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Objective Real-life management of patients with hypertension and chronic kidney disease (CKD) among European Society of Hypertension Excellence Centres (ESH-ECs) is unclear : we aimed to investigate it. Methods A survey was conducted in 2023. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed. Results Overall, 88 ESH-ECS representatives from 27 countries participated. According to the responders, renin-angiotensin system (RAS) blockers, calcium-channel blockers and thiazides were often added when these medications were lacking in CKD patients, but physicians were more prone to initiate RAS blockers (90% [interquartile range: 70-95%]) than MRA (20% [10-30%]), SGLT2i (30% [20-50%]) or (GLP1-RA (10% [5-15%]). Despite treatment optimisation, 30% of responders indicated that hypertension remained uncontrolled (30% (15-40%) vs 18% [10%-25%]) in CKD and CKD patients, respectively). Hyperkalemia was the most frequent barrier to initiate RAS blockers, and dosage reduction was considered in 45% of responders when kalaemia was 5.5-5.9 mmol/L. Conclusions RAS blockers are initiated in most ESH-ECS in CKD patients, but MRA and SGLT2i initiations are less frequent. Hyperkalemia was the main barrier for initiation or adequate dosing of RAS blockade, and RAS blockers' dosage reduction was the usual management.

Objective: Real-life management of hypertensive patients with chronic kidney disease (CKD) is unclear., Methods: A survey was conducted in 2023 by the European Society of Hypertension (ESH) to assess management of CKD patients referred to ESH-Hypertension Excellence Centres (ESH-ECs) at first referral visit. The questionnaire contained 64 questions with which ESH-ECs representatives were asked to estimate preexisting CKD management quality., Results: Overall, 88 ESH-ECs from 27 countries participated (fully completed surveys: 66/88 [75.0%]). ESH-ECs reported that 28% (median, interquartile range: 15-50%) had preexisting CKD, with 10% of them (5-30%) previously referred to a nephrologist, while 30% (15-40%) had resistant hypertension. The reported rate of previous recent (<6 months) estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) testing were 80% (50-95%) and 30% (15-50%), respectively. The reported use of renin-angiotensin system blockers was 80% (70-90%). When a nephrologist was part of the ESH-EC teams the reported rates SGLT2 inhibitors (27.5% [20-40%] vs. 15% [10-25], P  = 0.003), GLP1-RA (10% [10-20%] vs. 5% [5-10%], P  = 0.003) and mineralocorticoid receptor antagonists (20% [10-30%] vs. 15% [10-20%], P  = 0.05) use were greater as compared to ESH-ECs without nephrologist participation. The rate of reported resistant hypertension, recent eGFR and UACR results and management of CKD patients prior to referral varied widely across countries., Conclusions: Our estimation indicates deficits regarding CKD screening, use of nephroprotective drugs and referral to nephrologists before referral to ESH-ECs but results varied widely across countries. This information can be used to build specific programs to improve care in hypertensives with CKD., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

In the present work the impact of in situ photoreduction, by means of ultraviolet (UV) irradiation, on the nonlinear optical response (NLO) of some graphene oxide (GO), fluorographene (GF), hydrogenated fluorographene (GFH) and graphene (G) dispersions is studied. In situ UV photoreduction allowed for the extended modification of the degree of functionalization (i.e., oxidization, fluorination and hydrogenation), leading to the effective tuning of the corresponding sp 2 /sp 3 hybridization ratios. The nonlinear optical properties of the studied samples prior to and after UV irradiation were determined by means of the Z-scan technique using visible (532 nm), 4 ns laser excitation, and were found to change significantly. More specifically, while GO's nonlinear optical response increases with irradiation time, GF and GFH present a monotonic decrease. The graphene dispersions' nonlinear optical response remains unaffected after prolonged UV irradiation for more than an hour. The present findings demonstrate that UV photoreduction can be an effective and simple strategy for tuning the nonlinear optical response of these graphene derivatives in a controllable way, resulting in derivatives with custom-made responses, thus more suitable for different photonic and optoelectronic applications.

The present work reports on the transient nonlinear optical (NLO) responses of two different types of 2D silicon nanosheets (SiNSs), namely hydride-terminated silicon nanosheets (SiNS-H) and 1-dodecene-functionalized silicon nanosheets (SiNS-dodecene). The main motivation of this study was to extend the knowledge regarding the NLO properties of these Si-based materials, for which very few published studies exist so far. For that purpose, the NLO responses of SiNS-H and SiNS-dodecene were investigated experimentally in the nanosecond regime at 532 and 1064 nm using the Z-scan technique, while the obtained results were compared to those of certain recently studied graphene nanosheets. SiNS-dodecene was found to exhibit the largest third-order susceptibility χ (3) values at both excitation wavelengths, most probably ascribed to the presence of point defects, indicating the importance of chemical functionalization for the efficient enhancement and tailoring of the NLO properties of these emerging 2D Si-based materials. Most importantly, the results demonstrated that the present silicon nanosheets revealed comparable and even larger NLO responses than graphene nanosheets. Undoubtedly, SiNSs could be strong competitors of graphene for applications in 2D-material-based photonics and optoelectronics.

Objective: The efficacy of renal sympathetic denervation (RDN) has been affirmed by a number of recent clinical studies, despite controversies in this field over the last five years. Therefore, it is of paramount importance that hypertension experts debate the merits of RDN by revealing and expressing their personal beliefs and perspectives regarding this procedure., Methods: A cross-sectional survey was conducted among Greek leaders of the Hypertension Excellence Centers with the use of a closed-type questionnaire specifically designed to elicit information and evaluate the respondent's views and perspectives about RDN efficacy, safety and ideal target patient population., Results: A total of 36 participants completed the survey. Based on the results, RDN was considered efficient (91.7%) and safe (94.5%), while the overwhelming majority of the participants felt confident in the long-term efficacy (88.9%) of the intervention and that it lacks reliable predictors of blood pressure response (94.5%). Patients with resistant (91.7%), ultra-resistant (94.4%), and uncontrolled hypertension (80.6%) were suggested as ideal candidates for RDN. Establishing a close co-operation between interventionalists and hypertension experts was considered essential to ensure the efficacy (97.2%) as well as the safety (97.3%) of the procedure., Conclusion: The vast majority of Greek hypertension experts surveyed were convinced of the efficacy and safety of RDN based on the preponderance of available scientific and clinical data. Identification of the ideal patient group remains controversial. Respondents generally agreed on the necessity of building close collaborative relationships between interventionalists and hypertension experts in order to improve RDN clinical outcome., (Copyright © 2021 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

