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Background: We aimed to investigate the association between DNA-methylation biological age (B-age) calculated as age acceleration (ageAcc) and key aneurysmal subarachnoid haemorrhage (aSAH) complications such as vasospasm, delayed cerebral ischaemia (DCI), poor outcome, and mortality., Methods: We conducted a prospective study involving 277 patients with aSAH. B-age was determined in whole blood samples using five epigenetic clocks: Hannum's, Horvath's, Levine's and both versions of Zhang's clocks. Age acceleration was calculated as the residual obtained from regressing out the effect of C-age on the mismatch between C-age and B-age. We then tested the association between ageAcc and vasospasm, DCI and 12-month poor outcome (mRS 3-5) and mortality using linear regression models adjusted for confounders., Results: Average C-age was 55.0 years, with 66.8% being female. Vasospasm occurred in 143 cases (51.6%), DCI in 70 (25.3%) and poor outcomes in 99 (35.7%), with a mortality rate of 20.6%. Lower ageAcc was linked to vasospasm in Horvath's and Levine's clocks, whereas increased ageAcc was associated with 12-month mortality in Hannum's clock. No significant differences in ageAcc were found for DCI or poor outcome at 12 months with other clocks., Conclusions: Our study indicates that B-age is independently associated with vasospasm and 12-month mortality in patients with aSAH. These findings underscore the potential role of epigenetics in understanding the pathophysiology of aSAH-related complications and outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Extensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) infections are difficult to treat. We aimed to compare aminoglycosides or polymyxin monotherapy versus other antibiotic regimens (carbapenems, aztreonam, ceftazidime, cefepime, ceftolozane-tazobactam, or ceftazidime-avibactam) in complicated urinary tract infections (cUTI) caused by XDR-PA., Methods: Study performed at a tertiary-care hospital from 2010 to 2019. All consecutive adult patients with XDR-PA urine cultures and diagnosed with cUTI were retrospectively reviewed. XDR phenotype was defined according to Magiorakos et al. A propensity score was used as a covariate in multivariate analyses and for matching. Primary outcome was early clinical failure and at end of treatment (EOT). Main secondary outcomes were 30- and 90-day mortality, microbiological clearance, and antibiotic-related side effects., Results: Of the 465 episodes screened, 101 were included, 48% were treated with aminoglycoside or colistin monotherapy. Most XDR-PA were susceptible to colistin (100%) and amikacin (43%). Patients treated with antibiotic regimens other than aminoglycosides or polymyxin monotherapy were more likely to have hematologic malignancy (p < 0.001), higher SOFA score (p = 0.048), and bacteremia (p = 0.003). In multivariate models adjusted by propensity score, aminoglycoside or colistin monotherapy was not associated with worse outcomes. After propensity score matching, 28 episodes in each treatment group were matched. Adjusted ORs (95% CI) for early clinical failure and at EOT with aminoglycosides or polymyxin monotherapy were 0.53 (0.18-1.58) and 1.29 (0.34-4.83), respectively. Aminoglycoside or colistin monotherapy was not associated with higher 30-day (HR 0.93, 95% CI 0.17-5.08) or 90-day mortality (HR 0.68, 95% CI 0.20-2.31), nor with absence of microbiological clearance (OR 0.72, 95% CI 0.33-1.58). No statistically significant differences were found in terms of nephrotoxicity. Clostridioides difficile infection was observed only in the "other antibiotic regimens" group (n = 6, 11.3%)., Conclusions: Aminoglycosides or polymyxin monotherapy showed good efficacy and safety profile in treating cUTI caused by XDR-PA. These results may be useful for antibiotic stewardship activities., (© 2021. The Author(s).)

Purpose: To evaluate the relationship between the incidence of complications and functionally monocular patients' emotional reactions during phacoemulsification under topical anesthesia., Methods: We enrolled 22 functionally monocular patients (11 males and 11 females; group 1) and 19 age- and sex-matched controls (6 males and 13 females; group 2) in this prospective, interventional, cross-sectional, case control study. Demographics data, including age, sex, and educational background, were collected. Surgeries were performed by the same surgeon, and during surgery, the patients' vital signs (blood pressure and heart rate) and surgical events (duration, body movements, signs of increased vitreous cavity pressure, difficulty in performing capsulorhexis, and complications) were noted. Pre- and postoperative visual acuity was also analyzed., Results: The mean age of group 1 was 73.05 ± 13.31 years and of group 1 was 69.74 ± 16.81 years. There was no significant between-group difference in systolic and diastolic blood pressures. The average heart rate was similar in both groups, too. During surgery, the surgeon's perception of excessive eye, eyelid, or head movements in both groups was similar, in addition to signs of increased vitreous cavity pressure., Conclusion: It is safe to perform phacoemulsification under topical anesthesia in functionally monocular patients, who apparently behave similarly to binocular patients.

