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OBJECTIVE: Extracellular matrix deposition is tightly controlled by a network of regulatory cytokines. Among them, interleukin-1beta (IL-1beta) and transforming growth factor beta1 (TGFbeta1) have been shown to play antagonistic roles in tissue homeostasis. The purpose of this study was to determine the influence of IL-1beta on TGFbeta receptor type II (TGFbetaRII) regulation and TGFbeta1 responsiveness in human articular chondrocytes. METHODS: TGFbeta1-induced gene expression was analyzed through plasminogen activator inhibitor 1 and p3TP-Lux induction. Receptor-activated Smad (R-Smad) phosphorylation, TGFbeta receptors, and Smad expression were determined by Western blotting and real-time reverse transcription-polymerase chain reaction techniques. Signaling pathways were investigated using specific inhibitors, messenger RNA (mRNA) silencing, and expression vectors. RESULTS: IL-1beta down-regulated TGFbetaRII expression at both the protein and mRNA levels and led to inhibition of the TGFbeta1-induced gene expression and Smad2/3 phosphorylation. Moreover, IL-1beta strongly stimulated the expression of inhibitory Smad7. TGFbetaRII overexpression abolished the loss of TGFbeta1 responsiveness induced by IL-1beta. The decrease in TGFbetaRII required de novo protein synthesis and involved both the NF-kappaB and JNK pathways. CONCLUSION: We demonstrate that IL-1beta impairs TGFbeta1 signaling through down-regulation of TGFbetaRII, which is mediated by the p65/NF-kappaB and activator protein 1/JNK pathways, and secondarily through the up-regulation of Smad7. These findings show that there is cross-talk in the signaling of 2 regulatory cytokines involved in inflammation. [ABSTRACT FROM AUTHOR]

Paula D Galera1, Dennis E Brooks21College of Veterinary Medicine, University of Brasilia, DF, Brazil; 2Departments of Large and Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USAAbstract: Keratomycosis in the horse exists in several unique clinical forms. This paper discusses the diagnosis and clinical management of keratomycosis in the horse associated with tear film instability, epithelial keratopathy, subepithelial infiltrates, superficial and deep ulcers, plaques, melting ulcers, descemetoceles, iris prolapse, and stromal abscesses. Prompt diagnosis and aggressive treatment of equine keratomycosis can make a major difference in the maintenance of a cosmetic and visual eye.Keywords: fungal keratitis, keratomycosis, horse, cornea, melting, keratoplasty

Objective: To assess the link between childhood attention problems (AP) and substance use 18 years later. Study design: This cohort study was conducted in a community sample of 1103 French youths followed from 1991 to 2009. Exposures and covariates were childhood behavioral problems (based on parental report at baseline), early substance use, school difficulties, and family adversity. Outcome measures were regular tobacco smoking, alcohol problems, problematic cannabis use, and lifetime cocaine use (based on youth reports at follow-up). Results: Individuals with high levels of childhood AP had higher rates of substance use (regular tobacco smoking, alcohol problems, problematic cannabis use, and lifetime cocaine use). However, when taking into account other childhood behavioral problems, early substance use, school difficulties, and family adversity, childhood AP were related only to regular tobacco smoking and lifetime cocaine use. Early cannabis exposure was the strongest risk factor for all substance use problems. Conclusion: This longitudinal community-based study shows that, except for tobacco and cocaine, the association between childhood AP and substance use is confounded by a range of early risk factors. Early cannabis exposure plays a central role in later substance use. [Copyright &y& Elsevier]

Context: Osteoarthritis (OA) is an invalidating articular disease characterized by cartilage degradation and inflammatory events. In horses, OA is associated with up to 60% of lameness and leads to reduced animal welfare along with extensive economic losses; currently, there are no curative therapies to treat OA. The mesenchymal stromal cell (MSC) secretome exhibits anti-inflammatory properties, making it an attractive candidate for improving the management of OA. In this study, we determined the best storage conditions for conditioned media (CMs) and tested whether priming MSCs with cytokines can enhance the properties of the MSC secretome.Methods: First, properties of CMs collected from bone-marrow MSC cultures and stored at −80°C, −20°C, 4°C, 20°C or 37°C were assessed on 3D cultures of equine articular chondrocytes (eACs). Second, we primed MSCs with IL-1β, TNF-α or IFN-γ, and evaluated the MSC transcript levels of immunomodulatory effectors and growth factors. The primed CMs were also harvested for subsequent treatment of eACs, either cultured in monolayers or as 3D cell cultures. Finally, we evaluated the effect of CMs on the proliferation and the phenotype of eACs and the quality of the extracellular matrix of the neosynthesized cartilage.Results: CM storage at −80°C, −20°C, and 4°C improved collagen protein accumulation, cell proliferation and the downregulation of inflammation. The three cytokines chosen for the MSC priming influenced MSC immunomodulator gene expression, although each cytokine led to a different pattern of MSC immunomodulation. The cytokine-primed CM had no major effect on eAC proliferation, with IL-1β and TNF-α slightly increasing collagen (types IIB and I) accumulation in eAC 3D cultures (particularly with the CM derived from MSCs primed with IL-1β), and IFN-γ leading to a marked decrease. IL-1β-primed CMs resulted in increased eAC transcript levels of MMP1, MMP13 and HTRA1, whereas IFNγ-primed CMs decreased the levels of HTRA1 and MMP13.Conclusion: Although the three cytokines differentially affected the expression of immunomodulatory molecules, primed CMs induced a distinct effect on eACs according to the cytokine used for MSC priming. Different mechanisms seemed to be triggered by each priming cytokine, highlighting the need for further investigation. Nevertheless, this study demonstrates the potential of MSC-CMs for improving equine OA management.

