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This study evaluates variations in petrophysical properties within a mixed alluvial to lacustrine carbonate system (Miocene, Madrid Basin, Central Spain). The transition from alluvial environments to lake margins settings displays a shift from alluvial, siliciclastic red sandstones and mudstones to palustrine–lacustrine mudstones to packstones. Fluctuations in lake‐water level enabled land plants to occupy the lake margins during periods of low lake levels. The palustrine carbonates include features like pseudo‐microkarst, nodular and mottled limestones; the lacustrine deposits include enlarged root cavities, desiccation cracks and channel bodies. Scarce fresh water biota comprises charophytes, gastropods and ostracods. The sediments possess high natural, irregular varying, gamma‐ray values at the alluvial–lacustrine transition, and low, but constant values at full lacustrine sites. Acoustic properties agree with lithological variations within individual facies. Porosity is the most important parameter influencing P‐wave and S‐wave velocities. The scatter in the velocity–porosity relationship links to the porosity type; macro‐porosity or microporosity. The wide range of pore types and pore sizes results in a weak porosity to permeability relationship for the carbonate‐dominated rocks with low permeability for microporous and high permeability for macro‐porous carbonates. The sandstones (probably only inhibiting interparticle porosity), and to a lesser extent the sandy wackestones to packstones, show quite a strong relationship between porosity and permeability. Elastic properties of mixed alluvial–lacustrine deposits (this study) and marine deposits (literature data) overlap as variations in pore structures and porosity values are similar. Only 16% of the marine and lacustrine carbonate sediments display Equivalent Pore Aspect Ratio values above 0.2. In travertine deposits, 83% of the samples exceed Equivalent Pore Aspect Ratio values above 0.2, which highlights that travertine deposits are dominated by larger Equivalent Pore Aspect Ratios compared to lacustrine and marine carbonate deposits. Travertines display other rock frameworks with different pore types, pore distribution and amount of porosity. [ABSTRACT FROM AUTHOR]

Abstract: The formation of syn‐depositional fractures in carbonate platforms is considered an important feature in the understanding of platform evolution. This study investigates the mechanisms of fracture formation in rimmed flat‐topped carbonate platforms in the very well‐exposed Cariatiz Miocene Fringing Reef Unit, SE Spain. Fracture data were obtained using a combination of LIDAR and field mapping techniques, which proved useful in understanding general fracture trends. The morphological expression of fracture sets, preferred fracture localization, crosscutting relationships and fracture fill are characteristics that provide constraints on the timing of fracture formation and opening. Three dominant fracture populations were identified, amongst which a margin parallel and a margin perpendicular fracture set. Margin parallel fractures localize around the platform margin and form vertically extensive dikes that crosscut facies boundaries. The sedimentary fill of such fractures suggests syn‐depositional fracture formation under marine conditions. Together, fracture characteristics suggest a gravitational driver for the formation of tensile stress and the development of margin parallel fractures along the platform edge. Margin perpendicular structures form sub‐vertical dikes and fracture corridors. Margin perpendicular fractures localize on the platform slope and show two types of fracture fill, indicating marine and continental origins. Based on variations of fracture morphology along the carbonate platform, fracture localization, petrographic analysis of sedimentary fill and stable isotope analysis on sparite cements, we suggest a gravitational control on the formation of these fractures. Two mechanisms for the formation of subvertical margin perpendicular fractures are proposed: (1) principal stress rotation as a result of downslope loading. (2) Differential compaction over buried gulley systems on antecedent clinoform slopes. We suggest that the formation of sub‐vertical margin perpendicular fractures might be a systematic feature in slopes of flat‐topped carbonate platforms. [ABSTRACT FROM AUTHOR]

The primary goals of seismic interpretation and quantification are to understand and define reservoir architecture and the distribution of petrophysical properties. Since seismic interpretation is associated with major uncertainties, outcrop analogues are used to support and improve the resulting conceptual models. In this study, the Miocene carbonates of Cerro de la Molata (Las Negras, south-east Spain) have been selected as an outcrop analogue. The heterogeneous carbonate rocks of the Cerro de la Molata Platform were formed by a variety of carbonate-producing factories, resulting in various platform morphologies and a wide range of physical properties. Based on textural (thin sections) and petrophysical (porosity, density, carbonate content and acoustic properties) analyses of the sediments, eleven individual facies types were determined. The data were used to produce synthetic seismic profiles of the outcrop. The profiles demonstrate that the spatial distribution of the facies and the linked petrophysical properties are of key importance in the appearance of the synthetic seismic sections. They reveal that carbonate factory and facies-specific reflection patterns are determined by porosity contrasts, diagenetic modifications and the input of non-carbonate sediment. The reflectors of the seismograms created with high-frequency wavelets are coherent with the spatial distribution of the predefined facies within the depositional sequences. The synthetic seismograms resulting from convolution with lower frequency wavelets do not show these details - the major reflectors coincide with: (i) the boundary between the volcanic basement and the overlying carbonates; (ii) the platform geometries related to changes in carbonate factories, thus sequence boundaries; and (iii) diagenetic zones. Changes in seismic response related to diagenesis, switching carbonate producers and linked platform geometries are important findings that need to be considered when interpreting seismic data sets. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with presumed autoimmune origin, triggered by genetic and environmental risk factors. A recent genome-wide association study conducted on MS identified new biallelic markers outside the HLA (human leucocyte antigen) region involved in disease susceptibility: rs1109670 (DDEF2); rs1458175 (PDZRN4); rs1529316 and rs2049306 (CSMD1); rs16914086 (TBC1D2); rs1755289 (SH3GL2); rs1841770 (ZIC1); rs651477 (EN1); rs7607490 (TRIB2); rs397020 (C20orf46); rs908821 (SLC25A36); rs7672826 (MGC45800) and rs9523762 (GPC5). We aimed at replicating these top association signals in a Spanish cohort of 2863 MS patients and 2930 sex- and age-matched controls. Only rs9523762 mapping in the GPC5 gene was significantly associated (G allele, P=1.6 × 10−5; odds ratio (95% confidence interval)=1.23 (1.12-1.36)), supporting a role for this proteoglycan in MS predisposition. The independent replication of association signals to validate data generated by genome-wide association scans is a first step in the effort to improve patient care. [ABSTRACT FROM AUTHOR]

