Molecular Detection of Multiple Emerging Pathogens in Sputa from Cystic Fibrosis Patients

Background: There is strong evidence that culture-based methods detect only a small proportion of bacteria present in the respiratory tracts of cystic fibrosis (CF) patients. Methodology/Principal Findings: Standard microbiological culture and phenotypic identification of bacteria in sputa from CF patients have been compared to molecular methods by the use of 16S rDNA amplification, cloning and sequencing. Twenty-five sputa from CF patients were cultured that yield 33 isolates (13 species) known to be pathogens during CF. For molecular cloning, 760 clones were sequenced (7.263.9 species/sputum), and 53 different bacterial species were identified including 16 species of anaerobes (30%). Discrepancies between culture and molecular data were numerous and demonstrate that accurate identification remains challenging. New or emerging bacteria not or rarely reported in CF patients were detected including Dolosigranulum pigrum, Dialister pneumosintes, and Inquilinus limosus. Conclusions/Significance: Our results demonstrate the complex microbial community in sputa from CF patients, especially anaerobic bacteria that are probably an underestimated cause of CF lung pathology. Metagenomic analysis is urgentl

Rapport de synthèse

Lien familial, lien obligationnel, lien social. Journée prometteuse, nous disait, in limine, le Doyen Orsoni. Journée qui tint ses promesses et nous permit de jeter un nouvel éclairage sur ce thème. Sous un tour parfaitement technique, il ne sera discuté par personne, et cela ne l’a pas été aujourd’hui, que le lien entre les liens existe naturellement et inéluctablement. Lien entre le lien familial et le lien social. Certes, quant à lui, les philosophes se disputent. Madame Patricia Signorilé..

El contrato: acto de previsión

Como contrapeso a una visión cada vez más objetiva de la disciplina contractual, el análisis de la noción de contrato como acto de previsión permite confirmar el papel de primacía de la autonomía de la voluntad. Tomada la previsión en el momento de ser concebida por las partes, su análisis permite, de acuerdo con la naturaleza del contrato, reforzar la distinción entre el efecto del contrato y el efecto de la obligación y, al mismo tiempo, comprender la dicotomía Existente o aparente entre formación y ejecución del contrato y ejecución e incumplimiento del mismo, así como su incidencia en la concepción misma de la responsabilidad contractual, al servir como instrumento en la determinación de la noción de fuerza obligatoria del contrato. De igual forma, haciendo una proyección hacia el futuro para determinar la suerte de las previsiones contractuales, la explotación de su concepto permite depurar la noción y utilidad de la teoría de la imprevisión, que en el Derecho Civil francés no ha encontrado aún asidero y cuyo papel ha sido sustituido sea por la doctrina, sea por la jurisprudencia, haciendo uso del principio de buena fe y de la teoría de la causa, aunque de forma parcial y no de manera indiscutida

La modificación unilateral del contrato

¿Puede haber modificación unilateral del contrato en el Derecho Francés? Debido a la creciente influencia del unilateralismo en el derecho contractual francés, se analiza la manera en que dicho fenómeno, visto exclusivamente en su rol de modificación, se conjuga, choca, interactúa con la visión actual o actualizada de la fuerza obligatoria o de la buena fe, lo que guarda finalmente una íntima relación con la manera como pretende ser aprehendido el contrato. En efecto, partiendo de la definición de modificación unilateral, este ensayo busca demostrar que los grados de unilateralismo pueden ser variables tanto en la iniciativa como en la decisión de modificación, grados que serán aceptados o tolerados por el ordenamiento jurídico dependiendo de su influencia en el processus

Infection d'ascite à Escherichia coli (étude des facteurs bactériens et des facteurs de l'hôte)

PARIS-BIUP (751062107) / SudocSudocFranceF

Interaction de Neisseria meningitidis avec les cellules de l hôte : mécanismes de franchissement des barrières oropharyngée et hémato-encéphalique.

PARIS5-BU Méd.Cochin (751142101) / SudocSudocFranceF

Preclinical Models for Acquired Resistance to Third-Generation EGFR Inhibitors in NSCLC: Functional Studies and Drug Combinations Used to Overcome Resistance

International audienceEpidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are currently recommended as first-line treatment for advanced non-small-cell lung cancer (NSCLC) with EGFR-activating mutations. Third-generation (3rd G) EGFR-TKIs, including osimertinib, offer an effective treatment option for patients with NSCLC resistant 1st and 2nd EGFR-TKIs. However, the efficacy of 3rd G EGFR-TKIs is limited by acquired resistance that has become a growing clinical challenge. Several clinical and preclinical studies are being carried out to better understand the mechanisms of resistance to 3rd G EGFR-TKIs and have revealed various genetic aberrations associated with molecular heterogeneity of cancer cells. Studies focusing on epigenetic events are limited despite several indications of their involvement in the development of resistance. Preclinical models, established in most cases in a similar manner, have shown different prevalence of resistance mechanisms from clinical samples. Clinically identified mechanisms include EGFR mutations that were not identified in preclinical models. Thus, NRAS genetic alterations were not observed in patients but have been described in cell lines resistant to 3rd G EGFR-TKI. Mainly, resistance to 3rd G EGFR-TKI in preclinical models is related to the activation of alternative signaling pathways through tyrosine kinase receptor (TKR) activation or to histological and phenotypic transformations. Yet, preclinical models have provided some insight into the complex network between dominant drivers and associated events that lead to the emergence of resistance and consequently have identified new therapeutic targets. This review provides an overview of preclinical studies developed to investigate the mechanisms of acquired resistance to 3rd G EGFR-TKIs, including osimertinib and rociletinib, across all lines of therapy. In fact, some of the models described were first generated to be resistant to first- and second-generation EGFR-TKIs and often carried the T790M mutation, while others had never been exposed to TKIs. The review further describes the therapeutic opportunities to overcome resistance, based on preclinical studies

Carbapenem-Hydrolyzing GES-Type Extended-Spectrum β-Lactamase in Acinetobacter baumannii ▿

Acinetobacter baumannii isolate AP was recovered from a bronchial lavage of a patient hospitalized in Paris, France. A. baumannii AP was resistant to all β-lactams, including carbapenems, and produced the extended-spectrum β-lactamase (ESBL) GES-14, which differs from GES-1 by two substitutions, Gly170Ser and Gly243Ala. Cloning of the blaGES-14 gene followed by its expression in Escherichia coli showed that GES-14 compromised significantly the efficacy of all β-lactams, including cephalosporins, aztreonam, and carbapenems. The carbapenemase activity of purified GES-14 was confirmed by kinetic studies. The blaGES-14 gene was located into a class 1 integron structure and located onto a ca. 95-kb self-transferable plasmid. This study identified a very broad-spectrum β-lactamase in A. baumannii