Introduction Perinatal maternal depression and anxiety are associated with adverse maternal outcomes, and nutrition may play an important role in their emergence. Previous research shows that certain micro and macronutrients found in different dietary patterns may influence perinatal mood disorders. Objectives This study aims to explore relationships between nutrition during pregnancy and perinatal maternal depression and anxiety symptoms using network analyses. Methods Using data from the French EDEN mother-child cohort, the sample consisted of 1438 women with available perinatal mental health outcomes (CES-D, STAI and EPDS) and nutritional markers collected from food frequency questionnaires. Four networks were constructed to explore the relationships between prenatal nutrient status, dietary patterns, and perinatal mental health, while accounting for important confounders. Results The Healthy dietary pattern was associated with the presence of vital micronutrients, while the Western dietary pattern was consistently associated with poorer intake of vital micronutrients and contained an excess of certain macronutrients. Western dietary pattern and symptoms of postnatal depression were connected by a positive edge in both the macronutrient and micronutrient networks. Lower education levels were associated with higher Western dietary pattern scores, from which a positive edge linked to postnatal depression symptoms in both models. Conclusions A Western dietary pattern was associated with increased symptoms of postnatal depression in our adjusted network models; The Healthy dietary pattern was associated with essential micronutrients but not with symptoms of depression or anxiety. Perinatal mental health might be impacted by specific dietary patterns in the context of psychosocial and physical stress associated with pregnancy. Disclosure of Interest None Declared

Osteoarthritis (OA) is a degenerative disease that eventually leads to the complete degradation of articular cartilage. Articular cartilage has limited intrinsic capacity for self-repair and, to date, there is no curative treatment for OA. Humans and horses have a similar articular cartilage and OA etiology. Thus, in the context of a One Health approach, progress in the treatment of equine OA can help improve horse health and can also constitute preclinical studies for human medicine. Furthermore, equine OA affects horse welfare and leads to significant financial losses in the equine industry. In the last few years, the immunomodulatory and cartilage regenerative potentials of mesenchymal stromal cells (MSCs) have been demonstrated, but have also raised several concerns. However, most of MSC therapeutic properties are contained in their secretome, particularly in their extracellular vesicles (EVs), a promising avenue for acellular therapy. From tissue origin to in vitro culture methods, various aspects must be taken into consideration to optimize MSC secretome potential for OA treatment. Immunomodulatory and regenerative properties of MSCs can also be enhanced by recreating a pro-inflammatory environment to mimic an in vivo pathological setting, but more unusual methods also deserve to be investigated. Altogether, these strategies hold substantial potential for the development of MSC secretome-based therapies suitable for OA management. The aim of this mini review is to survey the most recent advances on MSC secretome research with regard to equine OA.