Polymorphisms from the TENR-IL2-IL21 block in the 4q27 chromosome were recently associated with type 1 diabetes, celiac disease, rheumatoid arthritis and psoriasis. We undertook this study to investigate the potential role of polymorphisms rs3136534, rs6822844 and rs2069762 (−330 T/G IL2) in multiple sclerosis (MS) (805 patients of Spanish Caucasian origin and 952 health controls). We did not find evidence for association with any single nucleotide polymorphisms (SNPs) tested. Allele and genotype frequencies of the SNPs, which were studied, were similar in DRB1*15-positive or DRB1*15-negative patients. After stratification of MS patients by clinical course, a weak association was observed with rs2069762 G allele and haplotype bearing this allele with secondary progressive MS, although these cases represent 22% of the MS cases. Our results did not show major influence of TENR-IL2-IL21 locus on susceptibility or disease progression in MS. However, we could not exclude completely the effect in MS for this region. Additional studies, using much larger sample sizes and analysis of additional polymorphisms in the gene and its flanking region, will be required to ascertain their contributions to MS susceptibility. [ABSTRACT FROM AUTHOR]

The article discusses the findings of a study conducted in Spain on the role played by X chromosome methylation in spontaneous abortion of a male fetus. The study involved a family who underwent DNA analysis. The phosphoglycerate kinase (PGK) locus was analysed in order to inactivate the X chromosome. It is said that another form of X chromosome inactivation occurs in male spermatogenesis.

The aim of this work is to describe the diversity and phylogeny of rhizobial bacteria associated to nodules of Ononis tridentata L. in different geographical regions of Spain. Twenty-two bacterial isolates were characterized using several molecular techniques (16S amplified ribosomal deoxyribonucleic acid restriction analysis, fingerprinting, and sequencing) and phylogenies were inferred from their 16S and nodC gene sequences. Phylogenetically, the isolates grouped with the genera Rhizobium, Mesorhizobium, Phylobacterium, and Bosea. The nodC gene, essential for nodulation, was detected for the first time in isolates close to the genera Bosea and Phyllobacterium. The bacteria isolated showed a high diversity at the genus, species, and strain level regardless of the geographical origin of the host plant. This is the first report describing bacteria associated to nodules of O. tridentata. This shrub legume is highly prized for the revegetation of gypsum soils in semiarid Mediterranean areas. Our molecular description of bacteria associated to this legume improves the current understanding of the ecology of this plant species. Our findings have implications for formulating suitable bacterial inocula to recover gypsum ecosystems. [ABSTRACT FROM AUTHOR]

Objectives: Bacille Calmette-Guérin (BCG) vaccine has immunomodulatory effects that may provide protection against unrelated infectious diseases. We aimed to determine whether BCG vaccination protects adults against COVID-19., Design: Phase III double-blind randomised controlled trial., Setting: Healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom during the COVID-19 pandemic., Participants: 3988 healthcare workers with no prior COVID-19 and no contraindication to BCG., Intervention: Randomised 1:1 using a web-based procedure to receive a single 0.1 mL intradermal dose of BCG-Denmark (BCG group, n = 1999) or saline (placebo group, n = 1989)., Main Outcome Measures: Difference in incidence of (i) symptomatic and (ii) severe COVID-19 during the 12 months following randomisation in the modified intention to treat (mITT) population (confirmed SARS-CoV-2 naïve at inclusion)., Results: Of the 3988 participants randomised, 3386 had a negative baseline SARS-CoV-2 test and were included in the mITT population. The 12-month adjusted estimated risk of symptomatic COVID-19 was higher in the BCG group (22.6%; 95% confidence interval [CI] 20.6 to 24.5%) compared with the placebo group (19.6%; 95% CI 17.6 to 21.5%); adjusted difference +3.0% points (95% CI 0.2 to 5.8%; p = 0.04). The 12-month adjusted estimated risk of severe COVID-19 (mainly comprising those reporting being unable to work for ≥3 consecutive days) was 11.0% in the BCG group (95% CI 9.5 to 12.4%) compared with 9.6% in the placebo group (95% CI 8.3 to 11.1%); adjusted difference +1.3% points (95% CI -0.7 to 3.3%, p = 0.2). Breakthrough COVID-19 (post COVID-19 vaccination) and asymptomatic SARS-CoV-2 infections were similar in the two groups. There were 18 hospitalisations due to COVID-19 (11 in BCG group, 7 in placebo group; adjusted hazard ratio 1.56, 95% CI 0.60 to 4.02, p = 0.4) and two deaths due to COVID-19, both in the placebo group., Conclusions: Compared to placebo, vaccination with BCG-Denmark increased the risk of symptomatic COVID-19 over 12 months among healthcare workers and did not decrease the risk of severe COVID-19 or post-vaccination breakthrough COVID-19., Trial Registration: ClinicalTrials.gov NCT04327206., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The trial is financially supported by the Foundations listed in the Funding section. Authors disclose funding support over the past 36 months: National Health and Medical Research Council (NHMRC) Ideas Grant (NM), NHMRC Investigator Grant (NC), Melbourne Children’s Clinician-Scientist Fellowship Grant (KPP). Outside of the submitted work, JCr has received grants or contracts from Sanofi, MSD & CEPI; payment or honoraria for presentations from Pfizer and participates on Latin American data safety monitoring/advisory boards for mRNA-1273 (Modern/Zodiac), RSV maternal vaccine (Pfizer), Qdenga vaccine (Takeda) and Nirmatrelvir/Ritonavir-Paxlovid (Pfizer). KG is a member of the Royal Children’s Hospital (RCH) Human Research Ethics Committee (the primary ethics committee providing approval for the BRACE trial) and Director of Research Operations at RCH; she abstained from all discussion, voting, approval and review related to the BRACE trial. All other authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Medieval Iberia witnessed the complex negotiation of religious, social, and economic identities, including the formation of religious orders that played a major role in border disputes and conflicts. While archival records provide insights into the compositions of these orders, there have been few direct dietary or osteoarchaeological studies to date. Here, we analysed 25 individuals discovered at the Zorita de los Canes Castle church cemetery, Guadalajara, Spain, where members of one of the first religious orders, the Order of Calatrava knights, were buried between the 12th to 15th centuries CE. Stable carbon (δ 13 C) and nitrogen (δ 15 N) isotope analyses of bone collagen reveal dietary patterns typical of the Medieval social elite, with the Bayesian R model, 'Simmr' suggesting a diet rich in poultry and marine fish in this inland population. Social comparisons and statistical analyses further support the idea that the order predominantly comprised the lower nobility and urban elite in agreement with historical sources. Our study suggests that while the cemetery primarily served the order's elite, the presence of individuals with diverse dietary patterns may indicate complexities of temporal use or wider social interaction of the medieval military order., (© 2024. The Author(s).)