There is no agreement of data on the subject of implant failure and the development of osteonecrosis in patients receiving antiresorptive agents. The purpose of this systematic review is to evaluate whether dental implants placed in patients on antiresorptive medication have an increased failure rate and whether the implant placement or the implant existence are risk factors for developing medication-related osteonecrosis of the jaw (MRONJ). An electronic search was conducted in PubMed/Medline, and all publications fulfilling the inclusion criteria were included. The search was completed by a hand research of the references cited in all electronic identified publications, resulting in 411 articles. Based on the inclusion criteria, 32 studies were included, with a total of 5221 patients, 12 751 implants, 618 cases of implants loss, and 136 cases of MRONJ analyzed. Because of the small number of studies, most of which were characterized by a low level of quality, it cannot be established that the use of antiresorptive medication affects dental implant survival rates. The risk of MRONJ as an early or late complication is also not well established. Therefore, successful dental implant procedures in patients receiving antiresorptive medication might be possible, but more studies need to be carried out in the future to verify this topic. Apart from intravenous antiresorptive drugs, which remain an absolute contraindication, the use of antiresorptive medication is not a contraindication to dental implantology, but it must be accompanied by careful treatment planning, informing patients about possible complications, and essential long follow-up periods.

Silicene, the silicon analogue of graphene, represents a new class of two-dimensional (2D) materials, which shares some of the outstanding physical properties of graphene. Furthermore, it has the advantage of being compatible with the current Si-based technology. However, this 2D material is not stable and is quite prone to oxidation. The hydride-terminated silicene, called silicane, is a more stable form of 2D silicon, if functionalized via, for example, the hydrosilylation reaction. In this work, the third-order nonlinear optical (NLO) properties of two functionalized silicanes, namely hydride-terminated silicon nanosheets (SiNS-H) and 1-dodecene-functionalized silicon nanosheets (SiNS-dodecene), are accessed and compared to those of single-layer graphene, under 35 ps, 532 and 1064 nm excitation. The present results show that the functionalized silicanes exhibit comparable and even higher NLO response than that of single-layer graphene, making them strong competitors of graphene and very interesting candidates for future photonic and optoelectronic applications.

Fluorographene has been recently shown to be a suitable platform for synthesizing numerous graphene derivatives with desired properties. In that respect, N -octylamine-modified fluorographenes with variable degrees of functionalization are studied and their nonlinear optical properties are assessed using 4 ns pulses. A very strong enhancement of the nonlinear optical response and a very efficient optical limiting action are observed, being strongly dependent on the degree of functionalization of fluorographene. The observed enhanced response is attributed to the increasing number of defects because of the incorporation of N-heteroatoms in the graphitic network upon functionalization with N -octylamine. The present work paves the way for the controlled covalent functionalization of graphene enabling a scalable access to a wide portfolio of graphene derivatives with custom-tailored properties.

Graphene derivatives and defect-engineered graphenes have attracted the interest of researchers owing to the excellent and tunable properties they exhibit. In this work the optical limiting performance of two defect-engineered boron- and nitrogen-doped reduced graphene oxides is investigated. Both graphenes are found to exhibit exceptional and broadband optical limiting action ranging from 532 to 2200 nm. Their optical limiting efficiency was found to be superior to that of all the other graphene derivatives studied to date, exhibiting a gradually decreasing optical limiting onset, reaching the record low value of ∼0.002 J cm -2 at 2200 nm. The results demonstrate the potential of engineering the defects of such reduced graphene oxides, resulting in very broadband and efficient optical limiting graphene derivatives, showing a promising method to further tailor their optical and optoelectronic properties.

Purpose: Vascular calcification (VC) is an independent risk factor for cardiovascular disease in hemodialysis patients while Matrix GLA protein (MGP) is one of the most potent inhibitors of VC and its activation is vitamin K dependent. The aim of this study is to investigate the role of oral vitamin K2 supplementation in the prevention of VC progression in haemodialysis patients., Methods: We conducted a prospective randomized interventional study in patients on hemodialysis. Patients were randomly assigned to either receiving orally 200 μgr of vitamin K2 (vitamin K2/MK-7, Solgar) every day for 1 year or no treatment. Uncarboxylated MGP (uc-MGP) concentrations were quantified using ELISA at randomization, at 3 and at 12 months. Aortic calcification was evaluated using Agatston score after an abdominal computed tomography scan that was performed at the beginning and at 12 months of follow-up., Results: There were 102 patients that were randomized. After 1 year of follow-up, 22 patients from the vitamin K2 group and 30 patients from the control group were included in the analysis. After 3 months of treatment, uc-MGP values remained unchanged in the vitK2 group but after 1 year were reduced by 47% (p = 0.005). Furthermore, uc-MGP at 1 year was increased by 12% in the control group. At 1 year, vitK2 group had significantly lower values of uc-MGP in comparison to controls (p = 0.03). Agatston score was increased significantly both in vitamin K2 and control group at 1 year with no difference between groups., Conclusions: Oral administration of vitamin K2 in patients on haemodialysis reduced serum uc-MGP levels but did not have an effect in the progression of aortic calcification.

