Variation in Susceptibility to Downy Mildew Infection in Spanish Minority Vine Varieties.

Downy mildew is one of the most destructive diseases affecting grapevines (Vitis vinifera L.). Caused by the oomycete Plasmopara viticola (Berk. and Curt.) Berl. and de Toni, it can appear anywhere where vines are cultivated. It is habitually controlled by the application of phytosanitary agents (copper-based or systemic) at different stages of the vine growth cycle. This, however, is costly, can lead to reduced yields, has a considerable environmental impact, and its overuse close to harvest can cause fermentation problems. All grapevines are susceptible to this disease, although the degree of susceptibility differs between varieties. Market demands and European legislation on viticulture and the use of phytosanitary agents (art. 14 of Directive 128/2009/EC) now make it important to know the sensitivity of all available varieties, including minority varieties. Such knowledge allows for a more appropriate use of phytosanitary agents, fosters the commercial use of these varieties and thus increases the offer of wines associated with different terroirs, and helps identify material for use in crop improvement programmes via crossing or genetic transformation, etc. Over 2020-2021, the susceptibility to P. viticola of 63 minority vine varieties from different regions of Spain was examined in the laboratory using the leaf disc technique. Some 87% of these varieties were highly susceptible and 11% moderately susceptible; just 2% showed low susceptibility. The least susceptible of all was the variety Morate (Madrid, IMIDRA). Those showing intermediate susceptibility included the varieties Sanguina (Castilla la Mancha, IVICAM), Planta Mula (Comunidad Valenciana, ITVE), Rayada Melonera (Madrid, IMIDRA), Zamarrica (Galicia, EVEGA), Cariñena Roja (Cataluña, INCAVI), Mandrègue (Aragón, DGA) and Bastardo Blanco (Extremadura, CICYTEX). The highly susceptible varieties could be differentiated into three subgroups depending on sporulation severity and density.

Genome-wide association study biomarkers in T-cell mediated rejection: selective effect according to the Banff classification.

BACKGROUND: A genome-wide association study (GWAS) in kidney transplant recipients reported the association of two polymorphisms located in the PTPRO gene and upstream of the CCDC67 (DEUP1) gene with increased risk of acute T cell-mediated rejection (TCMR). We aimed at replicating the assessment of mentioned associations and additionally ascertaining the influence of treatment and clinical features of the patients. METHODS: The polymorphisms, PTPRO-rs7976329 and CCDC67-rs10765602 were genotyped by TaqMan chemistry in 641 consecutive kidney transplant recipients. The diagnosis of rejection was confirmed by biopsy and categorized according to the Banff classification. Associations were evaluated by Chi-square test or Fisher's exact test when necessary and multivariate logistic regression. RESULTS: Considering the GWAS study we only replicated the association of the PTPRO-rs7976329*C allele in the Banff grade < II subjects. However, the homozygous mutant genotypes of both polymorphism seemed to increase the risk of TCMR Banff grade < II in the overall cohort and after stratification by Thymoglobulin induction therapy. In the multivariate analysis, we confirmed the association of PTPRO-rs7976329 with TCMR Banff grade < II, independently of the Thymoglobulin induction therapy and of CCDC67-rs10765602 only in the group of patients not receiving Thymoglobulin induction therapy. No association of these polymorphisms with TCMR Banff grade ≥ II was observed in either the overall cohort or in the subgroups stratified by Thymoglobulin therapy. CONCLUSIONS: Our study shows that the increased risk of TCMR related to polymorphisms PTPRO-rs7976329 and CCDC67-rs10765602 previously reported in a GWAS was replicated only in homozygous patients who presented TCMR Banff grade < II and for the minor allele of either polymorphism.

Evaluation and Pre-selection of New Grapevine Genotypes Resistant to Downy and Powdery Mildew, Obtained by Cross-Breeding Programs in Spain.

The need to develop an environmentally friendly, sustainable viticulture model has led to numerous grapevine improvement programmes aiming to increase resistance to downy and powdery mildew. The success of such programmes relies on the availability of protocols that can quantify the resistance/susceptibility of new genotypes, and on the existence of molecular markers of resistance loci that can aid in the selection process. The present work assesses the degree of phenotypic resistance/susceptibility to downy and powdery mildew of 28 new genotypes obtained from crosses between "Monastrell" and "Regent." Three genotypes showed strong combined resistance, making them good candidates for future crosses with other sources of resistance to these diseases (pyramiding). In general, laboratory and glasshouse assessments of resistance at the phenotype level agreed with the resistance expected from the presence of resistance-associated alleles of simple sequence repeat (SSR) markers for the loci Rpv3 and Ren3 (inherited from "Regent"), confirming their usefulness as indicators of likely resistance to downy and powdery mildew, respectively, particularly so for downy mildew.

