The French ecology of medical care. A nationwide population-based cross sectional study.

PURPOSE: Studies in the United States, Canada, Belgium, and Switzerland showed that the majority of health problems are managed within primary health care; however, the ecology of French medical care has not yet been described. METHODS: Nationwide, population-based, cross sectional study. In 2018, we included data from 576,125 beneficiaries from the General Sample of Beneficiaries database. We analysed the reimbursement of consultations with (i) a general practitioner (GP), (ii) an outpatient doctor other than a GP, (iii) a doctor from a university or non-university hospital; and the reimbursement of (iv) hospitalization in a private establishment, (v) general hospital, and (vi) university hospital. For each criterion, we calculated the average monthly number of reimbursements reported on 1,000 beneficiaries. For categorical variables, we used the χ2 test, and to compare means we used the z test. All tests were 2-tailed with a P-value < 5% considered significant. RESULTS: Each month, on average, 454 (out of 1,000) beneficiaries received at least 1 reimbursement, 235 consulted a GP, 74 consulted other outpatient doctors in ambulatory care and 24 in a hospital, 13 were hospitalized in a public non-university hospital and 10 in the private sector, and 5 were admitted to a university hospital. Independently of age, people consulted GPs twice as much as other specialists. The 13-25-year-old group consulted the least. Women consulted more than men. Individuals covered by complementary universal health insurance had more care. CONCLUSIONS: Our study on reimbursement data confirmed that, like in other countries, in France the majority of health problems are managed within primary health care.

Genetic analysis of the blood transcriptome of young healthy pigs to improve disease resilience.

BACKGROUND: Disease resilience is the ability of an animal to maintain productive performance under disease conditions and is an important selection target. In pig breeding programs, disease resilience must be evaluated on selection candidates without exposing them to disease. To identify potential genetic indicators for disease resilience that can be measured on selection candidates, we focused on the blood transcriptome of 1594 young healthy pigs with subsequent records on disease resilience. Transcriptome data were obtained by 3'mRNA sequencing and genotype data were from a 650 K genotyping array. RESULTS: Heritabilities of the expression of 16,545 genes were estimated, of which 5665 genes showed significant estimates of heritability (p < 0.05), ranging from 0.05 to 0.90, with or without accounting for white blood cell composition. Genes with heritable expression levels were spread across chromosomes, but were enriched in the swine leukocyte antigen region (average estimate > 0.2). The correlation of heritability estimates with the corresponding estimates obtained for genes expressed in human blood was weak but a sizable number of genes with heritable expression levels overlapped. Genes with heritable expression levels were significantly enriched for biological processes such as cell activation, immune system process, stress response, and leukocyte activation, and were involved in various disease annotations such as RNA virus infection, including SARS-Cov2, as well as liver disease, and inflammation. To estimate genetic correlations with disease resilience, 3205 genotyped pigs, including the 1594 pigs with transcriptome data, were evaluated for disease resilience following their exposure to a natural polymicrobial disease challenge. Significant genetic correlations (p < 0.05) were observed with all resilience phenotypes, although few exceeded expected false discovery rates. Enrichment analysis of genes ranked by estimates of genetic correlations with resilience phenotypes revealed significance for biological processes such as regulation of cytokines, including interleukins and interferons, and chaperone mediated protein folding. CONCLUSIONS: These results suggest that expression levels in the blood of young healthy pigs for genes in biological pathways related to immunity and endoplasmic reticulum stress have potential to be used as genetic indicator traits to select for disease resilience.

Screen exposure time of children under 6 years old: a French cross-sectional survey in general practices in the Auvergne-Rhône-Alpes region.

BACKGROUND: The advent of miniature, easy-to-use and accessible multimedia products is leading to screen exposure that begins in early childhood. Overexposure in preschool may lead to adverse effects. The main objective of this study was to determine the average daily time (ADT) spent by children under 6 years of age, followed in general practice, in front of television or interactive screens. METHODS: A cross-sectional survey was conducted in the Auvergne-Rhône-Alpes region among randomly selected General Practitioners (GPs). The average daily screen time (ADST), regardless of the type of device (TVs, computers, tablets, smartphones, video game consoles), of the included children aged 0 to 2 years and 2 to 5 years was calculated from a self-questionnaire completed by the parents. A multivariate Poisson regression model was performed to analyse daily screen time, adjusted by factors selected on their clinical relevance and statistical significance. RESULTS: The 26 participating GPs included 486 parents. They reported an ADST of 26 (± 44) minutes on weekdays and 30 (± 46) minutes on weekends for children under 2 years of age. For children over 2 years of age, the ADST was 66 (± 82) minutes on weekdays and 103 (±91) minutes on weekends. There was an association between the children's average screen time and certain sociodemographic and environmental factors. Children whose parents had higher levels of education, those living in a family without TV screens or those who were well informed about the possible adverse health consequences of overuse of screens had lower average screen time. On the other hand, children of parents who spent more than 2 hours a day in front of screens, were more exposed. CONCLUSIONS: In our survey, the ADST of children under 6 years of age followed in general practice was higher than the current recommendations. GPs can warn parents of preschool children of the effects of overexposure to screens, particularly parents of at-risk children.