The synthesis and characterization of two thiophenol-modified fluorographene derivatives, namely methoxythiophenol-and dimethylaminothiophenol-modified fluorographenes, are reported, while their third-order nonlinear optical response were thoroughly investigated under both visible (532 nm) and infrared (1064 nm) with 35 ps and 4 ns laser pulses. The graphene derivatives were obtained by partial nucleophilic substitution/reduction of fluorographene by the corresponding organic thiophenols, and were fully characterized by techniques including infrared/Raman spectroscopy, X-ray photoelectron spectroscopy, atomic force spectroscopy, and high-resolution transmission microscopy. This type of modification resulted in graphenic structures where the attached thiol groups, sp 2 domains, and the residual fluorine groups act as donors, π bridges, and acceptors, respectively. Both derivatives exhibited large nonlinear optical response compared to fluorographene, and have potential applications in optical limiting as an alternative to fullerenes., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Several studies regarding the imposition of stresses simultaneously in plants have shown that plant responses are different under individual and combined stress. Pathogen infection in combination with drought can act both additively and antagonistically, suggesting a tailored-made plant response to these stresses. The aforementioned combination of stresses can be considered as one of the most important factors affecting global crop production. In the present research we studied eggplant responses to simultaneous Verticillium dahliae infection and drought with respect to the application of the individual stresses alone and investigated the extent to which these responses were cultivar dependent. Two eggplant cultivars (Skoutari and EMI) with intermediate resistance to V. dahliae were subjected to combined stress for a 3-week period. Significant differences in plant growth, several physiological and biochemical parameters (photosynthesis rate, leaf gas exchanges, Malondialdehyde, Proline) and gene expression, were found between plants subjected to combined and individual stresses. Furthermore, plant growth and molecular (lipid peroxidation, hydrogen peroxide, gene expression levels) changes highlight a clear discrimination between the two cultivars in response to simultaneous V. dahliae infection and drought. Our results showed that combined stress affects significantly plants responses compared to the application of individual stresses alone and that these responses are cultivar dependent.

The nonlinear optical response of some O-doped polycyclic aromatic hydrocarbons (PAHs) is systematically investigated in the present work aiming to understand the influence of structural effects on their nonlinear optical response. In that view, the third-order nonlinear optical properties of these PAHs were measured under 4 ns visible (532 nm) and infrared (1064 nm) laser excitation. The O-doped PAHs were found to exhibit large saturable absorption and negative sign nonlinear refraction under visible excitation, increasing both with the addition of naphthalene units and with the number of O atoms. Their nonlinear optical response was found to be negligible under infrared excitation. Similar measurements performed on thin films of these PAHs have shown that they maintain their large nonlinear optical response even in the solid state, confirming their high potential for optoelectronic and photonic applications.

Background: Limited data exist concerning the biomechanical and central hemodynamic changes induced by endograft implantation in the descending thoracic aorta. The aim of this prospective ongoing study was to evaluate changes in arterial stiffness, assessed by pulse wave velocity (PWV; m/sec), and N-terminal pro-brain natriuretic peptide (NT-proBNP; pg/mL) levels in patients undergoing endovascular repair of descending thoracic aorta (thoracic endovascular aortic repair [TEVAR])., Methods: Twenty-seven patients with thoracic aorta pathology who underwent elective TEVAR were included in the study. Blood samples were obtained preoperatively, 24 hr, 48 hr, and 6 months postoperatively, and serum levels of NT-proBNP were measured. PWV was determined before and 6 months after TEVAR. One-way analysis of variance by ranks was used to test the alterations in PWV (from baseline to 6 months) and NT-proBNP (along the 4 phases of evaluation). Post hoc analyses were appropriately performed., Results: We recorded an increase in values of NT-proBNP from baseline (median = 96.1, interquartile range [IQR] = 82.7-117.9) to 24 hr postoperative (median = 201.6, IQR = 82.8-425.9), 48 hr postoperative (median = 317.0, IQR = 102.5-1,479.5), and 6 months postoperative (median = 144, IQR = 82.8-276.4). The Kruskal-Wallis H test showed a statistically significant increase (x 2 (3) = 11.17, P = 0.01) in NT-proBNP from baseline (rank mean = 22.19) toward the postoperative time points of evaluation (24 hr postoperative: 35.17 [change: +12.9, P = 0.02]; 48 hr postoperative: 42.64 [change: +20.5, P < 0.001]; 6 month postoperative: 34.91 [change: +12.7, P = 0.03]). An increase in PWV values was recorded from baseline (median = 11.9, IQR = 10.0-13.5) to 6 months postoperatively (median = 13.9, IQR = 11.9-16.4). That change achieved statistically significant level [x 2 (1) = 4.86, P = 0.03], with an increase in mean rank PWV (+7.5)., Conclusions: Implementation of thoracic stent grafts may be associated with considerable increase of both arterial stiffness and NT-proBNP serum levels along time. Those results may indicate an adverse cardiac impact of TEVAR. However, the early and long-term effects of TEVAR on cardiovascular outcomes require further investigation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

There is a shortage of data in everyday clinical practice about the anticoagulant effects caused by the new oral anticoagulants (NOAs). Our aim was to estimate the intensity of anticoagulant activity induced by rivaroxaban 20 mg qd and dabigatran 110 mg bid among patients with nonvalvular atrial fibrillation (NV-AF).We studied 20 patients with NV-AF treated with dabigatran, and 20 patients treated with rivaroxaban. We performed conventional coagulation tests, thrombin generation (TG) test, thromboelastometry (ROTEM), and epinephrine-induced light transmission aggregometry (LTA) in all 40 patients and 20 controls. Hemoclot Thrombin Inhibitors (HTI) and Factor Xa Direct Inhibitor (DiXaI) assay were used to measure dabigatran and rivaroxaban plasma levels, respectively.Measurements of all assays estimating anticoagulant activity across the 2 patient groups were similar, except for aPTT. Patients on dabigatran exhibited statistically significantly prolonged aPTT values (P < 0.001). In LTA, patients on dabigatran also showed decreased aggregation compared to those on rivaroxaban (P = 0.045). Regarding the TG test, there was no association between endogenous thrombin potential (ETP) and rivaroxaban plasma levels (P = 0.33) as opposed to dabigatran levels (P < 0.001), but significant correlations were observed between rivaroxaban plasma concentrations and kinetic parameters of TG assay (Tlag, P = 0.045; Tmax, P = 0.016; and Cmax, P = 0.003).Based on ROTEM and TG assays, the anticoagulant effects induced by the 2 drugs given in the specific dose regimens in real-world patients were comparable. Only platelet aggregation was found to be more affected by dabigatran as compared to rivaroxaban., Competing Interests: Potential conflicts of interest: Prof. John Lekakis reports personal fees from Bayer and Pfizer. All other authors have no conflicts of interest to disclose.