ObjectiveTo examine the relationship between young adults' labor force participation and depression in the context of the COVID-19 pandemic.Design, setting, participantsData come from the nationally-representative EPICOV cohort study set up in France, and were collected in 2020 and 2021 (3 waves of online or telephone interviews: 02/05/2020–12/06/2020; 26/10/2020–14/12/2020; 24/06/2021–09/08/2021) among 2,217 participants aged 18–30 years. Participants with prior mental health disorder (n = 50) were excluded from the statistical analyses.ResultsUsing Generalized Estimating Equation (GEE) models controlled for participants' socio-demographic and health characteristics and weighted to be nationally-representative, we found that compared to young adults who were employed, those who were studying or unemployed were significantly more likely to experience depression assessed using the PHQ-9 (multivariable ORs, respectively: OR: 1.29, 95% CI 1.05–1.60 and OR: 1.50, 1.13–1.99). Stratifying the analyses by age, we observed that unemployment was more strongly associated with depression among participants 25–30 years than among those who were 18–24 years (multivariable ORs, respectively, 1.78, 95% CI 1.17–2.71 and 1.41, 95% CI 0.96–2.09). Being out of the labor force was, to the contrary, more significantly associated with depression among participants 18–24 years (multivariable OR: 1.71, 95% CI 1.04–2.82, vs. 1.00, 95% CI 0.53–1.87 among participants 25–30 years). Stratifying the analyses by sex, we found no significant differences in the relationships between labor market characteristics and depression (compared to participants who were employed, multivariable ORs associated with being a student: men: 1.33, 95% CI 1.01–1.76; women: 1.19, 95% CI 0.85–1.67, multivariable ORs associated with being unemployed: men: 1.60, 95% CI 1.04–2.45; women: 1.47, 95% CI 1.01–2.15).Conclusions and relevanceOur study shows that in addition to students, young adults who are unemployed also experience elevated levels of depression in the context of the COVID-19 pandemic. These two groups should be the focus of specific attention in terms of prevention and mental health treatment. Supporting employment could also be a propitious way of reducing the burden of the COVID-19 pandemic on the mental health of young adults.

AbstractBackgroundCannabis use in university students is associated with academic achievement failure and health issues. The objective of the study was to evaluate the association between attention deficit hyperactivity disorder (ADHD) symptoms and cannabis use after 1 year among students according to previous cannabis use.MethodsStudents in France were recruited from February 2013 to July 2020 in the i-Share cohort. 4,270 participants were included (2,135 who never used cannabis at inclusion and 2,135 who did). The Adult ADHD Self-Report Scale (ASRS) was used to assess ADHD symptoms at inclusion. Cannabis use frequency was evaluated 1 year after inclusion. Multinomial regressions were conducted to assess the association between inclusion ADHD symptoms and cannabis use after 1 year.ResultsIncrease in ASRS scores was linked with a greater probability to use cannabis after 1 year and to have a higher cannabis use frequency (once a year—once a month adjusted odds ratio [OR]: 1.24 (1.15–1.34), more than once a month adjusted OR: 1.43 (1.27–1.61)). Among participants who never used cannabis at inclusion, this association disappeared (once a year—once a month adjusted OR: 1.15 (0.95–1.39), more than once a month adjusted OR: 1.16 (0.67–2)) but remained in participants who ever used cannabis at inclusion (once a year—once a month adjusted OR: 1.17 (1.06–1.29), more than once a month adjusted OR: 1.35 (1.18–1.55)).ConclusionsHigh levels of ADHD symptoms in students could lead to continued cannabis use rather than new initiations.

Osteoarthritis is a common cause of pain and economic loss in both humans and horses. The horse is recognized as a suitable model for human osteoarthritis, because the thickness, structure, and mechanical properties of equine articular cartilage are highly comparable to those of humans. Although a number of equine experimental osteoarthritis models have been described in the literature, these cases generally involve the induction of osteoarthritis in just one joint of each animal. This approach necessitates the involvement of large numbers of horses to obtain reliable data and thus limits the use of this animal model, for both economic and ethical reasons. This study adapts an established equine model of post-traumatic osteoarthritis to induce osteoarthritis-associated lesions in all 4 fetlock joints of the same horse in order to reduce the number of animals involved and avoid individual variability, thus obtaining a more reliable method to evaluate treatment efficacy in future studies. The objectives are to assess the feasibility of the procedure, evaluate variability of the lesions according to interindividual and operated-limb position and describe the spontaneous evolution of osteoarthritis-associated pathological changes over a twelve-week period. The procedure was well tolerated by all 8 experimental horses and successfully induced mild osteoarthritis-associated changes in the four fetlock joints of each horse. Observations were carried out using clinical, radiographic, ultrasonographic, and magnetic resonance imaging methods as well as biochemical analyses of synovial fluid and postmortem microscopic and macroscopic evaluations of the joints. No significant differences were found in the progression of osteoarthritis-associated changes between horses or between the different limbs, with the exception of higher synovial effusion in hind fetlocks compared to front fetlocks and higher radiographic scores for left fetlocks compared to the right. This model thus appears to be a reliable means to evaluate the efficacy of new treatments in horses, and may be of interest for translational studies in human medicine.

