A semantically-aided architecture for a web-based monitoring system for carotid atherosclerosis.

Carotid atherosclerosis is a multifactorial disease and its clinical diagnosis depends on the evaluation of heterogeneous clinical data, such as imaging exams, biochemical tests and the patient's clinical history. The lack of interoperability between Health Information Systems (HIS) does not allow the physicians to acquire all the necessary data for the diagnostic process. In this paper, a semantically-aided architecture is proposed for a web-based monitoring system for carotid atherosclerosis that is able to gather and unify heterogeneous data with the use of an ontology and to create a common interface for data access enhancing the interoperability of HIS. The architecture is based on an application ontology of carotid atherosclerosis that is used to (a) integrate heterogeneous data sources on the basis of semantic representation and ontological reasoning and (b) access the critical information using SPARQL query rewriting and ontology-based data access services. The architecture was tested over a carotid atherosclerosis dataset consisting of the imaging exams and the clinical profile of 233 patients, using a set of complex queries, constructed by the physicians. The proposed architecture was evaluated with respect to the complexity of the queries that the physicians could make and the retrieval speed. The proposed architecture gave promising results in terms of interoperability, data integration of heterogeneous sources with an ontological way and expanded capabilities of query and retrieval in HIS.

The relationship of novel adipokines, RBP4 and omentin-1, with carotid atherosclerosis severity and vulnerability.

OBJECTIVE: We investigated the relationship of circulating novel adipokines, retinol-binding protein 4 (RBP4) and omentin-1, with advanced carotid atherosclerosis and ultrasound indexes of severity (total plaque area-TPA) and plaque echogenicity and vulnerability (Gray-Scale median - GSM score). METHODS: We enrolled 225 patients with high-grade carotid stenosis (HGCS) who underwent carotid revascularization (73 Symptomatic patients, 152 asymptomatic patients) and 75 age- and sex-matched, asymptomatic individuals with low-grade (<50%) carotid stenosis (LGCS). Seventy-three individuals without current manifestations of atherosclerotic disease served as control group (COG). All participants underwent carotid ultrasound with TPA and GSM score assessment. Moreover, clinical parameters, metabolic profile, and circulating levels of hsCRP and adipokines were assessed. RESULTS: RBP4 was significantly elevated in HGCS (51.44 ± 16.23 mg/L) compared to LGCS (38.39 ± 8.85 mg/L), independent of symptoms existence, whereas RBP4 levels in COG were even lower (25.74 ± 10.72 mg/L, p < 0.001 compared to either HGCS or LGCS). Inversely, serum omentin-1 levels were significantly lower across HGCS (490.41 ± 172 ng/ml) and LGCS (603.20 ± 202.43 ng/ml) than COG (815.3 ± 185.32, p < 0.001). Moreover, the considerable difference between HGCS and LGCS (p < 0.001) was exclusively attributed to the excessive suppression of omentin-1 concentrations in symptomatic versus asymptomatic (p = 0.004) patients. HGCS and LGCS did not differ in the rest of clinical and biochemical parameters. In multiple regression analysis, RBP4 (beta = 0.232, p = 0.025) and hsCRP (beta = 0.300, p = 0.004) emerged as independent determinants of TPA in patients with carotid atherosclerosis. Low serum levels of omentin-1 correlated with GSM score and symptoms but that association was lost in multivariate analysis.. CONCLUSION: RBP4 serum levels were significantly elevated in patients with established carotid atherosclerosis and were positively associated with atherosclerosis severity. The association of low serum omentin-1 with carotid plaque echolucency requires further investigation.. ClinicalTrials.gov Identifier: NCT00636766.

Clusterin/Apolipoprotein J immunolocalization on carotid artery is affected by TNF-alpha, cigarette smoking and anti-platelet treatment.

