Intranasal administration of the synthetic polypeptide from the C-terminus of the circumsporozoite protein of Plasmodium berghei with the modified heat-labile toxin of Escherichia coli (LTK63) induces a complete protection against malaria challenge.

Needle-free procedures are very attractive ways to deliver vaccines because they diminish the risk of contamination and may reduce local reactions, pain or pain fear especially in young children with a consequence of increasing the vaccination coverage for the whole population. For this purpose, the possible development of a mucosal malaria vaccine was investigated. Intranasal immunization was performed in BALB/c mice using a well-studied Plasmodium berghei model antigen derived from the circumsporozoite protein with the modified heat-labile toxin of Escherichia coli (LTK63), which is devoid of any enzymatic activity compared to the wild type form. Here, we show that intranasal administration of the two compounds activates the T and B cell immune response locally and systemically. In addition, a total protection of mice is obtained upon a challenge with live sporozoites.

Early apoptosis of rod photoreceptors in Rpe65(-/-) mice is associated with the upregulated expression of lysosomal-mediated autophagic genes.

RPE65-related Leber's congenital amaurosis (LCA) is a rod-cone dystrophy whose clinical outcome is mainly attributed to the loss of rod photoreceptors followed by cone degeneration. Pathogenesis in Rpe65(-/-) mice is characterized by a slow and progressive degeneration of rods dependent on the constitutive activation of unliganded opsin. We previously reported that this opsin-mediated apoptosis of rods was dependent on Bcl-2-apoptotic pathway and Bax-induced pro-death activity. In this study, we report early initial apoptosis in the newly differentiated retina of Rpe65(-/-) mice. Apoptotic photoreceptors were identified as rods and resulted from pathological phototransduction signaling. This wave of early apoptosis triggered Bcl-2-related pathway and Bax apoptotic activity, while activation of the caspases was not induced. Following cellular stress, multiple signaling pathways are initiated which either commit cells to death or trigger pro-survival responses including autophagy. We report that Bcl-2-related early rod apoptosis was associated with the upregulation of autophagy markers including chaperone-mediated autophagy (CMA) substrate receptor LAMP-2 and lysosomal hydrolases Cathepsin S and Lysozyme. This suggests that lysosomal-mediated autophagy may be triggered in response to early rod apoptosis in Rpe65-LCA disease. These results highlight that Rpe65-related primary stress induces early signaling events, which trigger Bax-induced-apoptotic pathway and autophagy-mediated cellular response. These events may determine retinal cell fate, progression and severity of the disease.

A systems perspective on the integrative child psychiatry approach. Discussion of paper: "Working here and now with the individual and family system: A case of a traumatized child"

In this discussion, after a few general comments, I will propose a systems reading of the intervention so elegantly described by Kaija Puura. I will draw parallels between the therapeutic and the family groups as framing-developing systems and formalize the steps taken by the family toward healing under the influence of the therapist's team. En esta discusión, después de algunos comentarios generales, propongo una lectura sistemática de la intervención tan elegantemente descrita por Kaija Puura. Buscaré paralelos entre los grupos terapéuticos y de familia como sistemas de desarrollo enmarcado y formalizaré los pasos tomados por la familia hacia la cicatrización bajo la influencia del equipo del terapista. Après quelques commentaires généraux, je proposerai dans cette discussion une lecture systémique de l'intervention si élégamment décrite par Kaija Puura. J'établirai des parallèles entre les groupes thérapeutiques et familiaux en tant que systèmes d'encadrement-développement et je formaliserai les étapes de guérison franchies par la famille grâce à l'influence de l'équipe thérapeutique. In dieser Diskussion, werde ich nach einigen allgemeineren Aussagen, eine systemische Lesart der von Kaija Puura so eingängig beschriebenen Intervention vorschlagen. Ich werde darin Parallelen zwischen der therapeutischen und Rahmengebenden Familiengruppen ziehen, und die Schritte der Familien hin zu einer Heilung unter dem Einfluss des Therapeutenteams formalisieren.

