In vivo importance of homologous recombination DNA repair for mouse neural stem and progenitor cells

We characterized the in vivo importance of the homologous recombination factor RAD54 for the developing mouse brain cortex in normal conditions or after ionizing radiation exposure. Contrary to numerous homologous recombination genes, Rad54 disruption did not impact the cortical development without exogenous stress, but it dramatically

High Content Screening Identifies Decaprenyl-Phosphoribose 2′ Epimerase as a Target for Intracellular Antimycobacterial Inhibitors

A critical feature of Mycobacterium tuberculosis, the causative agent of human tuberculosis (TB), is its ability to survive and multiply within macrophages, making these host cells an ideal niche for persisting microbes. Killing the intracellular tubercle bacilli is a key requirement for efficient tuberculosis treatment, yet identifying potent inhibitors has been hampered by labor-intensive techniques and lack of validated targets. Here, we present the development of a phenotypic cell-based assay that uses automated confocal fluorescence microscopy for high throughput screening of chemicals that interfere with the replication of M. tuberculosis within macrophages. Screening a library of 57,000 small molecules led to the identification of 135 active compounds with potent intracellular anti-mycobacterial efficacy and no host cell toxicity. Among these, the dinitrobenzamide derivatives (DNB) showed high activity against M. tuberculosis, including extensively drug resistant (XDR) strains. More importantly, we demonstrate that incubation of M. tuberculosis with DNB inhibited the formation of both lipoarabinomannan and arabinogalactan, attributable to the inhibition of decaprenyl-phospho-arabinose synthesis catalyzed by the decaprenyl-phosphoribose 2′ epimerase DprE1/DprE2. Inhibition of this new target will likely contribute to new therapeutic solutions against emerging XDR-TB. Beyond validating the high throughput/content screening approach, our results open new avenues for finding the next generation of antimicrobials

Safety Concern between Autologous Fat Graft, Mesenchymal Stem Cell and Osteosarcoma Recurrence

Background: Osteosarcoma is the most common malignant primary bone tumour in young adult treated by neo adjuvant chemotherapy, surgical tumor removal and adjuvant multidrug chemotherapy. For correction of soft tissue defect consecutive to surgery and/or tumor treatment, autologous fat graft has been proposed in plastic and reconstructive surgery. Principal Findings: We report here a case of a late local recurrence of osteosarcoma which occurred 13 years after the initial pathology and 18 months after a lipofilling procedure. Because such recurrence was highly unexpected, we investigated the possible relationship of tumor growth with fat injections and with mesenchymal stem/stromal cell like cells which are largely found in fatty tissue. Results obtained in osteosarcoma pre-clinical models show that fat grafts or progenitor cells promoted tumor growth. Significance: These observations and results raise the question of whether autologous fat grafting is a safe reconstructive procedure in a known post neoplasic context

Intraoperative optical imaging for neurosurgery guidance

International audienc

Intraoperative optical imaging for neurosurgery guidance

International audienc

Intraoperative optical imaging for neurosurgery guidance

International audienc

Prise en charge de la toxoplasmose oculaire en France : résultats d’une étude Delphi modifiée

International audienceOBJECTIVE: To evaluate diagnostic and therapeutic practices and then establish a consensus on the management of ocular toxoplasmosis in France through a Delphi study. MATERIALS AND METHODS: Twenty-three French experts in ocular toxoplasmosis were invited to respond to a modified Delphi study conducted online, in the form of two questionnaires, in an attempt to establish a consensus on the diagnosis and management of this pathology. The threshold for identical responses to reach consensus was set at 70 %. RESULTS: The responses of 19 experts out of the 23 selected were obtained on the first questionnaire and 16 experts on the second. The main elements agreed upon by the experts were to treat patients with a decrease in visual acuity or an infectious focus within the posterior pole, to treat peripheral lesions only in the presence of significant inflammation, the prescription of first-line treatment with pyrimethamine-azithromycin, the use of corticosteroid therapy after a period of 24 to 48hours, the prophylaxis of frequent recurrences (more than 2 episodes per year) with trimethoprim-sulfamethoxazole as well as the implementation of prophylactic treatment of recurrences in immunocompromised patients. On the other hand, no consensus emerged with regard to the examinations to be carried out for the etiological diagnosis (anterior chamber paracentesis, fluorescein angiography, serology, etc.), second-line treatment (in the case of failure of first-line treatment), or treatment of peripheral foci. CONCLUSION: This study lays the foundations for possible randomized scientific studies to be conducted to clarify the management of ocular toxoplasmosis, on the one hand to confirm consensual clinical practices and on the other hand to guide practices for which no formal consensus has been demonstrated.RésuméObjectifÉvaluer les pratiques diagnostiques et thérapeutiques puis établir un consensus sur la prise en charge de la toxoplasmose oculaire en France grâce à une étude Delphi.MéthodesVingt-trois experts français de la toxoplasmose oculaire ont été invités à répondre à une étude Delphi modifiée menée en ligne, sous forme de deux questionnaires, afin de tenter d’établir un consensus sur le diagnostic et la prise en charge de cette pathologie. Le seuil de réponses identiques pour aboutir à un consensus a été fixé à 70 %.RésultatsLes réponses de 19 experts sur les 23 sélectionnés ont été obtenues au premier questionnaire et de 16 experts au second. Les principaux éléments qui font consensus auprès des experts sont de traiter les patients avec une baisse d’acuité visuelle ou un foyer infectieux au pôle postérieur, l’instauration d’un traitement face à un foyer périphérique seulement en cas d’inflammation importante, la prescription d’un traitement de première intention par l’association pyriméthamine–azithromycine, l’utilisation d’un traitement par corticostéroïdes après un délai de 24 à 48 h, la prophylaxie des récidives fréquentes (plus de 2 épisodes par an) par triméthoprime-sulfaméthoxazole ainsi que la mise en place d’un traitement prophylactique des récidives chez les patients immunodéprimés. En revanche, aucun consensus ne se dégage pour les examens à réaliser pour le diagnostic étiologique (ponction de chambre antérieure, angiographie à la fluorescéine, sérologie…), pour les traitements de seconde intention (en cas d’échec du traitement de première ligne) ni pour le traitement des foyers périphériques.ConclusionLa présente étude pose les bases d’éventuelles études scientifiques randomisées à mener afin de clarifier les prises en charge la toxoplasmose oculaire, d’une part pour confirmer les habitudes cliniques qui font consensus, d’autre part pour guider les pratiques pour lesquelles aucun consensus formel n’est mis en évidence