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Remote ischemic conditioning (RIC) is a promising therapeutic approach for ischemic stroke patients. It has been proven that RIC reduces infarct size and improves functional outcomes. RIC can be applied either before ischemia (pre-conditioning; RIPreC), during ischemia (per-conditioning; RIPerC) or after ischemia (post-conditioning; RIPostC). Our aim was to systematically determine the efficacy of RIC in reducing infarct volumes and define the cellular pathways involved in preclinical animal models of ischemic stroke. A systematic search in three databases yielded 50 peer-review articles. Data were analyzed using random effects models and results expressed as percentage of reduction in infarct size (95% CI). A meta-regression was also performed to evaluate the effects of covariates on the pooled effect-size. 95.3% of analyzed experiments were carried out in rodents. Thirty-nine out of the 64 experiments studied RIPostC (61%), sixteen examined RIPreC (25%) and nine tested RIPerC (14%). In all studies, RIC was shown to reduce infarct volume (− 38.36%; CI − 42.09 to − 34.62%) when compared to controls. There was a significant interaction caused by species. Short cycles in mice significantly reduces infarct volume while in rats the opposite occurs. RIPreC was shown to be the most effective strategy in mice. The present meta-analysis suggests that RIC is more efficient in transient ischemia, using a smaller number of RIC cycles, applying larger length of limb occlusion, and employing barbiturates anesthetics. There is a preclinical evidence for RIC, it is safe and effective. However, the exact cellular pathways and underlying mechanisms are still not fully determined, and its definition will be crucial for the understanding of RIC mechanism of action. [ABSTRACT FROM AUTHOR]

The micromorphological characters of leaves in the genus Quercus have proved very useful in their taxonomy. A microhistological study of the most representative species of the genus Quercus in the eastern part of Sierra Morena (southern Iberian Peninsula) is carried out in this work: Q. coccifera, Q. faginea subsp. faginea, Q. pyrenaica, Q. rotundifolia and Q. suber. The leaves microcharacters were studied, measured, photographed and compared in order to provide a good description by optical microscope. In particular, features related to trichomes, stomata and epidermal cells on adaxial and abaxial leaf surface have been used. The data for 21 variables were collected. Our study confirms the usefulness of the micromorphological characters of the leaf epidermis and optical microscopy to distinguish between Quercus species, and has helped to identify the studied species. Some of the species can be identified by a single diagnostic character, and others by a combination of few characters. Based on the set of analyzed characteristics, a dichotomy key for the differentiation of the five taxa studied in this work is proposed. [ABSTRACT FROM AUTHOR]

Collaborative learning incorporates a social component in distance education to minimize the disadvantages of studying in solitude. Frequent analysis of student interactions is required for assessing collaboration. Collaboration analytics arose as a discipline to study student interactions and to promote active participation in e-learning environments. Unfortunately, researchers have been more focused on finding methods to solve collaboration problems than on explaining the results to tutors and students. Yet if students do not understand the results of collaboration analysis methods, they will rarely follow their advice. In this paper we propose a tool that analyzes student interactions and visually explains the collaboration circumstances to provoke the self-reflection and promote the sensemaking about collaboration. The tool presents a visual explanatory decision tree that graphically highlights student collaboration circumstances and helps to understand the reasoning followed by the tool when prescribing a recommendation. An assessment of the tool has demonstrated: (1) the students collaboration circumstances showed by the tool are easy to understand and (2) the students could realize the possible actions to improve the collaboration process. [ABSTRACT FROM AUTHOR]

Background: Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer and the most difficult to predict. When there are no distant metastases, the optimal therapy depends mainly on whether there are malignant lymph nodes in the mediastinum. Given the vigorous debate among specialists about which tests should be used, our goal was to determine the optimal sequence of tests for each patient.Methods: We have built an influence diagram (ID) that represents the possible tests, their costs, and their outcomes. This model is equivalent to a decision tree containing millions of branches. In the first evaluation, we only took into account the clinical outcomes (effectiveness). In the second, we used a willingness-to-pay of € 30,000 per quality adjusted life year (QALY) to convert economic costs into effectiveness. We assigned a second-order probability distribution to each parameter in order to conduct several types of sensitivity analysis.Results: Two strategies were obtained using two different criteria. When considering only effectiveness, a positive computed tomography (CT) scan must be followed by a transbronchial needle aspiration (TBNA), an endobronchial ultrasound (EBUS), and an endoscopic ultrasound (EUS). When the CT scan is negative, a positron emission tomography (PET), EBUS, and EUS are performed. If the TBNA or the PET is positive, then a mediastinoscopy is performed only if the EBUS and EUS are negative. If the TBNA or the PET is negative, then a mediastinoscopy is performed only if the EBUS and the EUS give contradictory results. When taking into account economic costs, a positive CT scan is followed by a TBNA; an EBUS is done only when the CT scan or the TBNA is negative. This recommendation of performing a TBNA in certain cases should be discussed by the pneumology community because TBNA is a cheap technique that could avoid an EBUS, an expensive test, for many patients.Conclusions: We have determined the optimal sequence of tests for the mediastinal staging of NSCLC by considering sensitivity, specificity, and the economic cost of each test. The main novelty of our study is the recommendation of performing TBNA whenever the CT scan is positive. Our model is publicly available so that different experts can populate it with their own parameters and re-examine its conclusions. It is therefore proposed as an evidence-based instrument for reaching a consensus. [ABSTRACT FROM AUTHOR]