Co-Adjuvant Therapy Efficacy of Catechin and Procyanidin B2 with Docetaxel on Hormone-Related Cancers In Vitro.

Prostate (PC) and breast cancer (BC) are heterogeneous hormonal cancers. Treatment resistance and adverse effects are the main limitations of conventional chemotherapy treatment. The use of sensitizing agents could improve the effectiveness of chemotherapeutic drugs as well as obviate these limitations. This study analyzes the effect of single catechin (CAT), procyanidin B2 (ProB2) treatment as well as the co-adjuvant treatment of each of these compounds with docetaxel (DOCE). We used PC- and BC-derived cell lines (PC3, DU-145, T47D, MCF-7 and MDA-MB-231). The short and long-term pro-apoptotic, anti-proliferative and anti-migratory effects were analyzed. RT-qPCR was used to discover molecular bases of the therapeutic efficacy of these compounds. ProB2 treatment induced a two- to five-fold increase in anti-proliferative and pro-apoptotic effects compared to single DOCE treatment, and also had a more sensitizing effect than DOCE on DU145 cells. Regarding BC cells, ProB2- and CAT-mediated sensitization to DOCE anti-proliferative and pro-apoptotic effects was cell-independent and cell-dependent, respectively. Combined treatment led to high-efficacy effects on MCF-7 cells, which were associated to the up-regulation of CDKN1A, BAX, caspase 9 and E-cadherin mRNA under combined treatment compared to single DOCE treatment. CAT and ProB2 can enhance the efficacy of DOCE therapy on PC and BC cells by the sensitizing mechanism.

Association of Polymorphisms in T-Cell Activation Costimulatory/Inhibitory Signal Genes With Allograft Kidney Rejection Risk.

The genes CD28, CD86 and CTLA-4 conform the costimulatory (CD28-CD86) or inhibitory (CTLA-4-CD86) signal in T-cell activation. T-cell immune response has a critical role in allograft rejection, and single nucleotide polymorphisms (SNPs) located in these genes have been widely analyzed with controversial results. We analyzed a group of SNPs located in the three genes: CD28: rs3116496; CD86: rs1129055; and CTLA-4: rs231775 and rs3087243 in a cohort of 632 consecutively recruited kidney transplanted subjects. All polymorphisms were genotyped by TaqMan chemistry and the diagnosis of rejection was confirmed by biopsy and categorized according to the Banff classification. The analyses showed a statistically significant protective effect to T cell-mediated rejection (TCMR) in carriers of the CTLA-4 rs3087243*G allele, especially in patients with TCMR Banff ≥2 in the overall cohort and in patients without thymoglobulin induction therapy. Both associations were corroborated as independent factors in the multivariate analysis. Interestingly, associations with rejection were not found for any SNP in patients with thymoglobulin induction therapy. As expected, considering the major role of these genes in T-cell activation, no effect was observed for antibody-mediated rejection (ABMR). In conclusion, the SNP rs3087243 located in the CTLA-4 gene may be considered a useful independent biomarker for TCMR risk especially for severe TCMR in patients who did no received thymoglobulin induction therapy.

Hypercytokinemia in COVID-19: Tear cytokine profile in hospitalized COVID-19 patients.

The aim of this study is to analyze the concentrations of cytokines in tear of hospitalized COVID-19 patients compared to healthy controls. Tear samples were obtained from 41 healthy controls and 62 COVID-19 patients. Twenty-seven cytokines were assessed: interleukin (IL)-1b, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL9, IL-10, IL-12, IL-13, IL-15, IL-17, eotaxin, fibroblast growth factor basic, granulocyte colony-stimulating factor (G-CSF), granulocyte-monocyte colony-stimulating factor (GM-CSF), interferon (IFN)-γ, interferon gamma-induced protein, monocyte chemo-attractant protein-1, macrophage inflammatory protein (MIP)-1a, MIP-1b, platelet-derived growth factor (PDGF), regulated on activation normal T cell expressed and secreted, tumor necrosis factor-α and vascular endothelial growth factor (VEGF).In tear samples of COVID-19 patients, an increase in IL-9, IL-15, G-CSF, GM-CSF, IFN-γ, PDGF and VEGF was observed, along with a decrease in eotaxin compared to the control group (p < 0.05). A poor correlation between IL-6 levels in tear and blood was found. IL-1RA and GM-CSF were significantly lower in severe patients and those who needed treatment targeting the immune system (p < 0.05). Tear cytokine levels corroborate the inflammatory nature of SARS-CoV-2.

