NCube/papyrus huggingface dataset:
Critique du modèle neurophysiologique de la desphinothérapie. Sonophorèse et écholocation

Un certain nombre de chercheurs (Birch, 1996; Cole, 1995, 1996; De Bergerac, 1998) fondent sur un modèle neurophysiologique leurs arguments en faveur de la delphinothérapie pour traiter divers désordres (DSM-IV) cognitifs et émotifs chez les enfants et les jeunes. Ce modèle recourt à des analogies avec les mécanismes de sonophorèse, d'écholocation et de transmission neurohormonale dans son application thérapeutique. Dans le but de démystifier les éléments pseudo-scientifiques auprès d'un lectorat non spécialisé, cet article critique les postulats et les implications relatifs à ces mécanismes et il conclut à l'absence d'un soutien pertinent et valide concernant ce modèle. A number of researchers (Birch, 1996 ; Cole, 1995, 1996 ; De Bergerac, 1998), claim a neurophysiological model in order to support therapeutic benefits of dolphin assisted therapy in treating various DSM-IV cognitive and emotional disorders in children and youth. The model is based on analogies with mechanisms of sonophoresis, echolocation and neurohormonal transmission during therapy. In order to demystify pseudo scientific elements in view of a nonspecialized readership, the present article discusses the postulates and implications for each mechanism and concludes to the absence of reliable and valid support for this model.

Keyphrases: Delphinothérapie, Sonophorèse, Écholocation, Autisme, Troubles d'apprentissage, Troubles cognitifs, Troubles envahissants du développement, Dolphin assisted therapy, Sonophoresis, Echolocation, Autism, Learning disorders, Cognitive disorders, Developmental disorders
Optimisation du promoteur CR5 inductible au cumate

Les produits biologiques représentent une avenue thérapeutique très prometteuse pour diverses maladies actuellement sans traitement, dont le cancer. La demande pour ces produits est donc très forte et des bioprocédés industriels efficaces et fiables doivent être mis en place pour y répondre. Le système inductible au cumate (CR5) développé par le groupe de Bernard Massie permet d’exprimer des protéines d’intérêt de façon finement régulable et à haut niveau dans les cellules CHO. Un travail d’optimisation est toutefois nécessaire afin de maximiser l’expression tout en améliorant l’étanchéité du système. Dans cette optique, diverses constructions du promoteur comportant des configurations différentes d’espacement entre ses constituants, des transactivateurs comportant des domaines d’activation différents, et une séquence opératrice synthétique ont été testées pour évaluer leur capacité à améliorer le rendement et l’étanchéité du CR5. Ainsi, un protomoteur comportant trois séquences opératrices avec six paires de bases entre chacune de ces dernières s’est montré plus efficace en termes de rendement et d’étanchéité que la configuration actuelle du CR5. De plus, une nouvelle configuration du CR5 où le transactivateur est régulé par le système inductible à la coumermycine a été étudiée et a montré une régulation très fine. Le travail d’optimisation effectué dans ce projet s’applique seulement dans le but d’optimiser un procédé dans des conditions spécifiques. Son application à d’autres lignées cellulaires et d’autres promoteurs reste à démontrer. Biologics are a very promising therapeutic avenue for the treatment of incurable diseases such as cancer. The market’s demand for these products is very high, so reliable and efficient industrial bioprocesses must be set up in order to answer it. The cumate gene switch (CR5) developed by Bernard Massie’s group allows high and fine-tuned expression of proteins of interest in CHO cells. Optimisation of this system is however a necessary work to maximise the expression and improve the leakiness of the system. For this purpose, promoters with different spacing configurations, transactivators with different activation domains, and a synthetic operator sequence have been assayed to evaluate their ability to drive high protein expression while improving the leakiness of the CR5 system. Thus, a promoter containing three operator sequences with a six base pairs spacing between them has been found to be the most efficient configuration in terms of yield and leakiness in comparison to the current CR5 configuration. Also, a new configuration of the CR5 where the transactivator is regulated by the coumermycin gene regulation system has been studied, showing very tight regulation ability. This optimisation work can only be applied to our specific experimental conditions and its application to other cell lines and promoters needs to be demonstrated.

