Using dispersion models at microscale to assess long-term air pollution in urban hot spots: A FAIRMODE joint intercomparison exercise for a case study in Antwerp.

In the framework of the Forum for Air Quality Modelling in Europe (FAIRMODE), a modelling intercomparison exercise for computing NO2 long-term average concentrations in urban districts with a very high spatial resolution was carried out. This exercise was undertaken for a district of Antwerp (Belgium). Air quality data includes data recorded in air quality monitoring stations and 73 passive samplers deployed during one-month period in 2016. The modelling domain was 800 × 800 m2. Nine modelling teams participated in this exercise providing results from fifteen different modelling applications based on different kinds of model approaches (CFD - Computational Fluid Dynamics-, Lagrangian, Gaussian, and Artificial Intelligence). Some approaches consisted of models running the complete one-month period on an hourly basis, but most others used a scenario approach, which relies on simulations of scenarios representative of wind conditions combined with post-processing to retrieve a one-month average of NO2 concentrations. The objective of this study is to evaluate what type of modelling system is better suited to get a good estimate of long-term averages in complex urban districts. This is very important for air quality assessment under the European ambient air quality directives. The time evolution of NO2 hourly concentrations during a day of relative high pollution was rather well estimated by all models. Relative to high resolution spatial distribution of one-month NO2 averaged concentrations, Gaussian models were not able to give detailed information, unless they include building data and street-canyon parameterizations. The models that account for complex urban geometries (i.e. CFD, Lagrangian, and AI models) appear to provide better estimates of the spatial distribution of one-month NO2 averages concentrations in the urban canopy. Approaches based on steady CFD-RANS (Reynolds Averaged Navier Stokes) model simulations of meteorological scenarios seem to provide good results with similar quality to those obtained with an unsteady one-month period CFD-RANS simulations.

Impact of single and combined local air pollution mitigation measures in an urban environment.

Urban air pollution is one of the most important environmental problems for human health and several strategies have been developed for its mitigation. The objective of this study is to assess the impact of single and combined mitigation measures on concentrations of air pollutants emitted by traffic at pedestrian level in the same urban environment. The effectiveness of different scenarios of green infrastructure (GI), the implementation of photocatalytic materials and traffic low emission zones (LEZ) are investigated, as well as several combinations of LEZ and GI. A wide set of scenarios is simulated through Computational Fluid Dynamics (CFD) modelling for two different wind directions (perpendicular (0°) and 45° wind directions). Wind flow for the BASE scenario without any measure implemented was previously evaluated using wind-tunnel measurements. Air pollutant concentrations for this scenario are compared with the results obtained from the different mitigation scenarios. Reduction of traffic emissions through LEZ is found to be the most effective single measure to improve local air quality. However, GI enhances the effects of LEZ, which makes the combination of LEZ + GI a very effective measure. The effectiveness of this combination depends on the GI layout, the intensity of emission reduction in the LEZ and the traffic diversion in streets surrounding the LEZ. These findings, in line with previous literature, suggest that the implementation of GI may increase air pollutant concentrations at pedestrian level for some cases. However, this study highlights that this negative effect on air quality can turn into positive when used in combination with reductions of local traffic emissions.

Estimates of population exposure to atmospheric pollution and health-related externalities in a real city: The impact of spatial resolution on the accuracy of results.

Health impacts of atmospheric pollution is an important issue in urban environments. Its magnitude depends on population exposure which have been frequently estimated by considering different approaches relating pollutant concentration and population exposed to it. However, the uncertainties due to the spatial resolution of the model used to estimate the pollutant concentration or due to the lack of representativeness of urban air quality monitoring station (AQMS) have not been evaluated in detail. In this context, NO2 annual average concentration at pedestrian level in the whole city of Pamplona (Spain) modelled at high spatial resolution (~1 m) by Computational Fluid Dynamic (CFD) simulations is used to estimate the total population exposure and health-related externalities by using different approaches. Air pollutant concentration and population are aggregated at different spatial resolutions ranging from a horizontal grid cell size of 100 m × 100 m to a coarser resolution where the whole city is covered by only one cell (6 km × 5 km). In addition, concentrations at AQMS locations are also extracted to assess the representativeness of those AQMS. The case with a spatial resolution of 100 m × 100 m for both pollutant-concentration distribution and population data is used as a reference (Base case) and compared with those obtained with the other approaches. This study indicates that the spatial resolution of concentration and population distribution in the city should be 1 km × 1 km or finer to obtain appropriate estimates of total population exposure (underestimations <13%) and health-related externalities (underestimations <37%). For the cases with coarser resolutions, a strong underestimation of total population exposure (>31%) and health-related externalities (>76%) was found. On the other hand, the use of AQMS concentrations can induce important errors due to the limited spatial representativeness, in particular in terms of population exposure.

