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Clustering has proved to be a successful classification method when it comes to dealing with multiview data. Each method and technique tries to achieve efficiency and accuracy in classifying the multiview data. Multi-source data contains noise and divergence. Another problem is that each view contains many features, so usually the multiview dataset is multi-dimensional. This raises basic problems like the need for a dimensionality reduction technique for optimal selection of features, fusing the data of different views, and maintaining the inter- and intra-consensus of the multiview dataset. The fusion technique should merge the complementary information efficiently. The goal of this study is to use a promising technique for dimension reduction that reduces the noise but maintains the inter-view and cross-view consensus. A self-organizing map is one of the well-known unsupervised neural network algorithms used for preserving typologies during mapping from the input space (high-dimensional) to the display (low-dimensional).An algorithm called Local Adaptive Receptive Field Dimension Selective Self-Organizing Map 2 is a modified form of a self-organizing Map to cater different data types in the dataset. It calculates the dimension relevance with various data instances. These further place the relevant dimension samples in one group. The method does not need to know the number of clusters before hand, as it dynamically determines it during the process. Finally, this study proposed a novel multi-view learning framework that analyzes multi-source data and generates fine clusters efficiently.

Image denoising and super-resolution play vital roles in imaging systems, greatly reducing the preprocessing cost of many AI techniques for object detection, segmentation, and tracking. Various advancements have been accomplished in this field, but progress is still needed. In this paper, we have proposed a novel technique named the Enhanced Learning Enriched Features (ELEF) mechanism using a deep convolutional neural network, which makes significant improvements to existing techniques. ELEF consists of two major processes: (1) Denoising, which removes the noise from images; and (2) Super-resolution, which improves the clarity and details of images. Features are learned through deep CNN and not through traditional algorithms so that we can better refine and enhance images. To effectively capture features, the network architecture adopted Dual Attention Units (DUs), which align with the Multi-Scale Residual Block (MSRB) for robust feature extraction, working sidewise with the feature-matching Selective Kernel Extraction (SKF). In addition, resolution mismatching cases are processed in detail to produce high-quality images. The effectiveness of the ELEF model is highlighted by the performance metrics, achieving a Peak Signal-to-Noise Ratio (PSNR) of 42.99 and a Structural Similarity Index (SSIM) of 0.9889, which indicates the ability to carry out the desired high-quality image restoration and enhancement.

In this paper, a convolved feature vector based adaptive fuzzy filter is proposed for impulse noise removal. The proposed filter follows traditional approach, i.e., detection of noisy pixels based on certain criteria followed by filtering process. In the first step, proposed noise detection mechanism initially selects a small layer of input image pixels, convolves it with a set of weighted kernels to form a convolved feature vector layer. This layer of features is then passed to fuzzy inference system, where fuzzy membership degrees and reduced set of fuzzy rules play an important part to classify the pixel as noise-free, edge or noisy. Noise-free pixels in the filtering phase remain unaffected causing maximum detail preservation whereas noisy pixels are restored using fuzzy filter. This process is carried out traditionally starting from top left corner of the noisy image to the bottom right corner with a stride rate of one for small input layer and a stride rate of two during convolution. Convolved feature vector is very helpful in finding the edge information and hidden patterns in the input image that are affected by noise. The performance of the proposed study is tested on large data set using standard performance measures and the proposed technique outperforms many existing state of the art techniques with excellent detail preservation and effective noise removal capabilities.

Today, data center networks (DCNs) are built using multi-tier architecture. These large-scale networks face many challenges, such as security, delay, low throughput, loops, link oversubscription, TCP Incast and Outcast, etc. In this paper, a TCAM (Ternary Content Addressable Memory) based routing technique is proposed, augmenting the routing capabilities of multi-tier architectures in large scale networks. The routing complexities in these architectures are rectified and improved by implementing an additional TCAM based routing table in Leaf/ToR switches for a specific number of compute nodes in particular Pods, and it is scalable to whole datacenter nodes. To test the model, we implemented two prototype models: one depicting our proposed TCAM based switch and the other is a typical Top-of-the-Rack (ToR) switch and compared the performance of the proposed model and if any overhead introduced in it. The preliminary results show that our TCAM based routing table technique is fast and it forwards the network packets at line-rate, does not introduce considerable latency, on-chip resources power consumptions is less than 3%, and helps to solve or mitigate the above critical problems that are present in the current large DC's three-tier architecture, especially in Top of the Rack and aggregation layers switches.

