Blood Signature of Pre-Heart Failure: A Microarrays Study

International audienceBACKGROUND: The preclinical stage of systolic heart failure (HF), known as asymptomatic left ventricular dysfunction (ALVD), is diagnosed only by echocardiography, frequent in the general population and leads to a high risk of developing severe HF. Large scale screening for ALVD is a difficult task and represents a major unmet clinical challenge that requires the determination of ALVD biomarkers. METHODOLOGY/PRINCIPAL FINDINGS: 294 individuals were screened by echocardiography. We identified 9 ALVD cases out of 128 subjects with cardiovascular risk factors. White blood cell gene expression profiling was performed using pangenomic microarrays. Data were analyzed using principal component analysis (PCA) and Significant Analysis of Microarrays (SAM). To build an ALVD classifier model, we used the nearest centroid classification method (NCCM) with the ClaNC software package. Classification performance was determined using the leave-one-out cross-validation method. Blood transcriptome analysis provided a specific molecular signature for ALVD which defined a model based on 7 genes capable of discriminating ALVD cases. Analysis of an ALVD patients validation group demonstrated that these genes are accurate diagnostic predictors for ALVD with 87% accuracy and 100% precision. Furthermore, Receiver Operating Characteristic curves of expression levels confirmed that 6 out of 7 genes discriminate for left ventricular dysfunction classification. CONCLUSIONS/SIGNIFICANCE: These targets could serve to enhance the ability to efficiently detect ALVD by general care practitioners to facilitate preemptive initiation of medical treatment preventing the development of HF

Les reprises de prothèses du genou (étude rétrospective et comparative à partir de 212 cas)

LYON1-BU Santé (693882101) / SudocSudocFranceF

Comparison of quality of life following total ankle arthroplasty and ankle arthrodesis: Retrospective study of 54 cases

INTRODUCTION: The benefit of ankle arthroplasty compared to arthrodesis continues to be debated, but the quality of life after these two interventions has rarely been assessed. We conducted a case-control study to compare quality of life and functional and athletic ability. HYPOTHESIS: Functional results, athletic ability, and quality of life after total ankle arthroplasty (TAA) are better than after ankle arthrodesis. MATERIAL AND METHODS: Two continuous series of 59 TAAs and 46 arthrodeses (operated on between 1997 and 2009) were evaluated retrospectively using a questionnaire including the functional items of the AOFAS score, the Foot Function Index (FFI) score, the Foot Ankle Ability Measure (FAAM), and the SF-36. RESULTS: Eighty-three responses (79% of the overall series) were matched in two groups: 32 TAAs [age at the intervention, 51.4years (range, 21-63years); follow-up, 52.2months (range, 30-146months); age at revision, 55.8years (range, 26-67years); BMI, 27.7 (range, 21.7-36.7)] and 22 arthrodeses [age at intervention, 50.1years (range, 24-72years); follow-up 57.9months (range, 12-147months); age at revision 54.9 years (range, 31-75years); BMI, 26.8 (range, 17.6-37)] (NS on all items between the two groups). The pain results were better after TAA, but with no statistically significant difference: AOFAS pain, (/40) 28.1±8.2 vs. 24.5±9.6; FFI pain, 16.6±18.8 vs. 24.3±21.5. The overall FFI score (/100) was better (P=0.048) after TAA (16.2±16.5 vs. 24.8±18.2). The overall mean athletic level compared to the state prior to the injury was relatively low in both groups, but significantly (p=0.007) higher in the TAA group: FAAM sports score (/100), 49.5±24.4 vs. 29.8±26.2. The quality-of-life scores, SF-36 physical health, mental health, and general health were not significantly different after TAA and arthrodesis: mental health score, 63.1±14.7 vs. 57.8±21.5; physical health score, 61.3±17.8 vs. 53.7±23.9, overall score, 63.2±16.4 vs. 55.9±23.5. DISCUSSION: Very few publications describe activities and quality of life after TAA and arthrodesis. Despite weaknesses, this comparative study demonstrates a tendency toward better functional results after TAA than after ankle arthrodesis, without the difference between the two groups being very significant. On the other hand, there was no difference in terms of quality of life. After the doubts raised by publications on severe periprosthetic osteolysis at the intermediate term with certain TAA models, these results encourage pursuit of implantation and development of TAA. LEVEL OF PROOF: Comparative retrospective. Level III study

Altered social behavior and sensory responses to pheromones in mice deficient for the G-protein subunit Galphai2

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Metabonomics analysis of plasma reveals the lactate to cholesterol ratio as an independent prognostic factor of short-term mortality in acute heart failure.