A simple blood-culture bacterial pellet preparation for faster accurate direct bacterial identification and antibiotic susceptibility testing with the VITEK 2 system.

An ammonium chloride procedure was used to prepare a bacterial pellet from positive blood cultures, which was used for direct inoculation of VITEK 2 cards. Correct identification reached 99% for Enterobacteriaceae and 74% for staphylococci. For antibiotic susceptibility testing, very major and major errors were 0.1 and 0.3% for Enterobacteriaceae, and 0.7 and 0.1% for staphylococci, respectively. Thus, bacterial pellets prepared with ammonium chloride allow direct inoculation of VITEK cards with excellent accuracy for Enterobacteriaceae and a lower accuracy for staphylococci.

Taxonomic status and origin of the shrews (Soricidae) from the Canary islands inferred from a mtDNA comparison with the European Crocidura species.

European island shrews are either relicts of the endemic Pleistocene fauna, e.g.,. Crocidura zimmermanni, or were introduced from continental source populations. In order to clarify the taxonomic status and the origin of the two shrew species from the Canary islands, a 981bp fragment of cytochrome b gene was investigated in all European Crocidura species and compared with the Canary shrew (Crocidura canariensis) and the Osorio shrew (Crocidura osorio). The first shares its karyotype with the Sicilian shrew Crocidura sicula (2N=36), the second with the Greater white-toothed shrew Crocidura russula (2N=42), suggesting possible sister species relationships. Results confirm the monophyly of taxa sharing the same karyotype. Genetic distances between C. sicula and C. canariensis suggest a separation since 5 Myr. The first was probably isolated from the North African ancestor after the Messinian desiccation; the second arrived on the Canary islands by natural jump dispersal. Within the 2N=42 cluster, a first split separated an Eastern line (Tunisia) from a western line (Morocco/Europe) of C. russula. C. osorio clusters together with C. russula from Spain, indicating conspecificy. This suggests a recent introduction from Spain by human.

Stereologic estimates of total spinophilin-immunoreactive spine number in area 9 and the CA1 field: Relationship with the progression of Alzheimer's disease

The loss of presynaptic markers is thought to represent a strong pathologic correlate of cognitive decline in Alzheimer's disease (AD). Spinophilin is a postsynaptic marker mainly located to the heads of dendritic spines. We assessed total numbers of spinophilin-immunoreactive puncta. in the CA I and CA3 fields of hippocampus and area 9 in 18 elderly individuals with various degrees of cognitive decline. The decrease in spinophilin-immunoreactivity was significantly related to both Braak neurofibrillary tangle (NFT) staging and clinical severity but not A beta deposition staging. The total number of spinophilin-immunoreactive puncta in CA I field and area 9 were significantly related to MMSE scores and predicted 23.5 and 61.9% of its variability. The relationship between total number of spinophilin-immunoreactive puncta in CA I field and MMSE scores did not persist when adjusting for Braak NFT staging. In contrast, the total number of spinophilin-immunoreactive puncta in area 9 was still significantly related to the cognitive outcome explaining an extra 9.6% of MMSE and 25.6% of the Clinical Dementia Rating scores variability. Our data suggest that neocortical dendritic spine loss is an independent parameter to consider in AD clinicopathologic correlations.

Regions of mouse mammary tumor virus superantigen involved in interaction with the major histocompatibility complex class II I-A molecule.

To study the major histocompatibility complex class II I-E dependence of mouse mammary tumor virus (MMTV) superantigens, we constructed hybrids between the I-E-dependent MMTV(GR) and the I-E-independent mtv-7 superantigens and tested them in vivo. Our results suggest that, although the C-terminal third mediates I-A interaction, additional binding sites are located elsewhere in the superantigen.