Abstract Background Suicidal ideation and suicidal risk assessment are major concerns for health professionals. The perception of a low level of parental support is a risk factor for suicidal tendencies among adolescents, but little is known about its long-term impact on the vulnerability to suicidal behavior in young adults. We investigated whether the perceived level of parental support during childhood and adolescence was associated with current suicidal ideation in young adults. Methods We retrieved data collected in the i-Share study from February 1st, 2013 through January 30, 2017. This cross-sectional study included 10,015 French students, aged 18–24 years that completed an on-line self-reported questionnaire about suicidal ideation in the last 12 months and their perceived parental support in childhood and adolescence. We performed multinomial logistic regressions and sensitivity analyses to assess associations between the degree of perceived parental support and the frequency suicidal thoughts, after adjusting for the main known risk factors of suicidal ideation. We employed multiple imputations to account for missing data. Results The study sample included 7539 female (75.7%) and 2436 male (24.3%) students (mean [SD] age 20.0 [1.8] years). About one in five students reported occasional suicidal thoughts (n = 1775, 17.7%) and 368 students (3.7%) reported frequent suicidal thoughts. The adjusted multinomial logistic regression revealed a significant negative association between perceived parental support and suicidal thoughts. A lack of perceived parental support in childhood and adolescence was associated with > 4-fold elevated risk of occasional (adjusted OR, 4.55; 95% CI: 2.97–6.99) and nearly 9-fold elevated risk of frequent (adjusted OR, 8.58; 95% CI: 4.62–15.96) suicidal thoughts, compared to individuals that perceived extremely strong parental support. This association was strongest among students with no personal history of depression or suicide attempts. Conclusions Students that perceived low levels of past parental support had a higher risk of suicidal ideation. Past perceived parental support appeared to be a potent marker of suicidal risk in young adults. This marker should be routinely collected in studies on suicidal risk in young adults, and it could be considered an additional screening tool.

Abstract Mesenchymal stem cells (MSCs) hold promise for cartilage engineering. Here, we aimed to determine the best culture conditions to induce chondrogenesis of MSCs isolated from bone marrow (BM) of aged osteoarthritis (OA) patients. We showed that these BM-MSCs proliferate slowly, are not uniformly positive for stem cell markers, and maintain their multilineage potential throughout multiple passages. The chondrogenic lineage of BM-MSCs was induced in collagen scaffolds, under normoxia or hypoxia, by BMP-2 and/or TGF-β1. The best chondrogenic induction, with the least hypertrophic induction, was obtained with the combination of BMP-2 and TGF-β1 under hypoxia. Differentiated BM-MSCs were then transfected with siRNAs targeting two markers overexpressed in OA chondrocytes, type I collagen and/or HtrA1 protease. siRNAs significantly decreased mRNA and protein levels of type I collagen and HtrA1, resulting in a more typical chondrocyte phenotype, but with frequent calcification of the subcutaneously implanted constructs in a nude mouse model. Our 3D culture model with BMP-2/TGF-β1 and COL1A1/HtrA1 siRNAs was not effective in producing a cartilage-like matrix in vivo. Further optimization is needed to stabilize the chondrocyte phenotype of differentiated BM-MSCs. Nevertheless, this study offers the opportunity to develop a combinatory cellular therapy strategy for cartilage tissue engineering.

ObjectivesThe aim of the study was to estimate the association between self-esteem and subsequent self-rated health during college years, taking into account a wide range of potential confounders.DesignProspective longitudinal study.SettingThe French i-Share cohort.ParticipantsThe sample consisted of 1011 college students.Primary and secondary outcome measuresThe association between self-esteem and later self-rated health was evaluated using multivariate modelling.Data regarding self-rated health, global self-esteem and demographic, educational, social, behavioural, environmental and financial characteristics were collected through an internet-based questionnaire.ResultsThe 1011 participants had a median age of 21.9 years and 79% (795/1011) were females. Self-rated health was assessed a median of 8 months after the self-esteem measurement. Twenty per cent of the students declared average to very poor health (203/1011). Students with higher levels of self-esteem were more likely to declare good or very good self-rated health (adjusted OR=1.40, 95% CI 1.15 to 1.72, p value=0.001). Other factors associated with good or very good self-rated health were low body mass index, a comfortable financial situation during childhood and three personality traits (low persistence and harm avoidance and high cooperativeness).ConclusionsThis study offers novel findings on the impact of self-esteem on self-rated health among college students. Interventions targeting self-esteem should be experimented during university years in order to improve health outcomes.

