Femtosecond Resolution of the Nonballistic Electron Energy Transport in Warm Dense Copper.

The ultrafast electron energy transport is investigated in laser-heated warm dense copper in a high flux regime (2.5±0.7×10^{13} W/cm^{2} absorbed). The dynamics of the electron temperature is retrieved from femtosecond time-resolved x-ray absorption near-edge spectroscopy near the Cu L3 edge. A characteristic time of ∼1 ps is observed for the increase in the average temperature in a 100 nm thick sample. Data are well reproduced by two-temperature hydrodynamic simulations, which support energy transport dominated by thermal conduction rather than ballistic electrons.

Transfer of elements released by aluminum galvanic anodes in a marine sedimentary compartment after long-term monitoring in harbor and laboratory environments.

Cathodic protection by galvanic anodes (GACP) is often used to protect immerged metallic structures in harbor environments, especially GACP employing aluminum-based anodes. To follow a previous study that was performed in a laboratory on Al-anode, two monitoring periods were performed in parallel, one in an in situ environment (in the Port of Calais) for 42 months and the other in a laboratory for 18 months, to evaluate the transfer of metals constituting the Al-anode towards the sedimentary compartment. During each monitoring, two conditions of agitation of water (weak and strong) were compared, and different factors of sediment quality were used to assess the enrichment and potential toxic effects of these released metals. The results showed that the dissolution of Al-anode-induced a greater Zn enrichment of sediment than an Al enrichment. This is in contrast with the abundance of these elements present in the composition of the anode and suggested a potential toxic effect for marine organisms with regards to the discovered Zn level, especially in confined areas.

Parkinson's disease incidence and prevalence assessment in France using the national healthcare insurance database.

BACKGROUND AND PURPOSE: The incidence and prevalence of Parkinson's disease are important for public health planning yet there is a lack of representative, up-to-date estimations for France. METHODS: For this cross-sectional study, subjects with suspected Parkinson's were identified in the EGB database, a 1/97 random sample of the national healthcare insurance database, linked to the national hospital-discharge summary database. Incidence and prevalence were estimated using a specific definition that included those with a diagnosis (hospitalization or listed as a long-term chronic disease for full reimbursement) and a sensitive definition that also included those with an indicative drug reimbursement profile. Estimations were extrapolated to the national population, standardizing on age and gender. RESULTS: According to either the specific or the sensitive definitions, the annual incidence of Parkinson's disease during the study period was respectively 36 and 49 per 100,000 person-years and prevalence in 2010 was 308-410 per 100,000 persons in the population as a whole. According to the age groups 55-64, 65-74, 75-84 and ≥85 years incidence was respectively 33-46, 139-172, 301-363 and 442-560 per 100,000 person-years amongst men and 32-55, 81-117, 203-270 and 251-313 per 100,000 person-years amongst women. The 2010 prevalence stratified by the same age groups was 293-376, 898-1161, 2524-3011 and 3760-4578 per 100,000 persons amongst men and 199-351, 618-889, 1910-2433 and 2504-3263 per 100,000 persons amongst women. CONCLUSIONS: The specific and sensitive definitions of disease bracket the true values; the relatively small range indicates that the current study provides good estimations of incidence and prevalence of Parkinson's disease for recent years in France.

Characteristics associated with use of homeopathic drugs for psychiatric symptoms in the general population.

