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We seek to examine the efficacy and safety of prereperfusion emergency medical services (EMS)–administered intravenous metoprolol in anterior ST-segment elevation myocardial infarction patients undergoing eventual primary angioplasty. This is a prespecified subgroup analysis of the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction trial population, who all eventually received oral metoprolol within 12 to 24 hours. We studied patients receiving intravenous metoprolol by EMS and compared them with others treated by EMS but not receiving intravenous metoprolol. Outcomes included infarct size and left ventricular ejection fraction on cardiac magnetic resonance imaging at 1 week, and safety by measuring the incidence of the predefined combined endpoint (composite of death, malignant ventricular arrhythmias, advanced atrioventricular block, cardiogenic shock, or reinfarction) within the first 24 hours. From the total population of the trial (N=270), 147 patients (54%) were recruited during out-of-hospital assistance and transferred to the primary angioplasty center (74 intravenous metoprolol and 73 controls). Infarct size was smaller in patients receiving intravenous metoprolol compared with controls (23.4 [SD 15.0] versus 34.0 [SD 23.7] g; adjusted difference –11.4; 95% confidence interval [CI] –18.6 to –4.3). Left ventricular ejection fraction was higher in the intravenous metoprolol group (48.1% [SD 8.4%] versus 43.1% [SD 10.2%]; adjusted difference 5.0; 95% CI 1.6 to 8.4). Metoprolol administration did not increase the incidence of the prespecified safety combined endpoint: 6.8% versus 17.8% in controls (risk difference –11.1; 95% CI –21.5 to –0.6). Out-of-hospital administration of intravenous metoprolol by EMS within 4.5 hours of symptom onset in our subjects reduced infarct size and improved left ventricular ejection fraction with no excess of adverse events during the first 24 hours. Sin financiación 5.008 JCR (2015) Q1, 2/24 Emergency medicine UEM

In voltage clamped frog skeletal muscle fibres 0.2 mM tetracaine strongly suppresses Ca2+ release. After this treatment Ca2+ release flux lacks its characteristic initial peak and the remaining steady component is strongly reduced when compared with the control condition. We studied the effect of two agonists of Ca2+ release on these tetracaine treated fibres. 8 mM ClO 4 − added after tetracaine potentiated release flux from 0.11 ± 0.03 mM s−1 to 0.34 ± 0.07 mM s−1 (n = 6) although without recovery of the peak at any test voltage. The voltage dependence of the increased release was shifted towards more negative potentials (approximately −10 mV). The effects of ClO 4 − on charge movement under these conditions showed the previously described characteristic changes consisting in a left shift of its voltage dependence (approximately −9 mV) together with a slower kinetics, both at the ON and OFF transients. Caffeine at 0.5 mM in the presence of the same concentration of tetracaine failed to potentiate release flux independently of the test voltage applied. When the cut ends of the fibre were exposed to a 10 mM BAPTA intracellular solution, in the absence of tetracaine, the peak was progressively abolished. Under these conditions caffeine potentiated release restoring the peak (from 0.63 ± 0.12 mM s−1 to 1.82 ± 0.23 mM s−1) with no effect on charge movement. Taken together the present results suggest that tetracaine is blocking a Ca2+ sensitive component of release flux. It is speculated that the suppressed release includes a component that is dependent on Ca2+ and mainly mediated by the activation of the β ryanodine receptors (the RyR3 equivalent isoform). These receptors are located parajunctionally in the frog and are not interacting with the dihydropyridine receptor.

A benchmark problem was defined to evaluate the performance of different mathematical biofilm models. The biofilm consisted of heterotrophic bacteria degrading organic substrate and oxygen. Mathematical models tested ranged from simple analytical to multidimensional numerical models. For simple and more or less flat biofilms it was shown that analytical biofilm models provide very similar results compared to more complex numerical solutions. When considering a heterogeneous biofilm morphology it was shown that the effect of an increased external mass transfer resistance was much more significant compared to the effect of an increased surface area inside the biofilm.

Structural and microbial heterogeneity occurs in almost any type of biofilm system. General approaches for the design of biofilm systems consider biofilms as homogeneous and of constant thickness. In order to improve the design of biofilms systems, models need to incorporate structural heterogeneity and the effect of inert microbial mass. We have improved a 2D biofilm model based on cellular automata (CA) and used it to simulate multidimensional biofilms with active and inert biomass including a self-organizing development. Results indicate that the presence of inert biomass within biofilm structures does not change considerably the substrate flux into the biofilm because the active biomass is located at the surface of the biofilm. Long-term simulations revealed that although the biofilm system is highly heterogeneous and the microstructure is continuously changing, the biofilm reaches a dynamic steady-state with prediction of biofilm thickness and substrate flux stabilizing on a delimited range.

In skeletal muscle, the waveform of Ca(2+) release under clamp depolarization exhibits an early peak. Its decay reflects an inactivation, which locally corresponds to the termination of Ca(2+) sparks, and is crucial for rapid control. In cardiac muscle, both the frequency of spontaneous sparks (i.e., their activation) and their termination appear to be strongly dependent on the Ca(2+) content in the sarcoplasmic reticulum (SR). In skeletal muscle, no such role is established. Seeking a robust measurement of Ca(2+) release and a way to reliably modify the SR content, we combined in the same cells the "EGTA/phenol red" method (Pape et al., 1995) to evaluate Ca(2+) release, with the "removal" method (Melzer et al., 1987) to evaluate release flux. The cytosol of voltage-clamped frog fibers was equilibrated with EGTA (36 mM), antipyrylazo III, and phenol red, and absorbance changes were monitored simultaneously at three wavelengths, affording largely independent evaluations of Delta[H(+)] and Delta[Ca(2+)] from which the amount of released Ca(2+) and the release flux were independently derived. Both methods yielded mutually consistent evaluations of flux. While the removal method gave a better kinetic picture of the release waveform, EGTA/phenol red provided continuous reproducible measures of calcium in the SR (Ca(SR)). Steady release permeability (P), reached at the end of a 120-ms pulse, increased as Ca(SR) was progressively reduced by a prior conditioning pulse, reaching 2.34-fold at 25% of resting Ca(SR) (four cells). Peak P, reached early during a pulse, increased proportionally much less with SR depletion, decreasing at very low Ca(SR). The increase in steady P upon depletion was associated with a slowing of the rate of decay of P after the peak (i.e., a slower inactivation of Ca(2+) release). These results are consistent with a major inhibitory effect of cytosolic (rather than intra-SR) Ca(2+) on the activity of Ca(2+) release channels.