Estimates of pedestrian exposure to atmospheric pollution using high-resolution modelling in a real traffic hot-spot.

Atmospheric pollution is a very relevant risk for the human health, in particular in urban environments, where most people lives and high levels of pollution are found. Population exposure is traditionally estimated through concentration recorded at air quality monitoring stations (AQMS) or modelled at a spatial resolution of the order of 1 km2. However, these methodologies have limitations in urban areas where strong gradients of concentration, even in the same street, exist. In addition, the movements of pedestrians make difficult to compute reliable estimates of pollutant concentration to which people are exposed to. In this context, the main objective of this study is to estimate the exposure of pedestrians to ambient nitrogen oxides (NOx) concentrations with high spatial resolution in a real urban traffic hot-spot under different methodologies. To achieve this objective, a novel methodology which combines high-resolution NOx concentrations from computational fluid dynamic (CFD) simulations with the pedestrian flows obtained by pedestrian mobility microsimulations is applied to an urban area of Madrid, Spain. High-resolution maps show pedestrian exposure peaks, at bus stops and crosswalks, that cannot be captured by the simpler methods based on spatial average concentration (SAC) or concentration measured in an AQMS. Total daily exposure obtained is 1.19 · 109 person s µg m-3, while SAC and AQMS concentration methods yielded 9-23% and 30-40% lower values. In conclusion, the proposed methodology allows to determine the areas with higher exposure in order to design local strategies to reduce the impact on human health. In addition, from a more general point of view, the total exposure in the studied area is better estimated by using spatial average concentration than through concentration recorded by AQMS. The assessment of the spatial representative of AQMS becomes necessary to use AQMS concentration to evaluate air quality and population exposure of an urban area.

[Development of animal experimental model for bacterial peritonitis]. / Desarrollo de modelo experimental animal de peritonitis bacteriana.

OBJECTIVE: The aim of the study was to develop a model of abdominal sepsis in the experimental animal. METHODS: Sprague-Dawley male rats of 5 weeks (N=39) were used. Initially, a pilot study (N = 9) was performed and distributed in 3 groups with 1cc inoculum of Escherichia coli ATCC 25922 intraperitoneally at concentrations of 10E8, 10E9 and 10E10 CFU. Subsequently, concentrations of 10E10 CFU are used in two groups of 3 rats with dilutions of 10 cc and 15 cc of distilled water respectively. Finally, a randomized trial of 24 rats was started in three treatment groups after intraperitoneal infection: Group I with physiological serum (N = 6), Group II with ceftriaxone (N = 9), Group III with ceftriaxone plus allicin (N = 9). Microbiological samples of blood and peritoneal fluid were made, as well as histopathological study of intraperitoneal organs (liver, diaphragm and peritoneum). RESULTS: Death of 100% of the rats infected with 10E10 E. coli UFC concentration with the dilution of 15 ml of distilled water and without antibiotic was oberved. The blood culture and peritoneal fluid culture was positive for the same strain in all of them. The formation of abscesses on the liver surface and polymorphonuclear infiltration in tissues were observed. CONCLUSIONS: The lethal dose of E. coli is 10E10 CFU diluted in 15 cc distilled water by intraperitoneal injection.

Evaluation of a CFD-based approach to estimate pollutant distribution within a real urban canopy by means of passive samplers.

