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Debido al largo proceso administrativo que habitualmente sigue en España el proyecto y construcción de las grandes obras públicas, ha ocurrido algunas veces que, una vez establecido un trazado o un emplazamiento, resulta extremadamente difícil y costoso cambiarlo sustancialmente, incluso aunque los estudios posteriores demuestren la existencia de una geología problemática. En algunas ocasiones, los aspectos geológicos no han tenido la suficiente profundidad en las primeras etapas de proyecto (anteproyecto, estudio de factibilidad, estudio informativo): podrían citarse ejemplos de obras en las que el presupuesto inicial se ha triplicado por problemas geológicos no detectados en las primeras fases de estudio. En este trabajo, pretendemos dar a conocer un ejemplo de lo contrario, como (y gracias a una serie de dilaciones en proceso administrativo), ha sido posible variar sustancialmente el trazado de una línea ferroviaria en fase temprana de proyecto, evitando un terreno salino muy desfavorable.

The COVID-19 pandemic ushered in a shift to a video format for pain medicine fellowship interviews for the 2021-2022 academic year, which represented a major change in the fellowship interview paradigm.Our aim was to assess the experience of a video-only format in place of in-person interviews for Pain Medicine fellowship program directors and applicants after the 2020 fellowship interview season to determine the feasibility for continuation beyond COVID-19 travel restrictions.Survey via Qualtrics.Academic pain medicine programs.A consortium of program directors converged to discuss methods for determining the effectiveness and future direction of the video format for pain medicine fellowship interviews. Two surveys were formulated, one targeting pain medicine fellowship program directors and the other for candidates interviewing for the year 2021-2022.For applicants, 55 out of 170 responded for a response rate of 32.3%, and for program directors, 38 out of 95 responded for a response rate of 40%. Of the applicants, 45.7% stated that they would prefer video interviews, whereas 27.3% of program directors preferred video interviews. Savings of time and money were the most common reason for preferring video interviews.The number of pain fellowship applicants invited was limited to those who interviewed at a subset of pain fellowships, which may not have been representative of all pain fellow applicants.The video format for pain medicine fellowship interviews was viewed positively by both candidates and program directors. We suspect that the video format alone or as a part of a hybrid model will become a routine method for the interview process in the future, given its time and cost benefits.

Background The aim of the BSP090 project is the establishment of European Pharmacopoeia Chemical Reference Substances (CRSs) in combination with corresponding standard ELISA methods for quantification of major allergens in allergen products. Here, we present data of a Phl p 5-specific sandwich ELISA that proved suitable for the quantification of Phl p 5, one of the major Timothy grass (Phleum pratense) pollen allergens. Methods A Phl p 5-specific ELISA system was assessed with respect to accuracy, precision, inter-assay (within laboratory) and inter-laboratory variations, in a ring trial including 14 laboratories in Europe and the USA. Model samples containing recombinant Phl p 5a CRS as well as native grass pollen extracts were analysed. Each participant was instructed to perform at least one preliminary assay to familiarise with the protocol, followed by three independent assays. Results The candidate standard ELISA proved suitable to quantify recombinant and native Phl p 5 with satisfactory precision (93% of results within ±30% acceptance range). Inter-assay variation (max. GCV 24%) and especially inter-laboratory variation (max. GCV 13%) showed conclusive results. When assessing accuracy by means of recovery of recombinant spikes from a grass pollen extract matrix, similarly satisfactory spike recovery results were observed for the two spikes with higher concentrations (all within ±30% acceptance range), whereas recovery of the lowest concentration spike was slightly poorer with mean results of six laboratories exceeding acceptance range. Conclusions Based on the collaborative study results, the assessed Phl p 5-specific immunoassay is appropriate to be proposed as European Pharmacopoeia standard method.

Objective To determine the outcomes of chronic hepatitis B virus (HBV) infection in a large, prospectively studied cohort of children in the US and Canada. Study design This was a prospective, observational study of children with chronic HBV enrolled in 7 clinical centers and evaluated at baseline, weeks 24 and 48, and annually thereafter, with analysis of demographic, clinical, physical examination, and blood test data. Results Among 362 children followed for a median of 4.2 years, elevated alanine aminotransferase (ALT) levels (>1 upper limit of normal) were present in 72% at last evaluation, including in 60% of children with loss of hepatitis B e antigen during follow-up and 70% of those who were hepatitis B e antigen negative at baseline. Significant ALT flares (male patients ≥400 U/L, female patients ≥350 U/L) occurred in 13 children. Of 129 children who fulfilled the American Association for the Study of Liver Diseases treatment criteria during follow-up, anti-HBV treatment was initiated in only 25. One child died (unrelated to liver disease), 1 developed cirrhosis, but no episodes of cirrhotic decompensation or hepatocellular carcinoma were observed. Decline in platelet count was inversely associated with ALT elevations. Conclusions In a cohort of children with chronic HBV infection in the US and Canada, many children remained at risk of progressive liver disease due to active hepatitis, but major clinical outcomes such as cirrhosis, cancer, and death were rare. Many children who met criteria for treatment remained untreated.

The aim of this study was to purify potential allergenic components of Vespa velutina venom, the yellow legged Asian Hornet, and perform a preliminary characterization of the purified proteins. Starting from the whole venom of V.velutina, several chromatographic steps allowed to purify the phospholipase (named Vesp v 1), as well as the antigen 5 (Vesp v 5, the only allergenic component described as such so far). The two hyaluronidase isoforms found (Vesp v 2A and Vesp v 2B) cannot be separated from each other, but they are partially purified and characterized. Purity of the isolated proteins in shown by SDSPAGE, as well as by the results of the N-terminal sequencing. This characterization and nLC-MS/MS data provide most of the sequence for Vesp v 1 and Vesp v 5 (72 and 84% coverage, respectively), confirming that the whole sequences of the isolated natural components match with the data available in public transcriptomic databases. It is of particular interest that Vesp v 1 is a glycosylated phospholipase, a fact that had only described so far for the corresponding allergen components of Dolichovespula maculata and Solenopsis invicta.The availability of the complete sequences of Vespa velutina components permits comparison with homologous sequences from other Hymenoptera. These data demonstrate the higher similarity among the species of the genera Vespa and Vespula, in comparison to Polistes species, as it is especially observed with the hyaluronidases isoforms: the isoform Vesp v 2A only exists in the former genera, and not in Polistes; in addition, the most abundant isoform (Vesp v 2B) exhibits 93% sequence identity with the Ves v 2 isoform of Vespula vulgaris.Finally, the isolated components might be useful for improving the diagnosis of patients that could be allergic to stings of this invasive Asian hornet, as it has been the case of an improved diagnosis and treatment of other Hymenoptera-sensitized patients.Data Availability StatementProteomic study data are deposited and made available publicly when data are published with the ProteomeExchange identifier PXD015381 in the Mass spectrometry Interactive Virtual Environment (MassIVE).Allergen nomenclature for Vesp v 5 (and also for any future demonstrated allergen from Vespa velutina) has been approved by the WHO/IUIS Committee (www.allergen.org); when this manuscript is accepted, the WHO/IUIS Committee will be informed so that the complete sequences included in this manuscript are also included in their database (with links to the UNIPROT database, who will also be informed that the data can be made public).