OBJECTIVE: To explore which patient characteristics are associated in naturalistic conditions with the lifetime use of homeopathic treatment for psychiatric symptoms. METHOD: Lifetime use of psychotropic treatment was explored in a sample of 36,785 persons, participating in the Mental Health Survey in the General Population. Characteristics associated with use of homeopathic treatments, associated or not with conventional psychotropic drugs, were explored using multivariate analyses. RESULTS: Use of homeopathic treatment for psychiatric symptoms was reported by 1.3% of persons. Younger age, female gender and high educational level were associated with use of homeopathy. Half of homeopathy users presented at least one Mini International Neuropsychiatric Interview (MINI) diagnosis, most frequently anxiety disorders. Their diagnostic profile was similar to that of persons reporting use of anxiolytics or hypnotics. Compared to persons with no lifetime use of psychotropic drugs, persons using homeopathy were more likely to present with a diagnosis of mood disorder or anxiety disorder. Compared to those using conventional psychotropic drugs, they presented less frequently with psychiatric disorders, with the exception of anxiety disorders. CONCLUSION: Homeopathic treatment for psychiatric symptoms appears to be used mainly to reduce anxiety symptoms in the general population.

The prognostic impact of psychotropic drugs in intentional drug overdose.

INTRODUCTION: Psychotropic drugs belong to the drugs most frequently involved in intentional drug overdose (IDO). Few studies have explored their prognostic impact during hospitalisation for IDO. METHODS: In order to assess which types of psychotropic drugs ingested during IDOs were associated with an increased morbidity, a cohort study included 1,974 patients consecutively hospitalised for IDO. IDOs were categorised as serious if associated with one of the following criteria: death, hospitalisation longer than 48 h, respiratory support, vasopressive drugs, cardiac massage or dialysis. RESULTS: Nearly all the patients ingested psychotropic medications during the IDO (88.4%), most often benzodiazepines (71.6%). Serious IDO was associated with tricyclics (OR 5.7; 95% CI 3.3-9.8), lithium (OR 4.3; 95% CI 1.6-11.6), carbamates (OR 2.7; 95% CI 1.8-4), anticonvulsants (OR 2.4: 95% CI 1.4-4.3), first-generation antipsychotics (OR 2.4; 95% CI 1.7-3.5) or selective serotonin reuptake inhibitors (SSRIs) (OR 1.6; 95% CI 1.1-2.3). DISCUSSION: Some drugs may be dangerous because of low toxic doses; hence, prescriptions of short duration may be recommended. Moreover, for safety reasons, prescribers may prefer SSRIs to tricyclics and benzodiazepines to carbamates or phenothiazines.

Impact of antidepressants on the risk of suicide in patients with depression in real-life conditions: a decision analysis model.

BACKGROUND: The impact of antidepressant drug treatment (ADT) on the risk of suicide is uncertain. The aim of this study was to determine in a real-life setting whether ADT is associated with an increased or a reduced risk of suicide compared to absence of ADT (no-ADT) in patients with depression. METHOD: A decision analysis method was used to estimate the number of suicides prevented or induced by ADT in children and adolescents (10-19 years old), adults (20-64 years old) and the elderly (65 years) diagnosed with major depression. The impact of gender and parasuicide history on the findings was explored within each age group. Sensitivity analyses were used to assess the robustness of the models. RESULTS: Prescribing ADT to all patients diagnosed with depression would prevent more than one out of three suicide deaths compared to the no-ADT strategy, irrespective of age, gender or parasuicide history. Sensitivity analyses showed that persistence in taking ADT would be the main characteristic influencing the effectiveness of ADT on suicide risk. CONCLUSIONS: Public health decisions that contribute directly or indirectly to reducing the number of patients with depression who are effectively administered ADT may paradoxically induce a rise in the number of suicides.

[Psychotropic drug use and correspondence with psychiatric diagnoses in the mental health in the general population survey]. / Usage et congruence diagnostique des traitements à visée psychotrope: résultats de l'enquête santé mentale en population générale en France métropolitaine.