Background and Purpose- Our aim was to describe variables associated with initial misdiagnosis of subarachnoid hemorrhage (SAH). We also analyzed the relationship of misdiagnosis with poor outcome and complications in good Hunt and Hess (HH) cases. Methods- In a prospective cohort of 401 patients with SAH, misdiagnosis was defined as failure to correctly identify, at first physician contact, a subsequently documented SAH; this meant no urgent radiological study and lumbar puncture was performed. Poor outcome was defined as modified Rankin Scale score 3 to 6 at 3-month follow-up. We recorded age, sex, hypertension, diabetes mellitus, current smoking, previous antithrombotic treatment, initial HH and radiological severity, presence of aneurysm, first therapeutic procedure, hydrocephalus, delayed cerebral ischemia (DCI), rebleeding, and procedure-related complications. Results- Misdiagnosis was confirmed in 104/401 (25.9%) patients, who also had a longer time-to-admission to hospital. Misdiagnosis was associated with less clinical and radiological severity, compared with a correct diagnosis; the 2 groups did not differ in age or cardiovascular risk factor profile. Poor outcome was registered in 167/401 patients (41.6%). Age, misdiagnosis, and greater clinical and radiological initial severity were independent predictors of poor outcome. In the 236 patients (58.8% of cohort) with HH 1-2, misdiagnosis was associated with poor outcome in univariate and multivariate analysis, respectively (odds ratio=3.89; 95% CI, 1.89-8.01). Delayed cerebral ischemia (odds ratio=2.47; 95% CI, 1.2-5.09) and procedure-related complications (odds ratio=2.27; 95% CI, 1.07-4.82) were independently associated with misdiagnosis. Conclusions- Misdiagnosis is an unresolved problem in SAH, and it is a missed opportunity for good outcome in patients with HH 1-2. The poor outcome is partially explained by a higher risk of delayed cerebral ischemia and procedure-related complications in misdiagnosed patients. There is a need to improve the diagnostic strategy in patients reporting only a headache (HH 1-2) after SAH.

The Spanish Barley Core Collection (SBCC) is a source of genetic variability of potential interest for breeding, particularly for adaptation to Mediterranean environments. Two backcross populations (BC 2 F 5 ) were developed using the elite cultivar Cierzo as the recurrent parent. The donor parents, namely SBCC042 and SBCC073, were selected from the SBCC lines due to their outstanding yield in drought environments. Flowering time, yield and drought-related traits were evaluated in two field trials in Zaragoza (Spain) during the 2014-15 and 2015-16 seasons and validated in the 2017-18 season. Two hundred sixty-four lines of each population were genotyped with the Barley Illumina iSelect 50k SNP chip. Genetic maps for each population were generated. The map for SBCC042 × Cierzo contains 12,893 SNPs distributed in 9 linkage groups. The map for SBCC073 × Cierzo includes 12,026 SNPs in 7 linkage groups. Both populations shared two QTL hotspots. There are QTLs for flowering time, thousand-kernel weight (TKW), and hectoliter weight on a segment of 23 Mb at ~515 Mb on chromosome 1H, which encompasses the HvFT3 gene. In both populations, flowering was accelerated by the landrace allele, which also increased the TKW. In the same region, better soil coverage was contributed by SBCC042 but coincident with a lower hectoliter weight. The second large hotspot was on chromosome 6H and contained QTLs with wide intervals for grain yield, plant height and TKW. Landrace alleles contributed to increased plant height and TKW and reduced grain yield. Only SBCC042 contributed favorable alleles for "green area," with three significant QTLs that increased ground coverage after winter, which might be exploited as an adaptive trait of this landrace. Some genes of interest found in or very close to the peaks of the QTLs are highlighted. Strategies to deploy the QTLs found for breeding and pre-breeding are proposed.

Purpose: Ventilator-induced diaphragm dysfunction or damage (VIDD) is highly prevalent in patients under mechanical ventilation (MV), but its analysis is limited by the difficulty of obtaining histological samples. In this study we compared diaphragm histological characteristics in Maastricht III (MSIII) and brain-dead (BD) organ donors and in control subjects undergoing thoracic surgery (CTL) after a period of either controlled or spontaneous MV (CMV or SMV)., Methods: In this prospective study, biopsies were obtained from diaphragm and quadriceps. Demographic variables, comorbidities, severity on admission, treatment, and ventilatory variables were evaluated. Immunohistochemical analysis (fiber size and type percentages) and quantification of abnormal fibers (a surrogate of muscle damage) were performed., Results: Muscle samples were obtained from 35 patients. MSIII (n = 16) had more hours on MV (either CMV or SMV) than BD (n = 14) and also spent more hours and a greater percentage of time with diaphragm stimuli (time in assisted and spontaneous modalities). Cross-sectional area (CSA) was significantly reduced in the diaphragm and quadriceps in both groups in comparison with CTL (n = 5). Quadriceps CSA was significantly decreased in MSIII compared to BD but there were no differences in the diaphragm CSA between the two groups. Those MSIII who spent 100 h or more without diaphragm stimuli presented reduced diaphragm CSA without changes in their quadriceps CSA. The proportion of internal nuclei in MSIII diaphragms tended to be higher than in BD diaphragms, and their proportion of lipofuscin deposits tended to be lower, though there were no differences in the quadriceps fiber evaluation., Conclusions: This study provides the first evidence in humans regarding the effects of different modes of MV (controlled, assisted, and spontaneous) on diaphragm myofiber damage, and shows that diaphragm inactivity during mechanical ventilation is associated with the development of VIDD.

