Ensemble species distribution modeling and multilocus phylogeography provide insight into the spatial genetic patterns and distribution dynamics of a keystone forest species, Quercus glauca.

BACKGROUND: Forests are essential for maintaining species diversity, stabilizing local and global climate, and providing ecosystem services. Exploring the impact of paleogeographic events and climate change on the genetic structure and distribution dynamics of forest keystone species could help predict responses to future climate change. In this study, we combined an ensemble species distribution model (eSDM) and multilocus phylogeography to investigate the spatial genetic patterns and distribution change of Quercus glauca Thunb, a keystone of East Asian subtropical evergreen broad-leaved forest. RESULTS: A total of 781 samples were collected from 77 populations, largely covering the natural distribution of Q. glauca. The eSDM showed that the suitable habitat experienced a significant expansion after the last glacial maximum (LGM) but will recede in the future under a general climate warming scenario. The distribution centroid will migrate toward the northeast as the climate warms. Using nuclear SSR data, two distinct lineages split between east and west were detected. Within-group genetic differentiation was higher in the West than in the East. Based on the identified 58 haplotypes, no clear phylogeographic structure was found. Populations in the Nanling Mountains, Wuyi Mountains, and the southwest region were found to have high genetic diversity. CONCLUSIONS: A significant negative correlation between habitat stability and heterozygosity might be explained by the mixing of different lineages in the expansion region after LGM and/or hybridization between Q. glauca and closely related species. The Nanling Mountains may be important for organisms as a dispersal corridor in the west-east direction and as a refugium during the glacial period. This study provided new insights into spatial genetic patterns and distribution dynamics of Q. glauca.

Impact of Premature Ventricular Complex (PVC) Burden on the Left Ventricle in the Structurally Normal Heart: Hemodynamic Alterations of Idiopathic PVC on Echocardiography.

Background: Premature ventricular complex (PVC) without structural heart disease is mostly viewed as a benign arrhythmia. However, the high burden of PVC causes cardiomyopathy due to intraventricular dyssynchrony. The effects of ectopic contraction on left ventricular (LV) hemodynamics in the structurally normal heart are unclear. Objectives: To examine the effect of PVC burden on LV dimension, LV systolic function, and intraventricular blood flow, and to determine whether ectopic ventricular contraction affects LV hemodynamics. Methods: Patients aged ≥ 18 years with PVC ≥ 5% on Holter recording were enrolled and divided into groups G1 (5-10%), G2 (10-20%), and G3 (≥ 20%). We excluded patients with structural heart diseases, pacemakers, and LV systolic dysfunction [LV ejection fraction (LVEF) < 50%]. Clinical characteristics and routine transthoracic echocardiography parameters were compared. Results: The end-systolic LV internal dimension increased according to the PVC burden from G1 to G3 (p = 0.001). LVEF was inversely associated with PVC burden from G1 to G3 (p = 0.002). The same pattern was seen for LV outflow tract (LVOT) maximal velocity (p = 0.005) and maximal pressure gradient (PG) (p = 0.005), LVOT velocity time integral (VTI) (p = 0.03) and LV stroke volume index (LVSI) (p = 0.008). Conclusions: Systolic function and LV end-systolic dimension were inversely associated with PVC burden. Decreased LVOT flow velocity and PG were related to increased PVC burden. LVOT VTI and LVSI were smaller when the PVC burden exceeded 20%. These negative hemodynamic manifestations of idiopathic PVC were considerable even in structure normal hearts, hence the early elimination of PVC is strongly advised.

Clinical Outcomes of Patients with Intermediate-to-High-Risk Pulmonary Embolism Undergoing Ultrasound-Assisted Catheter-Based Fibrinolysis Therapy in a Mid-Term Follow-Up Period - A Retrospective Observational Study.

