matrix operations. However, the threshold property of Rey's (2, n)-MSIS scheme is compromised. Elsheh and Hamza showed a weakness that if the ranks of the singular matrices used in Rey's scheme are not low enough then one can retrieve the secret information from only one shadow image. In this paper, we overcome this weakness. Our new (2, n)-MSIS scheme satisfies the threshold condition, and has low computational complexity for recovery.

Objectives To compare clinical outcomes between mechanical thrombectomy devices with hydrodynamic mechanism and rotational mechanism. Background A number of advantages and concerns have been raised for different mechanical devices but the comparisons of clinical outcomes are absent, especially for the treatment of autogenous hemodialysis arteriovenous (AV) fistulas. Methods The authors retrospectively reviewed 275 percutaneous thrombectomy procedures in AV fistulas. Procedures included were thrombectomy using devices with hydrodynamic mechanism, the AngioJet rheolytic catheter (AngioJet) (n = 134) or devices with rotational mechanism, the Arrow-Trerotola percutaneous thrombectomy device (PTD) (n = 141). Measured outcomes included clinical success, complications and patency rates. Results Clinical success was achieved in 76% (102 of 134) of the AngioJet procedures and in 91% (128 of 141) of the PTD procedures (P = 0.002). The procedure time for the PTD method was significantly shorter than that of the AngioJet method (52 vs. 88 min, P < 0.001). Complications occurred in 14% of the AngioJet procedures and 11% of the PTD procedures. The post-intervention primary patency rates at 6 months were 45% for the AngioJet group and 43% for the PTD group (P = 0.70). The postintervention secondary patency rates at 1 year were 74% for the AngioJet group and 87% for the PTD group (P = 0.01). Conclusions For the salvage of thrombosed AV fistulas, a device using rotational mechanism is more time-saving with a higher immediate success rate and secondary patency rate. However, the long-term patency results were not different. © 2012 Wiley Periodicals, Inc.

Recently, Wang introduced a novel (2, n ) region incrementing visual cryptographic scheme (RIVCS), which can gradually reconstruct secrets in a single image with multiple security levels. In RIVCS, the secret image is subdivided into multiple regions in such a way that any t shadow images, where 2 ≤ t ≤ n, can be used to reveal the (t-1) th region. However, Wang's scheme suffers from the incorrect-color problem, which the colors of reconstructed images may be reversed (i.e., the black and white are reversed). If the color of text is also the secret information, the incorrect-color problem will compromise the secret. Additionally, Wang's scheme is only suitable for the 2-out-of-n case, i.e., (k,n)-RIVCS where k=2. In this paper, we propose a general (k,n)-RIVCS, where k and n are any integers, that is able to reveal correct colors of all regions. This paper has made three main contributions: 1) our scheme is a general (k,n)-RIVCS, where k and n can be any integers; 2) the incorrect-color problem is solved; and 3) our (k,n)-RIVCS is theoretically proven to satisfy the security and contrast conditions.

There is an ongoing discussion on whether serum uric acid (SUA) predicts ischemic heart disease (IHD) independently of other metabolic factors, which, if confirmed, would signify a role for uric acid in the pathogenesis of cardiovascular disease. We investigated whether such a relation exists for ethnic Chinese with low CVD risk.Enrolled, between 1994 and 1996, were 128,569 adults ≥ 20 years from four 'MJ' Health Check-up Clinics in Taiwan. Excluded were those with heart disease, previous stroke(s), renal disease, and/or cancer. Physical examinations, biospecimen collections, and structured questionnaires were executed according to standardised protocols. We identified IHD events according to the ICD-9-CM codes 410-414 using hospitalisation records obtained from the National Health Insurance and the Death Certification Registry databases. The Cox proportional hazard model was used to estimate the hazard ratios (HRs) between SUA and IHD events. A total of 2049 subjects (1239 men, 810 women) developed IHD from baseline to Dec. 31, 2002. Men had a higher IHD incidence than did women (2.84 vs. 1.61 1/1000 person-years; p0.0001). The risk-factor-adjusted HRs (95% confidence-interval [CI]) for hyperuricemiae (SUA ≥ 7.0/≥ 6.0mg/dL) were 1.25 (1.11-1.40) for men and 1.19 (1.02-1.38) for women. In the low-risk population (lacking the NCEP-ATPIII metabolic syndrome components), a significant association was still observed (adjusted HR: 1.54 [1.09-2.17]).The hyperuricemia was independently associated with the development of IHD not only in the general population but also in those without any metabolic risk factor for NCEP ATPIII. Hyperuricemia may be considered as a potential risk factor for IHD.

