Medulloblastomas with ELP1 pathogenic variants: A weakly penetrant syndrome with a restricted spectrum in a limited age window

Background: ELP1 pathogenic variants (PV) have been recently identified as the most frequent variants predisposing to Sonic Hedgehog (SHH) medulloblastomas (MB); however, guidelines are still lacking for genetic counseling in this new syndrome. Methods: We retrospectively reviewed clinical and genetic data of a French series of 29 ELP1-mutated MB. Results: All patients developed SHH-MB, with a biallelic inactivation of PTCH1 found in 24 tumors. Other recurrent alterations encompassed the TP53 pathway and activation of MYCN/MYCL signaling. The median age at diagnosis was 7.3 years (range: 3-14). ELP1-mutated MB behave as sporadic cases, with similar distribution within clinical and molecular risk groups and similar outcomes (5 y - OS=86%); no unusual side effect of treatments was noticed. Remarkably, a germline ELP1 PV was identified in all patients with available constitutional DNA (n=26); moreover, all tested familial trio (n=11) revealed that the PVs were inherited. Two of the 26 index cases from the French series had a family history of MB; pedigrees from these patients and from 1 additional Dutch family suggested a weak penetrance. Apart from MB, no cancer was associated with ELP1 PVs; second tumors reported in 4 patients occurred within the irradiation fields, in the usual time-lapse for expected radiotherapy-induced neoplasms. Conclusions: The low penetrance, the "at risk' age window limited to childhood and the narrow tumor spectrum, question the actual benefit of genetic screening in these patients and their family. Our results suggest restricting ELP1 germline sequencing to patients with SHH-MB, depending on the parents"request

La maladie pieds-mains-bouche, de l'épidémie asiatique au développement d'un arsenal thérapeutique innovant en Chine

AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocSudocFranceF

Evaluation du test "Hyplex Staphylo Resist" par comparaison avec des méthodes classiques d'identification du genre Staphylococcus

AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocSudocFranceF

Recherche et caractérisation de nouveaux microorganismes intracellulaires d'amibes dans l'environnement

