Mild-stretch mechanical ventilation upregulates toll-like receptor 2 and sensitizes the lung to bacterial lipopeptide

INTRODUCTION: Mechanical ventilation (MV) could prime the lung toward an inflammatory response if exposed to another insult such as bacterial invasion. The underlying mechanisms are not so far clear. Toll-like receptors (TLRs) allow the host to recognize selectively bacterial pathogens and in turn to trigger an immune response. We therefore hypothesized that MV modulates TLR2 expression and in turn modifies responsiveness to agonists such as bacterial lipopeptide (BLP). METHOD: Both in vitro and in vivo experiments were conducted. First, TLR2 expression and protein were measured in the A549 pulmonary epithelial cell line submitted to 8-hour cyclic stretch (20% elongation; 20/minute rate). After a 24-hour period of cyclic stretch, the inflammatory response of the A549 cells to the synthetic BLP, Pam(3)CSK(4), was tested after 8 hours of exposure. In a second set of experiments, healthy anesthetized and paralyzed rabbits were submitted to 8-hour MV (tidal volume = 12 ml/kg, zero end-expiratory pressure; FIO(2 )= 50%; respiratory rate = 20/minute) before being sacrificed for TLR2 lung expression assessment. The lung inflammatory response to BLP was then tested in animals submitted to 24-hour MV before being sacrificed 8 hours after the tracheal instillation of Pam(3)CSK(4). RESULTS: Cyclic stretch of human pulmonary epithelial cell lines increased both TLR2 mRNA and protein expression. Cells submitted to cyclic stretch also increased IL-6 and IL-8 secretion in response to Pam(3)CSK(4), a classical TLR2 ligand. A mild-stretch MV protocol induced a 60-fold increase of TLR2 mRNA expression in lung tissue when compared with spontaneously breathing controls. Moreover, the combination of MV and airway exposure to Pam(3)CSK(4 )acted synergistically in causing lung inflammation and injury. CONCLUSIONS: Mild-stretch MV increases lung expression of TLR2 and sensitizes the lung to bacterial TLR2 ligands. This may account for the propensity of mechanically ventilated patients to develop acute lung injury in the context of airway bacterial colonization/infection

Comparative assimilation of Topex/poseidon and ERS altimetric data and of TAO temperature data in the tropical Pacific Ocean during 1994-1998, and the mean sea-surface height issue

International audienceFive years of Topex/Poseidon (T/P) and ERS sea level anomaly (SLA) data (1994–1998) are assimilated every 10 days into a primitive equation model of the tropical Pacific ocean. The data assimilation technique used here is a reduced-order Kalman filter derived from the Singular Evolutive Extended Kalman (SEEK) filter [J. Mar. Syst. 16(3–4) (1998) 323] with an error covariance matrix parameterised by a subset of multivariate 3D global empirical orthogonal functions (EOFs). The assimilation run is compared to the free run and to independent data from the TAO network. The impact of sea-surface height (SSH) assimilation on surface and subsurface temperature and currents is estimated in the equatorial band. In a second stage, temperature data from the TAO array are assimilated in the same conditions as in the first stage. The comparison between the results of the two assimilation experiments is made mainly with a view to gaining insights into the mean sea-surface height (MSSH) for the assimilation of altimeter data, and more generally, into the question of biases. XBT observations and TAO array data are then used to build a physically more consistent mean sea-surface height for assimilation of SLA data. Results from the assimilation of altimeter data referenced to this new MSSH show significant improvements

Urogenital dysfunction in male patients with Charcot-Marie-Tooth: a systematic review

Aims Purposes of this study were to describe lower urinary tract symptoms (LUTS) and related urodynamic patterns in patients with hereditary spastic paraplegia (HSP), and to characterize LUTS management and associated uronephrological complications. Methods We retrospectively reviewed medical files of HSP patients, consecutively followed in our Physical and Rehabilitation Medicine Department between 1999 and 2016. Clinical, urodynamic, and radiological data were collected and analyzed. Different treatments which have been prescribed and uronephrological complications were also recorded. Patients with other neurological or urological diseases were excluded. Results Thirty-three patients with HSP were included. Mean duration of follow-up was 8.1 ± 5 years, mean age 62 ± 14 years, and 70% were men. The most frequent LUTS was urgency and voiding dysfunction (both 69.7%). Incontinence and retention with a significant postvoid residue above 100 mL accounted for 66.7% and 57.6% of initial symptoms respectively. Neurogenic detrusor overactivity was diagnosed in 80.7% of patients. Two-thirds of our cohort were treated with anticholinergics and 9.1% required intradetrusor botulinum-toxin injections. Only 27.3% of patients performed clean intermittent self-catheterization. Febrile urinary tract infections (21.2%), urolithiasis (15,1%), hydronephrosis (6%), and chronic renal failure (9.1%) were found. Conclusion Given their high prevalence and the risk of uronephrological complications, LUTS should be systematically assessed in HSP patients. The systematic screening of urological dysfunction in this population would improve its management, decrease the incidence of uronephrological complications, and increase the quality of life

Mössbauer spectroscopy study of MgAl2O4-matrix nanocomposite powders containing carbon nanotubes and iron-based nanoparticles