Narcea-an unknown, ancient cultivated rose variety from northern Spain.

The present work reports the discovery and the complete characterisation of an ancient cultivated rose variety found growing in a private garden in the southwest of the Principality of Asturias (northern Spain). The variety is here given the name Narcea. The majority of roses currently cultivated belong to the so-called group of 'Modern Roses', all of which were obtained after 1867 via artificial crosses and improvement programmes. All are destined for ornamental use. Until the 19th century, the great majority of the many ancient cultivated roses in Europe were used in perfumery and cosmetics, or had medicinal uses. Rosa damascena and Rosa centifollia are still grown and used by the French and Bulgarian perfume industries. The Asturian Massif of the Cantabrian Mountain Range provides a natural habitat for some 75% of the wild members of the genus Rosa, but until now there was no evidence that this area was home to ancient cultivated roses. A complete botanical description is here provided for a discovered ancient rose. It is also characterised according to a series of sequence tagged microsatellite sites, and its agronomic features are reported. In addition, a histological description (optical and scanning electronic microscope studies) of the petals is offered, along with an analysis of the volatile compounds present in these organs as determined by solid phase microextraction and gas chromatography-mass spectroscopy. The results reveal the uniqueness of this ancient type of rose and suggest it may be of interest to the perfume industry.

Impacts of Interleukin-18 Polymorphisms on the Incidence of Delayed-Onset Cytomegalovirus Infection in a Cohort of Kidney Transplant Recipients.

BACKGROUND: The incidence of cytomegalovirus (CMV) infection in solid organ transplant recipients may be reduced by antiviral prophylaxis, but this strategy may lead to delayed-onset CMV infection. The proinflammatory cytokine interleukin (IL)-18 plays a major role in viral host defense responses. This study examines the impacts of 2 single-nucleotide polymorphisms (SNPs) in the promoter region of the IL-18 gene, -607C/A (rs1946518) and -137G/C (rs187238), on the incidence of delayed-onset CMV infection in patients undergoing kidney transplant. METHODS: This retrospective study analyzed 2 IL-18 SNPs in consecutive adult kidney transplant recipients using real-time polymerase chain reaction with TaqMan probes. Participants were enrolled over the period 2005-2013 and stratified according to their IL-18 SNP genotype. The concordance index (Harrell's c-index) was used as a measure of the discriminatory power of the predictive models constructed with bootstrapping to correct for optimistic bias. RESULTS: Seven hundred nine patients received transplants in the study period, and 498 met selection criteria. Cytomegalovirus infection and disease incidence were 38% and 7.5%, respectively. In multivariate competing risk regression models, carriers of the -607C/-137G haplotype who received prophylaxis showed a higher incidence of CMV replication after antiviral agent discontinuation (hazard ratio = 2.42 [95% confidence interval, 1.11-5.26]; P = .026), whereas CMV disease was not observed in those given prophylaxis who were noncarriers of this polymorphism (P = .009). CONCLUSIONS: Our findings suggest that the -607C/-137G IL-18 haplotype is associated with a higher incidence of postprophylaxis CMV replication. The prior identification of this polymorphism could help select alternative measures to prevent delayed-onset CMV infection in these patients.

Factors Affecting the Vineyard Populational Diversity of Plasmopara viticola.

Vitis vinifera is very susceptible to downy mildew (Plasmopara viticola). A number of authors have suggested different genetic populations of this fungus exist in Europe, each showing a different degree of virulence. Work performed to date indicates this diversity to be the result of different factors. In areas where gene flow is greater and recombination more frequent, the diversity of P. viticola appears to be wider. In vineyards isolated by geographic barriers, a race may become dominant and produce clonal epidemics driven by asexual reproduction. The aim of the present work was to identify the conditions that influence the genetic diversity of P. viticola populations in the vineyards of northwestern Spain, where the climatic conditions for the growth of this fungus are very good. Vineyards situated in a closed, narrow valley of the interior, in more open valleys, and on the coast were sampled and the populations of P. viticola detected were differentiated at the molecular level through the examination of microsatellite markers. The populations of P. viticola represented in primary and secondary infections were investigated in the same way. The concentration of airborne sporangia in the vegetative cycle was also examined, as was the virulence of the different P. viticola populations detected. The epidemiological characteristics of the fungus differed depending on the degree of isolation of the vineyard, the airborne spore concentration, and on whether the attack was primary or secondary. Strong isolation was associated with the appearance of dominant fungal races and, therefore, reduced populational diversity.