Microglia polarization of classical activation state is crucial to the induction of neuroinflammation, and has been implicated in the pathogenesis of numerous neurodegenerative diseases. Fungal immunomodulatory proteins are emerging health-promoting natural substances with multiple pharmacological activities, including immunomodulation. Herein, we investigated the anti-inflammatory and neuroprotective potential of fungal immunomodulatory protein extracted from Ganoderma microsporum (GMI) in an in vitro rodent model of primary cultures. Using primary neuron/glia cultures consisting of neurons, astrocytes, and microglia, a GMI showed an alleviating effect on lipopolysaccharide (LPS)/interferon-&gamma, (IFN-&gamma, )-induced inflammatory mediator production and neuronal cell death. The events of neuroprotection caused by GMI were accompanied by the suppression of Nitric Oxide (NO), Tumor Necrosis Factor-&alpha, (TNF-&alpha, ), Interleukin-1&beta, (IL-1&beta, ), and Prostaglandin E2 (PGE2) production, along with the inhibition of microglia activation. Mechanistic studies showed that the suppression of microglia pro-inflammatory polarization by GMI was accompanied by the resolution of oxidative stress, the preservation of protein tyrosine phosphatase and serine/threonine phosphatase activity, and the reduction of NF-&kappa, B, AP-1, cyclic AMP response element-binding protein (CREB), along with signal transducers and activators of transcription (Stat1) transcriptional activities and associated upstream activators. These findings suggest that GMI may have considerable potential towards the treatment of neuroinflammation-mediated neurodegenerative diseases.

Amniotic rupture sequence or amniotic band syndrome is a rare, non-recurrent disease complex. We preferred the former term because its wide spectra of fetal malformation appear to depend on the timing and the consequent changes following a single event of amniotic rupture. However, the exact etiology and pathogenesis still remain obscure; and the disease is often mis- or under-diagnosed, thus leading to inappropriate genetic counselling. Prenatal diagnosis is sometimes possible with the aid of ultrasound. We reported our experience of 5 cases of amniotic rupture sequence with special emphasis on different clinical pictures, possible pathogenesis and pathologic findings. Hopefully this will aid in the recognition of this disorder, thus offer appropriate genetic counselling to the patients.

Thrombophilia has been proposed to be an important risk factor hemodialysis vascular access thrombosis. Nonetheless, the role of thrombophilia on post-angioplasty thrombosis remained unknown. From Jan 2015 to Dec 2015, a nested case-control study was performed in patients who received endovascular

Percutaneous transluminal angioplasty (PTA) -induced venous rupture is a common complication of hemodialysis access intervention. Various management strategies have been reported but the patency outcome was poor. We aim to report the immediate and patency results with a self-expandable stent graft

This paper utilizes the Taguchi design method to optimize the design parameters of a light-emitting diode (LED) backlight unit for wide color gamut liquid crystal displays (LCDs). In optimizing the design, the parametric analyses consider two particular regions of the backlight unit, namely, the color-mixing zone and the extractor zone. The Taguchi experiments are configured in L9 (34 ) orthogonal arrays and are designed to evaluate the effects of the design parameters on the color-difference, optical efficiency and luminance of the unit. The analysis of variance (ANOVA) results reveal that the optical efficiency and color-difference properties are determined primarily by the reflector design and the length of the color mixing zone, respectively, while the luminance to the LCD panel is affected principally by the taper angle of the optical microstructures in the extractor zone. The optimal design parameters of the color-mixing zone and extractor zone are estimated from the Taguchi S/N ratio data and the ANOVA results, and are verified via ray-tracing simulations. For an input flux of 1501 lm, the optimal design shows 0.01 of the color differences in CIE 1976 color space, 85% of the optical efficiency, and 10675 nits of luminance. Thus, the optimized backlight unit provides an ideal solution for the illumination of large-scale LCD display devices.

Plasma levels of asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide production, correlate with endothelial dysfunction and the development of cardiovascular events in patients with uremia. It is not known whether endothelial dysfunction contributes to the dysfunction of arteriovenous fistulas (AVFs) in hemodialysis patients. Here, we studied the predictive value of baseline plasma ADMA for symptomatic restenosis of an AVF after percutaneous transluminal angioplasty in dialysis patients. We obtained baseline plasma ADMA levels before percutaneous transluminal angioplasty in 100 consecutive patients with dysfunctional AVFs. Patients were followed up clinically for up to 6 mo after angioplasty for recurrent dysfunction. During the 6 mo after angioplasty, 46 patients experienced recurrent dysfunction of their AVF; of these, follow-up fistulography showed restenosis at the same location in 41, new stenosis at different locations in two, and no significant stenosis in three patients. Up to 60% of the patients with high levels of ADMA (>0.910 microM) had target lesion restenosis compared with 25% of those with low levels (

