Fluoxetine reduces murine graft-versus-host disease by induction of T cell immunosuppression

Serotonin reuptake inhibitors (SRIs) are widely used drugs in the treatment of depression and anxiety disorders. Although SRIs are generally regarded as safe drugs with relatively few side effects, literature suggests that high concentrations of SRIs may alter immune function. We investigated whether high-dose treatment with fluoxetine was able to suppress acute graft-versus-host disease (GvHD) in a MHC-matched, minor histocompatibility antigen mismatched murine bone marrow transplantation model. We found that high doses fluoxetine induce a significant reduction of clinical symptoms and increase survival of these animals. The amelioration of clinical GvHD was accompanied by a reduced expansion of alloreactive T cells. We further analyzed the direct in vitro effect of six SRIs on the viability and proliferation of human T cells and found an anti-proliferative and pro-apoptotic effect that was significantly larger in activated than in resting T cells. We discuss these results in the light of potential future exploration of SRIs as a novel class of T cell immunosuppressive drugs

Status of the light ion source developments at CEA/Saclay

ACC NIMInternational audienceSILHI (High Intensity Light Ion Source) is an ECR ion source producing high intensity proton ordeuteron beams at 95 keV. It is now installed in the IPHI site building, on the CEA/Saclay center. IPHI is a frontend demonstrator of high power accelerator. The source regularly delivers more than 130 mA protons in CWmode and already produced more than 170 mA deuterons in pulsed mode at nominal energy. The last beamcharacterisations, including emittance measurements, space charge compensation analysis and diagnosticimprovements, will be reported. Taking into account the SILHI experience, new developments are in progress tobuild and test a 5 mA deuteron source working in CW mode. This new source will also operate at 2.45 GHz andpermanent magnets will provide the magnetic configuration. This source, of which the design will be discussed,will have to fit in with the SPIRAL 2 accelerator developed at GANIL to produce Radioactive Ion Beams. TheH- test stand status is briefly presented here and detailed in companion papers.This work is partly supported by the European Commission under contract n°: HPRI-CT-2001-50021

Deciphering hybrid larch reaction norms using random regression

The link between phenotypic plasticity and heterosis is a broad fundamental question, with stakes in breeding. We report a case-study evaluating temporal series of wood ring traits of hybrid larch (Larix decidua × L. kaempferi and reciprocal) in relation to soil water availability. Growth rings record the tree plastic responses to past environmental conditions, and we used random regressions to estimate the reaction norms of ring width and wood density with respect to water availability. We investigated the role of phenotypic plasticity on the construction of hybrid larch heterosis and on the expression of its quantitative genetic parameters. The data came from an intra-/interspecific diallel mating design between both parental species. Progenies were grown in two environmentally contrasted sites, in France. Ring width plasticity with respect to water availability was confirmed, as all three taxa produced narrower rings under the lowest water availability. Hybrid larch appeared to be the most plastic taxon as its superiority over its parental species increased with increasing water availability. Despite the low heritabilities of the investigated traits, we found that the expression of a reliable negative correlation between them was conditional to the water availability environment. Finally, by means of a complementary simulation, we demonstrated that random regression can be applied to model the reaction norms of non-repeated records of phenotypic plasticity bound by a family structure. Random regression is a powerful tool for the modeling of reaction norms in various contexts, especially perennial species

Psychotherapeutic Interventions for Type 2 Diabetes Mellitus

This chapter explores the efficacy of psychotherapeutic interventions for patients with type 2 diabetes mellitus (T2DM). This condition can lead to serious adverse health outcomes (e.g., cardiovascular disease, blindness, loss of limbs, etc.). Medical interventions alone are often not sufficient to manage the disease. Psychotherapy can promote behavioral change that improves medication adherence, dietary choices, exercise, stress, and other variables that affect blood sugar levels. The current chapter summarizes the trends in recent research for psychotherapeutic interventions for the management of T2DM. The results from 16 randomized controlled trials on cognitive-behavioral therapy, motivational interviewing, counseling, and mindfulness-based therapies are discussed. These interventions varied in length (3 to 18 months) and were conducted in many geographic regions (e.g., Australia, Netherlands, Saudi Arabia, Thailand, and more). Changes in biological health outcomes (i.e., HbA1c levels) were the primary focus of this chapter, but diabetes-related behavioral changes (e.g., diet and exercise) and psychological variables (e.g., stress, depression, and well-being) are also discussed. This chapter highlights that recent research has provided the most support for mindfulness-based therapies for improving blood sugar levels in patients with T2DM