Observation of Genetic Gain with Instrumental Insemination of Honeybee Queens.

Controlling mating in the honeybee (Apis mellifera) is part of one of the greatest challenges for the beekeeping industry's genetic selection programs due to specific characteristics of their reproduction. Several techniques for supervising honeybee mating with relative effective control have been developed over the years to allow honeybee selection. As part of this project, we compared the genetic gains for several colony performance traits, obtained using the BLUP-animal method, according to the selection pressure applied in controlled reproduction (directed fertilization versus instrumental insemination). Our results show similar genetic gains for hygienic behavior and honey production between colonies whether queens were fertilized naturally or via instrumental insemination, as well as similar or lower genetic gains for colonies with queens inseminated for spring development. In addition, we noticed greater fragility in queens following insemination. These findings show that instrumental insemination is an effective tool for reproductive control in genetic selection and for estimating breeding values more precisely. However, this technique does not result in queens of superior genetic quality for commercial purposes.

Plasma protein levels of young healthy pigs as indicators of disease resilience.

Selection for disease resilience, which refers to the ability of an animal to maintain performance when exposed to disease, can reduce the impact of infectious diseases. However, direct selection for disease resilience is challenging because nucleus herds must maintain a high health status. A possible solution is indirect selection of indicators of disease resilience. To search for such indicators, we conducted phenotypic and genetic quantitative analyses of the abundances of 377 proteins in plasma samples from 912 young and visually healthy pigs and their relationships with performance and subsequent disease resilience after natural exposure to a polymicrobial disease challenge. Abundances of 100 proteins were significantly heritable (false discovery rate (FDR) <0.10). The abundance of some proteins was or tended to be genetically correlated (rg) with disease resilience, including complement system proteins (rg = -0.24, FDR = 0.001) and IgG heavy chain proteins (rg = -0.68, FDR = 0.22). Gene set enrichment analyses (FDR < 0.2) based on phenotypic and genetic associations of protein abundances with subsequent disease resilience revealed many pathways related to the immune system that were unfavorably associated with subsequent disease resilience, especially the innate immune system. It was not possible to determine whether the observed levels of these proteins reflected baseline levels in these young and visually healthy pigs or were the result of a response to environmental disturbances that the pigs were exposed to before sample collection. Nevertheless, results show that, under these conditions, the abundance of proteins in some immune-related pathways can be used as phenotypic and genetic predictors of disease resilience and have the potential for use in pig breeding and management.

A challenge of selection for disease resilience is that it is difficult to directly select pigs that have greater resilience to multiple diseases in the healthy nucleus herd environment which is essential for breeding programs. A possible alternative is to select an indicator trait or marker that can be measured in a healthy setting, is heritable, and is associated with the genetics of disease resilience. In this study, we investigated plasma protein levels measured on young healthy pigs as indicator traits to select for disease resilience. For this purpose, we used plasma proteome data collected prior to the natural exposure of nursery pigs to multiple diseases, performed phenotypic and genetic quantitative analyses, and investigated their relationships with disease resilience. Our results suggest that plasma protein levels of young healthy pigs have the potential as biomarkers to select for disease resistance.

Exploration of plasma metabolite levels in healthy nursery pigs in response to environmental enrichment and disease resilience.