OBJECTIVES: Endovascular therapy with ultrasound-assisted catheter-directed thrombolysis (UACDT) theoretically provides higher efficacy while reducing the bleeding risk compared with conventional systemic thrombolysis. The clinical outcomes of UACDT in treating intermediate-to-high-risk pulmonary embolism (PE) are lacking in an Asian population. METHODS: Forty-two patients who presented with intermediate-to-high-risk PE received UACDT. The patients were divided into two groups based on the incidence of procedure-related bleeding events, and baseline demographics were compared between the two groups. A paired-Student's t test was conducted to evaluate the efficacy of UACDT. Univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for significant bleeding events. RESULTS: The average age was 58.93 ± 20.48 years, and 33.33% of the study participants were male. A total of 85.7% of the participants had intermediate-risk PE. Compared with pre-intervention pulmonary artery pressure, the mean pulmonary artery pressure decreased significantly (37.61 ± 9.57 mmHg vs. 25.7 ± 9.84 mmHg, p < 0.01) after UACDT. The cumulative total tissue plasminogen activator dosage and total infusion duration were 44.54 ± 20.55 mg and 39.14 ± 19.06 hours respectively. Overall, 21.43% of the participants had severe bleeding events during the endovascular fibrinolysis treatment period. Forward conditional multivariate logistic regression analysis revealed that the lowest fibrinogen level during thrombolysis was an independent factor associated with moderate-to-severe bleeding (odds ratio: 0.40, 95% confidence interval: 0.19-0.88, p = 0.02). CONCLUSIONS: UACDT exhibited high efficacy, but resulted in a higher-than-expected bleeding rate in this real-world study of an Asian population. The lowest fibrinogen level during thrombolysis was an independent risk factor associated with procedure-related bleeding events.

Spironolactone ameliorates endothelial dysfunction through inhibition of the AGE/RAGE axis in a chronic renal failure rat model.

BACKGROUND: Spironolactone can improve endothelial dysfunction in the setting of heart failure and diabetes models. However, its beneficial effect in the cardiovascular system is not clear in the setting of non-diabetic renal failure. We conducted this study to investigate whether spironolactone can ameliorate endothelial dysfunction in a 5/6 nephrectomy model, and to determine the underlying mechanism. METHODS: Twenty-four Sprague-Dawley rats were divided into four groups. A renal failure model was created using the 5/6 nephrectomy method. The four groups included: Sham-operation group (Group1), chronic kidney disease (CKD; Group2), CKD + ALT-711 (advanced glycation end products [AGEs] breaker; Group 3), and CKD + spironolactone group (Group4). Acetylcholine (Ach)-mediated vasodilatation responses were compared between the four groups. To investigate the underlying mechanism, we cultured human aortic endothelial cells (HAECs) for in-vitro assays. Differences between two groups were determined with the paired student's t test. Differences between three or more groups were determined through one-way analysis of variance (ANOVA) with post-hoc analysis with LSD method. RESULTS: Compared with Group 1, Group 2 has a significantly impaired Ach-mediated vasodilatation response. Group 3 and 4 exhibited improved vasoreactivity responses. To determine the underlying mechanism, we performed an in-vitro study using cultured HAECs. We noted significant sirtuin-3 (SIRT3) protein downregulation, reduced phosphorylation of endothelial nitric oxide synthase at serine 1177 (p-eNOS), and increased intracellular oxidative stress in cultured HAECs treated with AGEs (200 µg/mL). These effects were counter-regulated when cultured HAECs were pretreated with spironolactone (10 µM). Furthermore, the increased p-eNOS production by spironolactone was abrogated when the HAECs were pretreated with tenolvin (1 µM), a SIRT3 inhibitor. CONCLUSIONS: Spironolactone could ameliorate endothelial dysfunction in a 5/6 nephrectomy renal failure model through AGEs/Receptor for AGEs (RAGEs) axis inhibition, SIRT3 upregulation, and nicotinamide adenine dinucleotide phosphate oxidase-2 (NOX-2) and its associated intracellular oxidative stress attenuation.

Skin autofluorescence is associated with inappropriate left ventricular mass and diastolic dysfunction in subjects at risk for cardiovascular disease.

BACKGROUND: Enhanced advanced glycation end products deposition within myocardial tissue may cause diastolic dysfunction. However, whether this is related to left ventricular hypertrophy or inappropriate left ventricular mass remains unclear. METHODS: We prospectively enrolled 139 subjects at risk for cardiovascular diseases. We used echocardiography for measurements of left ventricular mass and cardiac systolic and diastolic functional parameters. An advanced glycation end product reader was applied for measurements of skin autofluorescence values. Comparisons of left ventricular mass and echocardiographic parameters between the higher and lower skin autofluorescence groups were analyzed. RESULTS: Compared with the lower skin autofluorescence group, left ventricular mass index and the ratio of observed left ventricular mass/predicted left ventricular mass (oLVM/pLVM) was significantly higher in the higher skin autofluorescence group (61.22 ± 17.76 vs. 47.72 ± 11.62, P < 0.01, 1.62 ± 0.38 vs. 1.21 ± 0.21, P < 0.01). After adjustment for potential confounding factors, skin autofluorescence was an independent factor for left ventricular mass index (ß = 0.32, P < 0.01) and the ratio of oLVM/pLVM (ß = 0.41, P < 0.01). Skin autofluorescence ≥2.35 arbitrary unit predicted left ventricular hypertrophy at a sensitivity of 58.8%, and a specificity of 73.0% (P < 0.01). Skin autofluorescence ≥2.25 arbitrary unit predicted inappropriate left ventricular mass at a sensitivity of 71.1%, and a specificity of 83.9% (P < 0.01). Skin autofluorescence was positively correlated with E/E', an indicator for diastolic dysfunction (r = 0.21, P = 0.01). CONCLUSIONS: Skin autofluorescence is a useful tool for detecting left ventricular hypertrophy, inappropriate left ventricular mass and diastolic dysfunction.