Osteoarthritis is a significant and costly cause of pain for both humans and horses. The horse has been identified as a suitable model for human osteoarthritis. Regenerative therapy with allogeneic mesenchymal stem cells (MSCs) is a promising treatment, but the safety of this procedure continues to be debated. The aim of this study is to evaluate the safety of intra-articular injections of allogeneic MSCs on healthy joints by comparing two different dosages and two different tissue sources, namely, bone marrow and umbilical cord blood, with a placebo treatment on the same individuals. We also assessed the influence of autologous versus allogeneic cells for bone marrow-derived MSC treatment. Twelve clinically sound horses were subjected to injections in their 4 fetlock joints. Each of the three fetlocks was administered a different MSC type, and the remaining fetlock was injected with phosphate-buffered saline as a control. Six horses received 10 million cells per joint, and the 6 other horses received 20 million cells per joint. Clinical and ultrasound monitoring revealed that allogeneic bone marrow-derived MSCs induced significantly more synovial effusion compared to umbilical cord blood-derived MSCs but no significant difference was noted within the synovial fluid parameters. The administration of 10 million cells in horses triggered significantly more inflammatory signs than the administration of 20 million cells. Mesenchymal stem cell injections induced mild to moderate local inflammatory signs compared to the placebo, with individual variability in the sensitivity to the same line of MSCs. Understanding the behavior of stem cells when injected alone is a step towards the safer use of new strategies in stem cell therapy, where the use of either MSC secretome or MSCs combined with biomaterials could enhance their viability and metabolic activity.

Depuis le bilan établi en 1932 par Rodolfo Usigli, qui soulignait dans son essai México en el teatro la nécessité de se détacher des modèles imposés pour réintroduire la réalité mexicaine dans le répertoire « national », plusieurs générations de dramaturges se sont succédées et leurs apports ont contribué à exaucer les souhaits de leur précurseur. Les artistes dont les œuvres ont été mises en scène à la charnière du xxe et du xxie siècle offrent à la scène internationale des œuvres qui allient les réalités nationales et une portée plus universelle. Au-delà de la grande variété formelle et thématique des créations, certaines convergences se dessinent, dont l’intégration, depuis les années 1990, d’influences qui découlent des tragiques grecs par l’intermédiaire d’auteurs français tels que Jean Racine, Jean Giraudoux et Marguerite Yourcenar. Ce réseau d’échos et de résonnances sera particulièrement illustré par les pièces des mexicains Hugo Salcedo, Edgar Chías et Ximena Escalante.

While human mesenchymal stem cells (hMSCs), either in the bone marrow or in tumour microenvironment could be targeted by radiotherapy, their response is poorly understood. The oxic effects on radiosensitivity, cell cycle progression are largely unknown, and the radiation effects on hMSCs differentiation capacities remained unexplored. Here we analysed hMSCs viability and cell cycle progression in 21% O2 and 3% O2 conditions after medical X-rays irradiation. Differentiation towards osteogenesis and chondrogenesis after irradiation was evaluated through an analysis of differentiation specific genes. Finally, a 3D culture model in hypoxia was used to evaluate chondrogenesis in conditions mimicking the natural hMSCs microenvironment. The hMSCs radiosensitivity was not affected by O2 tension. A decreased number of cells in S phase and an increase in G2/M were observed in both O2 tensions after 16 hours but hMSCs released from the G2/M arrest and proliferated at day 7. Osteogenesis was increased after irradiation with an enhancement of mRNA expression of specific osteogenic genes (alkaline phosphatase, osteopontin). Osteoblastic differentiation was altered since matrix deposition was impaired with a decreased expression of collagen I, probably through an increase of its degradation by MMP-3. After induction in monolayers, chondrogenesis was altered after irradiation with an increase in COL1A1 and a decrease in both SOX9 and ACAN mRNA expression. After induction in a 3D culture in hypoxia, chondrogenesis was altered after irradiation with a decrease in COL2A1, ACAN and SOX9 mRNA amounts associated with a RUNX2 increase. Together with collagens I and II proteins decrease, associated to a MMP-13 expression increase, these data show a radiation-induced impairment of chondrogenesis. Finally, a radiation-induced impairment of both osteogenesis and chondrogenesis was characterised by a matrix composition alteration, through inhibition of synthesis and/or increased degradation. Alteration of osteogenesis and chondrogenesis in hMSCs could potentially explain bone/joints defects observed after radiotherapy.

