A segurança sanitária num mundo global: os aspectos legais. O sistema de segurança sanitária na França

O tema da saúde pública está ligado hoje ao da reorganização administrativa e da atualização institucional. Na França esse questionamento é patente, dadas as crises sanitárias verificadas, as quais desencadearam, ao longo da história, a reforma da saúde pública. Dessa forma, o novo campo de ação da segurança sanitária se resume em duas preocupações: uma reforma institucional e sua expansão aos domínios alimentares e ambientais. Estas preocupações, por sua vez, têm sido alvo de interesse do legislador. As decisões em saúde pública são moldadas por elementos de uma crise sanitária: a urgência, um elemento catalisador que leva a criações institucionais; a reincidência, que provoca uma análise de suas causas e do sistema; a percepção dos riscos pelo público, ligada às políticas de gestão de riscos. A visão da saúde pública, como um sistema fragmentado, é transformada pela noção de segurança sanitária como função essencial do governo. O direito, portanto, progride estimulado pelas crises, visando a um sistema coerente de preservação da saúde, cujos princípios se fundam na separação das funções e na precaução. Nesse sentido, a resposta do sistema francês a essa evolução levou ao surgimento das agências, distintas do Estado e sob tutela ministerial, e à criação da Lei n. 98-535, de 1o de julho de 1998, que regulamentou novas instituições de gestão por setores e iluminou a conveniência de uma política com outros Estados

Analysis of X chromosome inactivation in autism spectrum disorders.

International audienceAutism spectrum disorders (ASD) are complex genetic disorders more frequently observed in males. Skewed X chromosome inactivation (XCI) is observed in heterozygous females carrying gene mutations involved in several X-linked syndromes. In this study, we aimed to estimate the role of X-linked genes in ASD susceptibility by ascertaining the XCI pattern in a sample of 543 informative mothers of children with ASD and in a sample of 163 affected girls. The XCI pattern was also determined in two control groups (144 adult females and 40 young females) with a similar age distribution to the mothers sample and affected girls sample, respectively. We observed no significant excess of skewed XCI in families with ASD. Interestingly, two mothers and one girl carrying known mutations in X-linked genes (NLGN3, ATRX, MECP2) showed highly skewed XCI, suggesting that ascertainment of XCI could reveal families with X-linked mutations. Linkage analysis was carried out in the subgroup of multiplex families with skewed XCI (> or = 80:20) and a modest increased allele sharing was obtained in the Xq27-Xq28 region, with a peak Z-score of 1.75 close to rs719489. In summary, our results suggest that there is no major X-linked gene subject to XCI and expressed in blood cells conferring susceptibility to ASD. However, the possibility that rare mutations in X-linked genes could contribute to ASD cannot be excluded. We propose that the XCI profile could be a useful criteria to prioritize families for mutation screening of X-linked candidate genes

An investigation of ribosomal protein L10 gene in autism spectrum disorders

<p>Abstract</p> <p>Background</p> <p>Autism spectrum disorders (ASD) are severe neurodevelopmental disorders with the male:female ratio of 4:1, implying the contribution of X chromosome genetic factors to the susceptibility of ASD. The ribosomal protein L10 (RPL10) gene, located on chromosome Xq28, codes for a key protein in assembling large ribosomal subunit and protein synthesis. Two non-synonymous mutations of <it>RPL10</it>, L206M and H213Q, were identified in four boys with ASD. Moreover, functional studies of mutant RPL10 in yeast exhibited aberrant ribosomal profiles. These results provided a novel aspect of disease mechanisms for autism – aberrant processes of ribosome biosynthesis and translation. To confirm these initial findings, we re-sequenced <it>RPL10 </it>exons and quantified mRNA transcript level of <it>RPL10 </it>in our samples.</p> <p>Methods</p> <p>141 individuals with ASD were recruited in this study. All <it>RPL10 </it>exons and flanking junctions were sequenced. Furthermore, mRNA transcript level of <it>RPL10 </it>was quantified in B lymphoblastoid cell lines (BLCL) of 48 patients and 27 controls using the method of SYBR Green quantitative PCR. Two sets of primer pairs were used to quantify the mRNA expression level of <it>RPL10</it>: RPL10-A and RPL10-B.</p> <p>Results</p> <p>No non-synonymous mutations were detected in our cohort. Male controls showed similar transcript level of RPL10 compared with female controls (RPL10-A, U = 81, P = 0.7; RPL10-B, U = 61.5, P = 0.2). We did not observe any significant difference in RPL10 transcript levels between cases and controls (RPL10-A, U = 531, P = 0.2; RPL10-B, U = 607.5, P = 0.7).</p> <p>Conclusion</p> <p>Our results suggest that RPL10 has no major effect on the susceptibility to ASD.</p