Introduction: The classical teaching methodology was based on passive transmission-based learning. The model has changed towards an orientation based on student-centred learning., Objective: The objective of the study has been to evaluate the students' perception when learning about urinary tract infections, and their perspective about the teaching imparted on this pathology in the various subjects that include ITU in their syllabus., Methods: A cross-sectional analytical study of the responses to an anonymous survey entitled: "Methodology on urine infections. Teaching aspects "issued by 228 students at their fifth year of Medical School, from two promotions. They referred to the following subjects: Pharmacy, Pathophisiology, Gynecology and Obstetrics, Infectious diseases, Microbiology, Nephrology, Pediatrics and Urology., Results: The following variables have been analysed: teaching content, teaching basic aspects of the disease, consideration of teaching methodology and improvement suggestions. Descriptive and inferential statistics were used., Conclusion: The study has concluded that teaching urinary tract infection is perceived in specific subjects related to microorganism (Microbiology), the target organ (Infectious diseases, Urology), affected patients (Pediatrics, Gynecology and Obstetrics) rather than transversal subjects such as Pathophysiology or Pharmacy. The teaching methodology has been considered appropriate by more than 50% of the students in five from the 8 subjects that teach the concept of urinary tract infection. The students suggest convenient changes in current teaching methodology in several subjects that impart the urinary tract infection concept., (Copyright © 2019 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)

Animal-vehicle collisions have become a serious traffic safety issue. Collisions have steadily increased over the last few decades, as have their associated socio-economic costs. Here, we explore the spatial and temporal patterns of animal-vehicle collisions reported to authorities in the province of Seville, southern Spain. Most animal-vehicle collisions involved domestic animals (>95%), particularly dogs (>80%), a pattern that sharply contrasts with that found in other Spanish and European regions, where collisions are mostly caused by game species. Dog-vehicle collisions were related to the traffic intensity of the roads and they were more frequent around dawn and dusk, coinciding with the peaks of activity of dogs. This pattern was consistent throughout the week, although on weekends there were fewer collisions due to lower traffic density at those times. These findings suggest that the aggregation of dog-vehicle collisions around twilight likely resulted from a combined effect of the activity peaks of dogs and traffic density. Seasonally, collisions increased in autumn and winter, coinciding with the period of intense hunting activity in the region. Further, during autumn and winter, rush hour partly overlaps with twilight due to longer nights in comparison with summer and spring, which may contribute to the increased rate of dog-vehicle collisions in these seasons. Spatially, satellite images of nighttime lights showed that dog-vehicle collisions were clustered near urban areas. Overall, the high incidence of stray dogs involved in animal-vehicle collisions highlights a road safety issue with this type of animals in the region., Competing Interests: The authors have declared that no competing interests exist.

Cystic echinococcosis (CE) is one of the most widespread helminthic zoonoses and is caused by the tapeworm Echinococcus granulosus complex. CE diagnosis and monitoring primarily rely on imaging techniques, complemented by serology. This is usually approached by the detection of IgG antibodies against hydatid fluid (HF), but the use of this heterogeneous antigenic mixture results in a variable percentage of false positive and negative results, and has shown to be useless for follow-up due to the long persistence of anti-HF antibodies in cured patients. To improve test performances and standardization, a number of recombinant antigens mainly derived from HF have been described, among them the B2t and 2B2t antigens. The performance of these antigens in the diagnosis and follow up of patients with CE has been so far evaluated on a limited number of samples. Here, we evaluated the performances of tests based on B2t and 2B2t recombinant antigens compared to HF in IgG-ELISA and immunochromatography (IC) for the diagnosis and follow-up of patients with CE in a retrospective cohort study. A total of 721 serum samples were collected: 587 from 253 patients with CE diagnosed by ultrasonography (US), 42 from patients with alveolar echinococcosis and 92 from healthy donors from Salamanca (Spain). The highest overall sensitivity was obtained with HF in ELISA (85.5%), followed by IC containing HF and 2B2t-HF (83.0% and 78.2%, respectively). The lowest sensitivity was obtained with B2t and 2B2t in ELISA (51.8%). The highest specificity was obtained with IC containing 2B2t-HF (100%), and the lowest with HF-ELISA (78.0%). The lowest cross-reactivity with sera from patients with alveolar echinococcosis was detected with the recombinant antigens in ELISA (9.5% - 16.7%) and the highest with the HF-IC (64.3%). The results of B2t and 2B2t-ELISA were influenced by cyst stage, as classified by US according to the WHO-Informal Working Group on Echinococcosis (WHO-IWGE), with low sensitivity for inactive (CE4 and CE5) cysts, and by the drug treatment, with higher sensitivity in patients after drug treatment compared with patients not subjected to drug treatment. The two recombinant antigens in ELISA provided promising results for monitoring patients in follow-up, although their use is limited to patients with positive serology against them at the beginning of the follow-up. Potential biological reasons behind the low sensitivity of the recombinant antigens and possible strategies to enhance the performance of CE serology are discussed., Competing Interests: José Manuel Delgado, Teresa Pardo-García, and Francisco Soriano-Gálvez are employed by Parque Tecnológico de la Salud (see Financial Disclosure). The authors declare no other competing interests exist.