Enhancing LULC scenarios impact assessment in hydrological dynamics using participatory mapping protocols in semiarid regions

Land use and land cover (LULC) scenarios in rural catchment hydrology are crucial to describe the effects of future water dynamics. However, there is a lack of understanding of the effectiveness of including static land covers at the subbasin level to provide inter-annual stability in changing the different water balance components. We developed a step-by-step mapping protocol to extend and enrich the hydrological assessment of future LULC scenarios defined through participatory stakeholder involvement. This novelty included specific allocation of static and dynamic LULC change among the scenarios and then compared the change of water dynamics to the current situation. For this, we quantified the LULC impact on the components of the water balance from three contrasting participatory scenarios implemented with the SWAT model in a rural basin in central Spain. The Land-sharing scenario (LSH) had the highest percentage of permanent grassland and shrubs and no increase of irrigated land compared to baseline. The land-sparing scenario (LSP) intensified agricultural land use close to urban areas, and the land balance scenario (LBA) was intermediate. The LSH increased the aquifer recharge by +1.7% and streamflow by +1.5%, while evapotranspiration and soil water storage decreased by -0.2%. In contrast, the LBA decreased in the riverine flux of -0.5%, an aquifer recharge of -0.6%, a soil water storage of -3.5%, and an evapotranspiration rate of +0.3%. Thus, LSH revealed that the allocation of permanent land cover such as grassland could buffer water dynamics, suggesting that dedicated planning and allocation of permanently vegetated LULC will favour land and water conservation

The African surgical outcomes-2 (Asos-2) pilot trial, a mixed-methods implementation study

Funding Information: The ASOS-2 Pilot Trial was supported by a grant (OPP#1161108) from the Bill & Melinda Gates Foundation.Peer reviewe

Interventions sur les facteurs de risque psychosociaux dans la lombalgie aiguë ou subaiguë en soins primaires : revue de littérature

Contexte. La lombalgie chronique est un problème récurrent en médecine générale. Des facteurs psychosociaux semblent impliqués dans le passage à la chronicité. L’objectif principal de cette revue était d’identifier et de décrire les études traitant d’interventions sur des facteurs psychosociaux dans la lombalgie (sub)aiguë en soins primaires. L’objectif secondaire était d’en analyser l’efficacité.Méthode. Une recherche systématique a été réalisée dans les principales bases de données biomédicales, et les articles pertinents ont été sélectionnés. Les caractéristiques des interventions ont été décrites, et les principaux résultats analysés. Résultats. Parmi les 513 études identifiées, 10 ont été retenues. Toutes les interventions comprenaient une part éducationnelle, surtout fondée sur une brochure : le « Back Book ». Certaines reposaient, en plus, sur une thérapie à orientation cognitivo-comportementale. Une autre était centrée sur la coordination en milieu de travail. Dans ces articles, la description des interventions et de la théorie sous-jacente était souvent insuffisante. Leur impact était modeste sur le pronostic des patients. Conclusion. Les recommandations actuelles sur la prise en charge de la lombalgie (sub)aiguë en soins primaires n’intègrent pas encore les résultats de ces études, mais cette revue apporte peu d’arguments pour les modifier en faveur des interventions identifiées. Des interventions plus individualisées pourraient être une autre voie pour améliorer le pronostic des patients ayant des facteurs de risque psychosociaux

Imatinib Mesylate Exerts Anti-Proliferative Effects on Osteosarcoma Cells and Inhibits the Tumour Growth in Immunocompetent Murine Models

Osteosarcoma is the most common primary malignant bone tumour characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments shows the importance of exploring new therapeutic methods. Imatinib mesylate (Gleevec, Novartis Pharma), a tyrosine kinase inhibitor, was originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that imatinib mesylate inhibits osteoclast differentiation through the M-CSFR pathway and activates osteoblast differentiation through PDGFR pathway, two key cells involved in the vicious cycle controlling the tumour development. The present study investigated the in vitro effects of imatinib mesylate on the proliferation, apoptosis, cell cycle, and migration ability of five osteosarcoma cell lines (human: MG-63, HOS; rat: OSRGA; mice: MOS-J, POS-1). Imatinib mesylate was also assessed as a curative and preventive treatment in two syngenic osteosarcoma models: MOS-J (mixed osteoblastic/osteolytic osteosarcoma) and POS-1 (undifferentiated osteosarcoma). Imatinib mesylate exhibited a dose-dependent anti-proliferative effect in all cell lines studied. The drug induced a G0/G1 cell cycle arrest in most cell lines, except for POS-1 and HOS cells that were blocked in the S phase. In addition, imatinib mesylate induced cell death and strongly inhibited osteosarcoma cell migration. In the MOS-J osteosarcoma model, oral administration of imatinib mesylate significantly inhibited the tumour development in both preventive and curative approaches. A phospho-receptor tyrosine kinase array kit revealed that PDGFRα, among 7 other receptors (PDFGFRβ, Axl, RYK, EGFR, EphA2 and 10, IGF1R), appears as one of the main molecular targets for imatinib mesylate. In the light of the present study and the literature, it would be particularly interesting to revisit therapeutic evaluation of imatinib mesylate in osteosarcoma according to the tyrosine-kinase receptor status of patients