Keyphrases: systèmes inductibles, cumate, CR5, cellules CHO, optimisation, transactivateur, coumermycine, coumermycin, cumate, CR5, optimisation, coumermycin, inducible systems, CHO cells
Investigating the thymopoiesis stimulating property of interleukin-21 in aging mice

La vaccination est largement utilisée pour la génération de lymphocytes T spécifiques contre les tumeurs. Malheureusement, cette stratégie n'est pas adaptée aux personnes âgées car leur thymus régresse avec l'âge conduisant ainsi à une baisse dans la production de cellules T et à l'accumulation de cellules immunitaires âgées ayant des défauts liés à leurs stimulations. Comme il a été démontré auparavant que L’IL-21 est capable d’induire des fonctions thymiques, nous avons émis l’hypothèse que l’injection d’IL-21 à des souris âgées stimulera la thymopoïèse. Nos résultats montrent que l’administration de l’IL-21 augmente le nombre absolu de thymocytes chez les souris âgées et augmente la migration de ces cellules vers la périphérie ou ils contribuent à la diversité du TCR. De plus les cellules T en périphérie expriment un niveau plus élevé de miR181-a, et par conséquent moins de phosphatase comme SHP2, DUSP5/6 qui inhibent le TCR. En vaccinant des souris âgées avec le peptide Trp2, les souris traitées avec l’IL-21 montrent un retard dans la croissance des cellules B16 tumorales. Cette étude montre que l’IL-21 pourrait être utilisé comme stratégie pour le rétablissement du systeme immunitaire chez les personnes âgées. Vaccines have been largely sought for the generation of protective tumor-specific T cells. Unfortunately however, this strategy is not suitable for the elderly as their thymus regresses with age leading to a decline in T-cell production and accumulation of aged lymphocytes endowed with stimulation-related defects. Interleukin (IL)-21 has been shown to display thymostimulatory properties. Therefore, we hypothesized that IL-21 administration to ageing host may boost T-cell production and restore a competent peripheral T-cell compartment. Our study shows that IL-21 injection to aged mice lead to an increase in the thymocytes absolute number and an increase in thymocytes egress to the periphery where they enhance the T-cell receptor (TCR) diversity. Furthermore T-cell in the periphery express higher level of miR-181a and thus less TCR-inhibiting phosphatases SHP-2 and DUSP5/6 enable them to be more responsive upon stimulation. Consequently, aged rIL-21-treated mice vaccinated using a tyrosinase-related protein 2 (Trp2)-derived peptide exhibited a substantial delay in B16 tumor growth and improved survival. The results of this study highlight the immunorestorative function of rIL-21 paving its use as a strategy for the re-establishment of effective immunity in the elderly.

Keyphrases: Involution thymique, Cellules T, Signalisation, Vaccin, Interleukine-21, miR-181a, Vaccin, Thymic Involution, Interleukin-21, T cells, Signaling, miR-181a, Tumor Vaccine
Predictors and Consequences of Simultaneous Alcohol and Cannabis Use in Adolescents

Background/Aims: The simultaneous use of alcohol and cannabis is common among adolescents, but has been little studied. In this study, we examine predictors and consequences of this behavior in a population-based sample of high school students. Method: Self-reports were obtained from students in Quebec (Canada) followed throughout high school (N=6589). Logistic regressions were used to test the association between individual, family, and peerrelated predictors in grades 7–8 and simultaneous alcohol and cannabis use in grade 10, as well as between simultaneous alcohol and cannabis use in grade 10 and experiencing 3 or more substance-related problems of various types (legal, physical, etc.) in grade 11. Results: Most predictors in grades 7–8 were associated with simultaneous alcohol and cannabis use in grade 10. Only variables reflecting early-onset substance use involvement — alcohol intoxication, cannabis use, and drug use by close friend(s) — remained predictive in a multivariate model. Simultaneous alcohol and cannabis use was associated with increased substance-related problems in grade 11, above and beyond baseline problems and the concurrent use of the two substances in separate episodes in grade 10. Conclusions: Simultaneous alcohol and cannabis use 1) is anticipated by multiple psychosocial risk factors which come together with individual and peer substance use in early high school and 2) is independently predictive of subsequent substance-related problems. Providing adolescents with adequate information regarding the potential harm of simultaneous use may be a useful prevention strategy.