OBJECTIVE: Mortality in heart failure (AHF) remains high, especially during the first days of hospitalization. New prognostic biomarkers may help to optimize treatment. The aim of the study was to determine metabolites that have a high prognostic value. METHODS: We conducted a prospective study on a training cohort of AHF patients (n = 126) admitted in the cardiac intensive care unit and assessed survival at 30 days. Venous plasmas collected at admission were used for (1)H NMR--based metabonomics analysis. Differences between plasma metabolite profiles allow determination of discriminating metabolites. A cohort of AHF patients was subsequently constituted (n = 74) to validate the findings. RESULTS: Lactate and cholesterol were the major discriminating metabolites predicting 30-day mortality. Mortality was increased in patients with high lactate and low total cholesterol concentrations at admission. Accuracies of lactate, cholesterol concentration and lactate to cholesterol (Lact/Chol) ratio to predict 30-day mortality were evaluated using ROC analysis. The Lact/Chol ratio provided the best accuracy with an AUC of 0.82 (P < 0.0001). The acute physiology and chronic health evaluation (APACHE) II scoring system provided an AUC of 0.76 for predicting 30-day mortality. APACHE II score, Cardiogenic shock (CS) state and Lact/Chol ratio ≥ 0.4 (cutoff value with 82% sensitivity and 64% specificity) were significant independent predictors of 30-day mortality with hazard ratios (HR) of 1.11, 4.77 and 3.59, respectively. In CS patients, the HR of 30-day mortality risk for plasma Lact/Chol ratio ≥ 0.4 was 3.26 compared to a Lact/Chol ratio of < 0.4 (P = 0.018). The predictive power of the Lact/Chol ratio for 30-day mortality outcome was confirmed with the independent validation cohort. CONCLUSION: This study identifies the plasma Lact/Chol ratio as a useful objective and simple parameter to evaluate short term prognostic and could be integrated into quantitative guidance for decision making in heart failure care

Novel polyesteramide-based di- and triblock copolymers From thermo-mechanical properties to hydrolytic degradation

International audienceTwo types of biodegradable poly(epsilon-caprolactone (CLo))-co-poly(epsilon caprolactam (CLa)) copolymers were prepared by catalyzed hydrolytic ring-opening polymerization For the first type of materials the respective cyclic comonomers were added simultaneously in the reaction medium leading to the formation of copolymers having a random distribution of co-units within the polyesteramide sequence as evidenced by H-1 and C-13 NMR For the second type of copolymers the cyclic comonomers were added sequentially in the reaction medium yielding diblock polyesteramides again evidenced by NMR The thermal and thermo-mechanical properties of the copolymers were investigated by DSC and DMA and correlated with the copolymer topology and composition The copolymers were char acterized by a storage modulus and alpha transition temperature intermediate to the modulus and T-g of the corresponding homopolymers The chemical composition and molecular weight of the copolymers proved to have only a limited effect on the thermo-mechanical properties of the materials The hydrolytic degradation of random copolymers was studied in a phosphate buffer at 60 degrees C and discussed in terms of chemical composition and molecular weight of the copolymer

Activation of the hydrolytic polymerization of epsilon-caprolactam by ester functions: Straightforward route to aliphatic polyesteramides

International audienceThe hydrolytic polymerization of ε-caprolactam (CLa) was carried out in bulk (in absence of solvent) at 250 °C in the presence of carboxylic esters and aqueous H3PO2. It turned out that by conducting the ring opening polymerization (ROP) of CLa in the presence of PEO-C(O)-O-C5H11, a selected model ester (PEO = poly(ethylene oxide)), a remarkable activating effect of the ester function on the hydrolytic polymerization of the lactam was observed yielding PEO-b-PCLa diblock copolymers. The comparison of the CLa monomer conversions obtained with or without the model ester activated by H3PO2, as determined by 1H NMR spectroscopy, has enabled to propose a multi-step mechanism in which three major reactions occurred: (i) ester and lactam hydrolysis, (ii) aminolysis of the carboxylic ester by the resulting primary amine of the hydrolyzed/opened lactam ring and (iii) condensation reactions between carboxylic acids and both amine/hydroxyl functions. The overall result of this multi-step mechanism can be assimilated as an “insertion” of the opened lactam into the ester function. By conducting the hydrolytic polymerization of CLa in the presence of an aliphatic polyester chain, such as poly(ε-caprolactone) (PCLo), polyesteramides were recovered with high yields and random distributions of the CLa and CLo repetitive units as determined by 13C NMR

Influence of the Spatial Conformation of Charged Ligands on the Optical Properties of Gold Nanoclusters

International audiencePhotoluminescent gold nanoclusters (Au NCs) were synthesized in one step in aqueous conditions using a mixture of glutathione and (mono or multivalent) glutathione-modified arginine peptides. By controlling the ratio of coligands, we investigated how the multivalency and the amount of arginines influenced the growth of Au NCs, their surface chemistry, their colloidal stability, and their optical properties. We demonstrated using two-dimensional nuclear magnetic resonance spectroscopy that the organization of the ligand on the Au surface was composed by an inner rigid layer and an outer flexible part via inter- and/or intraligand spatial proximity. This directly impacted the structure of the Au NCs, as confirmed by gel electrophoresis, high-resolution transmission electron microscopy, diffusion-ordered spectroscopy, and mass spectrometry. Increasing arginine content also induced an increase of positive surface charge and an enhancement of the near infrared emission intensity at ∼670 nm with quantum yield up to 10% validating the significant influence of the ligands to the optical properties of Au NCs

Les éclaireurs : recette de vulgarisation scientifique sans gros mots

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