Association between serum soluble CD40 ligand levels and mortality in patients with severe sepsis.

INTRODUCTION: CD40 Ligand (CD40L) and its soluble counterpart (sCD40L) are proteins that exhibit prothrombotic and proinflammatory properties on binding to their cell surface receptor CD40. The results of small clinical studies suggest that sCD40L levels could play a role in sepsis; however, there are no data on the association between sCD40L levels and mortality of septic patients. Thus, the aim of this study was to determine whether circulating sCD40L levels could be a marker of adverse outcome in a large cohort of patients with severe sepsis. METHODS: This was a multicenter, observational and prospective study carried out in six Spanish intensive care units. Serum levels of sCD40L, tumour necrosis factor-alpha and interleukin-10, and plasma levels of tissue factor were measured in 186 patients with severe sepsis at the time of diagnosis. Serum sCD40L was also measured in 50 age- and sex-matched controls. Survival at 30 days was used as the endpoint. RESULTS: Circulating sCD40L levels were significantly higher in septic patients than in controls (P = 0.01), and in non-survivors (n = 62) compared to survivors (n = 124) (P = 0.04). However, the levels of CD40L were not different regarding sepsis severity. Logistic regression analysis showed that sCD40L levels >3.5 ng/mL were associated with higher mortality at 30 days (odds ratio = 2.89; 95% confidence interval = 1.37 to 6.07; P = 0.005). The area under the curve of sCD40L levels >3.5 ng/mL as predictor of mortality at 30 days was 0.58 (95% CI = 0.51 to 0.65; P = 0.03). CONCLUSIONS: In conclusion, circulating sCD40L levels are increased in septic patients and are independently associated with mortality in these patients; thus, its modulation could represent an attractive therapeutic target.

Association of serum soluble Fas concentrations and mortality of septic patients.

INTRODUCTION: Scarce data on Fas, one of the main receptors that activates the apoptosis extrinsic pathway, in septic patients exists. Higher blood soluble Fas (sFas) concentrations in non-survivor septic patients compared with survivors have been found in small studies; however, the association of blood sFas concentrations with mortality controlling for sepsis severity has not been stablished due to this small sample size in those studies. Thus, our main objective study was to determine whether an association between blood sFas concentrations and sepsis mortality controlling for sepsis severity exists. METHODS: We included septic patients in this observational and prospective study carried out in three Spanish Intensive Care Units. We obtained serum samples at sepsis diagnosis sepsis for sFas levels determination. RESULTS: Thirty-day non-surviving patients (n=85) compared to surviving patients (n=151) had higher serum sFas levels (p<0.001). We found in multiple logistic regression analysis an association of serum sFas levels with mortality controlling for age and SOFA (OR=1.004; 95% CI=1.002-1.006; p<0.001), and for age and APACHE-II (OR=1.004; 95% CI=1.002-1.006; p<0.001). Serum sFas levels showed and area under the curve for mortality prediction of 71% (95% CI=65-71%; p<0.001). Kaplan-Meier analysis showed higher mortality rate in patients with serum sFas levels>83.5ng/mL (Hazard ratio=3.2; 95% CI=2.1-5.0; p<0.001). CONCLUSIONS: That an association between blood sFas concentrations and sepsis mortality controlling for sepsis severity exists was our main new finding study.

Temperature increase prevails over acidification in gene expression modulation of amastigote differentiation in Leishmania infantum.