The purpose of this study was to explore plasma metabolite levels in young healthy pigs and their potential association with disease resilience and estimate genetic and phenotypic correlation with the change in lymphocyte concentration following disease challenge. Plasma samples were collected from 968 healthy nursery pigs over 15 batches at an average of 28 ± 3.23 d of age. Forty-four metabolites were identified and quantified by nuclear magnetic resonance. Pigs were then introduced into a natural disease challenge barn, and were classified into four groups based on the growth rate of each animal in the grow-to-finish phase (GFGR) and treatment rate (TR): resilient (RES), average (MID), susceptible (SUS), and dead (pigs that died before harvest). Blood samples were collected from all pigs before and 2 wk after disease challenge and complete blood count was determined. Environmental enrichment (inedible point source objects) was provided for half of the pigs in seven batches (N = 205) to evaluate its impact on resilience and metabolite concentrations. Concentration of all metabolites was affected by batch, while entry age affected the concentration of 16 metabolites. The concentration of creatinine was significantly lower for pigs classified as "dead" and "susceptible" when compared to "average" (P < 0.05). Pigs that received enrichment had significantly lower concentrations of six metabolites compared with pigs that did not receive enrichment (P ≤ 0.05). Both, group classification and enrichment affected metabolites that are involved in the same pathways of valine, leucine, and isoleucine biosynthesis and degradation. Resilient pigs had higher increase in lymphocyte concentration after disease challenge. The concentration of plasma l-α-aminobutyric acid was significantly negatively genetically correlated with the change in lymphocyte concentration following challenge. In conclusion, creatinine concentration in healthy nursery pigs was lower in pigs classified as susceptible or dead after disease challenge, whilst l-α-aminobutyric may be a genetic biomarker of lymphocyte response after pathogen exposure, and both deserve further investigation. Batch, entry age, and environmental enrichment were important factors affecting the concentration of metabolites and should be taken into consideration in future studies.

The focus of this study was to explore plasma metabolite levels in young healthy pigs and their potential association with health outcome classification following the exposure to a polymicrobial disease challenge. In addition, we explored the effect of the environmental enrichment on metabolite concentrations. Finally, we estimated genetic and phenotypic correlations between metabolites and the magnitude of change in lymphocytes levels following exposure to a polymicrobial disease challenge. We found that concentration of creatinine was lower in pigs that died before marketing, classified as "dead" and susceptible when compared to average group. This indicates that creatinine can be used as an early indicator of death and/or susceptibility of disease in pigs. Providing environmental enrichment affected the concentration of six metabolites and branched chain amino acids index. Such results would be very useful to design environmental enrichment strategies when pigs are challenged by disease in commercial farms. The magnitude of change in lymphocytes level was negatively genetically correlated with l-α-aminobutyric acid. This result indicates that l-αs-aminobutyric acid can be an early indicator of the magnitude of change in lymphocytes level. Such indicator can be collected from nucleus breeding herds in healthy animals and could provide an early biomarker of resilience.

Real-Life Testing of the Prescription Opioid Misuse Index in French Primary Care.

Analgesic opioid (AO) misuse by patients ranges from 0% to 50%. General practitioners are the first prescribers of AO. Our objective was to validate the Prescription Opioid Misuse Index (POMI) in primary care. We conducted a psychometric study in patients with chronic pain who had been taking AOs for at least 3 months and were followed in general practice. Patients responded to the POMI at inclusion and after 2 weeks. The reference used was the DSM-V. Sixty-nine GPs included 160 patients (87 women, 54.4%), mean age 56.4 ± 15.2 years. The total POMI score was 1.50 ± 1.27, and 73/160 (45.6.0%) had a score ≥ 2 (misuse threshold). Internal validity was measured with the Kuder-Richardson coefficient, which was 0.44. Correlations between each item and the total score ranged from 0.06 to 0.35. Test-retest reliability was determined from 145 patients: Lin's concordance coefficient was 0.57 [0.46, 0.68]. Correlation with the DSM-V (Spearman's coefficient) was 0.52. The POMI does not have sufficient psychometric properties to be recommended as a tool to identify the misuse of AOs in primary care. This study clearly showed that there is a need to create a monitoring tool specific to primary care.

Barriers and Expectations of Adolescents Regarding the Identification and Management of Their Psychoactive Substance Use by Their General Practitioner.

AIMS: General practitioners (GPs), who are the most frequently consulted health professionals by adolescents, play a key role in screening for psychoactive substance (PAS) use. The purpose of our study was to determine the barriers and expectations of adolescents regarding the identification and management of their PAS use by their general practitioner. METHODS: Descriptive, cross-sectional study of a population of adolescents aged 12 to 17 years, followed up in general practice in France. Adolescents were recruited from general practice offices by open-access questionnaires. An opaque box was provided to ensure the anonymity of the adolescents. RESULTS: A total of 277 adolescents were included: 155 girls, mean age 14.5 ± 1.7 years, 113 adolescents (41%) had used a PAS at least once in the past 12 months. Alcohol was the most used PAS, followed by tobacco and cannabis. Three groups were identified: the nonusers group (n = 134); the group of moderate users (n = 71); the group of users at risk of substance abuse or misusing (n = 38). Regardless of group, adolescents felt that their GP was attentive, responsive, competent, understanding, and took the time to ask the appropriate questions in their role. The at-risk group was less confident and less comfortable, and they felt more judged and more afraid of the GP telling their parents. Despite this, the at-risk group was the most willing to talk to their GP about their PAS. Almost half of the adolescents surveyed found it useful to use a questionnaire to discuss PAS. CONCLUSIONS: Reminding each consultation of the principles of the relationship of trust and confidentiality while maintaining an empathetic attitude would make it easier for GPs to remove adolescents' inhibitions about communicating about their PAS use.