The distribution of pollutants is spatially heterogeneous within urban streets making difficult to build a realistic concentration map. In this paper, a methodology based on computational fluid dynamic modeling with Reynolds-averaged Navier-Stokes approach is used to compute maps of concentration for a period of several weeks. The methodology is evaluated by comparing simulation results against experimental data from two different campaigns where a large number of passive samplers deployed in an area with heavy vehicular traffic in Madrid (Spain). The evaluation shows that the methodology is able to reproduce the general pattern of several-week averaged pollutant distribution in an urban area with heavy vehicular traffic, resolving the spatial variability up to a resolution of 1-2m. In addition, the model results fit satisfactorily the time evolution of the pollutant concentration measured at an air quality station deployed in the studied area. However, problems were detected close to zones with complex emissions patterns (tunnels, street forks, etc.), where the model compared poorly against passive sampler measurements. A preliminary assessment of the uncertainties induced in the numerical methodology due to consider NO2 as non-reactive pollutant under winter conditions indicates that it would be an acceptable approach for this particular case study. Overall, our analysis contributes to raise the confidence in that approached similar to the one presented in this study can be adopted for dealing with several aspects of the air quality management such as air quality assessment, optimization of the location of measurement stations, and the evaluation of air pollution reduction strategies.

Monitoring the John Cunningham virus throughout natalizumab treatment in multiple sclerosis patients.

BACKGROUND AND PURPOSE: Progressive multifocal leukoencephalopathy (PML) cases have arisen amongst multiple sclerosis patients treated with natalizumab. Our objective was to gain a better understanding of the mechanisms that underlie the John Cunningham virus (JCV) infection which causes PML. METHODS: A study was made of (i) the quarterly JCV DNA levels in peripheral blood mononuclear cells (PBMCs), serum and urine samples in 100 multiple sclerosis patients during their natalizumab treatment (3-39 months), (ii) the association between human leukocyte antigen (HLA) class II and the previous viral detection and (iii) the identification of the JCV variants in those patients suspected of having PML. RESULTS: (i) JCV DNA in PBMCs and/or serum was detected in 23% of our cohort. Patients with an intermittent JCV excretion in urine had a significant increase of the viral load and prevalence in this compartment during natalizumab treatment. (ii) The frequency of the DRB1*07/DQA1*02:01/DQB1*02:02 haplotype tended to be higher in patients with detectable versus undetectable JCV DNA in PBMCs (P(corrected) = 0.108). (iii) The variants in PBMCs and serum of the non-PML patient matched the archetype. In the patient with non-fatal PML, the archetype and the same neurotropic variant in PBMCs, serum and cerebrospinal fluid was identified at the time PML was diagnosed, whereas in the patient with a worse PML prognosis, four neurotropic variants in the three previous compartments were found by the PML diagnosis. CONCLUSIONS: The detection of the neurotropic variant in blood during natalizumab treatment could be critical in the prevention of the development of severe PML, since this variant appears simultaneously with the clinical symptoms of PML and mutates quickly.

Prevención y diagnóstico precoz del melanoma con dermatoscopia: una perspectiva biológica / Dermoscopy in the Prevention and Early Diagnosis of Melanoma: A Biological Perspective

No disponible

Assessment of the reproducibility of oligoclonal IgM band detection for its application in daily clinical practice.

BACKGROUND: The presence of oligoclonal IgM bands (OCMB) in cerebrospinal fluid (CSF) is an unfavourable prognostic marker in multiple sclerosis. There is no commercial test to investigate OCMB status. However, a sensitive and specific isoelectrofocusing (IEF) and western blot method was described. We aimed to study the inter-centre reproducibility of this technique, a necessary condition for a reliable test to be incorporated into clinical practice. METHODS: The presence of OCMB was analysed by IEF and western blot with prior reduction of pentameric IgM. We assayed the reproducibility of this test in a blinded multicentre study performed in 13 university hospitals. Paired-CSF and serum samples from 52 neurological patients were assayed at every centre. RESULTS: Global analysis rendered a concordance of 89.8% with a kappa value of 0.71. CONCLUSION: These data indicate that OCMB detection by means of IEF and western blot with IgM reduction shows a good interlaboratory reproducibility and thus can be used in daily clinical setting.

Future prospects in dermatologic applications of lasers, nanotechnology, and other new technologies.

