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The comorbidity between physical and mental health conditions is challenging and frequently goes unrecognized in practice. Associations between Attention-Deficit/Hyperactivity Disorder (ADHD) and physical conditions have been reported in youth. However, prior research failed to: (1) address the patterns of associations in early childhood, middle childhood, and adolescence within the same population sample; (2) consider a large set of physical disorders at the same time; (3) take confounders into account. Our goal was to assess the associations between ADHD symptoms and a broad set of physical conditions across developmental periods. This birth cohort study (n= 2057) is the first to explore the associations between ADHD and a wide range of medical conditions by encompassing the whole early development from 5 months to 17 years in the same sample and relying on innovative network analyses. We found significant associations between ADHD symptoms and several physical conditions, some of which were observed in early childhood, middle childhood, and adolescence (e.g., asthma, sleep problems) or were confounded by socioeconomic status or psychiatric comorbidities (e.g., body mass index, dental caries). The study calls for an effective integrated care model encompassing mental and general healthcare across the developmental period.

L’agriculture expose à différents troubles respiratoires. Un excès de bronchite chronique a été mis en évidence dans la plupart des secteurs agricoles et notamment en milieu de production laitière. Un sur-risque de broncho pneumopathie chronique obstructive (BPCO) a été observé en France dans les secteurs d’élevage de porcs, de volailles ainsi que chez les producteurs laitiers. À tabagisme égal, le risque de BPCO est environ 2 fois plus élevé dans les secteurs sus-cités que dans la population générale. Le service santé sécurité au travail (SST) de la MSA Lorraine en collaboration avec la caisse d’Assurance accidents agricole de Moselle a mené une étude sur l‘exposition aux poussières sur des exploitations en polyculture élevage (bovins, ovins). Cette action s’est inscrite dans notre Plan santé sécurité au travail (SST) 2020–2025 au titre de l’amélioration de la connaissance des expositions professionnelles. Deux activités ont été ciblées : le paillage mécanique ou manuel et le nettoyage des engins agricoles. Une campagne de prélèvements dans des exploitations a été réalisée sur l’année 2022 avec la coopération de la CARSAT Nord Est et de l’INRS avec des analyses à la fois quantitative et qualitative. Les premiers résultats montrent que tous les opérateurs réalisant du paillage sont exposés à des concentrations intenses de poussières sur des courtes durées mais quotidiennement quel que soit les machines et les bâtiments dans et avec lesquelles les opérations sont réalisées. Les opérations se répètent tous les jours entre novembre et mars de chaque année ce qui constitue en soi une exposition importante sur une carrière. Les expositions diminuent en moyenne de 50 à 70 % lorsque l’opération est faite avec un engin avec cabine fermée mais elle reste toutefois toujours au-dessus des seuils réglementaires. Sur le plan qualitatif, des endotoxines, bactéries et moisissures ont été retrouvées. Pendant les phases de nettoyages des engins, l’exposition est très importante également même si les tâches se font le plus souvent en milieu extérieur. Cette étude nous permettra d’adapter nos messages de prévention et d’agir aussi sur les tâches les plus exposantes avec propositions de protection collective et/ou individuelle. Nous adapterons aussi le suivi en santé au travail avec la réalisation de spirométrie ciblée. Enfin, une démarche auprès des fabricants de matériel est également envisagée afin de faire évoluer le matériel en limitant ou éliminant l’exposition aux poussières.

Because articular cartilage does not self-repair, tissue-engineering strategies should be considered to regenerate this tissue. Autologous chondrocyte implantation is already used for treatment of focal damage of articular cartilage. Unfortunately, this technique includes a step of cell amplification, which results in dedifferentiation of chondrocytes, with expression of type I collagen, a protein characteristic of fibrotic tissues. Therefore, the risk of producing a fibrocartilage exists. The aim of this study was to propose a new strategy for authorizing the recovery of the differentiated status of the chondrocytes after their amplification on plastic. Because the bone morphogenetic protein (BMP)-2 and the transforming growth factor (TGF)-β1 are cytokines both proposed as stimulants for cartilage repair, we undertook a detailed comparative analysis of their biological effects on chondrocytes. As a cellular model, we used mouse chondrocytes after their expansion on plastic and we tested the capability of BMP-2 or TGF-β1 to drive their redifferentiation, with special attention given to the nature of the proteins synthesized by the cells. To prevent any fibrotic character of the newly synthesized extracellular matrix, we silenced type I collagen by transfecting small interfering RNA (siRNA) into the chondrocytes, before their exposure to BMP-2 or TGF-β1. Our results showed that addition of siRNA targeting the mRNA encoded by the Col1a1gene (Col1a1siRNA) and BMP-2 represents the most efficient combination to control the production of cartilage-characteristic collagen proteins. To go one step further toward scaffold-based cartilage engineering, Col1a1siRNA-transfected chondrocytes were encapsulated in agarose hydrogel and cultured in vitrofor 1 week. The analysis of the chondrocyte–agarose constructs by using real-time polymerase chain reaction, Western-blotting, immunohistochemistry, and electron microscopy techniques demonstrated that the BMP-2/Col1a1siRNA combination is effective in reinitializing correct production and assembly of the cartilage-characteristic matrix in agarose hydrogel, without production of type I collagen. Because agarose is known to favor long-term expression of the chondrocyte phenotype and agarose-based hydrogels are approved for clinical trials, this strategy appears very promising to repair hyaline cartilage.