Background: In winter barley plants, vernalization and photoperiod cues have to be integrated to promote flowering. Plant development and expression of different flowering promoter (HvVRN1, HvCO2, PPD-H1, HvFT1, HvFT3) and repressor (HvVRN2, HvCO9 and HvOS2) genes were evaluated in two winter barley varieties under: (1) natural increasing photoperiod, without vernalization, and (2) under short day conditions in three insufficient vernalization treatments. These challenging conditions were chosen to capture non-optimal and natural responses, representative of those experienced in the Mediterranean area., Results: In absence of vernalization and under increasing photoperiods, HvVRN2 expression increased with day-length, mainly between 12 and 13 h photoperiods in our latitudes. The flowering promoter gene in short days, HvFT3, was only expressed after receiving induction of cold or plant age, which was associated with low transcript levels of HvVRN2 and HvOS2. Under the sub-optimal conditions here described, great differences in development were found between the two winter barley varieties used in the study. Delayed development in 'Barberousse' was associated with increased expression levels of HvOS2. Novel variation for HvCO9 and HvOS2 is reported and might explain such differences., Conclusions: The balance between the expression of flowering promoters and repressor genes regulates the promotion towards flowering or the maintenance of the vegetative state. HvOS2, an ortholog of FLC, appears as a strong candidate to mediate in the vernalization response of barley. Natural variation found would help to exploit the plasticity in development to obtain better-adapted varieties for current and future climate conditions.

Objectives: To evaluate the prevalence of vitamin D deficiency in critically ill patients upon admission to an Intensive Care Unit (ICU) and its prognostic implications., Design: A single-center, prospective observational study was carried out from January to November 2015. Patients were followed-up on until death or hospital discharge., Setting: The department of Critical Care Medicine of a university hospital., Patients: All adults admitted to the ICU during the study period, without known factors capable of altering serum 25(OH)D concentration., Interventions: Determination of serum 25(OH)D levels within the first 24h following admission to the ICU., Main Variables of Interest: Prevalence and mortality at 28 days., Results: The study included 135 patients, of which 74% presented deficient serum 25(OH)D levels upon admission to the ICU. Non-survivors showed significantly lower levels than survivors (8.14ng/ml [6.17-11.53] vs. 12ng/ml [7.1-20.30]; P=.04], and the serum 25(OH)D levels were independently associated to mortality (OR 2.86; 95% CI 1.05-7.86; P=.04]. The area under the ROC curve was 0.61 (95% CI 0.51-0.75), and the best cut-off point for predicting mortality was 10.9ng/ml. Patients with serum 25(OH)D<10.9ng/ml also showed higher acute kidney injury rates (13 vs. 29%; P=.02)., Conclusion: Vitamin D deficiency is highly prevalent upon admission to the ICU. Severe Vitamin D deficiency (25[OH]D<10.9ng/ml) upon admission to the ICU is associated to acute kidney injury and mortality., (Copyright © 2017 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.)

Drought causes important losses in crop production every season. Improvement for drought tolerance could take advantage of the diversity held in germplasm collections, much of which has not been incorporated yet into modern breeding. Spanish landraces constitute a promising resource for barley breeding, as they were widely grown until last century and still show good yielding ability under stress. Here, we study the transcriptome expression landscape in two genotypes, an outstanding Spanish landrace-derived inbred line (SBCC073) and a modern cultivar (Scarlett). Gene expression of adult plants after prolonged stresses, either drought or drought combined with heat, was monitored. Transcriptome of mature leaves presented little changes under severe drought, whereas abundant gene expression changes were observed under combined mild drought and heat. Developing inflorescences of SBCC073 exhibited mostly unaltered gene expression, whereas numerous changes were found in the same tissues for Scarlett. Genotypic differences in physiological traits and gene expression patterns confirmed the different behavior of landrace SBCC073 and cultivar Scarlett under abiotic stress, suggesting that they responded to stress following different strategies. A comparison with related studies in barley, addressing gene expression responses to drought, revealed common biological processes, but moderate agreement regarding individual differentially expressed transcripts. Special emphasis was put in the search of co-expressed genes and underlying common regulatory motifs. Overall, 11 transcription factors were identified, and one of them matched cis -regulatory motifs discovered upstream of co-expressed genes involved in those responses.

