Pesticides in the Ebro River basin: Occurrence and risk assessment

In this study, 50 pesticides were analyzed in the Ebro River basin in 2010 and 2011 to assess their impact in water, sediment and biota. A special emphasis was placed on the potential effects of both, individual pesticides and their mixtures, in three trophic levels (algae, daphnia and fish) using Risk Quotients (RQs) and Toxic Units (TUs) for water and sediments. Chlorpyrifos, diazinon and carbendazim were the most frequent in water (95, 95 and 70% of the samples, respectively). Imazalil (409.73 ng/L) and diuron (150 ng/L) were at the highest concentrations. Sediment and biota were less contaminated. Chlorpyrifos, diazinon and diclofenthion were the most frequent in sediments (82, 45 and 21% of the samples, respectively). The only pesticide detected in biota was chlorpyrifos (up to 840.2 ng g−1). Ecotoxicological risk assessment through RQs showed that organophosphorus and azol presented high risk for algae; organophosphorus, benzimidazoles, carbamates, juvenile hormone mimic and other pesticides for daphnia, and organophosphorus, azol and juvenile hormone mimics for fish. The sum TUsite for water and sediments showed values < 1 for the three bioassays. In both matrices, daphnia and fish were more sensitive to the mixture of pesticide residues present.This work has been supported by the Spanish Ministry of Economy and Competitiveness through the projects NET-SCARCE project (CTM2015-69780-REDC); “Evaluation of Emerging Contaminants in the Turia River Basins: From Basic Research to the Application of Environmental Forensics (EMERFOR)” (GCL2011- 29703-C02-02, http://mefturia.es) and European Communities 7th Framework Programme funding under Grant Agreement No. 603629-ENV-2013-6.2.1-Globaqua. A, Ccanccapa gratefully acknowledges the Conselleria DEducaci o, Cultura y Sport de Valencia for the financial support through “Santiago Grisolía” Scholarship Program.Peer reviewe

Circulating nucleic acids in plasma and serum (CNAPS): Applications in oncology

The presence of small amounts of circulating nucleic acids in plasma and serum (CNAPS) is not a new finding. The verification that such amounts are significantly increased in cancer patients, and that CNAPS might carry a variety of genetic and epigenetic alterations related to cancer development and progression, has aroused great interest in the scientific community in the last decades. Such alterations potentially reflect changes that occur during carcinogenesis, and include DNA mutations, loss of heterozygosity, viral genomic integration, disruption of microRNA, hypermethylation of tumor suppressor genes, and changes in the mitochondrial DNA. These findings have led to many efforts toward the implementation of new clinical biomarkers based on CNAPS analysis. In the present article, we review the main findings related to the utility of CNAPS analysis for early diagnosis, prognosis, and monitoring of cancer, most of which appear promising. However, due to the lack of harmonization of laboratory techniques, the heterogeneity of disease progression, and the small number of recruited patients in most of those studies, there has been a poor translation of basic research into clinical practice. In addition, many aspects remain unknown, such as the release mechanisms of cell-free nucleic acids, their biological function, and the way by which they circulate in the bloodstream. It is therefore expected that in the coming years, an improved understanding of the relationship between CNAPS and the molecular biology of cancer will lead to better diagnosis, management, and treatmen