The Interferon-Gamma +874 A/T Polymorphism Is Not Associated With CMV Infection After Kidney Transplantation.

The +874 A/T polymorphism in the interferon gamma (IFNG) gene has been associated with Cytomegalovirus (CMV) infection risk in lung and kidney transplant recipients. To replicate this association, we performed a retrospective observational study of this polymorphism and immunosuppressive therapies considering the prophylactic treatment in 600 consecutive kidney transplanted recipients. We found no association of the aforementioned polymorphism with CMV infection in univariate and multivariate analyses regardless of the prophylactic treatment. In addition, the immunosuppressive treatment with mammalian target of rapamycin inhibitors (imTOR) showed a protective effect in all patients independently of prophylaxis. Moreover, in the adjusted model, we found interactions between prophylaxis with high-risk (Donor+/Recipient-, D+/R-) status (p-interaction = 0.01), with thymoglobulin induction therapy (p-interaction = 0.03) and with thymoglobulin anti-rejection therapy (p-interaction = 0.002). Data also revealed that prophylaxis was not an advantage in the not D+/R- and without thymoglobulin therapy group (HR = 0.98, p = 0.95). The benefit of prophylaxis was observed in all groups with thymoglobulin therapy, but it was maximal in the high-risk CMV infection group with both thymoglobulin induction therapy and thymoglobulin anti-rejection therapy (HR = 0.01, p < 0.001). In conclusion, the IFNG +874 polymorphism is not a predictive marker of CMV infection. The protective effect of imTOR is not improved with prophylaxis. Interestingly, the thymoglobulin therapy associated with prophylaxis is not a risk factor for CMV infection, and prophylaxis is not effective in recipients with no high-risk CMV status and without thymoglobulin therapy.

CFD modelling of air quality in Pamplona City (Spain): Assessment, stations spatial representativeness and health impacts valuation.

A methodology based on CFD-RANS simulations (WA CFD-RANS, Weighted Averaged Computational Fluid Dynamic-Reynolds-Averaged Navier-Stokes simulations) which includes appropriate modifications, has been applied to compute the annual, seasonal, and hourly average concentration of NO2 and NOX throughout the city of Pamplona (Spain) at pedestrian level during 2016. The results have been evaluated using measurements provided both by the city's network of air quality monitoring stations and by a network of mobile microsensors carried around by cyclists during their daily commutes, obtaining a maximum relative error lower than 30% when computing NO2 annual average concentrations. The model has taken into account the actual city layout in three dimensions, as well as the traffic emissions. The resulting air pollution maps provided information critical for studying the traffic-related health effects of NO2 and their associated external costs in the city of Pamplona and the spatial representativeness of the current network of air quality monitoring stations (it has not been carried out for an entire city to date). The developed methodology can be applied to similar cities, providing useful information for the decision-makers.

Application of a short term air quality action plan in Madrid (Spain) under a high-pollution episode - Part II: Assessment from multi-scale modelling.

Air pollution continues to be one of the main issues in urban areas. In addition to air quality plans and emission abatement policies, additional measures for high pollution episodes are needed to avoid exceedances of hourly limit values under unfavourable meteorological conditions such as the Madrid's short-term action NO2 protocol. In December 2016 there was a strong atmospheric stability episode that turned out in generalized high NO2 levels, causing the stage 3 of the NO2 protocol to be triggered for the first time in Madrid (29th December). In addition to other traffic-related measures, this involves access restrictions to the city centre (50% to private cars). We simulated the episode with and without measures under a multi-scale modelling approach. A 1 km2 resolution modelling system based on WRF-SMOKE-CMAQ was applied to assess city-wide effects while the Star-CCM+ (RANS CFD model) was used to investigate the effect at street level in a microscale domain in the city centre, focusing on Gran Vía Avenue. Changes in road traffic were simulated with the mesoscale VISUM model, incorporating real flux measurements during those days. The corresponding simulations suggest that the application of the protocol during this particular episode may have prevented concentrations to increase by 24 µg·m-3 (14% respect to the hypothetical no action scenario) downtown although it may have cause NO2 to slightly increase in the city outskirts due to traffic redistribution. Speed limitation and parking restrictions alone (stages 1 and 2 respectively) have a very limited effect. The microscale simulation provides consistent results but shows an important variability at street level, with reduction above 100 µg·m-3 in some spots inside Gran Vía. Although further research is needed, these results point out the need to implement short-term action plans and to apply a consistent multi-scale modelling assessment to optimize urban air quality abatement strategies.