OBJECTIVES: The aims of this study were to assess the lifetime prevalence rate of psychotropic drugs use in the French general population and the correspondence between psychotropic drug use and psychiatric diagnoses. METHODS: Data were derived from the multicentric survey mental health in the general population, carried out in 47 French public sites between 1999 and 2003. A face-to-face questionnaire was used to interview a representative sample of French metropolitan subjects, aged 18 and over, noninstitutionalized or homeless. These subjects were recruited using quota sampling for age, sex, socioprofessional and education levels, according to data from the 1999 national French population census. Lifetime use of psychotropic drugs was explored by an open question. Psychiatric diagnoses were identified using the mini international neuropsychiatric interview (MINI). A national database was then constituted by pooling data from all sites, weighted for age, sex, level of education, socioprofessional level and work status, to be representative of the French general population. RESULTS: Of the 36785 individuals included in this study, more than one out of three subjects reported having used at least one psychotropic drug during their life. Anxiolytics were the most commonly used drugs, reported by 19.4% of the sample. The other frequently used psychotropic drugs were antidepressants (11.6%) and hypnotics (9.2%). Nearly half of the subjects with a MINI diagnosis reported no lifetime psychotropic drug use. Among the subjects meeting criteria for a diagnosis of mood disorder, 66.3% used psychotropic drugs. However, less than one out of three subjects with a diagnosis of major depressive disorder used antidepressants while 37.2% reported having used anxiolytics. Less than one out of four subjects with a diagnosis of anxiety disorder used antidepressants while 34.3% used anxiolytics. Among subjects with a diagnosis of anxiety disorder, antidepressants and anxiolytics were the most commonly used drugs for subjects with a diagnosis of panic disorder with agoraphobia (46.4 and 58.1%, respectively). Conversely, these were the treatments used the least by subjects with a diagnosis of generalized anxiety disorder (21.9 and 31.5%, respectively). Only 14.9% of subjects with a psychotic syndrome reported having used neuroleptics. Lastly, the highest proportion of subjects with at least one psychiatric diagnosis was found in mood stabilizer and neuroleptic users. However, one third of mood stabilizer users, a quarter of neuroleptic users and less than half of antidepressant and anxiolytic users presented no psychiatric disorder identified by the MINI. CONCLUSION: This study highlights the high frequency of exposure to psychotropic drugs in the general French population, and the marked inadequacy between the presence or absence of a psychiatric diagnosis and the lifetime presence or absence of a psychotropic drug treatment.

Congruence between diagnosis of recurrent major depressive disorder and psychotropic treatment in the general population.

OBJECTIVE: We explored in a sample representative of the French general population the congruence between lifetime use of psychotropic drugs and diagnosis of recurrent major depressive disorder (rMDD). METHOD: A total of 2111 (5.6%) subjects with rMDD were identified in the sample of 36 785 subjects assessed in the Mental Health survey in the General Population. A treatment congruent with a diagnosis of rMDD was defined as lifetime use of antidepressants or mood stabilizers. RESULTS: Only one-third of subjects with rMDD reported having ever used a congruent treatment. Female gender, higher income and presence of anxiety disorder were associated with a higher probability of having used a congruent treatment. CONCLUSION: Although these findings indicate that a large proportion of subjects with rMMD do not benefit from adequate treatment, community surveys not primarily designed to assess utilization and adequacy of psychotropic treatment in the community may overestimate the frequency of unmet need for care.

[Prescription practices of antipsychotic medication in early psychosis: a two-year follow-up survey of subjects admitted in two psychiatric hospitals of South-Western France]. / Pratiques de prescription des traitements antipsychotiques dans les premières hospitalisations pour épisode psychotique: étude sur une cohorte de patients hospitalisés dans deux hôpitaux girondins.