PCB-contaminated concrete is a significant environmental management issue for many industrial facilities. The U.S. EPA has authorized exposure control in operating facilities via encapsulation or use of physical barriers when complete PCB removal is not technically achievable and/or is not cost-effective. Achievement of effective encapsulation with epoxy coatings is challenging for PCB-contaminated concrete as oil and/or other chemicals are often present. This work involved experimental investigation of encapsulation via cleaning and epoxy-coating of PCB-contaminated concrete. Experimental studies were performed with three cleaning techniques for removal of PCBs, and three epoxy-coating systems for encapsulating PCBs. Resurfacing of oils and PCBs from concrete after cleaning, or “bleedback”, was also studied. These tests were conducted using PCB/oil-contaminated concrete core samples from industrial plants. Results indicated that no cleaning system alone is effective as a long-term solution for PCB-contaminated concrete, and that bleedback occurred within days after cleaning due to capillary rise, affected by changes in wetting characteristics of the concrete pore surfaces and by elevated temperature induced by heating, which affects the density of the oil. The presence of free oil on the concrete surface resulted in failure of the coating systems, which occurred faster if heating was applied. Where appropriate surface preparation was performed, the integrity of the coatings remained intact throughout the experimental period (eight months). In such cases, the coating system acted effectively as a barrier against diffusion of PCBs. This study demonstrated that, except in high-temperature areas, an epoxy coating can be an appropriate encapsulation system if proper surface preparation is applied. Metal sheet barriers can be used for high-temperature applications.

It is widely accepted that edema occurs early in the ischemic zone and persists in stable form for at least 1 week after myocardial ischemia/reperfusion. However, there are no longitudinal studies covering from very early (minutes) to late (1 week) reperfusion stages confirming this phenomenon.This study sought to perform a comprehensive longitudinal imaging and histological characterization of the edematous reaction after experimental myocardial ischemia/reperfusion.The study population consisted of 25 instrumented Large-White pigs (30 kg to 40 kg). Closed-chest 40-min ischemia/reperfusion was performed in 20 pigs, which were sacrificed at 120 min (n = 5), 24 h (n = 5), 4 days (n = 5), and 7 days (n = 5) after reperfusion and processed for histological quantification of myocardial water content. Cardiac magnetic resonance (CMR) scans with T2-weighted short-tau inversion recovery and T2-mapping sequences were performed at every follow-up stage until sacrifice. Five additional pigs sacrificed after baseline CMR served as controls.In all pigs, reperfusion was associated with a significant increase in T2 relaxation times in the ischemic region. On 24-h CMR, ischemic myocardium T2 times returned to normal values (similar to those seen pre-infarction). Thereafter, ischemic myocardium-T2 times in CMR performed on days 4 and 7 after reperfusion progressively and systematically increased. On day 7 CMR, T2 relaxation times were as high as those observed at reperfusion. Myocardial water content analysis in the ischemic region showed a parallel bimodal pattern: 2 high water content peaks at reperfusion and at day 7, and a significant decrease at 24 h.Contrary to the accepted view, myocardial edema during the first week after ischemia/reperfusion follows a bimodal pattern. The initial wave appears abruptly upon reperfusion and dissipates at 24 h. Conversely, the deferred wave of edema appears progressively days after ischemia/reperfusion and is maximal around day 7 after reperfusion.

Background Exercise has been proposed as a trigger for arrhythmogenic right ventricular cardiomyopathy (ARVC) phenotype manifestation; however, research is hampered by the limited availability of animal models in which disease-associated mutations can be tested. Objectives This study evaluated the impact of exercise on ARVC cardiac manifestations in mice after adeno-associated virus (AAV)–mediated gene delivery of mutant human PKP2 , which encodes the desmosomal protein plakophilin-2. Methods We developed a new model of cardiac tissue–specific transgenic-like mice on the basis of AAV gene transfer to test the potential of a combination of a human PKP2 mutation and endurance training to trigger an ARVC-like phenotype. Results Stable cardiac expression of mutant PKP2 (c.2203C>T), encoding the R735X mutant protein, was achieved 4 weeks after a single AAV9-R735X intravenous injection. High-field cardiac magnetic resonance over a 10-month postinfection follow-up did not detect an overt right ventricular (RV) phenotype in nonexercised (sedentary) mice. In contrast, endurance exercise training (initiated 2 weeks after AAV9-R735X injection) resulted in clear RV dysfunction that resembled the ARVC phenotype (impaired global RV systolic function and RV regional wall motion abnormalities on cardiac magnetic resonance). At the histological level, RV samples from endurance-trained R735X-infected mice displayed connexin 43 delocalization at intercardiomyocyte gap junctions, a change not observed in sedentary mice. Conclusions The introduction of the PKP2 R735X mutation into mice resulted in an exercise-dependent ARVC phenotype. The R735X mutation appears to function as a dominant-negative variant. This novel system for AAV-mediated introduction of a mutation into wild-type mice has broad potential for study of the implication of diverse mutations in complex cardiomyopathies.

We appreciate the interest of and comments by Drs Argulian and Messerli on our recently published study.1 Defining inclusion and exclusion criteria, along with dose selection of the administered pharmacological therapy, is critical in the early stages of a clinical trial design. The scientific method strongly recommends performing a profound bibliographic research in this regard, and for this purpose, we carefully reviewed previously conducted trials on the use of β-blockers in the setting of ST-segment–elevation acute myocardial infarction, taking note of the strengths and weaknesses of each of them. Thus, for the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CNIC) trial, we randomized anterior myocardial infarctions revascularized by primary angioplasty in