Background:There is presently a lack of information on the role of healthcare in suicidal ideation in adults. Aims:To assess the frequencies, patterns, and factors associated with the communication of suicidal ideation toward a health professional. Methods:Participants stem from a French cross-sectional survey of 22,133 randomly selected adults. Lifetime suicidal behaviors and 12-month mental disorder patterns were assessed using the short form of the Composite International Diagnostic Interview. Participants with suicidal ideation were asked whether they had talked about it and, if they had, to whom. Results:Around 20% of people with suicidal ideation had talked about this distress to a health professional. It was more frequent for people with more severe suicidal behaviors (plan or a prior attempt), among women, those aged 30 or more, those suffering from major depressive episode, panic disorder, or drug use disorder. Above all, it was more frequent among those who had also talked to friends or relatives. Conclusions:Prevention strategies that encourage suicidal persons to seek help for their distress, whoever that is, may be the more important strategies to develop.

Costello syndrome (CS) is a rare genetic condition due to germline mutations in HRAS proto‐oncogene and characterized by increased birth weight, postnatal growth retardation, distinctive facial appearance, typical medical problems (including feeding problems in the neonatal period), cutaneous anomalies, and developmental delay. Outgoing personality has often been noted in case reports, but few studies have focused specifically on the behavioral aspects of CS. A preliminary survey described irritability in younger patients with improvement between age 2 and 4, but a standardized psychometric tool was not used. A second study using the Child Behavior Checklist (CBCL) showed relatively high (albeit subclinical) levels of internalizing problems. These descriptive investigations lacked a control group. We describe a comparative survey to evaluate the behavioral and temperamental features of children with CS. We conducted a cross‐sectional assessment using the CBCL and the Emotionality, Activity, Shyness, Sociability (EAS) temperament questionnaire to evaluate behavior and temperament in 11 CS children (2 years 5 months to 9 years) comparing them to 33 gender‐ and age‐matched children without disability. The results suggest that the high levels of internalizing problems found before age 4 in CS patients might decrease with age. They also point to possible “hyperemotionality.” Further studies using a larger sample size and IQ‐matched control groups are needed to more accurately characterize individuals with this rare syndrome. © 2006 Wiley‐Liss, Inc.

Although transforming growth factor beta1 (TGF-beta1) is generally considered as a stimulator of type I collagen production in smooth organs, we found that it can inhibit type II collagen biosynthesis in primary rabbit articular chondrocytes (RAC) at transcriptional levels. Constructs of promoter and first intron sequences associated with the luciferase reporter gene were used to delineate the gene sequences involved in TGF-beta1 control of human COL2A1 gene transcription. Cotransfection of these DNA fragments with a TbetaRII/I cDNA hybrid receptor, capable of inducing a TGF-beta1 dominant negative effect, showed that TGF-beta1 inhibits specifically COL2A1 gene transcription in RAC by a 63-bp proximal promoter. Footprint and gel retardation analyses revealed that the TGF-beta1-induced inhibition effect exerted through the 63-bp promoter sequence implies a multimeric complex that binds to the -41/-33 sequence and involves Sp1 and Sp3 transcription factors. Transfection of decoy Sp-binding oligonucleotides corroborated the implication of the proximal promoter in the TGF-beta1-induced inhibition of COL2A1 gene transcription. In addition, TGF-beta1 was found to increase the expression of Sp3 without significant changes to its binding level, but repressed both the biosynthesis and binding activity of Sp1. In functional assays, Sp3 inhibited the 63-bp promoter activity and prevented Sp1 induction of transcription. These findings suggest that TGF-beta1 inhibition of COL2A1 gene transcription in RAC is mediated by an increase of the Sp3/Sp1 ratio and by the repression of Sp1 transactivating effects on that gene.