We review novel technologies with diagnostic and therapeutic applications in dermatology. Among the diagnostic techniques that promise to become part of dermatologic practice in the future are optical coherence tomography, multiphoton laser scanning microscopy, Raman spectroscopy, thermography, and 7-T magnetic resonance imaging. Advances in therapy include novel light-based treatments, such as those applying lasers to new targets and in new wavelengths. Devices for home therapy are also appearing. We comment on the therapeutic uses of plasma, ultrasound, radiofrequency energy, total reflection amplification of spontaneous emission of radiation, light stimulation, and transepidermal drug delivery. Finally, we mention some basic developments in nanotechnology with prospects for future application in dermatology.

Prevalencia de la epidermólisis ampollosa distrófica en España: estudio poblacional usando el método de captura-recaptura con 3 fuentes de datos. Evidencia de la necesidad de mejora en la atención sociosanitaria / Prevalence of Dystrophic Epidermolysis Bullosa in Spain: A Population-Based Study Using the 3-Source Capture-Recapture Method. Evidence of a Need for Improvement in Care

Antecedentes: No existen datos sobre la prevalencia de la epidermólisis ampollosa distrófica en España (EAD). La EAD es una enfermedad rara que conlleva una gran carga para el paciente que la sufre y para el sistema de salud que le atiende. Objetivo: Describir la prevalencia de la EAD en España. Métodos: Hemos empleado datos procedentes de 3 fuentes incompletas de pacientes: departamentos de Dermatología, 2 laboratorios de diagnóstico y la Asociación española de pacientes con epidermólisis ampollosa, DEBRA España, y los hemos combinado usando el método de captura-recaptura. Resultados: Hemos identificado 152 pacientes vivos. La prevalencia estimada de EAD fue de 6,0 casos por millón de habitantes (IC 95%: 4,2-11,8). La prevalencia en niños menores de 18 años fue de 15,3 por millón (IC 95%: 10,4-40,8). De acuerdo con el modelo de captura-recaptura el 77% no son seguidos en unidades de referencia, el 65% no tienen diagnóstico genético y el 76% no pertenecen a DEBRA. Conclusiones: La prevalencia de EAD en España es de 6,0 pacientes por millón de habitantes (IC 95%: 4,2 a 11,8), un número mayor que el estimado en otras zonas del mundo, pero similar a otros encontrados en otros países del Sur de Europa. Este resultado puede ser debido a auténticas variaciones geográficas, o a que los otros registros recogen un número incompleto de casos. La mayoría de los pacientes no son seguidos en unidades de referencia, no tienen diagnóstico genético y no son miembros de la asociación de pacientes, lo cual quiere decir que su situación sociosanitaria es muy mejorable (AU)

Background: Dystrophic epidermolysis bullosa (DEB) is a rare disease that represents a heavy burden for both the patient and the health care system. There are currently no data on the prevalence of DEB in Spain. Objective: To determine the prevalence of DEB in Spain. Methods: We used data from 3 incomplete population-based sources (hospital dermatology departments, diagnostic laboratories performing antigenic mapping, genetic testing or both, and the Spanish Association of Epidermolysis Bullosa Patients [DEBRA]) and combined them using the 3-source capture–recapture methodology. Results: We identified 152 living DEB patients. The estimated prevalence of DEB was 6.0 cases per million (95% CI, 4.2–11.8) in adults and 15.3 (95% CI, 10.4–40.8) in children under 18 years of age. The data indicated that 77% of the patients were not being followed up in specialized centers of reference; 65% had not had a genetic diagnosis, and 76% were not members of DEBRA. Conclusions: The prevalence of DEB in Spain is 6.0 patients per million (95% CI, 4.2–11.8), a figure higher than previous estimates in many areas, but similar to those found in other southern Europe countries. The north–south difference may represent real geographic differences in prevalence, but it might be due to the fact that most of the data come from registries with a lower than expected catchment. Many patients are not being followed up in centers of reference, do not have genetic diagnosis, and are not members of patients’ associations, suggesting that there is room for considerable improvement in their care (AU)

Prevalence of dystrophic epidermolysis bullosa in Spain: a population-based study using the 3-source capture-recapture method. Evidence of a need for improvement in care.

