Exploring metabolic pathways in genome-scale networks via generating flux modes.

MOTIVATION: The reconstruction of metabolic networks at the genome scale has allowed the analysis of metabolic pathways at an unprecedented level of complexity. Elementary flux modes (EFMs) are an appropriate concept for such analysis. However, their number grows in a combinatorial fashion as the size of the metabolic network increases, which renders the application of EFMs approach to large metabolic networks difficult. Novel methods are expected to deal with such complexity. RESULTS: In this article, we present a novel optimization-based method for determining a minimal generating set of EFMs, i.e. a convex basis. We show that a subset of elements of this convex basis can be effectively computed even in large metabolic networks. Our method was applied to examine the structure of pathways producing lysine in Escherichia coli. We obtained a more varied and informative set of pathways in comparison with existing methods. In addition, an alternative pathway to produce lysine was identified using a detour via propionyl-CoA, which shows the predictive power of our novel approach. AVAILABILITY: The source code in C++ is available upon request.

Hydrogeochemical, isotopic and geophysical characterization of saline lake systems in semiarid regions: The Salada de Chiprana Lake, Northeastern Spain.

Most of the athalassic saline and hypersaline lakes are located in arid and semiarid regions where water availability drives the hydrological dynamics of the lake itself and the associated ecosystems. This is the case of the Salada de Chiprana Lake, in the Ebro River basin (Spain). It is the only athalassic permanent hypersaline lake in Western Europe, and where rare and endangered bacterial mats exist. This work presents a robust hydrogeological conceptual model for the lake system. The model evaluates the contribution of groundwater discharge to the whole water budget and explains the hydrological behaviour of the lake system. The lake behaves as a flow-through system rather than a closed basin. About 40% of total water outflow from the lake occurs as groundwater, whereas evaporation accounts for the remaining 60%. The surface water inflows are variable, but the groundwater contribution seems almost constant, amounting to 13% of the average total water inflow and contributing 1.9% of salt income. The high water salinity of the lake is controlled by evaporation, by saline water inflows from irrigation return flows, and the by groundwater outflows. The role of groundwater should be taken into account when drafting the water and land planning, once the conditions for the conservation of the algal mats are defined. A major contribution of this study is the water balance in the Salada de Chiprana Lake, which is consistent with a robust hydrogeological conceptual model defined upon scarce hydrogeological, hydrochemical and isotopic data in the local context as conditioned by the regional behaviour. The water balance is a key tool to help to correctly manage this unique athalassic saline lake, and the approach used here can be extrapolated to other similar ecosystems around the world.

African dust and air quality over Spain: Is it only dust that matters?

The 2001-2016 contribution of African dust outbreaks to ambient regional background PM10 and PM2.5 levels over Spain, as well as changes induced in the PMx composition over NE Spain in 2009-2016, were investigated. A clear decrease in PMx dust contributions from the Canary Islands to N Iberia was found. A parallel increase in the PM2.5/PM10 ratio (30% in the Canary Islands to 57% in NW Iberia) was evidenced, probably due to size segregation and the larger relative contribution of the local PMx with increasing distance from Africa. PM1-10 and PM2.5-10 measured in Barcelona during African dust outbreaks (ADOs) were 43-46% higher compared to non-ADO days. The continental background contribution prevailed in terms of both PM1-10 and PM2.5-10 during ADO days (62 and 69%, respectively, and 31 and 27% for non-ADO days). The relative contributions of Al2O3/Fe2O3/CaO to PMx fraction showed that Al2O3 is a suitable tracer for African dust in our context; while CaO at the urban site is clearly affected by local resuspension, construction and road dust, and Fe2O3 by dust from vehicle brake discs. The results also provide evidence that PM increases during ADOs are caused not only by the mineral dust load, but by an increased accumulation of locally emitted or co-transported anthropogenic pollutants as compared with non-ADO days. Possible causes for this accumulation are discussed. We recommend that further epidemiological studies should explore independently the potential effects of mineral dust and the anthropogenic PM during ADOs, because, at least over SW Europe, not only mineral dust affects the air quality during African dust episodes.

Interpretation of the variability of levels of regional background aerosols in the Western Mediterranean.