Sp1 and Sp3 effects on the transcription of the human α1(II) procollagen gene (COL2A1) were investigated in both differentiated and de-differentiated rabbit articular chondrocytes. Transient transfection with constructs of deletedCOL2A1promoter sequences driving the luciferase reporter gene revealed that the region spanning −266 to +121 base pairs showed Sp1-enhancing effects, whatever the differentiation state. In contrast, Sp3 did not influence COL2A1gene transcription. Concomitant overexpression of the two Sp proteins demonstrated that Sp3 blocked the Sp1 induction of COL2A1promoter activity. Moreover, inhibition of Sp1/Sp3 binding to their target DNA sequence decreased both COL2A1gene transcription and Sp1-enhancing effects. DNase I footprinting and gel retardation assays revealed that Sp1 and Sp3 bind specifically to cis-sequences of theCOL2A1gene promoter whereby they exert their transcriptional effects. Sp1 and Sp3 levels were found to be reduced in de-differentiated chondrocytes, as revealed by DNA-binding and immunochemical study. Sp1 specifically activated collagen neosynthesis whatever the differentiation state of chondrocytes, suggesting that this factor exerts a major role in the expression of collagen type II. However, our data indicate that type II collagen-specific expression in chondrocytes depend on both the Sp1/Sp3 ratioand cooperation of Sp1 with other transcription factors, the amounts of which are also modulated by phenotype alteration.

Decorin, a small leucine-rich proteoglycan may play an important role in the attempt of cartilage repair initiated by chondrocytes in early stages of osteoarthritis, through its ability to bind collagen fibrils and growth factors such as transforming growth factor-β (TGF-β). We previously demonstrated that TGF-β decreased decorin mRNA steady state levels in articular chondrocytes (Demoor, M., Rédini, F., Boittin, M., and Pujol, J.-P. (1998)Biochim. Biophys. Acta1398, 179–191). Here, we investigated the effect of TGF-β on decorin gene expression in both primary cultures of articular chondrocytes and chondrocytes dedifferentiated by serial passages. Transient transfection of cells with plasmid constructs of the decorin promoter linked to the luciferase reporter gene revealed transcriptional repression by TGF-β, in fully differentiated as well as dedifferentiated chondrocytes. Experiments with 5′-deleted constructs allowed characterization of a TGF-β-responsive element in the shortest construct (base pairs (bp) −155/+269). DNase I footprinting analysis delineated a negative TGF-β-responsive region between −140 and −111 bp in the decorin proximal promoter. Gel retardation assays demonstrated that TGF-β modulates decorin gene expression through transcription factors, the nature and mode of action of which depend on the differentiation state of the chondrocytes; two DNA-protein complexes were formed in the region −144/−127 bp with nuclear extracts from primary chondrocytes, whereas a higher mobility complex was observed in the −127/−111 bp region for dedifferentiated cells. Antibodies against vitamin D and retinoic acid receptors used in supershift experiments showed that these nuclear receptors are involved in the regulation of decorin gene expression in articular chondrocytes.

To identify control motifs involved in human type II collagen gene transcription in both differentiated and dedifferentiated rabbit articular chondrocytes, transient transfection experiments were performed. A 715-base pair (bp) region of the first intron (+2127/+2842), including a 153-bp sequence so far uncharacterized (+2689/+2842), was found to mediate enhancer activity. In dedifferentiated chondrocytes, this enhancer activity was shown to be less effective than in primary cultures but still present. We then demonstrated that a zinc finger protein, C-Krox, activates COL2A1 gene transcription in differentiated chondrocytes through the enhancer region, whereas in subcultured cells, it inhibited the gene activity via a 266-bp promoter. Multicopies of the C-Krox binding site were found to mediate transactivation in both primary cultures and passaged cells, whereas C-Krox overexpression inhibited transcription in dedifferentiated chondrocytes. Additionally, we showed that C-Krox binds to several cis sequences that mediate its transcriptional effects. During chondrocyte dedifferentiation, the protein levels and binding activity of C-Krox were reduced, whereas those of NF-kappaB were increased. This was not associated with variations of mRNA levels, suggesting that post-transcriptional regulatory mechanisms could be involved in C-Krox expression. These results suggest that C-Krox plays a major role in type II collagen expression and the chondrocyte phenotype modulation.