The Polymorphism -308G/A of Tumor Necrosis Factor-α Gene Modulates the Effect of Immunosuppressive Treatment in First Kidney Transplant Subjects Who Suffer an Acute Rejection.

The -308G/A SNP of tumor necrosis factor-alpha (TNF-α) gene affects TNF-α production. As its impact on transplant outcome remains open to debate, we decided to genotype it in a cohort of transplant subjects. A retrospective analysis of 439 first kidney recipients randomly divided into two subgroups (discovery and validation cohorts) was performed to identify the best predictors of acute rejection (AR). The effect on transplant outcome was analyzed by an adjusted logistic regression model. Carriers of the A allele, associated with elevated TNF-α production, presented a higher risk of AR (OR = 2.78; 95% CI = 1.40-5.51). Logistic regression analyses for AR showed an interaction between the polymorphism and treatment with thymoglobulin (p-interaction = 0.03). In recipients who did not receive thymoglobulin, carriers of A allele had higher risk of AR (OR = 4.05; 95% CI = 1.76-9.28). Moreover, carriers of A allele not treated with thymoglobulin presented higher risk of AR than those who received thymoglobulin (OR = 13.74; 95% CI = 1.59-118.7). The AUC of the model in the discovery cohort was 0.70 and in the validation cohort was 0.69. Our findings indicate that the -308G/A TNF-α polymorphism is associated with AR risk and it modulates the effectiveness of thymoglobulin treatment. This pharmacogenetic effect lets us propose this SNP as a useful predictor biomarker to tailor immunosuppressive regimens.

Clinical implications of different biomarkers in elderly patients with heart failure.

AIMS: The aim of this article was to determine the importance of neuroendocrine and inflammatory biomarkers in elderly patients (>70 years) with heart failure (HF). METHODS: In this retrospective and observational study, TNF-α, IL-6, IL-18, Fas (Apo1), BNP, C-reactive protein and cystatin C values were calculated, as well as the relationship between them and the clinical evolution of patients. RESULTS: A total of 124 patients (mean age ± standard deviation: 83±5 years) were included. After a mean follow-up of 2.4 years, 40.3% of patients were hospitalized for HF and 15.3% of patients died. Those patients who were hospitalized for HF compared with those that did not were hospitalized for HF showed higher values of IL-6 (9.8±13.1 vs 4.65±5.8 pg/ml; p=0.003) and those who died compared with those who are alive higher values of IL-18 (437.1±137.4 vs 299.7±167.2 pg/ml; p=0.01), C-reactive protein (12.6±19.4 vs 6.1±9.4 mg/l; p=0.03), BNP (704.2±428.6 vs 418.5±410.6 pg/ml; p=0.008) and cystatin C (1.76±0.6 vs 1.45±0.5 mg/l; p=0.04). In the multivariate analysis, only IL-18 (hazard ratio: 1.4; 95% CI: 1.05-1.8; p=0.027) remained as an independent predictor for mortality. CONCLUSION: In elderly patients with HF, the determination of biomarkers may be helpful to establish those patients at higher risk.

Importance of Bnp changes during the follow-up in elderly outpatients with heart failure.

BACKGROUND: The aim of the present study was to analyze whether absolute BNP and relative BNP change values during follow-up of elderly patients with chronic HF could predict the development of acute decompensated episodes. METHODS AND RESULTS: A total population of 108 elderly outpatients with the diagnosis of HF was retrospectively reviewed. Available BNP levels after at least one stable visit and one acute decompensated episode were required. Follow-up period was 12 months (343 visits, 42.6% decompensated HF episodes). Relative BNP changes were analyzed: "CC period" (patients who remained stable) and "CD period" (patient who suffered from a decompensated HF episode). Changes in BNP levels were significantly higher in CD than in CC periods (mean and median differences 138% and 85%, vs 16% and 0%, respectively; p<0.001). The clinical model (AUC=0.83) had a sensitivity of 67.06%, and a specificity of 80.36%. Relative BNP change (29%) showed by itself, a similar AUC (0.83) and specificity (79%) and an improved sensitivity (0.80) than the clinical model. When relative BNP change was introduced at the clinical model, a similar specificity was obtained and the diagnostic accuracy, AUC (0.89 vs 0.83, p=0.01) and sensitivity were improved. Absolute BNP changes showed worse AUC than that derived from relative BNP changes or clinical assessment. CONCLUSIONS: Percent BNP change values during the follow-up showed better results than absolute BNP values and improved the clinical assessment for diagnostic of decompensated HF episodes in elderly outpatients.