Background: Our aim was to identify laboratory assays in order to assess the anticoagulant effects of dabigatran etexilate (DE)., Methods: Twenty patients with nonvalvular atrial fibrillation treated on DE (110 mg per os twice daily) and 20 on acenocoumarol were studied. Conventional coagulation tests, endogenous thrombin potential (ETP), thromboelastometry (ROTEM), epinephrine-induced light transmission aggregometry (LTA), and Hemoclot Thrombin Inhibitors (HTI) were performed in all patients., Results: In ROTEM analysis, the lysis index at 60 minutes was significantly lower in patients receiving DE (P = .011). In LTA, patients on DE showed decreased aggregation compared to those on acenocoumarol, marginally insignificant (P = .068). Regarding ETP, acenocoumarol affected thrombin generation more than dabigatran (area under the curve [AUC], P < .001), while statistically significant associations were detected between dabigatran levels, as determined by the HTI assay, and almost all parameters of ETP assay (AUC, P < .001)., Conclusion: The role of ETP in estimating anticoagulant activity of dabigatran possibly requires further research., (© The Author(s) 2014.)

Endovascular abdominal aortic aneurysm repair (EVAR) and thoracic aortic aneurysm repair (TEVAR) have been widely incorporated into clinical practice. However, changes in arterial stiffness and post-implantation syndrome after aortic endografting remain important issues under investigation. The aneurysm sac wall motion after successful EVAR and TEVAR reflects complex interactions between all the components of the excluded aneurysm, including true compliance of the aneurysm wall itself, intra-aneurysm sac pressure, remodeling of the thrombus, and mechanical characteristics of the endograft. Experimental and clinical studies have shown that aortic endografting results in increased arterial stiffness in animal models. It can be assumed that the alterations of aortic mechanical properties can have a direct impact on heart output. The long-term impact of these mechanical changes on cardiovascular outcomes and the potential effects of different endografts on hemodynamics are important issues under investigation. Post-implantation syndrome (PIS) is a systemic inflammatory response frequently observed after endovascular treatment of aortic pathologies. The main features of PIS include fever, leukocytosis, elevated C-reactive protein levels, and coagulation disturbances. Endograft design appears to influence this inflammatory response following aortic endografting; woven polyester endografts have been shown to be associated with greater inflammatory response compared to PTFE stent grafts. The purpose of this paper is to review the literature to elucidate arterial stiffness alterations and inflammatory response after EVAR and TEVAR and the impact of endograft design on aortic stiffness and the post-inflammatory response., Competing Interests: The authors have no conflict of interest relevant to this publication.

Purpose: To evaluate the differential effects of endograft fabric types on pulse wave velocity (PWV), a valid, clinically feasible marker of arterial stiffness, in patients undergoing endovascular repair (EVAR) of abdominal aortic aneurysms (AAAs)., Methods: As part of a registered study (ClinicalTrials.gov identifier NCT00636766), 118 consecutive men (mean age 71 ± 8 years) with AAA undergoing elective EVAR were divided into groups according to the type of fabric in the implanted endografts: 46 had polytetrafluoroethylene (PTFE)-covered stent-grafts and 72 received stent-grafts covered with polyester fabric. Patients with Marfan syndrome, collagen-related disorders, and end-stage renal failure were excluded. PWV, clinical characteristics (comorbidities, body mass index, blood pressure, lipids, and glucose profile), novel biomarkers [interleukin (IL)-6, IL-8, IL-10, and osteoprotegerin (OPG)] were determined at baseline and prospectively after 12 months., Results: At baseline, standard multiple regression analysis revealed the independent association of mean blood pressure, OPG, and AAA diameter with PWV after adjustment for age (R(2)=0.729, p=0.036). At follow-up, serum levels of both IL-8 and IL-10 were significantly increased, while OPG decreased in both groups (p<0.05). However, between-group comparison revealed a more adverse effect of polyester covered endografts on serum IL-8 (p<0.001) and OPG (p=0.048) levels. At the same time, PWV was considerably increased in both polyester (+4.12±0.33 m/s, p<0.001) and PTFE (+2.82 ± 0.25 m/s, p=0.003) groups; the effect was more pronounced in the former group (p=0.033). In multivariate analysis, the polyester endograft type emerged as an independent determinant of PWV change after EVAR (R(2)=0.460, p=0.040)., Conclusion: Both endograft types increased PWV, while recipients of polyester covered stent-grafts showed greater PWV elevation. Further investigation will clarify the inflammatory response and the differential clinical impact of endograft types.