Effectiveness of brief interventions in primary care for cannabis users aged from 12 to 25 years old: a systematic review.

INTRODUCTION: The aim of this systematic review was to assess the effectiveness of brief interventions realized in primary care in reducing cannabis use for adolescents and emerging adults. METHODS: PubMed, CINAHL, Embase, PsycInfo, and Central (Cochrane Library) were searched until December 2020. Randomized controlled trials conducted in primary care, concerning in-person brief interventions for non-medical cannabis users aged from 12 to 25 years old were eligible for inclusion. Brief interventions had to last 30 min or less. Patients with comorbid mental health disorder or very specific populations were not included. RESULTS: One thousand eighty hundred and fifty-five studies were identified through database searching; only 8 studies involving 2,199 patients were included for qualitative synthesis after double reading and data extraction. Randomized controlled trials selected were heterogeneous regarding screening tools, initial levels of cannabis use and cannabis outcomes measures. Brief interventions were all based on motivational interviewing techniques or personalized feedback. Seven studies consisted in a single session of brief intervention. Six studies involved also other substance users. No significant reduction of cannabis use after brief intervention was found for most studies, especially in the long term. A trend of decreased cannabis consequences, such as negative psychosocial repercussions, perception of cannabis use by peers, or driving under the influence of cannabis, was reported. CONCLUSION: The current state of knowledge does not allow us to say that the brief intervention is effective in reducing cannabis use among adolescents in primary care. We found a mild positive effect on cannabis consequences after brief intervention. Mixed qualitative and quantitative studies are need to better evaluate the impact of brief intervention and his faisability. PROSPERO (International Prospective Register of Systematic Reviews): n° CRD42016033080.

Genetic analysis of disease resilience of wean-to-finish pigs under a natural disease challenge model using reaction norms.

BACKGROUND: Disease resilience is the ability to maintain performance across environments with different disease challenge loads (CL). A reaction norm describes the phenotypes that a genotype can produce across a range of environments and can be implemented using random regression models. The objectives of this study were to: (1) develop measures of CL using growth rate and clinical disease data recorded under a natural polymicrobial disease challenge model; and (2) quantify genetic variation in disease resilience using reaction norm models. METHODS: Different CL were derived from contemporary group effect estimates for average daily gain (ADG) and clinical disease phenotypes, including medical treatment rate (TRT), mortality rate, and subjective health scores. Resulting CL were then used as environmental covariates in reaction norm analyses of ADG and TRT in the challenge nursery and finisher, and compared using model loglikelihoods and estimates of genetic variance associated with CL. Linear and cubic spline reaction norm models were compared based on goodness-of-fit and with multi-variate analyses, for which phenotypes were separated into three traits based on low, medium, or high CL. RESULTS: Based on model likelihoods and estimates of genetic variance explained by the reaction norm, the best CL for ADG in the nursery was based on early ADG in the finisher, while the CL derived from clinical disease traits across the nursery and finisher was best for ADG in the finisher and for TRT in the nursery and across the nursery and finisher. With increasing CL, estimates of heritability for nursery and finisher ADG initially decreased, then increased, while estimates for TRT generally increased with CL. Genetic correlations for ADG and TRT were low between high versus low CL, but high for close CL. Linear reaction norm models fitted the data significantly better than the standard genetic model without genetic slopes, while the cubic spline model fitted the data significantly better than the linear reaction norm model for most traits. Reaction norm models also fitted the data better than multi-variate models. CONCLUSIONS: Reaction norm models identified genotype-by-environment interactions related to disease CL. Results can be used to select more resilient animals across different levels of CL, high-performance animals at a given CL, or a combination of these.

Genome-wide association study of disease resilience traits from a natural polymicrobial disease challenge model in pigs identifies the importance of the major histocompatibility complex region.

