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Despite progress with diagnostic criteria, the type and timing of laboratory tests used to diagnose infective endocarditis (IE) have not been standardized. This is especially true with serological testing. Patients with suspected IE were evaluated by a standard diagnostic protocol. This protocol mandated an evaluation of the patients according to the modified Duke criteria and used a battery of laboratory investigations, including three sets of blood cultures and systematic serological testing for Coxiella burnetii , Bartonella spp., Aspergillus spp., Legionella pneumophila , and rheumatoid factor. In addition, cardiac valvular materials obtained at surgery were subjected to a comprehensive diagnostic evaluation, including PCR aimed at documenting the presence of fastidious organisms. The study included 1,998 suspected cases of IE seen over a 9-year period from April 1994 to December 2004 in Marseilles, France. They were evaluated prospectively. A total of 427 (21.4%) patients were diagnosed as having definite endocarditis. Possible endocarditis was diagnosed in 261 (13%) cases. The etiologic diagnosis was established in 397 (93%) cases by blood cultures, serological tests, and examination of the materials obtained from cardiac valves, respectively, in 348 (81.5%), 34 (8%), and 15 (3.5%) definite cases of IE. Concomitant infection with streptococci and C. burnetii was seen in two cases. The results of serological and rheumatoid factor evaluation reclassified 38 (8.9%) possible cases of IE as definite cases. Systematic serological testing improved the performance of the modified Duke criteria and was instrumental in establishing the etiologic diagnosis in 8% (34/427) cases of IE.

Evaluation of loads acting on the spine requires the knowledge of the muscular forces acting on it, but muscles redundancy necessitates developing a muscle forces attribution strategy. Optimisation, EMG, or hybrid models allow evaluating muscle force patterns, yielding a unique muscular arrangement or/and requiring EMG data collection. This paper presents a regulation model of the trunk muscles based on a proprioception hypothesis, which searches to avoid the spinal joint overloading. The model is also compared to other existing models for evaluation. Compared to an optimisation model, the proposed alternative muscle pattern yielded a significant spine postero-anterior shear decrease. Compared to a model based on combination of optimisation criteria, present model better fits muscle activation observed using EMG (38% improvement). Such results suggest that the proposed model, based on regulation of all spinal components, may be more relevant from a physiologic point of view.

A prospective study of infective endocarditis (IE) was conducted between 1994 and 2000 in Marseilles, France, and included 170 definite cases diagnosed with the use of modified Duke criteria. Classification of IE based on the aetiological agent was related to epidemiological characteristics, including age, gender and the nature of the injured valve. Enterococci and Streptococcus bovis were identified more frequently in older subjects (p 0.02), and S. bovis was also associated with mitral valve infection (p 0.03). Streptococcus spp. were found to be associated with native valves (p < 10−3), whereas coagulase-negative staphylococci and Coxiella burnetii were associated with intracardiac prosthetic material (p

Nosocomial infections in neonatal intensive care units are a preoccupying issue. Bacillus sp. can be pathogenic in immuno-compromised hosts, including premature infants. Central catheters and mechanical ventilation are potential sources of infection. We report for the first time a case of Bacillus licheniformis bacteremia in a premature infant. Recovery necessitated treatment with vancomycin and cefotaxime in combination with removal of the central catheter.