Disorder-Driven Pretransitional Tweed in Martensitic Transformations

Defying the conventional wisdom regarding first--order transitions, {\it solid--solid displacive transformations} are often accompanied by pronounced pretransitional phenomena. Generally, these phenomena are indicative of some mesoscopic lattice deformation that ``anticipates'' the upcoming phase transition. Among these precursive effects is the observation of the so-called ``tweed'' pattern in transmission electron microscopy in a wide variety of materials. We have investigated the tweed deformation in a two dimensional model system, and found that it arises because the compositional disorder intrinsic to any alloy conspires with the natural geometric constraints of the lattice to produce a frustrated, glassy phase. The predicted phase diagram and glassy behavior have been verified by numerical simulations, and diffraction patterns of simulated systems are found to compare well with experimental data. Analytically comparing to alternative models of strain-disorder coupling, we show that the present model best accounts for experimental observations.Comment: 43 pages in TeX, plus figures. Most figures supplied separately in uuencoded format. Three other figures available via anonymous ftp

The African Surgical OutcomeS-2 (ASOS-2) Pilot Trial, a mixed-methods implementation study

Background: The African Surgical Outcomes Study (ASOS) showed that surgical patients in Africa have a mortality twice the global average. The working hypothesis is that patients die as a result of failure to rescue following complications in the postoperative period. The African Surgical OutcomeS-2 (ASOS-2) Trial plans to test the efficacy of increased postoperative surveillance in high risk patients for decreasing perioperative morbidity and mortality. This pilot trial aimed i) to evaluate the adequacy of data produced by the data collection strategies of the ASOS-2 Trial, ii) to evaluate the fidelity of implementation of the increased postoperative surveillance intervention, and iii) to understand the acceptability, appropriateness and feasibility of the intervention and the trial processes.Methods: The ASOS-2 Pilot Trial was a mixed-methods (quantitative-qualitative) implementation study focusing on the intervention arm of the proposed ASOS-2 Trial. The intervention is increased postoperative surveillance for high-risk surgical patients. The intervention protocol was implemented at all sites for a seven-day period. A post pilot trial survey was used to collect data on the implementation outcomes.Results: 803 patients were recruited from 16 hospitals in eight African countries. The sampling and data collection strategies provided 98% complete data collection. Seventy-three percent of respondents believed that they truly provided increased postoperative surveillance to high risk patients. In reality 83/125 (66%) of high-risk patients received some form of increased postoperative surveillance. However, the individual components of the increased postoperative surveillance intervention were implemented in less than 50% of high-risk patients (excepting increasing nursing observations). The components most frequently unavailable were the ability to provide care in a higher care ward (32.1%) and assigning the patient to a bed in view of the nurses’ station (28.4%). Failure to comply with available components of the intervention ranged from 27.5% to 54.3%. The post pilot survey had a response rate of 30/40 (75%). In Likert scale questions about acceptability, appropriateness, and feasibility of the ASOS-2 intervention, 63% to 87% of respondents indicated agreement. Respondents reported barriers related to resources, trial processes, teamwork and communication as reasons for disagreement.Conclusions: The proposed ASOS-2 Trial appears to be appropriate, acceptable and feasible in Africa. This pilot trial provides support for the proposed ASOS-2 Trial. It emphasises the need for establishing trial site teams which address the needs of all stakeholders during the trial. A concerted effort must be made to help participating hospitals to increase compliance with all the components of the proposed intervention of ‘increased postoperative surveillance’ during the ASOS-2 Trial.Keywords: Trial, cluster randomised, Trial, pilot, Implementation science, Mixed methods, Mortality, Surger