Highlights: [•] Proposed a recommender system in a collaborative learning environment. [•] Created an influence diagram using expert knowledge and student interactions data. [•] The influence diagram offers a recommendation decision table. [•] Machine learning methods analyze the decisions and offer a recommendation tree. [•] The expert identifies four different scenarios in the recommendation tree. [ABSTRACT FROM AUTHOR]

Bayesian networks (BNs) and influence diagrams (IDs) are probabilistic graphical models that are widely used for building diagnosis- and decision-support expert systems. Explanation of both the model and the reasoning is important for debugging these models, alleviating users' reluctance to accept their advice, and using them as tutoring systems. This paper describes some explanation options for BNs and IDs that have been implemented in Elvira and how they have been used for building medical models and teaching probabilistic reasoning to pre- and postgraduate students. [ABSTRACT FROM AUTHOR]

Blood pressure (BP) control at recently established goals of <130/80 mm Hg is often difficult to achieve in diabetic patients. This work examines the effect of pioglitazone on 24-hour ambulatory BP monitoring in patients with type 2 diabetes and difficult-to-control hypertension. Twenty-seven participants with difficult-to-control hypertension (defined as ambulatory BP monitoring ≥125/75 mm Hg) taking antihypertensive medications (mean, 4.1±0.8 drugs) were enrolled in an open, prospective, blinded end point study of add-on therapy with pioglitazone 30 to 45 mg for 20 weeks. After 20 weeks of treatment, 24-hour ambulatory BP monitoring showed significant reductions (from 144±13 to 136±16 mm Hg systolic BP and from 79±9 to 76±10 mm Hg diastolic BP [P =.001]). Treatment was also associated with improvements in insulin sensitivity and glycemic and lipid profile. These findings suggest that pioglitazone could be a therapeutic option in diabetics who still have elevated BP values in spite of receiving treatment with at least 3 antihypertensive drugs. [ABSTRACT FROM AUTHOR]

Left ventricular hypertrophy increases the risk for cardiovascular target organ damage, myocardial infarction, and stroke. The authors assessed the patterns of ventricular adaptation in 107 essential hypertensives whose treatment had been withdrawn and its modification after 1 year of hypertension treatment. Blood pressure decreased from 158 ±17/96 ±12 mm Hg to 137 ±15/83 ±10 mm Hg (mean ± SD; p<0.001); 45% of the patients (49 of 107) had their blood pressure controlled below 140 mm Hg and 90 mm Hg. Although a significant decrease of left ventricular mass index was found in the study, the percentage of patients with normal left ventricular geometry at the completion of the study increased by only 9% (27% to 36%, p >0.05). Left ventricular mass geometry improved in 31% of the patients, remained unaffected in 51%, and worsened in 18%. The data suggest that even while suboptimal antihypertensive treatment reduces left ventricular mass index, either left ventricular hypertrophy or concentric remodeling remains present in a significant number of patients at the end of a 1-year treatment period. The authors conclude that these patients should be considered as a subgroup at high risk and should be treated more aggressively. [ABSTRACT FROM AUTHOR]

