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Abstract Diabetes constitutes a major public health problem, with dramatic consequences for patients. Both genetic and environmental factors were shown to contribute to the different forms of the disease. The monogenic forms, found both in humans and in animal models, specially help to decipher the role of key genes in the physiopathology of the disease. Here, we describe the phenotype of early diabetes in a colony of NOD mice, with spontaneous invalidation of Akt2, that we called HYP. The HYP mice were characterised by a strong and chronic hyperglycaemia, beginning around the age of one month, especially in male mice. The phenotype was not the consequence of the acceleration of the autoimmune response, inherent to the NOD background. Interestingly, in HYP mice, we observed hyperinsulinemia before hyperglycaemia occurred. We did not find any difference in the pancreas’ architecture of the NOD and HYP mice (islets’ size and staining for insulin and glucagon) but we detected a lower insulin content in the pancreas of HYP mice compared to NOD mice. These results give new insights about the role played by Akt2 in glucose homeostasis and argue for the ß cell failure being the primary event in the course of diabetes.

Hair cortisol is a stress indicator and could be used to assess the pigs’ exposure to stressors in the weeks/months prior to non-invasive hair sampling. The main aim of this study was to describe the hair cortisol concentration (HCC) variability between individuals within a batch, between farms and between batches within a farm. The secondary aim was to determine how the number of sampled pigs influences the characterization of HCC within a batch. Twenty farrow-to-finish pig farms were recruited considering the diversity of their management practices and health status (data collected). Hair was sampled in two separate batches, 8 months apart. The necks of 24 finishing pigs were clipped per batch the week prior to slaughter. To describe the variability in HCC, an analysis of the variance model was run with three explanatory variables (batch, farm and their interaction). To identify farm clusters, a principal component analysis followed by a hierarchical clustering was carried out with four active variables (means and standard deviations of the two batches per farm) and 17 supplementary variables (management practices, herd health data). We determined how the number of sampled pigs influenced the characterization of HCC within a batch by selecting subsamples of the results. HCC ranged from 0.4 to 121.6 pg/mg, with a mean of 25.9 ± 16.2 pg/mg. The variability in HCC was mainly explained by differences between pigs (57%), then between farms (24%), between batches within the same farm (16%) and between batches (3%). Three clusters of farms were identified: low homogeneous concentrations (n = 3 farms), heterogeneous concentrations with either higher (n = 7) or lower (n = 10) HCC in batch 2 than in batch 1. The diversity of management practices and health statuses allowed to discuss hypotheses explaining the HCC variations observed. We highlighted the need to sample more than 24 pigs to characterize HCC in a pig batch. HCC differences between batches on six farms suggest sampling pigs in more than one batch to describe the HCC at the farm level. HCC variations described here confirm the need to study its links with exposure of pigs to stressors.

Abstract Background Multiple antigenic stimulations are crucial to immune system training during early post-natal life. These stimulations can be either due to commensals, which accounts for the acquisition and maintenance of tolerance, or to pathogens, which triggers immunity. In pig, only few works previously explored the influence of natural exposition to pathogens upon immune competence. We propose herein the results of a multicentric, field study, conducted on 265 piglets exposed to contrasted pathogen levels in their living environment. Piglets were housed in 15 different commercial farms, sorted in two groups, low (HSLOW)- and high (HSHIGH)-health status farms, depending on their recurrent exposition to five common swine pathogens. Results Using animal-based measures, we compared the immune competence and growth performances of HSLOW and HSHIGH pigs around weaning. As expected, we observed a rise in the number of circulating leucocytes with age, which affected different cell populations. Monocyte, antigen-experienced and cytotoxic lymphocyte subpopulation counts were higher in piglets reared in HSLOW farms as compared to their HSHIGH homologs. Also, the age-dependent evolution in γδ T cell and neutrophil counts was significantly affected by the health status. With age, circulating IFNα level decreased and IgM level increased while being greater in HSLOW piglets at any time. After weaning, LPS-stimulated blood cells derived from HSLOW piglets were more prone to secrete IL-8 than those derived from HSHIGH pigs did. Monocytes and granulocytes issued from HSLOW pigs also exhibited comparable phagocytosis capacity. Altogether our data emphasize the more robust immunophenotype of HSLOW piglets. Finally, piglets raised under higher pathogen pressure grew less than HSHIGH piglets did and exhibited a different metabolic profile. The higher cost of the immune responses associated with the low farm health status may account for lower HSLOW piglet performances. Conclusions Altogether, our data, obtained in field conditions, provide evidence that early exposure to pathogens shapes the immune competence of piglets. They also document the negative impact of an overstimulation of the immune system on piglets’ growth.

Abstract The change of the century saw the emergence of a series of discourses that conceptualised different aspects related with culture as key elements in the future of urban realities. The fact that these notions have become encompassed within the celebrated label of “the creative city” leads us to think that they form a self-evident model, fully assimilated and of general value. However, the review of the process through which a reasonably cohesive and accepted framework was constructed unveils the complex nature of the creative city. This article introduces the idea of the creative city as an “approach”, in the sense of an epistemological and methodological focus that is distinguishable, yet neither rigid nor closed. An understanding of this type is useful for assessing the validity and the imbalances of the creative city in the midst of an epoch of problematic transition, in which culture and the city are alternatively defined as spaces of conflict or spaces of hope.

