Bladder Mucosal CO2 Compared with Gastric Mucosal CO2 as a Marker for Low Perfusion States in Septic Shock

Recent reports indicate the possible role of bladder CO2 as a marker of low perfusion states. To test this hypothesis, shock was induced in six beagle dogs with 1 mg/kg of E. coli lipopolysaccharide, gastric CO2 (CO2-G) was measured with a continuous monitor, and a pulmonary catheter was inserted in the bladder to measure CO2 (CO2-B). Levels of CO2-B were found to be lower than those of CO2-G, with a mean difference of 36.8 mmHg (P < 0.001), and correlation between both measurements was poor (r2 = 0.16). Even when the correlation between CO2-G and ΔCO2-G was narrow (r2 = 0.86), this was not the case for the relationship between CO2-B and ΔCO2-B (r2 = 0.29). Finally, the correlation between CO2-G and base deficit was good (r2 = 0.45), which was not the case with the CO2-B correlation (r2 = 0.03). In our experience, bladder CO2 does not correlate to hemodynamic parameters and does not substitute gastric CO2 for detection of low perfusion states

Robust projections of Fire Weather Index in the Mediterranean using statistical downscaling

The effect of climate change on wildfires constitutes a serious concern in fire-prone regions with complex fire behavior such as the Mediterranean. The coarse resolution of future climate projections produced by General Circulation Models (GCMs) prevents their direct use in local climate change studies. Statistical downscaling techniques bridge this gap using empirical models that link the synoptic-scale variables from GCMs to the local variables of interest (using e.g. data from meteorological stations). In this paper, we investigate the application of statistical downscaling methods in the context of wildfire research, focusing in the Canadian Fire Weather Index (FWI), one of the most popular fire danger indices. We target on the Iberian Peninsula and Greece and use historical observations of the FWI meteorological drivers (temperature, humidity, wind and precipitation) in several local stations. In particular, we analyze the performance of the analog method, which is a convenient first choice for this problem since it guarantees physical and spatial consistency of the downscaled variables, regardless of their different statistical properties. First we validate the method in perfect model conditions using ERA-Interim reanalysis data. Overall, not all variables are downscaled with the same accuracy, with the poorest results (with spatially averaged daily correlations below 0.5) obtained for wind, followed by precipitation. Consequently, those FWI components mostly relying on those parameters exhibit the poorest results. However, those deficiencies are compensated in the resulting FWI values due to the overall high performance of temperature and relative humidity. Then, we check the suitability of the method to downscale control projections (20C3M scenario) from a single GCM (the ECHAM5 model) and compute the downscaled future fire danger projections for the transient A1B scenario. In order to detect problems due to non-stationarities related to climate change, we compare the results with those obtained with a Regional Climate Model (RCM) driven by the same GCM. Although both statistical and dynamical projections exhibit a similar pattern of risk increment in the first half of the 21st century, they diverge during the second half of the century. As a conclusion, we advocate caution in the use of projections for this last period, regardless of the regionalization technique applied.We are grateful to the Spanish Meteorological Agency (AEMET) and to the Hellenic National Meteorological Service (HNMS) for providing the observational data used in this study. We would also like to thank Erik van Meijgaard from the Royal Netherlands Meteorological Institute for making available ENSEMBLES RACMO2 climate model output verifying at 12:00 UTC and to the Max Planck Institute for providing the appropriate data for the ECHAM5 model used in this work. This work was partly funded by European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreements 243888 (FUME Project) and from Spanish Ministry MICINN under grant EXTREMBLES (CGL2010-21869). We thank tw

Effects of PI and PIII Snake Venom Haemorrhagic Metalloproteinases on the Microvasculature: A Confocal Microscopy Study on the Mouse Cremaster Muscle