Powdery mildew causes severe yield losses in barley production worldwide. Although many resistance genes have been described, only a few have already been cloned. A strong QTL (quantitative trait locus) conferring resistance to a wide array of powdery mildew isolates was identified in a Spanish barley landrace on the long arm of chromosome 7H. Previous studies narrowed down the QTL position, but were unable to identify candidate genes or physically locate the resistance. In this study, the exome of three recombinant lines from a high-resolution mapping population was sequenced and analyzed, narrowing the position of the resistance down to a single physical contig. Closer inspection of the region revealed a cluster of closely related NBS-LRR (nucleotide-binding site-leucine-rich repeat containing protein) genes. Large differences were found between the resistant lines and the reference genome of cultivar Morex, in the form of PAV (presence-absence variation) in the composition of the NBS-LRR cluster. Finally, a template-guided assembly was performed and subsequent expression analysis revealed that one of the new assembled candidate genes is transcribed. In summary, the results suggest that NBS-LRR genes, absent from the reference and the susceptible genotypes, could be functional and responsible for the powdery mildew resistance. The procedure followed is an example of the use of NGS (next-generation sequencing) tools to tackle the challenges of gene cloning when the target gene is absent from the reference genome., (Copyright © 2016 Crop Science Society of America.)

Objective: To describe the case-mix of patients admitted to intensive care units (ICUs) in Spain during the period 2006-2011 and to assess changes in ICU mortality according to severity level., Design: Secondary analysis of data obtained from the ENVN-HELICS registry. Observational prospective study., Setting: Spanish ICU., Patients: Patients admitted for over 24h., Interventions: None., Variables: Data for each of the participating hospitals and ICUs were recorded, as well as data that allowed to knowing the case-mix and the individual outcome of each patient. The study period was divided into two intervals, from 2006 to 2008 (period 1) and from 2009 to 2011 (period 2). Multilevel and multivariate models were used for the analysis of mortality and were performed in each stratum of severity level., Results: The study population included 142,859 patients admitted to 188 adult ICUs. There was an increase in the mean age of the patients and in the percentage of patients >79 years (11.2% vs. 12.7%, P<0.001). Also, the mean APACHE II score increased from 14.35±8.29 to 14.72±8.43 (P<0.001). The crude overall intra-UCI mortality remained unchanged (11.4%) but adjusted mortality rate in patients with APACHE II score between 11 and 25 decreased modestly in recent years (12.3% vs. 11.6%, odds ratio=0.931, 95% CI 0.883-0.982; P=0.008)., Conclusion: This study provides observational longitudinal data on case-mix of patients admitted to Spanish ICUs. A slight reduction in ICU mortality rate was observed among patients with intermediate severity level., (Copyright © 2015 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.)

Objective: To describe the characteristics of the patients case-mix admitted to ICUs due to medical and surgical disease, and to compare both groups., Design: Analysis of data covering the period 2006-2011 in the ENVIN-HELICS registry. An observational, prospective, multicenter and voluntary participation study., Setting: A total of 188 Spanish ICUs., Patients: All patients admitted for more than 24 hours., Main Variables: Demographic data, cause of admission, severity scores, length of stay, mortality., Results: A total of 138,999 patients were analyzed. Of these, 65,467 (47.1%) were admitted due to a non-coronary medical cause, 27,785 (20,0%) due to coronary-related illness, 28,044 (20,2%) after elective surgery and 17,613 (12.7%) after urgent surgery. Use of devices, nosocomial infections and isolation of multirresistant organisms were more prevalent in urgent surgery patients. Longer length of stay (median 5 days; interquartile range 2-11) as well as higher severity scale values (APACHE II and SAPS II) corresponded to this same group of patients. Mortality was higher in non-coronay medical patients. On categorizing the patients according to the APACHE II score, mortality was seen to be higher in urgent surgery cases than in elective surgery patients in all groups. The largest difference was observed in the APACHE II score 6-10 group (3% vs. 0.9%) (OR: 2.14, 95% CI 1.825-2.513; p<0.001)., Conclusions: The mortality rate is higher in non-coronary medical patients, though resource use per patient is greater in the urgent surgery cases. The APACHE II scale underestimates mortality in emergency surgery patients., (Copyright © 2013 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.)

Flowering time in plants is a tightly regulated process. In barley (Hordeum vulgare L.), HvFT1, ortholog of FLOWERING LOCUS T, is the main integrator of the photoperiod and vernalization signals leading to the transition from vegetative to reproductive state of the plant. This gene presents sequence polymorphisms affecting flowering time in the first intron and in the promoter. Recently, copy number variation (CNV) has been described for this gene. An allele with more than one copy was linked to higher gene expression, earlier flowering, and an overriding effect of the vernalization mechanism. This study aims at (1) surveying the distribution of HvFT1 polymorphisms across barley germplasm and (2) assessing gene expression and phenotypic effects of HvFT1 alleles. We analyzed HvFT1 CNV in 109 winter, spring, and facultative barley lines. There was more than one copy of the gene (2-5) only in spring or facultative barleys without a functional vernalization VrnH2 allele. CNV was investigated in several regions inside and around HvFT1. Two models of the gene were found: one with the same number of promoters and transcribed regions, and another with one promoter and variable number of transcribed regions. This last model was found in Nordic barleys only. Analysis of HvFT1 expression showed that association between known polymorphisms at the HvFT1 locus and the expression of the gene was highly dependent on the genetic background. Under long day conditions the earliest flowering lines carried a sensitive PpdH1 allele. Among spring cultivars with different number of copies, no clear relation was found between CNV, gene expression and flowering time. This was confirmed in a set of doubled haploid lines of a population segregating for HvFT1 CNV. Earlier flowering in the presence of several copies of HvFT1 was only seen in cultivar Tammi, which carries one promoter, suggesting a relation of gene structure with its regulation. HvCEN also affected to a large extent flowering time.