Objective The aim of the study was to define chronic HBV phenotypes in a large, cohort of United States and Canadian children utilizing recently published population-based upper limit of normal alanine aminotransferase levels (ULN ALT), compared with local laboratory ULN; identify relationships with host and viral factors. Background Chronic hepatitis B virus (HBV) infection has been characterized by phases or phenotypes, possibly associated with prognosis and indications for therapy. Methods Baseline enrollment data of children in the Hepatitis B Research Network were examined. Phenotype definitions were inactive carrier: HBeAg-negative with low HBV DNA and normal ALT levels; immune-tolerant: HBeAg-positive with high HBV DNA but normal ALT levels; or chronic hepatitis B: HBeAg-positive or -negative with high HBV DNA and abnormal ALT levels. Results Three hundred seventy-one participants were analyzed of whom 274 were HBeAg-positive (74%). Younger participants were more likely be HBeAg-positive with higher HBV DNA levels. If local laboratory ULN ALT levels were used, 35% were assigned the immune tolerant phenotype, but if updated ULN were applied, only 12% could be so defined, and the remaining 82% would be considered to have chronic hepatitis B. Among HBeAg-negative participants, only 21 (22%) were defined as inactive carriers and 14 (14%) as HBeAg-negative chronic hepatitis B; the majority (61%) had abnormal ALT and low levels of HBV DNA, thus having an indeterminant phenotype. Increasing age was associated with smaller proportions of HBeAg-positive infection. Conclusions Among children with chronic HBV infection living in North America, the immune tolerant phenotype is uncommon and HBeAg positivity decreases with age.

Background The extent of coronary disease affects clinical outcomes and may predict the effectiveness of coronary revascularization with either coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score quantifies the extent of coronary disease. Objectives This study sought to determine whether SYNTAX scores predicted outcomes and the effectiveness of coronary revascularization compared with medical therapy in the BARI-2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial. Methods Baseline SYNTAX scores were retrospectively calculated for BARI-2D patients without prior revascularization (N = 1,550) by angiographic laboratory investigators masked to patient characteristics and outcomes. The primary outcome was major cardiovascular events (a composite of death, myocardial infarction, and stroke) over 5 years. Results A mid/high SYNTAX score (≥23) was associated with a higher risk of major cardiovascular events (hazard ratio: 1.36, confidence interval: 1.07 to 1.75, p = 0.01). Patients in the CABG stratum had significantly higher SYNTAX scores: 36% had mid/high SYNTAX scores compared with 13% in the PCI stratum (p Conclusions Among patients with diabetes and stable ischemic heart disease, higher SYNTAX scores predict higher rates of major cardiovascular events and were associated with more favorable outcomes of revascularization compared with medical therapy among patients suitable for CABG. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes; NCT00006305)

BACKGROUND: Alcohol consumption is associated with enhanced Th2 immune responses. Aim: To investigate the frequency of false-positive serological tests of allergy in alcoholics.METHODS: A total of 138 alcoholic patients consecutively admitted to hospital underwent a panel of allergy tests that included serum total IgE, a multiallergen IgE test (UniCAP Phadiatop), and skin prick tests to relevant aeroallergens in the area, which were considered the standard reference for atopy. In selected cases with positive specific IgE (sIgE) to cross-reactive carbohydrate determinants (CCDs) on ImmunoCAP, we determined sIgE to Hymenoptera venom components (ADVIA Centaur) and a microarray of 103 allergen components (ISAC).RESULTS: Increased (>170 IU/mL) serum total IgE was observed in 59/110 (54%) of non-atopic (skin prick test-negative) alcoholics. Forty-six non-atopic alcoholics (42%) had a positive multiallergen IgE test. This finding was closely associated with high serum concentrations of total IgE and sIgE to CCDs. The vast majority of alcoholics with positive CCD-sIgE showed positivity to glycosylated plant and Hymenoptera allergen components on ISAC and ADVIA Centaur. Only one out of 26 patients with positive sIgE to CCD and Hymenoptera venoms developed honeybee venom allergy after a median follow-up of 166 months. Measurements of sIgE to CCD markers on ImmunoCAP, ADVIA Centaur, and ISAC showed imperfect correlation.CONCLUSIONS: Serological tests for allergy should be interpreted with caution in alcoholics, who frequently show increased levels of total IgE, CCD-sIgE and subsequent positivity of sIgE to glycosylated allergen components, irrespective of the method used.

BACKGROUND & AIMS: The incidence and outcomes of alanine aminotransferase (ALT) flares during the natural history of chronic HBV infection has not been determined in a large, racially heterogeneous group of patients in North America. METHODS: We collected data from the Hepatitis B Research Network—an observational cohort study of untreated adults with chronic HBV infection enrolled at 21 sites in the United States and Canada. Clinical and laboratory data were collected from 1587 participants (49.9% male, 73.7% Asian, 35.2% genotype B infection, mean age of 42.6 years) at enrollment, at weeks 12 and 24, and every 24 weeks thereafter for a planned 5 years of follow up (from January 2011 through May 2016). Participants were excluded if they had a history of hepatic decompensation, hepatocellular carcinoma, solid organ or bone marrow transplantation, chronic immune suppression, or antiviral therapy within 6 months before enrollment. Levels of ALT were measured in serum samples and flares were defined as at least 10 times the upper limit of normal (300 U/L in males and 200 U/L in females). RESULTS: ALT flares occurred in 102 participants (6%), with 31 flares (30%) occurring at baseline. The 4-year cumulative incidence of ALT flares was 5.7%. The median peak level of ALT was 450 U/L (25th–75th percentile, 330 U/L to 747 U/L) with a maximum of 2578 U/L. In multivariable analysis, factors associated with the occurrence of an ALT flares were: male sex (odds ratio [OR], 3.02; P=.0007), higher baseline HBV DNA values (OR per log10, 1.41; P

OBJECTIVE Metabolic syndrome (MS) is prevalent and is associated with adverse outcomes of liver disease. We evaluated the prevalence of MS and its influence on alanine aminotransferase (ALT) levels and fibrosis, as estimated by the aspartate aminotransferase–to–platelet ratio index (APRI), in a large, multiethnic North American cohort with chronic hepatitis B (HBV) infection. RESEARCH DESIGN AND METHODS Adults with chronic HBV from 21 centers within the U.S. and Canada were evaluated at baseline and for up to 5 years (median 3.7 years) of follow-up. MS was defined as the presence of at least three of five criteria including waist circumference, blood pressure, glucose, triglyceride, and HDL levels. RESULTS Analysis included 777 participants, of whom 171 (22%) had MS. Participants with MS (vs. those without MS) were older (median age 54.4 vs. 40.2 years), more often male (61% vs. 51%), and born in the U.S./Canada or had immigrated >20 years ago (60% vs. 43%). MS was not associated with ALT or APRI at baseline. Upon adjusted multivariable analysis of serial ALT values, ALT was significantly higher (mean 12%; P = 0.02) among those with MS at baseline and even higher (mean 19%; P = 0.003) among those with persistent MS compared with those with persistent absence of MS. MS was not associated with serial APRI on follow-up. CONCLUSIONS MS was prevalent in this HBV cohort and was independently associated with higher ALT levels longitudinally. These findings highlight the importance of screening for MS and the potential for MS to influence ALT and its interpretation in the context of HBV treatment decisions.