Background: Lipoprotein-associated Phospholipase A2 (Lp-PLA2), has a powerful inflammatory and atherogenic action in the vascular wall and is an independent marker of poor prognosis in coronary artery disease (CAD). We investigate the association of Lp-PLA2 with markers of vascular dysfunction and atherosclerosis with proven prognostic value in CAD., Methods: In 111 patients with angiographically documented chronic CAD, we measured 1) carotid intima-media thickness (CIMT), 2) reactive hyperemia using fingertip peripheral arterial tonometry (RH-PAT), 3) coronary flow reserve (CFR), by Doppler echocardiography 4) pulse wave velocity (PWV) and 5) blood levels of Lp-PLA2., Results: Patients with Lp-PLA2 concentration >234.5 ng/ml (50th percentile) had higher CIMT (1.44 ± 0.07 vs. 1.06 ± 0.06 mm), PWV (11.0 ± 2.36 vs. 9.7 ± 2.38 m/s) and lower RH-PAT(1.24 ± 0.25 vs. 1.51 ± 0.53) and CFR (2.39 ± 0.75 vs. 2.9 ± 0.86) compared to those with lower Lp-PLA (p < 0.05 for all comparisons). Lp-PLA2 was positively associated with CIMT (regression coefficient b: 0.30 per unit of Lp-PLA2, p = 0.02), PWV (b:0.201, p = 0.04) and inversely with RHI-PAT (b: -0.371, p < 0.001) and CFR (b:-0.32, p = 0.002). In multivariate analysis, Lp-PLA2 was an independent determinant of RHI-PAT, CFR, CIMT and PWV in a model including age, sex, smoking, diabetes, dyslipidemia and hypertension (p < 0.05 for all vascular markers). Lp-PLA2, RHI-PAT and CFR were independent predictors of cardiac events during a 3-year follow-up., Conclusions: Elevated Lp-PLA2 concentration is related with endothelial dysfunction, carotid atherosclerosis, impaired coronary flow reserve and increased arterial stiffness and adverse outcome in CAD patients. These findings suggest that the prognostic role of Lp-PLA2 in chronic CAD may be explained by a generalized detrimental effect of this lipase on endothelial function and arterial wall properties., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Previous studies suggested a possible negative interference of proton pump inhibitors (PPIs) on clopidogrel's antiplatelet effect because of the competitive inhibition of the CYP 2C19 isoenzyme. Moreover, carriers of the loss-of-function allele of CYP2C19 polymorphism (CYP2C19*2) display significantly lower responses to clopidogrel. In this study, we investigated the association between CYP2C19*2 genotype, PPI intake and clopidogrel resistance in patients with coronary artery disease (CAD) and their effect on clinical outcome., Methods: We recruited 95 patients with CAD receiving chronic clopidogrel therapy in combination with aspirin. Platelet reactivity was simultaneously assessed by INNOVANCE PFA-100 P2Y, ADP-induced light transmission aggregometry (LTA), flow-cytometric vasodilator-stimulated phosphoprotein (VASP)-phosphorylation assay and multiple electrode aggregometry (Multiplate). Cardiovascular outcomes were recorded during 1-year follow-up period., Results: Only platelet reactivity assessed by measuring platelet phosphorylated-VASP demonstrated a significant higher platelet reactivity in carriers of CYP2C19*2 (p=0.023). The other methods displayed higher - but not statistically significant - platelet reactivity in patients carrying the CYP2C19*2 variant as compared with non-carriers. Patients on PPIs demonstrated almost similar suppression of platelet reactivity in comparison with those not treated with PPIs by all platelet function assays. In logistic regression analysis none of the platelet function assays measurements were related with clinical outcomes. Similarly neither CYP2C19*2 genetic variant nor PPI treatment were associated with adverse clinical events., Conclusions: PPI co-administration did not influence clopidogrel's antiplatelet effect on laboratory testing by all platelet function assays used. On the contrary, patients carrying CYP2C19*2 genotype had significantly higher residual platelet reactivity as estimated by VASP-phosphorylation assay., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Solitary fibrous tumor (SFT) belongs to a group of mesenchymal tumors, also known as benign fibrous mesotheliomas or submesothelial fibromas. SFTs of the sinonasal tract are extremely rare., Methods: We report a rare case of an atypical SFT of the sinonasal tract presenting with ipsilateral nasal obstruction and recurrent epistaxis. Endoscopy and imaging studies showed a well-circumscribed mass of the nose and the maxillary sinus. The patient underwent total endoscopic resection of the tumor., Results: Permanent histology and immunohistochemical studies revealed an atypical variant of SFT of the sinonasal tract, with negative surgical margins. The patient did not receive any adjuvant treatment. Postoperative monitoring was uneventful., Conclusion: In general, these tumors are reported to follow an indolent course. SFTs adopt a biological behavior that cannot be determined as malignant. Total surgical resection of the tumor remains the gold-standard method of treatment., (Copyright © 2011 Wiley Periodicals, Inc.)

Aims: Coronary microcirculation is disturbed in hypertensive patients. We investigated the association of coronary flow reserve (CFR) with the response of left ventricular (LV) function as assessed by tissue Doppler imaging (TDI) during adenosine stress echocardiography in never-treated hypertensive patients., Methods and Results: We studied 90 hypertensive patients and 30 control subjects, matched for age and sex, by adenosine stress echocardiography. We measured: (i) CFR, E and A Doppler, S', E', A' mitral annulus velocities with TDI, as well as the E'/A' ratio and the E/E' ratio before and during adenosine infusion (ii) the %changes of the measured indices between baseline and adenosine infusion. After adenosine infusion, there was an increase in S', E', and A' in all patients and controls (P < 0.05). Compared with controls and patients with CFR ≥ 2.5, patients with CFR <2.5 showed a smaller increase in S' (28.6 vs. 30.0 vs. 11.1%, F for interaction = 14.592) and E' (33.3 vs. 33.3 vs.1.5%, F = 28.927) as well as a decrease in E'/A' (9.2 vs. 6.4% vs. -20.0%, F = 5.128) and an increase in E/E' (-6.1 vs. -1.6 vs. 30.5%. F = 12.780) after adenosine infusion (P < 0.05 for all comparisons). CFR was independently related to %changes of TDI parameters (regression coefficient b = 0.576 for S'; b = 0.517 for E'; b = 0.473 for E'/A'; b = -0.520 for E/E', respectively, P < 0.001). By the receiver operating curve, a CFR <2.5 predicted the median changes of all measured TDI markers, with a sensitivity and specificity over 70% (AUC >75%, P < 0.05)., Conclusion: An abnormal response of the LV longitudinal function during adenosine stress echocardiography is related to impaired CFR in untreated hypertensive patients.

