[Clinical research in general hospital centres in France, strengths and weaknesses]. / Recherche clinique au sein des centres hospitaliers généraux en France, forces et faiblesses.

Clinical research is an essential activity in cancer care. Both for patients, who can gain access to innovative therapies, and for practitioners, who can maintain their skills and stay at the forefront of new treatment approaches. First developed in university hospitals, clinical research is now established in general hospitals and private health institutions. The number of patient inclusions in clinical trials has doubled over the last ten years, thus reflecting the dynamism of it. Strengths and weaknesses, opportunities and threats concerning clinical research, and more specifically clinical research in general hospitals, are exposed in this article.

Analytical indicators to characterize Particulate Organic Matter (POM) and its evolution in French Vertical Flow Constructed Wetlands (VFCWs).

The design of French VFCWs leads to the formation of a sludge layer at the surface of the first filters due to the retention of suspended solids from the percolation of unsettled wastewater. This layer plays a major role in the system but still little is known on its characteristics and evolutions. In this study, suspended solids and sludge deposits sampled from two French VFCW plants were analyzed by different methods in the objective to assess the evolution of particulate organic matter (POM) along the treatment chain and within the sludge layer, and identify relevant analytical indicators of these phenomena. The treatment chain included an aerobic trickling filter followed by FeCl3 injection and two successive stages of filters. Thermal analyses showed that OM contents of suspended solids decreased along the treatment chain. POM in inflow suspended solids was predominantly composed of reactive, biodegradable compounds which were partly hydrolyzed and mineralized notably at the trickling filter stage. 3D fluorescence spectra collected from aqueous POM extracts confirmed the evolution of organic matter from low-molecular reactive compounds to more complex and stable structures such as humic-like substances. FTIR confirmed the mineralization of POM's reactive constituents along the treatment chain by the decrease in the intensities of the characteristics bands of aliphatic compounds or proteins, and its humification in the sludge deposits through the relative increase of the bands at 1634cm-1 (vC=O) and 1238cm-1 (δC=O and/or δOH). Isotopic ratios δ2H/1H and δ15N/14N were found to be good indicators of POM evolutions. The higher values of δ2H/1H and δ15N/14N ratios measured in sludge deposits as compared to inflow suspended solids were related to POM humification and to microbial processes of POM hydrolysis and mineralization, respectively.

Mineralization and Preservation of an extremotolerant Bacterium Isolated from an Early Mars Analog Environment.

The artificial mineralization of a polyresistant bacterial strain isolated from an acidic, oligotrophic lake was carried out to better understand microbial (i) early mineralization and (ii) potential for further fossilisation. Mineralization was conducted in mineral matrixes commonly found on Mars and Early-Earth, silica and gypsum, for 6 months. Samples were analyzed using microbiological (survival rates), morphological (electron microscopy), biochemical (GC-MS, Microarray immunoassay, Rock-Eval) and spectroscopic (EDX, FTIR, RAMAN spectroscopy) methods. We also investigated the impact of physiological status on mineralization and long-term fossilisation by exposing cells or not to Mars-related stresses (desiccation and radiation). Bacterial populations remained viable after 6 months although the kinetics of mineralization and cell-mineral interactions depended on the nature of minerals. Detection of biosignatures strongly depended on analytical methods, successful with FTIR and EDX but not with RAMAN and immunoassays. Neither influence of stress exposure, nor qualitative and quantitative changes of detected molecules were observed as a function of mineralization time and matrix. Rock-Eval analysis suggests that potential for preservation on geological times may be possible only with moderate diagenetic and metamorphic conditions. The implications of our results for microfossil preservation in the geological record of Earth as well as on Mars are discussed.

Sandwich organization of non-ionic surfactant liquid crystalline phases as induced by large inorganic K4Nb6O17 nanosheets.

While retaining its lamellar liquid crystal phase, K4Nb6O17 nanosheets were used as a template to sandwich and stabilize an alkylpoly(ethylene oxide) nonionic surfactant-water system showing monodomain (lamella) formation within the inorganic niobate sheets that appears to be not dependent on the surfactant liquid crystalline state in solution but more its concentration.

Effect of organic amendments on the mobility of trace elements in phytoremediated techno-soils: role of the humic substances.