Key Message: In two Spanish barley landraces with outstanding resistance to scald, the Rrs1 Rh4 locus was fine mapped including all known markers used in previous studies and closely linked markers were developed. Scald, caused by Rhynchosporium commune, is one of the most prevalent barley diseases worldwide. A search for new resistance sources revealed that Spanish landrace-derived lines SBCC145 and SBCC154 showed outstanding resistance to scald. They were crossed to susceptible cultivar Beatrix to create large DH-mapping populations of 522 and 416 DH lines that were scored for disease resistance in the greenhouse using two R. commune isolates. To ascertain the pattern of resistance, parents and reference barley lines with known scald resistance were phenotyped with a panel of differential R. commune isolates. Subpopulations were genotyped with the Illumina GoldenGate 1,536 SNP Assay and a large QTL in the centromeric region of chromosome 3H, known to harbour several scald resistance genes and/or alleles, was found in both populations. Five SNP markers closest to the QTL were converted into CAPS markers. These CAPS markers, together with informative SSR markers used in other scald studies, confirmed the presence of the Rrs1 locus. The panel of differential scald isolates indicated that the allele carried by both donors was Rrs1 Rh4 . The genetic distance between Rrs1 and its flanking markers was 1.2 cM (11&#95;0010) proximally and 0.9 cM (11&#95;0823) distally, which corresponds to a distance of just below 9 Mbp. The number and nature of scald resistance genes on chromosome 3H are discussed. The effective Rrs1 allele found and the closely linked markers developed are already useful tools for molecular breeding programs and provide a good step towards the identification of candidate genes.

Cerebral blood flow is the most important physiologic parameter in the setting of brain injury. A regional measurement of the flow (rCBF), can be obtained using continuous methods such as thermal diffusion flowmetry (TD-rCBF). This technology of monitoring allows us to detect and quantify ischemic events related with the temporary artery clipping or malposition of the definitive clip and in patients who have suffered a subarachnoid hemorrhage (SAH) or a traumatic brain injury. Likewise, the precocious detection of ischemic events might help us to adopt more rapidly therapeutic measures and more efficienty. Three cases show during aneurysm clipping procedures and at intensive care: the effects of different hypnotics on TD-rCBF values; the relationship between TD-rCBF and somatosensory and motor evoked potentials; and changes in TD-rCBF and transcranial Doppler ultrasonography (TDU) during a vasospasm. TD-rCBF showed in real-time flow variations induced by anaesthetics and detected changes of CBF earlier than evoked potentials and TDU., (Copyright © 2011 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.)

Background: Understanding the adaptation of cereals to environmental conditions is one of the key areas in which plant science can contribute to tackling challenges presented by climate change. Temperature and day length are the main environmental regulators of flowering and drivers of adaptation in temperate cereals. The major genes that control flowering time in barley in response to environmental cues are VRNH1, VRNH2, VRNH3, PPDH1, and PPDH2 (candidate gene HvFT3). These genes from the vernalization and photoperiod pathways show complex interactions to promote flowering that are still not understood fully. In particular, PPDH2 function is assumed to be limited to the ability of a short photoperiod to promote flowering. Evidence from the fields of biodiversity, ecogeography, agronomy, and molecular genetics was combined to obtain a more complete overview of the potential role of PPDH2 in environmental adaptation in barley., Results: The dominant PPDH2 allele is represented widely in spring barley cultivars but is found only occasionally in modern winter cultivars that have strong vernalization requirements. However, old landraces from the Iberian Peninsula, which also have a vernalization requirement, possess this allele at a much higher frequency than modern winter barley cultivars. Under field conditions in which the vernalization requirement of winter cultivars is not satisfied, the dominant PPDH2 allele promotes flowering, even under increasing photoperiods above 12 h. This hypothesis was supported by expression analysis of vernalization-responsive genotypes. When the dominant allele of PPDH2 was expressed, this was associated with enhanced levels of VRNH1 and VRNH3 expression. Expression of these two genes is needed for the induction of flowering. Therefore, both in the field and under controlled conditions, PPDH2 has an effect of promotion of flowering., Conclusions: The dominant, ancestral, allele of PPDH2 is prevalent in southern European barley germplasm. The presence of the dominant allele is associated with early expression of VRNH1 and early flowering. We propose that PPDH2 promotes flowering of winter cultivars under all non-inductive conditions, i.e. under short days or long days in plants that have not satisfied their vernalization requirement. This mechanism is indicated to be a component of an adaptation syndrome of barley to Mediterranean conditions.