BACKGROUND: Dystrophic epidermolysis bullosa (DEB) is a rare disease that represents a heavy burden for both the patient and the health care system. There are currently no data on the prevalence of DEB in Spain. OBJECTIVE: To determine the prevalence of DEB in Spain. METHODS: We used data from 3 incomplete population-based sources (hospital dermatology departments, diagnostic laboratories performing antigenic mapping, genetic testing or both, and the Spanish Association of Epidermolysis Bullosa Patients [DEBRA]) and combined them using the 3-source capture-recapture methodology. RESULTS: We identified 152 living DEB patients. The estimated prevalence of DEB was 6.0 cases per million (95% CI, 4.2-11.8) in adults and 15.3 (95% CI, 10.4-40.8) in children under 18 years of age. The data indicated that 77% of the patients were not being followed up in specialized centers of reference; 65% had not had a genetic diagnosis, and 76% were not members of DEBRA. CONCLUSIONS: The prevalence of DEB in Spain is 6.0 patients per million (95% CI, 4.2-11.8), a figure higher than previous estimates in many areas, but similar to those found in other southern Europe countries. The north-south difference may represent real geographic differences in prevalence, but it might be due to the fact that most of the data come from registries with a lower than expected catchment. Many patients are not being followed up in centers of reference, do not have genetic diagnosis, and are not members of patients' associations, suggesting that there is room for considerable improvement in their care.

Evolution of flavonoids in Mouratón berries taken from both bunch halves.

Galicia (N.W. Spain) is a Spanish region with several old-traditional winegrowing areas. There are autochthonous grapevine varieties, such as Vitis vinifera L. cv. Mouratón, considered a biodiversity resource in viticulture and an opportunity for Galician sustainable wine production. Therefore, it is necessary to assess the potential of traditional cultivars to produce quality red wines. In this work, anthocyanin and flavonol evolution was followed in red berries from V. vinifera L. cv. Mouratón. The novelty of this study is that grapes were separately collected from two different positions (tips and shoulders) within the cluster, over ripening to examine the effects of berry position within the fruit cluster on the flavonoid compounds. Derivatives of five anthocyanins (malvidin, peonidin, petunidin, delphinidin and cyanidin) and derivatives of six flavonols (quercetin, myricetin, kaempherol, laricitrin isorhamnetin and syringetin) were detected in both positions within the cluster. Dynamic of anthocyanins (from 819 mg/kg to 1206 mg/kg in tips; and from 786 mg/kg to 1077 mg/kg in shoulders) and dynamic of flavonols (from 25mg/kg to 41 mg/kg in tips; and from 18 mg/kg to 21 mg/kg in shoulders) confirmed their upward trends over ripening. Grapes located inside the shoulder bunch receive less sunlight radiation than those located inside the tip bunch and this fact could explain the different accumulation observed for both positions. These results can be useful for winemakers in order to obtain different final red wine quality.

Floral, spicy and herbaceous active odorants in Gran Negro grapes from shoulders and tips into the cluster, and comparison with Brancellao and Mouratón varieties.

Within the framework of a more and more competitive market, the opportunity to obtain different wines from the same variety cultivated in the same vineyard is becoming of increasing importance. In this study the presence of aroma compounds in Gran Negro (Vitis vinifera L.) grapes was investigated in order to obtain its aroma potential fingerprint taking into consideration the separation of apical (tips) and basal (shoulders) berries of the clusters. In the final stages of maturation, differences were searched in the probable alcohol content, total acidity of the must, as well as in the aromatic composition of skin and flesh from shoulder and cluster tip berries. A GC-MS method was used to determine the aromatic composition. The obtained results showed that there was variability for their aromatic composition. These results are promising for those wine cellars that are considering the separation of berries from tips and shoulders of the clusters for the elaboration of wines with different qualities. For the berries from the tips of the clusters, aromatic alcohols and volatile phenols were mainly found in the flesh (15 and 2 times higher than in the skin, respectively); whereas aldehydes and C6 alcohols were mainly in the skin (4 and 3 times higher than in the flesh, respectively). For this reason, it could be recommended to separate berry skin before enzymatic maceration of the berry flesh must. For the berries from the shoulders of the clusters, the group of volatile phenols showed 2 times more concentration in the skin than in the flesh; it could be recommended to maintain berry skin during enzymatic maceration of the must. Overall, the tips showed a 40% lower level of C6 alcohols (contributing to herbaceous nuances). These results from Gran Negro were compared with those of Brancellao and Mouratón cultivars.

