[Vaccination Uptake in Newly-Arrived Migrants in France]. / Le rattrapage vaccinal des personnes migrantes arrivant sur le territoire français.

The issue of catching up vaccines among children and adult migrants is of concern in France. Migrants do not represent a homogeneous population, but a majority of them are insufficiently vaccinated on the basis of the French vaccination schedule that includes more vaccine than those of their countries of origin. Among migrants, people in precarious situations or belonging to certain social groups have poorer immunization coverage, are exposed to a delay in the implementation of their catch-up and are at higher risk of vaccine-preventable infectious diseases. Epidemic situations of vaccine-preventable diseases have been observed in France, accelerating the awareness of the need to implement catch-up vaccination programs and highlighting the difficulties to implement this catch-up in people who have, for the most, already received vaccinations in their countries of origin but have no vaccine proof. Different catch-up strategies are possible with or without pre- or post-vaccination serologies and were the subject of recommendations co-developed by the French High Authority in Health (HAS) and the French Infectious Disease Society (SPILF).

La problématique du rattrapage vaccinal chez les enfants et adultes migrants s'installant en France est un enjeu de santé publique. Les migrants ne représentent pas une population homogène, mais une majorité d'entre eux sont insuffisamment vaccinés au regard du calendrier vaccinal français qui est plus exigeant que ceux des pays d'origine. Au sein des populations migrantes, les personnes en situation de précarité ou appartenant à certains groupes sociaux sont plus souvent insuffisamment vaccinées, sont exposées à un retard de la mise en œuvre de son rattrapage, alors qu'elles sont surexposées au risque de maladies infectieuses à prévention vaccinale comme la rougeole ou la varicelle. Des situations épidémiques de maladies à prévention vaccinale ont été observées en France, accélérant la prise de conscience de la nécessité de mettre en place des programmes de rattrapage vaccinal. Leur mise en œuvre est confrontée à la problématique des modalités pratiques de ce rattrapage chez des personnes ayant pour la grande majorité déjà reçu des vaccinations dans leur pays d'origine, mais n'ayant pas de trace de ces dernières. Différentes stratégies de rattrapage sont possibles avec ou sans recours à des sérologies préou postvaccinales notamment et ont fait l'objet de discussions et de l'élaboration de recommandations sous l'égide de la Haute Autorité de santé (HAS) et de la Société de pathologie infectieuse de langue française (SPILF).

Biotinidase deficiency in a newborn.

INTRODUCTION: Biotinidase deficiency is an inherited disorder of biotin metabolism that is untreated may present within the first few month of life. OBJECTIVE: We report the exceptional observation of a biotinidase deficiency in Morocco. The rarity of this pathology, its age of onset, its mode of revelation and the lack of treatment in Morocco make the particularity of this observation. OBSERVATION: A newborn child born from a 24-year-old mother, followed by an estimated pregnancy of 37 weeks of amenorrhea according to the Farr score (morphological maturation score used for the dating of the pregnancy term). The infant presented at 7 days of life with a cutaneous-mucous eruption with icithiosic dry erythroderma of interest to the trunk, the face, the scalp associated with alopecia and depilation of the eyebrow. The biotinoidase deficiency was confirmed by its low serum concentration at 49 nka / l. The newborn died at 20 days of life before starting the specific treatment. CONCLUSION: Biotinidase deficiency is a rare condition requiring early screening and rapid management. The delay in diagnosis and the unavailability of treatment in Morocco can have fatal consequences.

In-vitro validation of 4D flow MRI measurements with an experimental pulsatile flow model.

PURPOSE: The purpose of this study was to assess the precision of four-dimensional (4D) phase-contrast magnetic resonance imaging (PCMRI) to measure mean flow and peak velocity (Vmax) in a pulsatile flow phantom and to test its sensitivity to spatial resolution and Venc. MATERIAL AND METHODS: The pulsatile flow phantom consisted of a straight tube connected to the systemic circulation of an experimental mock circulatory system. Four-dimensional-PCMR images were acquired using different spatial resolutions (minimum pixel size: 1.5×1.5×1.5mm3) and velocity encoding sensitivities (up to three times Vmax). Mean flow and Vmax calculated from 4D-PCMRI were compared respectively to the reference phantom flow parameters and to Vmax obtained from two-dimensional (2D)-PCMRI. RESULTS: 4D-PCI measured mean flow with a precision of -0.04% to+5.46%, but slightly underestimated Vmax when compared to 2D-PCMRI (differences ranging from -1.71% to -3.85%). 4D PCMRI mean flow measurement was influenced by spatial resolution (P<0.001) with better results obtained with smaller voxel size. There was no effect of Venc on mean flow measurement. Regarding Vmax, neither spatial resolution nor Venc did influence the precision of the measurement. CONCLUSION: Using an experimental pulsatile flow model 4D-PCMRI is accurate to measure mean flow and Vmax with better results obtained with higher spatial resolution. We also show that Venc up to 3 times higher than Vmax may be used with no effect on these measurements.