Introduction: Cost-effectiveness analysis (CEA) is used increasingly in medicine to determine whether the health benefit of an intervention is worth the economic cost. Decision trees, the standard decision modeling technique for non-temporal domains, can only perform CEAs for very small problems. Influence diagrams can model much larger problems, but only when the decisions are totally ordered.Objective: To develop a CEA method for problems with unordered or partially ordered decisions, such as finding the optimal sequence of tests for diagnosing a disease.Methods: We explain how to model those problems using decision analysis networks (DANs), a new type of probabilistic graphical model, somewhat similar to Bayesian networks and influence diagrams. We present an algorithm for evaluating DANs with two criteria, cost and effectiveness, and perform some experiments to study its computational efficiency. We illustrate the representation framework and the algorithm using a hypothetical example involving two therapies and several tests and then present a DAN for a real-world problem, the mediastinal staging of non-small cell lung cancer.Results: The evaluation of a DAN with two criteria, cost and effectiveness, returns a set of intervals for the willingness to pay, separated by incremental cost-effectiveness ratios (ICERs). The cost, the effectiveness, and the optimal intervention are specific for each interval, i.e., they depend on the willingness to pay.Conclusion: Problems involving several unordered decisions can be modeled with DANs and evaluated in a reasonable amount of time. OpenMarkov, an open-source software tool developed by our research group, can be used to build the models and evaluate them using a graphical user interface. [ABSTRACT FROM AUTHOR]

In this study, we studied the genetic diversity and population genetic structure of the endangered endemic Crepis granatensis, using amplified fragments length polymorphism (AFLP) and plastid DNA (cpDNA). No genetic divergences were obtained using cpDNA markers. Three primers combinations selected from a total of 12 produced a total of 421 fragments, of which 418 (99.3%) were polymorphic. The total genetic diversity of C. granatensis was moderate (Ht = 0.260). Neís gene diversity ranged from 0.202 to 0.258. The fixation index (Fst) was 0.137, suggesting low to moderate genetic differentiation among populations. The AMOVA analysis revealed that genetic diversity was mainly concentrated among individuals within populations (74%), while 8% was found among populations and 18% among regions. The Bayesian analysis and PCoA identified two genetic clusters: one corresponded to La Sagra population and the other corresponded to the Mágina populations. Based on our genetic results, it is necessary to preserve the evolutionary potential of C. granatensis by protecting all extant populations. Both in situ and ex-situ conservation measures should be considered. Reinforcement, reintroduction, and translocation programmes could be performed if necessary. Finally, such conservation strategies should be considered both in the current recovery plan and management actions for the species. [ABSTRACT FROM AUTHOR]

Online peer assessment tasks are very popular and have unique characteristics that improve learning and encourage social interactions in a distance education environment. Unfortunately, social factors have usually been ignored in the process of selecting reviewers for online peer assessment tasks. We hypothesise that this fact could have some influence on the lack of engagement and participation by some learners. For this reason, we propose an approach in which social network analysis techniques, expert criteria, and Bayesian reasoning are applied to select reviewers with the objective of increasing participation in peer review tasks. The approach is divided into two elements. On the one hand, we have developed an influence diagram template that structures a set of proposed social network analysis variables in accordance with expert criteria. This influence diagram template can be easily updated for any course simply by eliciting a minimal set of parameters. On the other hand, we have instantiated the proposed influence diagram template to produce an influence diagram network to quantify the quality of reviewer assignment for an online peer assessment task. In an online experiment, we verified that the consideration of social factors can increase participation in a peer assessment task. [ABSTRACT FROM AUTHOR]

ITGAM–ITGAX (rs11150612, rs11574637), VAV3 rs17019602, CARD9 rs4077515, DEFA (rs2738048, rs10086568), and HORMAD2 rs2412971 are mucosal immune defence polymorphisms, that have an impact on IgA production, described as risk loci for IgA nephropathy (IgAN). Since IgAN and Immunoglobulin-A vasculitis (IgAV) share molecular mechanisms, with the aberrant deposit of IgA1 being the main pathophysiologic feature of both entities, we assessed the potential influence of the seven abovementioned polymorphisms on IgAV pathogenesis. These seven variants were genotyped in 381 Caucasian IgAV patients and 997 matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of these seven polymorphisms when the whole cohort of IgAV patients and those with nephritis were compared to controls. Similar genotype and allele frequencies of all polymorphisms were disclosed when IgAV patients were stratified according to the age at disease onset or the presence/absence of gastrointestinal or renal manifestations. Likewise, no ITGAM–ITGAX and DEFA haplotype differences were observed when the whole cohort of IgAV patients, along with those with nephritis and controls, as well as IgAV patients, stratified according to the abovementioned clinical characteristics, were compared. Our results suggest that mucosal immune defence polymorphisms do not represent novel genetic risk factors for IgAV pathogenesis. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyse the progress and current status of endangered autochthonous Spanish breeds exploring relationships between the main factors that determine the degree of endangered and the scientific and technical production related to the breed. The status of each breed was determined from official data published by Ministry of Agriculture during 2009-2013. The scientific and disclosure production related to each breed was collected from Web of Science and Google for 1950-2012. Each breed was classified according to its risk of extinction, based on demographic criteria and the annual growth rate of the population during 2009-2013. Results showed the risk of extinction was high in approximately the half of breeds, intermediate in 12.4% and very high in 36.1%. The highest levels of extinction risk corresponded to breed with recent official recognition and spread in small areas, with reduced population and herds of small size. Scientific literature on genetics has been significantly higher in breeds at greatest risk of extinction, while productive issues and products have been significantly studied most intensively in breeds with less risk of extinction. The disclosure literature on zootechnical issues and production systems has been significantly higher in breeds at lower risk of extinction. Therefore, it is recommended conservation policies focus, in a first stage, on genetic aspects and breed features, and secondly on productive issues and production systems. [ABSTRACT FROM AUTHOR]