Evaluation of endothelial function and subclinical atherosclerosis in association with hepatitis C virus in HIV-infected patients: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Relationship of hepatitis C virus (HCV) infection with an increased risk of cardiovascular disease (CVD) in HIV-infected patients remains controversial. We evaluated endothelial function and subclinical atherosclerosis in HIV-infected patients with and without HCV.</p> <p>Methods</p> <p>Flow-mediated dilatation (FMD) of the brachial artery and circulating levels of cell adhesion molecules (CAM) were measured in HCV/HIV-coinfected and HIV-monoinfected patients. Subclinical atherosclerosis was assessed by carotid intima-media thickness (cIMT).</p> <p>Results</p> <p>63 (31%) HCV/HIV-coinfected and 138 (69%) HIV-monoinfected patients were included. Median soluble vascular CAM-1 (sVCAM-1) and intercellular CAM-1 (sICAM-1) levels were significantly higher in HIV/HCV-coinfected patients (P < 0.001 for both cases). Median (interquartile range) FMD was 6.21% (2.86-9.62) in HCV/HIV-coinfected and 5.54% (2.13-9.13) in HIV-monoinfected patients (P = 0.37). Adjustment for variables associated with HCV and FMD disclosed similar results. FMD correlated inversely with cIMT and age. Carotid IMT did not differ between HCV/HIV-coinfected and HIV-monoinfected patients in unadjusted (0.61 [0.55-0.65] mm vs 0.60 [0.53-0.72] mm; P = 0.39) or adjusted analyses.</p> <p>Conclusion</p> <p>HCV infection was associated with higher levels of sICAM-1 and sVCAM-1, but no evidence of increased subclinical atherosclerosis was found when endothelial function was evaluated through FMD, or when assessing the cIMT.</p

Evaluation of the passive safety in cars adapted with steering control devices for disabled drivers

The purpose of this research is to analyse the influence of steering control devices for disabled people on passive safety. It is based on the advances made in the modelling and simulation of the driver position and in the suit verification test. The influence of these devices is studied through airbag deployment and/or its influence on driver safety. We characterise the different adaptations that are used in adapted cars that can be found mounted in vehicles in order to generate models that are verified by experimental test. A three-dimensional design software package was used to develop the model. The simulations were generated using a dynamic simulation program employing LS-DYNA finite elements. This program plots the geometry and assigns materials. The airbag is shaped, meshed and folded just as it is mounted in current vehicles. The thermodynamic model of expansion of gases is assigned, and the contact interfaces are defined. Static tests were carried out on the deployment of the airbag to contrast with and to validate the computational models and to measure the behaviour of the airbag when there are steering adaptations mounted in the vehicle. © 2011 Taylor & Francis.Masiá Vañó, J.; Eixerés Tomás, B.; Dols Ruiz, JF. (2011). Evaluation of the passive safety in cars adapted with steering control devices for disabled drivers. International Journal of Crashworthiness. 16(1):75-83. doi:10.1080/13588265.2010.514772S7583161Bedewi, N. E., Marzougui, D., & Motevalli, V. (1996). Evaluation of parameters affecting simulation of airbag deployment and interaction with occupants. International Journal of Crashworthiness, 1(4), 339-354. doi:10.1533/cras.1996.0025Chawla, A., Mukherjee, S., & Sharma, A. (2005). Development of FE meshes for folded airbags. International Journal of Crashworthiness, 10(3), 259-266. doi:10.1533/ijcr.2005.0343Cheng, Z., Rizer, A. L., & Pellettiere, J. A. (2003). Modeling and Simulation of OOP Occupant-Airbag Interaction. SAE Technical Paper Series. doi:10.4271/2003-01-0510Crandall, J. R., Bass, C. R., Pikey, W. D., Miller, H. J., Sikorski, J., & Wilkins, M. (1996). Thoracic response and injury with belt, driver side airbag, and force limited belt restraint systems. International Journal of Crashworthiness, 2(1), 119-132. doi:10.1533/cras.1997.0039Dalrymple, G. (1996). Effects of Assistive Steering Devices on Air Bag Deployment. SAE Technical Paper Series. doi:10.4271/960223Khan, M. U., & Moatamedi, M. (2008). A review of airbag test and analysis. International Journal of Crashworthiness, 13(1), 67-76. doi:10.1080/13588260701731674Khan, M. U., Moatamedi, M., Souli, M., & Zeguer, T. (2008). Multiphysics out of position airbag simulation. International Journal of Crashworthiness, 13(2), 159-166. doi:10.1080/13588260701788385Richert, J., Coutellier, D., Götz, C., & Eberle, W. (2007). Advanced smart airbags: The solution for real-life safety? International Journal of Crashworthiness, 12(2), 159-171. doi:10.1080/13588260701433461Ruff, C., Jost, T., & Eichberger, A. (2007). Simulation of an airbag deployment in out-of-position situations. Vehicle System Dynamics, 45(10), 953-967. doi:10.1080/0042311070153830