Early detection of right ventricular (RV) involvement in chronic pulmonary hypertension (PH) is essential due to prognostic implications. T1 mapping by cardiac magnetic resonance (CMR) has emerged as a noninvasive technique for extracellular volume fraction (ECV) quantification. We assessed the association of myocardial native T1 time and equilibrium contrast ECV (Eq-ECV) at the RV insertion points with pulmonary hemodynamics and RV performance in an experimental model of chronic PH. Right heart catheterization followed by immediate CMR was performed on 38 pigs with chronic PH (generated by surgical pulmonary vein banding) and 6 sham-operated controls. Native T1 and Eq-ECV values at the RV insertion points were both significantly higher in banded animals than in controls and showed significant correlation with pulmonary hemodynamics, RV arterial coupling, and RV performance. Eq-ECV values also increased before overt RV systolic dysfunction, offering potential for the early detection of myocardial involvement in chronic PH. Sin financiación 7.815 JCR (2015) Q1, 6/124 Cardiac and cardiovascular system, 1/124 Radiology, nueclear medicine and medicine imaging UEM

Forest fires have become a major threat to some soils in the Chilean Patagonia. More than 36,000 ha of predominantly native forest have been burned in the last four decades in the Serrano River basin, most of them in the Torres del Paine National Park, a world biosphere reserve. A study was conducted to evaluate the effects of forest fires and water erosion on the soil organic carbon (SOC) in the Serrano River basin. A total of 17 sites were sampled, three major soil types were found (Dystric Cambisols, Lithosols, and Luvic Phaeozems), and three main forest fires were identified. Soils were sampled at two depths and analyzed to determine their texture, SOC, cation exchange capacity, total N, P, and K, and aggregate stability. Soil erosion rates were estimated using the Water Erosion Prediction Project (WEPP) model with actual soil, vegetation, and weather data. The SOC content was the main significant difference between samples at depths of 0.2 and 0.4 m, at both burned and unburned sites. The 0.2-m-depth samples had an average SOC of 5.1 %, compared to 3.2 % for the 0.4-m-depth samples. The nutrient contents and CEC were also higher in the upper layer. The burned and unburned sites were not found to be different in their SOC contents or other soil properties, with the exception of P availability. As a result of the bareness of their soil, the burned sites had the highest water erosion rates (9.3 t ha−1 year−1) and SOC losses (0.5 t ha−1 year−1).

Microbially influenced corrosion (MIC) is recognized as an unusual and severe type of corrosion that causes costly failures around the world. A microbial biofilm could enhance the copper release from copper plumbing into the water by forming a reactive interface. The biofilm increases the corrosion rate, the mobility of labile copper from its matrix and the detachment of particles enriched with copper under variable shear stress due to flow conditions. MIC is currently considered as a series of interdependent processes occurring at the metal-liquid interface. The presence of a biofilm results in the following effects: (a) the formation of localized microenvironments with distinct pH, dissolved oxygen concentrations, and redox conditions; (b) sorption and desorption of labile copper bonded to organic compounds under changing water chemistry conditions; (c) change in morphology by deposition of solid corrosion by-products; (d) diffusive transport of reactive chemical species from or towards the metal surface; and (e) detachment of scale particles under flow conditions. Using a multi-technique approach that combines pipe and coupon experiments this paper reviews the effects of microbial biofilms on the corrosion of copper plumbing systems, and proposes an integrated conceptual model for this phenomenon supported by new experimental data.

Summary El Tatio geothermal field is the principal natural source of arsenic for the Loa River, the main surface water resource in the hyper-arid Atacama Desert (Antofagasta Region, Northern Chile). Prior investigations by bulk X-ray absorption spectroscopy have identified hydrous ferric oxides as the principal arsenic-containing phase in sinter material from El Tatio, suggesting sorption as the main mechanism for arsenic scavenging by the solid phases of these hot spring environments. Here we examine siliceous sinter material sampled from a hydrothermal channel using synchrotron based X-ray micro-probe techniques, including As and Fe Kα X-ray fluorescence (μ-XRF), As K-edge X-ray absorption near edge structure (μ-XANES), and X-ray diffraction (μ-XRD). Least-squares linear fitting of μ-XANES spectra shows that arsenic is predominantly present as arsenate sorbed on hydrous ferric oxides (63% molar proportion), but we also identify nodular arsenide micro-mineralizations (37% molar proportion) similar to loellingite (FeAs 2 ), not previously detected during bulk-scale analysis of the sinter material. Presence of arsenide mineralizations indicates development of anoxic environments on the surface of the siliceous sinter, and suggests a more complex biogeochemistry for arsenic than previously observed for circum-neutral pH brine hot spring environments.

Copper is used for household drinking water distribution systems given its physical and chemical properties that make it resistant to corrosion. However, there is evidence that, under certain conditions, it can corrode and release unsafe concentrations of copper to the water. Research on drinking water copper pipes has developed conceptual models that include several physical-chemical mechanisms. Nevertheless, there is still a necessity for the development of mathematical models of this phenomenon, which consider the interaction among physical-chemical processes at different spatial scales. We developed a conceptual and a mathematical model that reproduces the main processes in copper release from copper pipes subject to stagnation and flow cycles, and corrosion is associated with biofilm growth on the surface of the pipes. We discuss the influence of the reactive surface and the copper release curves observed. The modeling and experimental observations indicated that after 10h stagnation, the main concentration of copper is located close to the surface of the pipe. This copper is associated with the reactive surface, which acts as a reservoir of labile copper. Thus, for pipes with the presence of biofilm the complexation of copper with the biomass and the hydrodynamics are the main mechanisms for copper release.

Rivers in northern Chile have arsenic (As) concentrations at levels that are toxic for humans and other organisms. Microorganism-mediated redox reactions have a crucial role in the As cycle; the microbial oxidation of As (As(III) to As(V)) is a critical transformation because it favors the immobilization of As in the solid phase. We studied the role of microbial As oxidation for controlling the mobility of As in the extreme environment found in the Chilean Altiplano (i.e., > 4000 meters above sea level (masl) and < 310 mm annual rainfall), which are conditions that have rarely been studied. Our model system was the upper Azufre River sub-basin, where the natural attenuation of As from hydrothermal discharge (pH 4-6) was observed. As(III) was actively oxidized by a microbial consortium, leading to a significant decrease in the dissolved As concentrations and a corresponding increase in the sediment's As concentration downstream of the hydrothermal source. In-situ oxidation experiments demonstrated that the As oxidation required biological activity, and microbiological molecular analysis confirmed the presence of As(III)-oxidizing groups (aroA-like genes) in the system. In addition, the pH measurements and solid phase analysis strongly suggested that the As removal mechanism involved adsorption or coprecipitation with Fe-oxyhydroxides. Taken together, these results indicate that the microorganism-mediated As oxidation contributed to the attenuation of As concentrations and the stabilization of As in the solid phase, therefore controlling the amount of As transported downstream. This study is the first to demonstrate the microbial oxidation of As in Altiplano basins and its relevance in the immobilization of As.

