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Acute kidney injury (AKI) occurs in one-fourth of children and young adults admitted to pediatric intensive care unit (PICU). Severe AKI (sAKI; Kidney Disease: Improving Global Outcomes stage 2 or 3) is associated with morbidity and mortality. An AKI risk stratification system, the Renal Angina Index (RAI) calculated at 12 hours of admission, exhibits excellent performance to rule out sAKI at 72 hours of admission. We found that integration of urine neutrophil gelatinase-associated lipocalin (NGAL) with RAI improves prediction of sAKI. We now report the first-year results after implementation of our prospective automated RAI-NGAL clinical decision support (CDS) program.Patients 3 months to 25 years of age were eligible. Admission order sets have a conditional order for urine NGAL released when a 12-hour RAI ≥8. The primary outcome was sAKI any time at days 2 to 4 of admission. We assessed performance of the RAI and RAI+/NGAL to predict the primary outcome.A total of 1427 unique patients accounted for 1575 admissions. In 147 admissions, RAI was ≥8. RAI 8 had negative predictive value (NPV) of 0.98 (95% CI 0.97-0.99); RAI ≥ 8 had positive predictive value (PPV) of 0.37 (95% CI 0.30-0.46) to predict days 2 to 4 sAKI (area under the receiver operating characteristic curve [AUC-ROC] 0.88 [95% CI 0.84-0.92]). Of 147 RAI+ patients, 89 had NGAL available. RAI/NGAL combination improved PPV (0.64, 95% CI 0.50-0.79) without decrement in NPV (0.98, 95% CI 0.97-0.98).AKI biomarker assessment directed by risk stratification improves prediction of sAKI in critically ill children and young adults. This CDS process has potential to enrich the population for interventional study, although improvement to adherence to CDS is needed.

Staphylococcus chromogenes (SC) is a common coagulase-negative staphylococcus described as an emerging mastitis pathogen and commonly found in dairy farms. This study investigated the potential involvement of DNA methylation in subclinical mastitis caused by SC. The whole-genome DNA methylation patterns and transcriptome profiles of milk somatic cells from four cows with naturally occurring SC subclinical mastitis (SCM) and four healthy cows were characterized by next-generation sequencing, bioinformatics, and integration analyses. Comparisons revealed abundant DNA methylation changes related to SCM, including differentially methylated cytosine sites (DMCs, n = 2,163,976), regions (DMRs, n = 58,965), and methylation haplotype blocks (dMHBs, n = 53,098). Integration of methylome and transcriptome data indicated a negative global association between DNA methylation at regulatory regions (promoters, first exons, and first introns) and gene expression. A total of 1486 genes with significant changes in the methylation levels of their regulatory regions and corresponding gene expression showed significant enrichment in biological processes and pathways related to immune functions. Sixteen dMHBs were identified as candidate discriminant signatures, and validation of two signatures in more samples further revealed the association of dMHBs with mammary gland health and production. This study demonstrated abundant DNA methylation changes with possible involvement in regulating host responses and potential as biomarkers for SCM.

In the past 20 years, in the province of Quebec, Canada, there has been an active social response to men’s health issues, from local initiatives to research and national public health policies, such as the Men’s Health Action Plan 2017–2022, created by the Ministry of Health and Social Services. Although Quebec has developed and implemented many initiatives in this field of study, they remain largely unknown outside of the French-speaking regions. This paper seeks to make Quebec’s model available for an international audience and to inform a wider debate about gender and health issues. The main focus was to review the key community and institutional milestones that brought about this model. Challenges and limitations to the model are discussed within a wider debate on gender and health studies. Closing remarks support the relevance ofgreater inclusion of men’s health content in university courses.