Both distractions (external and internal) and attention-deficit/hyperactivity disorder (ADHD) are serious risk factors for traffic crashes and injuries. However, it is still unknown if ADHD (a chronic condition) modifies the effect of distractions (irregular hazards) on traffic crashes. The objective of this study was to assess the effects of distractions and ADHD on traffic crash responsibility.A responsibility case-control study was conducted in the adult emergency department of Bordeaux University Hospital, France. Subjects were recruited among drivers injured in a motor vehicle crash between April 2010 and August 2011. Responsibility levels were estimated using a standardized method. Frequencies of exposures were compared between drivers responsible and drivers not responsible for the crash. Independent risk factors were identified using a multivariate logistic regression including test interactions between distractions and ADHD.A total of 777 subjects were included in the analysis. Factors associated with responsibility were distraction induced by an external event (adjusted OR (aOR) = 1.47; 95% confidence interval (CI) [1.06-2.05]), distraction induced by an internal thought (aOR = 2.38; CI: [1.50-3.77]) and ADHD (aOR = 2.18 CI: [1.22-3.88]). The combined effect of ADHD and external distractions was strongly associated with responsibility for the crash (aOR = 5.79 CI: [2.06-16.32]). Interaction assessment showed that the attributable proportion due to the interaction among participants with both exposures was 68%.Adults with ADHD are a population at higher risk of being responsible for a road traffic crash when exposed to external distractions. This result reinforces the need to diagnose adult ADHD and to include road safety awareness messages delivered by the physician. Developing advanced driver assistance systems devoted to the management of attention lapses is also increasingly relevant for these drivers.

Common negative events can precipitate the onset of internalizing symptoms. We studied whether their occurrence in childhood is associated with mental health trajectories over the course of development.Using data from the TEMPO study, a French community-based cohort study of youths, we studied the association between negative events in 1991 (when participants were aged 4-16 years) and internalizing symptoms, assessed by the ASEBA family of instruments in 1991, 1999, and 2009 (n = 1503). Participants' trajectories of internalizing symptoms were estimated with semi-parametric regression methods (PROC TRAJ). Data were analyzed using multinomial regression models controlled for participants' sex, age, parental family status, socio-economic position, and parental history of depression.Negative childhood events were associated with an increased likelihood of concurrent internalizing symptoms which sometimes persisted into adulthood (multivariate ORs associated with > = 3 negative events respectively: high and decreasing internalizing symptoms: 5.54, 95% CI: 3.20-9.58; persistently high internalizing symptoms: 8.94, 95% CI: 2.82-28.31). Specific negative events most strongly associated with youths' persistent internalizing symptoms included: school difficulties (multivariate OR: 5.31, 95% CI: 2.24-12.59), parental stress (multivariate OR: 4.69, 95% CI: 2.02-10.87), serious illness/health problems (multivariate OR: 4.13, 95% CI: 1.76-9.70), and social isolation (multivariate OR: 2.24, 95% CI: 1.00-5.08).Common negative events can contribute to the onset of children's lasting psychological difficulties.

Mollusc shells are composed of more than 95% calcium carbonate and less than 5% of an organic matrix consisting mostly of proteins, glycoproteins and polysaccharides. Previous studies have elucidated the biological activities of the shell matrices from bivalve molluscs on skin, especially on the expression of the extracellular matrix components of fibroblasts. In this work, we have investigated the potential biological activities of shell matrix components extracted from the shell of the scallop Pecten maximus on human fibroblasts in primary culture. Firstly, we demonstrated that shell matrix components had different effects on general cellular activities. Secondly, we have shown that the shell matrix components stimulate the synthesis of type I and III collagens, as well as that of sulphated GAGs. The increased expression of type I collagen is likely mediated by the recruitment of transactivating factors (Sp1, Sp3 and human c-Krox) in the -112/-61 bp COL1A1 promoter region. Finally, contrarily to what was obtained in previous works, we demonstrated that the scallop shell extracts have only a small effect on cell migration during in vitro wound tests and have no effect on cell proliferation. Thus, our research emphasizes the potential use of shell matrix of Pecten maximus for dermo-cosmetic applications.

Research shows that children with Attention Deficit/Hyperactivity Disorder are at elevated risk of criminality. However, several issues still need to be addressed in order to verify whether hyperactivity in itself plays a role in the prediction of criminality. In particular, co-occurrence with other behaviors as well as the internal heterogeneity in ADHD symptoms (hyperactivity and inattention) should be taken into account. The aim of this study was to assess the unique and interactive contributions of hyperactivity to the development of criminality, whilst considering inattention, physical aggression and family adversity.We monitored the development of a population-based sample of kindergarten children (N = 2,741). Hyperactivity, inattention, and physical aggression were assessed annually between the ages of 6 and 12 years by mothers and teachers. Information on the presence, the age at first charge and the type of criminal charge was obtained from official records when the participants were aged 25 years. We used survival analysis models to predict the development of criminality in adolescence and adulthood: high childhood hyperactivity was highly predictive when bivariate analyses were used; however, with multivariate analyses, high hyperactivity was only marginally significant (Hazard Ratio: 1.38; 95% CI: 0.94-2.02). Sensitivity analyses revealed that hyperactivity was not a consistent predictor. High physical aggression was strongly predictive (Hazard Ratio: 3.44; 95% CI: 2.43-4.87) and its role was consistent in sensitivity analyses and for different types of crime. Inattention was not predictive of later criminality.Although the contribution of childhood hyperactivity to criminality may be detected in large samples using multi-informant longitudinal designs, our results show that it is not a strong predictor of later criminality. Crime prevention should instead target children with the highest levels of childhood physical aggression and family adversity.

