Aix-Marseille University

About: Aix-Marseille University is a education organization based out in Marseille, France. It is known for research contribution in the topics: Population & Galaxy. The organization has 24326 authors who have published 54240 publications receiving 1455416 citations. The organization is also known as: University Aix-Marseille & université d'Aix-Marseille.

Chronic dopaminergic stimulation in Parkinson's disease: from dyskinesias to impulse control disorders

Abstract: Dopamine is an essential neurotransmitter for many brain functions, and its dysfunction has been implicated in both neurological and psychiatric disorders. Parkinson's disease is an archetypal disorder of dopamine dysfunction characterised by motor, cognitive, behavioural, and autonomic symptoms. While effective for motor symptoms, dopamine replacement therapy is associated not only with motor side-effects, such as levodopa-induced dyskinesia, but also behavioural side-effects such as impulse control disorders (eg, pathological gambling and shopping, binge eating, and hypersexuality), punding (ie, abnormal repetitive non-goal oriented behaviours), and compulsive medication use. We review clinical features, overlapping molecular mechanisms, and a specific cognitive mechanism of habit learning that might underlie these behaviours. We integrate these mechanisms with the emerging view of the basal ganglia as a distributive system involved in the selection and facilitation of movements, acts, and emotions.

Selective blockade of T lymphocyte K+ channels ameliorates experimental autoimmune encephalomyelitis, a model for multiple sclerosis

Abstract: Adoptive transfer experimental autoimmune encephalomyelitis (AT-EAE), a disease resembling multiple sclerosis, is induced in rats by myelin basic protein (MBP)-activated CD4+ T lymphocytes. By patch-clamp analysis, encephalitogenic rat T cells stimulated repeatedly in vitro expressed a unique channel phenotype (“chronically activated”) with large numbers of Kv1.3 voltage-gated channels (≈1500 per cell) and small numbers of IKCa1 Ca2+-activated K+ channels (≈50–120 per cell). In contrast, resting T cells displayed 0–10 Kv1.3 and 10–20 IKCa1 channels per cell (“quiescent” phenotype), whereas T cells stimulated once or twice expressed ≈200 Kv1.3 and ≈350 IKCa1 channels per cell (“acutely activated” phenotype). Consistent with their channel phenotype, [3H]thymidine incorporation by MBP-stimulated chronically activated T cells was suppressed by the peptide ShK, a blocker of Kv1.3 and IKCa1, and by an analog (ShK-Dap22) engineered to be highly specific for Kv1.3, but not by a selective IKCa1 blocker (TRAM-34). The combination of ShK-Dap22 and TRAM-34 enhanced the suppression of MBP-stimulated T cell proliferation. Based on these in vitro results, we assessed the efficacy of K+ channel blockers in AT-EAE. Specific and simultaneous blockade of the T cell channels by ShK or by a combination of ShK-Dap22 plus TRAM-34 prevented lethal AT-EAE. Blockade of Kv1.3 alone with ShK-Dap22, but not of IKCa1 with TRAM-34, was also effective. When administered after the onset of symptoms, ShK or the combination of ShK-Dap22 plus TRAM-34 greatly ameliorated the clinical course of both moderate and severe AT-EAE. We conclude that selective targeting of Kv1.3, alone or with IKCa1, may provide an effective new mode of therapy for multiple sclerosis.

Clinical presentation, aetiology and outcome of infective endocarditis. Results of the ESC-EORP EURO-ENDO (European infective endocarditis) registry: a prospective cohort study

Abstract: Aims: The EURO-ENDO registry aimed to study the management and outcomes of patients with infective endocarditis (IE). Methods and results: Prospective cohort of 3116 adult patients (2470 from Europe, 646 from non-ESC countries), admitted to 156 hospitals in 40 countries between January 2016 and March 2018 with a diagnosis of IE based on ESC 2015 diagnostic criteria. Clinical, biological, microbiological, and imaging [echocardiography, computed tomography (CT) scan, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)] data were collected. Infective endocarditis was native (NVE) in 1764 (56.6%) patients, prosthetic (PVIE) in 939 (30.1%), and device-related (CDRIE) in 308 (9.9%). Infective endocarditis was community-acquired in 2046 (65.66%) patients. Microorganisms involved were staphylococci in 1085 (44.1%) patients, oral streptococci in 304 (12.3%), enterococci in 390 (15.8%), and Streptococcus gallolyticus in 162 (6.6%). 18F-fluorodeoxyglucose positron emission tomography/computed tomography was performed in 518 (16.6%) patients and presented with cardiac uptake (major criterion) in 222 (42.9%) patients, with a better sensitivity in PVIE (66.8%) than in NVE (28.0%) and CDRIE (16.3%). Embolic events occurred in 20.6% of patients, and were significantly associated with tricuspid or pulmonary IE, presence of a vegetation and Staphylococcus aureus IE. According to ESC guidelines, cardiac surgery was indicated in 2160 (69.3%) patients, but finally performed in only 1596 (73.9%) of them. In-hospital death occurred in 532 (17.1%) patients and was more frequent in PVIE. Independent predictors of mortality were Charlson index, creatinine > 2 mg/dL, congestive heart failure, vegetation length > 10 mm, cerebral complications, abscess, and failure to undertake surgery when indicated. Conclusion: Infective endocarditis is still a life-threatening disease with frequent lethal outcome despite profound changes in its clinical, microbiological, imaging, and therapeutic profiles.

Wintertime aerosol chemical composition and source apportionment of the organic fraction in the metropolitan area of Paris

Abstract: The effect of a post-industrial megacity on local and regional air quality was assessed via a month-long field measurement campaign in the Paris metropolitan area during winter 2010. Here we present source apportionment results from three aerosol mass spectrometers and two aethalometers deployed at three measurement stations within the Paris region. Submicron aerosol composition is dominated by the organic fraction (30-36%) and nitrate (28-29%), with lower contributions from sulfate (14-16%), ammonium (12-14%) and black carbon (7-13%). Organic source apportionment was performed using positive matrix factorization, resulting in a set of organic factors corresponding both to primary emission sources and secondary production. The dominant primary sources are traffic (11-15% of organic mass), biomass burning (13-15%) and cooking (up to 35% during meal hours). Secondary organic aerosol contributes more than 50% to the total organic mass and includes a highly oxidized factor from indeterminate and/or diverse sources and a less oxidized factor related to wood burning emissions. Black carbon was apportioned to traffic and wood burning sources using a model based on wavelength-dependent light absorption of these two combustion sources. The time series of organic and black carbon factors from related sources were strongly correlated. The similarities in aerosol composition, total mass and temporal variation between the three sites suggest that particulate pollution in Paris is dominated by regional factors, and that the emissions from Paris itself have a relatively low impact on its surroundings.