Les amibes sont des protozoaires unicellulaires représentés de manière ubiquitaire dans l environnement. Plusieurs études ont déjà montré que certains microorganismes, bactéries ou virus, ont la capacité d entrer dans les amibes et de s y multiplier au lieu d y être digérés. Ces microorganismes, qui échappent aux mécanismes de phagocytose, sont par analogie entre l amibe et le macrophage, des pathogènes humains potentiels. Le plus connu et le plus étudié d entre eux est Legionella pneumophila dont la relation étroite avec les amibes a été montrée comme étant un facteur augmentant la pathogénicité de la bactérie, mais aussi le risque de prolifération et de contamination. D autres types de microorganismes ont également été isolés dans l eau, et ont montré la même capacité à se multiplier dans les amibes. Afin d isoler de manière spécifique les microorganismes ayant cette propriété, des méthodes de co-culture sur amibes ont été mises au point. Il s agit d inoculer des échantillons d eau sur des cultures cellulaires pures d amibes axénisées. Ainsi, les bactéries capables de résister aux mécanismes de la phagocytose par les amibes peuvent être isolées, les autres sont digérées par le protozoaire. Cette technique a déjà permis d isoler de nombreux types de microorganismes différents, dans différents types d eau, principalement des réseaux d eau potable. Dans cette étude, nous avons dans un premier temps recherché, au moyen de cette technique de co-culture, de nouveaux microorganismes associés aux amibes dans des eaux de l environnement humain (puits, cours d eau, lacs, fontaines ). En effet, la co-culture est un bon outil permettant de sélectionner de nouvelles espèces bactériennes qui ne sont pas capables de se multiplier en dehors des amibes. Nous avons ainsi pu isoler plusieurs nouvelles espèces de bactéries. Dans un deuxième temps, nous nous sommes plus précisément intéressés au milieu très particulier des tours aéro-réfrigérantes. En effet, dans l environnement, très peu de Légionelles ont pu être trouvées, alors qu elles se multiplient facilement dans ce type d installations. Nous avons donc cherché, toujours au moyen de co-cultures, à isoler de nouveaux microorganismes intracellulaires d amibes dans ce milieu favorisant la prolifération de bactéries et de virus qui se retrouvent plus rarement dans la nature. Nous avons ainsi pu isoler de nouveaux genres et de nouvelles espèces 4 de microorganismes : un virus géant et un virophage (Mamavirus et Sputnik), une nouvelle espèce de virus géant (Marseille virus), un nouveau genre de bactérie intracellulaire stricte (Candidatus Babela massiliensis gen. nov., sp. nov.) et un nouveau genre de bactérie intracellulaire facultative (Reyranella massiliensis gen. nov., sp. nov.). Par ailleurs, dans plusieurs installations, nous avons constaté la présence de nombreuses Mycobacterium sp., dont certaines sont des pathogènes humains déjà reconnus. Ces résultats suggèrent que le risque microbiologique associé aux tours aéro-réfrigérantes ne se limite pas au risque Légionelles , et soulève le problème des autres microorganismes potentiellement pathogènes qui se multiplient également de manière préférentielle dans ce type d installation. Par ailleurs, la grande variété des microorganismes retrouvés au moyen des amibes montre que ces dernières peuvent être un important carrefour de rencontre de différents types de microorganismes, et le lieu d échanges génétiques pouvant aboutir à la création de nouvelles espèces, notamment de virus géants.Free living amoeba are ubiquitous and have been isolated worldwild in the environment. Several studies showed that many microorganisms, bacteria or viruses, are able to enter the amoeba and multiply within the cell. Those kind of microorganisms are potentially human pathogens, as they may act the same way in human macrophages. The most studied is Legionella pneumophila. It s tight relationship to amoeba was demonstrated as a factor of pathogenicity, proliferation and dissemination of the bacteria. After, other types of microorganisms were isolated in water and had the same property. In order to isolate those amoeba-resisting microorganisms, co-culture methods were done. Water samples are inoculated onto an amoebal axenic monolayer. We can by this way specifically isolate the microorganisms that are able to resist amoebal phagocytosis, and the other are digested by the amoeba. This method already allowed isolating several new species of microorganisms, principally in potable water. Our study focuses first on the research of new amoeba-associated microorganisms in environmental water, and allowed us to isolate several new species of bacteria. However, almost no Legionnella were found. In a second part, we focused specifically on cooling-towers, which represent a favorable middle for Legionella sp. proliferation. We looked specifically for new species of microorganisms, bacteria or virus, which could multiply the same way in this kind of installations. During this study, we could isolate several new microorganisms: a new giant virus Mamavirus and a virophage Sputnik; a new giant virus Marseille virus; a new strictly intracellular bacteria, Candidatus Babela massiliensis gen. nov., sp. nov.; and a new facultative intracellular bacteria, Reyranella massiliensis gen. nov., sp. nov. Our results confirm first that co-culture with amoeba is a very good tool to isolate new genus and new species of bacteria, which cannot be isolated with classical methods. Second, they highlight the problem of the microbiological development in cooling towers. Indeed, control is principally focused on the level of Legionella sp., while many other pathogens can be found in these installations. Moreover, many different types of microorganisms could be isolated, using amoebas. It suggests that amoeba, naturally present world wild, can be a natural crossroad for meetings between several microorganisms, and can be the center of genetic exchanges that could lead to the creation of new microorganisms, principally giant viruses.AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

La dépression post-partum et ses conséquences chez le nourrisson et le jeune enfant (à partir d'une expérience de médecine générale)