Genetic Risk Factors of Venous Thromboembolism in the East Algerian Population.

Many genetic risk factors have been identified for causing venous thromboembolism (VTE). Most of them affect the function of natural anticoagulant pathways, particularly the protein C system, although recent studies suggest a role of components of the hematopoietic pathway in the etiology of venous thrombosis. In this case-control study, we aimed to determine the frequency of prothrombin G20210A and factor V Leiden (FVL) G1691A polymorphisms and protein C, protein S, and antithrombin III deficiencies in the East Algerian population and to investigate whether these genetic factors are associated with VTE. On the other hand, our study tends to evaluate the status of JAK2V617F and calreticulin (CALR) mutations among these cases. The participants consisted of 121 cases with VTE and 146 healthy controls. Polymorphisms of FVL G1691A and prothrombin G20210A were genotyped by polymerase chain reaction (PCR) restriction fragment length polymorphism. JAK2-V617F and calreticulin mutations were analyzed by quantitative PCR and PCR followed by capillary electrophoresis sequencing, respectively. Protein C, protein S, and antithrombin levels were determined and then hereditary deficiencies were identified. Of all cases and controls, none was a carrier of the antithrombin III deficiency, prothrombin gene G20210A, and CALR mutations. Only 1 case reported having a positive JAK2 mutation (mutant allele burden was 15%). The FVL mutation (GA/AA) was found in 14 (11.6%) cases and 2 (1.4%) controls and it was significantly different between both the groups ( P = .001). Deficiencies of protein S and protein C were detected in 17 (18.8%) cases. The univariate analysis resulted in a significant impact of FVL (odds ratio [OR] = 9.4, 95% confidence interval [CI] = 2.1-42.3; P = .003) and of protein S deficiency (OR = 16.9, 95% CI =2.1-132.8, P = .007) on the VTE status. Both factors stayed significant after adjustment for sex and age. The OR of the protein C deficiency was slightly elevated (OR = 6.4, 95% CI = 0.7-55.5), but it did not reach the level of statistical significance ( P = .091), and it was therefore not considered as a risk factor. In conclusion, coagulant factor V gene G1691A mutation and protein S deficiency constitute important genetic risk factors in patients with VTE in Eastern Algeria. The somatic mutation of JAK2 V617F and CALR mutations are less frequent causes of VTE, thus routine testing for these mutations is not recommended.

Two dimensional IR-FID-CPMG acquisition and adaptation of a maximum entropy reconstruction.

By acquiring the FID signal in two-dimensional TD-NMR spectroscopy, it is possible to characterize mixtures or complex samples composed of solid and liquid phases. We have developed a new sequence for this purpose, called IR-FID-CPMG, making it possible to correlate spin-lattice T1 and spin-spin T2 relaxation times, including both liquid and solid phases in samples. We demonstrate here the potential of a new algorithm for the 2D inverse Laplace transformation of IR-FID-CPMG data based on an adapted reconstruction of the maximum entropy method, combining the standard decreasing exponential decay function with an additional term drawn from Abragam's FID function. The results show that the proposed IR-FID-CPMG sequence and its related inversion model allow accurate characterization and quantification of both solid and liquid phases in multiphasic and compartmentalized systems. Moreover, it permits to distinguish between solid phases having different T1 relaxation times or to highlight cross-relaxation phenomena.

Nanoscale sub-100 picosecond all-optical magnetization switching in GdFeCo microstructures.