Results on interpretation of the variability of regional background PM levels in the Western Mediterranean basin (WMB) are presented. Mean PM levels recorded at Montseny, MSY (North-Eastern Spain) in the 2002--2007 period reached 17, 13 and 11 microg/m3 of PM10, PM2.5 and PM1, respectively. The daily evolution of PM levels is regulated by the breeze circulation (mountain and sea breezes). PM levels are lower at the rural sites at night owing to the nocturnal drainage flows and to the lowering of the mixing layer height below the MSY high. These nocturnal low levels allowed us to estimate the continental background PM levels. At midday, the atmospheric pollutants accumulated in the pre-coastal depression are transported upwards by the breeze, increasing PM levels. Maximum PM10 levels were recorded in summer, and February--March and November, and minimum values in the rest of the year coinciding with the highest frequency of Atlantic advection. PM peak episodes attributed to Saharan dust outbreaks were recorded in summer and February-March. In addition, anticyclonic situations (February--March and November) may impact in elevated rural areas by increasing hourly levels of PM1 up to 75 microg/m3. This scenario induces the stagnation of pollutants in the pre-coastal depression. Solar radiation activates mountain winds, transporting polluted air masses from the valleys to elevated areas resulting in an increase of fine PM levels in areas outside the boundary layer. A significant decrease in PM annual means (40% and 34% for the entire monitoring period, 7 microgPM10/m3 and 5 microgPM2.5/m3) was recorded at MSY between 2002 and 2007. There appears to be no single cause behind these trends. This could partially be ascribed to the varying frequency and intensity of Saharan dust episodes, but also to large-scale meteorological processes or cycles, and/or to local or meso-scale processes such as nearby anthropogenic emission sources.

Myocardial bridging and hypertrophic cardiomyopathy: relief of ischemia by surgery.

We describe a case of myocardial bridging of the anterior descending coronary artery associated with a non-obstructive hypertrophic cardiomyopathy which was corrected by surgery because of a poor response to standard drug therapy. The clinical significance of the association is discussed. The possibility of repair by surgery should be considered when an area of ischemia supplied by the affected vessel is detected and previous medical treatment has been ineffective.

[Agenesis of the left coronary trunk. A case report and bibliographic review]. / Agenesia del tronco coronario izquierdo. Descripción de un caso y revisión de la bibliografía.

Clinical and angiographic features are described in a fifty-five years old man, with long-standing clinical manifestations of ischemic heart disease. In addition to severe coronary atherosclerosis, congenital atresia of the left main coronary was present. A description of the coronary anomaly found and a discussion of its meaning and significance are presented.

[Anomalous origin of the right coronary artery from the left sinus of Valsalva. Apropos of 2 cases]. / Origen anómalo de la arteria coronaria derecha del seno de Valsalva izquierdo. A propósito de dos casos.

Anomalous origin of right coronary artery from the left sinus of Valsalva is a uncommon congenital anomaly which is difficult to demonstrate angiographically. For many years pathologists classified it as a minor anomaly of no clinical significance. It has only recently been associated with significant manifestations of myocardial ischemia. These manifestations have included acute myocardial infarction, angina pectoris, syncope, ventricular tachycardia and fibrillation, and sudden death. Two patients with this anomaly are reported. One patient had angina pectoris in the absence of significant atheromatous coronary lesions. In the second patient the aberrant origin of the right coronary artery was associated to aortic valve disease. The possible physiopathology mechanisms responsible for manifestations of myocardial ischemia in patients with this anomaly are analyzed.

[Left heart catheterization by the transseptal route]. / Cateterismo cardíaco esquerdo por via transeptal.

PURPOSE: To analyse the transseptal catheterization technique, its indications and possible complications. METHODS: The transseptal catheterization has been undertaken in 233 patients, 202 children (aged 0.1 to 16 years) with congenital heart disease and 31 adults (aged 37 to 73 years) submitted to mitral valvuloplasty. The Mullins technique was employed to access left heart chambers. RESULTS: In the pediatric group, the indications for transseptal catheterization were coarctation of the aorta and valvular or subvalvular aortic stenosis. By this technique, multiple diagnostic analysis and therapeutic procedures, such as blade atrioseptostomy and mitral valvuloplasty, became available. Among the complications in the 2 groups, pericardial perforation was the most frequent, depending on the laboratory practice with this technique. CONCLUSION: The transseptal cardiac catheterization is a safe and effective technique to investigate hemodynamic data in several congenital heart diseases and is essential to many therapeutic procedures. The technique has a low incidence of complications when employed by experienced teams.

[Diagnostic value of gated-SPECT for each coronary artery in patients clinically diagnosed of coronary heart disease]. / Valor diagnóstico del gated-SPECT para cada arteria coronaria en pacientes con el diagnóstico clínico de cardiopatía isquémica.