House dust mites are a major source of allergy worldwide. While diagnosis and treatment based on mite extracts have remarkably advanced, little information exists on the expression of allergens in mites. We have studied gene expression of eight Dermatophagoides pteronyssinus (Trouessart) (Acari: Pyroglyphidae) allergens (Der p 1, 2, 3, 4, 5, 7, 10 and 21). All allergens showed higher transcription in nymphs compared with larvae or adults, with the only exception of Der p 10. The transcription of Der p 4 and Der p 10, together with the transcription and protein ratios Der p 1 to Der p 2, were higher in males than in females. One-week exposure of mite cultures to 16 or 35 °C (versus 24 °C) or low RH (44% versus 76%) significantly influenced the allergen gene transcription profile. Our results demonstrate that allergen expression is quantitatively and/or qualitatively influenced by mite development and sex, as well as by the environment. We suggest that monitoring allergen gene expression may be a useful tool to assist the optimization of mite cultures in the production of standardized allergenic extracts for clinical use.

The identification of allergy-causing mites is conventionally based on morphological characters. However, molecular taxonomy using ribosomal DNA (rDNA) may be particularly useful in the analysis of mite cultures and purified mite fractions in the production of allergenic extracts. Full-length internal transcribed spacers (ITS1 and ITS2) were obtained from Dermatophagoides farinae, Dermatophagoides pteronyssinus, Dermatophagoides microceras and Euroglyphus maynei (Astigmata: Pyroglyphidae), Glycyphagus domesticus and Lepidoglyphus destructor (Astigmata: Glycyphagidae), Tyrophagus fanetzhangorum, Tyrophagus putrescentiae, Tyrophagus longior, Tyrophagus neiswanderi, Acarus farris and Acarus siro (Astigmata: Acaridae), and Blomia tropicalis (Astigmata: Echymopodidae), using mite-specific primers. Polymerase chain reaction (PCR) products were digested with HpaII and RsaI restriction enzymes in order to produce species-specific PCR restricted fragment length polymorphism (RFLP) profiles. A semi-nested re-amplification step was introduced before the RFLP in order to apply the method to environmental samples. Results demonstrate that rDNA sequences can be used for the unambiguous identification of mite species. The PCR-RFLP system allows the identification of species in purified mite fractions when the availability of intact adult mite bodies for morphological identification is limited. This reliable and straightforward PCR-RFLP system and the rDNA sequences obtained can be of use in the identification of allergy-causing mite species.

The BARI 2D trial compared insulin provision (IP) versus insulin sensitization (IS) for the primary outcome of total mortality in participants with T2DM and cardiovascular disease (CVD). In this analysis we examine baseline characteristics that are associated with successful long-term glycemic control.In a 2×2 factorial design, 2368 participants were randomized to either IP or IS therapy, and to either prompt revascularization with medical therapy or medical therapy alone. Successful long-term glycemic control (success) was defined by simultaneously meeting 1) a mean HbA1c level of7.0% after each participant's third year of follow-up period, and 2) adherence with medications only from the assigned glycemic treatment arm during80% of the BARI 2D follow-up. The association between baseline variables and success was determined using unadjusted and adjusted logistic regression models.1917 participants (962 IP and 955 IS participants) had sufficiently long follow-up and data for this analysis. Among these IP and IS participants, 235 and 335 participants met both criteria of success, respectively (p0.001). Those not on insulin at entry had higher odds of success (OR 2.25; CI 1.79-2.82) when treated with IS versus IP medications, irrespective of baseline HbA1c levels. Younger age, shorter duration of T2DM, and lower HbA1c at baseline were also each independently associated with higher success when treated with IS versus IP medications.Patients similar to those in the BARI 2D trial may have a higher chance of achieving success with IS versus IP medications if they are younger, have shorter duration of T2DM, have lower HbA1c levels, have moderate or strenuous physically activity, and are not on insulin. In contrast, increasing age, longer duration of T2DM, higher HbA1c, and insulin therapy are associated with increased chance of success if treated with IP medications.

OBJECTIVE The aim of this manuscript was to report the risk of incident peripheral arterial disease (PAD) in a large randomized clinical trial that enrolled participants with stable coronary artery disease and type 2 diabetes and compare the risk between assigned treatment arms. RESEARCH DESIGN AND METHODS The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial randomly assigned participants to insulin sensitization (IS) therapy versus insulin-providing (IP) therapy for glycemic control. Results showed similar 5-year mortality in the two glycemic treatment arms. In secondary analyses reported here, we examine the effects of treatment assignment on the incidence of PAD. A total of 1,479 BARI 2D participants with normal ankle-brachial index (ABI) (0.91–1.30) were eligible for analysis. The following PAD-related outcomes are evaluated in this article: new low ABI ≤0.9, a lower-extremity revascularization, lower-extremity amputation, and a composite of the three outcomes. RESULTS During an average 4.6 years of follow-up, 303 participants experienced one or more of the outcomes listed above. Incidence of the composite outcome was significantly lower among participants assigned to IS therapy than those assigned to IP therapy (16.9 vs. 24.1%; P < 0.001). The difference was significant in time-to-event analysis (hazard ratio 0.66 [95% CI 0.51–0.83], P < 0.001) and remained significant after adjustment for in-trial HbA1c (0.76 [0.59–0.96], P = 0.02). CONCLUSIONS In participants with type 2 diabetes who are free from PAD, a glycemic control strategy of insulin sensitization may be the preferred therapeutic strategy to reduce the incidence of PAD and subsequent outcomes.

Background— Rosiglitazone improves glycemic control for patients with type 2 diabetes mellitus, but there remains controversy regarding an observed association with cardiovascular hazard. The cardiovascular effects of rosiglitazone for patients with coronary artery disease remain unknown. Methods and Results— To examine any association between rosiglitazone use and cardiovascular events among patients with diabetes mellitus and coronary artery disease, we analyzed events among 2368 patients with type 2 diabetes mellitus and coronary artery disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. Total mortality, composite death, myocardial infarction, and stroke, and the individual incidence of death, myocardial infarction, stroke, congestive heart failure, and fractures, were compared during 4.5 years of follow-up among patients treated with rosiglitazone versus patients not receiving a thiazolidinedione by use of Cox proportional hazards and Kaplan–Meier analyses that included propensity matching. After multivariable adjustment, among patients treated with rosiglitazone, mortality was similar (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.58–1.18), whereas there was a lower incidence of composite death, myocardial infarction, and stroke (HR, 0.72; 95% CI, 0.55–0.93) and stroke (HR, 0.36; 95% CI, 0.16–0.86) and a higher incidence of fractures (HR, 1.62; 95% CI, 1.05–2.51); the incidence of myocardial infarction (HR, 0.77; 95% CI, 0.54–1.10) and congestive heart failure (HR, 1.22; 95% CI, 0.84–1.82) did not differ significantly. Among propensity-matched patients, rates of major ischemic cardiovascular events and congestive heart failure were not significantly different. Conclusions— Among patients with type 2 diabetes mellitus and coronary artery disease in the BARI 2D trial, neither on-treatment nor propensity-matched analysis supported an association of rosiglitazone treatment with an increase in major ischemic cardiovascular events. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00006305.