Keyphrases: Polysubstance Use, Simultaneous Use, Alcohol use, Cannabis, Adolescence, Predictors
Prospective associations between meth/amphetamine (speed) and MDMA (ecstasy) use and depressive symptoms in secondary school students

Background Research has raised significant concern regarding the affective consequences of synthetic drug use. However, little evidence from well-controlled longitudinal studies exists on these consequences. The aim of this study was to determine whether use of meth/amphetamine (speed) and 63,4- methylenedioxymethamphetamine (MDMA, ecstasy) is independently predictive of subsequent depressive symptoms in adolescents. Methods A sample of 3880 adolescents from secondary schools in disadvantaged areas of Quebec, Canada, were followed over time (2003e2008). Logistic regression was used to test the association between meth/ amphetamine and MDMA use in grade 10 (ages 15e16 years) and elevated depressive symptoms on an abridged Center for Epidemiologic Studies-Depression scale in grade 11, controlling for pre-existing individual and contextual characteristics. Results After adjustment, both MDMA use (OR 1.7, 95% CI 1.1 to 2.6) and meth/amphetamine use (OR 1.6, 95% CI 1.1 to 2.3) in grade 10 significantly increased the odds of elevated depressive symptoms in grade 11. These relationships did not vary by gender or pre-existing depressive symptoms. Increased risk was particularly observed in concurrent usage (OR 1.9, 95% CI 1.2 to 2.9). Conclusions Adolescent use of meth/amphetamine and MDMA (particularly concurrent use) is independently associated with subsequent depressive symptoms. Further enquiry must determine whether these associations reflect drug-induced neurotoxicity and whether adolescence is a period of increased vulnerability to the hazards of synthetic drug exposure.

Keyphrases: MDMA, Methamphetamine, Depression, Adolescence, Longitudinal
Tachykinins Processing is Significantly Impaired in PC1 and PC2 Mutant Mouse Spinal Cord S9 Fractions

Substance P (SP) play a central role in nociceptive transmission and it is an agonist of the Neurokinin-1 receptor located in the lamina I of the spinal cord. SP is a major proteolytic product of the protachykinin-1 primarily synthesized in neurons. Proprotein convertases (PCs) are extensively expressed in the central nervous system (CNS) and specifically cleave at C-terminal of either a pair of basic amino acids, or a single basic residue. The proteolysis control of endogenous protachykinins has a profound impact on pain perception and the role of PCs remain unclear. The objective of this study was to decipher the role of PC1 and PC2 in the proteolysis surrogate protachykinins (i.e. Tachykinin 20-68 and Tachykinin 58-78) using cellular fractions of spinal cords from wild type (WT), PC1-/+ and PC2-/+ animals and mass spectrometry. Full-length Tachykinin 20-68 and Tachykinin 58-78 was incubated for 30 minutes in WT, PC1-/+ and PC2-/+ mouse spinal cord S9 fractions and specific C-terminal peptide fragments were identified and quantified by mass spectrometry. The results clearly demonstrate that both PC1 and PC2 mediate the formation of SP and Tachykinin 58-71, an important SP precursor, with over 50% reduction of the rate of formation in mutant PC 1 and PC2 mouse S9 spinal cord fractions. The results obtained revealed that PC1 and PC2 are involved in the C-terminal processing of protachykinin peptides and suggest a major role in the maturation of the protachykinin-1 protein.

Keyphrases: Tachykinin, Substance P, Proprotein convertases, Proteolysis, Pain, Spinal cords, Mass spectrometry
Comorbidity Between Major Depression and Alcohol Use Disorder From Adolescence to Adulthood

Background—Limited information exists regarding the long-term development of comorbidity between Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD; abuse/dependence). Using a representative prospective study, we examine multiple aspects pertaining to MDD+AUD comorbidity, with a focus on the relation between disorders across periods (adolescence, early adulthood, adulthood) and cumulative impairments by age 30. Method—816 participants were diagnostically interviewed at ages 16, 17, 24, and 30. Results—Rates of comorbid MDD+AUD were low in adolescence (2%), but increased in early adulthood (10%) and adulthood (7%). Rates of cumulative comorbidity were elevated (21%). Most individuals with a history of MDD or AUD had the other disorder, except for women with MDD. Prospectively, adolescent AUD predicted early adult MDD, while early adult MDD predicted adult AUD. Compared to pure disorders, MDD+AUD was associated with higher risk of alcohol dependence, suicide attempt, lower global functioning, and life dissatisfaction. Conclusions—Lifetime rates of comorbid MDD+AUD were considerably higher than in crosssectional studies. Comorbidity was partly explained by bidirectional and developmentally-specific associations and predicted selected rather than generalized impairments. Clinically, our findings emphasize the need to always carefully assess comorbidity in patients with MDD or AUD, taking into account concurrency and developmental timing.

