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With the emergence of antimicrobial resistance (AMR), many countries are implementing restrictive regulations to reduce antimicrobial use (AMU) in animal production. Although these measures are effective at the national level, their implementation may generate challenges for producers and veterinarians. The objective of this study was to explore the barriers and facilitators of implementing a new regulation restricting the use of antimicrobials of very high importance for human health in the dairy production sector in the province of Québec, Canada. Individual interviews were conducted with fifteen veterinarians and twenty-seven dairy producers. Thematic analysis was performed based on the COM-B model of behavior change (capability-opportunity-motivation-behavior). Our results indicated that the lack of availability of alternative treatments, the long delays related to diagnostic tests and the fear of economic consequences were major barriers to the implementation of the regulation. A small number of producers also perceived that the regulation negatively impacted the health and wellbeing of their animals. Additionally, participants acknowledged the importance of early education and training to better understand the purpose of the regulation and increase its acceptability. Lastly, most participants reported that they had not only reduced their use of antimicrobials of very high importance for human health following the regulation, but they had also increased preventive practices on their farm. This study reveals that the implementation of restrictive regulations to reduce AMU in animal production can lead to multiple challenges in practice. Our results highlight the need for better communication and training of producers and veterinarians before and during the implementation of similar regulations in the future and underline the importance of measuring the direct and indirect impacts of those regulations on productivity and on animal health and wellbeing. [ABSTRACT FROM AUTHOR]

Amyloid fibrils are proteinaceous nanostructures known for their ability to activate the innate immune system, which has been recently exploited for their use as self-adjuvanted antigen delivery systems for vaccines. Among mechanisms of immunostimulation, the activation of the heterodimeric toll-like receptor 2/6 (TLR2/TLR6) by the cross-β-sheet quaternary conformation appears important. Nonetheless, the lack of control over the process of self-assembly and the polydispersity of the resulting supramolecular architectures make it challenging to elucidate the molecular basis of TLR2/TLR6 engagement by amyloid assemblies. In this context, we harnessed the effects of N- and C-terminal modifications of a short 10-mer β-peptide derived from the islet amyloid polypeptide (I 10 ) to investigate the relationships between the morphology and physicochemical properties of amyloid assemblies and their TLR2/TLR6 activity. Chemical substitutions at the N- and C-termini of the I 10 peptide, including addition of charged residues at the N-terminus and α-amidation of C-terminus, allowed the controlled formation of a diversity of architectures, including belt-like filaments, rigid nanorods as well as flat and twisted fibrils. These fully cytocompatible peptide nanostructures showed different potencies to activate TLR2/TLR6, which correlated with the charge exposed on the surface. These results further demonstrate the potent modulatory effect of N- and C-terminal electrostatic capping on the self-assembly of short synthetic β-peptides. This study also indicates that self-assembly into cross-β-sheet nanostructures is essential for the activation of the TLR2/TLR6 by amyloidogenic peptides, albeit the structural requirements of the engagement of this promiscuous immune receptor by the nanostructures remain challenging to precisely untangle.

In this work, we synthesized an hexasaccharide derived from the capsular polysaccharide of group B Streptococcus type III capsular polysaccharide. Our convergent 3 + 3 strategy avoided the use of benzyl protecting groups allowing the installation of an azide anchoring group and providing a high yield for the final deprotection steps. Moreover, the minimal hexasaccharidic epitope was conjugated to CRM 197 and BSA via copper-catalyzed azide-alkyne cycloaddition for the preparation of a semisynthetic carbohydrate-based vaccine.

Antimicrobial resistance (AMR) is one of the greatest threats to global health worldwide and is threatening not only humans, but also animal production systems, including dairy farms. The objective of this paper was to describe risks factors associated with AMR on dairy farms in Québec, Canada. This observational cross-sectional study included 101 commercial dairy farms and took place between the springs of 2017 and 2018 for a one-year period. We explored risk factors such as farm practices and producer's knowledge (measured using a questionnaire), antimicrobial use (quantified using veterinary invoices), and the presence of Salmonella Dublin (tested by serology). We evaluated AMR with fecal Escherichia coli retrieved from pre-weaned calves and lactating cows using the following outcomes: the presence of extended-spectrum-β-lactamase/AmpC resistance and the number of resistances to antimicrobial classes. We used logistic regression models to evaluate the association between each risk factor and the 2 outcomes for the 2 types of samples (pre-weaned calves and lactating cows). Furthermore, we explored the relationships between these risk factors utilizing data dimensionality reduction and hierarchical clustering. Outputs of these analyses were used as regressors for AMR in regression models. While the results for univariate analyses were ambiguous, the unsupervised analysis naturally categorized the sample of farms according to their health/treatment status (dimension 1, explaining 12.9% of the variance) and herd size (dimension 2, explaining 7.8%). Three clusters of farms were identified (cluster 1: mainly healthy herds and low ceftiofur users, cluster 2: relatively high ceftiofur users, cluster 3: farms with a higher incidence of diseases and higher antimicrobial treatment rates). Dimension 1 and cluster membership were statistically associated with the presence of extended-spectrum-β-lactamase/AmpC resistance in lactating cows and in pre-weaned calves. Dimension 1 was also statistically associated with the number of resistances in lactating cows and in pre-weaned calves. This study highlights the complexity of analyzing risk factors associated with AMR. Our results suggest that the herd health status and the AMU-related practices used are associated with AMR in dairy farms. However, prospective studies are needed to confirm a causal relation., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)