Background The increasing use of electronic health records (EHRs) in clinical practice offers the potential to investigate cardiovascular outcomes over time in patients with type 2 diabetes (T2D). Objective To develop a methodology for identifying prevalent and incident cardiovascular disease (CVD) in patients with T2D who are candidates for therapeutic intensification of glucose-lowering therapy. Methods Patients with glycated hemoglobin (HbA1c) ≥7% (53 mmol/mol) while receiving 1–2 oral diabetes medications (ODMs) were identified from an EHR (2005–2011) and grouped according to intensification with insulin (INS) (n=372), a different class of ODM (n=833), a glucagon-like peptide receptor 1 agonist (GLP-1RA) (n=59), or no additional therapy (NAT) (n=2017). Baseline prevalence of CVD was defined by documented International Classification of Diseases Ninth Edition (ICD-9) codes for coronary artery disease, cerebrovascular disease, or other CVD with first HbA1c ≥7% (53 mmol/mol). Incident CVD was defined as a new ICD-9 code different from existing codes over 4 years of follow-up. ICD-9 codes were validated by a chart review in a subset of patients. Results Sensitivity of ICD-9 codes for CVD ranged from 0.83 to 0.89 and specificity from 0.90 to 0.96. Baseline prevalent (INS vs ODM vs GLP-1RA vs NAT: 65% vs 39% vs 54% vs 59%, p

Background: The role of profilin as a food allergen is well established, but little research has been done about its ability to elicit respiratory disease. Profilin is considered more of a confounding allergen on skin testing with whole pollen extracts than other airborne allergens. Our aim was to find out whether or not profilin can cause symptoms in sensitized individuals, which would be compatible with its role as an airborne allergen. Methods: We performed conjunctival allergen challenges with date palm profilin in a series of consecutive pollen-allergic patients with rhino-conjunctivitis, divided in two groups: profilin sensitized (n = 17) and not sensitized (n = 14), who served as controls. We investigated the possible association between profilin sensitization and profilin allergy in these groups of patients. Results: None of the patients from the not profilin-sensitized group had a positive result in conjunctival allergen challenges. In contrast, 65% of profilin sensitized patients had a positive conjunctival allergen challenge and were considered allergic to profilin. We found a significant statistical association between being profilin allergic and being profilin sensitized (χ2 = 10.39, p < 0.005). Conclusions: Profilin seems to work as an aeroallergen in a significant proportion of profilin-sensitized patients. This might explain the uselessness of conjunctival challenges with whole pollen extracts to disclose genuine sensitization. In the future, the possibility of quantifying this allergen in pollen immunotherapy vaccines should be considered.

OBJECTIVE To examine ankle-brachial index (ABI) abnormalities in patients with type 2 diabetes and coronary artery disease (CAD). RESEARCH DESIGN AND METHODS An ABI was obtained in 2,240 patients in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial. ABIs were classified as: normal, 0.91–1.3; low, ≤0.9; high, >1.3; or noncompressible artery (NC). Baseline characteristics were examined according to ABI and by multivariate analysis. RESULTS ABI was normal in 66%, low in 19%, and high in 8% of patients, and 6% of patients had NC. Of the low ABI patients, 68% were asymptomatic. Using normal ABI as referent, low ABI was independently associated with smoking, female sex, black race, hypertension, age, C-reactive protein, diabetes duration, and lower BMI. High ABI was associated with male sex, nonblack race, and higher BMI; and NC artery was associated with diabetes duration, higher BMI, and hypertension. CONCLUSIONS ABI abnormalities are common and often asymptomatic in patients with type 2 diabetes and CAD.

Tras la entrada en vigor del Tratado de Lisboa, el 1 de diciembre de 2009, el equilibrio de poderes dentro de la Unión Europea se ha visto sensiblemente modificado. Si bien el sistema de codecisión entre Consejo y Parlamento no es algo novedoso, se extiende desde entonces a un sinnúmero de materias. La no adopción del Acuerdo UE-EEUU sobre tratamiento y transferencia de datos de mensajería financiera de la UE a los EEUU, a efectos del programa de seguimiento de la financiación del terrorismo, que ya había entrado en vigor provisionalmente tras ser adoptado por el Consejo de la Unión, es una prueba de este cambio. Mediante este acuerdo, los EEUU tendrían acceso a los datos Swift, almacenados por esta sociedad en Europa y relativos a las transacciones bancarias intraeuropeas, a efectos de investigar la financiación del terrorismo. Anteriormente, los EEUU accedían a los mismos merced a un servidor de Swift ubicado en su territorio, donde se almacenaban también las transacciones intraeuropeas. Swift anuncia su intención de almacenar los datos de estas transferencias exclusivamente en Europa, obligando al gobierno de los EEUU a negociar un acuerdo con la UE, si no quiere quedar excluido del conocimiento de dichos datos. Dicho acuerdo es suscrito con el Consejo de la UE el día anterior a la entrada en vigor del Tratado de Lisboa, con lo que se excluye la participación del Parlamento Europeo en su negociación y conclusión. Éste rechaza finalmente el acuerdo, preocupado por las escasas garantías a la protección de datos que considera existen en el mismo, a la falta de reciprocidad y, posiblemente, a su anterior marginación del proceso.

Con más de dos años de retraso, el Gobierno ha remitido al Congreso el proyecto de ley de prevención del blanqueo de capitales y financiación del terrorismo. Nuestro país ha sido objeto de dos condenas por parte del TJCE por no haber transpuesto las Directivas 2005/60/CE y 2005/70/CE, relativas a la prevención del blanqueo de capitales. Con este proyecto se lleva, por fin, a cabo la transposición. El texto remitido por el Gobierno establece mayores exigencias que las establecidas por la Directiva 2005/60/CE. En lo esencial, sigue las líneas maestras del actual sistema, aunque se introducen sustanciales modificaciones en aspectos relevantes. La ley pasa de 16 a 70 artículos, por lo que puede adivinarse que desciende a detalles que antes eran objeto de regulación reglamentaria. Por otro lado, abarca una parte de la problemática que presenta la financiación del terrorismo, por la similitud de métodos que se observan en ambas amenazas (el blanqueo y la financiación del terrorismo). Se intenta coordinar la normativa de prevención con la normativa represiva, contenida en el Código Penal, y se integran en el concepto de blanqueo situaciones que antes no lo estaban, o al menos eran discutidas. Si bien, de cara a la galería, destaca la regulación que se efectúa de las personas del medio político, existen otros aspectos de mayor calado, como la ampliación de los sujetos obligados, el fichero de titularidades financieras, las medidas de diligencia debida y un largo etcétera. Estamos ante un intento de una regulación amplia y detallada, que quizá peque de ser un tanto voluntarista y que presenta algunos defectos de concepto y de técnica jurídica. Confiemos en la sabiduría y mesura del legislador para salvar estos problemas y llegar al resultado deseado.