The efficiency of aided phytostabilization using organic amendments such as ramial chipped wood (RCW) and composted sewage sludge (CSS) was studied on contaminated techno-soils, on nine experimental plots. The objective was to characterize the role of fulvic (FA) and humic acids (HA) on the mobilization of trace elements, specifically As, Cu, Mo, Pb and Zn. Results showed that the addition of CSS increased the total organic carbon and nitrogen content more than with RCW and as a result, the C/N ratio in the CSS soil was higher than in the RCW and non-amended (NE) soil, reflecting the high decomposition of soil organic matter in the CSS soil compared with the other soils. The RCW and CSS amendments increased the hydrogen index (HI) values and the oxygen index (OI) values compared with the NE soil, especially for the soil treated with CSS which contained more aliphatic than aromatic compounds. The addition of CSS to the techno-soil significantly increased the percentage of C org associated with the HA fractions compared with the RCW and NE soils. The soil amended with CSS showed the highest E 4/E 6 ratio and the lowest E 2/E 3 ratio of FA. Zn and As were more abundant in the FA fraction than in the HA fraction, whereas Pb, Cu and Mo were more associated to HA than to FA in the treated and untreated soils, which may explain the difference in their mobility and availability.

Rich polymorphism of a rod-like liquid crystal (8CB) confined in two types of unidirectional nanopores.

We present a neutron and X-rays scattering study of the phase transitions of 4-n-octyl-4' -cyanobiphenyl (8CB) confined in unidirectional nanopores of porous alumina and porous silicon (PSi) membranes with an average diameter of 30 nm. Spatial confinement reveals a rich polymorphism, with at least four different low temperature phases in addition to the smectic A phase. The structural study as a function of thermal treatments and conditions of spatial confinement allows us to get insights into the formation of these phases and their relative stability. It gives the first description of the complete phase behavior of 8CB confined in PSi and provides a direct comparison with results obtained in bulk conditions and in similar geometric conditions of confinement but with reduced quenched disorder effects using alumina anopore membranes.

Molecular dynamics of a short-range ordered smectic phase nanoconfined in porous silicon.

4-n-octyl-4-cyanobiphenyl has been recently shown to display an unusual sequence of phases when confined into porous silicon (PSi). The gradual increase of oriented short-range smectic (SRS) correlations in place of a phase transition has been interpreted as a consequence of the anisotropic quenched disorder induced by confinement in PSi. Combining two quasielastic neutron scattering experiments with complementary energy resolutions, the authors present the first investigation of the individual molecular dynamics of this system. A large reduction of the molecular dynamics is observed in the confined liquid phase, as a direct consequence of the boundary conditions imposed by the confinement. Temperature fixed window scans reveal a continuous glasslike reduction of the molecular dynamics of the confined liquid and SRS phases on cooling down to 250 K, where a solidlike behavior is finally reached by a two-step crystallization process.

Brachyspira (Serpulina) pilosicoli of human origin interfere with the growth of Clostridium perfringens alpha-toxin producer.

Brachyspira (Serpulina) pilosicoli of human origin interfere with the growth of Clostridium perfringens alpha-toxin producer reducing the clostridial growth area and colonies number when bacteria were cultivated together in sheep blood agar plates. The growth inhibition of C. perfringens was only observed when B. (S.) pilosicoli grew 72-96 hours sooner than C. perfringens and after the inoculum of this latter the plates were anaerobically incubated for additional 48 hours. The phenomenon was observed at concentrations of B. (S.) pilosicoli ranging from 10(7) to 10(4) CFU/ml and at concentrations of C. perfringens ranging from 10(7) to 10(1) CFU/ml when the bacteria were 0-10 mm away from each other. When B. (S.) pilosicoli and C. perfringens were inoculated at the same time and when B. (S.) pilosicoli grew 24-48 hours sooner than C. perfringens, the clostridial growth inhibition was not appreciated and only a cooperative haemolysis was observed between the bacteria.

Brachyspira (Serpulina) pilosicoli of human origin interfere with the haemolytic activity and the growth of Staphylococcus aureus beta-toxin producer.