For inter and intra cluster communication, member nodes jointly build a mutual session key called cluster key to allow secure communication. Most existing schemes for cluster key management use messages exchange among the member nodes within a cluster for the new cluster key establishment when a node leaves or joins a cluster. This causes significant communication and computation costs. Furthermore, the secure distribution of cluster keys among member nodes in frequently changing environments is a difficult task without encryption and decryption operations. For secure cluster key management, we utilized polynomial (P) to accomplish effective intra-cluster key management and produced polynomial for making an inter-cluster key distribution. The main contribution is to generate polynomials and broadcast to nodes whenever a change occurs in a network or demanding nodes for secure key management. The presented scheme supports scalability for an increasing number of nodes using polynomials. The proposed scheme increases the lifetime of the network by decreasing the key pool size.

Selecting a cluster head (CH) in wireless mobile sensor network is a crucial task. Numerous algorithms have been presented for this purpose in recent literature. In these algorithms, all nodes are permitted to contend in CH selection process regardless of their less resource. This meaningless participation of ineligible nodes in the CH selection process causes unnecessary communication cost. Similarly the use of real data for CH selection increases communication cost. Additionally, no one algorithm has focus in security aspect of CH selection process. In this article Pattern Based secure CH Selection algorithm has been presented. This algorithm filters the ineligible nodes, puts them to sleep mode thereby restricting them from not participating in the CH selection process. Additionally the uses of pattern instead of real data in CH selection decrease communication cost and increase security of CH selection process. The simulation results show the improvement in lifetime and enhancement in security of CH selection.

A 2-D Adaptive Trimmed Mean Autoregressive (ATMAR) model has been proposed for denoising of medical images corrupted with poisson noise. Unfiltered images are divided into smaller chunks and ATMAR model is applied on each chunk separately. In this paper, two 5x5 windows with 40% overlapping are used to predict the center pixel value of the central row. The AR coefficients are updated by sliding both windows forward with 60% shift. The same process is repeated to scan the entire image for prediction of a new denoised image. The Adaptive Trimmed Mean Filter (ATMF) eradicates the lowest and highest variations in pixel values of the ATMAR model denoised image and also average out the remaining neighborhood pixel values. Finally, power-law transformation is applied on the resultant image of the ATMAR model for contrast stretching. Image quality is judged in terms of correlation, Mean Squared Error (MSE), Structural Similarity Index Measure (SSIM) and Peak Signal to Noise Ratio (PSNR) of the image with latest denoising techniques. The proposed technique showed an efficient way to scale down poisson noise in scintigraphic images on a pixel-by-pixel basis.

The main benefit of selecting a suitable node as cluster head (CH) in clustering for wireless mobile sensor networks (MWSNs) is to prolong the network lifetime. But the safe selection of CH is a challenging task by taking security into account. Mostly CH selection algorithms in MWSN do not consider security when selecting CH. We have proposed secure CH selection algorithm by calculating weight of each node to deal with secure selection using minimum energy consumption. The weight of node is a combination of different metrics including trust metric (behaviors of sensor node) which promotes a secure decision of a CH selection; in terms of this, the node will never be a malicious one. The trust metric is definitive and permits the proposed clustering algorithm to keep away from any malignant node in the area to select a CH, even if the rest of the parameters are in its favor. Other metrics of node include waiting time, connectivity degree, and distance among nodes. The selection of CHs is completed utilizing weights of member nodes. The preparatory outcomes acquired through simulation exhibit the adequacy of our proposed scheme as far as average rate of avoiding malicious node as a CH, energy efficiency, and some other performance parameters are concerned.