BACKGROUND: Clusterin (CLU) /Apolipoprotein J is a protein biosensor of oxidative stress and inflammation, which is upregulated in many pathological processes including atherosclerosis. Previous studies have shown that in aortic tissue, CLU expression increases with atherosclerotic lesion progression and it has been coupled with vascular damage and coronary artery disease. A few studies enter into CLU and carotid atherosclerosis while the apolipoprotein's expression on human carotid tissue and its association with parameters related to the disease development has not been examined. The present study was designed to reveal the relationships between the degree of CLU immunolocalization on carotid artery and demographic characteristics, blood parameters and pharmacological treatment of patients underwent internal carotid artery endarterectomy. METHODS: CLU expression was detected by immunohistochemistry in 42 carotid endarterectomy specimens. Patients' serum levels of tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), high sensitive C-reactive protein (hsCRP) and classical parameters related to atherosclerosis such as lipid profile, as well as thrombosis related parameters such as fibrinogen, antithrombin III, protein C and protein S were determined. Demographic characteristics, smoking habits and the use of medications were recorded. Comparisons between groups were performed by students't-test and analysis of variance. Independent associations with CLU expression on carotid tissue were denoted by linear regression analysis. RESULTS: CLU imuunolocalization was denser in smokers than in non-smokers (p = 0.041) while it was rarefied in specimens of patients on cropidogrel treatment (p = 0.045) compared to the rest not taking this medication. Clopidogrel intake was independent predictor of lower CLU expression on carotid artery (p =0.045). CLU was positively correlated with serum TNF-a concentration (r = 0.33, p = 0.040) that was independent predictor of higher expression of the apolipoprotein (p = 0.001). IL-6, hsCRP and classical parameters related to atherosclerosis and thrombosis were not associated with CLU immunolocalization. CONCLUSION: Our study suggests that CLU expression on carotid artery is affected by TNF-alpha, cigarette smoking confirming its association with oxidative and cellular stress and anti-platelet medication reflecting the protective effects of such pharmacological treatment on vascular wall.

CAROTID - a web-based platform for optimal personalized management of atherosclerotic patients.

Carotid atherosclerosis is the main cause of fatal cerebral ischemic events, thereby posing a major burden for public health and state economies. We propose a web-based platform named CAROTID to address the need for optimal management of patients with carotid atherosclerosis in a twofold sense: (a) objective selection of patients who need carotid-revascularization (i.e., high-risk patients), using a multifaceted description of the disease consisting of ultrasound imaging, biochemical and clinical markers, and (b) effective storage and retrieval of patient data to facilitate frequent follow-ups and direct comparisons with related cases. These two services are achieved by two interconnected modules, namely the computer-aided diagnosis (CAD) tool and the intelligent archival system, in a unified, remotely accessible system. We present the design of the platform and we describe three main usage scenarios to demonstrate the CAROTID utilization in clinical practice. Additionally, the platform was evaluated in a real clinical environment in terms of CAD performance, end-user satisfaction and time spent on different functionalities. CAROTID classification of high- and low-risk cases was 87%; the corresponding stenosis-degree-based classification would have been 61%. Questionnaire-based user satisfaction showed encouraging results in terms of ease-of-use, clinical usefulness and patient data protection. Times for different CAROTID functionalities were generally short; as an example, the time spent for generating the diagnostic decision was 5min in case of 4-s ultrasound video. Large datasets and future evaluation sessions in multiple medical institutions are still necessary to reveal with confidence the full potential of the platform.

Why don't CD8+ T cells reduce the lifespan of SIV-infected cells in vivo?

In January 2010 two groups independently published the observation that the depletion of CD8+ cells in SIV-infected macaques had no detectable impact on the lifespan of productively infected cells. This unexpected observation led the authors to suggest that CD8+ T cells control SIV viraemia via non-lytic mechanisms. However, a number of alternative plausible explanations, compatible with a lytic model of CD8+ T cell control, were proposed. This left the field with no consensus on how to interpret these experiments and no clear indication whether CD8+ T cells operated primarily via a lytic or a non-lytic mechanism. The aim of this work was to investigate why CD8+ T cells do not appear to reduce the lifespan of SIV-infected cells in vivo.

Measuring the stoichiometry of functional PspA complexes in living bacterial cells by single molecule photobleaching.

We report a general method based on wide-field fluorescence imaging of single molecule photobleaching and the Chung-Kennedy algorithm to measure the stoichiometry of functional protein complexes in living bacterial cells.