Objectives: To study the incidence and prevalence of primary systemic vasculitides (PSV) in the Costa del Sol region (southern Spain) and to compare the major epidemiological studies in PSV with the results obtained in our area., Methods: Retrospective study including permanent residents ≥14 years (or older) diagnosed with PSV at the Hospital Costa del Sol (Marbella, Spain) between 1994 and 2010. Epidemiological data were collected and the annual incidence rate during the study period and the prevalence in 2010 were calculated per million population, except for GCA, which was estimated per 100,000 population >50 years., Results: Seventy-four adult patients were diagnosed with PSV, representing an annual incidence of 15.8 (95%CI 12.2-19.4) patients/million population. These diagnoses included 29 (39.1%) giant cell arteritis (GCA), 5 (6.7%) Takayasu's arteritis (TKA), 3 (4%) poly-arteritis nodosa (PAN), 29 (39.1%) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) [10 (13.5%) granulomatosis with polyangiitis (GPA) (Wegener), 16 (21.6%) microscopic polyangiitis (MPA) and 3 (4%) eosinophilic granulomatosis with polyangiitis (EGPA) (Churg-Strauss)], 7 (9.4%) IgA vasculitis (Henoch-Schönlein) (IgAV) and one (1.3%) cryobulinaemic vasculitis (CV). The annual incidence and 2010 prevalence for each of the PSV, respectively, were: GCA: 2.2/12.2; TKA: 1.1/10.5; PAN: 0.6/2.6; AAV: 6.2/44.8 (GPA: 2.1/15.8; MPA: 3.4/23.8; EGPA: 0.6/5.3); IgAV: 1.5/7.9; and CV: 0.2/0., Conclusions: The first epidemiological study of PSV in southern Spain corroborates their infrequency, with GCA and AAV as the PSV most often diagnosed. In southern Spain, the incidence and prevalence of PSV are lower than in northern Spain and in countries in the Northern Hemisphere.

CD6 has recently been identified and validated as risk gene for multiple sclerosis (MS), based on the association of a single nucleotide polymorphism (SNP), rs17824933, located in intron 1. CD6 is a cell surface scavenger receptor involved in T-cell activation and proliferation, as well as in thymocyte differentiation. In this study, we performed a haptag SNP screen of the CD6 gene locus using a total of thirteen tagging SNPs, of which three were non-synonymous SNPs, and replicated the recently reported GWAS SNP rs650258 in a Spanish-Basque collection of 814 controls and 823 cases. Validation of the six most strongly associated SNPs was performed in an independent collection of 2265 MS patients and 2600 healthy controls. We identified association of haplotypes composed of two non-synonymous SNPs [rs11230563 (R225W) and rs2074225 (A257V)] in the 2(nd) SRCR domain with susceptibility to MS (P max(T) permutation = 1×10(-4)). The effect of these haplotypes on CD6 surface expression and cytokine secretion was also tested. The analysis showed significantly different CD6 expression patterns in the distinct cell subsets, i.e. - CD4(+) naïve cells, P = 0.0001; CD8(+) naïve cells, P<0.0001; CD4(+) and CD8(+) central memory cells, P = 0.01 and 0.05, respectively; and natural killer T (NKT) cells, P = 0.02; with the protective haplotype (RA) showing higher expression of CD6. However, no significant changes were observed in natural killer (NK) cells, effector memory and terminally differentiated effector memory T cells. Our findings reveal that this new MS-associated CD6 risk haplotype significantly modifies expression of CD6 on CD4(+) and CD8(+) T cells.

Background: Previous review studies have suggested that computer games can serve as an alternative or additional form of treatment in several areas (schizophrenia, asthma or motor rehabilitation). Although several naturalistic studies have been conducted showing the usefulness of serious video games in the treatment of some abnormal behaviours, there is a lack of serious games specially designed for treating mental disorders., Aim: The purpose of our project was to develop and evaluate a serious video game designed to remediate attitudinal, behavioural and emotional processes of patients with impulse-related disorders., Method and Results: The video game was created and developed within the European research project PlayMancer. It aims to prove potential capacity to change underlying attitudinal, behavioural and emotional processes of patients with impulse-related disorders. New interaction modes were provided by newly developed components, such as emotion recognition from speech, face and physiological reactions, while specific impulsive reactions were elicited. The video game uses biofeedback for helping patients to learn relaxation skills, acquire better self-control strategies and develop new emotional regulation strategies. In this article, we present a description of the video game used, rationale, user requirements, usability and preliminary data, in several mental disorders.