Ultrafast magnetization reversal driven by femtosecond laser pulses has been shown to be a promising way to write information. Seeking to improve the recording density has raised intriguing fundamental questions about the feasibility of combining ultrafast temporal resolution with sub-wavelength spatial resolution for magnetic recording. Here we report on the experimental demonstration of nanoscale sub-100 ps all-optical magnetization switching, providing a path to sub-wavelength magnetic recording. Using computational methods, we reveal the feasibility of nanoscale magnetic switching even for an unfocused laser pulse. This effect is achieved by structuring the sample such that the laser pulse, via both refraction and interference, focuses onto a localized region of the structure, the position of which can be controlled by the structural design. Time-resolved photo-emission electron microscopy studies reveal that nanoscale magnetic switching employing such focusing can be pushed to the sub-100 ps regime.

Domain wall transformations and hopping in La(0.7)Sr(0.3)MnO(3) nanostructures imaged with high resolution x-ray magnetic microscopy.

We investigate the effect of electric current pulse injection on domain walls in La(0.7)Sr(0.3)MnO(3) (LSMO) half-ring nanostructures by high resolution x-ray magnetic microscopy at room temperature. Due to the easily accessible Curie temperature of LSMO, we can employ reasonable current densities to induce the Joule heating necessary to observe effects such as hopping of the domain walls between different pinning sites and nucleation/annihilation events. Such effects are the dominant features close to the Curie temperature, while spin torque is found to play a small role close to room temperature. We are also able to observe thermally activated domain wall transformations and we find that, for the analyzed geometries, the vortex domain wall configuration is energetically favored, in agreement with micromagnetic simulations.

The effect of magnetic anisotropy on the spin configurations of patterned La(0.7)Sr(0.3)MnO3 elements.

We study the effect of magnetocrystalline anisotropy on the magnetic configurations of La0.7Sr0.3MnO3 bar and triangle elements using photoemission electron microscopy imaging. The dominant remanent state is a low energy flux-closure state for both thin (15 nm) and thick (50 nm) elements. The magnetocrystalline anisotropy, which competes with the dipolar energy, causes a strong modification of the spin configuration in the thin elements, depending on the shape, size and orientation of the structures. We investigate the magnetic switching processes and observe in triangular shaped elements a displacement of the vortex core along the easy axis for an external magnetic field applied close to the hard axis, which is well reproduced by micromagnetic simulations.

Ultrafast heating as a sufficient stimulus for magnetization reversal in a ferrimagnet.

The question of how, and how fast, magnetization can be reversed is a topic of great practical interest for the manipulation and storage of magnetic information. It is generally accepted that magnetization reversal should be driven by a stimulus represented by time-non-invariant vectors such as a magnetic field, spin-polarized electric current, or cross-product of two oscillating electric fields. However, until now it has been generally assumed that heating alone, not represented as a vector at all, cannot result in a deterministic reversal of magnetization, although it may assist this process. Here we show numerically and demonstrate experimentally a novel mechanism of deterministic magnetization reversal in a ferrimagnet driven by an ultrafast heating of the medium resulting from the absorption of a sub-picosecond laser pulse without the presence of a magnetic field.

Artificial kagome arrays of nanomagnets: a frozen dipolar spin ice.

Magnetic frustration effects in artificial kagome arrays of nanomagnets are investigated using x-ray photoemission electron microscopy and Monte Carlo simulations. Spin configurations of demagnetized networks reveal unambiguous signatures of long range, dipolar interaction between the nanomagnets. As soon as the system enters the spin ice manifold, the kagome dipolar spin ice model captures the observed physics, while the short range kagome spin ice model fails.

Alzheimer's disease proteins in cerebellar and hippocampal synapses during postnatal development and aging of the rat.

Alzheimer's dementia may be considered a synaptic disease of central neurons: the loss of synapses, reflected by early cognitive impairments, precedes the appearance of extra cellular focal deposits of beta-amyloid peptide in the brain of patients. Distinct immunocytochemical patterns of amyloid precursor proteins (APPs) have previously been demonstrated in the synapses by ultrastructural analysis in the cerebellum and hippocampus of adult rats and mice. Now we show that during postnatal development and during aging in these structures, the immunocytochemical expression of APPs increases in the synapses in parallel with the known up-regulation of total APPs brain levels. Interestingly, as shown previously in the adult rodents, the presenilins (PSs) 1 and 2, which intervene in APPs metabolism, exhibit a synaptic distribution pattern similar to that of APPs with parallel quantitative changes throughout life. In the brain tissue, single and double immunocytochemistry at the ultrastructural level shows co-localisation of APPs and PSs in axonal and dendritic synaptic compartments during postnatal synaptogenesis, adulthood and aging. In addition, double-labelling immunocytofluorescence detects these proteins close to synaptophysin at the growth cones of developing cultured neurons. Thusly, the brain expression of APPs and PSs appears to be regulated synchronously during lifespan in the synaptic compartments where the proteins are colocated. This suggests that PS-dependent processing of important synaptic proteins such as APPs could intervene in age-induced adjustments of synaptic relationships between specific types of neurons.