Prevalence of Symptomatic and Asymptomatic Peripheral Arterial Disease and the Value of the Ankle-brachial Index to Stratify Cardiovascular Risk

AbstractObjectivesTo determine the prevalence of ankle-brachial index (ABI)<0.9 and symptomatic peripheral arterial disease (PAD), association with cardiovascular risk factors (CVRF), and impact of adding ABI measurement to coronary heart disease (CHD) risk screening.DesignPopulation-based cross-sectional survey of 6262 participants aged 35–79 in Girona, Spain.MethodsStandardized measurements (CVRF, ABI, 10-year CHD risk) and history of intermittent claudication (IC), CHD, and stroke were recorded. ABI<0.9 was considered equivalent to moderate-to-high CHD risk (≥10%).ResultsABI<0.9 prevalence was 4.5%. Only 0.62% presented low ABI and IC. Age, current smoker, cardiovascular disease, and uncontrolled hypertension independently associated with ABI<0.9 in both sexes; IC was also associated in men and diabetes in women. Among participants 35–74 free of cardiovascular disease, 6.1% showed moderate-to-high 10-year CHD risk; adding ABI measurement yielded 8.7%. Conversely, the risk function identified 16.8% of these participants as having 10-year CHD risk>10%. In participants 75–79 free of cardiovascular disease, the prevalence of ABI<0.9 (i.e., CHD risk≥10%) was 11.9%.ConclusionsABI<0.9 is relatively frequent in those 35–79, particularly over 74. However, IC and CHD risk≥10% indicators are often missing. Adding ABI measurement to CHD-risk screening better identifies moderate-to-high cardiovascular risk patients

M2 Macrophages Activate WNT Signaling Pathway in Epithelial Cells: Relevance in Ulcerative Colitis

Macrophages, which exhibit great plasticity, are important components of the inflamed tissue and constitute an essential element of regenerative responses. Epithelial Wnt signalling is involved in mechanisms of proliferation and differentiation and expression of Wnt ligands by macrophages has been reported. We aim to determine whether the macrophage phenotype determines the expression of Wnt ligands, the influence of the macrophage phenotype in epithelial activation of Wnt signalling and the relevance of this pathway in ulcerative colitis. Human monocyte-derived macrophages and U937-derived macrophages were polarized towards M1 or M2 phenotypes and the expression of Wnt1 and Wnt3a was analyzed by qPCR. The effects of macrophages and the role of Wnt1 were analyzed on the expression of β-catenin, Tcf-4, c-Myc and markers of cell differentiation in a co-culture system with Caco-2 cells. Immunohistochemical staining of CD68, CD206, CD86, Wnt1, β-catenin and c-Myc were evaluated in the damaged and non-damaged mucosa of patients with UC. We also determined the mRNA expression of Lgr5 and c-Myc by qPCR and protein levels of β-catenin by western blot. Results show that M2, and no M1, activated the Wnt signaling pathway in co-culture epithelial cells through Wnt1 which impaired enterocyte differentiation. A significant increase in the number of CD206+ macrophages was observed in the damaged mucosa of chronic vs newly diagnosed patients. CD206 immunostaining co-localized with Wnt1 in the mucosa and these cells were associated with activation of canonical Wnt signalling pathway in epithelial cells and diminution of alkaline phosphatase activity. Our results show that M2 macrophages, and not M1, activate Wnt signalling pathways and decrease enterocyte differentiation in co-cultured epithelial cells. In the mucosa of UC patients, M2 macrophages increase with chronicity and are associated with activation of epithelial Wnt signalling and diminution in enterocyte differentiation