OpenMarkov is an open-source software tool for probabilistic graphical models. It has been developed especially for medicine, but has also been used to build applications in other fields and for tuition, in more than 30 countries. In this paper we explain how to use it as a pedagogical tool to teach the main concepts of Bayesian networks and influence diagrams, such as conditional dependence and independence, d-separation, Markov blankets, explaining away, optimal policies, expected utilities, etc., and some inference algorithms: logic sampling, likelihood weighting, and arc reversal. The facilities for learning Bayesian networks interactively can be used to illustrate step by step the performance of the two basic algorithms: search-and-score and PC. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Arterial hypertension is an insulin-resistant condition that has been associated with an increased incidence of diabetes. We assessed the prevalence of glucose abnormalities in a population of patients with essential hypertension. Methods: In this cross-sectional study, 420 consecutively referred essential hypertensive patients were studied at 16 hypertension clinics in university and community hospitals of Spain. Fasting and 2-hour plasma glucose and insulin levels were determined in nondiabetic patients. Results: An abnormal glucose metabolism was diagnosed in 68.5% (95% confidence interval [CI], 63.7%-72.9%) of the patients. Isolated insulin resistance, defined by a homeostasis model assessment-estimated insulin resistance (HOMA-IR) equal to or above 3.8, was shown in 9.3% (95% CI, 6.7%-12.5%); impaired fasting glucose in 11.2% (95% CI, 8.6%-14.7%); impaired glucose tolerance in 22.5% (95% CI, 18.5%-26.9%); silent undiagnosed type 2 diabetes in 11.5% (95% CI, 8.6%-14.5%); and known diabetes mellitus in 13.9% (95% CI, 10.4%-17.2%) of the patients. According to the European Group for the Study of Insulin Resistance and the Adult Treatment Program III criteria, the metabolic syndrome was diagnosed in 41.5% (95% CI, 35.9%-47.3%) and 47.9% (95% CI, 43.1%-52.8%) of the patients, respectively. The prevalence of left ventricular hypertrophy (defined by a left ventricular mass index [LVMI] >125 g/m2) was 44.2%. The relation between HOMA-IR and LVMI was statistically nonsignificant, and the LVMI values in the HOMA-IR quartiles were similar. Only 27 patients (6.4%) showed good control of cardiovascular risk factors. In most patients (273, 65%; 95% CI, 60.3%-69.4%) 2 or more cardiovascular risk factors were identified as not being under control. Conclusions: Two thirds of the patients attending hypertension clinics with essential hypertension show an abnormal glucose metabolism. The metabolic syndrome can be identified in a substantial number of these patients, and 2 or more cardiovascular risk factors are not controlled in the majority of patients. [Copyright &y& Elsevier]

• A novel multi-input convolutional neural network is proposed to detect breast cancer. • The model combines thermal images of different views with personal and clinical data. • The model achieves better results than the ones only considering the front views. • Personal and clinical data helps to better detect patients with cancer. [Display omitted] Breast cancer is the most common cancer in women. While mammography is the most widely used screening technique for the early detection of this disease, it has several disadvantages such as radiation exposure or high economic cost. Recently, multiple authors studied the ability of machine learning algorithms for early diagnosis of breast cancer using thermal images, showing that thermography can be considered as a complementary test to mammography, or even as a primary test under certain circumstances. Moreover, although some personal and clinical data are considered risk factors of breast cancer, none of these works considered that information jointly with thermal images. We propose a novel approach for early detection of breast cancer combining thermal images of different views with personal and clinical data, building a multi-input classification model which exploits the benefits of convolutional neural networks for image analysis. First, we searched for structures using only thermal images. Next, we added the clinical data as a new branch of each of these structures, aiming to improve its performance. We applied our method to the most widely used public database of breast thermal images, the Database for Mastology Research with Infrared Image. The best model achieves a 97% accuracy and an area under the ROC curve of 0.99, with a specificity of 100% and a sensitivity of 83%. After studying the impact of thermal images and personal and clinical data on multi-input convolutional neural networks for breast cancer diagnosis, we conclude that: (1) adding the lateral views to the front view improves the performance of the classification model, and (2) including personal and clinical data helps the model to recognize sick patients. [ABSTRACT FROM AUTHOR]

