Ir-CPI, a coagulation contact phase inhibitor from the tick Ixodes ricinus, inhibits thrombus formation without impairing hemostasis

Blood coagulation starts immediately after damage to the vascular endothelium. This system is essential for minimizing blood loss from an injured blood vessel but also contributes to vascular thrombosis. Although it has long been thought that the intrinsic coagulation pathway is not important for clotting in vivo, recent data obtained with genetically altered mice indicate that contact phase proteins seem to be essential for thrombus formation. We show that recombinant Ixodes ricinus contact phase inhibitor (Ir-CPI), a Kunitz-type protein expressed by the salivary glands of the tick Ixodes ricinus, specifically interacts with activated human contact phase factors (FXIIa, FXIa, and kallikrein) and prolongs the activated partial thromboplastin time (aPTT) in vitro. The effects of Ir-CPI were also examined in vivo using both venous and arterial thrombosis models. Intravenous administration of Ir-CPI in rats and mice caused a dose-dependent reduction in venous thrombus formation and revealed a defect in the formation of arterial occlusive thrombi. Moreover, mice injected with Ir-CPI are protected against collagen- and epinephrine-induced thromboembolism. Remarkably, the effective antithrombotic dose of Ir-CPI did not promote bleeding or impair blood coagulation parameters. To conclude, our results show that a contact phase inhibitor is an effective and safe antithrombotic agent in vivo

Dietary intake of fish, omega-3, omega-6 polyunsaturated fatty acids and vitamin D and the prevalence of psychotic-like symptoms in a cohort of 33 000 women from the general population

<p>Abstract</p> <p>Background</p> <p>Low intake of fish, polyunsaturated fatty acids (PUFA) and vitamin D deficiency has been suggested to play a role in the development of schizophrenia. Our aim was to evaluate the association between the intake of different fish species, PUFA and vitamin D and the prevalence of psychotic-like symptoms in a population-based study among Swedish women.</p> <p>Methods</p> <p>Dietary intake was estimated using a food frequency questionnaire among 33 623 women aged 30-49 years at enrolment (1991/92). Information on psychotic-like symptoms was derived from a follow-up questionnaire in the years 2002/03. Participants were classified into three predefined levels: low, middle and high frequency of symptoms. The association between diet and psychotic-like symptoms was summarized in terms of relative risks (RR) and corresponding 95% confidence intervals and was evaluated by energy-adjusted multinomial logistic regression.</p> <p>Results</p> <p>18 411 women were classified as having a low level of psychotic-like symptoms, 14 395 as middle and 817 as having a high level. The risk of high level symptoms was 53% (95% CI, 30-69%) lower among women who ate fish 3-4 times per week compared to women who never ate fish. The risk was also lower for women with a high intake of omega-3 and omega-6 PUFA compared to women with a lower intake of these fatty acids. The effect was most pronounced for omega-6 PUFAs. The RR comparing the highest to the lowest quartile of omega-6 PUFAs intake was 0.78 (95% CI, 0.64-0.97). The associations were J-shaped with the strongest reduced risk for an intermediate intake of fish or PUFA. For fatty fish (herring/mackerel, salmon-type fish), the strongest inverse association was found for an intermediate intake (RR: 0.81, 95% CI, 0.66-0.98), whereas a high intake of fatty fish was associated with an increased risk of psychotic-like symptoms (RR: 1.90, 95% CI, 1.34-2.70). Women in the highest compared with the lowest quartile of vitamin D consumption experienced a 37% (95% CI, 22-50%) lower risk of psychotic-like symptoms.</p> <p>Conclusion</p> <p>Our findings raise a possibility that adult women with a high intake of fish, omega-3 or omega-6 PUFA and vitamin D have a lower rate of psychotic-like symptoms.</p

Research response to coronavirus disease 2019 needed better coordination and collaboration: a living mapping of registered trials

