The Third sector in France and the Labour Market Policy

In France, like in other Western European countries, the third sector has been on a steady increase during the last decade as the results of the Johns Hopkins comparative project shows it. Today nonprofit organisations play also an increasing role in labour market policies. In a country with a corporatist welfare state, the access to the labour-market represents the key for social rights

Oseltamivir-Resistant Pandemic A/H1N1 Virus Is as Virulent as Its Wild-Type Counterpart in Mice and Ferrets

The neuraminidase inhibitor oseltamivir is currently used for treatment of patients infected with the pandemic A/H1N1 (pH1N1) influenza virus, although drug-resistant mutants can emerge rapidly and possibly be transmitted. We describe the characteristics of a pair of oseltamivir-resistant and oseltamivir-susceptible pH1N1 clinical isolates that differed by a single change (H274Y) in the neuraminidase protein. Viral fitness of pH1N1 isolates was assessed in vitro by determining replication kinetics in MDCK α2,6 cells and in vivo by performing experimental infections of BALB/c mice and ferrets. Despite slightly reduced propagation of the mutant isolate in vitro during the first 24 h, the wild-type (WT) and mutant resistant viruses induced similar maximum weight loss in mice and ferrets with an identical pyrexic response in ferrets (AUC of 233.9 and 233.2, P = 0.5156). Similarly, comparable titers were obtained for the WT and the mutant strains on days 1, 3, 6 and 9 post-infection in mouse lungs and on days 1–7 in ferret nasal washes. A more important perivascular (day 6) and pleural (days 6 and 12) inflammation was noted in the lungs of mice infected with the H274Y mutant, which correlated with increased pulmonary levels of IL-6 and KC. Such increased levels of IL-6 were also observed in lymph nodes of ferrets infected with the mutant strain. Furthermore, the H274Y mutant strain was transmitted to ferrets. In conclusion, viral fitness of the H274Y pH1N1 isolate is not substantially altered and has the potential to induce severe disease and to disseminate

Effect of rs1561570 in NF-κB localization and in the expression of NF-κB target genes in osteoclasts of patients with PDB.

<p>(A) NF-κB localization in osteoclasts derived from healthy controls and patients PBCMs showing an increase of the translocation of NF-κB into the nucleus, in patients with genotype <i>CT</i> and <i>TT</i>. This was also confirmed by co-localization ratio between NF-κB and DAPI–the nuclear staining. Five different fields of view were analysed per sample and at least three different samples were analysed per patient. Co-localization coefficient was calculated by Volocity software as the ratio of NF-κB staining related to DAPI. (B) Analysis of <i>NFATc1</i>, <i>IL6</i>, <i>TRAP</i> and <i>ELK1</i> gene expression in several healthy controls (n = 16) and PDB patients (<i>CC</i> n = 10, <i>CT</i>/<i>TT</i> n = 22) with all genotypes. The levels of <i>NFATc1</i>, <i>IL6</i>, <i>TRAP</i> and <i>ELK1</i> expression were measured by qPCR related to levels of <i>PPIB</i>. Values are the mean of at least three independent replicates. (t-test, * represents a <i>p</i>-value < 0.05, ** represents a <i>p</i>-value < 0.01).</p

Effect of rs1561570 in bone resorption.

<p>(A) Representative images of <i>in vitro</i> bone resorption assays (left) with (B) quantification of the results (right) by using ImageJ. The bone resorption area was higher in patients with PDB carrying at least one <i>T</i> allele (Patients <i>CT/TT vs</i> Controls <i>CC p</i>-value < 0.001; Patients <i>CT/TT vs</i> Patients <i>CC p</i>-value < 0.01). This result was even more evident in one PDB patient carrying one <i>T</i> allele (<i>CT</i> genotype) plus the <i>SQSTM1/P392L</i> mutation (<i>p</i>-value < 0.001). At least three different wells per patient were analysed. (ANOVA, * represents a <i>p</i>-value < 0.05, ** represents a <i>p</i>-value < 0.01, *** represents a <i>p</i>-value < 0.001, **** represents a <i>p</i>-value < 0.0001; non-mutated controls with <i>CC</i> genotype (n = 3), non-mutated patients with <i>CC</i> genotype (n = 5) and patients carrying at least one <i>T</i> allele (n = 3)).</p

Rs1561570 effect in methylation and <i>OPTN</i> expression.