UNLABELLED: This study aimed to evaluate the diagnostic value of gated-SPECT for each coronary artery in patients with clinical diagnosis or suspicion of coronary heart disease. PATIENTS AND METHODS: The study population is made up of 43 patients (64 9 years, 88% male gender) with prior clinical diagnosis or suspicion of coronary heart disease who had undergone gated-SPECT (99mTc-tetrofosmin) and cardiac catheterization. Scintigraphic study after exercise treadmill test and rest study were performed on the same day. RESULTS: Gated-SPECT showed perfusion defects in 86% of patients, the mean number of territories with perfusion defects being 1.58 +/- 0.79. A total of 39 (91%) of the 43 patients had significant coronary heart disease. Single, two- and three-vessel disease was demonstrated in 12 (28%), 15 (35%) and 12 (28%) patients, respectively. Sensitivity and specificity were 81% and 91%, respectively, for left anterior descending artery, 88% and 65% for right coronary artery, and 55% and 81% for circumflex one. CONCLUSIONS: Myocardial scintigraphy with gated-SPECT offers high sensitivity and specificity for the diagnosis of left anterior descending artery disease. However, sensitivity for circumflex artery and specificity for right coronary artery were low in our series.

Natural sources of atmospheric aerosols influencing air quality across Europe.

Atmospheric aerosols are emitted by natural and anthropogenic sources. Contributions from natural sources to ambient aerosols vary widely with time (inter-annual and seasonal variability) and as a function of the distance to source regions. This work aims to identify the main natural sources of atmospheric aerosols affecting air quality across Europe. The origin, frequency, magnitude, and spatial and temporal variability of natural events were assessed for the years 2008 and 2009. The main natural sources of atmospheric aerosols identified were African dust, sea spray and wildfires. Primary biological particles were not included in the present work. Volcanic eruptions did not affect air quality significantly in Europe during the study period. The impact of natural episodes on air quality was significant in Southern and Western Europe (Cyprus, Spain, France, UK, Greece, Malta, Italy and Portugal), where they contributed to surpass the PM10 daily and annual limit values. In Central and Northern Europe (Germany, Austria and Latvia) the impact of these events was lower, as it resulted in the exceedance of PM daily but not annual limit values. Contributions from natural sources to mean annual PM10 levels in 2008 and 2009 ranged between 1 and 2 µg/m(3) in Italy, France and Portugal, between 1 and 4 µg/m(3) in Spain (10 µg/m(3) when including the Canary Islands), 5 µg/m(3) in UK, between 3 and 8 µg/m(3) in Greece, and reached up to 13 µg/m(3) in Cyprus. The evaluation of the number of monitoring stations per country reporting natural exceedances of the daily limit value (DLV) is suggested as a potential tool for air quality monitoring networks to detect outliers in the assessment of natural contributions. It is strongly suggested that a reference methodology for the identification and quantification of African dust contributions should be adopted across Europe.

Effect of atmospheric mixing layer depth variations on urban air quality and daily mortality during Saharan dust outbreaks.

Several epidemiological studies have shown that the outbreaks of Saharan dust over southern European countries can cause negative health effects. The reasons for the increased toxicity of airborne particles during dust storms remain to be understood although the presence of biogenic factors carried by dust particles and the interaction between dust and man-made air pollution have been hypothesized as possible causes. Intriguingly, recent findings have also demonstrated that during Saharan dust outbreaks the local man-made particulates can have stronger effects on health than during days without outbreaks. We show that the thinning of the mixing layer (ML) during Saharan dust outbreaks, systematically described here for the first time, can trigger the observed higher toxicity of ambient local air. The mixing layer height (MLH) progressively reduced with increasing intensity of dust outbreaks thus causing a progressive accumulation of anthropogenic pollutants and favouring the formation of new fine particles or specific relevant species likely from condensation of accumulated gaseous precursors on dust particles surface. Overall, statistically significant associations of MLH with all-cause daily mortality were observed. Moreover, as the MLH reduced, the risk of mortality associated with the same concentration of particulate matter increased due to the observed pollutant accumulation. The association of MLH with daily mortality and the effect of ML thinning on particle toxicity exacerbated when Saharan dust outbreaks occurred suggesting a synergic effect of atmospheric pollutants on health which was amplified during dust outbreaks. Moreover, the results may reflect higher toxicity of primary particles which predominate on low MLH days.

Size fractionate particulate matter, vehicle traffic, and case-specific daily mortality in Barcelona, Spain.

