Spodoptera frugiperda immune response to the nematobacterial complex Steinernema carpocapsae-Xenorhabdus nematophila

[i]Spodoptera frugiperda[/i] immune response to the nematobacterial complex [i]Steinernema carpocapsae-Xenorhabdus nematophila[/i]. Conférences Jacques Monod "Immunologie Intégrative des Insectes : Contrôle des Infections

Subjective sleep dysfunction and insomnia symptoms in Parkinson's disease: Insights from a cross-sectional evaluation of the French CoPark cohort

Introduction: Twenty-seven to 80% of patients with Parkinson's Disease (PD) complain of subjective sleep dysfunction and insomnia symptoms. Our aim is to describe the prevalence and features of subjective sleep dysfunction and insomnia symptoms in patients with PD compared to other patients. Methods: Cross-sectional analysis of 636 adult PD patients compared to 143 age and sex-matched non-PD control patients consulting their general practitioners. Insomnia symptoms and other sleep features were assessed by the Pittsburgh Sleep Quality Index (PSQI), a global score > 5 defining impaired sleep. The Chi-square test or the Student's t-test were used to assess the potential clinical and demographic differences between groups and between PD patients with vs. without sleep dysfunction. Logistic regression analysis was employed to test multivariate effects. Results: Sleep dysfunction and insomnia symptoms were more frequent in PD patients compared to control patients (63 vs. 45%, p = 0.001). Female gender, PD duration, presence of depression and anxiety were associated with the presence of insomnia in PD. Subjective sleep efficiency, habitual sleep quality, sleep disturbance and daytime dysfunction, but not sleep latency, were reduced in PD patients compared to controls. Conclusions: The prevalence of sleep dysfunction is higher in PD than in other general medical conditions. Insomnia in PD seems to affect sleep maintenance and consolidation, but not sleep onset.Fil: Ratti, Pietro Luca. Université Paul Sabatier; Francia. Inserm; Francia. Sleep and Epilepsy Center; Suiza. Toulouse University Hospital; FranciaFil: Negre Pages, Laurence. Toulouse University Hospital; Francia. Université Paul Sabatier; FranciaFil: Pérez Lloret, Santiago. Toulouse University Hospital; Francia. Université Paul Sabatier; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Manni, Raffaele. Istituto di Ricovero e Cura a Carattere Scientifico. Istituto Neurologico Nazionale a Carattere Scientifico; ItaliaFil: Damier, Philippe. Universite de Nantes; FranciaFil: Tison, Francois. Universite de Bordeaux; FranciaFil: Destée, Alain. Centre Hospitalier Universitaire de Lille. Pôle de Neurologie. Service de Neurologie et pathologie du mouvement; FranciaFil: Rascol, Olivier. Toulouse University Hospital; Francia. Inserm; Francia. Toulouse University Hospital; Francia. Université Paul Sabatier; Franci

Falls in ambulatory non-demented patients with Parkinson's disease

This study aimed at determining the prevalence of falling in PD patients, to assess generic and disease-specific clinical and pharmacological factors, relationship with health-related quality of life (HR-QoL) and changes in falls from OFF to ON in patients with motor fluctuations. Six-hundred and eighty-three PD patients of the COPARK survey were evaluated (11 had missing data and were excluded from the analysis). Patients with falls were identified as those with a UPDRS Item 13 ¡Ý 1 in the ON condition. All patients were assessed in a standardized manner [demographics, treatments, Unified PD Rating Scale (UPDRS), Hospital Anxiety and Depression Scale, Pittsburg questionnaire and HR-QoL scales (SF36, PDQ39)]. Falling was reported by 108/672 (16 %) PD patients during the ON state and prevalence increased according to PD severity, from 5 % in Hoehn and Yahr stage 1-60 % in stage 4. Falling was significantly related to lower HR-QoL. Falling correlated with (1) generic factors such as female gender, age at the end of academic studies and diuretics consumption, (2) motor PD-specific factors including disease severity, frozen gait, difficulties when arising from a chair, dyskinesia and higher levodopa daily equivalent dose and (3) non-motor PD-specific factors such as orthostatic hypotension and hallucinations. Falling was more frequent in OFF than in ON in 48/74 (64 %) patients with motor fluctuations and remained unchanged in 27 patients (36 %). In summary, falling affected a significant proportion of PD patients, especially in advanced stages. It was associated with a variety of generic and PD-specific factors and was related to reduced HR-QoL.Fil: Rascol, Olivier. NS-Park Network; Francia. Université Paul Sabatier; Francia. Inserm; FranciaFil: Pérez Lloret, Santiago. Université Paul Sabatier; Francia. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Damier, Philippe. Hôpital Laënnec; Francia. NS-Park Network; Francia. Inserm; FranciaFil: Delval, Arnaud. Seul Centre Hospitalier Universitaire; FranciaFil: Derkinderen, Pascal. Hôpital Laënnec; FranciaFil: Destée, Alain. NS-Park Network; Francia. Inserm; Francia. Seul Centre Hospitalier Universitaire; FranciaFil: Meissner, Wassilios G.. Universite de Bordeaux; Francia. Institut des Maladies Neurodégénératives; Francia. Centre Hospitalier Universitaire de Bordeaux; FranciaFil: Tison, Francois. Universite de Bordeaux; Francia. Centre Hospitalier Universitaire de Bordeaux; Francia. Institut des Maladies Neurodégénératives; Francia. NS-Park Network; FranciaFil: Negre Pages, Laurence. Inserm; Francia. NS-Park Network; Franci

Nonmotor versus motor symptoms: How much do they matter to health status in Parkinson's disease?