Los paraísos fiscales suponen un problema pendiente en la consideración internacional del tributo. En el estado actual de cooperación de la comunidad internacional, sorprende el mantenimiento de la opacidad fiscal de dichos territorios y la falta de una mayor presión sobre los mismos de cara a la desaparición de tal opacidad, que debería ser ejercida con mayor determinación desde ciertas instancias internacionales y desde las economías más poderosas, especialmente ante los momentos de crisis y recesión que se están viviendo. Pero ante una solución global en tal sentido en la sociedad internacional, es necesaria una revisión de las medidas impulsadas desde la Unión Europea y un replanteamiento de las medidas adoptadas en nuestro Derecho. La problemática de los paraísos fiscales no sólo debe ser vinculada con la defraudación tributaria, sino también con un problema más amplio, como es el del blanqueo de activos o capitales. Las soluciones con relación al blanqueo pueden incidir en la solución de los demás problemas relativos a los paraísos fiscales y, recíprocamente, las soluciones en materia de paraísos fiscales pueden ayudar a frenar dicho blanqueo de activos. Así, a los tradicionales análisis que en materia tributaria se han venido haciendo de los paraísos fiscales, hay que sumar una nueva perspectiva en su consideración, como es la del blanqueo de capitales.

OBJECTIVE To evaluate the effect of prior duration of diabetes, glycated hemoglobin level at study entry, and microalbuminuria or macroalbuminuria on the extent and severity of coronary artery disease (CAD) and peripheral arterial disease. PATIENTS AND METHODS We studied baseline characteristics of the 2368 participants of the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) study, a randomized clinical trial that evaluates treatment efficacy for patients with type 2 diabetes and angiographically documented stable CAD. Patients were enrolled from January 1, 2001, through March 31, 2005. Peripheral arterial disease was ascertained by an ankle-brachial index (ABI) of 0.9 or less, and extent of CAD was measured by presence of multivessel disease, a left ventricular ejection fraction (LVEF) of less than 50%, and myocardial jeopardy index. RESULTS Duration of diabetes of 20 or more years was associated with increased risk of ABI of 0.9 or less (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.04-2.26), intermittent claudication (OR, 1.61; 95% CI, 1.10-2.35), and LVEF of less than 50% (OR, 2.03; 95% CI, 1.37-3.02). Microalbuminuria was associated with intermittent claudication (OR, 1.53; 95% CI, 1.16-2.02) and ABI of 0.9 or less (OR, 1.31; 95% CI, 0.98-1.75), whereas macroalbuminuria was associated with abnormal ABI, claudication, and LVEF of less than 50%. There was a significant association between diabetes duration and extent of CAD as manifested by number of coronary lesions, but no other significant associations were observed between duration of disease, glycated hemoglobin levels, or albumin-to-creatinine ratio and other manifestations of CAD. CONCLUSION Duration of diabetes and microalbuminuria or macroalbuminuria are important predictors of severity of peripheral arterial disease and left ventricular dysfunction in a cohort of patients selected for the presence of CAD.

The influence of metabolic syndrome (MS) on long-term mortality and morbidity in multi-vessel coronary artery disease (MV-CAD) is unclear. We studied the impact of MS on long-term outcomes in non-diabetic patients (NDM) with MV-CAD undergoing coronary revascularization in the Bypass Angioplasty Revascularization Investigation (BARI) trial and registry.BARI trial and registry patients were separated into those with diabetes (DM) and those without. NDM fulfilling the NCEP definition of MS were identified. Ten year follow-up data were obtained on mortality, MI and development of diabetes. The data were analyzed using Cox proportional hazard modeling.In the BARI trial and registry 2962 NDM were identified. Of those, 510 patients had 3 or more components of the BARI-modified NCEP definition for MS, while 445 patients had 2 components of the definition and were classified as the "mixed group". Compared to patients without MS, both MS group (RR=3.2, p0.0001) and the mixed group (RR=1.9, p=0.02) had a higher incidence of DM over the 10-year follow-up. Type 2 DM was found to be highly associated with 10-year mortality (RR=1.65, p0.0001). However, there was no statistically significant difference in the rate of death or MI at 5 and 10 years between NDM with or without MS. In multivariate analysis, the presence of MS was not associated with 10-year mortality in the BARI population (RR=0.93, p=0.62).In this BARI follow-up study, we have affirmed the role of MS in predicting the development of diabetes in NDM at baseline. The 10-year risk of mortality and MI was not greater in NDM with MS who had MV-CAD and underwent revascularization, compared to patients without MS. Further studies to evaluate MS patients with MV-CAD undergoing coronary revascularization are warranted.

Background Contradictory results have been found when analyzing the IgE cross-reactivity among pyroglyphid mites and storage mites, as well as the role of these as true sensitizing agents. Objective We sought to study the prevalence of sensitization to Glycyphagus domesticus in patients naturally exposed to this mite together with the more ubiquitous Dermatophagoides pteronyssinus and the IgE cross-reactivity between them. Methods Mite species present in house dust samples of consecutive patients with mite allergy from Huelva (southwest Spain) were determined by means of light microscopy. Clinical sensitization was assessed by using skin prick and conjunctival provocation tests. Cross-reactivity at the IgE level was studied by using serum IgE determination and inhibition of RAST, IgE immunoblotting, and mite group 2 immunoassays. Results After D pteronyssinus , which is present in about 95% of house dust samples, G domesticus was the most important mite and present in about 50% of the samples. Tyrophagus putrescentiae and Lepidoglyphus destructor were detected in third and fourth place, respectively. About half of the patients with G domesticus at home were sensitized to this mite. A low IgE cross-reactivity was observed between D pteronyssinus and G domesticus , but an important IgE cross-reactivity was detected among glycyphagid mites at the level of group 2 allergens. Conclusion Glycyphagid mites can act as primary sensitizing agents independently of pyroglyphid mites in a subset of patients naturally exposed to them. Clinical implications The inclusion of glycyphagid mite extracts in the diagnostic battery in areas with adequate mite growing conditions is important to ensure proper diagnosis.

Background: Peach allergy has two different patterns: central Europe with oral allergy syndrome (OAS) related to a primary sensitization to birch pollen Bet v 1 and profilins and southern Europe with mostly systemic symptoms, in many cases due to sensitization to lipid-transfer proteins. Methods: Thirty peach-allergic patients with positive skin and food challenge tests and 29 control subjects were included. Skin prick tests (SPT) with inhalant allergens, commercial peach and apple extracts and native Pru p 3 were performed. In vitro specific immunoglobulin (Ig) E to grass pollen, birch pollen, peach, apple, rBet v 1, rBet v 2 and rPhl p 12 was determined by CAP, and rBet v 1, rMal d 1, rMal d 4, rMal d 3 and rPru p 3 using the ADVIA-Centaur platform. Basophil activation test (BAT) with commercial peach extract, commercial apple extract, nPru p 3, rMal d 3, rMal d 1 and rMal d 4 was also performed. Results: Pru p 3 was the major allergen in the patient group from northern Spain. Sensitization to this allergen was found in 100% of the patients with systemic symptoms or contact urticaria. Only 60% of OAS patients were sensitized to Pru p 3, being all of them sensitized to profilins and 60% of them to allergens of the Bet v 1 family. Specific IgE determination and BAT using recombinant allergens (rPru p 3) show specificity and sensitivity values close to 100%. Conclusions: Most peach-allergic patients coming from the north of Spain present systemic symptoms after ingestion of peach, Pru p 3 being the main allergen. Patients with OAS present profilin-Bet v 1-related sensitization. Thus, in the north of Spain our patients show a mixed central-south Europe pattern with LTP-profilin-Bet v 1 sensitization depending on the symptoms presented. The use of natural and recombinant plant allergens, allows establishing the sensitization patterns to the different allergens studied.