Q fever is a zoonosis with worldwide distribution caused by Coxiella burnetii, an obligate intracellular bacterium. Q fever is commonly divided into acute and chronic forms. Acute Q fever manifestations consist of self-limited febrile illness, pneumonia and granulomatous hepatitis as well as neurological disorders and miscellaneous manifestations [1]. The manifestations of chronic Q fever are endocarditis and, less frequently, vascular aneurysm and prosthesis infections. These usually occur in patients with previous vascular or valvular disease or in a context of immunosuppression. The chronic disease is characterised by impaired immune response, defective microbicidal activity of monocytes, and production of antibodies (Abs) directed against C. burnetii. Here, we examined the role of specific antibodies in the infection of human macrophages by C. burnetii. Immunoglobulins G (IgG) from three patients with chronic Q fever and three healthy controls were purified using protein A-sepharose columns (Pharmacia, Uppsala, Sweden). Their ability to opsonise C. burnetii was investigated by flow cytometry. About 85% of phase I organisms were opsonised by specific Abs (1 ⁄ 200 dilution) whereas irrelevant IgG were unable to opsonise bacteria. The intracellular fate of opsonised organisms within human monocyte-derived macrophages (MDM) was studied by real-time PCR as previously described [2]. Opsonised organisms intensively replicated within MDM whereas unopsonised organisms survived but poorly replicated: after 9 days, the bacterial load was 10 times higher in MDM infected with opsonised bacteria (98 400 vs. 10 200 C. burnetii DNA copies for 10 MDM). In addition, electron microscopy revealed that the replication of opsonised organisms was associated with the formation of spacious parasitophore vacuoles containing large amounts of bacteria (Fig. 1a), which were absent in MDM infected with unopsonised bacteria (Fig. 1b). At day 9 post-infection, about 30% of MDM infected with opsonised bacteria presented large vacuoles (Fig. 1c) whereas only 3% of MDM displayed large vacuoles when infected with unopsonised bacteria (Fig. 1c). Note that the large parasitophore vacuoles presented an electron-dense membrane and seemed unable to fuse with lysosomes (Fig. 1a). This prompted us to characterise the nature of the large vacuoles by scanning fluorescence confocal microscopy using cathepsin D as a marker of phagolysosomes [3]. It has been previously shown that C. burnetii prevents the phagosome conversion and survives in monocytes ⁄macrophages within late phagosomes, in contrast to avirulent and inactivated organisms, which are eliminated within phagolysosomes [3,4]. At day 9 post-infection, opsonised organisms did not co-localise with cathepsin D (Fig. 1d), demonstrating that the replicative large vacuoles are not phagolysosomes. Classically, it is believed that Abs provide protection against pathogens through different mechanisms, including opsonisation. We demonstrated here that the high levels of specific Abs found in chronic Q fever, which are likely to be related to the host inability to cure the infection, favoured C. burnetii replication within human MDM. In patients with C. burnetii endocarditis, the major manifestation of chronic Q fever, C. burnetii was found in infected cardiac valves as voluminous intracytoplasmic masses within infected mononuclear cells, and not extracellularly as for other aetiological agents of infective endocarditis [1]. We can hypothesise that C. burnetii-specific Abs produced during chronic Q fever are responsible for C. burnetii infection of cardiac valves. We also demonstrated that C. burnetii prevented the phagosome conversion because large parasitophore vacuoles containing organisms did not express cathepsin D, a specific Corresponding author and reprint requests: E. Ghigo, URMITE, Faculte de Medecine, 27 Bld. Jean Moulin, 13385 Marseille Cedex 05, France E-mail: eric.ghigo@univmed.fr

Summary: Drug development for CNS disorders faces the same formidable hurdles as other therapeutic areas: escalating development costs; novel drug targets with unproven therapeutic potential; and health care systems and regulatory agencies demanding more compelling demonstrations of the value of new drug products. Extensive clinical testing remains the core of registration of new compounds; however, traditional clinical trial methods are falling short in overcoming these development hurdles. The most common CNS disorders targeted for drug treatment are chronic, slowly vitiating processes manifested by highly subjective and context dependent signs and symptoms. With the exception of a few rare familial degenerative disorders, they have ill-defined or undefined pathophysiology. Samples selected for treatment trials using clinical criteria are inevitably heterogeneous, and dependence on traditional endpoints results in early proof-of-concept trials being long and large, with very poor signal to noise. It is no wonder that pharmaceutical and biotechnology companies are looking to biomarkers as an integral part of decision-making process supported by new technologies such as genetics, genomics, proteomics, and imaging as a mean of rationalizing CNS drug development. The present review represent an effort to illustrate the integration of such technologies in drug development supporting the path of individualized medicine.

The objectives of the study are to describe and use a muscular model to compare spinal loads and muscles recruitments between an unbalanced subject (patient) and a normal volunteer. Data collection was performed and imputed into the muscular model: from sagittal X-rays, together with plantar foot pressure measurements, external loads for the L3/L4 level were calculated. Using MRI of the thoraco-lumbar region and muscular testing, a personalized muscular model was constructed. The main results are as follow: external loads for the unbalanced subject were higher because of the postural default, especially for flexion moment. Running the model, simulations showed a higher erector spinae group activation for the patient. This induced a significant difference in joint compression. Setting the maximum admissible stress of the extensor muscles of the patient to an equivalent level as the one found for the volunteer to maintain the posture, a second simulation was performed. Joint compression was reduced, but postero-anterior shear and flexion moment increased drastically. The model suggests that either the muscular system needed a stronger activation, yielding a higher joint compression and probably a muscle fatigue in such an activation level, or the spinal loads increased to a higher and probably dangerous level.