Background/Aim: Amiodarone, a class III antiarrhythmic drug, has been found to be effective in the management of patients with life-threatening ventricular arrhythmias. The aim of this study was to test whether the co administration of vitamin-E with amiodarone can reduce amiodarone-induced liver damage. Materials and Methods: Twelve male albino rats were divided into three groups (ml vegetable oil/day by oral gavages daily for 2 weeks and were used as control group. The rats of the second group received 5.4 mg amiodarone/100 gm rat dissolved in vegetable oil daily by oral gavages for 2 weeks. In the third group, the rats received 5.4 mg amiodarone and 5 mg vitamin-E/100 gram rat dissolved in 2 ml vegetable oil by oral gavages daily for 2 weeks. Two weeks after treatment, the rats were sacrificed and liver specimens were immediately taken and processed for transmission electron microscopic examinations. Results : Sections from the rat liver receiving amiodarone examined by electron microscopy showed disrupted hepatocytes with increased vacuolations. Degenerated organelles and disrupted nuclei were observed. The microvilli of bile canaliculi were disrupted and the hepatocytes showed increased lipid contents. Both endothelial cells and Kupffer cells were damaged. Phospholipids inside the mitochondria showed a loss of cristae. Sections from the liver of rats received amiodarone and vitamin-E showed lesser effects, especially in depositions of phospholipids in the mitochondria and the whole organelles and the nucleus showed minor damage in comparison to the previous group. Conclusion: Milder hepatotoxic effects are seen in rats administered amiodarone and vitamin E simultaneously suggesting that vitamin-E may play a role in amelioration of the effects of amiodarone.

Background: The present study assessed the impact of thermomechanical aging on the marginal fit of hybrid ceramic, reinforced composite resin, and lithium disilicate ceramic., Methods: Eighteen human upper first premolars freshly extracted for orthodontic purposes were used to fabricate 18 CAD-CAM veneers and divided into three groups based on materials used: group H (n=6): hybrid ceramics (Vita Enamic), group R (n=6): reinforced composite resin (Brilliant crios), and group L (n=6): lithium disilicate ceramic (IPS e-max CAD). Each material's cementation procedure was carried out according to the manufacturer's instructions. The vertical marginal gap between the laminate veneer margin and the prepared tooth finish line was measured to assess the specimens by digital microscopy. Subsequently, all the samples were thermomechanically cycled (TMC) (5 °C to 55 °C, 30 seconds, 75000 cycles). Then, the vertical marginal gap was re-evaluated., Results: The Brilliant crios group displayed a significantly lower vertical marginal gap mean score (31.36±2.82 µm) followed by Vita Enamic (39.27±6.54 µm) and E max (41.39±3.97 µm) groups. Similarly, after thermomechanical aging, the Brilliant crios group displayed a significantly lower vertical marginal gap mean score (41.83±8.28 µm) followed by Vita Enamic (55.47±18.65 µm), and the E max group showed the greatest vertical marginal gap mean score (59.43±16.27 µm)., Conclusion: Thermomechanical aging affected the marginal fit of different materials employed in the current research, and these changes were under the established clinical limit., Competing Interests: No competing interests., (©2024 The Author(s).)

Background: Physical Therapy profession is known for its demanding physical requirements. This increases the risk of attrition and work-related accidents and disorders that affect physical therapists' quality of life and work performance. This study aimed to evaluate the effect of physical activity level and other contributing factors on quality of life of physical therapists., Methods: A cross-sectional study was conducted among practicing physical therapists ( n = 258). The International Physical Activity Questionnaires-Short Form was used to measure physical activity levels and the World Health Organization Quality of Life Questionnaire short form was used to measure the quality of life among physical therapists. Data was collected through a self-administered online survey using Microsoft Forms., Results: The eligible participants were 258 out of 297. The highest percentage of physical therapists had a moderate physical activity level (45.35%) and the median for overall quality of life score was 63.27(52.73-73.59). There was a significant positive correlation between physical activity and age with overall quality of life score (rs = 0.41, p < 0.001; rs = 0.13, p < 0.036) respectively and a significant negative correlation between body mass index and overall quality of life score (rs = -0.13, p < 0.04)., Conclusion: The results obtained revealed that physical therapists mostly have moderate physical activity level and relatively good perceived quality of Life. Furthermore, our study identified significant correlations between physical activity, age, body mass index, and the overall quality of life among practicing physical therapists., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Al Ali, Alrowaishd, Abu Thyab, Almarzuqi, Al Awaji, Aldhahi and Ibrahim.)