Twenty-two landrace-derived inbred lines from the Spanish Barley Core Collection (SBCC) were found to display high levels of resistance to a panel of 27 isolates of the fungus Blumeria graminis that exhibit a wide variety of virulences. Among these lines, SBCC145 showed high overall resistance and a distinctive spectrum of resistance compared with the other lines. Against this background, the main goal of the present work was to investigate the genetic basis underlying such resistance using a doubled haploid population derived from a cross between SBCC145 and the elite spring cultivar Beatrix. The population was genotyped with the 1,536-SNP Illumina GoldenGate Oligonucleotide Pool Assay (Barley OPA-1 or BOPA1 for short), whereas phenotypic analysis was performed using two B. graminis isolates. A major quantitative trait locus (QTL) for resistance to both isolates was identified on the long arm of chromosome 6H (6HL) and accounted for ca. 60% of the phenotypic variance. Depending on the B. graminis isolate tested, three other minor QTLs were detected on chromosomes 2H and 7H, which explained less than 5% of the phenotypic variation each. In all cases, the alleles for resistance derived from the Spanish parent SBCC145. The position, the magnitude of the effect observed and the proportion of phenotypic variation accounted for by the QTL on 6HL suggest this is a newly identified locus for broad-based resistance to powdery mildew.

In barley, three genes are responsible for the vernalization requirement: VrnH1, VrnH2 and VrnH3. The winter growth habit of barley requires the presence of a recessive VrnH1 allele, together with an active VrnH2 allele. The candidate for VrnH3 (HvFT1) has been recently identified, with evidences pointing at a central role in the integration of the vernalization and photoperiod pathways. Functional polymorphisms have been proposed, but experimental evidence of their role on agronomic performance and adaptation is needed. We examined allelic variation at the promoter and intron 1 of the HvFT1 gene in a landrace collection of barley, finding a high diversity level, with its geographic distribution correlated with latitude. Focusing on genotypes with winter alleles in VrnH1 and VrnH2, an association analysis of the four main HvFT1 haplotypes found in the landrace collection detected differences in time to flowering. Landraces with the intron 1 TC allele, prevalent in the south, flowered 6-7 days earlier than those with the AG allele, under natural conditions. These results were validated in an independent F(2) population. In both data sets, the effect found was similar, but in opposite direction to that described in literature. The polymorphism reported at intron 1 contributes to variation in flowering time under field conditions. We have found that polymorphisms at the promoter also contribute to the effect of the gene on flowering time under field and controlled conditions. The variety of HvFT1 alleles described constitutes an allelic series that may have been a factor in agro-ecological adaptation of barley.

The response to vernalization and the expression of genes associated with responses to vernalization (VRNH1, VRNH2, and VRNH3) and photoperiod (PPDH1 and PPDH2) were analysed in four barley (Hordeum vulgare L.) lines: 'Alexis' (spring), 'Plaisant' (winter), SBCC058, and SBCC106 (Spanish inbred lines), grown under conditions of vernalization and short days (VSD) or no vernalization and long days (NVLD). The four genotypes differ in VRNH1. Their growth habits and responses to vernalization correlated with the level of expression of VRNH1 and the length of intron 1. 'Alexis' and 'Plaisant' behaved as expected. SBCC058 and SBCC106 showed an intermediate growth habit and flowered relatively late in the absence of vernalization. VRNH1 expression was induced by cold for all genotypes. Under VSD, VRNH1 expression was detected in the SBCC genotypes later than in 'Alexis' but earlier than in 'Plaisant'. VRNH2 was repressed under short days while VRNH1 expression increased in parallel. VRNH3 was detected only in 'Alexis' under NVLD, whereas it was not expressed in plants with the active allele of VRNH2 (SBCC058 and 'Plaisant'). Under VSD, PPDH2 was expressed in 'Alexis', SBCC058, and SBCC106, but it was only expressed weakly in 'Alexis' under NVLD. Further analysis of PPDH2 expression in two barley doubled haploid populations revealed that, under long days, HvFT3 and VRNH2 expression levels were related inversely. The timing of VRNH2 expression under a long photoperiod suggests that this gene might be involved in repression of PPDH2 and, indirectly, in the regulation of flowering time through an interaction with the day-length pathway.

Bronchoscopic identification of an endobronchial foreign body is an unexpected finding in adults. Modern imaging techniques such as computerised tomography (CT) may identify bronchial obstruction but not the cause. Moreover, images may be suggestive of other pathologies, especially when the previous aspiration cases are unknown. The most common CT findings in this setting are atelectasis, lung hyperlucency, localised bronchiectases and lobar consolidation. CT diagnosis of false endobronchial tumors in patients who have swallowed a foreign body is rarely described in the bibliography. In view of the potential adverse outcome in the case of wrong diagnosis we consider it is of interest to report two cases of endobronchial tumors diagnosed by CT in which flexible bronchoscopy allowed identification and extraction of an endobronchial foreign body.