Objectives: Researchers worldwide are actively engaging in research activities to search for preventive and therapeutic interventions against coronavirus disease 2019 (COVID-19). Our aim was to describe the planning of randomized controlled trials (RCTs) in terms of timing related to the course of the COVID-19 epidemic and research question evaluated. Study Design and Setting: We performed a living mapping of RCTs registered in the WHO International Clinical Trials Registry Platform. We systematically search the platform every week for all RCTs evaluating preventive interventions and treatments for COVID-19 and created a publicly available interactive mapping tool at https://covid-nma.com to visualize all trials registered. Results: By August 12, 2020, 1,568 trials for COVID-19 were registered worldwide. Overall, the median ([Q1–Q3]; range) delay between the first case recorded in each country and the first RCT registered was 47 days ([33–67]; 15–163). For the 9 countries with the highest number of trials registered, most trials were registered after the peak of the epidemic (from 100% trials in Italy to 38% in the United States). Most trials evaluated treatments (1,333 trials; 85%); only 223 (14%) evaluated preventive strategies and 12 postacute period intervention. A total of 254 trials were planned to assess different regimens of hydroxychloroquine with an expected sample size of 110,883 patients. Conclusion: This living mapping analysis showed that COVID-19 trials have relatively small sample size with certain redundancy in research questions. Most trials were registered when the first peak of the pandemic has passed

Cent scientifiques répliquent à SEA (Suppression des Expériences sur l’Animal vivant) et dénoncent sa désinformation

La lutte contre la maltraitance animale est sans conteste une cause moralement juste. Mais elle ne justifie en rien la désinformation à laquelle certaines associations qui s’en réclament ont recours pour remettre en question l’usage de l’expérimentation animale en recherche

Constraints experienced by physical education teachers with overweight and obese students

Despite ‘antifat’ attitude of some PE teachers (Greenleaf & Weiller, 2005) and the PE public relations problem in regard to how obese students are treated (Irwin et al., 2003), it seems evident that this school subject represents a key element in the involvement of the education sector in the fight against the worldwide escalating global epidemic of obesity (Tappe & Burgeson, 2004). In fact, PE teachers consider that they lack of specific knowledge to implement instructional strategies dealing with overweight and obese students (Cloes & Ziant, 2009). Some authors proposed models to illustrate constraints that PE teachers encounter in their classes with obese students and their potential solutions (Cloes et al., 2013; Rukavina et al., 2010). On the other hand, data are missing when identifying those that are considered as their main concerns and the ways that they would prefer to receive some support regarding this specific topic. This study is focused on these two aspects. Five hundred thirteen PE teachers fulfilled an online questionnaire (Lickert scales) in which they had to determine (1) the perceived importance of 20 problems proposed by PE teachers and validated by 8 experts; (2) their relative interest toward the reception of support aiming to deal with those problems; (3) their preference for receiving information about the potential instructional strategies. Based on the answers, the top 3 problems are: (1) Students’ lack of awareness about the risks of overweight and obesity; (2) Constraints associated with the motor/physical disabling; (3) Parents’ lack of awareness about physical activity impact on health. Internet (3.49±.6/4), continuing professional development activities (3.29±.8/4), and educational info capsules (3.07±.8/4) were identified as the main resources that PE teachers would use preferentially. This study provides useful information for PE teachers’ educators who should develop now material to be shared with the practitioners

Étude des voies de signalisation MAPK et PI3K/Akt dans deux modèles animaux de la dystrophie musculaire de Duchenne (la souris mdx et le chien GRMD)