In daily practice, arterial hypertension (AHT) and hypercholesterolaemia are frequently associated with the existence of multiple common etiopathogenic interrelationships. This situation leads to an exponential increase in cardiovascular risk for these patients, so it is essential to know the prevalence and therapeutic management of hypercholesterolaemia in the hypertensive patient. This national study analyses the distribution of total cholesterol levels and low-density lipoprotein cholesterol as well as hypercholesterolaemia prevalence and its therapeutic management in the uncontrolled hypertensive Spanish population. We observed mean total cholesterol levels of 227 ± 41 mg/dl with a high prevalence of hypercholesterolaemia (34.2%) among hypertensive patients, and the percentage of those patients with “desirable” total cholesterol levels (<200 mg/dl) was <25%. The treated hypertensive patients presented both significantly higher mean cholesterol levels and greater hypercholesterolaemia prevalence than the untreated hypertensive patients. It appears that total cholesterol levels are scarcely related to the presence or non-presence of obesity, diabetes or smoking. Regarding treatment, only 14.6% of the hypercholesterolaemic hypertensive patients received hypolipaemic treatment with statins. These results support the need to introduce measures for better diagnostic and therapeutic management of hypercholesterolaemic hypertensive patients that will lead to a much higher reduction in cardiovascular risk for these patients. [ABSTRACT FROM AUTHOR]

We modelled the potential habitat of a threatened species D. fissum subsp. sordidum, an endemic hemicryptophyte with a disjunct distribution in the Iberian Peninsula. Maxent was used to predict the subspecies habitat suitability by relating field sample-based distributional information with environmental and topographic variables. Our results suggest that the model performed well, predicting with high accuracy the current distribution of the species. The variables that most contributed to the model were Mean Temperature of Wettest Quarter (MTWtQ), Precipitation of Warmest Quarter (PWmQ), Temperature Annual Range (TAR) and Slope (Slo). These variables are biological significant for the taxon, as they have decisive influence in the critical stages of germination and fruiting. The current and potential distributional areas identified by the model fall mainly in regions with some degree of environmental protection, with some exceptions. A recovery plan for the species should be considered. Species Distribution Modelling cannot substitute long-term monitoring programmes, yet it is a useful tool for identifying appropriate areas of taxon occurrence, and thus allow for efficient use of the economic and human resources. [ABSTRACT FROM AUTHOR]

Background/Aims: A genomic HABP2 variant was proposed to be responsible for familial nonmedullary thyroid carcinoma (FNMTC). However, its involvement has been questioned in subsequent studies. We aimed to identify genetic HABP2 mutations in a series of FNMTC patients and investigate their involvement in the disease. Methods:HABP2 was sequenced from 6 index patients. Presence of the variants was investigated in all members of one family. Somatic BRAF and RAS “hotspot” mutations were investigated by the IdyllaTM BRAF Mutation Test and/or Sanger sequencing. Results: Two HABP2 variants (p.E393Q and p.G534E) were identified in the index patient from one family with papillary thyroid carcinoma (PTC) (follicular variant). The prevalence of p.E393Q in Spanish control alleles was 0.5% and that of p.G534E was 5.1%. However, neither change cosegregated with the phenotype in 3 affected members and 5 healthy members of the kindred. Interestingly, all 3 members affected by PTC harbored the p.V600E somatic mutation in BRAF. Conclusions: The variant G534E is prevalent in the Spanish population (5.1%); however, p.E393Q is rare (< 1%) and none cosegregated with the FNMTC phenotype. The presence of the noninheritable V600E BRAF mutation in this family supports Knudson’s “double-hit” hypothesis for cancer development and suggests the involvement of more than 1 gene in the clinical expression of FNMTC. [ABSTRACT FROM AUTHOR]