Infectious diseases cause tremendous financial losses in the pork industry, emphasizing the importance of disease resilience, which is the ability of an animal to maintain performance under disease. Previously, a natural polymicrobial disease challenge model was established, in which pigs were challenged in the late nursery phase by multiple pathogens to maximize expression of genetic differences in disease resilience. Genetic analysis found that performance traits in this model, including growth rate, feed and water intake, and carcass traits, as well as clinical disease phenotypes, were heritable and could be selected for to increase disease resilience of pigs. The objectives of the current study were to identify genomic regions that are associated with disease resilience in this model, using genome-wide association studies and fine-mapping methods, and to use gene set enrichment analyses to determine whether genomic regions associated with disease resilience are enriched for previously published quantitative trait loci, functional pathways, and differentially expressed genes subject to physiological states. Multiple quantitative trait loci were detected for all recorded performance and clinical disease traits. The major histocompatibility complex region was found to explain substantial genetic variance for multiple traits, including for growth rate in the late nursery (12.8%) and finisher (2.7%), for several clinical disease traits (up to 2.7%), and for several feeding and drinking traits (up to 4%). Further fine mapping identified 4 quantitative trait loci in the major histocompatibility complex region for growth rate in the late nursery that spanned the subregions for class I, II, and III, with 1 single-nucleotide polymorphism in the major histocompatibility complex class I subregion capturing the largest effects, explaining 0.8-27.1% of genetic variance for growth rate and for multiple clinical disease traits. This single-nucleotide polymorphism was located in the enhancer of TRIM39 gene, which is involved in innate immune response. The major histocompatibility complex region was pleiotropic for growth rate in the late nursery and finisher, and for treatment and mortality rates. Growth rate in the late nursery showed strong negative genetic correlations in the major histocompatibility complex region with treatment or mortality rates (-0.62 to -0.85) and a strong positive genetic correlation with growth rate in the finisher (0.79). Gene set enrichment analyses found genomic regions associated with resilience phenotypes to be enriched for previously identified disease susceptibility and immune capacity quantitative trait loci, for genes that were differentially expressed following bacterial or virus infection and immune response, and for gene ontology terms related to immune and inflammatory response. In conclusion, the major histocompatibility complex and other quantitative trait loci that harbor immune-related genes were identified to be associated with disease resilience traits in a large-scale natural polymicrobial disease challenge. The major histocompatibility complex region was pleiotropic for growth rate under challenge and for clinical disease traits. Four quantitative trait loci were identified across the class I, II, and III subregions of the major histocompatibility complex for nursery growth rate under challenge, with 1 single-nucleotide polymorphism in the major histocompatibility complex class I subregion capturing the largest effects. The major histocompatibility complex and other quantitative trait loci identified play an important role in host response to infectious diseases and can be incorporated in selection to improve disease resilience, in particular the identified single-nucleotide polymorphism in the major histocompatibility complex class I subregion.

Profile of patients with type 2 diabetes and glycated haemoglobin ≥ 10% followed in general practice.

OBJECTIVE: To determine whether profiles of patients with unbalanced type 2 diabetes (T2DM) and glycated haemoglobin (HbA1c) ≥ 10% could be identified on the basis of socio-demographic, behavioural, clinical, and biological characteristics. METHODS: Retrospective, cross-sectional, factorial analysis study of patients with T2DM treated for at least 1 year, with HbA1c ≥ 10%. Patients were recruited via medical analysis laboratories, France. Patients were followed up in general practice with possible recourse to specialist consultations. Data were collected by means of self-administered questionnaires sent by post. RESULTS: A total of 104 patients were included: 69 men and 35 women, with a median age of 66 ± 12 years, body mass index 30.7 ± 6.2kg/m2 and 47% in a vulnerable socio-economic situation. Fifty patients (48%) were followed exclusively by their general practitioners and only 30% had no compliance problems. Creatinuria was measured at least once during the year in 92% of patients, but microalbuminuria was measured in only 20%. Age, socio-economic precariousness, insulin treatment, and follow-up by several health professionals had a negative influence on quality of life (QoL). Two patient profiles were defined by factor analysis: (i) young, rural, smoker, socially isolated, precarious patient with poor compliance and QoL; and (ii) elderly, urban, regular physical activity, in a couple, without precariousness and with satisfactory QoL. CONCLUSIONS: Analysis of the characteristics of patients with T2DM and glycaemic imbalance reveals profiles that are useful in clinical practice for a personalized approach to treatment and active prevention of diabetes complications.

Thyroid hormone suppression in feeder pigs following polymicrobial or porcine reproductive and respiratory syndrome virus-2 challenge.