Background: Circulating cell-free DNA (cfDNA) is a noninvasive substitute to liver biopsy for hepatocellular carcinoma (HCC) molecular profiling. This study aimed to use cfDNA to investigate copy number variation (CNV) in the BCL9 and RPS6KB1 genes and its impact on prognosis in HCC., Methods: Real-Time Polymerase Chain Reaction was used to determine the CNV and cfDNA integrity index in 100 HCC patients., Results: CNV gain in BCL9 and RPS6KB1 genes was detected in 14% and 24% of patients, respectively. Gain in CNV of BCL9 associated with risk of HCC in alcohol drinkers and hepatitis C seropositivity. In patients with RPS6KB1 gain, HCC risk increased with a high body mass index, smoking, schistosomiasis, and Barcelona clinical liver cancer stage (BCLC) A. Gain in both genes showed a high risk of HCC with elevated liver enzymes, Schistosomiasis, BCLC C, and PS > 1. The integrity of cfDNA was higher in patients with CNV gain in RPS6KB1 than those harboring CNV gain in BCL9. Lastly, BCL9 gain and BCL9 + RPS6KB1 gain led to higher mortality rates and reduced survival times., Conclusion: cfDNA was used to detect BCL9 and RPS6KB1 CNVs, which influence prognosis and can be used as independent predictors of HCC patient survival.

Purpose: To report a rare incidence of corneal endothelial cell loss following airbag injury., Observation: A 27-year-old female who sustained a motor vehicle accident with airbag deployment presented with hand motion vision in the left eye. Ocular examination demonstrated corneal abrasion, significant corneal stromal edema with descemet folds, and a central pachymetry of 999 µm. The patient was managed with topical steroids and antibiotic drops. One week later, specular microscopy revealed a central endothelial cell count of 2200/mm 2 with pleomorphism, polymegathism, and a decreased central corneal thickness of 569 µm. A repeat of specular microscopy 6 months later showed a decreased central endothelial cell count of 1611/mm 2 with recovered visual acuity of 20/30., Conclusion: Corneal endothelial loss is a severe complication of ocular airbag injury. Serial ophthalmic assessment is recommended because endothelial cell loss may continue for some time after the initial impact., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Peroral endoscopic myotomy (POEM) was proposed in 2010 as a minimally invasive procedure for the treatment of achalasia. In this article, we describe the Middle Eastern experience with the procedure in terms of efficacy, length of admission, and short- and long-term complications., Methods: A retrospective analysis of our prospectively collected data on patients who underwent a POEM procedure was conducted between March 2019 and May 2020. The primary outcome was clinical success rate, defined as a postprocedure Eckardt score ≤3 at ≥3 months. Secondary outcomes included the length of hospital stay, presence of reflux symptoms or need for proton pump inhibitors (PPIs) ≥3 months, and adverse events., Results: During the study period, 67 patients (35 females) underwent the procedure for achalasia. The participants' ages ranged from 11 to 80 years (mean 41 ± 18 years). Eckardt scores before the treatment ranged between 4 and 12 (mean 8.85 ± 1.75). Sixty-four patients (95.5%) achieved Eckardt scores of ≤3 at ≥3 months after the procedure (95% confidence interval [CI]: 91%-100%). The difference between pre- and post-procedural Eckardt scores averaged around -8 points (95% CI: -7.5 to -8.5 P < 0.0001). Adverse events were reported in 24 patients (35.8%) and included pneumoperitoneum (32.8%), reflux symptoms at 3 months (29.9%), and surgical emphysema (3%). Six patients had adverse events that led to prolongation of admission; 3% of whom had aspiration pneumonia, 3% had pneumoperitoneum, 1.5% had both, and 1.5% had an esophageal tear., Conclusions: POEM is a promising procedure for the treatment of achalasia with a high clinical success rate, short hospital admission, and a reassuring safety profile., Competing Interests: None