Evidence suggests that both motor and nonmotor symptoms contribute to health status in Parkinson's disease. Less clear is how much change in health status can be expected if these clinical variables change. In addition, anxiety, separate from depression, has rarely been examined as a predictor of health status. We used hierarchical multiple regression analysis and standardized beta coefficients in a prevalent cohort of 462 patients with Parkinson's disease to explore the relative impact on health status (measured using the Parkinson's Disease Questionnaire) of 5 well-recognized symptom domains in Parkinson's disease: motor signs, depression, anxiety, cognition, and other nonmotor symptoms. In the health status scores, 19.6% of variance was explained by age, number of comorbidities, disease duration, and levodopa equivalent dose. Younger age predicted worse health status. A full regression model containing baseline variables and all 5 symptom domains explained 56% of the variance in health status. The standardized beta coefficient for depression was 2.1, 1.6, and 1.3 times that of motor signs, anxiety, and other nonmotor symptoms, respectively. Our findings provide a ranking order of clinical variables for their relative impact on health status in Parkinson's disease and show that depression has more than twice the impact of motor signs on health status. Anxiety and other nonmotor symptoms are also important separate determinants of poor health status in Parkinson's disease. Our results will help to guide the development of individual care and service planning for patients with Parkinson's disease

Parkinson's disease motor subtypes and mood

Parkinson's disease is heterogeneous, both in terms of motor symptoms and mood. Identifying associations between phenotypic variants of motor and mood subtypes may provide clues to understand mechanisms underlying mood disorder and symptoms in Parkinson's disease. A total of 513 patients were assessed using the Hospital Anxiety and Depression Scale, and separately classified into anxious, depressed, and anxious-depressed mood classes based on latent class analysis of a semistructured interview. Motor subtypes assessed related to age-of-onset, rate of progression, presence of motor fluctuations, lateralization of motor symptoms, tremor dominance, and the presence of postural instability and gait symptoms and falls. The directions of observed associations tended to support previous findings with the exception of lateralization of symptoms, for which there were no consistent or significant results. Regression models examining a range of motor subtypes together indicated increased risk of anxiety in patients with younger age-of-onset and motor fluctuations. In contrast, depression was most strongly related to axial motor symptoms. Different risk factors were observed for depressed patients with and without anxiety, suggesting heterogeneity within Parkinson's disease depression. Such association data may suggest possible underlying common risk factors for motor subtype and mood. Combined with convergent evidence from other sources, possible mechanisms may include cholinergic system damage and white matter changes contributing to non-anxious depression in Parkinson's disease, while situational factors related to threat and unpredictability may contribute to the exacerbation and maintenance of anxiety in susceptible individuals

The interest of gait markers in the identification of subgroups among fibromyalgia patients

<p>Abstract</p> <p>Background</p> <p>Fibromyalgia (FM) is a heterogeneous syndrome and its classification into subgroups calls for broad-based discussion. FM subgrouping, which aims to adapt treatment according to different subgroups, relies in part, on psychological and cognitive dysfunctions. Since motor control of gait is closely related to cognitive function, we hypothesized that gait markers could be of interest in the identification of FM patients' subgroups. This controlled study aimed at characterizing gait disorders in FM, and subgrouping FM patients according to gait markers such as stride frequency (SF), stride regularity (SR), and cranio-caudal power (CCP) which measures kinesia.</p> <p>Methods</p> <p>A multicentre, observational open trial enrolled patients with primary FM (44.1 ± 8.1 y), and matched controls (44.1 ± 7.3 y). Outcome measurements and gait analyses were available for 52 pairs. A 3-step statistical analysis was carried out. A preliminary single blind analysis using k-means cluster was performed as an initial validation of gait markers. Then in order to quantify FM patients according to psychometric and gait variables an open descriptive analysis comparing patients and controls were made, and correlations between gait variables and main outcomes were calculated. Finally using cluster analysis, we described subgroups for each gait variable and looked for significant differences in self-reported assessments.</p> <p>Results</p> <p>SF was the most discriminating gait variable (73% of patients and controls). SF, SR, and CCP were different between patients and controls. There was a non-significant association between SF, FIQ and physical components from Short-Form 36 (p = 0.06). SR was correlated to FIQ (p = 0.01) and catastrophizing (p = 0.05) while CCP was correlated to pain (p = 0.01). The SF cluster identified 3 subgroups with a particular one characterized by normal SF, low pain, high activity and hyperkinesia. The SR cluster identified 2 distinct subgroups: the one with a reduced SR was distinguished by high FIQ, poor coping and altered affective status.</p> <p>Conclusion</p> <p>Gait analysis may provide additional information in the identification of subgroups among fibromyalgia patients. Gait analysis provided relevant information about physical and cognitive status, and pain behavior. Further studies are needed to better understand gait analysis implications in FM.</p