Thyroid hormones are powerful regulators of growth, development, and basal metabolic rate and can be dysregulated under conditions of severe stress or illness. To understand the role of these hormones in porcine disease response, serum samples were obtained from three batches of nursery-aged pigs (n = 208) exposed to a natural polymicrobial disease challenge with an array of bacterial and viral pathogens. Levels of total thyroxin (T4) and triiodothyronine (T3) assessed in sera by radioimmunoassay, decreased significantly by 14 days post-exposure (DPE). Levels of T3 partially rebounded by 48 DPE, while T4 levels remain depressed. Post-exposure T3 and T4 levels were positively correlated with acute and long-term average daily gain (ADG). Cross-sectional sampling of animals maintained at the high health source farms, showed no equivalent change in either hormone when managed under standard industrial conditions. To further elucidate the effect of porcine reproductive and respiratory syndrome virus (PRRSV)-infection on thyroid hormone levels, archived sera over 42 days post inoculation (DPI) from nursery pigs (N = 190) challenged with one of two PRRSV2 strains by the PRRS Host Genetics Consortium were similarly assessed, with animals selected in a two-by-two design, to investigate biological extremes in ADG and viral load (VL). All animals showed a similar decrease in both thyroid hormones reaching a minimum at 7 DPI and returning to near pre-challenge levels by 42 DPI. Post-challenge T3 and T4 levels were significantly greater in high ADG groups, with no significant association with VL or strain. The results of this study demonstrate porcine susceptibility to thyroid disruption in response to disease challenge and demonstrate a relationship between this response and growth performance.

Genetic parameters of drinking and feeding traits of wean-to-finish pigs under a polymicrobial natural disease challenge.

BACKGROUND: The pork industry faces unprecedented challenges from disease, which increases cost of production and use of antibiotics, and reduces production efficiency, carcass quality, and animal wellbeing. One solution is to improve the overall resilience of pigs to a broad array of common diseases through genetic selection. Behavioral changes in feeding and drinking are usually the very first clinical signs when animals are exposed to stressors such as disease. Changes in feeding and drinking behaviors in diseased pigs may reflect the way they cope with the challenge and, thus, could be used as indicator traits to select for disease resilience. The objectives of this study were to estimate genetic parameters of feeding and drinking traits for wean-to-finish pigs in a natural polymicrobial disease challenge model, to estimate genetic correlations of feeding and drinking traits with growth rate and clinical disease traits, and to develop indicator traits to select for disease resilience. RESULTS: In general, drinking traits had moderate to high estimates of heritability, especially average daily water dispensed, duration, and number of visits (0.44 to 0.58). Similar estimates were observed for corresponding feeding traits (0.35 to 0.51). Most genetic correlation estimates among drinking traits were moderate to high (0.30 to 0.92) and higher than among feeding traits (0 to 0.11). Compared to other drinking traits, water intake duration and number of visits had relatively stronger negative genetic correlation estimates with treatment rate and mortality, especially across the challenge nursery and finisher (- 0.39 and - 0.45 for treatment rate; - 0.20 and - 0.19 for mortality). CONCLUSION: Most of the recorded drinking and feeding traits under a severe disease challenge had moderate to high estimates of heritability, especially for feed or water intake duration and number of visits. Phenotypic and genetic correlations among the recorded feeding traits under disease were generally low but drinking traits showed high correlations with each other. Water intake duration and number of visits are potential indicator traits to select for disease resilience because of their high heritability and had moderate genetic correlations with treatment and mortality rates under severe disease.

Quantitative analysis of the blood transcriptome of young healthy pigs and its relationship with subsequent disease resilience.

BACKGROUND: Disease resilience, which is the ability of an animal to maintain performance under disease, is important for pigs in commercial herds, where they are exposed to various pathogens. Our objective was to investigate population-level gene expression profiles in the blood of 912 healthy F1 barrows at ~ 27 days of age for associations with performance and health before and after their exposure to a natural polymicrobial disease challenge at ~ 43 days of age. RESULTS: Most significant (q < 0.20) associations of the level of expression of individual genes in blood of young healthy pigs were identified for concurrent growth rate and subjective health scores prior to the challenge, and for mortality, a combined mortality-treatment trait, and feed conversion rate after the challenge. Gene set enrichment analyses revealed three groups of gene ontology biological process terms that were related to disease resilience: 1) immune and stress response-related terms were enriched among genes whose increased expression was unfavorably associated with both pre- and post-challenge traits, 2) heme-related terms were enriched among genes that had favorable associations with both pre- and post-challenge traits, and 3) terms related to protein localization and viral gene expression were enriched among genes that were associated with reduced performance and health traits after but not before the challenge. CONCLUSIONS: Gene expression profiles in blood from young healthy piglets provide insight into their performance when exposed to disease and other stressors. The expression of genes involved in stress response, heme metabolism, and baseline expression of host genes related to virus propagation were found to be associated with host response to disease.

Investigating the genetic architecture of disease resilience in pigs by genome-wide association studies of complete blood count traits collected from a natural disease challenge model.