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide versus dolutegravir /abacavir/lamivudine in antiretroviral-naïve adults (SYMTRI): a multicenter randomized open-label study (PReEC/RIS-57)

D/C/F/TAF is the reference for combination therapy based on protease inhibitors but has not been compared with regimens containing integrase inhibitors as initial ART. We could not demonstrate D/C/F/TAF noninferiority relative to DTG/ABC/3TC, although both regimens were similarly well tolerated. Background Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) is the reference for combination therapy based on protease inhibitors due to its efficacy, tolerability, and convenience. Head-to-head randomized comparisons between D/C/F/TAF and combination therapy based on integrase inhibitors in antiretroviral-naive patients are lacking. Methods Adult (>18 years old) human immunodeficiency virus-infected antiretroviral-naive patients (HLA-B*5701 negative and hepatitis B virus negative), with viral load (VL) >= 500 c/mL, were centrally randomized to initiate D/C/F/TAF or dolutegravir/abacavir/lamivudine (DTG/3TC/ABC) after stratifying by VL and CD4 count. Clinical and analytical assessments were performed at weeks 0, 4, 12, 24, and 48. The primary endpoint was VL 100 000 copies/mL, and 13% had <200 CD4 cells/mu L. Median weight was 73 kg and median body mass index was 24 kg/m(2). At 48 weeks, 79% (D/C/F/TAF) versus 82% (DTG/3TC/ABC) had VL <50 c/mL (difference, -2.4%; 95% confidence interval [CI], -11.3 to 6.6). Eight percent versus four percent experienced virologic failure but no resistance-associated mutations emerged. Four percent versus six percent had drug discontinuation due to adverse events. In the per-protocol analysis, 94% versus 96% of patients had VL <50 c/mL (difference, -2%; 95% CI, -8.1 to 3.5). There were no differences in CD4 cell count or weight changes. Conclusions We could not demonstrate the noninferiority of D/C/F/TAF relative to DTG/ABC/3TC as initial antiretroviral therapy, although both regimens were similarly well tolerated

Progastrin Represses the Alternative Activation of Human Macrophages and Modulates Their Influence on Colon Cancer Epithelial Cells

Macrophage infiltration is a negative prognostic factor for most cancers but gastrointestinal tumors seem to be an exception. The effect of macrophages on cancer progression depends on their phenotype, which may vary between M1 (pro-inflammatory, defensive) to M2 (tolerogenic, pro-tumoral). Gastrointestinal cancers often become an ectopic source of gastrins and macrophages present receptors for these peptides. The aim of the present study is to analyze whether gastrins can affect the pattern of macrophage infiltration in colorectal tumors. We have evaluated the relationship between gastrin expression and the pattern of macrophage infiltration in samples from colorectal cancer and the influence of these peptides on the phenotype of macrophages differentiated from human peripheral monocytes in vitro. The total number of macrophages (CD68+ cells) was similar in tumoral and normal surrounding tissue, but the number of M2 macrophages (CD206+ cells) was significantly higher in the tumor. However, the number of these tumor-associated M2 macrophages correlated negatively with the immunoreactivity for gastrin peptides in tumor epithelial cells. Macrophages differentiated from human peripheral monocytes in the presence of progastrin showed lower levels of M2-markers (CD206, IL10) with normal amounts of M1-markers (CD86, IL12). Progastrin induced similar effects in mature macrophages treated with IL4 to obtain a M2-phenotype or with LPS plus IFNγ to generate M1-macrophages. Macrophages differentiated in the presence of progastrin presented a reduced expression of Wnt ligands and decreased the number and increased cell death of co-cultured colorectal cancer epithelial cells. Our results suggest that progastrin inhibits the acquisition of a M2-phenotype in human macrophages. This effect exerted on tumor associated macrophages may modulate cancer progression and should be taken into account when analyzing the therapeutic value of gastrin immunoneutralization