Pre-existing immunity to SARS-CoV-2 before the COVID-19 pandemic era in Cameroon: A comparative analysis according to HIV-status

BackgroundThe lower burden of COVID-19 in tropical settings may be due to preexisting cross-immunity, which might vary according to geographical locations and potential exposure to other pathogens. We sought to assess the overall prevalence of SARS-CoV-2 antibodies and determine SARS-CoV-2 seropositivity according to HIV-status before the COVID-19 pandemic era. MethodsA cross-sectional and comparative study was conducted at the Chantal BIYA International Reference Centre (CIRCB) on 288 stored plasma samples (163 HIV-positive versus 125 HIV-negative); all collected in 2017-2018, before the COVID-19 pandemic era. Abbott Panbio (TM) COVID-19 IgG/IgM assay was used for detecting SARS-CoV-2 immunoglobulin G (IgG) and M (IgM). Among people living with HIV (PLHIV), HIV-1 viral load and TCD4 cell count (LTCD4) were measured using Abbott Real Time PCR and BD FACSCalibur respectively. Statistical analyses were performed, with pResultsThe median [IQR] age was 25 [15-38] years. Overall seropositivity to SARS-CoV-2 antibodies was 13.5% (39/288) of which 7.3% (21) was IgG, 7.3% (21) IgM and 1.0% (3) IgG/IgM. According to HIV-status in the study population, SARS-CoV-2 seropositivity was 11.0% (18/163) among HIV-positive versus 16.8% (21/125) among HIV-negative respectively, p=0.21. Specifically, IgG was 6.1% (10/163) versus 8.8% (11/125), p=0.26; IgM was 5.5% (9/163) versus 9.6%, (12/125), p=0.13 and IgG/IgM was 0.6% (1/163) versus 1.6% (2/125) respectively. Among PLHIV, SARS-CoV-2 seropositivity according to CD4 count was 9.2% (&gt;= 500 cells/mu L) versus 1.8% (200-499 cells/mu L), (OR=3.5; p=0.04) and 0.6% (&lt;200 cells/mu L), (OR=17.7; p&lt;0.01). According to viral load, SARS-CoV-2 seropositivity was 6.7% (&gt;= 40 copies/mL) versus 4.9% (&lt;40 copies/mL), (OR= 3.8; p&lt;0.01). ConclusionBefore COVID-19 in Cameroon, cross-reactive antibodies to SARS-CoV-2 were in circulation, indicating COVID-19 preexisting immunity. This preexisting immunity may contribute in attenuating disease severity in tropical settings like Cameroon. Of relevance, COVID-19 preexisting immunity is lower with HIV-infection, specifically with viral replication and poor CD4-cell count. As poor CD4-count leads to lower cross-reactive antibodies (regardless of viral load), people living with HIV appear more vulnerable to COVID-19 and should be prioritized for vaccination

Genome sequencing of Xanthomonas axonopodis pv. phaseoli CFBP4834-R reveals that flagellar motility is not a general feature of xanthomonads.

Xanthomonads are plant-associated bacteria that establish neutral, commensal or pathogenic relationships with plants. The list of common characteristics shared by all members of the genus Xanthomonas is now well established based on the entire genome sequences that are currently available and that represent various species, numerous pathovars of X. axonopodis (sensu Vauterin et al., 2000), X. oryzae and X. campestris, and many strains within some pathovars. These ?-proteobacteria are motile by a single polar flagellum. Motility is an important feature involved in biofilm formation, plant colonization and hence considered as a pathogenicity factor. X. axonopodis pv. phaseoli var. fuscans (Xapf) is one of the causal agents of common bacterial blight of bean and 4834-R is a highly aggressive strain of this pathogen that was isolated from a seed-borne epidemic in France in 1998. We obtained a high quality assembled sequence of the genome of this strain with 454-Solexa and 2X Sanger sequencing. Housekeeping functions are conserved in this genome that shares core characteristics with genomes of other xanthomonads: the six secretion systems which have been described so far in Gram negative bacteria are all present, as well as their ubiquitous substrates or effectors and a rather usual number of mobile elements. Elements devoted to the adaptation to the environment constitute an important part of the genome with a chemotaxis island and dispersed MCPs, numerous two-component systems, and numerous TonB dependent transporters. Furthermore, numerous multidrug efflux systems and functions dedicated to biofilm formation that confer resistance to stresses are also present. An intriguing feature revealed by genome analysis is a long deletion of 35 genes (33 kbp) involved in flagellar biosynthesis. This deletion is replaced by an insertion sequence called ISXapf2. Genes such as flgB to flgL and fliC to fleQ which are involved in the flagellar structure (rod, P- and L-ring, hook, cap and filament) are absent in the genome of strain 4834-R that is not motile. Primers were designed to detect this deletion by PCR in a collection of more than 300 strains representing different species and pathovars of Xanthomonas, and less than 5% of the tested xanthomonads strains were found nonmotile because of a deletion in the flagellum gene cluster. We observed that half of the Xapf strains isolated from the same epidemic than strain 4834-R was non-motile and that this ratio was conserved in the strains colonizing the next bean seed generation. Isolation of such variants in a natural epidemic reveals that either flagellar motility is not a key function for fitness or that some complementation occurs within the bacterial population. (Résumé d'auteur

Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders.