Objectives: Pulse wave velocity (PWV) constitutes a valid index of arterial stiffness osteoprotegerin (OPG) and osteopontin (OPN) which are well-established vascular calcification inhibitors, highly correlated with inflammation, and cardiovascular events incidence. We investigated the association of PWV with the aforementioned novel biomarkers in patients with abdominal aortic aneurysm (AAA)., Methods: We enrolled 108 men with AAA (AAA group) candidates for endovascular repair. We excluded patients with Marfan syndrome or other collagen-related disorders. Forty-one age-matched men, with stable coronary artery disease (CAD), but without AAA, served as controls (CO group). PWV, clinical parameters and serum levels of osteoprotegerin (OPG), osteopontin (OPN), interleukin-6 (IL-6) and IL-10 were determined., Results: With the exception of higher smoking rate and the lower statin's usage in the AAA group, there were non-significant differences in the rest of demographic and clinical parameters (p>0.05). We found significantly higher levels of PWV in AAA than CO group (12.99±3.75 m/s vs 10.03±1.57 m/s, p<0.001). In parallel, serum OPG, OPN, IL-6 levels were considerably increased, while IL-10 levels were downregulated (p<0.001) in AAA group. PWV positively correlated with mean blood pressure, OPG concentrations and AAA diameter in univariate and multivariate analysis (R(2)=0.498, p=0.008). Finally, age and OPG remained independent determinants of AAA presence in the whole study cohort., Conclusions: Arterial stiffness, circulating vascular calcification inhibitors and inflammatory mediators seem to be significantly upregulated in patients with AAA. An independent association of PWV with mean blood pressure, OPG and AAA diameter is of clinical importance which requires further investigation., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The method of surrogates is one of the key concepts of nonlinear data analysis. Here, we demonstrate that commonly used algorithms for generating surrogates often fail to generate truly linear time series. Rather, they create surrogate realizations with Fourier phase correlations leading to nondetections of nonlinearities. We argue that reliable surrogates can only be generated, if one tests separately for static and dynamic nonlinearities.

Purpose: To assess changes in pulse wave velocity (PWV), a valid index of arterial stiffness, in patients undergoing endovascular repair (EVAR) of abdominal aortic aneurysm (AAA). Arterial stiffness is an independent marker of all-cause mortality and cardiovascular morbidity and mortality., Methods: Forty-eight consecutive male patients (mean age 71±4 years) underwent elective EVAR (AAA group) after exclusion of patients with Marfan syndrome or other collagen-related disorders. Thirty-one age-matched men (mean age 69±5 years) without overt cardiovascular disease served as controls. PWV and clinical parameters were determined at baseline in both groups and after 6 months in the AAA group., Results: At baseline, the groups did not differ in demographic characteristics, lipid profile, or blood pressure levels (p>0.05). PWV was considerably higher in AAA than controls (p<0.001). PWV positively correlated with mean blood pressure, AAA diameter, and age in univariate and multivariate analysis (R(2)=0.498, p=0.008). At 6 months after EVAR, PWV significantly increased from 13.11±3.57 m/s to 16.41±2.33 m/s (p<0.001) in the AAA group., Conclusion: Patients with AAA present with significantly elevated PWV levels compared to controls, and stent-graft repair is associated with a significant increase in the PWV. Whether those changes contribute to the cardiovascular risk in AAA patients needs further investigation.

B cell-activating factor (BAFF) is a cytokine that plays a major role in the maintenance of normal B-cell development and homeostasis. It has been suggested that in multiple myeloma (MM) it might have regulatory effects on the proliferation and viability of malignant plasma cells. The aim of this study was to evaluate serum levels of BAFF in 52 newly diagnosed MM patients, with varying disease severity, in order to see the correlations between BAFF and indices of MM activity, such as interleukin-6, C-reactive protein, lactate dehydrogenase, and beta-2 microglobulin, and to explore the clinical significance of BAFF in predicting the disease activity of MM. We found increased BAFF serum levels in MM patients, increased in advanced stages, and decreased in plateau phase. We also found significant correlations between BAFF serum levels with the above parameters of disease activity. We conclude that BAFF may play an important role in pathogenesis of MM, could be used as a marker of disease activity, and a possible therapeutic target.

Coronary artery disease (CAD) is one of the most common manifestations of atherosclerosis. Inflammation is considered one of the major processes that contribute to atherogenesis. Inflammation plays an important role not only on the initiation and progression of atherosclerosis but also on plaque rupture, an event that leads to acute vascular events. Various biomarkers express different pathways and pathophysiologic mechanisms of cardiovascular disease, and inflammatory biomarkers express different parts of the atherogenic process, regarding the initiation and progression of atherosclerosis or the destabilization of the atherosclerotic plaque. Therefore, inflammatory biomarkers may prove to be useful in the detection, staging, and prognosis of patients with CAD. Furthermore, the fact that inflammatory processes are essential steps in the course of the disease offers future therapeutic targets for the interruption of the atherogenic process or for the management of acute events., (Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.)

Metastasis to regional lymph nodes constitutes the main route toward progression and dissemination of head and neck carcinoma; at the same time it is the most significant adverse prognostic indicator for this disease. In recent years, significant focus has been given on the molecular mechanisms behind lymph node metastasis of head and neck cancer. The aim of this study is to assess the role of growth factor expression and function in association with lymph node metastasis and overall prognosis of head and neck cancer. Current literature, searching for experimental data regarding the molecular pathways of lymph node dissemination of head and neck cancer, is reviewed giving special emphasis on the expression and prognostic significance of specific growth factors. Members of the vascular endothelial growth factor (VEGF), mostly VEGF-C and VEGF-D, with their action through the receptors VEGFR-3 and VEGFR-2, constitute the most extensively studied growth factors associated with lymphangiogenesis so far. High expression of these as well as other molecules, including angiopoietins, insulin-like growth factor, and fibroblast growth factor, has been associated with lymph node metastasis and poor prognosis in head and neck squamous cell carcinoma. Numerous growth factors seem to play an important role regarding the lymph node metastatic potential of head and neck cancer. Further research is necessary in order to further clarify the molecular pathways and introduce novel therapeutic options.

Light transmittance aggregometry (LTA) has been extensively used in monitoring clopidogrel therapy. However, the availability of simple and rapid point-of-care platelet function assays is of great clinical importance. Thus, the manufacturer of the Platelet Function Analyzer (PFA)-100 System has recently produced the INNOVANCE PFA P2Y test cartridge. We assessed the ability of this new test to reliably detect clopidogrel resistance. We enrolled 90 consecutive patients with coronary artery disease receiving chronic clopidogrel maintenance therapy in combination with aspirin. Twenty healthy volunteers served as controls. Clopidogrel resistance was simultaneously analysed by the INNOVANCE PFA P2Y test cartridge, ADP-induced LTA, the flow-cytometric vasodilator-stimulated phosphoprotein (VASP)-phosphorylation assay and the multiple electrode aggregometry (Multiplate). Agreement among the four platelet function methods by two was assessed using Cohen's kappa coefficient. According to the cut-off points for clopidogrel resistance proposed by the literature, agreement was fair between INNOVANCE PFA-100 P2Y and LTA (74.4%) and Multiplate (75.6%), while poor agreement was noticed in VASP assay (63.3%). Based on cut-off points indicating a higher thrombotic risk, agreement between the PFA-100 System and the other three methods did not significantly differ compared to the previous cut-offs (72.2%, 71.1% and 55.1%, respectively). The INNOVANCE PFA-100 P2Y test seems to be comparable to other established platelet function assays in detecting clopidogrel resistance. However, the modest agreement among platelet function methods makes the performance of platelet function testing crucial with more than one technique in order to reliably identify poor responders to clopidogrel treatment.