To evidence a collagen synthesis and identify which type(s) of collagen is present in hemocytes from the mollusc Haliotis tuberculata, we have performed three separate approaches, namely, de novo synthesis by cultured cells, immunological approaches, and northern blot analysis. We demonstrated first that after 40-hr labeling, the de novo synthesis of collagen in the cell layer of cultured hemocytes represents 9.48 ± 1.25% with respect to the total [³H]proline-labeled protein synthesis. In addition, IGF-I elicited a significant stimulation of collagen synthesis in cultured hemocytes in a dose-dependent manner from 10^–10 to 10^–8 M. The maximal stimulation (10^–9 M) induced an increase of 286 ± 56% with respect to 100% control. By immunocytochemistry and immunoblotting, we showed that hemocytes present immunoreactive molecules to antibodies directed against the type I fibrillar collagen. In addition, using as a probe Hf 677 corresponding to a human proα1(I) collagen cDNA and which encompasses the (Gly-X-Y) repeated sequence found in all Metazoa, four collagen transcripts of approximately 6.4, 5, 2.2, and 2 kb in length have been detected. These data suggest the presence of fibrillar type I collagen in hemocytes and are compatible with the concept that these cells are involved in the extracellular matrix deposition, a cardinal function in tissue repair as well as in developmental processes. Our model may appear as an excellent system to study the role of growth factors on the regulation of collagen synthesis by molluscan hemocytes. J. Exp. Zool. 287:275–284, 2000. © 2000 Wiley-Liss, Inc.

Chez l’homme, il est maintenant bien établi que les hormones stéroïdiennes sécrétées par le testicule comme la testostérone et l’œstradiol, sont essentielles pour l’acquisition du pic pubertaire de masse osseuse et sont également impliquées dans le maintien de l’intégrité osseuse au cours de la vie. Chez les équidés, la castration est une pratique courante d’élevage, cependant, l’existence de cette interaction entre le testicule et le tissu ostéoarticulaire n’a pas été étudiée chez cette espèce. Nous avons étudié l’impact de la castration sur le métabolisme ostéoarticulaire sur des animaux castrés à des âges variables (à la naissance, à la puberté mais pendant la phase de croissance osseuse, à l’âge adulte après la fin de croissance). Des biomarqueurs testiculaires (testostérone et estradiol) et ostéoarticulaires (collagène, ostéocalcine, prostaglandine, acide hyaluronique) ont été dosés et quantifiés sur prélèvements sanguins et quantifiés en regard des taux circulants de stéroïdes. Des analyses morphométriques ont également été menées chez ces animaux afin d’évaluer l’effet sur la croissance. Cette étude ne montre aucune modification significative des biomarqueurs de croissance et du métabolisme ostéoarticulaire avant et après castration, et ceci, même après la chute de stéroïdes sexuels observée après castration. L’évolution globale du métabolisme cartilagineux et osseux ne semble pas être influencée par la castration, ni par l’âge auquel elle est pratiquée. Cela montre une indépendance de la croissance et du maintien osseux vis-à-vis des stéroïdes testiculaires ce qui diffère de ce qui a été décrit chez l’homme. Le cheval représente un modèle d’exception en termes d’endocrinologie comparée.

We previously showed that TGF-β1 exerted a bifunctional effect on the proliferation of cultured rabbit articular cells (RAC), depending on the serum level present in the medium. Slowly proliferating cells (2% fetal calf serum, FCS) were growth-inhibited by TGF-β1, whereas actively dividing cells (10% FCS) exhibited a transient growth increase in response to the factor. Here we demonstrate that both of these cycling populations of RAC display two distinct systems of high-affinity binding sites for TGF-β1. However, a significant increase (60%) in the number of the highest affinity receptors was observed in the 2% FCS-treated cells compared to those cultured in 10% FCS (in 2% FCS: Kd1= 295 ± 78 pM, 1899 ± 99 sites/cell; Kd2= 1106 ± 61 pM, 9935 ± 940 sites/cell; in 10% FCS: Kd1= 287 ± 10 pM, 1054 ± 65 sites/cell; Kd2= 1128 ± 101 pM, 8257 ± 61 sites/cell). This finding was correlated with the greater number of G0/G1 cells in the population cultured in 2% FCS (70%) compared to that exposed to 10% FCS (55%). The data was further confirmed using cells synchronized in late G1/early S phase (> 80% of S phase). This cell population exhibited a single class of TGF-β1 high-affinity binding sites (Kd= 1140 ± 85 pM, 6836 ± 1787 sites/cell). In contrast, cells synchronized in G0/G1 (> 80% of cells in G0/G1) expressed one binding system of Kd= 402 ± 59 pM(940 ± 56 sites/cell). These results clearly demonstrate that cultured RAC express different TGF-β1 receptor systems as a function of the cell cycle.