A fully quantitative cellular automaton (CA) biofilm model was developed. The model describes substrate and biomass as discrete particles existing and interacting in a specified physical domain. Substrate particles move by random walks, simulating molecular diffusion. Microbial particles grow attached to a surface or to other microbial particles, consume substrate particles, and duplicate if a sufficient amount of substrate is consumed. The dynamics of the system are simulated using stochastic processes that represent the occurrence of specific events, such as substrate diffusion, substrate utilization, biofilm growth, and biofilm decay and detachment. The ability of the CA model to predict substrate gradients and fluxes was evaluated by comparing model simulations to predictions from a traditional differential equations model. One and 2D CA models were evaluated. In general, CA model predictions of steady-state flux, biofilm thickness, and substrate gradients inside the biofilm fitted well with the differential equations model results; the 2D model had a better agreement at high substrate concentrations. Fully quantitative CA biofilm models offer an alternative approach to simulate biofilm activity and development. Specific advantages of CA modeling include the ability to simulate growth of heterogeneous biofilms with irregular boundary conditions, and the possibility of developing computationally efficient parallel processing algorithms for the quantitative simulation of biofilms in two and three dimensions.

In skeletal and cardiac muscle, calcium release from the sarcoplasmic reticulum, leading to contraction, often results in calcium sparks. Because sparks are recorded by confocal microscopy in line-scanning mode, their measured amplitude depends on their true amplitude and the position of the spark relative to the scanned line. We present a method to derive from measured amplitude histograms the actual distribution of spark amplitudes. The method worked well when tested on simulated distributions of experimental sparks. Applied to massive numbers of sparks imaged in frog skeletal muscle under voltage clamp in reference conditions, the method yielded either a decaying amplitude distribution (6 cells) or one with a central mode (5 cells). Caffeine at 0.5 or 1mM reversibly enhanced this mode (5 cells) or induced its appearance (4 cells). The occurrence of a mode in the amplitude distribution was highly correlated with the presence of a mode in the distribution of spark rise times or in the joint distribution of rise times and spatial widths. If sparks were produced by individual Markovian release channels evolving reversibly, they should not have a preferred rise time or amplitude. Channel groups, instead, could cooperate allosterically or through their calcium sensitivity, and give rise to a stereotyped amplitude in their collective spark.

During a major study focusing on the fate of primary production through the food web in an upwelling system located in the Humboldt Current System, Antofagasta, Chile (23–24°S), we examined the spatial variation of phytoplankton size structure. One of the main objectives was to estimate primary production (14C) and chlorophyll-a biomass for three phytoplankton size fractions; pico-, nano- and micro-phytoplankton, at coastal ( 23 μm) increased its relative contribution to primary production from oceanic (12%) to coastal (21%) stations and was related to an upwelling process which was restricted to a narrow inshore band (

A mathematical model for the counter-diffusional membrane-attached methanotrophic biofilm reactor was developed. The model included competitive inhibition between trichloroethylene (TCE) and methane, production of inactive cells by TCE byproduct toxicity, and biomass detachment as a function of inactive cell concentration. Simulation results indicated that the optimum oxygen to methane ratio was dependent on the biofilm and the membrane thickness. Furthermore, the model confirmed experimental observations that the efficiency of the process is not limited by competitive inhibition or substrates mass transfer, but by the back-diffusion of TCE through the membrane and the consequent TCE accumulation in the gas phase.

An algorithm for the calculation of Ca2+ release flux underlying Ca2+ sparks (Blatter, L.A., J. Hüser, and E. Ríos. 1997. Proc. Natl. Acad. Sci. USA. 94:4176–4181) was modified and applied to sparks obtained by confocal microscopy in single frog skeletal muscle fibers, which were voltage clamped in a two-Vaseline gap chamber or permeabilized and immersed in fluo-3–containing internal solution. The performance of the algorithm was characterized on sparks obtained by simulation of fluorescence due to release of Ca2+ from a spherical source, in a homogeneous three-dimensional space that contained components representing cytoplasmic molecules and Ca2+ removal processes. Total release current, as well as source diameter and noise level, was varied in the simulations. Derived release flux or current, calculated by volume integration of the derived flux density, estimated quite closely the current used in the simulation, while full width at half magnitude of the derived release flux was a good monitor of source size only at diameters >0.7 μm. On an average of 157 sparks of amplitude >2 U resting fluorescence, located automatically in a representative voltage clamp experiment, the algorithm reported a release current of 16.9 pA, coming from a source of 0.5 μm, with an open time of 6.3 ms. Fewer sparks were obtained in permeabilized fibers, so that the algorithm had to be applied to individual sparks or averages of few events, which degraded its performance in comparable tests. The average current reported for 19 large sparks obtained in permeabilized fibers was 14.4 pA. A minimum estimate, derived from the rate of change of dye-bound Ca2+ concentration, was 8 pA. Such a current would require simultaneous opening of between 8 and 60 release channels with unitary Ca2+ currents of the level recorded in bilayer experiments. Real sparks differ from simulated ones mainly in having greater width. Correspondingly, the algorithm reported greater spatial extent of the source for real sparks. This may again indicate a multichannel origin of sparks, or could reflect limitations in spatial resolution.

A mathematical model to simulate the three-dimensional growth of multispecies anaerobic biofilms is developed and tested with a two-species biofilm composed of sulfate-reducing bacteria and methanogens. The numerical approach is based on the separation of biological, physical, and chemical phenomena so that quasi-steady-state conditions can be used in the solution. Simulations with Desulfovibrio vulgaris and Methanobacterium formicicum result in the formation of a biofilm heterogeneous in structure and composition. The model predicts different biofilm structures in the absence of sulfate, when a syntrophic association between the two organisms develops, and in the presence of sulfate, when the two organisms compete for the available hydrogen.

Ca2+ sparks have intrigued researchers since their discovery (Cheng et al., 1993). No one anticipated their existence; therefore, they must be telling us something we did not know. Also appealing are the esthetics of a sharp rise in local Ca2+, extremely limited in space and time but large compared with the recording noise.