A Hash Based Remote User Authentication and Authenticated Key Agreement Scheme for the Integrated EPR Information System.

To protect patient privacy and ensure authorized access to remote medical services, many remote user authentication schemes for the integrated electronic patient record (EPR) information system have been proposed in the literature. In a recent paper, Das proposed a hash based remote user authentication scheme using passwords and smart cards for the integrated EPR information system, and claimed that the proposed scheme could resist various passive and active attacks. However, in this paper, we found that Das's authentication scheme is still vulnerable to modification and user duplication attacks. Thereafter we propose a secure and efficient authentication scheme for the integrated EPR information system based on lightweight hash function and bitwise exclusive-or (XOR) operations. The security proof and performance analysis show our new scheme is well-suited to adoption in remote medical healthcare services.

An Optimization-Based Technology Applied for Face Skin Symptom Detection.

Face recognition segmentation is very important for symptom detection, especially in the case of complex image backgrounds or noise. The complexity of the photo background, the clarity of the facial expressions, or the interference of other people's faces can increase the difficulty of detection. Therefore, in this paper, we have proposed a method to combine mask region-based convolutional neural networks (Mask R-CNN) with you only look once version 4 (YOLOv4) to identify facial symptoms by this new method. We use the face image dataset from the public image databases DermNet and Freepic as the training source for the model. Face segmentation was first applied with Mask R-CNN. Then the images were imported into ResNet-101, and the facial features were fused with region of interest (RoI) in the feature pyramid networks (FPN) structures. After removing the non-face features and noise, the face region has been accurately obtained. Next, the recognized face area and RoI data were used to identify facial symptoms (acne, freckle, and wrinkles) with YOLOv4. Finally, we use Mask R-CNN, and you only look once version 3 (YOLOv3) and YOLOv4 are matched to perform the performance analysis. Although, the facial images with symptoms are relatively few. We still use a limited amount of data to train the model. The experimental results show that our proposed method still achieves 57.73%, 60.38%, and 59.75% of mean average precision (mAP) for different amounts of data. Compared with other methods, the mAP was more than about 3%. Consequently, using the method proposed in this paper, facial symptoms can be effectively and accurately identified.

Comparison of pharmaco-mechanical thrombolysis and catheter-directed thrombolysis for treating thrombotic or embolic arterial occlusion of the lower limb.

BACKGROUND: Whether pharmaco-mechanical thrombolysis (PMT) results in superior outcomes to catheter-directed thrombolysis (CDT) in treating thrombotic or embolic arterial occlusion of the lower limbs is unclear. METHODS: We enrolled 94 patients with Rutherford class I-IIb due to thrombotic or embolic arterial occlusion in the lower limbs and who received emergency endovascular treatment. Baseline demographics, laboratory data, angiography and clinical outcomes were collected through chart reviews and fluoroscopic imaging. The procedural characteristics (thrombolytic drug dosage, treatment duration, and additional procedures), immediate angiographic outcomes (patency of calf vessels, and complete lysis), complications (major bleeding, and fasciotomy), and primary composite end-points (30-day mortality, amputation, and reocclusion) were compared between patients who received CDT versus PMT. RESULTS: Compared with CDT, PMT was independently associated with lower total UK dosage (standardized coefficient ß=- 0.44; P<0.01) and higher prevalence of complete lysis (odds ratio =1.78, 95% confidence interval: 1.03-3.06; P=0.04) after adjustments of covariates. The PMT group had significantly shorter treatment duration (23.00 [7.25-39.13] vs. 41.00 [27.00-52.50]; P<0.01). No significant intergroup differences were observed for the primary composite end point (10.7% vs. 9.1%; P=0.81), or prevalence of the major bleeding (9.1% vs. 0.0%; P=0.10) despite the PMT group comprising patients with more advanced chronic kidney disease and more diffuse thrombosis. CONCLUSIONS: PMT with a Rotarex is a safe and effective strategy for treating thrombotic or embolic lower limb ischemia. It significantly reduced the thrombolytic drug dosage, and resulted in the complete lysis being more likely.