Objective: Massive bleeding that cannot be controlled by the usual means, such as transfusion, is a serious medical problem with high associated mortality. Our aim was to assess the efficacy and safety of treatment with activated recombinant factor VII (rFVIIa) to control massive bleeding after the failure of other methods., Patients and Methods: This was a retrospective study of all cases of rFVIIa-treated massive bleeding in patients without a history of coagulation disorder from January 2003 through June 2007., Results: The prevalence of rFVIIa treatment for this indication was 1 in 5200 hospitalized patients. Thirty patients were treated. Bleeding was reduced or stopped in 80% and consumption of blood products was reduced after administration of rFVIIa. Mortality was 43% and death was due to continued bleeding in 5 cases. No deaths were due to thromboembolism., Conclusions: rFVIIa is efficacious for controlling bleeding and reducing transfusion requirements in cases of massive hemorrhage, but mortality unrelated to bleeding is high in patients experiencing this complication. Further study is needed to better assess the utility, dosing, and ideal timing in the use of this drug.

The pool of Western Mediterranean landraces has been under-utilised for barley breeding so far. The objectives of this study were to assess genetic diversity in a core collection of inbred lines derived from Spanish barley landraces to establish its relationship to barleys from other origins, and to correlate the distribution of diversity with geographical and climatic factors. To this end, 64 SSR were used to evaluate the polymorphism among 225 barley (Hordeum vulgare ssp. vulgare) genotypes, comprising two-row and six-row types. These included 159 landraces from the Spanish barley core collection (SBCC) plus 66 cultivars, mainly from European countries, as a reference set. Out of the 669 alleles generated, a large proportion of them were unique to the six-row Spanish barleys. An analysis of molecular variance revealed a clear genetic divergence between the six-row Spanish barleys and the reference cultivars, whereas this was not evident for the two-row barleys. A model-based clustering analysis identified an underlying population structure, consisting of four main populations for the whole genotype set, and suggested further possible subdivision within two of these populations. Most of the six-row Spanish landraces clustered into two groups that corresponded to geographic regions with contrasting environmental conditions. The existence of wide genetic diversity in Spanish germplasm, possibly related to adaptation to a broad range of environmental conditions, and its divergence from current European cultivars confirm its potential as a new resource for barley breeders, and make the SBCC a valuable tool for the study of adaptation in barley.

Objective: Assess the opinion of health care professions on the awarding of resources when the patient has a bad prognosis., Design: Survey type test where a scenario of a patient with a 6 month life prognosis is posed, differentiating between good and bad quality of life. It is evaluated if the following resources would be indicated if necessary: admission to ICU, hemodialysis, hip prosthesis, transplant, Hospital admission, antibiotics for bacterial infection, permanent pacemaker and surgery. To analyze the possible association between the variables, the Pearson's Chi Square Test or that of linear tendency was used. To determine if each person interviewed was appropriate in a different way based on the patient's quality of life status, the McNemar test was used., Setting: University Hospital of 480 beds., Participants: Sample of 256 volunteers (physicians and nurses) from the Emergency Service, Intensive Care Unit and Operating Room., Interventions: A responsible physician was in charge of personally distributing the survey during a 2-week period and to explain the possible doubts that could arise on it., Results: A total of 23.8% of those surveyed considered that transplant would be indicated and 79.8% that permanent pacemaker would be indicated if the patient had a good quality of life. If there was bad quality of life, 9.1% would have always indicated hemodialysis (60.5% never), 2.8% hip prosthesis (81.1% never) and 4% complex surgery (78.8% never). There were also significant differences in all the variables studied, depending on whether the patient had good or bad quality of life., Conclusion: There is great variability on the allotment of resources for patients with limited possibilities of survival.

Monitoring biomedical signals obtained from a patient generates information that processed conveniently, it has to allow detecting as soon as possible changes in the predicted evolution. The systematic register of one of these biomedical signals is named a time series. In this paper, a brief introduction appears to the Box-Jenkins methodology applied to time series analysis and it is applied this methodology to an example as illustration.

Seven thousand years of barley cultivation under the environmental hardships typical of the Mediterranean climate have generated genetic singularity of the Spanish barleys, consistently reported in the literature. From the Spanish National Collection of 2289 accessions, a core subset with 159 landraces and 16 old varieties was constituted. Twenty-seven characters were evaluated for the core collection, to define the structure of the diversity. Several evaluation trials were carried out in 1999-2000, whereas yield trials were performed in earlier years. Phenotypic diversity was large for most of the characters studied. Comparisons of genetic diversity between the core and the original collections suggested that the core is a good representation of the existing diversity in the BNG. Comparisons with results of studies on Spanish materials from other collections seem to indicate that the Spanish diversity is not well represented in some world collections. Principal component analyses for quantitative and qualitative characters revealed a clear distinction between two- and six-row cultivars, and also between landraces and commercial varieties. Geographical origins of the landraces were correlated with grain yield, heading date, duration of grain filling period, and growth class. In relation to diseases, altitude played an important role on the resistance to powdery mildew and brown rust. For brown rust, all the resistant landraces came from low altitudes. These geographical gradients seemed consistent with prior knowledge about barley adaptation, and would confirm the agreement between passport data and true adaptive origin of these landraces from a geographical point of view.

