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

A Novel Antibacterial Compound Decreases MRSA Biofilm Formation Without the Use of Antibiotics in A Murine Model

Despite significant advancements in material science, surgical site infection (SSI) rates remain high and prevention is key. This study aimed to demonstrate the in-vivo safety and antibacterial efficacy of titanium implants treated with a novel broad-spectrum biocidal compound (DBG21) against methicillin-resistant Staphylococcus aureus (MRSA). Titanium (Ti) discs were covalently bound with DBG21. Untreated Ti discs were used as controls. All discs were implanted either untreated for 44 control mice or DBG21-treated for 44 treated mice. After implantation, 1x107 colony forming units (CFU) of MRSA were injected into the operating site. Mice were sacrificed at day 7 and 14 to determine the number of adherent bacteria (biofilm) on implants and in the peri-implant surrounding tissues. Systemic and local toxicity were assessed. At both 7 and 14 days, DBG21-treated implants yielded a significant decrease in MRSA biofilm (3.6 median log10 CFU (99.97%) reduction (p<0.001) and 1.9 median log10 CFU (98.7%) reduction (p=0.037), respectively) and peri-implant surrounding tissues (2.7 median log10 CFU/g (99.8%) reduction (p<0.001) and 5.6 median log10 CFU/g (99.9997%) reduction (p<0.001), respectively). There were no significant differences between control and treated mice in terms of systemic and local toxicity. DBG-21 demonstrated a significant decrease in the number of biofilm bacteria without associated toxicity in a small animal implant model of SSI. Preventing biofilm formation has been recognized as a key element of preventing implant-related infections

Ebola virus disease in West Africa — the first 9 Months of the epidemic and forward projections

BACKGROUND On March 23, 2014, the World Health Organization (WHO) was notified of an outbreak of Ebola virus disease (EVD) in Guinea. On August 8, the WHO declared the epidemic to be a "public health emergency of international concern." METHODS By September 14, 2014, a total of 4507 probable and confirmed cases, including 2296 deaths from EVD (Zaire species) had been reported from five countries in West Africa - Guinea, Liberia, Nigeria, Senegal, and Sierra Leone. We analyzed a detailed subset of data on 3343 confirmed and 667 probable Ebola cases collected in Guinea, Liberia, Nigeria, and Sierra Leone as of September 14. RESULTS The majority of patients are 15 to 44 years of age (49.9% male), and we estimate that the case fatality rate is 70.8% (95% confidence interval [CI], 69 to 73) among persons with known clinical outcome of infection. The course of infection, including signs and symptoms, incubation period (11.4 days), and serial interval (15.3 days), is similar to that reported in previous outbreaks of EVD. On the basis of the initial periods of exponential growth, the estimated basic reproduction numbers (R-0) are 1.71 (95% CI, 1.44 to 2.01) for Guinea, 1.83 (95% CI, 1.72 to 1.94) for Liberia, and 2.02 (95% CI, 1.79 to 2.26) for Sierra Leone. The estimated current reproduction numbers (R) are 1.81 (95% CI, 1.60 to 2.03) for Guinea, 1.51 (95% CI, 1.41 to 1.60) for Liberia, and 1.38 (95% CI, 1.27 to 1.51) for Sierra Leone; the corresponding doubling times are 15.7 days (95% CI, 12.9 to 20.3) for Guinea, 23.6 days (95% CI, 20.2 to 28.2) for Liberia, and 30.2 days (95% CI, 23.6 to 42.3) for Sierra Leone. Assuming no change in the control measures for this epidemic, by November 2, 2014, the cumulative reported numbers of confirmed and probable cases are predicted to be 5740 in Guinea, 9890 in Liberia, and 5000 in Sierra Leone, exceeding 20,000 in total. CONCLUSIONS These data indicate that without drastic improvements in control measures, the numbers of cases of and deaths from EVD are expected to continue increasing from hundreds to thousands per week in the coming months

From Reinforcement to High-Performance Damping:An Oligopeptide Toolbox for Tailored Elastomers