In the province of Quebec, Canada, a new regulation restricting usage of antimicrobials of very high importance for human health (Health Canada: category 1 antimicrobials) in production animals is effective since February 2019. The objective of this study was to estimate changes in AM sales in dairy herds after the implementation of the regulation. Therefore, invoice data were extracted from veterinary software, Vet-Expert, used by most dairy veterinarians in the province of Quebec, and antimicrobial quantities were transformed in Canadian defined course doses for cattle (DCDbovCA). The sum of antimicrobials sales monthly in each herd was estimated in DCDbovCA from June 2016 to May 2020. To evaluate the herd-level change in AM sales and the impact of different factors, the number of DCDbovCA by herd from June 2017 to May 2018 (pre-regulation period) were compared with those of June 2019 to May 2020 (post-regulation period). Total category 1 AM sales of 3,569 Quebec's herds went from a range of 14,258 to 21,528 DCDbovCA/month to a range of 1,494 to 4,707 DCDbovCA/month after the implementation of the new regulation. Moreover, using data from 3,337 herds, we estimated a mean (95% confidence interval) reduction in 19 DCDbovCA/herd-year (14.8, 24.2), while the pre-regulation herd-level category 1 AM sales was 26 DCDbovCA/herd-year. This reduction was achieved without evidence of an increase in other antimicrobials. Finally, the veterinary facility associated with the herd was an important determinant of the herd-level reduction in category 1 antimicrobials. This study was the first to quantify a significant reduction in category 1 AM sales following the implementation of a restrictive regulation in dairy production in Canada. These results demonstrate that such an approach is effective to reduce the sales of a specific category of antimicrobial in animal production.

The objective of this observational cross-sectional study was to describe the cleanliness of various equipment used for colostrum harvest and calf feeding procedures on dairy farms in Quebec, Canada. The study was performed on 42 commercial dairy herds also enrolled in another study aiming to determine the transfer of passive immunity over a 14-mo period. Information on colostrum quality (using Brix value) and cleanliness (total aerobic and total coliform count) were recorded as well as various practices focused on colostrum-feeding equipment and preweaning period using a standard questionnaire. During the study period, colostrum and milk-feeding equipment cleanliness was assessed using direct surface swabbing with Hygiena Ultrasnap swabs. A total of 155 swab samples were obtained from 6 pieces of equipment. Adenosine triphosphate collected from the swabbed surface reacts with the luciferase solution present in the swab by bioluminescence, which is proportional to the quantity of ATP present and quantified as relative light units (RLU). The description of feed equipment cleanliness (defined as the maximal RLU found for a specific herd, dichotomized as

Sinapic acid is found in many edible plants and fruits, such as rapeseed, where it is the predominant phenolic compound. New sinapic acid phenethyl ester (SAPE) analogues were synthesized and screened as inhibitors of the biosynthesis of 5-lipoxygenase (5-LO) in stimulated HEK293 cells and polymorphonuclear leukocytes (PMNL). Inhibition of leukotriene biosynthesis catalyzed by 5-LO is a validated therapeutic strategy against certain inflammatory diseases and allergies. Unfortunately, the only inhibitor approved to date has limited clinical use because of its poor pharmacokinetic profile and liver toxicity. With the new analogues synthesized in this study, the role of the phenolic moiety, ester function, and bioisosterism was investigated. Several of the 34 compounds inhibited the biosynthesis of 5-LO products, and 20 compounds were 2-11 times more potent than zileuton in PMNL, which are important producers of 5-LO products. Compounds

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.

The reception of the Second Vatican Council by traditionalist Catholics is a complex phenomenon. First, the traditionalist world is a universe unto itself, consisting of networks of many individuals and movements. Added to this is the passage of time and varying situations, which has led to an ever-changing interpretation of the council by traditionalists. This chapter will examine the reception of Vatican II by traditionalists over three different eras. The first runs from 8 December 1965 to 30 November 1969; that is, from the closing of the council to the entry into force of the prescriptions of the Apostolic Constitution Missale Romanum (3 April 1969). From this date, the reception of Vatican II by opponents of the council entered a new, second phase. That continued until the year 2000, when the Society of St Pius X organized a pilgrimage to Rome, which gave rise to doctrinal discussions between the society and the Holy See. These discussions opened a new period in the reception of Vatican II by traditionalists, which continues to the present day.

Four-wave mixing is investigated when chirped pump and signal pulses are injected in a photonic crystal fiber. The shot-to-shot stability of the amplified coherent signal was measured by using the dispersive Fourier transform method and compared with numerical simulations. We highlight that the signal-to-noise ratio (SNR) of the pulsed signal increases with the injected power and show that it is not deteriorated through the amplification when the fiber optical parametric amplifier is strongly saturated. The SNR of the signal remains nearly constant after the amplifier.