Protective effects of glutamine preconditioning on ischemia-reperfusion injury in rats.

BACKGROUND: Hepatic ischemia-reperfusion injury is a common phenomenon in hepatic surgical procedures and can result in further severe damage. This study aimed to investigate the protective effects of glutamine preconditioning on hepatic ischemia-reperfusion injury in rats and its dose-dependency. METHODS: Thirty-two healthy male Wistar rats were randomly divided into four groups (n=8 per group). One group received 0.9% NaCl (control) and the other three received glutamine (Gln groups) 4 hours before ischemia. The Gln groups were named GL, GM, and GH according to the glutamine dose. The liver was subjected to 1 hour of ischemia and 2 hours of reperfusion. Two hours later, the levels of alanine aminotransferase (ALT), intracellular free calcium (Ca2+), and activity of Na+/K+ adenosine triphosphatase (ATPase) and superoxide dismutase (SOD) were assessed, and liver tissue sections were examined under a microscope. RESULTS: The Gln and control groups differed in the concentration of intracellular free calcium (P<0.05), and the activity of Na+/K+ ATPase and SOD in the Gln groups was higher than in the control group (P<0.05). The ALT level was lower in the GM and GH groups than in the control group (P<0.05). The levels of Na+/K+ ATPase and SOD rose gradually with increasing glutamine dose (P<0.05), and the concentration of Ca2+ declined gradually with increasing glutamine dose (P<0.05). The degree of hepatocyte injury was milder in the Gln groups than in the control group. CONCLUSIONS: Glutamine preconditioning protected effectively against hepatic ischemia-reperfusion injury. These protective effects were related to the dose of glutamine and due to the reduction of intracellular calcium overload and the improvements in the activity of Na+/K+ ATPase and SOD.

Comparison of optical and crystal properties of three translucent yttria-stabilized tetragonal zirconia polycrystals with those of lithium disilicate glass-ceramic material.

BACKGROUND/PURPOSE: Among the ceramic materials used for all-ceramic crowns, zirconia has high biocompatibility and favorable mechanical properties, but its main drawbacks include low translucency and stress-induced phase transformation. To stabilize high-strength tetragonal zirconia polycrystal (TZP), 3-5 mol% yttria is usually added to prepare yttria-stabilized TZP (Y-TZP). In this study, the optical properties of three commercial Y-TZP ceramics were compared with those of the clinically available glass-ceramic material of lithium disilicate, and the relationship between translucency and crystal properties was analyzed in vitro. MATERIALS AND METHODS: Twelve 5-mm-thick standardized disks were prepared from three Y-TZP ceramics and one lithium disilicate block. Absolute translucency was measured using a spectrophotometer with an integrating sphere. X-ray diffraction was used to quantify the main structural parameters (i.e., preferred plane, quantitative phase, and grain size) of Y-TZP crystals. RESULTS: The product-dominated phase of Y-TZP exhibited a tetragonal lattice pattern, and the preferred planes had minor variations. The diffraction patterns of the three Y-TZP ceramics demonstrated minor effects on translucency, without significant differences (p > 0.05). The grain size of 54-70 nm was negatively related to translucency in Y-TZP. Lithium disilicate specimens had significantly higher translucency than the three Y-TZP specimens (p < 0.001). CONCLUSION: Grain size reduction played an essential role in developing highly translucent Y-TZP ceramics. The three Y-TZP ceramics were essentially opaque but exhibited poorer translucency than lithium disilicate in terms of esthetics.

Preconditioning and postconditioning reduce hepatic ischemia-reperfusion injury in rats.

BACKGROUND: Ischemia-reperfusion injury occurs when ischemic tissues or organs suffer from further functional and structural damage when their blood supply recovers. This study aimed to contrast the protective effects of ischemic preconditioning and ischemic postconditioning in hepatic ischemia-reperfusion injury in rats. METHODS: Thirty-two healthy male Wistar rats were randomly divided into four groups: sham-operated (SO), ischemia-reperfusion (IR), ischemic preconditioning (I-pre), and ischemic postconditioning (I-post). Blood samples and hepatic tissue were taken from all groups after the experiments. RESULTS: There were significant differences between the IR, I-pre and I-post groups in alanine aminotransferase and aspartate aminotransferase levels, NF-kappaB p65 expression, apoptosis index and superoxide dismutase activity in hepatic tissue. There were no significant differences between the I-pre and I-post groups. CONCLUSIONS: Ischemic postconditioning and ischemic preconditioning reduce hepatic ischemia-reperfusion injury, but in clinical practice the former is a more appropriate choice.