Recent epidemiological research suggests that short-term effects of particle matter (PM) in urban areas may preferentially be driven by fine fractions. Questions remain concerning the adversehealth effects of coarse particles generated by noncombustion, traffic-related processes and the mechanism of action of PM. Using a time-stratified case-crossover design, we investigated the association between three independent size fractions, coarse (PM10-2.5), intermodal (PM2.5-1), and very fine PMs (PM1), and three health outcomes, respiratory, cardiovascular, and cerebrovascular mortality in Barcelona, Spain, during the period of March 2003-December 2005. Using existing data, we examined the chemical composition of each fraction to explore the effects of PM from different sources and the mechanisms of action. We found that increased levels of PM, and PM10-2.5 were associated with increased levels of cardiovascular and cerebrovascular mortality at lag 1 and lag 2. At lag 1, the odds ratio (OR) for a 1 microg/m3 increase in PM1 was 1.028 [95% confidence interval (CI), 1.000-1.058] for cardiovascular mortality and 1.063 (95% CI, 1.004-1.124) for cerebrovascular mortality. At lag 1, the odds ratio per a 10 microg/ m3 increase of PM10-2.5 was 1.059 (95% CI, 1.026-1.094) for cardiovascular mortality and 1.098 (95% CI, 1.030-1.171) for cerebrovascular mortality. Association with respiratory mortality was only detected for PM2.5-1 at lag 2 (OR, 1.206 per a 10 microg/ m3 increase; 95% CI, 1.028-1.416). Chemical composition data showed that PM in Barcelona was generated in a large proportion by vehicle traffic. Vehicle traffic PM, generated by combustion and noncombustion processes, should be considered in air pollution mitigation strategies in urban areas.

Spatial and temporal variations in inhalable CuZnPb aerosols within the Mexico City pollution plume.

We report on the CuPbZn content of PM10 and PM2.5 samples collected from three sites (urban T0, suburban T1 and rural T2) during the Mexico City MILAGRO campaign of March 2006. Daytime city centre concentrations of summation operator CuZnPb(PM10) were much higher (T0 > 450 ng m(-3)) than at the suburban site (T1 < 200 ng m(-3)). Rural site (T2) summation operator CuZnPb(PM10) concentrations exceeded 50 ng m(-3) when influenced by the megacity plume but dropped to 10 ng m(-3) during clean northerly winds. Nocturnal metal concentrations more than doubled at T0, as pollutants became trapped in the nightly inversion layer, but decreased at the rural site. Transient spikes in concentrations of different metals, e.g. a "copper event" at T0 (CuPM10 281 ng m(-3)) and "zinc event" at T1 (ZnPM10 1481 ng m(-3)) on the night of March 7-8, demonstrate how industrial pollution sources produce localised chemical inhomogeneities in the city atmosphere. Most metal aerosols are <2.5 microm and SEM study demonstrates the dominance of Fe, Ti, Ba, Cu, Pb and Zn (and lesser Sn, Mo, Sb, W, Ni, V, As, Bi) in metalliferous particles that have shapes including spherical condensates, efflorescent CuZnClS particles, cindery Zn, and Cu wire. Metal aerosol concentrations do not change in concert with PM10 mass, which is more influenced by wind resuspension than industrial emissions. Metalliferous particles can induce cell damage, and PM composition is probably more important than PM mass, with respect to negative health effects, so that better monitoring and control of industrial emissions would likely produce significant improvements in air quality.

Characterization of a long range transport pollution episode affecting PM in SW Spain.

A multidisciplinary study on aerosol characterization was performed at the regional background monitoring station of El Arenosillo, in SW Spain, between 28 June and 5 July 2006. The main aim of the Arenosillo aerosol measurement campaign 2006 was to compare the results of aerosol characterization obtained by different groups by measuring physical and chemical parameters using optical methods and in situ sampling. The campaign coincided with a long-range transport episode from Western Iberia, passing through the Gulf of Cadiz and the Straits of Gibraltar towards the study area. The results of the variability of PM levels and chemical composition of PM10, PM2.5 and PM1 at El Arenosillo and at three nearby regional and urban background sites were interpreted. Mean levels measured during the campaign reached 23, 15 and 12 microg m(-3) for PM10, PM2.5 and PM1, respectively, at El Arenosillo. PM during the Arenosillo campaign 2006 was dominated by the secondary inorganic aerosols (SIA, 24, 38 and 39% of PM10, PM2.5 and PM1 mass), carbonaceous aerosols (17, 21 and 23% of the mass), crustal material (13, 9 and 4%), and sea spray (10, 5 and 1%). These values are within the usual range of regional background sites of Southern Spain with the exception of the relatively low crustal load and the high SIA levels. Two major PM episodes were differentiated. The first one was characterized by high levels of Bi, As, Pb, Se, P and Zn, which are the main tracers of the industrial emissions near the town of Huelva. High concentrations of these elements were also recorded at the nearby sites. In the second episode, maximum levels of SO4(2-), V and coarse Cu as well as the bulk mass of PM1 were determined, tracing the polluted air mass transport from Western Iberia through the Straits of Gibraltar. These results underline the importance of the influence of long-range transport of pollutants on the levels and composition of regional background PM in SW Iberia, where local emissions may also play a role.