The precise mechanisms by which Snake Venom Metalloproteinases (SVMPs) disrupt the microvasculature and cause haemorrhage have not been completely elucidated, and novel in vivo models are needed. In the present study, we compared the effects induced by BaP1, a PI SVMP isolated from Bothrops asper venom, and CsH1, a PIII SVMP from Crotalus simus venom, on cremaster muscle microvasculature by topical application of the toxins on isolated tissue (i.e., ex vivo model), and by intra-scrotal administration of the toxins (i.e., in vivo model). The whole tissue was fixed and immunostained to visualize the three components of blood vessels by confocal microscopy. In the ex vivo model, BaP1 was able to degrade type IV collagen and laminin from the BM of microvessels. Moreover, both SVMPs degraded type IV collagen from the BM in capillaries to a higher extent than in PCV and arterioles. CsH1 had a stronger effect on type IV collagen than BaP1. In the in vivo model, the effect of BaP1 on type IV collagen was widespread to the BM of arterioles and PCV. On the other hand, BaP1 was able to disrupt the endothelial barrier in PCV and to increase vascular permeability. Moreover, this toxin increased the size of gaps between pericytes in PCV and created new gaps between smooth muscle cells in arterioles in ex vivo conditions. These effects were not observed in the case of CsH1. In conclusion, our findings demonstrate that both SVMPs degrade type IV collagen from the BM in capillaries in vivo. Moreover, while the action of CsH1 is more directed to the BM of microvessels, the effects of BaP1 are widespread to other microvascular components. This study provides new insights in the mechanism of haemorrhage and other pathological effects induced by these toxins

Soluble concentrations of the terminal complement complex C5b-9 correlate with end-organ injury in preeclampsia

Q3Q1Pacientes embarazadas hipertensasObjective: We sought to determine if soluble levels of C5b-9, the terminal complement complex, correlate with end-organ injury in preeclampsia. Study Design: Project COPA (Complement and Preeclampsia in the Americas), a multi-center observational study in Colombia from 2015 to 2016, enrolled hypertensive pregnant women into four groups: chronic hypertension, gestational hypertension, preeclampsia, and preeclampsia with severe features. Trained coordinators collected clinical data, blood and urine. End-organ injury was defined by serum creatinine ≥ 1.0 mg/dl, aspartate transaminase ≥ 70U/L, platelet count < 150,000/µl, or lactate dehydrogenase ≥ 500 U/L. Data were analyzed by χ2 or Fisher’s exact test with significance at P < 0.05. Main Outcome Measure: C5b-9 concentrations in plasma and urine, using enzyme linked immunosorbent assays. Results: In total, 298 hypertensive participants were enrolled. Plasma and urine C5b-9 levels were measured in all participants and stratified by quartile (Q1-4), from lowest to highest C5b-9 concentration. Participants with low plasma C5b-9 levels (Q1) were more likely to have end-organ injury compared to those with higher levels (Q2-Q4) [platelet count < 150,000/μl (20.8% vs. 8.4%, P = 0.01); elevated serum creatinine ≥ 1.0 mg/dl (14.9% vs. 4.5%, P = 0.009)]. In contrast, participants with high urinary C5b-9 levels (Q4) were more likely to have end-organ injury compared to those with lower levels (Q1-Q3) [platelet count < 150,000/μl (19.7% vs. 7.4%, P = 0.003); elevated serum creatinine ≥ 1.0 mg/dl (12.3% vs. 4.4%, P = 0.025)]. Conclusion: We identified a pattern of increased urine and low plasma C5b-9 levels in patients with preeclampsia and end-organ injury. Soluble C5b-9 levels may be used to identify complement-mediated end-organ injury in preeclampsia.https://orcid.org/0000-0001-6822-0374Revista Internacional - IndexadaA1N

Urethro-cutaneous fistula: a rare complication in anti-incontinence surgery with trans-obturator tapes sling