Coxiella burnetii, an obligate intracellular bacterium, is the agent of Q fever. The chronic disease is characterized by impaired cell-mediated immune response and microbicidal activity of monocytes. We hypothesized that interleukin(IL)-4, a Th2 cytokine, interferes with the fate of C. burnetii inside monocytes. C. burnetii survived without multiplication in resting monocytes, but replicated in IL-4-treated monocytes. The effect of IL-4 is specific for monocytes since IL-4 did not stimulate C. burnetii replication in monocyte-derived macrophages. The effects of IL-4 on bacterial replication and on tumor necrosis factor (TNF) production in monocytes were apparently not related. Although IL-4 inhibited C. burnetii-stimulated release of TNF, the addition of recombinant TNF to IL-4-treated monocytes did not prevent the IL-4 effect. These results suggest that IL-4 enables monocytes to support C. burnetii replication and a Th2 polarization of immune response that may interfere with immune control of Q fever.

Q fever manifests as primary infection or acute Q fever and may become chronic in patients with underlying valvulopathy. Because Coxiella burnetii infection depends on host response, we measured tumor necrosis factor (TNF), interleukin (IL)-6, IL-12, and IL-10 in patients with different clinical presentations of acute Q fever. Compared with control subjects, patients with uncomplicated acute Q fever exhibited increased release of the 4 cytokines. Their amounts were higher in patients with hepatitis than in patients with fever or pneumonia. In patients with valvulopathy, who exhibited the highest risk of chronic evolution, the amounts of TNF and IL-10 were higher than in patients without valvulopathy. TNF production was specifically enhanced in patients who developed Q fever endocarditis. These results show that acute Q fever is associated with cytokine overproduction. Persistent TNF amounts were associated with the occurrence of endocarditis in patients with valvulopathy, and that may be a marker of chronic evolution of Q fever.

The capacitance coefficient beta of an ideal gas mixture depends only on its temperature T, and its value is derived from the ideal gas law (i.e., beta = 1/RT, R being the ideal gas constant). But real gases behave as ideal gases only at low pressures, and this would not be the case in deep diving. High pressures of helium-oxygen are used in human and animal experimental dives (up to 7 or 12 MPa or more, respectively). At such pressures deviations from the ideal gas law cannot be neglected in hyperbaric atmospheres with respect to current accuracy of measuring instruments. As shown both theoretically and experimentally by this study, the non-ideal nature of helium-oxygen has a significant effect on the capacitance coefficient of hyperbaric atmospheres. The theoretical study is based on interaction energy in either homogeneous (He-He and O2-O2) or heterogeneous (He-O2) molecular pairs, and on the virial equation of state for gas mixtures. The experimental study is based on weight determination of samples of known volume of binary helium-oxygen mixtures, which are prepared in well-controlled pressure and temperature conditions. Our experimental results are in good agreement with theoretical predictions. 1) The helium compressibility factor ZHe increases linearly with pressure [ZHe = 1 + 0.0045 P (in MPa) at 30 degrees C]; and 2) in same temperature and pressure conditions (T = 303 K and P = 0.1 to 15 MPa), the same value for Z is valid for a helium-oxygen binary mixture and for pure helium. As derived from the equation of state of real gases, the capacitance coefficient is inversely related to Z (beta = 1/ZRT); therefore, for helium-oxygen mixtures, this coefficient would decrease with increasing pressure. A table is given for theoretical values of helium-oxygen capacitance coefficient, at pressures ranging from 0.1 to 15.0 MPa and at temperatures ranging from 25 degrees C to 37 degrees C.

Surgical masks have become critical for protecting human health against the COVID-19 pandemic, even though their environmental burden is a matter of ongoing debate. This study aimed at shedding light on the environmental impacts of single-use (i.e., MD-Type I) versus reusable (i.e., MD-Type IIR) face masks via a comparative life cycle assessment with a cradle-to-grave system boundary. We adopted a two-level analysis using the ReCiPe (H) method, considering both midpoint and endpoint categories. The results showed that reusable face masks created fewer impacts for most midpoint categories. At the endpoint level, reusable face masks were superior to single-use masks, producing scores of 16.16 and 84.20 MPt, respectively. The main environmental impacts of single-use masks were linked to raw material consumption, energy requirements and waste disposal, while the use phase and raw material consumption made the most significant contribution for reusable type. However, our results showed that lower environmental impacts of reusable face masks strongly depend on the use phase since reusable face masks lost their superior performance when the hand wash scenario was tested. Improvement of mask eco-design emerged as another key factor such as using more sustainable raw materials and designing better waste disposal scenarios could significantly lower the environmental impacts.