Keyphrases: Comorbidity, Major Depression, Alcohol Use Disorder, Longitudinal, Adolescence, Adulthood
Moderators of two Indicated Cognitive-Behavioral Depression Prevention Approaches for Adolescents in a School-Based Effectiveness Trial

Objective: Our aim was to identify moderators of the effects of a cognitive behavioral group-based prevention program (CB group) and CB bibliotherapy, relative to an educational brochure control condition and to one another, in a school-based effectiveness randomized controlled prevention trial. Method: 378 adolescents (M age ¼ 15.5, 68% female) with elevated depressive symptoms were randomized in one of three conditions and were assessed at pretest, posttest, and 6-month follow-up. We tested the moderating effect of three individual (baseline depressive symptoms, negative attributional style, substance use), three environmental (negative life events, parental support, peer support), and two sociodemographic (sex, age) characteristics. Results: Baseline depressive symptoms interacted with condition and time. Decomposition indicated that elevated baseline depressive symptoms amplified the effect of CB bibliotherapy at posttest (but not 6-month follow-up) relative to the control condition, but did not modify the effect of CB group relative to the control condition or relative to bibliotherapy. Specifically, CB bibliotherapy resulted in lower posttest depressive symptoms than the control condition in individuals with elevated, but not average or low baseline symptoms. We found no interaction effect for other putative moderators. Conclusions: Our findings suggest that bibliotherapy is effective only in participants who have elevated depressive symptoms at baseline. The fact that no study variable moderated the effects of CB group, which had a significant main effect in reducing depressive symptoms relative to the control condition, suggests that this indicated prevention intervention is effective for a wide range of adolescents.

Keyphrases: Moderators, Depression, Prevention, Cognitive-behavioral, Adolescence, Bibliotherapy
Adolescent suicide attempts and adult adjustment

Background: Adolescent suicide attempts are disproportionally prevalent and frequently of low severity, raising questions regarding their long-term prognostic implications. In this study, we examined whether adolescent attempts were asso- ciated with impairments related to suicidality, psychopathology, and psychosocial functioning in adulthood (objective 1) and whether these impairments were better accounted for by concurrent adolescent confounders (objective 2). Method: Eight hundred and sixteen adolescents were assessed using interviews and question- naires at four time points from adolescence to adulthood. We examined whether lifetime suicide attempts in adolescence (by T2, mean age 17) predicted adult out- comes (by T4, mean age 30) using linear and logistic regressions in unadjusted models (objective 1) and adjusting for sociodemographic background, adolescent psychopathology, and family risk factors (objective 2). Results: In unadjusted analyses, adolescent suicide attempts predicted poorer adjustment on all outcomes, except those related to social role status. After adjustment, adolescent attempts remained predictive of axis I and II psychopathology (anxiety disorder, antisocial and borderline personality disorder symptoms), global and social adjustment, risky sex, and psychiatric treatment utilization. However, adolescent attempts no longer predicted most adult outcomes, notably suicide attempts and major depressive disorder. Secondary analyses indicated that associations did not differ by sex and attempt characteristics (intent, lethality, recurrence). Conclusions: Adolescent suicide attempters are at high risk of protracted and wide-ranging im- pairments, regardless of the characteristics of their attempt. Although attempts specifically predict (and possibly influence) several outcomes, results suggest that most impairments reflect the confounding contributions of other individual and family problems or vulnerabilites in adolescent attempters.