Diabetes is associated with liver disease progression and increased hepatocellular carcinoma risk, but factors associated with diabetes in patients with chronic hepatitis B virus (HBV) infection in North America are unknown. We aimed to determine factors predictive of diabetes and impaired fasting glucose (IFG) in a large HBV-infected multiethnic cohort. Adults with chronic HBV not receiving antiviral therapy were enrolled from 21 centers in North America. Diabetes was defined by history/medication use or fasting glucose ≥126 mg/dL and IFG as fasting glucose 100-125 mg/dL. Of 882 patients included, 47.2% were female, 71.3% Asian, 83.7% foreign born, median age was 44 years, and median body mass index BMI 24.3 kg/m2. In this cohort, 26.0% were hepatitis B envelope antigen (HBeAg) positive, 43.9% had HBV DNA ≥20,000 IU/mL, and 26.7% alanine aminotransferase (ALT) ≥2× upper limit of normal (≥40 U/L women, ≥60 U/L men). Overall, 12.5% had diabetes and 7.8% IFG. The combined prevalence of diabetes or IFG was highest among blacks (36.7%) and those either born in the United States/Canada or foreign born with migration >20 years ago (25.5%). Obesity (odds ratio [OR]: 2.13), hyperlipidemia (OR, 4.13), hypertension (OR, 3.67), high ALT level (OR, 1.86), and family history of diabetes (OR, 3.43) were associated with diabetes. Factors associated with IFG were obesity (OR, 4.13) and hypertension (OR, 3.27), but also HBeAg positivity (OR, 0.39). Recent migration was negatively associated with diabetes among non-Asians (OR, 0.30). Conclusions: Diabetes is more prevalent in HBV-infected North American adults than the general population and is associated with known metabolic risk factors and liver damage, as determined by ALT levels. Among the foreign born, longer duration of North America residence predicted diabetes risk in non-Asians. These results highlight the opportunities for interventions to prevent diabetes especially among at-risk ethnic groups with HBV. (Hepatology 2015;62:1364–1374)

To test the hypothesis that children with chronic hepatitis B living in the US and Canada would have international origins and characteristic hepatitis B virus (HBV) genotypes and laboratory profiles.Clinical characteristics of children enrolled in the Hepatitis B Research Network were collected from 7 US and Canadian centers.Children (n = 343) with an age range of 1.0-17.8 years were enrolled; 78% of the children were Asian, 55% were adopted, and 97% had international origins with either the child or a parent born in 1 of 31 countries. The majority had HBV genotype B (43%) or C (32%), and the remainder had genotype A (5%), D (16%), E (4%), or multiple (1%). Children with genotype B or C were more likely to be Asian (98% and 96%), more consistently hepatitis B envelope antigen positive (95% and 82%), had higher median HBV DNA levels (8.2 and 8.3 log10 IU/mL), and less frequently had elevated alanine aminotransferase values (43% and 57%) compared with children with other genotypes. The percentage of hepatitis B envelope antigen positivity and of those with HBV DNA ≥6 log₁₀ IU/mL declined with age.The majority of children in the Hepatitis B Research Network have HBV genotypes that reflect their international origins. Clinical and laboratory data differ substantially by patient age and HBV genotype. Use of these data can help drive the development of optimal strategies to manage and treat children with chronic hepatitis B.

Background.Research has shown less aggressive treatment and poorer control of cardiovascular disease (CVD) risk factors in women than men.Methods.We analyzed sex differences in pharmacotherapy strategies and attainment of goals for hemoglobin A1c (HbA1c), blood pressure (BP), and low density lipoprotein cholesterol (LDL-C) in patients with type 2 diabetes and established coronary artery disease enrolled into the BARI 2D trial.Results.Similar numbers of drugs were prescribed in both women and men. Women were less frequent on metformin or sulfonylurea and more likely to take insulin and to be on higher doses of hydroxymethylglutaryl-CoA reductase inhibitors (statins) than men. After adjusting for baseline differences and treatment prescribed, women were less likely to achieve goals for HbA1c (OR = 0.71, 95% CI 0.57, 0.88) and LDL-C (OR = 0.64, 95% CI 0.53, 0.78). More antihypertensives were prescribed to women, and yet BP ≤ 130/80 mmHg did not differ by sex.Conclusions.Women entering the BARI 2D trial were as aggressively treated with drugs as men. Despite equivalent treatment, women less frequently met targets for HbA1c and LDL-C. Our findings suggest that there may be sex differences in response to drug therapies used to treat diabetes, hypertension, and hyperlipidemia.

Background: Lentils are the most common legume involved in allergic reactions in the Mediterranean area and India. Lentil crops could be attacked by a wide range of insect species. Occupational asthma caused by the lentil pest Bruchus lentis has been described in the present study. Objective: We studied the possibility of immunoglobulin (Ig)E-mediated hypersensitivity to lentil pests in 16 patients who suffered from allergic symptoms (asthma and anaphylaxis) related to inhalation of lentil particles or ingestion of lentils, in which sensitization to legume proteins was not clear. Methods: Extracts prepared either from noninfested and infested lentils, and from the lentil parasite B. lentis were used for skin prick testing (SPT), bronchial and oral challenges and in vitro determinations. Results: Skin prick test were positive to infested lentils and B. lentis in all patients and negative to noninfested lentil extracts. Five asthmatic patients reacted in the bronchial challenge test with Bruchus extract. Oral challenges performed with boiled infested lentils were positive in six of seven patients. Immunoglobulin E immunoblotting with Bruchus and infested lentils extracts revealed protein bands that were reactive to serum IgE from six and four, respectively, out of 16 patients. These patients had no IgE to lentil-specific proteins as determined by immunoblotting and Len c 1-specific IgE test. Conclusions: Lentil pest proteins can be a cause of IgE-mediated rhinoconjunctivitis and asthma in patients eating or inhaling infested lentil particles.

Background: New IgE sensitizations to proteins in allergen extracts have been shown to occur during allergen-specific immunotherapy (IT). Methods: Twenty-four healthcare workers (HCWs) – patients included in a latex IT study – were analysed, 16 in active treatment and eight in placebo. Sera were obtained at baseline and after 6 months of IT and analysed with immunoblotting and CAP System with eight single recombinant latex allergens (rHev b 1, 3, 5, 6.01, 8, 9, 10, 11, and a mix of rHev b1, 5, 6.01 and 8). Results: After IT with latex, three patients in the active treatment group had new IgE sensitizations, one to Hev b 5, one to Hev b 11 and another to Hev b 6.01. No other significant variation in mean of specific IgE to latex or recombinant allergens were observed in patients who received placebo or active treatment. A significant (P = 0.012) negative correlation (−0.72) was observed between maximal tolerated dose and specific IgE to Hev b 6.01 at baseline. After IT, immunoblot analysis demonstrated a significant increase in IgE binding in a band of approximately 22 kDa (P = 0.032) that may correspond to Hev b 6.01. New or more intense bands appeared in seven patients of the active group, while in three subjects a reduction was observed. Conclusions: Hev b 6.01 seems to be the most relevant latex allergen in HCWs. New or more intense IgE binding to latex allergenic components occurs during latex immunotherapy. However, the levels of specific IgE against these new components are low and do not seem to have clinical relevance.