Objective IgA vasculitis (Henoch-Schönlein) (IgAV), formerly called Henoch-Schönlein purpura, is the most common vasculitis in children, but it is not rare in adults. Increased familial occurrence supports a genetic predisposition to IgAV. In this context, an association with the HLA-DRB1*01 phenotype has been suggested in Caucasian individuals with IgAV. However, data on the potential association of IgAV with HLA-DRB1*01 were based on small case series. We undertook this study to further investigate this potential association by performing HLA-DRB1 genotyping in the largest series of IgAV patients ever assessed for genetic studies in Caucasians. Methods We assessed 342 Spanish patients with IgAV as well as 303 controls matched for sex and ethnicity. IgAV patients were required to fulfill the classification criteria described by Michel et al as well as the American College of Rheumatology 1990 classification criteria. HLA-DRB1 alleles were determined using the polymerase chain reaction-sequence-specific oligonucleotide probe method. Results We found a statistically significant increase in the frequency of the HLA-DRB1*01 phenotype in IgAV patients compared with controls (43% versus 27%; P < 0.001) (odds ratio 2.03 [95% confidence interval 1.43-2.87]). This was due to the increased frequency of the HLA-DRB1*0103 allele in IgAV patients compared with controls (14.3% versus 2.0%; P < 0.001) (odds ratio 8.27 [95% confidence interval 3.46-23.9]). These results remained statistically significant after Bonferroni adjustment. In contrast, a statistically significant decrease in the frequency of the HLA-DRB1*03 phenotype, due to the presence of the HLA-DRB1*0301 allele, was observed in IgAV patients compared with controls (5.6% versus 18.2%; P < 0.001) (odds ratio 0.26 [95% confidence interval 0.14-0.47]), even after Bonferroni adjustment. No association of HLA-DRB1 with specific features of the disease was found. Conclusion Our study confirms an association of IgAV with HLA-DRB1*01 in Caucasians. There also appears to be a protective effect against the development of IgAV in Caucasians carrying the HLA-DRB1*03 phenotype. [ABSTRACT FROM AUTHOR]

Pseudomonas pseudoalcaligenes CECT5344 is a Gram-negative bacterium able to tolerate cyanide and to use it as the sole nitrogen source. We report here the first draft of the whole genome sequence of a P. pseudoalcaligenes strain that assimilates cyanide. Three aspects are specially emphasized in this manuscript. First, some generalities of the genome are shown and discussed in the context of other Pseudomonadaceae genomes, including genome size, G + C content, core genome and singletons among other features. Second, the genome is analysed in the context of cyanide metabolism, describing genes probably involved in cyanide assimilation, like those encoding nitrilases, and genes related to cyanide resistance, like the cio genes encoding the cyanide insensitive oxidases. Finally, the presence of genes probably involved in other processes with a great biotechnological potential like production of bioplastics and biodegradation of pollutants also is discussed. [ABSTRACT FROM AUTHOR]

A proteomic approach was used to identify several proteins induced by cyanide in the alkaliphilic bacterium Pseudomonas pseudoalcaligenes CECT5344, two of them, NitB and NitG, encoded by genes that belong to the nit1C gene cluster. The predicted products of the nit1C gene cluster are a Fis-like σ54-dependent transcriptional activator (NitA), a nitrilase (NitC), an S-adenosylmethionine superfamily member (NitD), an N-acyltransferase superfamily member (NitE), a trifunctional polypeptide of the AIRS/GARS family (NitF), an NADH-dependent oxidoreductase (NitH) and two hypothetical proteins of unknown function (NitB and NitG). RT-PCR analysis suggested that nitBCDEFGH genes were co-transcribed, whereas the regulatory nitA gene was divergently transcribed. Real-time RT-PCR revealed that expression of the nitBCDEFGH genes was induced by cyanide and repressed by ammonium. The P. pseudoalcaligenes CECT5344 nit1C gene cluster was found to be involved in assimilation of free and organic cyanides (nitriles) as deduced for the inability to grow with cyanides showed by the NitA, NitB and NitC mutant strains. The wild-type strain CECT5344 showed a nitrilase activity that allows growth on cyanide or hydroxynitriles. The NitB and NitC mutants only presented low basal levels of nitrilase activity that were not enough to support growth on either free cyanide or aliphatic nitriles, suggesting that nitrilase NitC is specific and essential for cyanide and aliphatic nitriles assimilation. [ABSTRACT FROM AUTHOR]