Background: Wind farms have shown a spectacular growth during the last 15 years. Avian mortality through collision with moving rotor blades is well-known as one of the main adverse impacts of wind farms. In Spain, the griffon vulture incurs the highest mortality rates in wind farms., Methodology/principal Findings: As far as we know, this study is the first attempt to predict flight trajectories of birds in order to foresee potentially dangerous areas for wind farm development. We analyse topography and wind flows in relation to flight paths of griffon vultures, using a scaled model of the wind farm area in an aerodynamic wind tunnel, and test the difference between the observed flight paths of griffon vultures and the predominant wind flows. Different wind currents for each wind direction in the aerodynamic model were observed. Simulations of wind flows in a wind tunnel were compared with observed flight paths of griffon vultures. No statistical differences were detected between the observed flight trajectories of griffon vultures and the wind passages observed in our wind tunnel model. A significant correlation was found between dead vultures predicted proportion of vultures crossing those cells according to the aerodynamic model., Conclusions: Griffon vulture flight routes matched the predominant wind flows in the area (i.e. they followed the routes where less flight effort was needed). We suggest using these kinds of simulations to predict flight paths over complex terrains can inform the location of wind turbines and thereby reduce soaring bird mortality.

Multiple Sclerosis (MS) is the most common progressive and disabling neurological condition affecting young adults in the world today. From a genetic point of view, MS is a complex disorder resulting from the combination of genetic and non-genetic factors. We aimed to identify previously unidentified loci conducting a new GWAS of Multiple Sclerosis (MS) in a sample of 296 MS cases and 801 controls from the Spanish population. Meta-analysis of our data in combination with previous GWAS was done. A total of 17 GWAS-significant SNPs, corresponding to three different loci were identified:HLA, IL2RA, and 5p13.1. All three have been previously reported as GWAS-significant. We confirmed our observation in 5p13.1 for rs9292777 using two additional independent Spanish samples to make a total of 4912 MS cases and 7498 controls (ORpooled = 0.84; 95%CI: 0.80-0.89; p = 1.36 × 10-9). This SNP differs from the one reported within this locus in a recent GWAS. Although it is unclear whether both signals are tapping the same genetic association, it seems clear that this locus plays an important role in the pathogenesis of MS.

TNFRSF6B and TNFRSF14 genes were recently associated with Crohn's disease and rheumatoid arthritis. TNFRSF14 is known as herpes virus entry mediator (HVEM), and herpes viruses have been involved in the aetiology of multiple sclerosis (MS). MS patients present human herpes virus 6 (HHV6) in active plaques and increased antibody responses to HHV6. We aimed to ascertain the role of these genes in MS susceptibility and to investigate the relationship of the gene encoding the widely expressed HVEM receptor with the active replication of HHV6 found in some MS patients. Genotyping of 1370 Spanish MS patients and 1715 ethnically matched controls was performed. HHV6A DNA levels (surrogate of active viral replication) were analysed in serum of MS patients during a 2-year follow-up. Both polymorphisms were associated with MS predisposition, with stronger effect in patients with HHV6 active replication-TNFRSF6B-rs4809330(*)A: P=0.028, OR=1.13; TNFRSF14-rs6684865(*)A: overall P=0.0008, OR=1.2; and HHV6-positive patients vs controls: P=0.017, OR=1.69.

Cystic echinococcosis (CE) remains an important health problem in many regions of the world, both where no control measures have been implemented, and where control programs have been incompletely successful with ensuing re-emergence of the disease. In Spain, official data on CE show an increase in the proportion of intermediate hosts with CE during the last few years, and autochthonous pediatric patients have been reported, a sign of active local transmission of disease. A similar picture emerges from data reported to the European Food Safety Authority by other European countries. Nevertheless, several crucial aspects related to CE that would help better understand and control the disease have not been tackled appropriately, in particular the emergence of infection in specific geographical areas. In this respect, while some data are missing, other data are conflicting because they come from different databases. We review the current situation of CE in Spain compared with areas in which similar problems in the CE field exist, and offer recommendations on how to overcome those limitations. Specifically, we believe that the introduction of national registries for CE with online data entry, following the example set by the European Registry for Alveolar Echinococcosis, would help streamline data collection on CE by eliminating the need for evaluating and integrating data from multiple regions, by avoiding duplication of data from patients who access several different health facilities over time, and by providing much needed clinical and epidemiological data that are currently accessible only to clinicians.

Genome-wide association studies (GWAS) have revealed that different diseases share susceptibility variants. Twelve single-nucleotide polymorphisms (SNPs) previously associated with different immune-mediated diseases in GWAS were genotyped in a Caucasian Spanish population of 2864 multiple sclerosis (MS) patients and 2930 controls. Three SNPs were found to be associated with MS: rs1678542 in KIF5A (P=0.001, odds ratio (OR)=1.13, 95% confidence interval (CI)=1.05-1.23); rs3184504 in SH2B3 (P=0.00001, OR=1.19, 95% CI=1.10-1.27) and rs763361 in CD226 (P=0.00007, OR=1.16, 95%CI=1.08-1.25). These variants have previously been associated with rheumatoid arthritis and type 1 diabetes. The SH2B3 polymorphism has additionally been associated with systemic lupus erythematosus. Our results, in addition to validating some of these loci as risk factors for MS, are consistent with shared genetic mechanisms underlying different immune-mediated diseases. These data may help to shape the contribution of each pathway to different disorders.

Objective: To determine the anesthetic, surgical, and postoperative characteristics of patients who underwent thoracic surgery in Catalonia, Spain, in 2003., Material and Methods: A prospective, cross-sectional survey was carried out on 14 randomly chosen days in 2003. All hospitals performing thoracic surgery in Catalonia took part. Data were collected on patient characteristics, anesthetic techniques, procedures, analgesia, and postoperative care., Results: Data on 171 anesthetic procedures in thoracic surgery were collected from 27 hospitals; these procedures represented 0.7% of the total anesthetic workload. Extrapolation from the collected data indicated that 4458 anesthetic procedures were performed in thoracic surgery in 2003 (95% confidence interval, 3624-4823 procedures). Of these procedures, 75.4% were performed in public hospitals and 24.6% in private hospitals. The median age of patients was 55 years (10th-90th percentiles, 22.4-73 years) and 63.9% were men. Surgical procedures were scheduled in 92.8% of the cases. The most common interventions were lung and bronchial surgery other than resection (36.8%), lung and/or bronchial resection (24.6%), and thoracoscopy and mediastinoscopy (20.5%). The median duration of pneumonectomies and lobectomies was 180 minutes (10th-90th percentiles, 90-221 minutes). General anesthesia was the most commonly used procedure (74.3%). Postoperative recovery took place in a conventional recovery room in 54.4% of cases, in a postanesthetic intensive care unit in 33.3% of cases, and in an intensive care unit in 12.3% of cases., Conclusions: This survey provided information on anesthesia in thoracic surgery, which represented 0.7% of all anesthesia procedures in an area with a population of 7 million.