OBJECTIVES: The aims of this pharmacoepidemiological study were to describe the antipsychotic medication received during the first admission and over a two-year follow-up in subjects with a first episode of psychosis, and to assess whether the prescriptions in naturalistic conditions were in adequacy with guidelines. METHOD: All first-admitted patients, less than 50 years old, consecutively hospitalised in 10 acute wards of two psychiatric hospitals serving Bordeaux's catchment area were included over a period of one year, if they presented with at least one overt psychotic symptom during the last month. Information on psychotropic medication received during the first admission was collected in medical records, and that received after the first admission was collected at the end of a two-year follow-up using multiple sources of information. RESULTS: Of the 86 patients included in the cohort, 53 presented with broadly defined schizophrenia and 33 with psychotic mood disorder. All except two subjects were prescribed at least one neuroleptic drug. Antipsychotic drugs (amisulpride, olanzapine, risperidone, clozapine) were the most frequently prescribed drugs during the first admission and over the two-year follow-up. If sedative neuroleptics were excluded, antipsychotic drugs were the first prescribed neuroleptic drugs in a large proportion (80%) of patients. Although few patients were first prescribed a conventional neuroleptic, the proportion of subjects treated with these drugs increased over the next prescriptions, and one out of three patients was prescribed at least one of these drugs during the follow-up. The mean dose of antipsychotic drugs at first discharge was higher than that recommended in first episode patients (amisulpride 616 mg, olanzapine 13 mg, risperidone 7 mg). Coprescription of neuroleptic drugs, found in one third of patients at all times of assessment, was especially due to coprescription of a sedative neuroleptic to a conventional or an antipsychotic one. Nearly half of the patients did not take any psychotropic medication at the end of the follow-up. CONCLUSION: The main recommendation specifying that the first neuroleptic treatment in subjects with a first episode of psychosis should use antipsychotic drugs instead of conventional neuroleptics was generally respected in this cohort of first-admitted subjects with psychosis. However, conventional neuroleptics were found in first or second rank prescriptions, although they should not be used before at least the third rank. The recommendations that the initial neuroleptic dose should be lower in subjects with a first episode, and that coprescription of neuroleptics should be avoided, were frequently not respected. This study highlights the fact that international guidelines should be better applied in naturalistic conditions, and that clinicians have to be better informed about these recommendations.

Profiling changes in gene expression during differentiation and maturation of monocyte-derived dendritic cells using both oligonucleotide microarrays and proteomics.

Dendritic cells (DCs) are antigen-presenting cells that play a major role in initiating primary immune responses. We have utilized two independent approaches, DNA microarrays and proteomics, to analyze the expression profile of human CD14(+) blood monocytes and their derived DCs. Analysis of gene expression changes at the RNA level using oligonucleotide microarrays complementary to 6300 human genes showed that approximately 40% of the genes were expressed in DCs. A total of 255 genes (4%) were found to be regulated during DC differentiation or maturation. Most of these genes were not previously associated with DCs and included genes encoding secreted proteins as well as genes involved in cell adhesion, signaling, and lipid metabolism. Protein analysis of the same cell populations was done using two-dimensional gel electrophoresis. A total of 900 distinct protein spots were included, and 4% of them exhibited quantitative changes during DC differentiation and maturation. Differentially expressed proteins were identified by mass spectrometry and found to represent proteins with Ca(2+) binding, fatty acid binding, or chaperone activities as well as proteins involved in cell motility. In addition, proteomic analysis provided an assessment of post-translational modifications. The chaperone protein, calreticulin, was found to undergo cleavage, yielding a novel form. The combined oligonucleotide microarray and proteomic approaches have uncovered novel genes associated with DC differentiation and maturation and has allowed analysis of post-translational modifications of specific proteins as part of these processes.

Impaired translational response and increased protein kinase PKR expression in T cells from lupus patients.

Activation of peripheral blood T cells results in a rapid and substantial rise in translation rates and proliferation, but proliferation in response to mitogen stimulation is impaired in systemic lupus erythematosus (SLE). We have investigated translation rates and initiation factor activities in T cells from SLE patients in response to activating signals. Activation by PMA plus ionomycin strongly increased protein synthesis in control T cells but not in T cells from SLE patients. The rate of protein synthesis is known to be strongly dependent on the activity of two eukaryotic translation initiation factors, eIF4E and eIF2alpha. We show that following stimulation, eIF4E expression and phosphorylation increased equivalently in control and SLE T cells. Expression of eIF4E interacting proteins - eIF4G, an inducer, and 4E-BP1 and 4E-BP2, two specific repressors of eIF4E function - and the phosphorylation level of 4E-BP1, were all identical in control and SLE T cells. In contrast, the protein kinase PKR, which is responsible for the phosphorylation and consequent inhibition of eIF2alpha activity, was specifically overexpressed in activated SLE T cells, correlating with an increase in eIF2alpha phosphorylation. Therefore, high expression of PKR and subsequent eIF2alpha phosphorylation is likely responsible, at least in part, for impaired translational and proliferative responses to mitogens in T cells from SLE patients.