Effective, patient-tailored rehabilitation to restore upper-limb motor function in severely impaired stroke patients is still missing. If suitably combined and administered in a personalized fashion, neurotechnologies offer a large potential to assist rehabilitative therapies to enhance individual treatment effects. AVANCER (clinicaltrials.gov NCT04448483) is a two-center proof-of-concept trial with an individual based cumulative longitudinal intervention design aiming at reducing upper-limb motor impairment in severely affected stroke patients with the help of multiple neurotechnologies. AVANCER will determine feasibility, safety, and effectivity of this innovative intervention. Thirty chronic stroke patients with a Fugl-Meyer assessment of the upper limb (FM-UE)

Abstract Background The sustainability of farming and animal welfare requires the reconsideration of current selection schemes. In particular, implementation of new selection criteria related to animal health and welfare should help to produce more robust animals and to reduce anti-microbial use. The hypothalamo-pituitary-adrenocortical (HPA) axis plays a major role in metabolic regulation and adaptation processes and its activity is strongly influenced by genetic factors. A positive association between HPA axis activity and robustness was recently described. To explore whether selecting pigs upon HPA axis activity could increase their robustness, a divergent selection experiment was carried out in the Large White pig breed. This allowed the generation of low (HPAlo) and high (HPAhi) responders to adrenocorticotropic hormone administration. Results In this study, we compared 23 hematologic and immune parameters of 6-week-old, HPAlo and HPAhi piglets and analysed their response to a low dose of lipopolysaccharide (LPS) two weeks later. At six weeks of age, HPAhi piglets displayed greater red blood cell and leucocyte number including CD8α+ γδ cells, cytotoxic T lymphocytes, naive T helper (Th) cells and B lymphocytes as compared to HPAlo individuals. The ability of blood cells to secrete TNFα in response to LPS ex vivo was higher for HPAhi pigs. At week eight, the inflammatory response to the LPS in vivo challenge was poorly affected by the HPA axis activity. Conclusions Divergent selection upon HPA axis activity modulated hematologic and immune parameters in 6-week-old pigs, which may confer an advantage to HPAhi pigs at weaning. However, HPAlo and HPAhi piglets did not exhibit major differences in the parameters analysed two weeks later, i. e. in 8-week-old pigs. In conclusion, chronic exposure to high cortisol levels in HPAhi pigs does not negatively impact immunity.

Features of intensive farming can seriously threaten pig homeostasis, well-being and productivity. Disease tolerance of an organism is the adaptive ability in preserving homeostasis and at the same time limiting the detrimental impact that infection can inflict on its health and performance without affecting pathogen burden per se. While disease resistance (DRs) can be assessed measuring appropriately the pathogen burden within the host, the tolerance cannot be quantified easily. Indeed, it requires the assessment of the changes in performance as well as the changes in pathogen burden. In this paper, special attention is given to criteria required to standardize methodologies for assessing disease tolerance (DT) in respect of infectious diseases in pigs. The concept is applied to different areas of expertise and specific examples are given. The basic physiological mechanisms of DT are reviewed. Disease tolerance pathways, genetics of the tolerance-related traits, stress and disease tolerance, and role of metabolic stress in DT are described. In addition, methodologies based on monitoring of growth and reproductive performance, welfare, emotional affective states, sickness behavior for assessment of disease tolerance, and methodologies based on the relationship between environmental challenges and disease tolerance are considered. Automated Precision Livestock Farming technologies available for monitoring performance, health and welfare-related measures in pig farms, and their limitations regarding DT in pigs are also presented. Since defining standardized methodologies for assessing DT is a serious challenge for biologists, animal scientists and veterinarians, this work should contribute to improvement of health, welfare and production in pigs.

The hepatocarcinoma-intestine-pancreas (HIP) gene, also called pancreatitis-associated protein-1 (PAP1) or Reg IIIα, is activated in most human hepatocellular carcinomas (HCCs) but not in normal liver, which suggests that HIP regulatory sequence could be used as efficient liver tumor-specific promoters to express a therapeutic polynucleotide in liver cancer. The sodium iodide symporter (NIS), which has recognized therapeutic and reporter gene properties, is appropriate to evaluate the transcriptional strength and specificity of the HIP promoter in HCC. For this purpose, we constructed a recombinant rat HIP–NIS adenoviral vector (AdrHIP-NIS), and evaluated its performance as a mediator of selective radioiodide uptake in tumor hepatocytes. Western blot, immunofluorescence, and iodide uptake assays were performed in AdrHIP-NIS-infected primary hepatocytes and transformed hepatic and nonhepatic cells. Nuclear imaging, tissue counting and immunohistochemistry were performed in normal and HCC-bearing Wistar rats infected with AdrHIP-NIS intratumorally or via the hepatic artery. In AdrHIP-NIS-infected transformed hepatic cells, functional NIS was strongly expressed, as in cells infected with a cytomegalovirus-NIS vector. No NIS expression was found in AdrHIP-NIS-infected normal hepatocytes or transformed nonhepatic cells. In rats bearing multinodular HCC, AdrHIP-NIS triggered functional NIS expression that was preferential in tumor hepatocytes. Administration of 18 mCi of 131I resulted in the destruction of AdrHIP-NIS-injected nodules. This study has identified the rHIP regulatory sequence as a potent liver tumor-specific promoter for the transfer of therapeutic genes, and AdrHIP-NIS-mediated 131I therapy as a valuable option for the treatment of multinodular HCC. [ABSTRACT FROM AUTHOR]