End-stage renal diseases (ESRD) are becoming more frequent in HIV-infected patients. In Europe there is little information about HIV-infected patients on dialysis. A cross-sectional multicenter survey in 328 Spanish dialysis units was conducted in 2006. Information from 14,876 patients in dialysis was obtained (81.6% of the Spanish dialysis population). Eighty-one were HIV infected (0.54%; 95% CI, 0.43-0.67), 60 were on hemodialysis, and 21 were on peritoneal dialysis. The mean (range) age was 45 (28-73) years. Seventy-two percent were men and 33% were former drug users. The mean (range) time of HIV infection was 11 (1-27) years and time on dialysis was 4.6 (0.4-25) years. ESRD was due to glomerulonephritis (36%) and diabetes (15%). HIV-associated nephropathy was not reported. Eighty-five percent were on HAART, 76.5% had a CD4 T cell count above 200 cells, and 73% had undetectable viral load. Thirty-nine percent of patients met criteria for inclusion on the renal transplant (RT) waiting list but only 12% were included. Sixty-one percent had HCV coinfection. HCV-coinfected patients had a longer history of HIV, more previous AIDS events, parenteral transmission as the most common risk factor for acquiring HIV infection, and less access to the RT waiting list (p < 0.05). The prevalence of HIV infection in Spanish dialysis units in 2006 was 0.54% HCV coinfection was very frequent (61%) and the percentage of patients included on the Spanish RT waiting list was low (12%).

Background: IRF5 is a transcription factor involved both in the type I interferon and the toll-like receptor signalling pathways. Previously, IRF5 has been found to be associated with systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel diseases. Here we investigated whether polymorphisms in the IRF5 gene would be associated with yet another disease with features of autoimmunity, multiple sclerosis (MS)., Methods: We genotyped nine single nucleotide polymorphisms and one insertion-deletion polymorphism in the IRF5 gene in a collection of 2337 patients with MS and 2813 controls from three populations: two case-control cohorts from Spain and Sweden, and a set of MS trio families from Finland., Results: Two single nucleotide polymorphism (SNPs) (rs4728142, rs3807306), and a 5 bp insertion-deletion polymorphism located in the promoter and first intron of the IRF5 gene, showed association signals with values of p<0.001 when the data from all cohorts were combined. The predisposing alleles were present on the same common haplotype in all populations. Using electrophoretic mobility shift assays we observed allele specific differences in protein binding for the SNP rs4728142 and the 5 bp indel, and by a proximity ligation assay we demonstrated increased binding of the transcription factor SP1 to the risk allele of the 5 bp indel., Conclusion: These findings add IRF5 to the short list of genes shown to be associated with MS in more than one population. Our study adds to the evidence that there might be genes or pathways that are common in multiple autoimmune diseases, and that the type I interferon system is likely to be involved in the development of these diseases.

Some polymorphisms in the FCRL3 gene, a member of the Fc-receptor like family, have been associated with several autoimmune diseases and recently with multiple sclerosis (MS). We performed a case-control study of three SNPs in FCRL3 gene in 645 MS patients and 786 controls, all Caucasians from the South of Spain. Genotype and allele frequencies of two SNPs (rs7528684/FCRL3&#95;3 and rs7522061/N28D), which were in high linkage disequilibrium (r(2) = 0.87), differed between MS cases and controls. The C allele of FCRL3&#95;3 was found to be protective for MS (per allele OR = 0.81, 95% C.I. = 0.70-0.94; P-value = 0.007) as was the G variant of N28D, but no association was found for rs11264799/FCRL3&#95;4. Haplotype analysis confirmed these associations with highly consistent effect sizes for haplotypes carrying the C allele of FCRL3&#95;3.

Background: The most widely used prognostic indices for estimation of survival, including for dialysis patients, were described by Charlson, and an adaptation was proposed by Hemmelgarn for dialysis patients. We present the first age-comorbidity prognostic index (ACPI) designed in a Mediterranean incident dialysis population and examine its concordance with other prognostic indices., Methods: Incident dialysis patients were scored in relation to age and 11 diseases. Cox regression analysis was performed to construct multiple regression models, and diseases with a hazard ratio (HR) higher than 1.2 were included in the index. The impact of age was assessed by including it in a separate multivariate model. Scores were categorized in 3 levels of risk: low (0-1 points), medium (2-4 points) and high levels (5 or more points). The probability of survival of each group was calculated according to the Kaplan-Meier method, and receiver operating characteristic (ROC) curves were plotted to examine the concordance with other prognostic indices., Results: A cohort of 304 patients on hemodialysis (80%) and peritoneal dialysis was analyzed. Global mortality rate was 31% (93/304). The mean score was 4.41 +/- 2.84. Diseases that received the highest scores were ischemic heart disease (IHD) with chronic heart failure (CHF), and malignancies of less than 5 years of evolution. With regard to age, the maximum score was received by patients over 60 years old. The probability of survival at 3 years was 89%, 77% and 54% for low-, medium- and high-risk groups, respectively (log-rank test, 19; p=0.0001). The ROC curves showed similar areas for our index (0.749), the Charlson index (0.758) and Hemmelgarn index (0.708), but our index scored higher than Charlson in older patients, IHD with CHF, CHF, peripheral vascular disease and systemic diseases., Conclusions: Although prospective external validation of this new index is required, this index adequately estimates the probability of survival at 3 years. The prognostic power of ACPI is similar to that of the Charlson index; however, relevant differences were found, concerning the weight of factors age, cardiovascular diseases and myocardial dysfunction. In end-stage renal disease we recommend estimating survival by indices established in incident dialysis patients, due to the particular comorbid conditions of this population.