Mathematical models for within-host competition of malaria parasites.

In this paper, we formulate two within-host infection models to simulate dynamics of the drug sensitive and drug resistant malaria parasites, where the first model solely considers the within-host competition between these two strains, and the second model further considers the immune re-sponse. Detailed theoretical analysis of the second model are made, including the existence, stability and bifurcation of the equilibrium, which have also been verified by numerical simulations. Both theoretical and numerical results show that competition or chronic control of drug sensitive parasites could inhibit the evolution of drug resistant ones to some extent. However, if the immune response is considered, periodic solution could be observed, and they will persist for all relatively small treatment rate. This may lead to the recurrence of resistance for the chronic control strategy, even though it could delay the resistance emergence. In addition, global sensitivity analysis is implemented to provide the information on the significance of model parameters on the state variables.

Skin autofluorescence is associated with rapid renal function decline in subjects at increased risk of coronary artery disease.

Skin autofluorescence (AF) has been validated as a tool for estimating tissue advanced glycation end products (AGEs) accumulation and predicting long-term cardiovascular outcomes. However, whether measurements of skin AF could predict renal function decline remains controversial. From April, 2014 to April, 2015, we enrolled 245 subjects with at least two conventional risk factors for coronary artery disease (CAD). All were measured for body height and weight, blood pressure, plasma creatinine level, and skin AF at the start of the study. Baseline demographics and laboratory tests data were obtained by chart reviews and patient interviews. Serial plasma creatinine levels were followed regularly every 6-12 months for 2 years. In a stepwise multivariate linear regression analysis, skin AF, was an independent factor for predicting the relative renal function decline rate after adjustment of multiple covariates (ß = -0.036±0.016; p = 0.03). Subgroups analysis revealed that skin AF was a significant factor for relative renal function decline rate in subgroups of age < 65 years (ß = -0.068±0.024; p = 0.02), male sex (ß = -0.053±0.016; p< 0.01), body mass index≧25 Kg/m2(ß = -0.042±0.021; p = 0.04), and estimated glomerular filtration rate ≥ 60 ml/min/1.73m2(ß = -0.043±0.020; p = 0.04). However, only an interaction between skin AF and age attained significance (p for interaction = 0.04). Skin AF is a useful predictor for renal function decline in patients at increased risk of CAD.

Cloud-assisted mutual authentication and privacy preservation protocol for telecare medical information systems.

BACKGROUND AND OBJECTIVE:  With the rapid development of wireless communication technologies and the growing prevalence of smart devices, telecare medical information system (TMIS) allows patients to receive medical treatments from the doctors via Internet technology without visiting hospitals in person. By adopting mobile device, cloud-assisted platform and wireless body area network, the patients can collect their physiological conditions and upload them to medical cloud via their mobile devices, enabling caregivers or doctors to provide patients with appropriate treatments at anytime and anywhere. In order to protect the medical privacy of the patient and guarantee reliability of the system, before accessing the TMIS, all system participants must be authenticated. METHODS:  Mohit et al. recently suggested a lightweight authentication protocol for cloud-based health care system. They claimed their protocol ensures resilience of all well-known security attacks and has several important features such as mutual authentication and patient anonymity. In this paper, we demonstrate that Mohit et al.'s authentication protocol has various security flaws and we further introduce an enhanced version of their protocol for cloud-assisted TMIS, which can ensure patient anonymity and patient unlinkability and prevent the security threats of report revelation and report forgery attacks. RESULTS:  The security analysis proves that our enhanced protocol is secure against various known attacks as well as found in Mohit et al.'s protocol. Compared with existing related protocols, our enhanced protocol keeps the merits of all desirable security requirements and also maintains the efficiency in terms of computation costs for cloud-assisted TMIS. CONCLUSIONS:  We propose a more secure mutual authentication and privacy preservation protocol for cloud-assisted TMIS, which fixes the mentioned security weaknesses found in Mohit et al.'s protocol. According to our analysis, our authentication protocol satisfies most functionality features for privacy preservation and effectively cope with cloud-assisted TMIS with better efficiency.