Intraneuronal Abeta accumulation precedes plaque formation in beta-amyloid precursor protein and presenilin-1 double-transgenic mice.

beta-Amyloid peptides are key molecules that are involved in the pathology of Alzheimer's disease (AD). The source and place of the neurotoxic action of Abeta, however, is still a matter of controversial debates. In the present report, we studied the neuropathological events in a transgenic mouse model expressing human mutant beta-amyloid precursor protein and human mutant presenilin-1 in neurons. Western blot and immunohistochemical analysis revealed that intracellular Abeta staining preceded plaque deposition, which started in the hippocampal formation. At later stages, many neuritic Abeta positive plaques were found in all cortical, hippocampal and many other brain areas. Interestingly, intraneuronal Abeta staining was no longer detected in the brain of aged double-transgenic mice, which correlates with the typical neuropathology in the brain of chronic AD patients.

Parkin immunoreactivity in the brain of human and non-human primates: an immunohistochemical analysis in normal conditions and in Parkinsonian syndromes.

The etiology of Parkinson's disease is unknown, but the gene involved in an autosomic recessive form of the disease with early onset has recently been identified. It codes for a protein with an unknown function called parkin. In the present study we produced a specific polyclonal antiserum against human parkin. Immunohistochemical analysis showed that parkin is expressed in neuronal perikarya and processes but also in glial and blood vessels in the primate brain (human and monkey). Electron microscopy indicated that parkin immunoreactivity is mostly located in large cytoplasmic vesicles and at the level of the endoplasmic reticulum. Parkin was expressed heterogeneously in various structures of the brain. It was detectable in the dopaminergic systems at the level of the perikarya in the mesencephalon but also in the striatum. However, parkin was also expressed by numerous nondopaminergic neurons. The staining intensity of parkin was particularly high in the hippocampal formation, the pallidal complex, the red nucleus, and the cerebellum. Comparison of control subjects with patients with Parkinson's disease and control animals with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated animals revealed a loss of parkin-immunoreactive neurons only in the substantia nigra pars compacta. Furthermore, the surviving dopaminergic neurons in the parkinsonian state continued to express parkin at a level similar to that observed in the control situation. These data indicate that parkin is a widely expressed protein. Thus, the degeneration of dopaminergic neurons in familial cases of Parkinson's disease with autosomal recessive transmission cannot be explained solely in terms of an alteration of this protein.

The antioxidant ebselen prevents neurotoxicity and clinical symptoms in a primate model of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), via its major metabolite 1-methyl-4-phenylpyridinium (MPP(+)), produces in primates including humans clinical, biochemical, and neuropathological changes similar to those which occur in idiopathic Parkinson's disease. Ebselen is an antioxidant drug with glutathione peroxidase-like activity and a proven neuroprotective action in stroke patients. Here we show that Ebselen, when administered before, during, and after MPTP injections, prevents both neuronal loss and clinical symptoms in a primate MPTP model of Parkinson's disease. Ebselen also prevents peroxide radical overproduction induced by serum withdrawal in cultured PC12 cells and hydroxyl radical generation induced by the mitochondrial toxin, MPP(+), in vivo in rat brain. Moreover, Ebselen inhibits MPP(+)-induced toxicity in PC12 cells, without interacting with the dopamine uptake system. Our results demonstrate that compounds which prevent mitochondrial dysfunction and free radical production may be useful as preventive treatment of Parkinson's disease.

The anti-oxidant ebselen antagonizes the release of the apoptogenic factor cytochrome c induced by Fe2+/citrate in rat liver mitochondria.