Aroma potential of Brancellao grapes from different cluster positions.

In this study the presence of aroma compounds in grapes of Brancellao (Vitis vinifera L.) was investigated in order to obtain its aroma potential fingerprint. It is well known that differences exist in aromatic compounds amongst grapevine varieties at ripening stages. Within the framework of an increasingly competitive market, the chance of obtaining different wines from vines of the same variety grown at the same vineyard is becoming of increasing importance. This can be done through the managing of the vineyard, but also some wineries have assayed the separation of the tip and shoulder berries of the clusters of a specific variety with this objective. In this work it is evaluated that, in the final stages of maturation, differences exist in the probable alcoholic degree, total acidity of the must, as well as in the aromatic composition of skin and flesh of berries coming from the tips and shoulders of the clusters. Gas chromatography coupled to mass spectrometry (GC-MS) was used to determine the aromatic composition, in the skin and flesh of each sample, either tip or shoulder berries from the clusters. The obtained results showed that there was not variability for the probable alcoholic degree and total acidity between the shoulders and tips, whereas there was variability for their aromatic composition. For the berries from the tips of the clusters most of volatiles were found in the flesh (except aldehydes) and spicy and floral nuances (with the only exception of ß-ionone) were in higher proportions. For the berries from the shoulders of the clusters, most of volatiles were found in the skin (monoterpenes, norisoprenoids, aldehydes, and C6 alcohols), where the flesh was slightly richer in aromatic alcohols, volatile phenols and pantolactone; ß-ionone and herbaceous nuances were in higher proportions. These results are promising for those wineries that are considering the chance of separating berries from tips and shoulders of the clusters for the elaboration of different quality wines.

Two novel recessive mutations in KRT14 identified in a cohort of 21 Spanish families with epidermolysis bullosa simplex.

BACKGROUND: Basal epidermolysis bullosa simplex (EBS) is a group of blistering genodermatoses mostly caused by mutations in the keratin genes, KRT5 and KRT14. Recessive mutations represent about 5% of all EBS mutations, being common and specific in populations with high consanguinity, where affected patients show severe phenotypes. OBJECTIVES: To accomplish the first mutational analysis in patients of Spanish origin with EBS and to delineate a comprehensive genotype-phenotype correlation. METHODS: Twenty-one EBS families were analysed. Immunofluorescence mapping at the dermoepidermal junction level was performed on skin biopsies from patients. Mutation screening of the entire coding sequences of KRT5 and KRT14 in genomic DNA was assessed by polymerase chain reaction and direct sequencing. RESULTS: KRT5 or KRT14 causative mutations were identified in 18 of the 21 EBS families. A total of 14 different mutations were disclosed, of which 12 were dominant missense mutations and two truncating recessive mutations. Five of the 14 mutations were novel including three dominant in KRT5 (p.V186E, p.T321P and p.A428T) and two recessive in KRT14 (p.K116X and p.K250RfsX8). The two patients with EBS carrying homozygous recessive mutations were affected by severe phenotypes and belonged to consanguineous families. All five families with the EBS Dowling-Meara subtype carried recurrent mutations affecting the highly conserved ends of the α-helical rod domain of K5 and K14. The seven mutations associated with the localized EBS subtype were widely distributed along the KRT5 and KRT14 genes. Two families with mottled pigmentation carried the P25L mutation in KRT5, commonly associated with this subtype. CONCLUSIONS: This study further confirms the genotype-phenotype correlation established for EBS in other ethnic groups, and is the first in a Mediterranean country (excluding Israel). This study adds two novel recessive mutations to the worldwide record to date, which includes a total of 14 mutations. As in previous reports, the recessive mutations resulted in a lack of keratin K14, giving rise to a generalized and severe presentation.

Polymorphisms in chromosome region 12q13 and their influence on age at onset of type 1 diabetes.