Severe clinical mastitis is a frequent disease of dairy cattle. An effective mean of predicting survival despite treatment would be helpful for making euthanasia decisions in poor prognosis cases. The objective was to develop a nomogram for prediction of death or culling in the 60 days following a severe mastitis episode in dairy cows at first veterinary visit in farm settings. A total of 224 dairy cows presenting severe clinical mastitis and examined for the first time by a veterinarian were included in a prospective study. Clinical and laboratory (complete blood cell count, L-lactate, cardiac troponin I, milk culture) variables were recorded. Animals were followed for 60 days. A nomogram was built with an adaptive elastic-net Cox proportional hazards model. Performances and relevance were evaluated by area under the receiver operating characteristic curve (AUC), Harrell’s concordance index (C-index), calibration curve, decision curve analysis (DCA) and misclassification cost term (MCT). The nomogram included: lactation number, recumbency, depression intensity, capillary refilling time, ruminal motility rate, dehydration level, lactates concentration, hematocrit, band neutrophils count, monocyte count, and milk bacteriology. The AUC and C-index showed a good calibration and ability to discriminate. The DCA suggested that the nomogram was clinically relevant. Euthanizing animals having less than 25% probability of survival is economically optimal. It could be used for early euthanasia decisions in animals that would not survive despite treatment. To facilitate the use of this nomogram by veterinarians, a web-based app was developed.

Background Mastitis caused by different pathogens including Streptococcus uberis (S. uberis) is responsible for huge economic losses to the dairy industry. In order to investigate the potential genetic and epigenetic regulatory mechanisms of subclinical mastitis due to S. uberis, the DNA methylome (whole genome DNA methylation sequencing) and transcriptome (RNA sequencing) of milk somatic cells from cows with naturally occurring S. uberis subclinical mastitis and healthy control cows (n = 3/group) were studied. Results Globally, the DNA methylation levels of CpG sites were low in the promoters and first exons but high in inner exons and introns. The DNA methylation levels at the promoter, first exon and first intron regions were negatively correlated with the expression level of genes at a whole-genome-wide scale. In general, DNA methylation level was lower in S. uberis-positive group (SUG) than in the control group (CTG). A total of 174,342 differentially methylated cytosines (DMCs) (FDR P-value S. uberis infection, especially cytokine activities. Furthermore, discriminant correlation analysis with DIABLO method identified 26 candidate biomarkers, including 6 DE genes, 15 CpG-DMCs and 5 dMHBs that discriminated between SUG and CTG. Conclusion The integration of methylome and transcriptome of milk somatic cells suggests the possible involvement of DNA methylation changes in the regulation of the host immune response to subclinical mastitis due to S. uberis. The presented genetic and epigenetic biomarkers could contribute to the design of management strategies of subclinical mastitis and breeding for mastitis resistance.

Warming in the Arctic causes strong environmental changes with degradation of permafrost (permanently frozen ground). Active layer deepening (gradual thaw) and permafrost erosion (abrupt thaw) results in the mobilization and lateral transport of organic carbon, altering current carbon cycling in the Arctic. Ground ice content is a crucial factor limiting our understanding and ability to determine the rates and dynamics of permafrost thaw and its impact on potential thaw subsidence rates, changes in lateral hydrological pathways and its driving mechanisms on a landscape scale.In this study we investigate ground ice content and its characteristics across the most dominant landscape units of the Yukon coastal plain (Canadian Arctic), using two spatially and technically contrasting approaches. In our bottom-up approach, twelve permafrost cores were collected from moraine, lacustrine, fluvial and glaciofluvial deposits using a SIPRE corer (mean drilling depth of 2 m) in spring of 2019. Ground ice and sediment contents within polygon centers were analyzed and classified using computed tomography and image recognition software (k-means). Our top-down approach quantified ice-wedge volumes from remote sensing imagery tracing the circumference of polygon troughs over the same area. Preliminary results - extrapolated to the entire coastal plain - show that the ground-ice content in polygon centers vary significantly from massive ice in the polygon troughs (wedge-ice). Total ice volume was estimated around 80.2 vol.-%, of which 68.2 ± 18.1 vol.-% was attributed to ground ice in polygon centers, and 12 ± 3.1 vol.-% of the landscape is massive ice in wedge-ice along polygon troughs. Additionally, differences among and between landscape units are also substantial, with highest ice volume contents in moraines landscapes, where polygon centers contain 58.8 vol.-% ground ice and wedge-ice volume is 16.2 vol.-%), while the lowest ice contents are found in glacio-fluvial deposits (22.1 vol.-% resp. 9.1 vol.-%).Our results reveal a higher average and a larger variability in ground ice contents than previously found, suggesting a need of both ground-based measurements and remote sensing imagery to further our understanding of the future landscape subsidence, but also to avoid a likely under- or overestimation associated with the chosen approach. We conclude that due to the high ground ice contents on the Yukon coastal plain, substantial changes of the permafrost landscape will occur under current warming trends. These will include subsidence, abrupt erosion, changes in hydrology and organic carbon mobilization, degradation and export processes, which will differ between landscape units.