Electronegative low-density lipoprotein increases the risk of ischemic lower-extremity peripheral artery disease in uremia patients on maintenance hemodialysis.

Electronegative low-density lipoprotein (LDL) has been shown to increase coronary artery disease risk in hemodialysis patients, but its effect on the risk of peripheral artery disease (PAD) remains unclear. We separated plasma LDL from 90 uremia patients undergoing hemodialysis into 5 subfractions (L1-L5) according to charge by using fast-protein liquid chromatography with an anion-exchange column and examined the distribution of L5-the most electronegative LDL subfraction-in total LDL (i.e. L5%). During a 5-year period, we followed up with these patients until the occurrence of ischemic lower-extremity PAD. During the follow-up period, ischemic lower-extremity PAD developed in 24.4% of hemodialysis patients. L5% was higher in hemodialysis patients in whom ischemic lower-extremity PAD occurred (3.03% [IQR, 2.36-4.54], n = 22) than in hemodialysis patients in whom PAD did not occur (1.13% [IQR, 0.90-1.83], n = 68) (p < 0.001). Furthermore, L5% significantly increased the adjusted hazard ratio of ischemic lower-extremity PAD (1.54 [95% CI, 1.14-2.10]) (p = 0.005). Flow-mediated dilation was negatively associated with L5% (p < 0.001). Additionally, in vivo experiments from mice showed that L5 compromised endothelium-dependent vascular relaxation through a nitric oxide-related mechanism. Our findings indicate that increased L5% may be associated with the occurrence of ischemic lower-extremity PAD in hemodialysis patients.

Spinal cord injury is associated with an increased risk of atrial fibrillation: A population-based cohort study.

BACKGROUND: Spinal cord injury (SCI) can result in substantial sensorimotor and autonomic dysfunctions and an adverse prognosis. Cardiovascular disease is the leading cause of death in patients with chronic SCI. OBJECTIVE: We conducted a retrospective cohort study to investigate the association between atrial fibrillation (AF) and SCI. METHODS: Using the National Health Insurance Research Database, we identified 41,691 patients without a history of AF who were newly hospitalized for SCI between 2000 and 2011. The comparison group included 166,724 patients without AF or SCI who were matched to the SCI group according to age, sex, and index year at a ratio of 4:1. Both cohorts were followed up until the end of 2011, and the cumulative incidence of AF was calculated. Univariate and multivariate Cox proportional hazards regression models and Kaplan-Meier curve analysis were used to compare differences in the cumulative incidence of AF between the 2 groups. RESULTS: During the mean follow-up periods of 5.69 years for the SCI group and 6.17 years for the non-SCI group, the overall incidence rates were 2.70 and 1.99 cases per 1000 person-years, respectively (crude hazard ratio 1.36; 95% confidence interval 1.24-1.48). After adjusting for age, sex, and all comorbidities, the risk of AF remained significantly higher in the SCI group than in the non-SCI group (adjusted hazard ratio 1.28; 95% confidence interval 1.17-1.40). CONCLUSION: SCI is associated with an increased risk of AF in a long-term follow-up period.

Skin Autofluorescence Is Associated with Endothelial Dysfunction in Uremic Subjects on Hemodialysis.

BACKGROUND: Elevated levels of advanced glycation end products (AGEs) within tissues may contribute to endothelial dysfunction, an early indicator of atherosclerosis. We aimed to investigate whether levels of skin AGEs could be a useful marker to predict endothelial dysfunction in uremic subjects on hemodialysis. METHODS AND RESULTS: One hundred and nineteen uremic patients on hemodialysis and 57 control subjects with moderate-to-high cardiovascular risk factors and without chronic kidney disease (CKD) were enrolled. We used ultrasound to measure flow-mediated vasodilation (FMD). An AGE reader measured skin autoflurorescence (AF). We then compared differences in FMD and skin AF values between the two groups. The uremic subjects had significantly higher levels of skin AF (3.47±0.76 AU vs. 2.21±0.45 arbitrary units; P<0.01) and significantly lower levels of FMD (4.79%±1.88% vs. 7.19%±2.17%; P<0.01) than the non-CKD subjects. After adjusting for all potential covariates, we found that skin AF level independently predicted FMD in both the hemodialysis and the non-CKD groups. In the hemodialysis group, skin AF ≥ 3.05 arbitrary units predicted abnormal FMD at a sensitivity of 87.9% and a specificity of 78.6% (P<0.01). CONCLUSIONS: Skin AF could be a useful marker to predict endothelial dysfunction in uremic subjects on hemodialysis.