<p>(A) <i>In silico</i> prediction using Methprimer tool showing a methylation site only in the presence of the allele <i>C</i> (not the allele <i>T</i>). (B) Sequencing results showing that rs1561570 <i>C</i> allele after bisulfite treatment remains a <i>C</i> (arrow head), while other <i>C</i> nucleotides that are not methylated change to <i>T</i> (asterisk). (C) Analysis of <i>OPTN</i> gene expression in lymphocytes from several healthy controls (<i>CC</i> genotype n = 10, <i>CT/TT</i> genotypes n = 6) and PDB patients (<i>CC</i> genotype n = 10, <i>CT/TT</i> genotypes n = 22) with the three genotypes. The levels of <i>OPTN</i> gene expression were measured by qPCR normalized to <i>PPIB</i> gene expression levels. Values are the mean of two replicates in each experiment and the experiment was repeated at least three independent times. (D) Quantification and (E) representative blots of OPTN protein expression in lymphocytes from non-mutated controls with <i>CC</i> genotype (n = 5), and patients carrying at least one <i>T</i> allele (n = 19). (F) Quantification and (G) representative blots of OPTN protein expression in osteoclasts from non-mutated controls with <i>CC</i> genotype (n = 3), non-mutated patients with <i>CC</i> genotype (n = 5) and patients carrying at least one <i>T</i> allele (n = 3). The levels of OPTN protein expression were measured by western blot analysis and related to levels of α-Tubulin (t-test and ANOVA, * represents a <i>p</i>-value < 0.05). The figures are representative of all the western blot analyses performed (n = 3).</p

<i>In vitro</i> effect of <i>OPTN</i> demethylation in NF-κB localization and expression of NF-κB target genes.

<p>(A) NF-κB localization in U937 cells (<i>CC</i> genotype). (B) NF-κB localization in T47D cells (<i>CT</i> genotype), following 5-Azacitidine (5-Aza) treatment. After <i>OPTN</i> demethylation, NF-κB was translocated exclusively to the nucleus. (C) Analysis of NF-κB target genes expression. The levels of <i>OPTN</i>, <i>NF-κB</i> and NF-κB target genes (<i>IL-6</i>, <i>ELK1</i>, <i>NFATc1</i>) expression were measured by qPCR related to levels of <i>GAPDH</i> gene. Values are the mean of at least three independent replicates. (t-test, * represents a <i>p</i>-value < 0.05, ** represents a <i>p</i>-value < 0.01 *** represents a <i>p</i>-value < 0.001, **** represents a <i>p</i>-value < 0.0001).</p

Case report: Acute pancreatitis induced by Clozapine

Two percent of acute pancreatitis are drug induced. In the present paper, we reported the case of a 39 year-old patient with chronic-hallucinatory schizophrenia who developed symptomatic pancreatitis during the clozapine dose titration performed to reach the therapeutic range. Diagnosis of pancreatitis was suggested by clinical examination and abnormal laboratory values of pancreatic enzymes and confirmed by C-T scan and ultrasonography. The causal incrimination of clozapine in this case seems likely as all other possible causes of pancreatitis were excluded, as AP developed shortly after the introduction of the drug and as the pancreatic enzymes normalized after clozapine was stopped. No rechallenge to confirm the causal relationship was however attempted. So far, only eight cases of acute pancreatitis have been reported in association with clozapine use. Clozapine is an atypical antipsychotic drug which belongs to the chemical class of dibenzodiazepines. The mechanism by which clozapine could produce acute pancreatitis remained unclear. Nevertheless, we advocate a careful biological follow-up (measuring periodically the concentrations of amylase, lipase and triglycerides) during the treatment by clozapine.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Effect of rs1561570 in osteoclast differentiation.

<p>(A) The osteoclast differentiation rate (displayed as a ratio between multinucleated osteoclasts (Multi OCL) and TRAP positive (+) cells) was higher in patients with PDB carrying at least one <i>T</i> allele (Patients <i>CT/TT vs</i> Controls <i>CC p</i>-value < 0.01; Patients <i>CT/TT vs</i> Patients <i>CC p</i>-value < 0.05). (B) Osteoclasts from patients carrying at least one <i>T</i> allele contained significantly more nuclei than osteoclasts from healthy controls (Patients <i>CT/TT vs</i> Controls <i>CC p</i>-value < 0.001; Patients <i>CT/TT vs</i> Patients <i>CC p</i>-value < 0.01). (C) The images are representative of the distribution of nuclei number observed in osteoclasts generated from PBMCs derived from healthy controls and PDB patients that were stained for TRAP and counterstained with haematoxylin. (ANOVA, * represents a <i>p</i>-value < 0.05, ** represents a <i>p</i>-value < 0.01, *** represents a <i>p</i>-value < 0.001, **** represents a <i>p</i>-value < 0.0001; non-mutated controls with <i>CC</i> genotype (n = 3), non-mutated patients with <i>CC</i> genotype (n = 5) and patients carrying at least one <i>T</i> allele (n = 3).</p