Materials involved in the catalytic formation of carbon nanotubes are for the first time systematically studied by Mössbauer spectroscopy between 11 K and room temperature. Mg1−xFexAl2O4 (x=0.1, 0.2, 0.3, 0.4) solid solutions are transformed into carbon nanotubes–Fe/Fe3C–MgAl2O4 composite powders by reduction in a H2–CH4 gas mixture. The oxides are defective spinels of general formulae (Mg1−x2+Fex−3α2+Fe2α3+□αAl23+)O42−. Ferromagnetic α-Fe, ferromagnetic Fe3C and a γ-Fe form, the latter possibly corresponding to a γ-Fe–C alloy, are detected in the composite powders. An attempt is made to correlate these results with the microstructure of the powder. It seems that the nanoparticles, which catalyze the formation of the carbon nanotubes, are detected as Fe3C in the post-reaction Mössbauer spectroscopy analysis

An interferometric study of the Fomalhaut inner debris disk. I. Near-infrared detection of hot dust with VLTI/VINCI

The innermost parts of dusty debris disks around main sequence stars are currently poorly known due to the high contrast and small angular separation with their parent stars. Using near-infrared interferometry, we aim to detect the signature of hot dust around the nearby A4 V star Fomalhaut, which has already been suggested to harbor a warm dust population in addition to a cold dust ring located at about 140 AU. Archival data obtained with the VINCI instrument at the VLTI are used to study the fringe visibility of the Fomalhaut system at projected baseline lengths ranging from 4 m to 140 m in the K band. A significant visibility deficit is observed at short baselines with respect to the expected visibility of the sole stellar photosphere. This is interpreted as the signature of resolved circumstellar emission, producing a relative flux of 0.88% +/- 0.12% with respect to the stellar photosphere. While our interferometric data cannot directly constrain the morphology of the excess emission source, complementary data from the literature allow us to discard an off-axis point-like object as the source of circumstellar emission. We argue that the thermal emission from hot dusty grains located within 6 AU from Fomalhaut is the most plausible explanation for the detected excess. Our study also provides a revised limb-darkened diameter for Fomalhaut (2.223 +/- 0.022 mas), taking into account the effect of the resolved circumstellar emission.Comment: 13 pages, accepted for publication in Ap

Serum procalcitonin for the early recognition of nosocomial infection in the critically ill patients: a preliminary report

<p>Abstract</p> <p>Background</p> <p>The usefulness of procalcitonin (PCT) measurement in critically ill medical patients with suspected nosocomial infection is unclear. The aim of the study was to assess PCT value for the early diagnosis of bacterial nosocomial infection in selected critically ill patients.</p> <p>Methods</p> <p>An observational cohort study in a 15-bed intensive care unit was performed. Seventy patients with either proven (n = 47) or clinically suspected but not confirmed (n = 23) nosocomial infection were included. Procalcitonin measurements were obtained the day when the infection was suspected (D0) and at least one time within the 3 previous days (D-3 to D0). Patients with proven infection were compared to those without. The diagnostic value of PCT on D0 was determined through the construction of the corresponding receiver operating characteristic (ROC) curve. In addition, the predictive value of PCT variations preceding the clinical suspicion of infection was assessed.</p> <p>Results</p> <p>PCT on D0 was the best predictor of proven infection in this population of ICU patients with a clinical suspicion of infection (AUROCC = 0.80; 95% CI, 0.68–0.91). Thus, a cut-off value of 0.44 ng/mL provides sensitivity and specificity of 65.2% and 83.0%, respectively. Procalcitonin variation between D-1 and D0 was calculated in 45 patients and was also found to be predictive of nosocomial infection (AUROCC = 0.89; 95% CI, 0.79–0.98) with a 100% positive predictive value if the +0.26 ng/mL threshold value was applied. Comparable results were obtained when PCT variation between D-2 and D0, or D-3 and D0 were considered. In contrast, CRP elevation, leukocyte count and fever had a poor predictive value in our population.</p> <p>Conclusion</p> <p>PCT monitoring could be helpful in the early diagnosis of nosocomial infection in the ICU. Both absolute values and variations should be considered and evaluated in further studies.</p

Breast tumor PDXs are genetically plastic and correspond to a subset of aggressive cancers prone to relapse.

The authors wish to thank the personnel of the IRCM animal facility team, the histology (RHEM) platform, the Affymetrix platform of Montpellier and Dr Caroline Mollevi from the Biostatistics platform at ICM for their help in this project. The constant support of ICM and SIRIC Montpellier-Cancer is gratefully acknowledged.International audiencePatient derived xenografts (PDXs) are increasingly appreciated models in cancer research, particularly for preclinical testing, as they reflect the patient's tumor biology more accurately than cancer cell lines. We have established a collection of 20 breast PDXs and characterized their biological and clinical features, as well as their genetic stability. While most PDXs originated from triple negative breast cancers (70%), our collection comprised five ER + cases (25%). Remarkably, the tumors that produced PDXs derived from a subset of aggressive breast cancers with a high proportion of grade 3 tumors and reduced recurrence-free survival. Consistent with this, we found significant differences between the transcriptomic signatures of tumors that produced a PDX (Take) and those that did not (No Take). The PDXs faithfully recapitulate the histological features of their primary tumors, and retain an excellent conservation of molecular classification assignment and Copy Number Change (CNC). Furthermore, the CNC profiles of different PDXs established from the same tumor overlap significantly. However, a small fraction of CNCs in the primary tumor that correspond to oligoclonal events were gradually lost during sequential passaging, suggesting that the PDXs' genetic structure eventually stabilizes around a dominant clone present in the tumor of origin. Finally, de novo occurring genetic events covering up to 9% of the genome were found in only a minority of the PDXs, showing that PDXs have limited genetic instability. These data show that breast cancer PDXs represent a subset of aggressive tumors prone to relapse, and that despite of an excellent conservation of original features, they remain genetically dynamic elements