Tetramicra brevifilum, a microsporidian parasite of Scophthalmus maximus, was found in Lophius budegassa for the first time. This parasite was detected in 5 of 199 hosts captured in the coastal waters of Barcelona (Northwest Mediterranean), which enlarges the geographic distribution of this microsporidian. Affected fish did not show any external sign of disease, and cysts of T. brevifilum were found associated with the body musculature but were easily differentiated from those of Spraguea lophii, another microsporidian present in this host. A case of simultaneous infection by both T. brevifilum and S. lophii was found.

Pathologic study of the lesions caused by Microgemma ovoidea has shown that after the formation of the xenoma (stage 1), the parasitized cell is infiltrated by host macrophages (stage 2) and quickly encysted by the activity of fibroblasts that form a xenoma wall composed of collagenous fibers (stage 3). The phagocytic activity of the macrophages leads to the formation of a granuloma (stage 4) in which the cyst contents comprise macrophages filled with phagocytosed spores. This phagocytic activity is limited by the fact that some parts of the microsporidian spores, such as the spore walls, cannot be lysed by macrophages, which leads to the formation of fused giant cells containing nondigestible spore remanants. The final step in the process is healing (stage 5), in which some cells may start proliferating to regenerate the damaged area. Nevertheless, the host occasionally fails to control M. ovoidea infections. This failure can take two forms: bursting of the granuloma, or the appearance of secondary infections in granulomas, probably through parasitism of macrophages.

Background: To study the delay time to arrive of the hospital and its relation with any variables, of patients with acute myocardial infarction from the province of Teruel (Spain)., Patients and Methods: A prospective study was carried out from January 1991 to October 1994. We included patients who were diagnosticated of the acute myocardial infarction (212 men and 63 women). We considered the time between the thoracic pain and their arrive at the urgency service. We based the diagnosis in clinical, electrocardiographic and enzymatic criteria., Results: The mean delay time was 8 h 46 m. The 66.5% arrives before 6 hours. We found no differences between rural or urban patients. The delay time was minor in men than women (7 h 12 m versus 14 h, p = 0.0019), in younger (< 65 years old) than in the older (6 h 3 m versus 10 h 18 m, p = 0.0278), and in those who were admitted to the ICU (7h 16 m versus 20 h 33 m, p = 0.0001). Was longer in patients with arterial hypertension and diabetes. Was minor in patients with dyslipemia and tobacco habit. Many patients to arrive of the hospital by physician order and with own vehicles, it took less time arrive at the hospital than by ambulance (8 h 30 m versus 18 h, p < 0.05). The medium delay in the emergency area was 2 h 35 m. The delay time was longer in patients who died (16 h versus 7h 30 m, p = 0.0018) and in those who present more frequently cardiac failure., Conclusions: The mean delay time to arrive at the hospital in patients with acute myocardial infarction from the province of Teruel (Spain) in unreasonable and in takes a poor prognosis, so we consider necessary to study the causes of this delay in order to correct them.

Food contamination with respect to microsporidiosis in humans (associated with acquired immunodeficiency syndrome) and in marine fish farming deserves particular attention. For the first time, a study on the longevity and resistance to both heat and freezing of the spores of a vertebrate microsporidian, Glugea stephani, parasitizing a commercial flatfish was carried out. As judged on the basis of determinations of the extrusion rate, the resistance of the spores to temperature stress was remarkable. The extrusion rate, which can be directly related to infectivity, was always lower than the viability (membrane integrity). It should be pointed out that neither heat (60 degrees C for 30 min) nor freezing (-19 degrees C for 24 h) caused a complete reduction in the extrusion rate or viability. Consequently, the ingestion of poorly cooked or raw fish (even if previously frozen) represents a danger for aquaculture and, probably, for immunodepressed patients.

Spore suspensions of microsporidian parasites of fish (Microsporidium ovoideum, Glugea stephani, Glugea atherinae and Spraguea lophii) have been analyzed by flow cytometry. Spore nuclei were dyed either by propidium iodide or bis-benzimide (Hoechst 33342). By observation of forward light scatter and fluorescence the four species could be distinguished and the mono- and diplokaryotic populations of S. lophii identified. Staining of DNA by bis-benzimide was better and easier than propidium iodide. Forward light scatter and fluorescence values were characteristic of each species and remained unchanged throughout the year, so flow cytometry can be used for distinction of spores of some microsporidian parasites once their flow cytometric parameters are known. However, special care has to be taken in tool calibration and material preparation for analysis because of the high precision of the technique.