A semiquantitative method based on proximal convergence zone to estimate the severity of the mitral regurgitation: design and clinical application.

AIMS: The analysis of the mitral regurgitation using the proximal isovelocity surface area method has not been extended to clinical practice because of its complexity. Our objective was to design and validate a simplified semi-quantitative method based on proximal isovelocity surface area to assess the severity of mitral regurgitation. METHODS AND RESULTS: We studied 58 patients with mitral regurgitation. We found a good correlation between the angiographic grade of mitral regurgitation and the parameters derived from proximal isovelocity surface area: maximal regurgitant flow, regurgitant orifice and volume (r: 0.90 to 0.92, P<0.05). The values of maximal regurgitant flow that best predicted the grades of angiographic severity (I--IV) were estimated by regurgitant orifice curves, with cut points of 16, 56 and 160ml.s(-1)kappa(p)=0.92). Considering that maximal regurgitant flow only depends on the radius of proximal isovelocity surface area and the velocity of aliasing used, we constructed a nomogram with the previously described limits. Twenty-four new patients were studied using this nomogram and angiography. An excellent degree of agreement was found (kappa(p)=0.93). The inter- and intraobserver variability showed a kappa(p)=0.89 and 0.91, respectively. CONCLUSION: This nomogram allows a fast semi-quantitative estimation of the grade of MR, feasible and highly correlative with the invasive methods.

Coronary arterial stenosis and subclavian steal in Takayasu's arteritis.

This report describes a young boy with previous myocardial infarction and hypertension. Demonstration of coronary arterial ostial stenosis and a variant of subclavian steal was documented by selective arteriography. Surgical resolution of the most important stenosis is descending aorta, permitted effective control of hypertension. It is considered that one could reach this arteritis through different etiologies, tuberculosis having a preponderant place, and that it is important in all cases to carry out coronary arteriography.

Valor diagnóstico del GATED-SPECT para cada arteria coronaria en pacientes con el diagnóstico clínico de cardiopatía isquémica / Diagnostic value of gated-spect for each coronary artery in patients clinically diagnosed of coronary heart disease

El objetivo de este estudio fue evaluar el valor diagnóstico del gated-SPECT para cada una de las arterias coronarias en pacientes con diagnóstico previo o sospecha de enfermedad coronaria. Pacientes y métodos: La población de estudio esta formada por 43 pacientes (64 ñ 9 años, 88 per cent varones) con diagnóstico previo o sospecha de cardiopatía isquémica a los que se les había realizado estudio gated-SPECT y coronariografía. El radiofármaco empleado fue 99mTc-tetrofosmina, realizándose en el mismo día el estudio tras ejercicio físico en tapiz rodante y el estudio de reposo. Resultados: El estudio gated-SPECT mostró defectos de perfusión en el 86 per cent de los pacientes, siendo el número de territorios con defecto de perfusión por paciente 1,58 ñ 0,79.De los 43 pacientes, 39 (91 per cent) tenían enfermedad coronaria significativa. La enfermedad fue de 1, 2 y 3 vasos en 12 (28 per cent), 15 (35 per cent) y 12 (28 per cent) pacientes, respectivamente. La sensibilidad y especificidad fueron, respectivamente, 81 per cent y 91 per cent para la descendente anterior, 88 per cent y 65 per cent para la coronaria derecha y 55 per cent y 81 per cent para la circunfleja. Conclusiones: En pacientes con diagnóstico previo o sospecha de cardiopatía isquémica, la gammagrafía mediante gated-SPECT posee una elevada sensibilidad y especificidad en el diagnóstico de enfermedad de la arteria descendente anterior. Sin embargo, la sensibilidad para la circunfleja y la especificidad para la coronaria derecha fueron bajas en nuestra serie. (AU)