Brachyspira (Serpulina) pilosicoli related to intestinal spirochaetosis were found to interfere in vitro with the haemolytic activity and the growth of Staphylococcus aureus beta-toxin producer. This interference was clearly appreciated because a reduction of the zone of the staphylococcal beta-toxin activity, the reduction and/or absence of cooperative haemolysis between bacteria, and the growth reduction of S. aureus were observed when B. (S.) pilosicoli were grown 72-96 hours sooner than S. aureus and after the inoculum of the latter the plates were anaerobically incubated for additional 48-72 hours. The phenomenon was more clearly observed when B. (S.) pilosicoli had a concentration of 8x10(6)-8x10(7) CFU/ml and S. aureus at a concentration ranging from 10(7) to 10(1) CFU/ml was inoculated at a distance from the streaks of B. (S.) pilosicoli ranging from 0-10 mm. When B. (S.) pilosicoli and S. aureus were inoculated at the same time and when B. (S.) pilosicoli grew 24-48 hours sooner than S. aureus only a cooperative haemolysis was observed.

Weakly beta-haemolytic human intestinal spirochaetes antagonize the haemolytic activity of Clostridium perfringens alpha-toxin producer.

The production of haemolytic antagonism between weakly beta-haemolytic human intestinal spirochaetes (wbetaHIS) related to human intestinal spirochaetosis and Clostridium perfringens alpha-toxin producer was investigated. A reduction of the clostridial haemolytic activity and a distortion of the haemolytic halo of clostridial alpha-toxin surrounded by a small zone of poorly cooperative haemolysis was clearly observed on the level of the spirochaetal growth area when 40 out of 41 wbetaHIS were cultivated in sheep blood agar plates together with Clostridium perfringens alpha-toxin producer. This phenomenon of haemolytic antagonism was observed only when wbetaHIS grew 72-96 hours sooner than C. perfringens and after the inoculum of the latter at a distance of 0 to 10 mm from wbetaHIS the plates were anaerobically incubated for an additional 48 hours and the bacteria were used at concentrations ranging from 10(7) to 10(4) CFU/ml. These results were also observed between C. perfringens and weakly beta-haemolytic intestinal spirochaetes related to animal intestinal spirochaetosis including avian strains and Brachyspira (Serpulina) pilosicoli of porcine origin.

A novel method for isolation of Brachyspira (Serpulina) hyodysenteriae from pigs with swine dysentery in Italy.

Brachyspira (Serpulina) hyodysenteriae was isolated from 10 of 11 pigs with clinically suspected swine dysentery in six herds in northern Italy. All strains were successfully isolated in the selective blood agar modified medium with spectinomycin and rifampin (BAM-SR) currently used in our laboratory to isolate B. (S.) pilosicoli of human origin, after pre-treatment of intestinal material with spectinomycin and rifampin in foetal calf serum. Isolates had phenotypic characteristics typical of B. (S.) hyodysenteriae.

Detection of same sized 4.3 Kb extrachromosomal DNA elements in weakly beta-haemolytic human intestinal spirochaetes and Serpulina pilosicoli of swine origin.

Agarose gel electrophoresis of total DNA from Italian strains of weakly beta-haemolytic human intestinal spirochaetes (w beta HIS) and porcine Serpulina pilosicoli reference strain P43/6/78 showed an extrachromosomal band having the same size and migrating at 4.3 Kb. The same results were observed after agarose gel electrophoresis of DNA obtained from the supernatant fluids of the spirochaetal cultures analysed. Swine Serpulina hyodysenteriae reference strain P18A was comparatively analysed and a 6.5 Kb extrachromosomal DNA element was found, as expected. Furthermore, S. hyodysenteriae reference strain P18A differed from all the other spirochaetes tested and had a higher number of flagella (8-12) at each cell end and was strongly beta-haemolytic. To the best of our knowledge, this is the first report on the detection of a band of extrachromosomal DNA having the same size in w beta HIS and S. pilosicoli from swine origin.

Pepstatin analogues as novel renin inhibitors.

Pepstatin analogues corresponding to the general formula A-X-Y-Sta-Ala-Sta-R were synthesized in solution phase. Various changes in the nature of the A, X, and Y groups were made to improve the inhibitory potency against human plasma renin activity. The results were interpreted by use of the active-site model based on the sequence of human angiotensinogen. The tert-butyloxycarbonyl group and the isovaleryl group were found to be the most effective acyl groups (A). The analogues having a Phe residue in place of Val1 (X) and His or amino acid with an aliphatic side chain such as norleucine or norvaline in the Y position showed the highest inhibition of human plasma renin activity with IC50 values of about 10(-8)M. Esterification or amidification of the carboxyl group of the C-terminal statine did not change the inhibitory potency. The selectivity for rat, dog, pig, and monkey plasma renin of the most interesting compounds was studied.