Middle-ear cholesteatoma is a serious illness of the ear, which untreated can often lead to serious complications. The treatment is always surgical. The operation focuses on removing the cholesteatoma and repairing damaged structures like the ossicular chain. It is of utmost importance, that primary care physicians maintain a high suspicion for the presence of cholesteatoma. The most accessible tool is otoscopy. This review gives an overview of symptoms, signs in otoscopy and treatment modalities of cholesteatoma patients in Denmark.

Sub-internal limiting membrane (sub-ILM) hemorrhage is a distinct type of retinal hemorrhage in which the blood accumulates between ILM and nerve fiber layer. Little is known about visual prognosis as well as ideal management of foveal sub-ILM hemorrhage in patients with acute leukemia. Herein, we presented a case of acute myeloid leukemia with foveal sub-ILM hemorrhage. Observation alone resulted in complete resolution of hemorrhage with good visual and anatomical outcome., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Middle East African Journal of Ophthalmology.)

Objective: Postoperative renal dysfunction necessitating hemodialysis after implantation of ventricular assist devices presents a challenge with respect to establishment of hemodialysis access. Lack of pulsatile flow has led to concerns that arteriovenous fistulas will not mature. This study aims to evaluate arteriovenous fistula as a method of hemodialysis., Methods: Consecutive patients who underwent implantation of a ventricular assist device between 1988 and 2016 with a subsequent need for hemodialysis were identified. Retrospective data were collected for patients requiring hemodialysis through an arteriovenous fistula or arteriovenous graft. Access flow rates and duration of patency are reported., Results: Sixty-four patients were identified (10 required long-term hemodialysis, 5 via arteriovenous fistula, 1 via arteriovenous graft). All six patients receiving long-term hemodialysis access were on continuous-flow ventricular assist devices. Brachiocephalic arteriovenous fistulas were performed in all arteriovenous fistula patients, and the average preoperative vein diameter was 4.1 ± 0.9 mm. On 30-day follow-up, the average flow rate was 1262 ± 643 mL/min (880-2220). In arteriovenous fistula patients, one died at 30 days, one arteriovenous fistula required ligation for steal syndrome at 5 months, and one was abandoned after 10.7 months for low flow. Of remaining fistulas, one was converted to an arteriovenous graft at 1.7 years for malfunction (with 5.3 month patency), and one remains open at 4.0 years., Conclusion: Arteriovenous fistulas should be considered in selected patients with ventricular assist devices as a means of long-term hemodialysis access to avoid use of catheters. Maturation and usage of primary arteriovenous fistulas is possible despite lack of pulsatile flow.

Purpose of Review: To give an overview of recently published articles about the management of vasculo-Behcet's with particular emphasis on anticoagulation., Recent Findings: Biologic agents are emerging as a potential therapeutic option in refractory vasculo-Behcet with a good safety profile. Evidence further shows that following nonpulmonary aneurysm repair, there is a reduced risk of recurrent aneurysmal formation at the operative site in patients treated with immunosuppressants in addition to their surgery, than those undergoing surgical intervention alone., Summary: Behcet disease patients are at risk of developing multiple vascular complications including thrombosis and aneurysms. Treatment should focus on reducing inflammation; and the role of anticoagulation is still debatable.