We studied the effects of ebselen (a seleno-organic anti-oxidant), on the release of the apoptogenic factor, cytochrome c, in two different experimental situations damaging mitochondria: (1) Fe(2+)/citrate, known to induce lipid peroxidation consecutively to an oxidative stress; and (2) atractyloside, a ligand of the adenine nucleotide translocator. The effects of ebselen were compared to those of butylated hydroxytoluene (BHT, an inhibitor of lipid peroxidation), and cyclosporine A (CsA, a classical pore antagonist). Ebselen, like BHT, inhibited Fe(2+)/citrate-induced release of cytochrome c, whereas CsA was inactive. On the contrary, neither ebselen nor BHT inhibited atractyloside-induced release of cytochrome c, whereas CsA was potently active. The antioxidant properties of ebselen may protect mitochondria from the consequences of the release of cytochrome c. Thus, it is suggested that the neuroprotective effect of ebselen previously demonstrated in humans and in animals may be due, at least in part, to a mitochondrial protection.

The protective effect of riluzole in the MPTP model of Parkinson's disease in mice is not due to a decrease in MPP(+) accumulation.

Riluzole, has previously been shown to be protective in animal models of Parkinson's disease in vivo. In the present study the effects of riluzole on the intrastriatal formation and accumulation of MPP(+), after i.p. injection of MPTP were tested in mice, using two different experimental protocols. In the first protocol, mice were treated with a single dose (15 mg/kg i.p.) of MPTP and MPP(+) accumulation was measured 30 min, 1 h and 3 h after the injection of the toxin. Riluzole (10 mg/kg p.o.), administered 30 min before MPTP, did not modify the accumulation kinetic of MPP(+). Contrarily to riluzole, a single dose of 50 mg/kg p.o. of 7-nitroindazole (7-NI), a non-selective non hypertensive inhibitor of nitric oxide synthase (NOS), significantly decreased MPP(+) levels. In the second protocol, consisting of 3 injections of MPTP (15 mg/kg i.p.), riluzole, administered 4 times at the dose of 5 mg/kg p.o., had no effect on MPP(+) levels. The protective effect of repeated treatments of riluzole and 7-NI against MPTP-induced depletion of dopamine (DA) is also reported. Our data obtained with 7-NI (in agreement with previous studies reported by others) suggest that a part of the protection observed with this NOS inhibitor is probably due to in vivo inhibition of monoamine oxidase-B (MAO-B). That riluzole does not modify MPP(+) accumulation demonstrates that its protective effect against MPTP toxicity was not due to an in vivo interference with MPTP metabolism.

Hemisynaptic distribution patterns of presenilins and beta-APP isoforms in the rodent cerebellum and hippocampus.

Healthy brain neurons co-express Alzheimer's disease (AD) related proteins presenilins (PS) and beta-amyloid precursor protein (beta-APP). Deposition of beta-amyloid and PS in the senile plaques of AD brain and their ability to interact in vitro suggest that AD pathology could arise from a defect in the physiological interactions between beta-APP and PS within and/or between neurons. The present study compares the immunocytochemical distribution of PS (1 and 2) and beta-APP major isoforms (695 and 751/770) in the synapses of the cerebellum and hippocampus of the adult rat and mouse. In the cerebellar cortex of both species, the four molecules are immunodetected in the presynaptic or the postsynaptic compartments of synapses, suggesting that they are involved in interneuronal relationships. In contrast, PS and beta-APP are postsynaptic in almost all the immunoreactive synapses of the hippocampus. The different distribution patterns of these proteins in cerebellar and hippocampal synapses may reflect specific physiological differences, responsible for differential vulnerability of neurons to AD synaptic pathology. Defective interactions between beta-APP and PS at the synapses could impede the synaptic functions of beta-APP, inducing the selective loss of synapses that accounts for cognitive impairment in AD.

Characterization of human presenilin 1 transgenic rats: increased sensitivity to apoptosis in primary neuronal cultures.

Mutations in the gene for presenilin 1 are causative for the majority of cases of early onset familial Alzheimer's disease. Yet, the physiological function of presenilin 1 and the pathological mechanisms of the mutations leading to Alzheimer's disease are still unknown. To analyse potential pathological effects of presenilin 1 over-expression, we have generated transgenic rats which express high levels of human presenilin 1 protein in the brain. The over-expression of presenilin 1 leads to saturation of its normal processing and to the appearance of full-length protein in the transgenic rat brain. The transgenic protein is expressed throughout the brain and is predominantly found in neuronal cells. Cultured primary cortical neurons derived from these transgenic rats are significantly more sensitive than non-transgenic controls to apoptosis induced by standard culture conditions and to apoptosis induced by trophic factor withdrawal. Furthermore, the observed apoptosis is directly correlated with the expression of the transgenic protein. The results further emphasize the role of presenilin 1 in apoptotic cell death in native neuronal cultures.