This case report presents a rare complication of tension-free mid-urethral tape surgery by the obturator approach (TOT) in the form of a urethro-cutaneous fistula. The patient underwent successful surgical repair, highlighting the importance of intraoperative cystoscopy to minimize surgical risks and complications. Tension-free mid-urethral tape surgery is a commonly performed procedure for the treatment of stress urinary incontinence (SUI). However, complications can occur, albeit rarely. In this case, a 52-year-old female patient developed a urethro-cutaneous fistula following TOT surgery. The fistula was identified by the presence of urine leakage at the right inguinal level, leading to significant distress and discomfort for the patient. Prompt diagnosis and appropriate management are crucial in such cases. The patient underwent surgical repair, which involved excision of the fistulous tract. The procedure was successful, resulting in complete resolution of the fistula and restoration of normal urinary function. In conclusion, this case report highlights the occurrence of a rare complication, namely a urethro-cutaneous fistula, following TOT surgery. The successful surgical repair emphasizes the importance of prompt diagnosis and appropriate management. Furthermore, the authors propose that an intraoperative cystoscopic evaluation be considered, even after a TOT procedure. Especially in cases that present risk factors or in hospital-school institutions. By implementing this practice, surgeons can enhance patient safety and improve surgical outcomes in anti-incontinence procedures

Binding Potassium to Improve Treatment With Renin-Angiotensin-Aldosterone System Inhibitors: Results From Multiple One-Stage Pairwise and Network Meta-Analyses of Clinical Trials.

This manuscript presents findings from the first dichotomous data pooling analysis on clinical trials (CT) regarding the effectiveness of binding potassium. The results emanated from pairwise and network meta-analyses aiming evaluation of response to commercial potassium-binding polymers, that is, to achieve and maintain normal serum potassium (n = 1,722), and the association between this response and an optimal dosing of renin-angiotensin-aldosterone system inhibitors (RAASi) needing individuals affected by heart failure (HF) or resistant hypertension, who may be consuming other hyperkalemia-inducing drugs (HKID) (e.g., β-blockers, heparin, etc.), and frequently are affected by chronic kidney disease (CKD) (n = 1,044): According to the surface under the cumulative ranking area (SUCRA), sodium zirconium cyclosilicate (SZC) (SUCRA &gt;0.78), patiromer (SUCRA &gt;0.58) and sodium polystyrene sulfonate (SPS) (SUCRA &lt;0.39) were different concerning their capacity to achieve normokalemia (serum potassium level (sK+) 3.5-5.0 mEq/L) or acceptable kalemia (sK+ ≤ 5.1 mEq/L) in individuals with hyperkalemia (sK+ &gt;5.1 mEq/L), and, when normokalemia is achieved, patiromer 16.8-25.2 g/day (SUCRA = 0.94) and patiromer 8.4-16.8 g/day (SUCRA = 0.41) can allow to increase the dose of spironolactone up to 50 mg/day in subjects affected by heart failure (HF) or with resistant hypertension needing treatment with other RAASi. The potential of zirconium cyclosilicate should be explored further, as no data exists to assess properly its capacity to optimize dosing of RAASi, contrarily as it occurs with patiromer. More research is also necessary to discern between benefits of binding potassium among all type of hyperkalemic patients, for example, patients with DM who may need treatment for proteinuria, patients with early hypertension, etc. Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020185614, CRD42020185558, CRD42020191430

Towards a fair comparison of statistical and dynamical downscaling in the framework of the EURO-CORDEX initiative