International audienceSHANK3 (also known as ProSAP2) regulates the structural organization of dendritic spines and is a binding partner of neuroligins; genes encoding neuroligins are mutated in autism and Asperger syndrome. Here, we report that a mutation of a single copy of SHANK3 on chromosome 22q13 can result in language and/or social communication disorders. These mutations concern only a small number of individuals, but they shed light on one gene dosage-sensitive synaptic pathway that is involved in autism spectrum disorders

Inflammatory profile of vertically HIV-1 infected adolescents receiving ART in Cameroon: a contribution toward optimal pediatric HIV control strategies

Antiretroviral therapy (ART) has improved the lifespan of people living with HIV. However, their immune system remains in a state of sustained activation/inflammation, which favors viral replication and depletion of helper T-cells with varying profiles according to ART-response. We herein sought to ascertain the inflammatory profile of adolescents living with perinatal HIV-1 infection (ALPHI) receiving ART in an African context. In this cross-sectional and comparative study among ART-experienced ALPHI in Yaoundé-Cameroon, HIV-1 RNA was measured by Abbott Real-time PCR; CD4 cells were enumerated using flow cytometry; serum cytokines were measured by ELISA; HIV-1 proviral DNA was genotyped by Sanger-sequencing; and archived drug resistance mutations (ADRMs) were interpreted using Stanford HIVdb.v9.0.1. Overall, 73 adolescents were enrolled (60 ALPHI and 13 HIV-1 negative peers) aged 15 (13-18) years; 60.00% were female. ART median duration was 92 (46-123) months; median viral load was 3.99 (3.17-4.66) RNA Log10 (copies)/mL and median CD4 count was 326 (201-654) cells/mm3. As compared to HIV-negative adolescents, TNFα was highly expressed among ALPHI (p&lt;0.01). Following a virological response, inflammatory cytokines (IFNγ and IL-12), anti-inflammatory cytokines (IL-4 and IL-10) and inflammation-related cytokines (IL-6 and IL-1β) were highly expressed with viral suppression (VS) vs. virological failure (VF), while the chemokine CCL3 was highly expressed with VF (p&lt;0.01). Regarding the immune response, the inflammatory cytokine TNFα was highly expressed in those that are immunocompetent (CD4≥500 cell/mm3) vs. immunocompromised (CD4&lt;500 cell/mm3), p ≤ 0.01; while chemokine CCL2 was highly expressed in the immunocompromised (p&lt;0.05). In the presence of ADRMs, IL-4 and CCL3 were highly expressed (p=0.027 and p=0.043 respectively). Among ART-experienced ALPHI in Cameroon, the TNFα cytokine was found to be an inflammatory marker of HIV infection; IFNγ, IL-1β, IL-6, and IL-12 are potential immunological markers of VS and targeting these cytokines in addition to antiretroviral drugs may improve management. Moreover, CCL3 and CCL2 are possible predictors of VF and/or being immunocompromised and could serve as surrogates of poor ART response

Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments.

International audienceSHANK genes code for scaffold proteins located at the post-synaptic density of glutamatergic synapses. In neurons, SHANK2 and SHANK3 have a positive effect on the induction and maturation of dendritic spines, whereas SHANK1 induces the enlargement of spine heads. Mutations in SHANK genes have been associated with autism spectrum disorders (ASD), but their prevalence and clinical relevance remain to be determined. Here, we performed a new screen and a meta-analysis of SHANK copy-number and coding-sequence variants in ASD. Copy-number variants were analyzed in 5,657 patients and 19,163 controls, coding-sequence variants were ascertained in 760 to 2,147 patients and 492 to 1,090 controls (depending on the gene), and, individuals carrying de novo or truncating SHANK mutations underwent an extensive clinical investigation. Copy-number variants and truncating mutations in SHANK genes were present in ∼1% of patients with ASD: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to profound intellectual disability. In summary, mutations of the SHANK genes were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment. Given the rare frequency of SHANK1 and SHANK2 deleterious mutations, the clinical relevance of these genes remains to be ascertained. In contrast, the frequency and the penetrance of SHANK3 mutations in individuals with ASD and intellectual disability-more than 1 in 50-warrant its consideration for mutation screening in clinical practice