10 and 30mm 2,3-butanedione monoxime (BDM) applied extracellularly to voltage-clamped frog skeletal muscle twitch fibres suppressed both Ca2+ release flux and intramembranous charge movement. Both effects could be clearly separated. The early peak of the Ca2+ release flux was suppressed at every test voltage. The steady level attained at the end of a 100ms clamp depolarization was relatively spared for lower depolarizing pulses, but was as suppressed as the peak at voltages above −20mV. The intramembranous charge movement was affected mainly in the Iγ component. The drug had a distinct effect on the kinetics of the intramembranous charge movement current around the threshold for Ca2+ release. The three kinetic components of Iγ were simultaneously affected. For more positive depolarizations where the kinetic effect was not evident, the oxime had no significant effect on the charge moved. Under conditions in which Iγ was absent (i.e. stretched fibres, intracellular solutions containing 6 to 10mm BAPTA), treatment with 10mm BDM had a small, not significant suppressive effect on the maximum charge moved (Qmax), while it affected Ca2+ release significantly. When 10mm BDM was applied in the presence of 0.2mm tetracaine, the local anaesthetic-resistant Ca2+ release flux was not further suppressed by the oxime.

This is a quantitative model of control of Ca2+ release from the sarcoplasmic reticulum in skeletal muscle, based on dual control of release channels (ryanodine receptors), primarily by voltage, secondarily by Ca2+ (Ríos, E., and G. Pizarro. 1988. NIPS. 3:223–227). Channels are positioned in a double row array of between 10 and 60 channels, where exactly half face voltage sensors (dihydropyridine receptors) in the transverse (t) tubule membrane (Block, B.A., T. Imagawa, K.P. Campbell, and C. Franzini-Armstrong. 1988. J. Cell Biol. 107:2587–2600). We calculate the flux of Ca2+ release upon different patterns of pulsed t-tubule depolarization by explicit stochastic simulation of the states of all channels in the array. Channels are initially opened by voltage sensors, according to an allosteric prescription (Ríos, E., M. Karhanek, J. Ma, A. González. 1993. J. Gen. Physiol. 102:449–482). Ca2+ permeating the open channels, diffusing in the junctional gap space, and interacting with fixed and mobile buffers produces defined and changing distributions of Ca2+ concentration. These concentrations interact with activating and inactivating channel sites to determine the propagation of activation and inactivation within the array. The model satisfactorily simulates several whole-cell observations, including kinetics and voltage dependence of release flux, the “paradox of control,” whereby Ca2+-activated release remains under voltage control, and, most surprisingly, the “quantal” aspects of activation and inactivation (Pizarro, G., N. Shirokova, A. Tsugorka, and E. Ríos. 1997. J. Physiol. 501:289–303). Additionally, the model produces discrete events of activation that resemble Ca2+ sparks (Cheng, H., M.B. Cannell, and W.J. Lederer. 1993. Science (Wash. DC). 262:740–744). All these properties result from the intersection of stochastic channel properties, control by local Ca2+, and, most importantly, the one dimensional geometry of the array and its mesoscopic scale. Our calculations support the concept that the release channels associated with one face of one junctional t-tubule segment, with its voltage sensor, constitute a functional unit, termed the “couplon.” This unit is fundamental: the whole cell behavior can be synthesized as that of a set of couplons, rather than a set of independent channels.

La neurotoxina botulinica es ampliamente usada para tratar una variedad de trastornos del movimiento, especialmente la distonia y la espasticidad. Existen diferentes preparados de toxina botulica tipo A, que por ser productos biologicos resultan dificilmente comparables. La abobotulinumtoxinA (Dysport®) ha sido introducida en Chile recientemente para el tratamiento de la distonia y la espasticidad. El objetivo de este trabajo es entregar una revision hecha por expertos sobre la evidencia existente y plantear una guia practica para el uso del medicamento. Metodos y Resultados: Un grupo de expertos chilenos se reunieron el 6 y 7 julio de 2012 para revisar las dosis abobotulinumtoxin A, junto con los protocolos de inyeccion para la distonia, la espasticidad y otros trastornos del movimiento. Se trabajo en dos grupos, uno compuesto por neurologos que revisaron las indicaciones en distonias y otro por fisiatras que revisaron las indicaciones para espasticidad. Conclusiones: Finalmente, se realiza una propuesta en cuanto a dosis, puntos a inyectar y recomendaciones para la distonia y espasticidad.

Fluvial sediments from two lower Loa River basin sites in northern Chile were compared in order to probe the effects of vegetation and organic matter (OM) on As accumulation in fluvial environments. The two sites were the Sloman dam, which lacks macrophytes and has a low OM content (2.4%) in sediments, and the Quillagua Oasis, which is 23 km downstream from the Sloman site and has a higher OM (6.2%) in sediments and abundant aquatic plant life. The Quillagua site had preferential As enrichment with a co-occurrence pattern that differed from that of the Sloman site, which had a lower As concentration (1528 vs. 262 mg/kg d.w., respectively). At the Quillagua site, As concentration was strongly correlated with Mn and OM (r = 0.91 and 0.85, respectively); while at the Sloman site, As concentration in sediments was significantly correlated with Ca and Sr (r = 0.63 and 0.54, respectively). Sequential extraction analyses showed that the Sloman site had higher percentage of easily exchangeable As within the surface sediment (12%, 45 mg/kg d.w.) compared with the Quillagua site (3%, 40 mg/kg d.w.). These contrasting results suggest that both vegetation and OM control the immobilization and accumulation of As in the arid Loa River basin.