BACKGROUND: The extracellular promastigote and the intracellular amastigote stages alternate in the digenetic life cycle of the trypanosomatid parasite Leishmania. Amastigotes develop inside parasitophorous vacuoles of mammalian phagocytes, where they tolerate extreme environmental conditions. Temperature increase and pH decrease are crucial factors in the multifactorial differentiation process of promastigotes to amastigotes. Although expression profiling approaches for axenic, cell culture- and lesion-derived amastigotes have already been reported, the specific influence of temperature increase and acidification of the environment on developmental regulation of genes has not been previously studied. For the first time, we have used custom L. infantum genomic DNA microarrays to compare the isolated and the combined effects of both factors on the transcriptome. RESULTS: Immunofluorescence analysis of promastigote-specific glycoprotein gp46 and expression modulation analysis of the amastigote-specific A2 gene have revealed that concomitant exposure to temperature increase and acidification leads to amastigote-like forms. The temperature-induced gene expression profile in the absence of pH variation resembles the profile obtained under combined exposure to both factors unlike that obtained for exposure to acidification alone. In fact, the subsequent fold change-based global iterative hierarchical clustering analysis supports these findings. CONCLUSIONS: The specific influence of temperature and pH on the differential regulation of genes described in this study and the evidence provided by clustering analysis is consistent with the predominant role of temperature increase over extracellular pH decrease in the amastigote differentiation process, which provides new insights into Leishmania physiology.

Association of serum soluble Fas concentrations and mortality of septic patients.

INTRODUCTION: Scarce data on Fas, one of the main receptors that activates the apoptosis extrinsic pathway, in septic patients exists. Higher blood soluble Fas (sFas) concentrations in non-survivor septic patients compared with survivors have been found in small studies; however, the association of blood sFas concentrations with mortality controlling for sepsis severity has not been stablished due to this small sample size in those studies. Thus, our main objective study was to determine whether an association between blood sFas concentrations and sepsis mortality controlling for sepsis severity exists. METHODS: We included septic patients in this observational and prospective study carried out in three Spanish Intensive Care Units. We obtained serum samples at sepsis diagnosis sepsis for sFas levels determination. RESULTS: Thirty-day non-surviving patients (n=85) compared to surviving patients (n=151) had higher serum sFas levels (p<0.001). We found in multiple logistic regression analysis an association of serum sFas levels with mortality controlling for age and SOFA (OR=1.004; 95% CI=1.002-1.006; p<0.001), and for age and APACHE-II (OR=1.004; 95% CI=1.002-1.006; p<0.001). Serum sFas levels showed and area under the curve for mortality prediction of 71% (95% CI=65-71%; p<0.001). Kaplan-Meier analysis showed higher mortality rate in patients with serum sFas levels>83.5ng/mL (Hazard ratio=3.2; 95% CI=2.1-5.0; p<0.001). CONCLUSIONS: That an association between blood sFas concentrations and sepsis mortality controlling for sepsis severity exists was our main new finding study.

The 2005 MARTE Robotic Drilling Experiment in Río Tinto, Spain: objectives, approach, and results of a simulated mission to search for life in the Martian subsurface.

The Mars Astrobiology Research and Technology Experiment (MARTE) simulated a robotic drilling mission to search for subsurface life on Mars. The drill site was on Peña de Hierro near the headwaters of the Río Tinto river (southwest Spain), on a deposit that includes massive sulfides and their gossanized remains that resemble some iron and sulfur minerals found on Mars. The mission used a fluidless, 10-axis, autonomous coring drill mounted on a simulated lander. Cores were faced; then instruments collected color wide-angle context images, color microscopic images, visible-near infrared point spectra, and (lower resolution) visible-near infrared hyperspectral images. Cores were then stored for further processing or ejected. A borehole inspection system collected panoramic imaging and Raman spectra of borehole walls. Life detection was performed on full cores with an adenosine triphosphate luciferin-luciferase bioluminescence assay and on crushed core sections with SOLID2, an antibody array-based instrument. Two remotely located science teams analyzed the remote sensing data and chose subsample locations. In 30 days of operation, the drill penetrated to 6 m and collected 21 cores. Biosignatures were detected in 12 of 15 samples analyzed by SOLID2. Science teams correctly interpreted the nature of the deposits drilled as compared to the ground truth. This experiment shows that drilling to search for subsurface life on Mars is technically feasible and scientifically rewarding.