Food insecurity (which can be defined as inadequate access to sufficient, safe, and nutritious food that meets individuals' dietary needs) is concurrently associated with children's psychological difficulties. However, the predictive role of food insecurity with regard to specific types of children's mental health symptoms has not previously been studied. We used data from the Longitudinal Study of Child Development in Québec, LSCDQ, a representative birth cohort study of children born in the Québec region, in Canada, in 1997-1998 (n = 2120). Family food insecurity was ascertained when children were 1½ and 4½ years old. Children's mental health symptoms were assessed longitudinally using validated measures of behaviour at ages 4½, 5, 6 and 8 years. Symptom trajectory groups were estimated to identify children with persistently high levels of depression/anxiety (21.0%), aggression (26.2%), and hyperactivity/inattention (6.0%). The prevalence of food insecurity in the study was 5.9%. In sex-adjusted analyses, children from food-insecure families were disproportionately likely to experience persistent symptoms of depression/anxiety (OR: 1.79, 95% CI 1.15-2.79) and hyperactivity/inattention (OR: 3.06, 95% CI 1.68-5.55). After controlling for immigrant status, family structure, maternal age at child's birth, family income, maternal and paternal education, prenatal tobacco exposure, maternal and paternal depression and negative parenting, only persistent hyperactivity/inattention remained associated with food insecurity (fully adjusted OR: 2.65, 95% CI 1.16-6.06). Family food insecurity predicts high levels of children's mental health symptoms, particularly hyperactivity/inattention. Addressing food insecurity and associated problems in families could help reduce the burden of mental health problems in children and reduce social inequalities in development.

The castration of stallions is traditionally performed after puberty, at around the age of 2 years old. No studies have focused on the effects of early castration on osteoarticular metabolism. Thus, we aimed to compare early castration (3 days after birth) with traditional castration (18 months of age) in horses. Testosterone and estradiol levels were monitored from birth to 33 months in both groups. We quantified the levels of biomarkers of cartilage and bone anabolism (CPII and N-MID) and catabolism (CTX-I and CTX-II), as well as of osteoarthritis (HA and COMP) and inflammation (IL-6 and PGE 2 ). We observed a lack of parallelism between testosterone and estradiol synthesis after birth and during puberty in both groups. The extra-gonadal synthesis of steroids was observed around the 28-month mark, regardless of the castration age. We found the expression of estrogen receptor (ESR1) in cartilage and bone, whereas androgen receptor (AR) expression appeared to be restricted to bone. Nevertheless, with respect to osteoarticular metabolism, steroid hormone deprivation resulting from early castration had no discernable impact on the levels of biomarkers related to bone and cartilage metabolism, nor on those associated with OA and inflammation. Consequently, our research demonstrated that early castration does not disrupt bone and cartilage homeostasis.

Osteoarthritis (OA) is a widespread osteoarticular pathology characterized by progressive hyaline cartilage degradation, exposing horses to impaired well-being, premature career termination, alongside substantial financial losses for horse owners. Among the new therapeutic strategies for OA, using mesenchymal stromal cell (MSC)-derived exosomes (MSC-exos) appears to be a promising option for conveying MSC therapeutic potential, yet avoiding the limitations inherent to cell therapy. Here, we first purified and characterized exosomes from MSCs by membrane affinity capture (MAC) and size-exclusion chromatography (SEC). We showed that intact MSC-exos are indeed internalized by equine articular chondrocytes (eACs), and then evaluated their functionality on cartilaginous organoids. Compared to SEC, mRNA and protein expression profiles revealed that MAC-exos induced a greater improvement of eAC-neosynthesized hyaline-like matrix by modulating collagen levels, increasing PCNA, and decreasing Htra1 synthesis. However, because the MAC elution buffer induced unexpected effects on eACs, an ultrafiltration step was included to the isolation protocol. Finally, exosomes from MSCs primed with equine pro-inflammatory cytokines (IL-1β, TNF-α, or IFN-γ) further improved the eAC hyaline-like phenotype, particularly IL-1β and TNF-α. Altogether, these findings indicate the importance of the exosome purification method and further demonstrate the potential of pro-inflammatory priming in the enhancement of the therapeutic value of MSC-exos for equine OA treatment.