Objective: We aimed to study clinical, radiological and molecular genetic features of patients with cerebral cavernous malformations (CCMs) from the Iberian Peninsula., Methods: We screened Krit1(CCM1), MGC4607(CCM2), and PDCD10(CCM3) by systematic SSCP and direct sequencing of coding exons in 48 nuclear families and 30 sporadic cases of CCM from Spain and Portugal., Results: Screening of CCM patients detected nine different mutations in 19 families. We found four new mutations in Krit1. Three of them were caused by either a small insertion or deletion, which lead to frameshift and premature termination codons. We also found a missense L308H mutation located in a highly conserved sequence within the ankyrin domain of Krit1. In CCM2, we found a redundant 14 bp deletion in exon 5 of MGC4607 which predicts a truncated protein at residue 230. We did not find mutations in CCM3., Conclusions: Finding that the 14 bp deletion was present in eleven families from the Iberian Peninsula indicates a high prevalence of this mutation. This redundant CCM2 mutation is worth considering in molecular diagnosis and genetic counselling of cerebral cavernous malformations.

Introduction: Its high rates of prevalence, mortality and disability make acute cerebrovascular disease (ACVD) a priority health problem. It is as the second most common cause of admission to internal medicine services., Aims: To examine inpatient care for ACVD during 2004 in the Valle de los Pedroches health area in the province of Cordoba, as well as survival at six months, so as to be able to carry out the changes needed to improve the attention offered for this condition., Patients and Methods: A longitudinal study of the acute phase of the illness and survival at six months was conducted by means of face-to-face interviews., Results: The prevalence of arterial hypertension (75.5%) stands out as a risk factor. The mean age was higher than in other series. There is no characteristic profile of clinical symptoms. The proportion of ischaemic to haemorrhagic strokes falls within the normal range. All 110 patients were submitted to a cranial computerised axial tomography scan in less than three hours. A compromised level of consciousness, senility, haemorrhagic stroke, poorer scoring on the Canadian Neurological Scale and complications all affected mortality rates. The study showed that 20% died while in hospital and 19.1% at six months. At discharge, 30.9% were undergoing rehabilitation. The spouse was the main caregiver in 55.5% of cases. A total of 79% had sequelae at six months., Conclusions: Instruments that allow fast effective diagnoses and treatments and guarantee proper clinical practice while reducing brain damage and its dependence should be made generally available. Improving primary and secondary prevention is essential in order to halt the progression of ACVD.

Currently available methods for the diagnosis of human schistosomiasis often lack enough sensitivity and specificity. Recently, several authors have developed more specific and sensitive diagnostic methods, mainly based on the polymerase chain reaction (PCR) technique. Nevertheless, these have been only applied for the diagnosis of 1 out of 4 Schistosoma species affecting man (S. mansoni). Additionally, application of specific PCR has been exclusively used for blood or faecal patients' samples. Here, we develop a new, high sensitive PCR approach that allows the genus- and species-specific amplification of the main 4 Schistosoma species causing disease in man plus S. bovis. We further successfully apply this technique for the detection of parasite DNA in easy-to-handle urine samples from patients with schistosomiasis. With these samples, we have found 94.4% sensitivity and 99.9% specificity when applying a genus-specific (Schistosoma spp.) primer pair, and 100% sensitivity and 98.9% specificity in a species-specific (S. mansoni) PCR.

Introduction: Sneeze is an ubiquitous phenomenon that happens to everyone. In spite of this, little attention has been paid to it, among medical literature in general, and even less in neurologic texts. A curious entity, called autosomal dominant compelling helio-ophthalmic outburst syndrome, has been scarcely described in the scientific literature. This reflex appears when subjects are exposed suddenly to intense sunlight and it consists of long incoercible sneeze bursts. There are no publications on this subject among the spanish literature.and intensity increase with time., Objective: To study the clinical and physiological features of the reflex in Spanish families., Patients and Method: Affected subjects were identified by personal interview and given a questionnaire drawn up for this study. Besides, they were instructed to give the questionnaire to their relatives.and intensity increase with time., Results: All the six families showed a high-penetrance, autosomal dominant inheritance. The reflex had a high consistency, a latency about 3 seconds, an intersneeze interval of 2 seconds and a frequency of 2-3 sneezes/ burst. Refractory period was long.and intensity increase with time., Discussion: Our study suggest a higher consistency, shorter latency and lower age of onset of the reflex in our patients than general population, and that frequency and intensity increase with time.

Introduction: Hydatid disease is a major health problem in endemic countries. In Spain, this disease was notifiable from 1981 to 1996, although its incidence kept increasing until the end of this period. From 1997 on, hydatid disease is only surveyed by endemic autonomous regions. Thus, true incidences for human hydatid disease in Spain are currently unknown. In this study the cases recorded from 1996 to 2003 at the Hospital Universitario (Salamanca) which receives patients from all Salamanca province, were analyzed. Method. We obtained epidemiological and clinical data from patients at the University Hospital (reference hospital in Salamanca province) with registered CIE-10 codification 122.0 to 122.9 (hydatid disease), from January 1996 to December 2003, excluding those patients not arriving from Salamanca. We estimated the incidence of hydatid disesase in Salamanca province regarding the total population of the province., Results: Our data show that the mean incidence (1996-2003) was 10,8/100.000 inhabitants, twice as many as previously reported by the notifiable diseases scheme. 30% of infected patients were younger than 45. In addition, during the last three years of study, several cases of paediatric hydatid disease were observed. The analysis of the origin of the cases showed a broad distribution throughout the whole province of Salamanca., Conclusions: The real incidence of this disease seems to be higher than previously estimated. Importantly, the several cases of paediatric hydatid disease detected within the last two years of our study, suggest a possible re-emergence of hydatid disease.