Cet article résume la mise en œuvre d’un projet pilote de formation destiné à promouvoir la santé mentale chez les agriculteurs. Cette initiative destinée tant aux intervenants qu’aux agriculteurs est née d’un partenariat entre un centre de prévention du suicide et le milieu universitaire québécois. On y présente de façon succincte le contexte ayant mené à sa mise sur pied, ses modalités, son appréciation et ses retombées. L’analyse de ce projet pilote met en lumière la pertinence des approches de codéveloppement unissant les agriculteurs, les intervenants et les chercheurs.

Le présent article est le résultat d’une recherche visant à présenter des parcours d’hommes ayant participé à des groupes pour pères dans le contexte des bouleversements que les familles occidentales ont connus au cours des dernières décennies. L’objectif de cette recherche était d’identifier les motivations des pères à s’engager dans un processus de réflexion et d’action au sein d’un groupe, d’en apprendre plus sur leur expérience tout au long de ce processus, de comprendre ce qui a changé dans leur vision de la masculinité et de la paternité, puis de connaître la manière dont ils actualisent leur projet de vie au regard d’éventuels changements. Des entrevues semi-dirigées ont été menées auprès de onze pères impliqués dans huit groupes de soutien au Québec. Les résultats révèlent que les rapports sociaux (par exemple, la relation avec la conjointe ou l’ex-conjointe, avec les enfants, avec les femmes et avec les autres hommes en général) s’en trouvent modifiés, voire améliorés. En outre, la reconstruction des rapports à soi-même et aux autres semble être à la fois le principal défi de ces hommes et la source de leur plus grande satisfaction.This article aims to understand the journeys of men who participated in fathers’ groups in the context of the upheavals that the Western family has experienced in recent decades. It is based on the results of a study that aimed to identify the motivations of fathers who engaged in a process of reflection and action within these support groups; to examine their experience of this process, to understand what has changed in their vision of masculinity and fatherhood through this experience; and explore how they update their life plans in the light of possible changes. Semi-structured interviews were conducted with eleven fathers involved in eight different groups in Quebec. The findings reveal that social relationships, including relationships with partners, or ex-partners, children, women, and other men in general, evolved and in some cases improved. In addition, the reconstruction of relationships with oneself and others seems to be both the main challenge as well as the greatest satisfaction of these men.

Digital dermatitis (DD) is a worldwide infectious disease of cattle that causes lameness, discomfort, and economic losses. The reference standard test to diagnose DD is visual observation in a trimming chute, which cannot be practically performed daily on dairy farms. Moreover, some lesion misclassification may occur using this standard diagnostic method. The possibility of misclassification makes the use of a trimming chute debatable as a perfect reference standard test. The objective of this study was, therefore, to assess the diagnostic accuracy of a commercial borescope and trimming chute exam. The accuracy (sensitivity and specificity) of the tests and DD prevalence were investigated using Bayesian latent class analyses. Our hypothesis was that a commercial borescope can be routinely used to diagnose DD in a milking parlor without previous feet cleaning. A cross-sectional study was performed in a freestall facility. The lesions were scored (M0, M1, M2, M3, M4, M4.1) in the milking parlor with a borescope, followed by an examination in the trimming chute 48 to 72 h after the borescope exam. A total of 870 hind feet were scored during 2 sessions of trimming chute exams and borescope exams in the milking parlor. The data were analyzed in 2 ways. First, data were dichotomized into DD lesions (M1, M2, M3, M4, M4.1) and absence of DD lesions (M0). Second, data were dichotomized into active DD lesions (M1, M2, M4.1) and inactive lesions (M0, M3, M4). A Bayesian latent class model allowing for conditional dependence between tests was used to estimate tests' accuracy, likelihood ratio, and DD prevalence. When the data were dichotomized into DD lesions (M1-M4.1) versus absence of DD (M0) lesions, the sensitivity and specificity of the borescope was 55% [95% credible interval (CrI) 40-71%] and 81% (95% CrI 75-88%). The sensitivity of trimming chute exams was 79% (95% CrI 68-88%), and specificity was 80% (95% CrI 71-89%). When the data were dichotomized into active lesions (M1, M2, M4.1) versus inactive lesions or absence of lesions (M3, M4, M0), the sensitivity and specificity of the borescope were, respectively, 32% (95% CrI 13-58%) and 91% (95% CrI 88-95%). The sensitivity and specificity of trimming chute exams were 91% (95% CrI 81-97%) and 81% (95% CrI 75-89%), respectively. In conclusion, it is possible to use the borescope in the milking parlor without cleaning the feet to monitor prevalence of DD lesions. However, an isolated borescope examination, especially for diagnosing active DD lesions, has low sensitivity for use as a surveillance method. For such use, the sensitivity could be improved by repeating the borescope exam on a regular basis.