Purpose: Supravalvular tachycardias form a subgroup of idiopathic outflow tract tachycardias that have their origin at the level of the aortic sinuses or the proximal pulmonary artery (PA). The existence of ventricular myocardium in close anatomic vicinity to the ventriculo-arterial junction is a known fact. However, the presence of myocardial extensions over the level of the sino-tubular junction has not been systematically analyzed. Methods: We examined 40 hearts of post-mortem adult humans (22 male; 56±8 y/o). We performed sagittal histological sections stained with Masson's trichrome. Optical microscopy techniques were used to observe the presence of extensions of myocardium at the pulmonary valve sinuses and over the sino-tubular junction. We measured the distance from the myocardial extensions to the basal insertion of the semilunar leaflets. Results: In all 40 hearts, the muscle fibers around the right ventricle outflow tract joined the ventriculo-arterial junction, forming part of the muscular ring that surrounds the PA. In 8 hearts (20%), the musculature of the ventriculo-arterial junction extended in its epicardial aspect over the pulmonary valve sinuses. These myocardial extensions continued above the sino-tubular junction to a distance of 10±2 mm from the basal insertion of the semilunar leaflets (range 7, 5-14 mm). The extensions were formed by viable myocytes surrounded by adipose tissue that reached the right ventricular infundibulum. ![Figure][1] Myocardium over the sinotubular junction Conclusion: The presence of ventricular myocardial extensions above the PA sino-tubular junction has implications for the anatomical substrate and percutaneous treatment of supravalvular tachycardias. [1]: pending:yes

Estimation of monthly runoff statistical properties, such as monthly means and variances, is usually needed to design and evaluate water resource systems. If no local recorded data are available, a transfer of information through different alternative procedures can be used. In this paper, the use of linear Transfer Function (TF) models with precipitation series as inputs is proposed to estimate statistical properties of the resulting runoff series. Empirical relationships based on data from watersheds in the mountainous zone of central Chile are suggested to estimate parameters of low-order TF models and some of their properties.

Stream flow rates with seasonal, daily, or hourly cycles due to freezing and thawing can control downstream chemical processes by changing the mixing ratio of reactive flows. The extent of these hydrologic-chemical interactions has not been fully realized yet. This work explored the link between daily freeze-thaw cycles and the fate and transport of metals at a model stream impacted by acid drainage. We characterized hydrological and physicochemical parameters at the confluence between the Caracarani River (pH ~8.6) and the Azufre River (pH < 2), in northern Chile. Hourly water depth, temperature, and electrical conductivity monitoring coupled with pH and turbidity measurements revealed that maximum flow rates from thawing of the Azufre River induced characteristic daily drops in pH and turbidity. Shifts in pH controlled the precipitation and dissolution of arsenic-rich iron and aluminum reactive phases. Thus freeze-thaw processes are critical at streams receiving acid drainage where iron and aluminum phases form and are likely to impact the fate and transport of toxic metals in the system. This work highlights the importance of assessing the hydrological controls on flows and mixing ratios when studying the chemical reactivity and fate of contaminants at systems affected by acid drainage.

The definition of atrial fibrillation (AF) as a functional electrical disorder does not reflect the significant underlying structural abnormalities. Atrial and Pulmonary Vein (PV) muscle sleeve microstructural remodeling is present, and establishes a vulnerable substrate for AF maintenance. In spite of an incomplete understanding of the anatomo-functional basis for AF, current evidence demonstrates that this arrhythmia usually requires a trigger for initiation and a vulnerable electrophysiological and/or anatomical substrate for maintenance. It is still unclear whether the trigger mechanisms include focal enhanced automaticity, triggered activity and/or micro re-entry from myocardial tissue. Initiation of AF can be favored by both parasympathetic and sympathetic stimulation, which also seem to play a role in maintaining AF. Finally, evolving clinical evidence demonstrates that inflammation is associated with new-onset and recurrent AF through a mechanism that possibly involves cellular degeneration, apoptosis, and subsequent atrial fibrosis. © 2012 Bentham Science Publishers. Sin financiación 0.546 SJR (2012) Q2, 2321/6630 Medicine, 139/332 Cardiology and cardiovascular medicine UEM

This paper presents an automated method to segment left ventricle (LV) tissues from functional and delayed-enhancement (DE) cardiac magnetic resonance imaging (MRI) scans using a sequential multi-step approach. First, a region of interest (ROI) is computed to create a subvolume around the LV using morphological operations and image arithmetic. From the subvolume, the myocardial contours are automatically delineated using difference of Gaussians (DoG) filters and GSV snakes. These contours are used as a mask to identify pathological tissues, such as fibrosis or scar, within the DE-MRI. The presented automated technique is able to accurately delineate the myocardium and identify the pathological tissue in patient sets. The results were validated by two expert cardiologists, and in one set the automated results are quantitatively and qualitatively compared with expert manual delineation. Furthermore, the method is patient-specific, performed on an entire patient MRI series. Thus, in addition to providing a quick analysis of individual MRI scans, the fully automated segmentation method is used for effectively tagging regions in order to reconstruct computerized patient-specific 3D cardiac models. These models can then be used in electrophysiological studies and surgical strategy planning. 1.435 JCR (2012) Q1, 21/90 Engineering, multidisciplinary; Q2, 21/57 Instruments & instrumentation

This editorial refers to ‘The anatomical characteristics of three different endocardial lines in the left atrium: evaluation by computed tomography prior to mitral isthmus block attempt’ by Y. Cho et al ., on page 1104 Early electrophysiological studies demonstrated the presence of an isthmus of conductive tissue in the low lateral left atrium (LA) during ablation of left free-wall accessory pathways.1 These studies introduced the LA ‘isthmus’ concept—a site of intra-atrial conduction block that shows the latest atrial activation during sinus rhythm. Although this posteroinferior area of the lateral LA wall between the orifice of the left inferior pulmonary vein (PV) and the mitral annulus cannot be considered an anatomic entity, it is now termed by electrophysiologists as the LA isthmus, or mitral isthmus. Linear ablation connecting the inferior margin of the ostium of the left inferior PV and the mitral annulus, particularly when complete linear block is achieved, appears to increase the success rate of catheter ablation in patients with atrial fibrillation (AF) and prevent macro-reentry around the mitral annulus or the left PVs.2,3 However, the creation of mitral isthmus lesions by catheter ablation is technically challenging and may be associated with significant complications. Factors that make obtaining a complete, transmural, and permanent ablation line across the mitral isthmus difficult may be electrical as well as anatomical because of the variable and complex endocardial geometry of the LA posterolateral region. Other factors include the unpredictable content of atrial myocardium and the cooling effect of the circumflex artery at different locations of this atrial territory. A better understanding of the anatomo-functional substrate is essential for developing a proper LA isthmus ablation strategy that can contribute to successful outcome. In a valuable anatomic study in 20 hearts, Anton Becker4 showed marked variability in the dimensions of the …