Nasal bleeding is a frequent problem for patients receiving anticoagulant agents. Most cases are successfully managed with anterior or posterior nasal packing. However, the complications of nasal packing should be always considered. We report the case of a 78-year-old man with Alzheimer's disease who was treated for anterior epistaxis with anterior nasal packing using three pieces of antibiotic-soaked gauze. Two days later, the patient was admitted to the emergency department in respiratory distress. A chest x-ray demonstrated atelectasis of the right lung. During an examination of the nasal cavities, the nasal packing was removed, and one of the gauze pieces was missing. The patient underwent rigid bronchoscopy, and the missing gauze was found to be obstructing the right main bronchus. The patient's respiratory function improved considerably after removal of the foreign body. It is assumed that gauze packs should be used with caution in patients with an impaired level of consciousness and neurodegenerative diseases.

The ontogeny of the digestive tract was studied histologically and histochemically in sharpsnout sea bream Diplodus puntazzo from hatching (0 DAH, Days After Hatching) until day 57 (57 DAH). At hatching, the digestive tract appeared as a histologically undifferentiated straight tube lying dorsally to the yolk sac. When the mouth opened at 3 DAH, the digestive tract was differentiated into buccopharynx, oesophagus, incipient stomach and intestine. The pancreas, liver and gall bladder were also differentiated at this stage and both the bile and pancreatic duct had opened into the anterior intestine. Active feeding began in 50% of larvae at 4 DAH, although permanence of yolk reserves until 7 DAH suggests a period of both endogenous and exogenous feeding. Nutrient absorption was first visible from 5 DAH, as colourless supra- and infranuclear vacuoles in the anterior intestinal mucosa, suggesting a lipid content, as well as supranuclear, eosinophilic vacuoles, containing protein, in the posterior intestinal mucosa. Early caecal development could be detected from 10 DAH, whereas gastric glands appeared at 30 DAH, indicating the transition from larval to juvenile stage and the acquisition of an adult mode of digestion. Goblet cells appeared in the digestive tract of sharpsnout sea bream larvae shortly after first feeding. The mucus content of goblet cells varied with the digestive region and, in the buccal cavity and oesophagus, also with the developmental phase. This study provides knowledge for better husbandry practices in the aquaculture industry, as well as for the implementation of future nutritional studies.

We investigated the uptake of aluminum (Al) and transport to shoots in two inbred maize lines (Zea mays L., VA-22 and A(4/67)) differing in Al tolerance. Seedlings were grown for 7 days in hydroponic culture with nutrient solution that contained 0, 240, 360, and 480microM Al at pH 4.2. After 7 days of exposure to Al, roots of sensitive maize line (A(4/67)) plants accumulated 2-2.5 times more Al than roots of tolerant line (VA-22) plants. Inductively coupled plasma atomic emission spectrometry (ICP-AES) showed that the tolerant line retained higher concentrations of Ca(2+), Mg(2+), and K(+) compared with the sensitive line. In response to Al treatment, proline (Pro) concentration increased three-fold in roots of tolerant plants, while a slight increase was observed in roots of sensitive-line plants. A substantial carbon surplus (two-fold increase) was observed in roots of the Al-tolerant maize line. Carbohydrate concentration remained almost unchanged in roots of Al-sensitive line plants. Al treatment triggered the enhancement of lipid peroxidation in the sensitive line, while no change in lipid peroxidation level was observed in the tolerant maize line. These data provide further support to the hypothesis that a mechanism exists that excludes Al from the roots of the tolerant maize line, as well as an internal mechanism of tolerance that minimizes accumulation of lipid peroxides through a higher Pro and carbohydrate content related to osmoregulation and membrane stabilization.

We have developed a mathematical model based on the underlying mechanisms concerning the responses of the photosynthetic apparatus of a microalga cell which grows under constant incident light intensity and ambient CO(2) concentration. Photosynthesis involves light and carbon-fixation reactions which are mutually dependent and affect each other, but existing models for photosynthesis don't account for both reactions at once. Our modeling approach allows us to derive distinct equations for the rates of oxygen production, NADPH production, carbon dioxide fixation, carbohydrate production, and rejected energy, which are generally different. The production rates of the photosynthesis products are hyperbolic functions of light and CO(2) concentration. The model predicts that in the absence of photoinhibition, CO(2)-inhibition, photorespiration, and chlororespiration, a cell acclimated to high light and/or CO(2) concentration has higher photosynthetic capacity and lower photosynthetic efficiency than does a cell acclimated to low conditions. This results in crossing between the two curves which represent the oxygen production rates and carbon fixation rates in low and high conditions. Finally, in the absence of photoinhibition and CO(2)-inhibition, the model predicts the carbohydrate production rate in terms of both light intensity and CO(2) concentration.

Actinomycosis is a chronic suppurative, granulomatous disease, which is characterized clinically by extensive necrosis and abscess formation, and histologically by the presence of the so-called "sulphur granules". Actinomycosis is generally classified as being of cervicofacial, thoracic or abdominal type. The objective of this study is the presentation of a case of actinomycotic liver abscess that we encountered in our department 5 years ago, along with a brief review of this rare disease. A 39-year-old male non-Greek Caucasian patient presented with high fever, malaise, anorexia, vomiting after food ingestion and right upper quadrant pain. Leucocytosis with a left shift was present, and ultrasonography demonstrated a mass of mixed composition in the anterior part of the right hepatic lobe, measuring 6.8 x 4.6 cm, suggestive of an abscess or haemangioma. MRI scan confirmed the presence of a space-occupying lesion, suggestive of an abscess. The patient was submitted to surgical drainage of the hepatic abscess. The culture of the purulent material was found to be sterile, while the histochemical examination of the specimen demonstrated the presence of actinomycosis. The patient had an uneventful postoperative course and after discharge received prolonged chemoprophylaxis. Actinomycotic liver abscess is a very rare clinical entity, and only 57 cases have been reported in the English literature. Due to the rarity of the disease and the limited number of reported cases, we considered it useful to report this case.