Context: Osteoarthritis (OA) is an invalidating articular disease characterized by cartilage degradation and inflammatory events. In horses, OA is associated with up to 60% of lameness and leads to reduced animal welfare along with extensive economic losses; currently, there are no curative therapies to treat OA. The mesenchymal stromal cell (MSC) secretome exhibits anti-inflammatory properties, making it an attractive candidate for improving the management of OA. In this study, we determined the best storage conditions for conditioned media (CMs) and tested whether priming MSCs with cytokines can enhance the properties of the MSC secretome. Methods: First, properties of CMs collected from bone-marrow MSC cultures and stored at -80°C, -20°C, 4°C, 20°C or 37°C were assessed on 3D cultures of equine articular chondrocytes (eACs). Second, we primed MSCs with IL-1β, TNF-α or IFN-γ, and evaluated the MSC transcript levels of immunomodulatory effectors and growth factors. The primed CMs were also harvested for subsequent treatment of eACs, either cultured in monolayers or as 3D cell cultures. Finally, we evaluated the effect of CMs on the proliferation and the phenotype of eACs and the quality of the extracellular matrix of the neosynthesized cartilage. Results: CM storage at -80°C, -20°C, and 4°C improved collagen protein accumulation, cell proliferation and the downregulation of inflammation. The three cytokines chosen for the MSC priming influenced MSC immunomodulator gene expression, although each cytokine led to a different pattern of MSC immunomodulation. The cytokine-primed CM had no major effect on eAC proliferation, with IL-1β and TNF-α slightly increasing collagen (types IIB and I) accumulation in eAC 3D cultures (particularly with the CM derived from MSCs primed with IL-1β), and IFN-γ leading to a marked decrease. IL-1β-primed CMs resulted in increased eAC transcript levels of MMP1, MMP13 and HTRA1 , whereas IFNγ-primed CMs decreased the levels of HTRA1 and MMP13 . Conclusion: Although the three cytokines differentially affected the expression of immunomodulatory molecules, primed CMs induced a distinct effect on eACs according to the cytokine used for MSC priming. Different mechanisms seemed to be triggered by each priming cytokine, highlighting the need for further investigation. Nevertheless, this study demonstrates the potential of MSC-CMs for improving equine OA management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jammes, Contentin, Audigié, Cassé and Galéra.)

Osteoarthritis (OA) is a degenerative disease that eventually leads to the complete degradation of articular cartilage. Articular cartilage has limited intrinsic capacity for self-repair and, to date, there is no curative treatment for OA. Humans and horses have a similar articular cartilage and OA etiology. Thus, in the context of a One Health approach, progress in the treatment of equine OA can help improve horse health and can also constitute preclinical studies for human medicine. Furthermore, equine OA affects horse welfare and leads to significant financial losses in the equine industry. In the last few years, the immunomodulatory and cartilage regenerative potentials of mesenchymal stromal cells (MSCs) have been demonstrated, but have also raised several concerns. However, most of MSC therapeutic properties are contained in their secretome, particularly in their extracellular vesicles (EVs), a promising avenue for acellular therapy. From tissue origin to in vitro culture methods, various aspects must be taken into consideration to optimize MSC secretome potential for OA treatment. Immunomodulatory and regenerative properties of MSCs can also be enhanced by recreating a pro-inflammatory environment to mimic an in vivo pathological setting, but more unusual methods also deserve to be investigated. Altogether, these strategies hold substantial potential for the development of MSC secretome-based therapies suitable for OA management. The aim of this mini review is to survey the most recent advances on MSC secretome research with regard to equine OA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jammes, Contentin, Cassé and Galéra.)

Osteoarthritis (OA) is a degenerative and heterogeneous disease that affects all types of joint structures. Current clinical treatments are only symptomatic and do not manage the degenerative process in animals or humans. One of the new orthobiological treatment strategies being developed to treat OA is the use of drug delivery systems (DDS) to release bioactive molecules over a long period of time directly into the joint to limit inflammation, control pain, and reduce cartilage degradation. Two vasoactive peptides, endothelin-1 and bradykinin, play important roles in OA pathogenesis. In this study, we investigated the effects of two functionalized nanogels as DDS. We assessed the effect of chitosan functionalized with a type A endothelin receptor antagonist (BQ-123-CHI) and/or hyaluronic acid functionalized with a type B 1 bradykinin receptor antagonist (R-954-HA). The biocompatibility of these nanogels, alone or in combination, was first validated on equine articular chondrocytes cultured under different oxic conditions. Further, in an OA equine organoid model via induction with interleukin-1 beta (IL-1β), a combination of BQ-123-CHI and R-954-HA (BR5) triggered the greatest decrease in inflammatory and catabolic markers. In basal and OA conditions, BQ-123-CHI alone or in equimolar combinations with R-954-HA had weak pro-anabolic effects on collagens synthesis. These new nanogels, as part of a composite DDS, show promising attributes for treating OA.