Purpose To compare the technical success, safety, and patency of cutting balloon angioplasty versus high-pressure balloon angioplasty in the treatment of resistant native hemodialysis fistula stenoses. Materials and Methods The authors retrospectively reviewed 1,220 percutaneous transluminal angioplasty procedures performed to treat dysfunctional native hemodialysis fistulas. Seventy patients with stenoses resistant to conventional balloon angioplasty (up to 24 atm) were included in this study: 35 patients underwent cutting balloon angioplasty from September 2003 through February 2005, and 35 patients underwent high-pressure balloon angioplasty from March 2005 through April 2006. Evaluation included technical success, complications, and postintervention patency rates up to 6 months. Results The technical success rates were similar between the cutting balloon (100%) and high-pressure balloon (97.1%) groups. After cutting balloon angioplasty, the primary lesion patency rates were 100% (35/35), 88.6% (31/35), and 71.4% (25/35) at 1 month, 3 months, and 6 months, respectively. After high-pressure balloon angioplasty, the primary lesion patency rates were 97.1% (34/35), 62.9% (22/35), and 42.9% (15/35) respectively. The primary lesion patency rates at 3 and 6 months were significantly better with cutting balloon angioplasty than with high-pressure balloon angioplasty ( P = .018 and .009, respectively). There were no device-related complications in the cutting balloon group. Six device-related extravasations occurred in the high-pressure balloon group. Conclusions The results of this retrospective study suggest that, for resistant stenoses in native hemodialysis fistulas, both high-pressure balloon and cutting balloon angioplasty are effective; however, cutting balloon angioplasty seems to provide more long-standing primary patency at 6-month follow-up.

The Kyoto Protocol attempts through political negotiations to guide participating industrialized countries’ greenhouse gas (GHG) emissions from a positive growing trend, to reach a peak point (or turning point), and then be reduced to a negative growth. That means the relationship between decreasing GHG emissions and economic growth may be described by an inverted-U curve (or called a bell-shaped curve), which is consistent with the concept of the Environmental Kuznets Curve (EKC) hypothesis. This research observed that the economic development and GHG emissions in Economies in Transition (EITs) exhibit a hockey-stick curve trend (or called quasi-L-shape curve), that also generates a lot of “hot air” which is significant to the implementation of the Kyoto Protocol. In addition, through the analysis of single-country time series data and GDP data, this research demonstrated that statistical data for most of the Annex II countries do not possess evidence that supports the EKC hypothesis for GHG emissions. The results from this study also indicated that the 38 industrialized countries are unable to meet their targets under the Kyoto Protocol within the specified time period, which are probably caused by the econometric method's inability to predict accurately the extents and development of innovative technologies and Clean Development Mechanism (CDM) projects. If the international community truly wants to reduce the GHG emissions, the effectiveness of the existing international framework for emissions reduction needs to be reconsidered seriously, and the global cooperation mechanism also needs to be greatly enhanced.

Autophagy and apoptosis represent important cellular processes involved in cancer cell killing mechanisms. Epidermal growth factor receptor inhibitor gefitinib and valproic acid have been implicated in the treatment of malignancies including glioma involving autophagic and apoptotic mechanisms. Therefore, it is interesting to investigate whether a combination of gefitinib and valproic acid shows better cancer cell killing effect on human glioma cells. We found that a nontoxic concentration of valproic acid sensitized U87 and T98G glioma cells to gefitinib cytotoxicity by inhibiting cell growth and long-term clonogenic survival. The augmented consequences were accompanied by the formation of autophagic vacuoles, conversion of microtubule-associated protein-1 light chain 3-II (LC3-II), and degradation of p62. Autophagy inhibitor 3-methyladenosine and chloroquine and genetic silencing of LC3 but not broad-spectrum caspase inhibitor attenuated gefitinib/valproic acid-induced growth inhibition. Gefitinib/valproic acid-induced autophagy was accompanied by the activation of liver kinase-B1 (LKB1)/AMP-activated protein kinase (AMPK)/ULK1. Silencing of AMPK and ULK1 suppressed gefitinib/valproic acid-induced autophagy and growth inhibition. Mechanistic studies showed that gefitinib/valproic acid increased intracellular reactive oxygen species generation and N-acetyl cysteine attenuated gefitinib/valproic acid-caused autophagy and growth inhibition. In addition to demonstrating the autophagic mechanisms of gefitinib/valproic acid, the results of this study further suggest that intracellular oxidative stress and the LKB1/AMPK signaling might be a potential target for the development of therapeutic strategy against glioma.

Acute mesenteric ischemia carries high morbidity and mortality rates unless urgently treated. In patients without evident bowel necrosis on computer tomography, the treatment remained conservative in less experienced hospital. When a suspicious case progressed into septic shock, the patient was