In IMEP-8, two samples of high purity CO(2)(g), with different carbon and oxygen isotope ratios were distributed to 27 participants, originating from 14 countries and from various isotopic measurement domains (geochemistry, atmospheric and food chemistry), but particularly set up for food laboratories. In total 19 laboratories reported results. The outcome of this comparison exercise shows that the laboratories reported carbon and oxygen isotope results in good agreement with the reference values across the domains. The reported results for delta(13)C(VPDB) (carbon) for both materials are within 1 per thousand. However, for the reported results of delta(18)O(VPDB) (oxygen) for both materials the overall spread of the reported results is about 11 per thousand. Within this spread two distinct groups of participants can be identified, where the results within each group vary about 2 per thousand. The latter seems to be caused by calculation errors by participants of the reporting delta(18)O(VPDB) values. As requested, participants also reported the isotope amount ratio for carbon and oxygen in the CO(2) samples. For carbon, all reported results for both materials agree with the isotope ratio value, which can be traced back to the value reported by Craig. For oxygen, all results are in good agreement and deviate by a maximum of 0.5% from the reference values measured at IRMM. Work carried out indicates the carbon isotope ratio, for both samples IMEP-8A and IMEP-8B, differ from those reported by Craig by as much as 1.2%. In the case of oxygen, this deviation is far smaller. Both data sets, i.e. the one realised by Craig and the one realised at IRMM, demonstrate traceability to SI. It is clear that both values significantly disagree.

In this paper, a secure medical digital library is presented. It is based on the CORBA specifications for distributed systems. The described approach relies on a three-tier architecture. Interaction between the medical digital library and its users is achieved through a Web server. The choice of employing Web technology for the dissemination of medical data has many advantages compared to older approaches, but also poses extra requirements that need to be fulfilled. Thus, special attention is paid to the distinguished nature of such medical data, whose integrity and confidentiality should be preserved at all costs. This is achieved through the employment of Trusted Third Parties (TTP) technology for the support of the required security services. Additionally, the proposed digital library employs smartcards for the management of the various security tokens that are used from the above services.

The International Measurement Evaluation Programme (IMEP) is an interlaboratory comparison scheme, founded, owned and coordinated by the Institute for Reference Materials and Measurements (IRMM) since 1988. IMEP-9 is the third round of trace elements in water evaluation following IMEP-3 and IMEP-6. Reference values for 15 elements stating total concentrations and combined uncertainties (according to GUM) were established. The reference values were established mainly by isotope dilution mass spectrometry (IDMS) as a primary method of measurement, and values traceable to the SI were obtained. The four elements that could not be certified by IDMS were assigned values by means of other measurement techniques. Results from 201 laboratories from 35 countries and four continents were evaluated against the reference values and the comparability between the laboratories is presented graphically.

Many fields in environmental analytical chemistry deal with very low limits and thresholds as set by governmental legislations or transnational regulations. The need for the accuracy, comparability and traceability of analytical measurements in environmental analytical chemistry has significantly increased and total uncertainties are even asked for by accreditation bodies of environmental laboratories. This paper addresses achieving these goals to guarantee accuracy, quality control, quality assurance or validation of a method by means of certified reference materials. The assessment of analytical results in certified reference materials must be as accurate as possible and every single step has to be fully evaluated. This paper presents the SI-traceable certification of Cu, Cr, Cd and Pb contents in geological and environmentally relevant matrices (three sediments and one fly ash sample). Certification was achieved using isotope dilution (ID) ICPMS as a primary method of measurement. In order to reduce significantly the number of analytical steps and intermediate samples a multiple spiking approach was developed. The full methodology is documented and total uncertainty budgets are calculated for all certified values. A non-element specific sample digestion process was optimised. All wet chemical digestion methods examined resulted in a more or less pronounced amount of precipitate. It is demonstrated that these precipitates originate mainly from secondary formation of fluorides (essentially CaF2) and that their formation takes place after isotopic equilibration. The contribution to the total uncertainty of the final values resulting from the formation of such precipitates was in general < 0.1% for all investigated elements. Other sources of uncertainty scrutinised included the moisture content determination, procedural blank determination, cross-contamination from the different spike materials, correction for spectral interferences, instrumental background and deadtime effects, as well as the use of either certified values or IUPAC data in the IDMS equation. The average elemental content in the sediment samples was 30-130 micrograms g-1 for Pb, 0.5-3 micrograms g-1 for Cd and 50-70 micrograms g-1 for Cu. Cr was measured in one sample and was about 60 micrograms g-1. The concentrations in the fly ash sample were up to 2 orders of magnitude higher. Expanded uncertainty for the investigated elements was about 3% (coverae factor k = 2) except for Cr, (measured by high resolution ICPMS), for which the expanded uncertainty was about 7% (k = 2).

In this paper, a secure medical digital library architecture is presented, that is based on the CORBA specifications for distributed systems. Special attention is given to the distinguished nature of medical data, whose integrity and confidentiality should be preserved at all costs. This is achieved through the employment of Trusted Third Parties (TTP) technology for the support of the required security services.

mu heavy chain deposition disease is very rare. We report the first case of glomerulonephritis in a woman without evidence of hematopoietic malignancy. Nodular glomerulosclerosis and monotypic mu heavy chain mesangial deposits were identified by immunofluorescence without kappa or lambda deposits. Electron microscopy showed fibrillar mesangial deposits of 16-18 nm in diameter. Serum immunoglobulins, cryoglobulins, serum immunoelectrophoresis, and immunofixation, bone marrow biopsy, and Bence Jones proteins in urine were negative. The patient has stable renal disease and is free of malignancy 6 years after the initial occurrence of proteinuria.