Keyphrases: Suicide attempt, Adolescence, Psychosocial functioning, Psychopathology, Longitudinal
The Impact of a Substance Abuse Treatment for Offenders in Relation to the Time Spent in Treatment

The objective of this research is to evaluate the outcomes of a treatment for addicts. 123 subjects were tested before treatment and at 5, 8 and 11 months follow-up periods with a French version of the Addiction Severity Index (ASI). Exposure to treatment was based on the number of clients’ contact-hours with a therapist. The sample was divided into three groups according to the number of hours spent in treatment. The data was analysed using MANOVA on the seven scales of the ASI for the three groups and the four time periods. Results showed that all groups improved significantly but that this improvement was not related to the number of hours spent in treatment.

Keyphrases: Alcohol, Drug, Treatment, Exposure, Impact
Pierre Camille Le Moine, un archiviste des Lumières dans l’obscurité de l’évaluation à l’ère du numérique

En 1765, le chartrier Pierre Camille Le Moine publie un traité portant le titre de Diplomatique pratique ou Traité de l’arrangement des archives et des trésors des chartes. Dans cet ouvrage, Le Moine expose sa vision concernant la gestion optimale des nombreuses chartres que les archivistes de son époque doivent gérer.  Ce « travail-fiction » imagine l’arrivée de Pierre Camille Le Moine dans le monde du numérique. Convaincu que sa théorie peut encore s’appliquer à cette nouvelle ère, le brave archiviste expose les similitudes entre sa théorie pluricentenaire et celle proposée par ses nouveaux collègues du 21e siècle. Il cherche également à démontrer que ses « plans généraux d’arrangement » peuvent et doivent servir de moyen pour sensibiliser chaque individu à l’archivage de documents qui ne cessent de se multiplier. In 1765, the chartrier Pierre Camille Le Moine publishes a treaty entitled «Diplomatique pratique ou Traité de l’arrangement des archives et des trésors des chartes ». In this publication , Pierre Camille Le Moine explains his vision concerning the optimal management of numerous documents that  the archivists of his period have to manage.  This "work-fiction" imagines the arrival of Pierre Camille Le Moine in the New World of the digital technology. Convinced that his theory can still, at least partially, apply to this new futuristic era, the nice archivist explains the similarities between his pluricentenaire theory and that explained by his new contemporary colleagues of the 21th century. He also tries to demonstrate that his" plans généraux d’arrangement " can and have to serve as way to make sensitive the set of the individuals on the archiving of documents which do not stop accumulating.

Keyphrases: Archives numériques, Lumières, Archives analogiques, Ère numérique, Pierre Camille Le Moine, Évaluation des archives, Chartrier, Préservation, Patrimoine documentaire, Pierre Camille Le Moine, Archival appraisal, Digital Archives, Enlightenment, Chartrier, Collection of charters, Conservation, Documentary heritage
Intimacy, sexual satisfaction and sexual distress in vulvodynia couples : an observational study

Objective. Vulvodynia is a prevalent idiopathic pain condition with deleterious consequences for the sexuality of affected women and their spouses. Intimacy has been identified as a facilitator of adjustment to health difficulties in couples. Two components of intimacy were examined among couples with vulvodynia – empathic response and disclosure – in relation to their sexual satisfaction and sexual distress. Methods. Using an observational design, 50 women (M age= 24.50, SD = 4.03) diagnosed with vulvodynia and their spouses (M age = 26.10, SD = 5.70) participated in a filmed discussion focusing on the impact of vulvodynia on their lives. Empathic response and disclosure were assessed by a trained observer and self-reported by participants after engaging in the discussion. The Actor-Partner Interdependence Model guided the data analyses. Results. Women’s and spouses’ higher observed and perceived empathic response were associated with their own and their partners’ greater sexual satisfaction. Women’s and spouses’ higher perceived disclosure were associated with their own and their partners’ greater sexual satisfaction. Women’s and spouses’ higher observed empathic response were associated with their own lower sexual distress. Women’s higher observed empathic response was associated with their spouses’ lower sexual distress. Women and spouses’ perceived greater empathic response were associated with their own lower sexual distress. Women’s and spouses’ greater perceived disclosure during the discussion were associated with their own and their partners’ lower sexual distress. Conclusions. Promoting empathic response and disclosure through couple interventions may buffer against the sexual distress and sexual dissatisfaction of couples coping with vulvodynia.

Keyphrases: Provoked vestibulodynia, Vulvodynia, Pain, Emotional intimacy, Empathy, Disclosure, Sexual satisfaction, Sexual distress, Couple, Observational study