BRAF mutational status as a prognostic marker for survival in malignant melanoma: a systematic review and meta-analysis.

Background: The analysis of the BRAF mutational status has been established as a standard procedure during diagnosis of advanced malignant melanoma due to the fact that BRAF inhibitors constitute a cornerstone in the treatment of metastatic disease. However, the general impact of BRAF mutational status on survival remains unclear. Our study aimed to assess the underlying prognostic significance of BRAF mutant versus wild type (WT) malignant melanoma on overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS).Material and methods: A systematic literature search in EMBASE, Medline and Cochrane CENTRAL was performed. Studies were included if they reported survival outcomes for BRAF mutant versus WT patients as hazard ratios (HR) or in Kaplan-Meier (KM) curves. Random-effects meta-analysis models were used to pool HRs across the studies.Results: Data from 52 studies, representing 7519 patients, were pooled for analysis of OS. The presence of a BRAF mutation was statistically significantly associated with a reduced OS (HR [95% confidence interval (CI)]: 1.23 [1.09-1.38]), however, with substantial heterogeneity between the studies (I2: 58.0%). Meta-regression and sensitivity analyses showed that age, sex and BRAF mutation testing method did not have a significant effect on the OS HR. BRAF mutant melanoma showed comparable effect on DFS to non-BRAF mutant melanoma in stage I-III melanoma (combined HR: 1.16, 95% CI: 0.92-1.46), and on PFS in stage III-IV (HR: 0.98 (95% CI: 0.68-1.40)).Conclusion: Although there was substantial heterogeneity between the studies, the overall results demonstrated a poorer prognosis and OS in patients harbouring BRAF mutations. Future studies should take this into account when evaluating epidemiological data and treatment effects of new interventions in patients with malignant melanoma.

Blood libel rebooted: traditional scapegoats, online media, and the H1N1 epidemic.

This study of comments posted on major French print and TV media websites during the H1N1 epidemic illustrates the relationship between the traditional media and social media in responding to an emerging disease. A disturbing "geography of blame" was observed suggesting the metamorphosis of the folk-devil phenomenon to the Internet. We discovered a subterranean discourse about the putative origins and "objectives" of the H1N1 virus, which was absent from the discussions in mainstream television channels and large-circulation print media. These online rumours attributed hidden motives to governments, pharmaceutical companies, and figures of Otherness that were scapegoated in the social history of previous European epidemics, notably Freemasons and Jews.

Activity of ethanol and daptomycin lock on biofilm generated by an in vitro dynamic model using real subcutaneous injection ports.

Vancomycin lock solution (LS) is recommended for the conservative treatment of subcutaneous injection port (SIP)-related infections, but may be associated with failure. We used an in vitro dynamic model of biofilm formation in an SIP, based on a continuous flow circulating via a real SIP, to assess the effectiveness of vancomycin (5 mg/ml), daptomycin (5 mg/ml) and ethanol 40 % LS in eradicating a pre-established Staphylococcus epidermidis biofilm. Heparin, Ringer's lactate and enoxaparin sodium LS were used as controls. The logarithmic reductions of colony-forming units (CFU) were compared by Student's t-test. After 24 h of exposure, the vancomycin LS did not exert a greater bactericidal effect than the heparin LS control (mean logarithmic reduction: 2.27 ± 0.58 vs. 1.34 ± 0.22, respectively, p = 0.3). The mean logarithmic reduction was greater with daptomycin LS (5.45 ± 0.14 vs. 0.39 ± 0.12, p < 0.01) and ethanol LS (6.79 ± 1.03 vs. 1.43 ± 0.54, p = 0.02). Bacterial revival after exposure to 24 h of LS was assessed. The mean viable bacteria count was significantly higher for vancomycin LS (9.36 ± 0.10 log(10)CFU) and daptomycin LS (9.16 ± 0.02 log(10)CFU) than for ethanol LS (2.95 ± 1.65 log(10)CFU). Ethanol appeared to be the most attractive option to treat SIP-related infection, but its poor ability to entirely disrupt the biofilm structure may require its use in association with a dispersal agent to avoid renewal of the biofilm.

Microbial transfers from permanent grassland ecosystems to milk in dairy farms in the Comté cheese area.

The specificity of dairy Protected Designation of Origin (PDO) products is related to their "terroir" of production. This relationship needs better understanding for efficient and sustainable productions preserving the agroecological equilibrium of agroecosystems, especially grasslands. Specificity of PDO Comté cheese was related to the diversity of natural raw milk bacterial communities, but their sources need to be determined. It is hypothesized that raw milk indigenous microbial communities may originate from permanent grazed grasslands by the intermediate of dairy cows according to the sequence soil-phyllosphere-teat-milk. This hypothesis was evaluated on a 44 dairy farms network across PDO Comté cheese area by characterizing prokaryotic and fungal communities of these compartments by metabarcoding analysis (16S rRNA gene: V3-V4 region, 18S rRNA gene: V7-V8 region). Strong and significant links were highlighted between the four compartments through a network analysis (0.34 < r < 0.58), and were modulated by soil pH, plant diversity and elevation; but also by farming practices: organic fertilization levels, cattle intensity and cow-teat care. This causal relationship suggests that microbial diversity of agroecosystems is a key player in relating a PDO product to its "terroir"; this under the dependency of farming practices. Altogether, this makes the "terroir" even more local and needs to be considered for production sustainability.

Genital mycoplasmas in patients with acquired immunodeficiency syndrome.

To determine whether Mycoplasma fermentans. Mycoplasma genitalium and Mycoplasma penetrans were present in the genitourinary tract of HIV infected patients in Nancy, France, we have used culture and polymerase chain reactions on urine from 54 HIV-infected patients. Both techniques failed to reveal these bacteria. This renders their presence very unlikely in our population.

[Clinical examination and complimentary investigations of the anus]. / Examen clinique et explorations complémentaires de l'anus.

Precise history-taking and a complete clinical examination including all the components of the perineum guide diagnosis in anorectal disorders and most often indicate treatment. Ancillary investigations are sometimes needed for more precise diagnosis or to complete pretreatment workup. Such additional investigations should always be discussed, indicated and interpreted in view of the clinical examination.

Preliminary characterization of microflora of Comté cheese.

The evolution of the microflora of three Comté cheeses made in duplicate with raw milk from three different sources was followed during ripening. The same starter was used with each type of milk. The comparison of the cheeses did not reveal any significant difference in the development of the microflora. Starter lactic acid bacteria (Streptococcus thermophilus and Lactobacillus helveticus), which are added at the beginning of manufacture, decreased quickly in the first stages of ripening supporting the hypothesis of cell autolysis. Other microorganisms, i.e. homofermentative and heterofermentative lactobacilli (Lact. delbrueckii ssp. lactis, Lact. paracasei ssp. paracasei, Lact. rhamnosus and Lact. fermentum), pediococci, enterococci and propionibacteria grew in cheese from small numbers in fresh curd. The characterization of Strep. thermophilus by pulsed-field gel electrophoresis showed that wild strains were also able to grow in the curd. The values for the genome size of 11 Strep. thermophilus strains determined in this investigation were in the range of 1.8-2.3 Mbp. The potential role of starter and raw milk microflora in cheese flavour development was considered.