Objective: Endoscopic vein harvest (EVH) has been demonstrated to improve early morbidity when compared with conventional open vein harvest (OVH) technique for infrainguinal bypass surgery. However, recent literature suggests conflicting results regarding mid- and long-term patency with EVH. The purpose of this study is to compare graft patency between harvest techniques specifically in patients with critical limb ischemia., Methods: This retrospective study compared two groups of patients (EVH = 39 and OVH = 49) undergoing lower extremity revascularization from January 2009 to December 2011. Outcome measures included patency rates, postoperative complications, and wound infection. Graft patency was assessed using Kaplan-Meier curves., Results: Both groups were matched for demographics and indications for bypass (critical limb ischemia). Median follow-up was 22 months. There was a significant reduction in the incidence of wound infection at the vein harvest site in the EVH group (OVH = 20%; EVH = 0%; P < .001), nevertheless, the difference was not significant when only the anastomotic sites were included (OVH = 12.2%; EVH = 15.4%; P = .43). The hospital length of stay was comparable between the two groups (EVH = 8.73 ± 9.69; OVH = 6.35 ± 3.28; P = .26) with no significant difference in the recovery time. Primary graft patency rate was 43.2% in the EVH group and 69.4% in the OVH group (P = .007) at 3 years. The most common reason for loss of primary patency was graft occlusion (61.5%) in the OVH group and vein graft stenosis (54.5%) in the EVH group. The average number of vascular reinterventions per bypass graft was significantly lower in the OVH group compared with the EVH group (OVH = 0.37; EVH = 1.28; P < .001)., Conclusions: Our findings demonstrate inferior primary patency when using the technique of EVH. Additionally, we identified a significantly higher rate of reintervention in the EVH cohort as well as a higher rate of vein graft body stenosis. However, EVH was associated with a decreased rate of wound complications with similar limb salvage and secondary patency rates when compared to OVH. EVH should therefore be selectively utilized in patients at high risk for wound complications., (Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Unlabelled: Ischemia-reperfusion (I/R) injury is a process whereby an initial hypoxic insult and subsequent return of blood flow leads to the propagation of innate immune responses and organ injury. The necessity of the pattern recognition receptor, Toll-like receptor (TLR)4, for this innate immune response has been previously shown. However, TLR4 is present on various cell types of the liver, both immune and nonimmune cells. Therefore, we sought to determine the role of TLR4 in individual cell populations, specifically, parenchymal hepatocytes (HCs), myeloid cells, including Kupffer cells, and dendritic cells (DCs) subsequent to hepatic I/R. When HC-specific (Alb-TLR4(-/-) ) and myeloid-cell-specific (Lyz-TLR4(-/-) ) TLR4 knockout (KO) mice were subjected to warm hepatic ischemia, there was significant protection in these mice, compared to wild type (WT). However, the protection afforded in these two strains was significantly less than global TLR4 KO (TLR4(-/-) ) mice. DC-specific TLR4(-/-) (CD11c-TLR4(-/-) ) mice had significantly increased hepatocellular damage, compared to WT mice. Circulating levels of high-mobility group box 1 (HMGB1) were significantly reduced in Alb-TLR4(-/-) mice, compared to WT, Lyz-TLR4(-/-) , CD11c-TLR4(-/-) mice and equivalent to global TLR4(-/-) mice, suggesting that TLR4-mediated HMGB1 release from HCs may be a source of HMGB1 after I/R. HCs exposed to hypoxia responded by rapidly phosphorylating the mitogen-activated protein kinases, c-Jun-N-terminal kinase (JNK) and p38, in a TLR4-dependent manner; inhibition of JNK decreased release of HMGB1 after both hypoxia in vitro and I/R in vivo., Conclusion: These results provide insight into the individual cellular response of TLR4. The parenchymal HC is an active participant in sterile inflammatory response after I/R through TLR4-mediated activation of proinflammatory signaling and release of danger signals, such as HMGB1., (Copyright © 2013 American Association for the Study of Liver Diseases.)