Bien que l origine de la dystrophie musculaire de Duchenne soit connue, des mutations dans le gène DMD aboutissant à l absence de dystrophine, les mécanismes globaux définissant la pathogénie ne sont toujours pas élucidés. L implication d un dérèglement des voies de signalisation a été suggéré et nous souhaitions utiliser la technologie des puces à anticorps pour obtenir une vision globale des modulations affectant les voies MAPK et PI3K/Akt dans le muscle dystrophique. Après une première étude chez la souris mdx, les travaux ont été poursuivis sur le modèle du chien GRMD qui, de part sa physio-pathologie extrêmement proche de celle de l homme, nous paraissait plus adapté. La comparaison du profil de phosphorylation de 19 kinases dans les muscles sain et GRMD révèle que Akt1, ses cibles directes et indirectes GSK3b et p70S6K, ainsi que les MAPK ERK1/2, p38d et p38g présentent toutes une phosphorylation réduite dans le muscle GRMD. Les tests d activité enzymatique montrent que le défaut de phosphorylation des kinases de la voie PI3K/Akt détecté est associé à une activité réduite pour Akt et augmentée pour GSK3b (corrélé par une sur-expression de la kinase). Des expériences de western blot et des tests enzymatiques révèlent une augmentation de l expression et de l activité de la phosphatase PTEN, alors que les expériences de double marquage immunologique montrent la présence dans le muscle GRMD de fibres PTEN/GSK3b-positives et ce, à plusieurs stades. L ensemble de ces travaux suggère que l activation de PTEN dans le muscle dystrophique pourrait empêcher l hypertrophie compensatoire régulée par la voie PI3K/Akt et aggraver les conséquences de l absence de dystrophineAlthough the origin of Duchenne muscular dystrophy is known, mutations in the DMD gene leading to the absence of dystrophin, the global mechanisms defining the pathogenesis are not yet understood. The implication of signaling pathway deregulation has been suggested and we wanted to take advantage of the antibody array technology to obtain a global overview of the modulations affecting the MAPK and PI3K/Akt pathways in dystrophic muscle. After a first study in the mdx mouse model, the work has been carried out in the GRMD dog that, thanks to its pathophysiology extremely close to that of human patients, appeared more pertinent to this study. The comparison of the phosphorylation profile of 19 different kinases between healthy and GRMD skeletal muscles reveale that Akt1, its direct and indirect targets GSK3b and p70S6K, along with the MAPK ERK1/2, p38d and p38g, all exhibit a reduced phosphorylation level in GRMD muscle. Enzymatic assays show that the phosphorylation defect of the PI3K/Akt pathway kinases detected in GRMD muscle is associated with decreased Akt and increased GSK3b activity (corroborated by an over-expression of the kinase). Western immunoblot experiments and enzymatic assays reveal increased expression and activity of the PTEN phosphatase, whereas immunohistochemcal double staining experiments show the presence in GRMD muscle sections of PTEN/GSK3b-positive fibers, and this at different stages of the disease. Taken together, these results suggest that PTEN activation in dystrophic muscle could prevent the compensatory hypertrophy response that is regulated by the PI3K/Akt pathway, and exacerbate the consequences of the absence of dystrophinNANTES-BU Sciences (441092104) / SudocSudocFranceF

Development of educational info capsules proposing instructional strategies aiming to deal with overweight and obese students

Irwin et al. (2003) pointed out the principles that quality PE teachers should incorporate into their pedagogical practice in order to take into account the increasing number of overweight and obese students in their classes. Fighting against obesity is so complex that no simple solution can be proposed. It means that the development of specific tools providing PE teachers with new instructional strategies inspired from public health is needed (Prusak et al., 2011). Inclusion of overweight students into PE can be linked with a social ecological model (Li & Rukavina, 2012). Even if PE teachers are able to develop and implement specific instructional strategies, it seems that they need support from health experts (Cloes et al., 2013). Internet, continuing professional development activities, and educational info capsules were identified as the preferred supports to be used by the practitioners (Cloes et al., 2014). The aims of this study were to produce and validate three pedagogical capsules focusing on specific concerns of PE teachers as well as to analyze the procedure of validation. Using an extensive analysis of the literature, the researchers first identified theoretical and practical resources to be mobilized in the understanding and development of solutions for the selected problems: (1) Students’ lack of awareness about the risks of overweight and obesity; (2) Constraints associated with the motor/physical disabling; (3) Parents’ lack of awareness about PA impact on health. The capsules were then submitted to 11 experts (health specialists, health educators, psychologists, PE teachers) who had to analyze the documents. They acknowledged the content and form of the capsules. Minor changes were requested in order to finalize them. The proposed evaluation sheet was also validated but face-to-face assessment was recommended. Dissemination of the existing capsules as well as development of additional ones should be the next steps of this project

Effects of mastication on salivary metabolome

International audienc