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Antivirulence strategies targeting bacterial behavior, such as adhesion and biofilm formation, are expected to exert low selective pressure and have been proposed as alternatives to biocidal antibiotic treatments to avoid the rapid occurrence of bacterial resistance. Here, we tested this hypothesis using group 2 capsule polysaccharide (G2cps), a polysaccharidic molecule previously shown to impair bacterium-surface interactions, and we investigated the nature of bacterial resistance to a nonbiocidal antibiofilm strategy. We screened an Escherichia coli mutant library for an increased ability to form biofilm in the presence of G2cps, and we identified several mutants displaying partial but not total resistance to this antibiofilm polysaccharide. Our genetic analysis showed that partial resistance to G2cps results from multiple unrelated mutations leading to modifications in surface physicochemical properties that counteract the changes in ionic charge and Lewis base properties induced by G2cps. Moreover, some of the identified mutants harboring improved biofilm formation in the presence of G2cps were also partially resistant to other antibiofilm molecules. This study therefore shows that alterations of bacterial surface properties mediate only partial resistance to G2cps. It also experimentally validates the potential value of nonbiocidal antibiofilm strategies, since full resistance to antibiofilm compounds is rare and potentially unlikely to arise in clinical settings.  相似文献   
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Objectives

This study sought to describe the current practices and compare outcomes according to the use of balloon aortic valvuloplasty (BAV) or not during transcatheter aortic valve replacement (TAVR).

Background

Since its development, aortic valve pre-dilatation has been an essential step of TAVR procedures. However, the feasibility of TAVR without systematic BAV has been described.

Methods

TAVR performed in 48 centers across France between January 2013 and December 2015 were prospectively included in the FRANCE TAVI (Registry of Aortic Valve Bioprostheses Established by Catheter) registry. We compared outcomes according to BAV during the TAVR procedure.

Results

A total of 5,784 patients have been included in our analysis, corresponding to 2,579 (44.6%) with BAV avoidance and 3,205 (55.4%) patients with BAV performed. We observed a progressive decline in the use of BAV over time (78% of procedures in 2013 and 49% in the last trimester of 2015). Avoidance of BAV was associated with similar device implantation success (97.3% vs. 97.6%; p = 0.40). TAVR procedures without BAV were quicker (fluoroscopy 17.2 ± 9.1 vs. 18.5 ± 8.8 min; p < 0.01) and used lower amounts of contrast (131.5 ± 61.6 vs. 141.6 ± 61.5; p < 0.01) and radiation (608.9 ± 576.3 vs. 667.0 ± 631.3; p < 0.01). The rates of moderate to severe aortic regurgitation were lower with avoidance of BAV (8.3% vs. 12.2%; p < 0.01) and tamponade rates (1.5% vs. 2.3%; p = 0.04).

Conclusions

We confirmed that TAVR without BAV is frequently performed in France with good procedural results. This procedure is associated with procedural simplification and lower rates of residual aortic regurgitation.  相似文献   
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Objective: To investigate the risk of cancer among veterinarians in a large record-linkage study from Sweden. Methods: We used the nationwide, Swedish Cancer Environment Registry III, which links the Cancer Register data for 1971–1989 to the national population censuses from 1960 and 1970, to compare the incidence of cancer among male veterinarians to that of the remaining part of the active population using multivariable Poisson regression models and standardized incidence ratios. One thousand one hundred and seventy eight men classified as veterinarians or workers in the veterinary industry at either census were identified. Results: Veterinarians in the veterinary industry experienced increased risk of esophageal (relative risk (RR) 3.78, 95% confidence interval (CI) 1.42–10.09), colon (RR: 2.36, 95% CI: 1.42–3.91), pancreatic (RR: 2.10, 95% CI: 0.94–4.68) and brain (RR: 2.51, 95% CI: 1.04–6.03) cancers as well as melanoma of the skin (RR: 2.77, 95% CI: 1.24–6.17). Similar excess risks were observed when veterinarians were compared with individuals of similar socio-economic status. Conclusion: The increased risks of esophageal, colon, pancreatic and brain cancers as well as melanoma observed among veterinarians did not seem to be explained by the high socio-economic status of this occupational group. Therefore, it is possible that some of these results reflect the carcinogenicity of occupational exposures, including animal viruses, solar or ionizing radiations and anesthetics.  相似文献   
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Thrombin Activatable Fibrinolytic Inhibitor (TAFI) is a plasma protein, which inhibits fibrinolysis by removing carboxyterminal lysine residues from partially degraded fibrin thereby decreasing plasminogen binding on its surface. In this study we have investigated the antigenic level variability (Inter and Intraindividual) of Thrombin Activatable Fibrinolysis Inhibitor in 120 healthy Asian Indians since no data on this is available regarding this population. TAFI antigen levels did not show a normal distribution in our population (p<0.001). Median TAFI antigen levels were found to be 11.683 microg/ml. It ranged from 33.9-202.5%of normal pool plasma (3.9-23.5 microg/ml). TAFI antigenic level showed high level of variability in the Indian population (coefficient of variation: 37.4%). TAFI antigenic levels were stable intraindividually (p=0.218).  相似文献   
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