We have cloned a mouse cDNA that is a member of the Krox gene family and encodes a protein we have named c-Krox. The c-Krox protein contains three zinc fingers of the Cys2His2 type. c-Krox binds specifically to a guanine-rich cis-acting element present twice in the promoter element of the mouse alpha 1(I) collagen gene. Study of c-Krox gene expression shows that c-Krox is markedly enriched in skin, one of the two major sites of type I collagen synthesis, but is absent in bone, the other main type I collagen-producing tissue, indicating that type I collagen gene expression is differentially regulated in skin and bone. DNA transfection experiments in mouse NIH 3T3 fibroblasts, cells that express the c-Krox gene, or in Drosophila S2 cells, which do not express c-Krox, reveal that c-Krox can activate transcription of a reporter gene linked to several copies of its binding site in the alpha 1(I) collagen promoter. Thus, c-Krox is only the second member of the Krox family for which a target gene has been identified. The selective spatial pattern of expression of its mRNA and its transcription activation ability suggest that c-Krox may be an important regulator of type I collagen skin specific expression in physiologic conditions and in fibrotic diseases such as scleroderma.

The Ho-50% Tb alloy orders in a magnetic spiral structure in the temperature range 83–185 K. Resonant magnetic X-ray scattering at Ho and Tb LIIIedges shows that the behaviors of both constituents through the transitions are equivalent. The dipolar resonance is about twice as strong in Tb than it is Ho.

We attempt a quantitative description of a (H-T) magnetic phase diagram of the cubic compound NdIn3. Below TN, this compound presents two spontaneous first-order phase transitions as well as several field induced transitions. Considering both the dipolar and quadrupolar interactions a self-consistent periodic-field model is proposed. Although the metamagnetic magnetization processes at low temperatures are not totally reproduced, the calculations account quantitatively for the spontaneous magnetic phase succession.

ObjectiveTo assess the association between mind wandering (thinking unrelated to the task at hand) and the risk of being responsible for a motor vehicle crash.DesignResponsibility case-control study.SettingAdult emergency department of a university hospital in France, April 2010 to August 2011.Participants955 drivers injured in a motor vehicle crash.Main outcome measuresResponsibility for the crash, mind wandering, external distraction, negative affect, alcohol use, psychotropic drug use, and sleep deprivation. Potential confounders were sociodemographic and crash characteristics.ResultsIntense mind wandering (highly disrupting/distracting content) was associated with responsibility for a traffic crash (17% (78 of 453 crashes in which the driver was thought to be responsible) v9% (43 of 502 crashes in which the driver was not thought to be responsible); adjusted odds ratio 2.12, 95% confidence interval 1.37 to 3.28).ConclusionsMind wandering while driving, by decoupling attention from visual and auditory perceptions, can jeopardise the ability of the driver to incorporate information from the environment, thereby threatening safety on the roads.

Introduction: Transforming growth factor beta (TGFβ) plays a central role in morphogenesis, growth, and cell differentiation. This cytokine is particularly important in cartilage where it regulates cell proliferation and extracellular matrix synthesis. While the action of TGFβ on chondrocyte metabolism has been extensively catalogued, the modulation of specific genes that function as mediators of TGFβ signalling is poorly defined. In the current study, elements of the Smad component of the TGFβ intracellular signalling system and TGFβ receptors were characterised in human chondrocytes upon TGFβ1 treatment. Methods: Human articular chondrocytes were incubated with TGFβ1. Then, mRNA and protein levels of TGFβ receptors and Smads were analysed by RT-PCR and western blot analysis. The role of specific protein 1 (Sp1) was investigated by gain and loss of function (inhibitor, siRNA, expression vector). Results: We showed that TGFβ1 regulates mRNA levels of its own receptors, and of Smad3 and Smad7. It modulates TGFβ receptors post-transcriptionally by affecting their mRNA stability, but does not change the Smad-3 and Smad-7 mRNA half-life span, suggesting a potential transcriptional effect on these genes. Moreover, the transcriptional factor Sp1, which is downregulated by TGFβ1, is involved in the repression of both TGFβ receptors but not in the modulation of Smad3 and Smad7. Interestingly, Sp1 ectopic expression permitted also to maintain a similar expression pattern to early response to TGFβ at 24 hours of treatment. It restored the induction of Sox9 and COL2A1 and blocked the late response (repression of aggrecan, induction of COL1A1 and COL10A1). Conclusions: These data help to better understand the negative feedback loop in the TGFβ signalling system, and enlighten an interesting role of Sp1 to regulate TGFβ response.