Defect in the regulation of 4E-BP1 and 2, two repressors of translation initiation, in the retinoid acid resistant cell lines, NB4-R1 and NB4-R2.

We recently reported evidence for differential regulation of the translation machinery during human myeloid differentiation, specific to the monocytic/macrophage pathway or to the granulocytic pathway. A decrease in translation rates and concomitant regulation of two repressors of translation initiation, 4E-BP1 and 4E-BP2 (eIF4E-binding proteins 1 and 2), occur in cells induced to differentiate along the monocytic/macrophage pathway or along the granulocytic pathway. Induction of HL-60 and U-937 cell differentiation into monocytes/macrophages results in a dephosphorylation and consequent activation of 4E-BP1. In contrast, following treatment of HL-60 cells with retinoic acid (RA) which results in a granulocytic differentiation of these cells, 4E-BP1 protein expression is decreased whereas 4E-BP2 protein expression is strongly increased. In this study, we further investigated the regulation of 4E-BP1 and 4E-BP2 in the RA-induced differentiation process using the NB4 promyelocytic cell line and the RA maturation-resistant NB4 subclones, NB4-R1 and NB4-R2. RA treatment resulted in a decrease in 4E-BP1 protein and mRNA expression and concomitant increase in 4E-BP2 protein expression, in NB4 cells, but not in NB4-R1 and NB4-R2 cells. The increase in 4E-BP2 protein expression was not correlated to an increase in 4E-BP2 mRNA level suggesting a post-transcriptional regulation of 4E-BP2 expression. In RA-primed cells, cAMP induce maturation of NB4-R1, but not NB4-R2 cells. cAMP treatment resulted in a down-regulation of 4E-BP1 protein and mRNA expression in RA-primed NB4-R1, but not NB4-R2 cells. However, 4E-BP2 expression was not modified in both cell types following cAMP treatment. This indicates that 4E-BP1 down-regulation is associated with granulocytic maturation, whereas post-transcriptional regulation of 4E-BP2 expression is associated with the early action of RA.

Differential regulation of 4E-BP1 and 4E-BP2, two repressors of translation initiation, during human myeloid cell differentiation.

Human myeloid differentiation is accompanied by a decrease in cell proliferation. Because the translation rate is an important determinant of cell proliferation, we have investigated translation initiation during human myeloid cell differentiation using the HL-60 promyelocytic leukemia cell line and the U-937 monoblastic cell line. A decrease in the translation rate is observed when the cells are induced to differentiate along the monocytic/macrophage pathway or along the granulocytic pathway. The inhibition in protein synthesis correlates with specific regulation of two repressors of translation initiation, 4E-BP1 and 4E-BP2. Induction of HL-60 and U-937 cell differentiation into monocytes/macrophages by IFN-gamma or PMA results in a dephosphorylation and consequent activation of 4E-BP1. Dephosphorylation of 4E-BP1 was also observed when U-937 cells were induced to differentiate into monocytes/macrophages following treatment with retinoic acid or DMSO. In contrast, treatment of HL-60 cells with retinoic acid or DMSO, which results in a granulocytic differentiation of these cells, decreases 4E-BP1 amount without affecting its phosphorylation and strongly increases 4E-BP2 amount. Taken together, these data provide evidence for differential regulation of the translational machinery during human myeloid differentiation, specific to the monocytic/macrophage pathway or to the granulocytic pathway.