Background: Current treatment guidelines for type 2 diabetes (T2D) recommend individualized intensification of therapy for glycated hemoglobin (A1C) ≥ 7% in most patients. The purpose of this investigation was to explore the ability of an electronic medical record (EMR) to identify glycemic intensification strategies among T2D patients receiving pharmacologic therapy. Methods: Patient records between 2005 and 2011 with documentation of A1C and active prescriptions for any diabetes medications were queried to identify potential candidates for intensification based on A1C ≥ 7% while on 1-2 oral diabetes medications (ODM). Patients with follow-up A1C values within 1 year of index A1C were grouped according to intensification with insulin, GLP-1 receptor agonists (GLP-1RA), a new class of ODM, or no intensification. Changes in A1C and continuation of intensification therapy were determined. Results: A total of 4921 patients meeting inclusion criteria were intensified with insulin (n = 416), GLP-1RA (n = 68), ODM (n = 1408), or no additional therapy (n = 3029). Patients receiving insulin had higher baseline (9.3 ± 2.0 vs 8.3 ± 1.2 vs 8.3 ± 1.3 vs 7.6 ± 1.0%, P < .0001) and follow-up A1C (8.1 ± 1.6 vs 7.5 ± 1.2 vs 7.6 ± 1.3 vs 7.2 ± 1.1%, P < .0001) despite experiencing larger absolute A1C reductions (−1.2 ± 2.1 vs −0.8 ± 1.4 vs −0.7 ± 1.4 vs −0.3 ± 1.1%, P < .0001). Patients receiving GLP-1RA were more obese at baseline (BMI: 33.6 ± 7.1 vs 37.7 ± 6.1 vs 33.7 ± 6.8 vs 32.9 ± 7.1 kg/m2, P < .0001) and follow-up (BMI: 33.9 ± 7.3 vs 36.6 ± 6.1 vs 33.8 ± 7.0 vs 32.4 ± 7.0 kg/m2, P < .0001) despite experiencing more absolute weight reduction. Insulin was the most and GLP-1RA the least likely therapy to be continued. Conclusions: An EMR allows identification of prescribing practices and compliance with T2D treatment guidelines. Patients receiving intensification of glycemic medications had baseline A1C >8% suggesting that treatment recommendations are not being followed.

Background: Orange is among the most widely consumed fruits, and among the plant food sources causing allergic reactions according to popular perception. However, its relevant allergenic components are virtually unknown. Profilin is a well-defined minor plant panallergen, showing prevalences around 30% in fruits and vegetables. Methods: Twenty-three orange-allergic patients were studied. Natural orange profilin, named Cit s 2, was purified by affinity chromatography and characterized by N-terminal amino acid sequencing, matrix-assisted laser desorption/ionization mass spectrometry analysis and isolation of its coding cDNA. Reactivity to Cit s 2 was analyzed in vivo by skin prick tests (SPT) and in vitro by IgE immunodetection, specific IgE determination in individual sera and enzyme-linked immunosorbent assay-inhibition assays. Results: The N-terminal amino acid sequence and molecular mass of natural Cit s 2, both fully in agreement with the complete amino acid sequence deduced from its coding cDNA, demonstrated its profilin nature. An unexpectedly high reactivity to Cit s 2 was found in vivo (78% of positive SPT responses) and in vitro (87% of sera from orange allergic patients had specific IgE to Cit s 2). The purified allergen inhibited around 50% of the IgE binding to an orange pulp extract. Conclusion: Orange profilin Cit s 2, unlike other plant food profilins, is a major and highly prevalent allergen.

Summary Background : The relationship between pet ownership and the risk of developing respiratory allergic sensitization to pet allergens is still controversial. Objective : To determine the degree of cutaneous immediate hypersensitivity and the levels of specific IgE and IgG4 antibodies to cat allergen in cat sensitized patients directly or indirectly exposed to this animal. Methods : We studied 112 adolescents and adults sensitized to cat allergens (43 with and 69 without a cat at home). There were also 52 control subjects, 27 atopic non-sensitized to cat and 25 non-atopic. The degree of immediate hypersensitivity was assessed by using, in duplicate, skin prick test with four five-fold dilutions of cat hair allergen extract with the content of its major allergen Fel d 1 quantified in micrograms plus positive (10mg/ml histamine chlorhydrate) and negative (saline solution) controls. The resulting wheal areas were analysed by means of Parallel Line Assay. A blood sample was collected from every patient and control subjects for the evaluation of serological cat specific IgE and IgG4 antibodies. Results : Patients with cat at home had a lower cutaneous response than patients without this pet. The difference in the skin sensitivity was estimated in 3.4 times \( P 0.01 \) . There was no statistical difference between the levels of cat specific IgE antibodies in the two groups of patients \( P = 0.065 \) . The levels of Fel d 1 specific IgG4 antibodies showed a statistically significant association with the presence of cat at home, with higher levels in patients owing cat at home than in patients without this pet \( P 0.001 \) . Conclusion : The results of this study demonstrate that direct cat exposure in adolescents and adults with respiratory allergy is associated with a lower cutaneous response to cat allergenic extract, assessed by SPT and compared with indirect exposure. In patients with cat at home mean levels of specific IgE are statistically comparable whereas the levels of IgG4 are higher in comparison with subjects not exposed to cats. The role of indirect exposure to cat allergens in airways sensitization also in adults is emphasized. Moreover, patients with cat at home show a cutaneous and serological sensitization to cat allergen not higher in comparison with subjects not exposed to cats.

Background: Lipid transfer proteins (LTPs) are relevant fruit allergens, recently proposed as model plant food allergens. No citrus fruit allergen has been characterized to date. We sought to identify and isolate citrus fruit LTPs and to explore their relevance in orange allergy. Methods: Twenty-seven patients, showing mainly oral allergy syndrome after orange ingestion, as well as positive prick responses and serum-specific IgE levels to orange, were selected. Natural orange and lemon LTPs, as well as a recombinant orange LTP isoform expressed in Pichia pastoris, were isolated by chromatographic methods and characterized by N-terminal amino acid sequencing and matrix-assisted laser desorption/ionizaion mass spectrometry, and DNA sequencing of the corresponding cDNA in the case of the recombinant allergen. Specific IgE determination, immunodetection, ELISA-inhibition assays and in vivo skin prick tests (SPTs) were performed with all three purified allergens and with the major peach LTP allergen, Pru p 3. Results: The natural allergens purified from orange (nCit s 3) and lemon (nCit l 3) showed very similar N-terminal amino acid sequences (18 out of 20 identical residues), typical of LTPs, and molecular masses of 9,610 and 9,618 Da, respectively. The recombinant orange isoform (rCit s 3) expressed in P. pastoris (16 out of 20 residues identical to its natural counterpart in the N-terminal region) presented 92 amino acid residues and 9,463 Da, and 67% sequence identity with rPru p 3. Of the 27 sera analyzed, specific IgE to the purified allergens was found in 54% for nCit l 3, 48% for nCit s 3, 46% for rCit s 3 and 37% for rPru p 3. Positive SPT responses were obtained in 7 out of 26 patients tested for nCit s 3, 3 out of 8 for nCit l 3 and 10 out of 26 for nPru p 3. ELISA-inhibition assays showed an equivalent IgE-binding pattern for the natural and recombinant orange LTPs, and IgE cross-reactivity among the purified orange, lemon and peach LTP allergens. Conclusions: Members of the LTP allergen family are involved in allergy to oranges, displaying positive in vitro and in vivo reactions in 30–50% of the patients studied. Both orange and lemon allergens show cross-reactivity with the major peach allergen Pru p 3.

