Neurotoxicant-induced inflammatory response in three-dimensional brain cell cultures.

Brain inflammatory response is triggered by the activation of microglial cells and astrocytes in response to various types of CNS injury, including neurotoxic insults. Its outcome is determined by cellular interactions, inflammatory mediators, as well as trophic and/or cytotoxic signals, and depends on many additional factors such as the intensity and duration of the insult, the extent of both the primary neuronal damage and glial reactivity and the developmental stage of the brain. Depending on particular circumstances, the brain inflammatory response can promote neuroprotection, regeneration or neurodegeneration. Glial reactivity, regarded as the central phenomenon of brain inflammation, has also been used as an early marker of neurotoxicity. To study the mechanisms underlying the glial reactivity, serum-free aggregating brain cell cultures were used as an in vitro model to test the effects of conventional neurotoxicants such as organophosphate pesticides, heavy metals, excitotoxins and mycotoxins. This approach was found to be relevant and justified by the complex cell-cell interactions involved in the brain inflammatory response, the variability of the glial reactions and the multitude of mediators involved. All these variables need to be considered for the elucidation of the specific cellular and molecular reactions and their consequences caused by a given chemical insult.

Migrating concepts: Immigrant integration and the regulation of religious dress in France and Canada

Religion in general, and Islam in particular, has become one of the main focal points of policy-making and constitutional politics in many Western liberal states. This article proposes to examine the legal and political dynamics behind new regulations targeting individual religious practices of Muslims. Although one could presuppose that church-state relations or the understanding of secularism is the main factor accounting for either accommodation or prohibition of Muslim religious practices, I make the case that the policy frame used to conceptualize the integration of immigrants in each national context is a more significant influence on how a liberal state approaches the legal regulation of individual practices such as veiling. However, this influence must be assessed carefully since it may have different effects on the different institutional actors in charge of regulating religion, such as the Courts and the legislature. To assess these hypotheses I compare two countries, France and Canada, which are solid examples of two contrasting national policy frames for the integration of immigrants.

The oceanic base of slope record of the Permian-Triassic crisis: view from Tethys (Oman)

The Oman Mountains provide some of the best sections of Permian and Triassic sediments from ocean sea floor to base-of-slope environments related to the distal South Tethyan margin. The central part of the range exposes the Buday'ah section of oceanic sediments in the so-called "Hawasina allochtons". The locality of Wadi Maqam in the north-western part of the Oman Mountains is among places where the thick Permian-Triassic base-of-slope sediments is exposed (Baud et al., 2001). Overlying 400 m of middle Permian limestones and dolomites, the upper Permian sediments consist of 50 m of ≈ 10 cm thick beds of cherts and dolomites rich in sponge spicules. The top of the Permian units is well bioturbated lime mudstone-wackestone, devoid of cherts and dated as late Changhsingian (Krystyn in Richoz et al., 2005). The boundary yellow shales are overlain by very thinly bedded, laminated microbial platy lime mudstone with H. parvus. The dramatic loss of the burrowing infauna indicates the appearance of oxygen-poor water. These Induan sediments are about 25 m thick and show at the top the first calcirudites, commonly clast-supported (edge-wise conglomerates), and are characterized by tabular clasts representing the sub- in situ reworking of the laminated, platy calcilutite. The very thick Smithian overlying litho-unit (up to 900 m) marks the onset on the base-of-slope of a deep-marine basin in which carbonate submarine fan deposits developed This very thick unit consists essentially of platy limestones, calcarenites and calcirudites. It comprises mainly grey-beige calcilutite, laminated and flaggy, interbedded with sparse beds of fine-grained calcarenite in cm beds. Channelized beds of intraformational calcirudite are also part of this succession which constitutes the greater part of the outcrop available. During the Spathian to Anisian, the sedimentation changes to terrigenous mudstone and siltstone that ended with Ladinian radiolarites.

Natalizumab treatment alters the expression of T-cell trafficking marker LFA-1 α-chain (CD11a) in MS patients.

OBJECTIVE: To determine the long-term effect of natalizumab (NTZ) treatment on the expression of integrins and chemokine receptors involved in the migration of T cells towards the central nervous system (CNS). METHODS: We drew the blood of 23 patients just before starting NTZ therapy and every 12 months thereafter, for up to 48 months of treatment. We assessed the ex-vivo expression of phenotype markers (CCR7 and CD45RA), CNS-addressing integrins (CD11a, CD49d and CD29) and chemokine receptors (CXCR3 and CCR6) in CD4+ or CD8+ T-cell subsets by flow cytometry. RESULTS: As compared to the pre-NTZ values, there was a marked increase in central memory (CCR7+/CD45RA-) CD4+ T cells and in effector memory (CCR7-/CD45RA-) CD8+ T cells at 12 and 24 months. In addition to an expected downregulation of both VLA-4 subunits (CD49d/CD29), we also found decreased T-cell expression of CXCR3 at 12 months, and of CD11a (LFA-1 αL subunit) at 12 months, but mostly at 24 months of NTZ treatment. CONCLUSION: Our data show a nadir of CD11a expression at 2 years of NTZ treatment, at the peak of incidence of progressive multifocal leukoencephalopathy (PML), indirectly suggesting that a lack of these molecules may play a role in the onset of PML in NTZ-treated patients.