Objectives: We have carried out electrophysiological studies and sural nerve biopsy evaluation in a Spanish family with genetically proven Machado-Joseph disease (SCA3/MJD) phenotype III., Patients and Methods: Two symptomatic and other two asymptomatic members of the family were clinically examined. Electrophysiological evaluation included multimodal evoked potentials, quantitative electromyography and nerve conduction studies, and central motor conduction time. We also report neuropathological findings in the sural nerve biopsy in the proband., Results: Analysis of the SCA3/MJD CAG trinucleotide repeat at the ataxin 3 gene in the DNA of the proband and one of his daughters demonstrated an expanded allele of 63 CAG repeat units. Ataxic pursuit was primary disturbed in MJD, followed by gaze evoked nystagmus, hypermetric saccades and glissades. Limitation of vertical and horizontal gaze, impaired sinusoidal vestibulo-ocular reflex and vestibulo-ocular reflex-fixation-suppression, and active and passive optokinetic nistagmus loss appeared at later stages. Evoked potential studies showed multimodal abnormalities. Electrophysiological and sural nerve biopsy findings correspond well to a pattern of both anterior horn and root ganglion cell distal dominant degeneration. Central motor conduction time was normal in our patients up to advanced stages of the disease., Conclusions: Electrophysiological and neuropathological studies suggested widespread peripheral and central affection in MJD. Repeated application of electrophysiological techniques may prove useful for monitoring disease progress.

Introduction: Multiple sclerosis (MS) is a demyelinating and inflammatory disease of the central nervous system (CNS) with a clear proved genetic susceptibility. The real frequency and clinical features of familial MS is although not well established in Spain., Objective: We studied the clinical and CSF features of familial MS (FMS) patients in comparison with the rest of our patients., Patients and Methods: We reviewed 308 definite MS patients looking for patients with other familial members with MS. We analyzed clinical characteristics (age, age at onset, sex, evolution time, evolution course, symptoms at onset, disability measured by EDSS scale) and IgG synthesis measured by Tibbling-Link index., Results: We found 23 patients (10 men and 13 women) in 18 independent families with at least other family member diagnosed of definite MS (7.47% of our total MS population). Age and age at onset were no different from non FMS cases. The clinical course was relapsing-remitting in 21 out of 23 FMS cases and secondary progressive in two. No primary progressive cases were found among FMS. At onset the symptom most frequently found in FMS was optic neuritis. Mean EDSS score was lower in FMS cases in comparison with the rest of cases. Link index was increase in 93.7% of patients with FMS., Conclusion: In comparison with non familiar forms FMS patients in Spain, present more often remitting courses, are less disabled, optical neuritis is more frequently seen as onset symptom and IgG synthesis is more often increased.

By understanding the size and characteristics of the potential donor pool, the concentration and location of the potential donors and factors influencing low rates of donation, it is possible to identify opportunities to improve the organ donation system. The exact donor gap needs to be established for each hospital/area, as published figures do not necessary reflect local potential. Nevertheless, marked differences with respect to the minimum standards in the number, location, and characteristics of organ donors should be considered as suggestive of low performance. The first stage where potential donors are lost is the detection of people who can be diagnosed as brain dead and, hence, could be considered a potential organ donor. Improving the donor identification implies the development of donor detection programmes. That and other initiatives to improve the donation rate need to be started in hospitals after the assessment of the local potential and local factors specifically implicated in the local performance.

A comparison was made, by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), of excretory/secretory (ES)-crude and immunopurified (with the corresponding anti-host serum) hydatid fluids-and somatic (S)-protoscoleces-proteins, from several ovine, equine, swine, bovine and human Echinococcus granulosus Spanish isolates. Likewise, the host influence on parasitic ES protein expression was studied, comparing purified hydatid fluids from ovine and equine cysts obtained from natural hosts and in RNMI mice. Purified hydatid fluids patterns, under reducing conditions, yielded the most precise differentiation of Spanish strains of E. granulosus into three groups (ovine-bovine-human, equine and swine), the finding of a characteristic 82 kDa band in equine isolates, and an unusual arrangement of bands between 50 and 6 kDa in swine samples. In addition, differences were found amongst crude and purified hydatid fluids, especially in bovine and swine isolates. The total protein patterns of protoscoleces were most complex, and therefore could not be used for strain differentiation. Finally, the purified hydatid fluids from cysts developed in natural and experimental hosts showed similar protein patterns, suggesting the lack of host influence, under our experimental conditions, on the expression of parasitic ES proteins.

The phenomenon on intraspecific variation in Echinococcus granulosus is already documented in Spain, where unilocular hydatidosis is an endemic disease. The first speciation studies, focused at a genomic level, showed the existence of three different strains: ovine-bovine-human, equine and swine-caprine. In the present study, the genomic identification, by random amplified polymorphic DNA technique (RAPD) of a larger number of Spanish E. granulosus isolates, using five different primers, showed the maintenance of these groups. Thus, some of these strains may not be infective for man. These conclusions were supported by a phenotypic characterization of the same isolates by zymodeme technique, showing the five isoenzyme systems used that Spanish E. granulosus strains can also be distinguished at a phenotypic level by isoenzymatic patterns. Both techniques (RAPD and zymodemes) were used for statistical analysis and for the construction of two dendrograms, which were slightly different. In addition, some intrastrain variation was detected with both techniques, a phenomenon that is directly related to the different speciation theories proposed for E. granulosus strains. The epidemiological implications of the results are discussed in the text.