Asymmetric membrane currents and calcium transients were recorded simultaneously from cut segments of frog skeletal muscle fibers voltage clamped in a double Vaseline-gap chamber in the presence of high concentration of EGTA intracellularly. An inward phase of asymmetric currents following the hump component was observed in all fibers during the depolarization pulse to selected voltages (congruent to -45 mV). The average value of the peak inward current was 0.1 A/F (SEM = 0.01, n = 18), and the time at which it occurred was 34 ms (SEM = 1.8, n = 18). A second delayed outward phase of asymmetric current was observed after the inward phase, in those experiments in which hump component and inward phase were large. It peaked at more variable time (between 60 and 130 ms) with amplitude 0.02 A/F (SEM = 0.003, n = 11). The transmembrane voltage during a pulse, measured with a glass microelectrode, reached its steady value in less than 10 ms and showed no oscillations. The potential was steady at the time when the delayed component of asymmetric current occurred. ON and OFF charge transfers were equal for all pulse durations. The inward phase moved 1.4 nC/microF charge (SEM = 0.8, n = 6), or about one third of the final value of charge mobilized by these small pulses, and the second outward phase moved 0.7 nC/microF (SEM = 0.8, n = 6), bringing back about half of the charge moved during the inward phase. When repolarization intersected the peak of the inward phase, the OFF charge transfer was independent of the repolarization voltage in the range -60 to -90 mV. When both pre- and post-pulse voltages were changed between -120 mV and -60 mV, the equality of ON and OFF transfers of charge persisted, although they changed from 113 to 81% of their value at -90 mV. The three delayed phases in asymmetric current were also observed in experiments in which the extracellular solution contained Cd2+, La3+ and no Ca2+. Large increases in intracellular [Cl-] were imposed, and had no major effect on the delayed components of the asymmetric current. The Ca2+ transients measured optically and the calculated Ca2+ release fluxes had three phases whenever a visible outward phase followed the inward phase in the asymmetric current. Several interventions intended to interfere with Ca release, reduced or eliminated the three delayed phases of the asymmetric current.(ABSTRACT TRUNCATED AT 400 WORDS)

Ca²⁺ influx across the plasma membrane upon drastic reduction of the sarcoplasmic reticulum Ca²⁺ content was studied in voltage clamped frog skeletal muscle fibers. Depletion was produced by the application of 30 μM cyclopiazonic acid (CPA) in Ca²⁺-free, [Mg²⁺] = 8 mM external salines and produced an increase in resting free myoplasmic [Ca²⁺]. Once depletion was attained the external solution was changed to one containing the same concentration of the drug but with Ca²⁺ instead of Mg²⁺. Of 27 fibers studied only nine showed a secondary increase in free myoplasmic [Ca²⁺] upon readmitting Ca²⁺ in the external perfusate. In the presence of CPA the resting myoplasmic [Ca²⁺] in Ca²⁺-free external saline was 0.08 ± 0.01 μM (Mean ± SEM), and in Ca²⁺-containing external saline 0.10 ± 0.02 μM when the intracellular solution contained [EGTA] = 5 mM (n = 18). In cells with lower (0.5 mM) intracellular [EGTA] resting [Ca²⁺] went from 0.35 +/- 0.08 μM in Ca²⁺-free external solution to 0.42 +/- 0.12 μM upon reapplication of Ca²⁺(n = 9). In both cases the differences between means were not statistically significant (paired t test, p = 0.13 in high EGTA and p = 0.25 in low EGTA). In the nine fibers that showed a secondary increase of resting [Ca²⁺] the holding current measured at -90 mV did not significantly change. These results suggest the Ca²⁺ entry secondary to store depletion is a labile mechanism in frog skeletal muscle and when present does not have an obvious electrical manifestation.

Enhancing the performance of clarifiers requires a thorough understanding of their hydraulics. Fluorescence spectroscopy and acoustic doppler velocimeter (ADV) profiling generally have been used separately to evaluate secondary settlers. We propose that simultaneous use of these techniques is needed to obtain a more reliable and useful evaluation. Experiments were performed on laboratory- and full-scale clarifiers. Factors affecting Fluorescein and Rhodamine 6G properties were identified. Underestimations up to 500% in fluorescence intensities may be derived from differential fluorescence quenching by oxygen. A careful control and interpretation of fluorescent dye experiments is needed to minimize artifacts in real settings. While flow-curve tests constructed under controlled conditions provided a more accurate overall quantitative estimation of the hydraulic performance, ADV velocity and turbulence profiling provided a detailed spatial understanding of flow patterns that was used to troubleshoot and fix the causes of hydraulic short-circuits.

This editorial refers to ‘Atrial fibrillation following lung transplantation: double but not single lung transplant is associated with long-term freedom from paroxysmal atrial fibrillation’, by G. Lee et al. doi:10.1093/eurheartj/ehq224 Atrial fibrillation (AF) is a complex disease most probably due to multiple aetiopathogenic mechanisms. This arrhythmia usually requires a trigger for initiation and a vulnerable electrophysiological and/or anatomic substrate for maintenance. It is still unclear whether the trigger mechanisms for AF initiation include focal enhanced automaticity, triggered activity, or microre-entry from myocardial tissue inside the pulmonary vein (PV). In spite of an incomplete understanding of the anatomo-functional basis for the initiation and maintenance of AF, various catheter and surgical ablation techniques have been shown to modify the substrate of this arrhythmia, achieving a stable sinus rhythm, free from AF, in a high proportion of cases. In the past 10 years, catheter ablation techniques in patients with AF have evolved from an initial approach focused on the PVs and their junctions with the left atrium (LA), to a more extensive intervention, mainly, but not exclusively, on the LA myocardium and its neuro-vegetative innervation ( Figure 1 ). It is now recognized that the cornerstone of most catheter and surgical ablation approaches is to isolate the PVs electrically from the LA wall. Despite more or less substantial differences among the various catheter techniques that are currently utilized worldwide, results seem to be uniformly similar, with success rates in the range from 50% to 80% in patients with long-standing, persistent, or paroxysmal AF. Notably, a median of two AF ablation procedures are usually necessary for a successful outcome.1,2 Figure 1 Schematic of the anatomo-functional arrhythmic mechanism and common ablation strategies in paroxysmal and long-standing/persistent AF. ( A ) Active triggers arising from the atrial myocardium within the PVs and other thoracic veins (CS, vein/ligament of Marshall, … *Corresponding author. Tel: +34 902 1515 016, Fax: +34 915183232, Email: jacabrera.mad{at}quiron.es; jac11339{at}yahoo.co.uk

Predictive models characterizing the evolution and interaction of key parameters of water chemistry are needed to better understand corrosion events in drinking water pipes. We performed experiments with new copper pipes under combinations of pH, dissolved oxygen (DO), temperature, chlorine, and dissolved inorganic carbon. We found that DO consumption during 24 h of stagnation was not limited by diffusion, thus the DO consumption rate in the bulk water could be used to probe the processes occurring at the pipe surface. We propose a quantitative dependency of the DO consumption rate on a rather limited set of physicochemical parameters.