Biomaterials such as structure proteins are constructed from limited sets of chemical building blocks and supramolecular motifs. Nevertheless, they exhibit extraordinary properties specifically tailored for a broad range of applications because hierarchical structure formation makes it possible to utilize similar supramolecular motifs without mutual interference. In the present thesis, we investigated how (β-sheet-forming oligopeptides can be used in a similar way to tailor the thermomechanical properties of elastomers in a versatile fashion. Differently from previous examples of supramolecular materials reported in literature, the formation of either small aggregates or (β-sheet fibrils was strictly controlled by the molecular structure. Moreover, due to 'self-sorting', these nanostructures coexisted in mixtures of polymers with different oligopeptide end groups of different length. Blends of polymers with matching oligopeptide termini gave rise to shape persistent thermoplastic elastomers that were inherently reinforced by the presence of cross-linked (β-sheet fibrils. In addition, these advanced materials had low melt viscosity at slightly elevated temperature, resulting in thermoresponsive materials or elastomers with good processing properties. On the other hand, blends of polymers with non-matching oligopeptide termini formed novel 'interpenetrating supramolecular networks' that may have a potential in self-healing applications and proved to be high-performance vibration damping materials. Finally, one of these novel 'interpenetrating supramolecular network' materials was used as matrix for the formation of nanocomposites. The addition of carbon black nanoparticle fillers to the matrix material gave rise to highly efficient damping materials for applications using constrained layer structures

Survey of volatile oxylipins and their biosynthetic precursors in bryophytes

Oxylipins are metabolites which are derived from the oxidative fragmentation of polyunsaturated fatty acids. These metabolites play central roles in plant hormonal regulation and defense. Here we survey the production of volatile oxylipins in bryophytes and report the production of a high structural variety of C5, C6, C8 and C9 volatiles of mosses. In liverworts and hornworts oxylipin production was not as pronounced as in the 23 screened mosses. A biosynthetic investigation revealed that both, C18 and C20 fatty acids serve as precursors for the volatile oxylipins that are mainly produced after mechanical wounding of the green tissue of mosses. (C) 2009 Elsevier Ltd. All rights reserved

Materials Taking a Lesson from Nature

Structural biomaterials with their often extraordinary properties and versatile functions are typically constructed from very limited sets of building blocks and types of supramolecular interactions. In this review we discuss how, inspired by nature's design principles for protein-based materials, oligopeptide-modified polymers can be used as a versatile toolbox to program nanostructure and hierarchical structure formation in synthetic materials

Formation of Boronate Ester Polymers with Efficient Intrastrand Charge Transfer Transitions by Three-Component Reactions

The three-component reaction of aryl boronic acids with 1,2,4,5-tetrahydroxybenzene and 1,2-bis(4-pyridyl)ethylene or 4,4-bipyridine leads to the formation of dark-purple boronate ester polymers. Crystallographic analyses show that the polymer strands have a zig-zag geometry, and the bis(dioxaborole) units are connected by dipyridyl linkers through dative B-N interactions. Upon dissolution of the polymers in hot chloroform, most of the B-N connections are broken, which indicates that polymer formation is a reversible process. A computational study provides evidence that the strong color of the polymers is due to efficient intrastrand charge-transfer excitations from the tetraoxobenzene to the dipyridyl linker

La lésion musculaire des ischio-jambiers chez le footballeur - Partim I : épidémiologie, facteurs de risque, mécanismes lésionnels et traitement

peer reviewe

Hamstring muscle injury in football players. Part 2 : preventive strategies.

editorial reviewedPrevention of hamstring injuries represents an important issue for football players and clubs. Preventive strategies can be effective if they include multiple dimensions and are well-structured. Five points appear essential in order to obtain a high-quality preventive strategy: progressive muscle strengthening, optimal workload management, lumbopelvic stability exercises, development of physical condition and optimization of sprint technique. While recognizing the limitations of preventive screening and the difficulty of predicting future injury, screening tests appear relevant for the identification of an individual risk profile for each footballer and in defining each player's work priorities. Finally, secondary prevention starts with the implementation of rigorous and high-level rehabilitation, as well as a special attention to players with a history of hamstring injury.La prévention des lésions musculaires des ischio-jambiers représente une thématique de première importance pour les joueurs et clubs de football. Les stratégies préventives peuvent se révéler efficaces, à condition d’inclure de multiples dimensions à celles-ci et de structurer ces démarches. Cinq points apparaissent incontournables dans l’optique d’obtenir une stratégie préventive de qualité : le renforcement musculaire progressif et raisonné, la gestion équilibrée de la charge de travail, le travail de la stabilité lombo-pelvienne, le développement de la condition physique et l’optimalisation de la gestuelle de course. Tout en reconnaissant les limites du screening préventif et la difficulté de prédire une future blessure, un état des lieux précis peut s’avérer pertinent pour identifier le profil de risque individuel de chaque footballeur et pour définir les priorités de travail de chacun. Enfin, la prévention secondaire démarre par la mise en place d’une rééducation rigoureuse et structurée, ainsi que par une attention particulière aux joueurs avec antécédents de lésions aux ischio-jambiers