BACKGROUND: Genetic improvement for disease resilience is anticipated to be a practical method to improve efficiency and profitability of the pig industry, as resilient pigs maintain a relatively undepressed level of performance in the face of infection. However, multiple biological functions are known to be involved in disease resilience and this complexity means that the genetic architecture of disease resilience remains largely unknown. Here, we conducted genome-wide association studies (GWAS) of 465,910 autosomal SNPs for complete blood count (CBC) traits that are important in an animal's disease response. The aim was to identify the genetic control of disease resilience. RESULTS: Univariate and multivariate single-step GWAS were performed on 15 CBC traits measured from the blood samples of 2743 crossbred (Landrace × Yorkshire) barrows drawn at 2-weeks before, and at 2 and 6-weeks after exposure to a polymicrobial infectious challenge. Overall, at a genome-wise false discovery rate of 0.05, five genomic regions located on Sus scrofa chromosome (SSC) 2, SSC4, SSC9, SSC10, and SSC12, were significantly associated with white blood cell traits in response to the polymicrobial challenge, and nine genomic regions on multiple chromosomes (SSC1, SSC4, SSC5, SSC6, SSC8, SSC9, SSC11, SSC12, SSC17) were significantly associated with red blood cell and platelet traits collected before and after exposure to the challenge. By functional enrichment analyses using Ingenuity Pathway Analysis (IPA) and literature review of previous CBC studies, candidate genes located nearby significant single-nucleotide polymorphisms were found to be involved in immune response, hematopoiesis, red blood cell morphology, and platelet aggregation. CONCLUSIONS: This study helps to improve our understanding of the genetic basis of CBC traits collected before and after exposure to a polymicrobial infectious challenge and provides a step forward to improve disease resilience.

Proliferation of peripheral blood mononuclear cells from healthy piglets after mitogen stimulation as indicators of disease resilience.

Disease resilience refers to the productivity of an animal under disease. Given the high biosecurity of pig nucleus herds, traits that can be measured on healthy pigs and that are genetically correlated with disease resilience, that is, genetic indicator traits, offer a strategy to select for disease resilience. Our objective was to evaluate mitogen stimulation assays (MSAs) on peripheral blood mononuclear cells (PBMCs) from young healthy pigs as genetic indicators for disease resilience. Data were from a natural disease challenge in which batches of 60 or 75 naïve Yorkshire × Landrace piglets were introduced every 3 wk into a continuous flow barn that was seeded with multiple diseases. In this environment, disease resilience traits, including growth, treatment, and mortality rates, were recorded on 3,136 pigs that were genotyped with a high-density marker panel. PBMCs from 882 of these pigs from 19 batches were isolated from whole blood collected prior to the disease challenge and stimulated with five mitogens: concanavalin A (ConA), phytohemagglutinin (PHA), pokeweed mitogen (PWM), lipopolysaccharide (LPS), and phorbol myristate acetate (PMA). The proliferation of cells was evaluated at 48, 72, and 96 h and compared with unstimulated samples (rest count). Heritabilities of cell proliferation were estimated using a model with batch as a fixed effect and covariates of entry age; rest count; complete blood count proportions of lymphocytes, monocytes, eosinophils, and basophils; and pen, litter, and animal genetics as random effects. Heritability estimates were highest for response to ConA (0.30 ± 0.09, 0.28 ± 0.10, 0.17 ± 0.10, and 0.25 ±0.10 at 48, 72, and 96 h after stimulation and for area under the curve across the three time points, respectively). Estimates were in a similar range for response to PHA and PMA but low for PWM and LPS. Responses to ConA, PHA, and PMA were moderately genetically correlated with several disease resilience traits and in the expected direction, but individual estimates were not significantly different from zero due to large SEs. In conclusion, although validation is needed, MSAss, in particular based on ConA, show promise as genetic indicator traits for disease resilience.

Protective effects of dietary carnosine during in-vitro digestion of pork differing in fat content and cooking conditions.