Different impact of pretransplant anti-HLA antibodies detected by Luminex in highly sensitized renal transplanted patients.

It is well know that anti-HLA antibodies are an important obstacle in kidney transplantation. Our aim was to study the clinical impact of pretransplant donor specific anti-HLA antibodies (HLA-DSA), in highly sensitized (HS) patients. We analyzed retrospectively the day-of-transplant sera by Luminex Single Antigen Assay (LSA) in HS patients, and the results were correlated with episodes of humoral and cellular rejection as well as with graft and patient survival. All HS subjects received the same induction therapy and rejection episodes were biopsy proven. Thirteen patients (56.5%) preformed HLA-DSA, and we observed higher incidence of acute rejection in aforementioned patients than in the pre-transplant negatives DSA recipients (77% versus 30%, P = 0.03). The one-year graft survival was significantly reduced in positive pre-transplant HLA-DSA patients (60% versus 100%, P = 0.01 Breslow). The positive predicted value of HLA-DSA in relation to rejection reached 100% if patients lost their previous graft in the first year after transplant. Among anti-HLA antibodies present in patients before transplant, HLA-DSA were significantly associated with high risk of acute humoral and cellular rejection and reduced graft survival in posttransplant outcome. The negative impact of these antibodies was even higher when patients suffered an early loss of the previous transplant.

Classification and characterization of different white grape juices by using a hybrid electronic tongue.

A multisensor system combined with multivariate analysis is applied for the characterization and classification of white grape juices. The proposed system, known as hybrid electronic tongue, consists of an array of electrochemical microsensors and a colorimetric optofluidic system. A total of 25 white grape juices representing the large variability of vines grown in the Northwest Iberian Peninsula were studied. The data obtained were treated with Principal Component Analysis (PCA) and Soft Independent Modeling Class Analogy (SIMCA). The first tool was used to train the system with the reference genotypes -Albariño, Muscat à Petit Grains Blanc and Palomino- and the second to study the feasibility of the hybrid electronic tongue to distinguish between different grape juice varieties. The results show that the three reference genotypes are well differentiated in the PCA model and this can be used to interpolate the rest of varieties and predict their basic characteristics. Besides, using the SIMCA, the system demonstrates high potential for classifying and discriminating grape varieties.

A computational fluid dynamic modelling approach to assess the representativeness of urban monitoring stations.

Air quality measurements of urban monitoring stations have a limited spatial representativeness due to the complexity of urban meteorology and emissions distribution. In this work, a methodology based on a set of computational fluid dynamics simulations based on Reynolds-Averaged Navier-Stokes equations (RANS-CFD) for different meteorological conditions covering several months is developed in order to analyse the spatial representativeness of urban monitoring stations and to complement their measured concentrations. The methodology has been applied to two urban areas nearby air quality traffic-oriented stations in Pamplona and Madrid (Spain) to analyse nitrogen oxides concentrations. The computed maps of pollutant concentrations around each station show strong spatial variability being very difficult to comply with the European legislation concerning the spatial representativeness of traffic-oriented air quality stations.

Lack of association between the functional c-kit rs6554199 polymorphism and achalasia in a Spanish population.

A functional polymorphism (rs6554199) located in the c-kit gene was associated with achalasia in a Turkish cohort. Our aim was to replicate this result in a large cohort of Spanish patients and controls. A case-control study was performed with 282 Spanish white unrelated patients and 687 healthy controls. All were genotyped for SNP rs6554199 using a TaqMan Assay. No association was found in our study (T allele frequency in patients and controls: 47.3% vs. 49.4%; OR=0.92, p=0.41). The finding that the T allele of the c-kit rs6554199 polymorphism could be associated with achalasia as reported in a Turkish population could not be replicated in a Spanish cohort. Although ethnic differences might explain these data, the sample size that compromised the statistical power in the Turkish cohort and is higher in our study, led us to suggest that the reported association seems to be a false positive.