Evolution of Salmonella excretion by sows during gestation in link with the faecal microbiome

Pork meat is estimated to be responsible of 10 to 20% of human salmonellosis cases. Control strategies at the farm could reduce contamination at the slaughterhouse. One of the targeted sector of the production is the maternity, where sows could be Salmonella reservoirs. The aim of this study was to characterize the faecal microbiome of sows excreting or not Salmonella during gestation phases. A total of 76 sows were selected and fecal matters were analysed at the beginning or the end of gestation period. Salmonella detection was conducted using a method including two selective enrichment media (MSRV and TBG). Nine (9) isolates per positive samples were collected. Among the 76 sows tested, 31 were shedding Salmonella. The sows in the first third of their gestation shed significantly more frequently Salmonella (22/29) than those in the last third (9/47) (χ² P \u3c 0.05). The shedding status of 19 of the sows that were previously sampled in the first third of their gestation was followed, this time in the last third, confirming reduction of the shedding. Association between changes in the intestinal microbiome and this evolution of Salmonella shedding will be explored. MiSeq sequencing is currently being conducted on the feces to identify shifts in the composition or diversity in the microbial community that could be associated to these variations. A large number of Salmonella isolates that were collected were genotyped by a high resolution melt (HRM) technique. These results showed the presence of a major HRM profile (136 isolates / 169) and two minor profiles (24 and 9 /169)

Comt1 genotype and expression predicts anxiety and nociceptive sensitivity in inbred strains of mice

Catechol-O-methyltransferase (COMT) is an ubiquitously expressed enzyme that maintains basic biologic functions by inactivating catechol substrates. In humans, polymorphic variance at the COMT locus has been associated with modulation of pain sensitivity (Andersen & Skorpen, 2009) and risk for developing psychiatric disorders (Harrison & Tunbridge, 2008). A functional haplotype associated with increased pain sensitivity was shown to result in decreased COMT activity by altering mRNA secondary structure-dependent protein translation (Nackley et al., 2006). However, the exact mechanisms whereby COMT modulates pain sensitivity and behavior remain unclear and can be further studied in animal models. We have assessed Comt1 gene expression levels in multiple brain regions in inbred strains of mice and have discovered that Comt1 is differentially expressed among the strains, and this differential expression is cis-regulated. A B2 Short Interspersed Element (SINE) was inserted in the 3′UTR of Comt1 in 14 strains generating a common haplotype that correlates with gene expression. Experiments using mammalian expression vectors of full-length cDNA clones with and without the SINE element demonstrate that strains with the SINE haplotype (+SINE) have greater Comt1 enzymatic activity. +SINE mice also exhibit behavioral differences in anxiety assays and decreased pain sensitivity. These results suggest that a haplotype, defined by a 3′ UTR B2 SINE element, regulates Comt1 expression and some mouse behaviors

Evolution of Salmonella excretion by sows during gestation in link with the faecal microbiome

Pork meat is estimated to be responsible of 10 to 20% of human salmonellosis cases. Control strategies at the farm could reduce contamination at the slaughterhouse. One of the targeted sector of the production is the maternity, where sows could be Salmonella reservoirs. The aim of this study was to characterize the faecal microbiome of sows excreting or not Salmonella during gestation phases. A total of 76 sows were selected and fecal matters were analysed at the beginning or the end of gestation period. Salmonella detection was conducted using a method including two selective enrichment media (MSRV and TBG). Nine (9) isolates per positive samples were collected. Among the 76 sows tested, 31 were shedding Salmonella. The sows in the first third of their gestation shed significantly more frequently Salmonella (22/29) than those in the last third (9/47) (χ² P < 0.05). The shedding status of 19 of the sows that were previously sampled in the first third of their gestation was followed, this time in the last third, confirming reduction of the shedding. Association between changes in the intestinal microbiome and this evolution of Salmonella shedding will be explored. MiSeq sequencing is currently being conducted on the feces to identify shifts in the composition or diversity in the microbial community that could be associated to these variations. A large number of Salmonella isolates that were collected were genotyped by a high resolution melt (HRM) technique. These results showed the presence of a major HRM profile (136 isolates / 169) and two minor profiles (24 and 9 /169).</p

Vorapaxar in the secondary prevention of atherothrombotic events

Item does not contain fulltextBACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. RESULTS: At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). CONCLUSIONS: Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.)