Background In this work we analyzed the allergological importance of Tyrophagus putrescentiae (Tp) in Huelva (SE Spain). We studied the level of exposition and the grade of sensitization to Tp in a group of patients sensitized to Dermatophagoides pteronyssinus (Dpt). The allergenic cross-reactivity between Dpt and Tp was determined by RAST inhibition.

Summary Background Artemisia vulgaris is a widespread weed in the Mediterranean area and several allergens have been detected in its pollen. One of them, Art v 3, belongs to the lipid-transfer protein (LTP) family and its prevalence in Artemisia-sensitized patients or its relationship with other LTP allergens is not clear. Objective To assess the pattern of sensitization to an array of mugwort allergens in a Mediterranean population, and to study the cross-reactivity of Art v 3 with Pru p 3 and Par j 1, relevant LTP allergens in the area. Methods Skin prick test was performed with whole extracts (A. vulgaris, Parietaria judaica and peach) and pure natural allergens Art v 1, Art v 3, Art v 60 kDa and Par j 1 in 24 mugwort-allergic patients from a Mediterranean area. In vitro assays included measurement of specific IgE and ELISA inhibition among LTP allergens. Results The three Artemisia allergens elicited a positive skin response in 70–80% of the patients. Seven patients were clearly sensitized to Par j 1 and 11 to Pru p 3. There was no correlation between Par j 1 and Pru p 3 sensitization, but a highly significant correlation was found between peach extract and Art v 3 as regards the skin response. No IgE cross-reactivity was observed between Art v 3/Par j 1 or Pru p 3/Par j 1. In contrast, Art v 3 significantly inhibited the binding to Pru p 3 of IgE from three patients' sera out of six studied, but Pru p 3 was not able to inhibit the IgE binding to Art v 3. Conclusion Art v 3 is a major mugwort allergen and in some patients with IgE to both Art v 3 and Pru p 3, Art v 3 behaves as the primary sensitizing agent.

The optical emission properties of several minerals components employed in electrode coatings of arc welding have been investigated. The X-ray diffraction analysis shows that the composition of 14 commercial electrode coatings collected from different countries (Spain, France, UK, Poland, Argentina and Germany), consists of quartz, calcite, sodium and potassium rich feldspars, muscovite and rutile. The natural thermal stimulated luminescence (TSL) of these mineral phases, measured in the range of 200-800 nm at different temperatures (from room temperature to 400 degrees C) displays UV-A (wavelengths of 320 nm to 400 nm) and UV-B (from 280 nm to 320 nm) emissions, with the exception of rutile. The UV-B radiation, commonly described as the most dangerous form of radiation to human life, is here associated with structural defects in the crystallographic lattice of the mineral components of electrode coatings.

Summary Background Several lipid-transfer proteins (LTPs) have been identified as important food allergens, especially in fruits of the Rosaceae family. The major peach (Prunus persica) allergen has been identified, sequenced and designated Pru p 3. Objective To present Pru p 3 as an aeroallergen able to induce occupational asthma. Methods A thorough investigation was performed in a fruit grower with occupational asthma. Skin prick–prick tests with peach leaves and prick tests with perennial respiratory allergens and pollens, fruits and peach leaf extracts were done. Serum-specific IgE was tested for peach leaf, peach fruit, peach skin and respiratory allergens that were positive in skin prick tests. Specific bronchial provocation tests (BPTs) with extracts of peach leaf were also done. Before and 24 h after the BPT, BPTs with methacholine and sputum induction were done. The IgE reactivity pattern to peach leaf and fruit extracts and to Pru p 3 was identified by using SDS-PAGE and immunoblotting. Blotting inhibition of peach leaf extract by Pru p 3 was also performed. The putative allergen was quantified in leaf and fruit skin extracts with ELISA based on an anti-Pru p 3 antibody. Results Skin tests were positive for peach leaf and fruit. The BPT was positive, with immediate and delayed response. This test induced a decrease in PD20 (dose of agonist that induces a 20% fall in FEV1) methacholine and an increase in eosinophils and eosinophil cationic protein in sputum. Peach leaf extract contained concentrations of Pru p 3 similar to those found in peach skin. Specific IgE immunodetection showed that patient's sera reacted with Pru p 3, and with a single major band from the peach leaf extract fully inhibited by Pru p 3. Conclusion Pru p 3 from peach leaves can act as a respiratory allergen and cause occupational rhinoconjunctivitis and asthma.

Background Lipid transfer proteins (LTPs) are clinically relevant plant food panallergens and have been proposed as ideal tools to study true food allergy. Pru p 3, the major peach allergen in the Mediterranean area, is among the best-characterized allergenic members of the LTP family. Its diagnostic value for Rosaceae fruit allergy has been demonstrated both in vivo and in vitro. Objective We sought to locate major IgE-binding epitopes of Pru p 3. Methods A serum pool and individual sera from patients with peach allergy and positive skin prick test results to Pru p 3 were used. Three-dimensional modeling was achieved by using experimentally available structures of Pru p 3 homologues as templates. Theoretical prediction of potential IgE-binding regions was performed by selecting specific residues on the molecular surface displaying prominent electrostatic potential features. Point mutants of Pru p 3 were constructed by standard polymerase chain reaction procedures with the appropriate primers. Mutants were expressed in P pastoris by means of the pPIC 9 vector and purified from the corresponding supernatants by gel-filtration chromatography followed by RP-HPLC. IgE binding by Pru p 3 mutants was tested by immu-nodetection and quantified by ELISA and ELISA inhibition assays. Synthetic peptides (10 mer; 5 amino acids overlapping) covering the full Pru p 3 sequence were used to detect IgE epitopes by 125 I–anti-IgE immunodetection. Results Pru p 3 showed a 3-dimensional structure comprising 4 α-helixes and a nonstructured C-terminal coil (residues 73 to 91). Regions around amino acids in positions 23 to 36, 39 to 44, and 80 to 91, particularly residues R39, T40, and R44, K80 and K91, were predicted as potential antibody recognition sites according to their relevant surface and electrostatic properties. Point mutants K80A and K91A were found to have an IgE-binding capacity similar to that of recombinant Pru p 3, but the triple mutant R39A/T40A/R44A showed a substantial decrease (approximately 5 times) of IgE binding. IgE immu-nodetection of synthetic peptides led to the identification of Pru p 3 sequence regions 11 to 25, 31 to 45, and 71 to 80 as major IgE epitopes. Conclusions Main IgE-binding regions of the Pru p 3 amino acid sequence were identified. The three major ones comprised the end of an α-helix and some residues of the following interhelix loop. These data can help to search for Pru p 3 hypoallergenic forms.