OBJECTIVE To describe the clinical and clinicopathologic characteristics, treatment, and outcome for cattle that developed a retroperitoneal abscess (RA) following paralumbar fossa laparotomy (PFL). ANIMALS 32 Holstein cows with RA. PROCEDURES The record database of a veterinary teaching hospital was searched to identify cattle that were treated for an RA between January 1995 and March 2017. Cattle with an RA > 30 cm in diameter located 3.5 cm subjacent to the skin that had undergone a PFL < 3 months before examination for the RA were evaluated. Information extracted from the record of each cow included signalment; physical examination, clinicopathologic, and transabdominal ultrasonographic findings; treatments administered; and outcome. Milk production data were analyzed for the lactations before, during, and after RA treatment. RESULTS Common physical examination findings were rumen hypomotility, anorexia, and fever, and common clinicopathologic findings were anemia and neutrophilia. Abdominal palpation per rectum and transabdominal ultrasonography facilitated RA diagnosis and identification of the optimal location for drainage. Thirty of 32 cows underwent surgical drainage of the RA and prolonged administration of systemic antimicrobials. Two cows were euthanized because of concurrent peritonitis, including 1 that underwent surgical RA drainage. Thirty cows were discharged from the hospital alive, and most returned to their previous level of milk production. CONCLUSIONS AND CLINICAL RELEVANCE Although uncommon, RA should be suspected in cows that develop anorexia and fever within 3 months after PFL. Cows with RA often returned to their previous level of milk production, but treatment was generally prolonged and costly.

Avant le concile Vatican II, l’Église catholique considérait le peuple juif comme déicide, réprouvé et maudit par Dieu ; après cet événement, elle renonça à ce qui fut appelé la « théologie de la substitution », s’engagea dans la voie du dialogue, affirma la permanence de l’élection d’Israël et considéra les juifs comme des « frères aînés ». Dans cet article, l’auteur étudie le rôle de la Congrégation Notre-Dame de Sion dans l’évolution du regard porté par l’Église catholique sur les juifs et le judaïsme, rôle qui a conduit à une remise en cause théologique et à un changement des mentalités qui ont mené, plus ou moins directement, à la déclaration Nostra Aetate du concile Vatican II., Before the Second Vatican Council, the Catholic Church considered the Jewish people to have committed deicide ; in the Church’s eyes, they were condemned and cursed by God. After this event, it gave up what was called “Replacement Theology,” engaged in dialogue, asserted the permanency of God’s choice of Israel, and considered Jews as “elder brothers.” In this article, the author explores the role of the Congregation of Our Lady of Sion in the evolution of the way in which the Catholic Church has viewed Jews and Judaism. This role has brought about a theological rethinking and a change of mindset, which led, more or less directly, to the declaration Nostra Aetate of the Second Vatican Council.