Public perceptions of animal experimentation across Europe

The goal of this article is to map out public perceptions of animal experimentation in 28 European countries. Postulating cross-cultural differences, this study mixes country-level variables (from the Eurostat database) and individual-level variables (from Eurobarometer Science and Technology 2010). It is shown that experimentation on animals such as mice is generally accepted in European countries, but perceptions are divided on dogs and monkeys. Between 2005 and 2010, we observe globally a change of approval on dogs and monkeys, with a significant decrease in nine countries. Multilevel analysis results show differences at country level (related to a post-industrialism model) and at individual level (related to gender, age, education, proximity and perceptions of science and the environment). These results may have consequences for public perceptions of science and we call for more cross-cultural research on press coverage of animal research and on the level of public engagement of scientists doing animal research

IRM cardiaque: imagerie de référence dans le diagnostic de la myocardite aiguë [Cardiac magnetic resonance in acute myocarditis: a new non-invasive diagnostic gold standard?].

Acute myocarditis was until recently one of the most difficult diagnoses in cardiology. The spectrum of signs and symptoms is very wide, the usual non-invasive tests lack specificity and the myocardial biopsy is only performed in a minority of cases to confirm the diagnosis. Due to its unique ability to directly image myocardial necrosis, fibrosis and oedema, cardiac magnetic resonance (CMR) is now considered the primary tool for noninvasive assessment of patients with suspected myocarditis. CMR is also useful for monitoring disease activity under treatment. Myocarditis has been associated with the development of dilated cardiomyopathy; CMR could play a role in the follow-up of such cases to detect the progression toward a dilatative phenotype. Precise mapping of myocardial lesions with cardiac MRI is invaluable to guide myocardial biopsy and increase its diagnostic yield by improving sensitivity.

When Preference Is Not Satisfied but the Individual Is: How Power Distance Affects Person-Job Fit

One aspect of person-job fit reflects congruence between personal preferences and job design; as congruence increases so should satisfaction. We hypothesized that power distance would moderate whether fit is related to satisfaction with degree of job formalization. We obtained measures of job-formalization, fit and satisfaction, as well as organizational commitment from employees (n = 772) in a multinational firm with subsidiaries in six countries. Confirming previous findings, individuals from low power-distance cultures were most satisfied with increasing fit. However, the extent to which individuals from high power-distance cultures were satisfied did not necessarily depend on increasing fit, but mostly on whether the degree of formalization received was congruent to cultural norms. Irrespective of culture, satisfaction with formalization predicted a broad measure of organizational commitment. Apart from our novel extension of fit theory, we show how moderation can be tested in the context of polynomial response surface regression and how specific hypotheses can be tested regarding different points on the response surface.

Effects of a treatment gap during adjuvant chemotherapy in node-positive breast cancer: results of International Breast Cancer Study Group (IBCSG) Trials 13-93 and 14-93.

BACKGROUND: The International Breast Cancer Study Group (IBCSG) conducted two complementary randomized trials to assess whether a treatment-free gap during adjuvant chemotherapy influenced outcome. PATIENTS AND METHODS: From 1993 to 1999, IBCSG Trials 13-93 and 14-93 enrolled 2215 premenopausal and postmenopausal women with axillary node-positive, operable breast cancer. All patients received cyclophosphamide (Cytoxan, C) plus either doxorubicin (Adriamycin, A) or epirubicin (E) for four courses followed immediately (No Gap) or after a 16-week delay (Gap) by classical cyclophosphamide, methotrexate, and fluorouracil (CMF) for three courses. The median follow-up was 7.7 years. RESULTS: The Gap and No-Gap groups had similar disease-free survival (DFS) and overall survival (OS). No identified subgroup showed a statistically significant difference, but exploratory subgroup analysis noted a trend towards decreased DFS for Gap compared with No Gap for women with estrogen receptor (ER)-negative tumors not receiving tamoxifen, especially evident during the first 2 years. CONCLUSIONS: A 16-week gap between adjuvant AC/EC and CMF provided no benefit and may have increased early recurrence rates in patients with ER-negative tumors.