La dépression du post-partum concerne 10 à 20% des jeunes mères. Seule une faible proportion est diagnostiquée et traitée de façon pertinente. Nombreuses sont les mères qui ne consultent pas directement pour leur mal-être et qui viennent en consultation de façon détournée. Les divers motifs de consultations pour nourrissons s avèrent très souvent être des signaux d alarmes, que nous, médecins de soins primaires en particulier, devons saisir. C est en ce sens que l impact de la dépression postnatale sur l enfant et le nourrisson en particulier, mérite d être étudiée. Tous les auteurs s accordent à dire qu il existe des effets de cette dépression sur le développement cognitif, comportemental, émotionnel mais aussi psychosomatique de l enfant. Il ne faut cependant pas considérer l impact de la dépression du post-partum comme un déterminisme simple et linéaire mais l approcher en termes de facteur de risque. Un nouveau concept mérite alors de naître : celui de trouble de la relation mère/enfant.The post-partum depression concerns 10-20 % of the young mothers. Only a small fraction of these is diagnosed and treated appropriately. Many mothers do not seek direct consultation for their malaise but may do so indirectly. We as primary care doctors must be attentive to signals of alarms which can often be read from the various motives of consultations for new-born babies. It is in this sense that the impact of postnatal depression on the child and the new-born baby in particular is worth studying. All authors agree on the fact that this depression may have consequences on the cognitive, behavioural and emotional development as well as on the psychosomatics of the child. The impact of a post-partum depression on the child should not be considered in terms of a simple and linear determinism but should be viewed instead as a risk factor. Further, a new concept needs to be defined: that of the mother/child bonding disorder.GRENOBLE1-BU Médecine pharm. (385162101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Potentially pathogenic amoeba-associated microorganisms in cooling towers and their control

Cooling towers provide a favorable environment for the proliferation of microorganisms. Cooling towers generate a biofilm and often aerosolize contaminated water, thereby increasing the risk of microorganism dissemination by human inhalation. This pathogen dissemination was first revealed by the epidemics of Legionnaires’ disease that were directly related to the presence of cooling towers, and since then, the ecology of Legionella pneumophila has been well studied. Each country has specific standards regarding the acceptable amount of microorganisms in cooling tower systems. However, those standards typically only concern L. pneumophila, even though many other microorganisms can also be isolated from cooling towers, including protozoa, bacteria and viruses. Microbiological control of the cooling tower system can be principally achieved by chemical treatments and also by improving the system’s construction. Several new treatments are being studied to improve the efficiency of disinfection. However, as most of these treatments continue to focus solely on L. pneumophila, reports of other types of pathogens continue to increase. Therefore, how their dissemination affects the human populous health should be addressed now. </jats:p

Alcohol Disinfection Procedure for Isolating Giant Viruses from Contaminated Samples

&lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; Giant viruses of the Megavirales order have been neglected in the literature because they are removed from samples during viral purification for viral metagenomic studies. Isolation via amoeba coculture has low efficiency and is extremely time-consuming. Thus, our objective was to improve Megavirales detection and recovery by using a new protocol that will eliminate most bacteria present in environmental samples while preserving giant virus viability. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; In this study, we tested the ability of a number of disinfection protocols to kill contaminating bacteria. These treatments were ethanol, UV irradiation, desiccation, glutaraldehyde and thermal shock. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Of all the treatments, a brief ethanol treatment did not significantly reduce the titer of viable viral particles of &lt;i&gt;Acanthamoeba polyphaga mimivirus &lt;/i&gt;or&lt;i&gt; Marseillevirus&lt;/i&gt;, whereas it efficiently killed &lt;i&gt;Escherichia coli&lt;/i&gt;. This treatment was applied to environmental samples that previously tested positive for giant viruses and was shown to eliminate contaminating bacteria, whereas it allowed for the isolation of the giant viruses. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Our results demonstrate that ethanol treatment can be used to evaluate large collections of environmental samples for the presence of giant viruses and to provide insight into understanding their ecology. This study should also facilitate the isolation of giant viruses using other species of protozoa in addition to &lt;i&gt;Acanthamoeba &lt;/i&gt;spp.</jats:p