Cardiac CT is an accurate and reasonable alternative modality for valvular imaging. It is used primarily for the evaluation of coronary artery disease; however, important information regarding valvular anatomy and function can be derived from CT. Calcification is a common CT finding in various valvular abnormalities and carries important diagnostic and prognostic value. In addition, valvular morphology, stenosis, and regurgitation also are detected on contrast enhanced scans, with good correlation with trans-thoracic echocardiography and other techniques.

Research on corrosion of copper pipes has given little consideration to the influence of solid corrosion by-products on the processes occurring at the metal-liquid interface. Consequently, the effect of such solid phases on the rate of dissolved oxygen (DO) consumption remains poorly understood. In-situ experiments were performed in copper pipes under different carbonate concentrations and ageing times. Our results show that the amount of solid corrosion by-products and concentration of hydrogen ions affect the rate of DO consumption during stagnation. Furthermore, our findings support the existing hypothesis that the available concentration of hydrogen ions, rather than DO, is the limiting factor for copper release into drinking water.

Asymmetric membrane currents and fluxes of Ca2+ release were determined in skeletal muscle fibers voltage clamped in a Vaseline-gap chamber. The conditioning pulse protocol 1 for suppressing Ca2+ release and the "hump" component of charge movement current (I gamma), described in the first paper of this series, was applied at different test pulse voltages. The amplitude of the current suppressed during the ON transient reached a maximum at slightly suprathreshold test voltages (-50 to -40 mV) and decayed at higher voltages. The component of charge movement current suppressed by 20 microM tetracaine also went through a maximum at low pulse voltages. This anomalous voltage dependence is thus a property of I gamma, defined by either the conditioning protocol or the tetracaine effect. A negative (inward-going) phase was often observed in the asymmetric current during the ON of depolarizing pulses. This inward phase was shown to be an intramembranous charge movement based on (a) its presence in the records of total membrane current, (b) its voltage dependence, with a maximum at slightly suprathreshold voltages, (c) its association with a "hump" in the asymmetric current, (d) its inhibition by interventions that reduce the "hump", (e) equality of ON and OFF areas in the records of asymmetric current presenting this inward phase, and (f) its kinetic relationship with the time derivative of Ca release flux. The nonmonotonic voltage dependence of the amplitude of the hump and the possibility of an inward phase of intramembranous charge movement are used as the main criteria in the quantitative testing of a specific model. According to this model, released Ca2+ binds to negatively charged sites on the myoplasmic face of the voltage sensor and increases the local transmembrane potential, thus driving additional charge movement (the hump). This model successfully predicts the anomalous voltage dependence and all the kinetic properties of I gamma described in the previous papers. It also accounts for the inward phase in total asymmetric current and in the current suppressed by protocol 1. According to this model, I gamma accompanies activating transitions at the same set of voltage sensors as I beta. Therefore it should open additional release channels, which in turn should cause more I gamma, providing a positive feedback mechanism in the regulation of calcium release.

Background: The aim of this study was to evaluate 2D Speckle Tracking radial strain by ultrasound in stunned and scarred myocardium as defined by cardiac magnetic resonance (CMR) in a porcine reperfusion model of acute MI. Methods: Seven pigs underwent MI induction by 90′ mid-LAD balloon occlusion. CMR was performed in a 1.5 T magnet 4 days post-MI. For edema imaging a T2-weighted sequence was employed. Delayed enhancement (DE) images were acquired 10–15 minutes after the administration of 0.2 mmol/kg of Gd-DTPA using an inversion recovery gradient-echo sequence. Before CMR, echocardiographic short axis images of the LV were obtained at the basal, mid and apical levels. Echo and CMR images were matched and divided into 6 segments per slice. DE and edema were defined as those regions with signal intensity >3 SD of the mean signal of remote normal myocardium, and quantified as % of the LV. Stunned myocardium was defined as edema- DE. Radial strain was compared in segments containing predominantly normal myocardium (25% (edema - DE); n=12] or predominantly scar (>75 % DE; n=19). Results: A total of 126 segments were analyzed. Radial strain was negatively correlated with the amount of edema (r=−0.41) and scar (r=−0.39, p ) Conclusions: Our study suggests that 2D Speckle Tracking radial strain can be a simple tool to differentiate stunned from scarred segments. This could be particularly useful in unstable patients after acute MI.

Subjects older than 80 years have more complicated acute myocardial infarctions and are subjected to less reperfusion procedures.To describe the hospital evolution and follow up of patients older than 80 years, suffering an acute myocardial infarction.Patients older than 80 years, were selected from a prospective registry of acute myocardial infarction. Among these, the hospital evolution, mortality and events during a period of five years of follow up, were recorded.Of a total of 1200 patients, 83 (7%) were aged 80 years or older. Among these, 59% were male and 22% were diabetic. The mean lapse between onset of symptoms and admission was 11 hours and 59% were admitted with less than 6 hours of evolution. Sixty-three percent had a history of a previous infarction and 24% had a Killip IV classification on admission. Reperfusion therapy was done in 19% and 70% had heart failure during evolution. A coronary angiography was done in 22% and 6% were subjected to revascularization. Mortality was 34%, specially due to cardiogenic shock or ventricular rupture. Of 55 patients discharged from the hospital, 31% died within one year and 64% within five years, mainly due to cardiac causes. conclusions: Patients aged 80 years or older have more complicated myocardial infarctions, most of them are managed conservatively and long term mortality is high.