Background and objective: Monotherapy with any class of antihypertensive drug effectively controls blood pressure (BP) in only about 50% of patients. Consequently, the majority of patients with hypertension require combined therapy with two or more medications. This study aimed to evaluate the effectiveness (systolic BP [SBP]/diastolic BP [DBP] control) and tolerability of the fixed-dose combination enalapril/nitrendipine 10 mg/20mg administered as a single daily dose in hypertensive patients. Methods: This was a post-authorization, multicentre, prospective, observational study conducted in primary care with a 3-month follow-up. Patients throughout Spain with uncontrolled hypertension (≥140/90mmHg for patients without diabetes mellitus, or ≥ 130/85 mmHg for patients with diabetes) on monotherapy or with any combination other than enalapril + nitrendipine, or who were unable to tolerate their previous antihypertensive therapy, were recruited. Change from previous to study treatment was according to usual clinical practice. BP was measured once after 5 minutes of rest in the sitting position. Therapeutic response was defined as follows: 'controlled" meant controlled BP (<140/90 mmHg for nondiabetic patients, or <130/85 mmHg for diabetic patients); 'response' meant controlled BP, or a decrease in SBP of ≥20 mmHg and in DBP of ≥l0 mmHg. The main laboratory test parameters were documented at baseline and after 3 months. Patients aged >65 years, with diabetes, with isolated systolic hypertension (ISH; SBP≥140 mmHg for patients without diabetes, SBP ≥130mmHg for patients with diabetes) and who were obese (body mass index [BMI] >30 kg/m2) were analysed separately. Results: Of 6537 patients included, 5010 and 6354 patients were assessed in effectiveness and tolerability analyses, respectively. In the tolerability analysis population, there were 3023 men (47.6%) and 3321 women (52.4%). The mean (± SD) age of the tolerability analysis group was 62.8 (:t: 10.7) years. A total of 71.1% of the patients presented at least one clinical cardiovascular risk factor other than hypertension, with the most frequent being dyslipidaemia (42.3%), obesity (29.2%) and diabetes (23.9%). After 3 months of treatment, SBP and DBP showed mean (±SD) decreases of 26.5 (± 14.4)mmHg and 14.9 (+9.0) mmHg, respectively, and 73.0% of patients responded to treatment while 40.9% achieved BP control (70.8%/36.1% in 2658 patients aged >65 years; 61.7%/46.8% in 1521 patients with diabetes; 55.3%/44.2% in 731 patients with ISH; 72.0%/36.4% in 1762 obese patients). Adverse events were reported in 10.8% of patients (n =689). During the follow-up period, ten patients died and seven patients had serious adverse events; in no case was a causal relationship attributed to the study product. Conclusions: The rate of SBP/DBP control achieved demonstrates the effectiveness of the fixed-dose enalapril/nitrendipine 10mg/20mg combination administered as a single daily dose in patients with essential hypertension not adequately controlled with monotherapy or with any combination other than enalapril + nitrendipine. The proportion and type of adverse events reported were as expected and have already been described for both components of the enalapril/nitrendipine 10 mg/20 mg combination. These results confirm the effectiveness of a strategy based on a fixed-dose enalapril/nitrendipine 10 mg/ 20 mg combination in reducing BP and achieving BP control goals. [ABSTRACT FROM AUTHOR]

Two-dimensional (2-D) electrophoresis approach has been used to test protein expression changes in response to cyanide in the alkaliphilic bacterium Pseudomonas pseudoalcaligenes CECT5344. This is a cyanide-assimilating strain which also grows in media containing cyanide-enriched effluent from the jewellery industry. The bacterium efficiently uses this residue as the sole nitrogen source for aerobic growth under alkaline pH with negligible nitrogen losses as HCN. Cell-free extracts isolated from P. pseudoalcaligenes grown with a jewellery residue, free cyanide or ammonium chloride as nitrogen source were subjected to 2-D electrophoresis and the spot patterns were examined to determine differential protein expression. Electrophoretic plates exhibiting an average of 1000 spots showed significant differences in the expression of about 44 proteins depending on the nitrogen source. Some of these protein spots were analysed by Matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS). Characterization of five of these proteins reveals that cyanide shock induces proteins related to iron acquisition, regulation of nitrogen assimilation pathways and oxidative stress repairing and protection. [ABSTRACT FROM AUTHOR]

A nas gene region from Rhodobacter capsulatus E1F1 containing the putative nasB gene for nitrite reductase was previously cloned. The recombinant His6-NasB protein overproduced in E. coli showed nitrite reductase activity in vitro with both reduced methyl viologen and NADH as electron donors. The apparent Km values for nitrite and NADH were 0.5 mM and 20 μM, respectively, at the pH and temperature optima (pH 9 and 30°C). The optical spectrum showed features that indicate the presence of FAD, iron-sulfur cluster and siroheme as prosthetic groups, and nitrite reductase activity was inhibited by sulfide and iron reagents. These results indicate that the phototrophic bacterium R. capsulatus E1F1 possesses an assimilatory NADH-nitrite reductase similar to that described in non-phototrophic organisms. [ABSTRACT FROM AUTHOR]