Both statistical and dynamical downscaling methods are well established techniques to bridge the gap between the coarse information produced by global circulation models and the regional-to-local scales required by the climate change Impacts, Adaptation, and Vulnerability (IAV) communities. A number of studies have analyzed the relative merits of each technique by inter-comparing their performance in reproducing the observed climate, as given by a number of climatic indices (e.g. mean values, percentiles, spells). However, in this paper we stress that fair comparisons should be based on indices that are not affected by the calibration towards the observed climate used for some of the methods. We focus on precipitation (over continental Spain) and consider the output of eight Regional Climate Models (RCMs) from the EURO-CORDEX initiative at 0.44? resolution and five Statistical Downscaling Methods (SDMs) ?analog resampling, weather typing and generalized linear models? trained using the Spain044 observational gridded dataset on exactly the same RCM grid. The performance of these models is inter-compared in terms of several standard indices ?mean precipitation, 90th percentile on wet days, maximum precipitation amount and maximum number of consecutive dry days? taking into account the parameters involved in the SDM training phase. It is shown, that not only the directly affected indices should be carefully analyzed, but also those indirectly influenced (e.g. percentile-based indices for precipitation) which are more difficult to identify. We also analyze how simple transformations (e.g. linear scaling) could be applied to the outputs of the uncalibrated methods in order to put SDMs and RCMs on equal footing, and thus perform a fairer comparison.We acknowledge the World Climate Research Programme’s Working Group on Regional Climate, and theWorking Group on CoupledModelling, former coordinating body of CORDEX and responsible panel for CMIP5. We also thank the climate modeling groups (listed in Table 1 of this paper) for producing and making available their model output. We also acknowledge the Earth System Grid Federation infrastructure and AEMET and University of Cantabria for the Spain02 dataset (available at http: //www.meteo.unican.es/en/datasets/spain02). All the statistical downscaling experiments have been computed using theMeteoLab software (http://www.meteo.unican.es/software/meteolab), which is an open-source Matlab toolbox for statistical downscaling. This work has been partially supported by CORWES (CGL2010-22158-C02) and EXTREMBLES (CGL2010-21869) projects funded by the Spanish R&D programme. AC thanks the Spanish Ministry of Economy and Competitiveness for the funding provided within the FPI programme (BES-2011-047612 and EEBB-I-13-06354), JMG acknowledges the support from the SPECS project (FP7-ENV-2012-308378) and JF is grateful to the EUPORIAS project (FP7-ENV-2012-308291). We also thank three anonymous referees for their useful comments that helped to improve the original manuscript

Radon and material radiopurity assessment for the NEXT double beta decay experiment

The Neutrino Experiment with a Xenon TPC (NEXT), intended to investigate the neutrinoless double beta decay using a high-pressure xenon gas TPC filled with Xe enriched in 136Xe at the Canfranc Underground Laboratory in Spain, requires ultra-low background conditions demanding an exhaustive control of material radiopurity and environmental radon levels. An extensive material screening process is underway for several years based mainly on gamma-ray spectroscopy using ultra-low background germanium detectors in Canfranc but also on mass spectrometry techniques like GDMS and ICPMS. Components from shielding, pressure vessel, electroluminescence and high voltage elements and energy and tracking readout planes have been analyzed, helping in the final design of the experiment and in the construction of the background model. The latest measurements carried out will be presented and the implication on NEXT of their results will be discussed. The commissioning of the NEW detector, as a first step towards NEXT, has started in Canfranc; in-situ measurements of airborne radon levels were taken there to optimize the system for radon mitigation and will be shown too.Comment: Proceedings of the Low Radioactivity Techniques 2015 workshop (LRT2015), Seattle, March 201

NEXT-100 Technical Design Report (TDR). Executive Summary

In this Technical Design Report (TDR) we describe the NEXT-100 detector that will search for neutrinoless double beta decay (bbonu) in Xe-136 at the Laboratorio Subterraneo de Canfranc (LSC), in Spain. The document formalizes the design presented in our Conceptual Design Report (CDR): an electroluminescence time projection chamber, with separate readout planes for calorimetry and tracking, located, respectively, behind cathode and anode. The detector is designed to hold a maximum of about 150 kg of xenon at 15 bar, or 100 kg at 10 bar. This option builds in the capability to increase the total isotope mass by 50% while keeping the operating pressure at a manageable level. The readout plane performing the energy measurement is composed of Hamamatsu R11410-10 photomultipliers, specially designed for operation in low-background, xenon-based detectors. Each individual PMT will be isolated from the gas by an individual, pressure resistant enclosure and will be coupled to the sensitive volume through a sapphire window. The tracking plane consists in an array of Hamamatsu S10362-11-050P MPPCs used as tracking pixels. They will be arranged in square boards holding 64 sensors (8 times8) with a 1-cm pitch. The inner walls of the TPC, the sapphire windows and the boards holding the MPPCs will be coated with tetraphenyl butadiene (TPB), a wavelength shifter, to improve the light collection.Comment: 32 pages, 22 figures, 5 table