Mass movement characterization using a reflexion and refraction seismic survey with the sloping local base level concept

This study proposes a new concept for upscaling local information on failure surfaces derived from geophysical data, in order to develop the spatial information and quickly estimate the magnitude and intensity of a landslide. A new vision of seismic interpretation on landslides is also demonstrated by taking into account basic geomorphic information with a numeric method based on the Sloping Local Base Level (SLBL). The SLBL is a generalization of the base level defined in geomorphology applied to landslides, and allows the calculation of the potential geometry of the landslide failure surface. This approach was applied to a large scale landslide formed mainly in gypsum and situated in a former glacial valley along the Rhone within the Western European Alps. Previous studies identified the existence of two sliding surfaces that may continue below the level of the valley. In this study. seismic refraction-reflexion surveys were carried out to verify the existence of these failure surfaces. The analysis of the seismic data provides a four-layer model where three velocity layers (<1000 ms(-1), 1500 ms(-1) and 3000 ms(-1)) are interpreted as the mobilized mass at different weathering levels and compaction. The highest velocity layer (>4000 ms(-1)) with a maximum depth of similar to 58 m is interpreted as the stable anhydrite bedrock. Two failure surfaces were interpreted from the seismic surveys: an upper failure and a much deeper one (respectively 25 and 50 m deep). The upper failure surface depth deduced from geophysics is slightly different from the results obtained using the SLBL, and the deeper failure surface depth calculated with the SLBL method is underestimated in comparison with the geophysical interpretations. Optimal results were therefore obtained by including the seismic data in the SLBL calculations according to the geomorphic limits of the landslide (maximal volume of mobilized mass = 7.5 x 10(6) m(3)).

Conversion of an administrative record system for compatibility with the ICIDH.

This paper presents an account of considerations relevant to conversion of data in an administrative record system into categories compatible with the ICIDH. Existing information recorded for the Swiss disablement insurance scheme fairly readily generates impairment and disability data relating to the time of first contact with the scheme, and the means for conversion are illustrated. The system does not generate data relevant to handicap.

Biomarkers of oxidative stress and its association with the urinary reducing capacity in bus maintenance workers.

BACKGROUND: Exposure to particles (PM) induces adverse health effects (cancer, cardiovascular and pulmonary diseases). A key-role in these adverse effects seems to be played by oxidative stress, which is an excess of reactive oxygen species relative to the amount of reducing species (including antioxidants), the first line of defense against reactive oxygen species. The aim of this study was to document the oxidative stress caused by exposure to respirable particles in vivo, and to test whether exposed workers presented changes in their urinary levels for reducing species.METHODS: Bus depot workers (n = 32) exposed to particles and pollutants (respirable PM4, organic and elemental carbon, particulate metal content, polycyclic aromatic hydrocarbons, NOx, O3) were surveyed over two consecutive days. We collected urine samples before and after each shift, and quantified an oxidative stress biomarker (8-hydroxy-2'-deoxyguanosine), the reducing capacity and a biomarker of PAH exposure (1-hydroxypyrene). We used a linear mixed model to test for associations between the oxidative stress status of the workers and their particle exposure as well as with their urinary level of reducing species.RESULTS: Workers were exposed to low levels of respirable PM4 (range 25-71 μg/m3). However, urinary levels of 8-hydroxy-2'-deoxyguanosine increased significantly within each shift and between both days for non-smokers. The between-day increase was significantly correlated (p < 0.001) with the concentrations of organic carbon, NOx, and the particulate copper content. The within-shift increase in 8OHdG was highly correlated to an increase of the urinary reducing capacity (Spearman ρ = 0.59, p < 0.0001).CONCLUSIONS: These findings confirm that exposure to components associated to respirable particulate matter causes a systemic oxidative stress, as measured with the urinary 8OHdG. The strong association observed between urinary 8OHdG with the reducing capacity is suggestive of protective or other mechanisms, including circadian effects. Additional investigations should be performed to understand these observations.