Approche translationnelle du concept de cible en cancérologie (étude de l'effet combiné du Docetaxel et du Bevacizumab sur la boucle autocrine VEGF / VEGF-R2 dans des modèles cellulaires de cancer du sein et de la prostate)

Les thérapies ciblées font partie de l arsenal thérapeutique quotidien en cancérologie. Dans le cadre de la prise en charge des patients, l oncologue doit désormais connaître et maîtriser les différentes cibles thérapeutiques, et comprendre la synergie entre les thérapies ciblées et les chimiothérapies. La néoangiogenèse tumorale est un phe nomène majeur dans la carcinogenèse. La principale thérapie ciblée antiangiogénique est le Bévacizumab. Il s agit d un anticorps monoclonal inhibant la liaison du VEGF, le Vascular Endothelial Growth Factor , principal facteur angiogénique, à son récepteur. Le Docetaxel est une des chimiothérapies les plus utilisées. Il inhibe la dépolymérisation des microtubules. Dans les cancers du sein et de la prostate, la combinaison Bevacizumab et Docetaxel augmente la réponse thérapeutique comparé au Docetaxel seul. Nous avons donc cherché à démontrer l effet de la combinaison de ces deux traitements sur la boucle autocrine VEGF / VEGF-R2, dans des cellules de cancer du sein et de la prostate. Nous avons montré qu en condition normale, la cellule n a pas besoin de la voie VEGF / VEGF-R2 pour assurer sa survie. Par contre, lors d un traitement par le Docetaxel, les principales voies de croissance sont partiellement inhibées : cette boucle autocrine devient donc nécessaire pour la survie cellulaire. L ajout du Bevacizumab au Docetaxel inactive la boucle autocrine en diminuant le VEGF extracellulaire et en diminuant le VEGF-R2 membranaire, ce qui conduit à un arrêt de la prolifération cellulaire. Ce travail propose donc une nouvelle explication de la synergie entre les Taxanes et le Bevacizumab, qui ciblent directement la boucle autocrine VEGF / VEGF-R2 sur les cellules tumorales. Une autre approche de la compréhension des thérapies ciblées est l identification de cibles pronostiques et thérapeutiques. Dans la seconde partie de ce travail, nous avons étudié l expression des microARNs, dans 27 cancers du poumon stade 1. Nous avons montré, en riblant la microARNome sur puce, qu il existe une signature microARN prédisant la récidive de ces cancers : il s agit de la sous-expression de mir 99a de mir30a, et de la sur-expression de mir297 et de mir21. Cette signature est en cours de validation sur une série plus large. Ces deux parties de ce travail abordent donc d une façon différente le concept de cible en cancérologie, en identifiant des mécanismes de synergie entre une thérapie ciblée et une chimiothérapie, et en recherchant de nouvelles cibles potentielles que sont les microARN.Targeted therapies are and important part of cancer treatment. Oncologist may have an overview of potential targets, and may understand the synergic effect of chemotherapies and targeted therapies. Tumor neoangiogenesis represent a critical step in tumor development. Main anti angiogenesis targeted therapy is Bevacizumab, which is a monoclonal antibodies inhibiting the binding VEGF (vascular endothelial growth factor) to its receptor. Docetaxel is one of the most important chemotherapy in cancer treatment. It inhibits microtubule depolymerisation. In breast and prostate cancer, Docetaxel delivered in association with Bevacizumab increases tumor response compared with Docetaxel alone. In this work, we investigated the combined effect of both treatments on the VEGF / VEGF-R2 autocrine loop, in breast and prostate cancer cells. We have demonstated that, in standard condition, the VEGF / VEGF-R2 loop is redundant in terms of cell survival. However, when cells are treated with Docetaxel, main growth pathways are inhibited: then, the VEGF / VEGF-R2 autocrin,e loop is useful for cell survival. The addition of Bevacizumab to Docetaxel inhibits the autocrine loop by decreasing extracellular VEGF and membrane expression of VEGF-R2, leading to cell proliferation arrest. Then, inthis work, we propose a new explanation for the synergiec effect of Taxane and Bevacizumab on tumor cells. Another approach in the understanding of targeted therapy action is the identification of prognostic and therapeutic targets. In the second part of this work, we have investigated the microRNA expression pattern of 27 stage I lung adenocarcinomas. By screening microRNA expression on microchip, we have highlighted the presence of a prognostic signature, predicting cancer outcome : under expression of mir99a and mir30a, over expression of mir 297 and mir 21. The signature is under validation on a large series of patient. As a conclusion, both parts of this work investigate two aspects of the target concept in oncology, by studying mechanism of synergy between a targeted therapy and chemotherapy, and by searching new targets such as microRNA.NICE-BU Sciences (060882101) / SudocSudocFranceF