Muscle carnosine represents an important health advantage of meat. Ground pork samples with intrinsic or added carnosine; fat content; and cooked under low or high intensity as a 2 × 2 × 2 factorial were digested in-vitro. Changes in free carnosine and in markers of lipid (hexanal, 4-hydroxynonenal (4-HNE), malondialdehyde (MDA) and protein (protein-carbonyls, thiols) oxidation, and of advanced glycation end-products (AGEs) Nε -(carboxymethyl)lysine (CML) were determined in the saliva, gastric, and duodenal digests. During digestion, the different markers overall indicated increased oxidation and decreased free carnosine. Increasing pork carnosine level significantly reduced protein carbonyls, loss of thiols, and 4-HNE during in-vitro gastric digestion, irrespective of fat and cooking level of the meat. Increased carnosine also significantly reduced hexanal, MDA and CML up to the duodenum phase in moderately cooked lean pork. Besides substantiating the formation of AGEs during digestion, these results show a potentially important role of dietary carnosine occurring in the gastrointestinal tract. PRACTICAL APPLICATIONS: The ailments epidemiologically associated with red meat consumption could be counteracted by ingesting carnosine into meat. The health advantages of dietary carnosine, however, have never been demonstrated during digestion, a unique and complex oxidative environment compounded by the composition and cooking of the meat. The results obtained substantiated that AGEs formation occurred in-vitro in the GIT. They also showed that increased carnosine had an immediate health beneficial role during pork digestion in reducing the formation of different harmful molecules, including AGEs, modulated by the composition and cooking of the meat. However, in exerting this protective role in the GIT, the remaining free level of carnosine, gradually decreased during digestion. Carnosine, as an important meat compositional factor may, depending on the fat content and cooking conditions, change the image of meat from representing a health risk to a health benefit. Carnosine level may also explain discrepancies observed in the literature.

The genetic basis of natural antibody titers of young healthy pigs and relationships with disease resilience.

BACKGROUND: Disease resilience is the ability to maintain performance under pathogen exposure but is difficult to select for because breeding populations are raised under high health. Selection for resilience requires a trait that is heritable, easy to measure on healthy animals, and genetically correlated with resilience. Natural antibodies (NAb) are important parts of the innate immune system and are found to be heritable and associated with disease susceptibility in dairy cattle and poultry. Our objective was to investigate NAb and total IgG in blood of healthy, young pigs as potential indicator traits for disease resilience. RESULTS: Data were from Yorkshire x Landrace pigs, with IgG and IgM NAb (four antigens) and total IgG measured by ELISA in blood plasma collected ~ 1 week after weaning, prior to their exposure to a natural polymicrobial challenge. Heritability estimates were lower for IgG NAb (0.12 to 0.24, + 0.05) and for total IgG (0.19 + 0.05) than for IgM NAb (0.33 to 0.53, + 0.07) but maternal effects were larger for IgG NAb (0.41 to 0.52, + 0.03) and for total IgG (0.19 + 0.05) than for IgM NAb (0.00 to 0.10, + 0.04). Phenotypically, IgM NAb titers were moderately correlated with each other (average 0.60), as were IgG NAb titers (average 0.42), but correlations between IgM and IgG NAb titers were weak (average 0.09). Phenotypic correlations of total IgG were moderate with NAb IgG (average 0.46) but weak with NAb IgM (average 0.01). Estimates of genetic correlations among NAb showed similar patterns but with small SE, with estimates averaging 0.76 among IgG NAb, 0.63 among IgM NAb, 0.17 between IgG and IgM NAb, 0.64 between total IgG and IgG NAb, and 0.13 between total IgG and IgM NAb. Phenotypically, pigs that survived had slightly higher levels of NAb and total IgG than pigs that died. Genetically, higher levels of NAb tended to be associated with greater disease resilience based on lower mortality and fewer parenteral antibiotic treatments. Genome-wide association analyses for NAb titers identified several genomic regions, with several candidate genes for immune response. CONCLUSIONS: Levels of NAb in blood of healthy young piglets are heritable and potential genetic indicators of resilience to polymicrobial disease.

Genetic Parameters of Honey Bee Colonies Traits in a Canadian Selection Program.

Genetic selection has led to spectacular advances in animal production in many domestic species. However, it is still little applied to honey bees (Apis mellifera), whose complex genetic and reproductive characteristics are a challenge to model statistically. Advances in informatics now enable creation of a statistical model consistent with honey bee genetics, and, consequently, genetic selection for this species. The aim of this project was to determine the genetic parameters of several traits important for Canadian beekeepers with a view to establishing a breeding program in a northern context. Our results show that the five traits measured (Varroa destructor infestation, spring development, honey production, winter consumption, and hygienic behavior) are heritable. Thus, the rate of V. destructor infestation has a high heritability (h2 = 0.44 ± 0.56), spring development and honey production have a medium heritability (respectively, h2 = 0.30 ± 0.14 and h2 = 0.20 ± 0.13), and winter consumption and hygienic behavior have a low heritability (respectively, h2 = 0.11 ± 0.09 and h2 = 0.18 ± 0.13). Furthermore, the genetic correlations between these traits are all positive or null, except between hygienic behavior and V. destructor infestation level. These genetic parameters will be instrumental to the development of a selection index that will be used to improve the capacity of honey bees to thrive in northern conditions.