Background: Prolonged air travel and the associated immobilization are risk factors for venous thromboembolism. The occurrence of pulmonary thromboembolism (PTE) under these circumstances is referred to as economy class syndrome. We assessed the incidence of symptomatic PTE in passengers on long-haul flights arriving at Madrid-Barajas Airport, Madrid, Spain, and the association with the number of flight hours. Methods: We retrospectively reviewed cases of PTE among international travelers arriving at Madrid-Barajas Airport between January 1995 and December 2000. Patients presenting with symptoms of deep venous thrombosis but without symptoms of PTE were excluded. Pulmonary thromboembolism was identified using an algorithm of diagnostic tests. The incidence of PTE and the association with flight duration was assessed. Results: The average number of passengers per year who arrived at the airport on flights originating abroad in the period analyzed was 6 839 222. Sixteen cases of PTE were detected over the 6-year period. All patients with travel-associated PTE had flight durations of greater than 6 hours. The overall incidence of PTE was 0.39 per 1 million passengers (95% confidence interval [CI], 0.20-0.58). On flights that lasted between 6 and 8 hours, the incidence was 0.25 per 1 million passengers (95% CI, 0-0.75), while on flights longer than 8 hours, the incidence was 1.65 per 1 million passengers (95% CI, 0.81-2.49) (P<.001). Conclusions: Air travel is a risk factor for PTE, and the incidence of PTE increases with the duration of the air travel. However, the low incidence of PTE among long-distance passengers, similar to that observed in other international airports, does not justify social alarm. [ABSTRACT FROM AUTHOR]

Objective: To determine causes of treatment resistance in patients with refractory hypertension, and to estimate the prevalence of true resistant hypertension. Methods: We studied 50 consecutive patients referred with refractory hypertension after exclusion of hypokalemia and stenosis of the renal artery. Ambulatory blood pressure monitoring was performed in all patients to detect white-coat effect. The patients were hospitalized, antihypertensive drugs were withdrawn and a screening for secondary hypertension was performed. In addition, these patients, and a control group of essential hypertensives controlled with three antihypertensive drugs, underwent a OGTT with 75 g of glucose. Results: Primary normokaliemic hyperaldosteronism was diagnosed in seven patients. Two patients had a pheochromocytoma and six had white-coat effect. The 35 remaining patients with true resistant hypertension shown significant differences in serum insulin and HOMA IR when compared with the control group. Conclusions: These findings show that among normokaliemic treatment-resistant hypertension, the presence of hyperaldosteronism and pheochromocitoma is quite high. Moreover, treatment resistance in hypertensive patients appears to be associated with insulin resistance. [ABSTRACT FROM AUTHOR]

Aim: Lercanidipine, a long-acting dihydropyridine with a good antihypertensive efficacy and tolerability in clinical use. With the aim to determine the efficacy and tolerability of this drug in usual clinical practice we performed the ELYPSE trial. Methods: Grade 1 or 2 essential hypertensive patients in whom their physicians considered to prescribe a dihydropyridine were conferred to Lercanidipine 10 mg once daily with a 3-month follow-up; 9059 patients were included (age: 63 ± 11 years; 58% women, 60% over 60 years, 56% grade 2 hypertensives and 69% previously treated with other antihypertensive drugs). A subgroup of 1267 patients (14%) who were included in the study had experienced adverse reactions with other drugs. Electronic case-report forms and a central database (Internet) were used in this trial. Results: At baseline, blood pressure (BP) was 160.1 ± 10.2/95.6 ± 6.6 mmHg; and heart rate (HR) 77.3 ± 9.3 beats/min. Significant reductions in both systolic and diastolic BP were attained at 1 month with slight additional decreases 2 months later. At 3 months, BP was 141.4 ± 11.3/83.1 ± 6.9 mmHg, and HR 75.2 ± 8.2 beats/min (p < 0.001 versus baseline). At the study end, 64% of the patients achieved a diastolic BP <90 mmHg, BP control (< 140/90 mmHg) was attained in 32%. In the subgroup of diabetics (n = 1269) an adequate BP control (lt;130/85) was attained in only 16.4%. The overall incidence of adverse events was 6.5%, of which the most frequent were headache (2.9%), ankle oedema (1.2%), flushing (1.1%) and palpitations (0.6%). Withdrawal rate was < 1%. The efficacy and tolerability in the subgroup of patients included in the study due to adverse events with other drugs were similar to the whole study group. Conclusion: In this study Lercanidipine has shown a good efficacy and tolerability in daily clinical practice. These findings are concordant with those reported in randomized controlled trials. 130/85) was attained in only 16.4%. [ABSTRACT FROM AUTHOR]