Background: Atherosclerosis is an inflammatory disease in which interferon (IFN)-gamma, the signature cytokine of Th1 cells, plays a central role. We investigated whether interleukin (IL)-17, the signature cytokine of Th17 cells, is also associated with human coronary atherosclerosis., Methods and Results: Circulating IL-17 and IFN-gamma were detected in a subset of patients with coronary atherosclerosis and in referent outpatients of similar age without cardiac disease but not in young healthy individuals. IL-17 plasma levels correlated closely with those of the IL-12/IFN-gamma/CXCL10 cytokine axis but not with known Th17 inducers such as IL-1beta, IL-6, and IL-23. Both IL-17 and IFN-gamma were produced at higher levels by T cells within cultured atherosclerotic coronary arteries after polyclonal activation than within nondiseased vessels. Combinations of proinflammatory cytokines induced IFN-gamma but not IL-17 secretion. Blockade of IFN-gamma signaling increased IL-17 synthesis, whereas neutralization of IL-17 responses decreased IFN-gamma synthesis; production of both cytokines was inhibited by transforming growth factor-beta1. Approximately 10-fold fewer coronary artery-infiltrating T helper cells were IL-17 producers than IFN-gamma producers, and unexpectedly, IL-17/IFN-gamma double producers were readily detectable within the artery wall. Although IL-17 did not modulate the growth or survival of cultured vascular smooth muscle cells, IL-17 interacted cooperatively with IFN-gamma to enhance IL-6, CXCL8, and CXCL10 secretion., Conclusions: Our findings demonstrate that IL-17 is produced concomitantly with IFN-gamma by coronary artery-infiltrating T cells and that these cytokines act synergistically to induce proinflammatory responses in vascular smooth muscle cells.

Interleukin (IL) 1alpha produced by human endothelial cells (ECs), in response to tumor necrosis factor (TNF) or to co-culture with allogeneic T cells in a TNF-dependent manner, can augment the release of cytokines from alloreactive memory T cells in vitro. In a human-mouse chimeric model of artery allograft rejection, ECs lining the transplanted human arteries express IL-1alpha, and blocking IL-1 reduces the extent of human T cell infiltration into the artery intima and selectively inhibits IL-17 production by infiltrating T cells. In human skin grafts implanted on immunodeficient mice, administration of IL-17 is sufficient to induce mild inflammation. In cultured cells, IL-17 acts preferentially on vascular smooth muscle cells rather than ECs to enhance production of proinflammatory mediators, including IL-6, CXCL8, and CCL20. Neutralization of IL-17 does not reduce T cell infiltration into allogeneic human artery grafts, but markedly reduces IL-6, CXCL8, and CCL20 expression and selectively inhibits CCR6(+) T cell accumulation in rejecting arteries. We conclude that graft-derived IL-1 can promote T cell intimal recruitment and IL-17 production during human artery allograft rejection, and suggest that targeting IL-1 in the perioperative transplant period may modulate host alloreactivity.

Inflammation is associated with the pathogenesis of coronary atherosclerosis, although the mechanisms remain unclear. We investigated whether cytokine secretion by innate immune responses could contribute to the production of proarteriosclerotic Th1-type cytokines in human coronary atherosclerosis. Cytokines were measured by ELISA in the plasma of patients with coronary atherosclerosis undergoing cardiac catheterization. IL-18 was detected in all subjects, whereas a subset of patients demonstrated a coordinated induction of other IFN-gamma-related cytokines. Specifically, elevated plasma levels of IL-12 correlated with that of IFN-gamma and IFN-gamma-inducible chemokines, defining an IFN-gamma axis that was activated independently of IL-6 or C-reactive protein. Systemic inflammation triggered by cardiopulmonary bypass increased plasma levels of the IFN-gamma axis, but not that of IL-18. Activation of the IFN-gamma axis was not associated with acute coronary syndromes, but portended increased morbidity and mortality after 1-year follow-up. IL-12 and IL-18, but not other monokines, elicited secretion of IFN-gamma and IFN-gamma-inducible chemokines in human atherosclerotic coronary arteries maintained in organ culture. T cells were the principal source of IFN-gamma in response to IL-12/IL-18 within the arterial wall. This inflammatory response did not require, but was synergistic with and primed for TCR signals. IL-12/IL-18-stimulated T cells displayed a cytokine-producing, nonproliferating, and noncytolytic phenotype, consistent with previous descriptions of lymphocytes in stable plaques. In contrast to cognate stimuli, IL-12/IL-18-dependent IFN-gamma secretion was prevented by a p38 MAPK inhibitor and not by cyclosporine. In conclusion, circulating IL-12 may provide a mechanistic link between inflammation and Th1-type cytokine production in coronary atherosclerosis.