To tackle antimicrobial resistance (AMR), one of the major health threats of this century, the World Health Organization (WHO) endorsed a global action plan in 2015. This plan calls countries to develop national actions to address AMR. The province of Québec, Canada, adopted a new regulation on the 25thof February 2019, to limit the use in food animals of antimicrobials of very high importance in human medicine. We aimed to establish the impact of this regulation by comparing the AMR situation in dairy cattle in Québec ~2 years before and 2 years after its introduction. We sampled calves, cows, and the manure pit in 87 farms. Generic and putative ESBL/AmpCE. coliwere tested for susceptibility to 20 antimicrobials. Logistic regression was used to investigate whether the probability of antimicrobial resistance differed between isolates obtained from the pre and post regulation periods by sample type (calves, cows, manure pit) and in general. To identify AMR genes dissemination mechanisms, we sequenced the whole genome of 15 generic isolates. In the generic collection, at the herd level, the proportion of multidrug resistant (MDR) isolates, decreased significantly from 83 to 71% (p= 0.05). Folate inhibitor and aminoglycoside resistances demonstrated a significant decrease. However, when analyzed by sample type (calves, cows, manure pit), we did not observe a significant AMR decrease in any of these categories. In the ESBL/AmpC collection, we did not detect any significant difference between the two periods. Also, the general resistance gene profile was similar pre and post regulation. We identified both clonal and plasmidic dissemination of resistance genes. In conclusion, as early as 2 years post regulation implementation, we observed a significant decrease in MDR in the dairy industry in Quebec in the genericE. colicollection with folate inhibitor and aminoglycoside resistances showing the most significant decrease. No other significant decreases were yet observed.

We report on the conception, fabrication and characterization of a new concept of optical fiber enabling a precise control of the ratio between the 2nd and 4th-order chromatic dispersion (respectively β2 and β4) at 1.55 μm which is primordial for ensuring an effective frequency conversion by far-detuned Four-Wave-Mixing (FWM). Experimental demonstration relying on an atypical discretized highly nonlinear fiber (D-HNLF) is shown and discussed.

We numerically demonstrate a broadband parametric gain around 2 µm using a tapered photonic crystal fiber.

Different high-power fiber laser designs based on commercially available components are compared using a free software. The MOPA architectures have the potential to reach up to 4 kW but are limited by TMI and SRS.

We demonstrate the characterization of nonlinear noise-driven dynamics with ultra-high sensitivity, resolution, and a theoretically unlimited dynamic range using a novel approach of dispersive Fourier transform-based measurements and multiple single photon detectors.

Staphylococcus aureus (S. aureus) is one of the most prevalent pathogens of bovine subclinical mastitis and a challenging pathogen in dairy production. DNA methylation involvement in regulating mammary gland inflammatory defense has been documented. This study adopted whole genome bisulfite sequencing and RNA-sequencing technologies to profile the genome-wide DNA methylation and transcriptome landscapes, respectively, of milk somatic cells (MSCs) from 15 cows with S. aureus-induced subclinical mastitis (SACs) and 13 healthy cows (HCs). Bioinformatics processing of data with standard tools indicated that the global DNA methylation patterns of MSCs demonstrated inverse correlations between gene expression and DNA methylation levels at promoter, first exon and first intron regions, suggesting potential regulatory roles of DNA methylation in transcriptional activities. Totally, 26,289 differential methylation regions (DMRs) were identified between SACs and HCs (1,000 bp window, 1,000 bp step, q-value < 0.05, >20% methylation difference and ≥3 differentially methylated cytosines). A total of 887, 334 and 3,414 DMRs were overlapped with promoter, first exon, and first intron regions, respectively, including 363 DMRs harboring transcription start sites. Among them, the methylation levels of 956 DMRs were strongly correlated with the expression levels of their overlapped genes (|Spearman’s correlation coefficient| >0.5, adjusted-p-value< 0.05). Functional annotation of the overlapped genes indicated significant (adjusted-p-value < 0.05) enrichment in 18 GO terms and 1 KEGG pathway related to cellular activities, notably in cell migration, epithelial cell differentiation and tight junction, among others (Figure 1). These results suggest the involvement of DNA methylation in mammary gland defense against S. aureus-invasion. Applying DIABLO method to integrate correlated DMRs and genes, a total of 20 DMR and 10 gene candidate markers were found to discriminate SACs from HCs. The identified candidate markers could serve as reference for enhancing breeding for mastitis resistance and for developing new mastitis management strategies.

To tackle antimicrobial resistance (AMR), one of the major health threats of this century, the World Health Organization (WHO) endorsed a global action plan in 2015. This plan calls countries to develop national actions to address AMR. The province of Québec, Canada, adopted a new regulation on the 25