AIMS/HYPOTHESIS: A complex region covering numerous genes in 12q13 was first associated with type 1 diabetes in the Wellcome Trust Case-Control Consortium (WTCCC) study. Two studies performed in a white population have tested the association of polymorphisms within this region with age at onset of the disease, with seemingly contradictory results. We aimed at replicating three of the strongest signals in a group of patients with early and late disease onset. METHODS: Polymorphisms rs773107, rs2292239 and rs10876864 were genotyped in 444 type 1 diabetic Spanish participants (age at onset 0-65 years) and 861 controls. The influence of single nucleotide polymorphisms (SNPs) on age at onset was tested through stratified and continuous analyses. RESULTS: rs773107 and rs2292239 were significantly associated with the disease, while rs10876864 showed a trend towards statistical significance in the whole population analyses. Comparison of early-onset patients to controls was significant for the three polymorphisms (allelic p < 0.006). Late-onset patients and controls did not reveal statistical differences. Analysis of age at onset in both rs773107 and rs2292239 showed differences between genotypes (p ≤ 0.002), alleles (p ≤ 0.013) and homozygotes for the risk genotype (p ≤ 4 × 10(-4)). Polymorphism rs10876864 showed trends towards statistical significance in the allelic frequencies (p = 0.051) and homozygotes for the risk genotype (p = 0.056). Subjects with risk genotypes had a disease onset between 2 and 5 years earlier than carriers of protective alleles. CONCLUSIONS/INTERPRETATION: We replicate two of the previously studied associations in a Spanish population and find new evidence of the influence of the 12q13 region on age at onset of type 1 diabetes.

De novo anti-HLA antibodies in renal allograft recipients: a cross-section study.

BACKGROUND: The occurrence of anti-HLA antibodies plays a well established role in solid organ rejection. The development of x-MAP multiple bead technology (Luminex) has enabled more accurate detection and definition of these alloantibodies. METHODS: In 267 kidney transplant patients with stable allograft function for ≥3 years, we analyzed the presence of anti-HLA antibodies by Luminex technology. These patients had no alloantibodies before transplantation, and the immunosuppression treatment was: tacrolimus, cyclosporine, mycophenolate mofetil, prednisone, everolimus, and/or sirolimus. RESULTS: Fifteen of the 267 patients showed anti-HLA class I antibodies and 12 showed anti-HLA class II antibodies, Seven patients had donor-specific antibodies (DSA): 1 anti-HLA class I, 5 anti-HLA class II, and 1 with both classes. No differences were found between DSA and the use or not of any specific therapy. However, in the retrospective review, we found a higher incidence of acute rejection episodes in the immediate posttransplant period among patients who developed class II DSA than those without DSA. CONCLUSIONS: The prevalence of patients with normal renal function who develop DSA beyond 3 years after transplantation was relatively low. Steroid or withdrawal replacement of calcineurin inhibitors with inhibitors of mammalian target of rapamycin seem to not be risk factors to increase the development of DSA. The finding that patients who developed DSA showed a higher rate of previous acute rejection episodes suggested that they should be monitored more frequently for HLA antibodies.

Association between idiopathic achalasia and IL23R gene.

BACKGROUND: Idiopathic achalasia is a primary esophageal motor disorder of unknown etiology. Different evidences have been reported in support of achalasia as the result of an autoimmune and inflammatory process leading to neuronal cell loss. According to this, idiopathic achalasia has been significantly associated with specific alleles of the human leukocyte antigen system class II, although few reports studying association with other loci can be found in the literature. Recent studies have shown association of a non-synonymous polymorphism within the IL23R gene with different chronic inflammatory disorders, including Barrett's esophagus. The purpose of this study was to assess whether the IL23R coding variant Arg381Gln polymorphism is involved in susceptibility to idiopathic achalasia. METHODS: We performed a case-control study including 262 patients with idiopathic achalasia and 802 healthy subjects, all of them white Spaniards. Achalasia patients were diagnosed on the basis of clinical, radiographic, endoscopic, and manometric criteria. All samples were genotyped for the IL23R Arg381Gln polymorphism using TaqMan technology. KEY RESULTS: The minor allele of the Arg381Gln polymorphism was significantly increased in patients compared with healthy controls (OR = 1.46, 95% CI = 1.01-2.11, P = 0.036). This association seems to be specific to male patients with disease onset after 40 years (OR = 2.33, 95% CI = 1.29-4.16, P = 0.002). CONCLUSIONS & INFERENCES: Our results suggest a role of IL23R in idiopathic achalasia predisposition and extend the evidence of the general influence of this gene in autoimmune and inflammatory diseases.