ADHD and addictive behavior in crack-cocaine users.

BACKGROUND: Crack consumption is a major public health issue in Martinique with a poor prognosis. A preliminary study has found a high prevalence of history of childhood ADHD (C-ADHD) in crack users. OBJECTIVE: To determine the prevalence of C-ADHD and adult ADHD (A-ADHD) in crack users and their potential associations with substance use behavior. METHODS: All consecutive patients consulting in the public academic hospital covering 376,000 inhabitants were included in the present study and received a comprehensive battery measuring addictive behavior, psychiatric and somatic comorbidities. C-ADHD groups and A-ADHD groups were defined with the Wender-Utah Rating Scale-25 and the Brown ADD Rating Scale, respectively. Impulsivity was evaluated with the Barratt Impulsiveness Scale (BIS-11). FINDINGS: In total, 111 participants were evaluated. Among them, 50 (45%) were classified in the C-ADHD group and 20 (18%) in the A-ADHD group. Compared to the patients without ADHD, those with ADHD were found to have higher impulsivity (C-ADHD: BIS total score 67.90 (10.1) vs. 63.28 (10.5), P=0.021, BIS attentional score 17.5 (3.6) vs. 15.3 (3.4), P=0.002, A-ADHD: BIS total score 75.1 (11.3) vs. 63.4 (9.2), P<0.001, BIS motor impulsivity 26.9 (5.3) vs. 22.6 (4.3), P<0.001, BIS attentional score 19.3 (3.3) vs. 15.6 (3.5), P<0.001, BIS planification 28.9 (5.7) vs. 25.10 (4.7), P=0.003). Fifty percent of A-ADHD patients were found with high impulsivity vs. 15% of patients without A-ADHD (P<0.001). However, ADHD was not associated with more severe addictive behavior or history of legal consequences. INTERPRETATION: ADHD prevalence is high in cocaine-crack users and associated with increased impulsivity. However, neither ADHD nor impulsivity explains addictive behaviors or legal consequences.

[Identification of factors associated with low access to psychiatric care. Concerning 516 psychiatric assessments carried out in the framework of the local medical committee of Martinique]. / Identification de facteurs associés à un faible recours aux soins spécialisés en psychiatrie. À propos de 516 cas d'expertises psychiatriques réalisées dans le cadre du Comité médical départemental de Martinique.

OBJECTIVE: Mental illness is noted for being in one of the first places in global burden of disease in terms of years lived with disability (YLDs). Notably, absences due to mental health problems greatly affect the world of work, and mental illness is one of the most economically important diseases. However, there is a high rate of those not seeking care in mental health, both in the general population but also in workers in private and public sectors with significant economic impacts. The aim of our study was to identify factors associated with low access to specialized psychiatric care among French Public Sector employees referred to a psychiatric expertise upon request from the Departmental Medical Board of Martinique (Comité médical départemental [CMD] de Martinique), between 2000 and 2013. METHODS: We carried out an observational and transversal study, analyzing sociodemographic and clinical data from psychiatric assessments done to help the CMD give notification on the medico-administrative situation of Public Sector employees, a large majority of whom had been on sick leave due to mental health for at least 6 months. The variable of interest - low access to psychiatric care - was defined as the absence of consultation at the time of the assessment provided by a psychiatrist since at least 12 months. Descriptive analyses were performed first, then univariate analysis using a non-adjusted binary logistic regression model, to identify factors associated with low access to psychiatric care. Finally, multivariate analyses using a binary logistic regression model were performed after excluding non-relevant factors (with significance level above 5%) during the univariate analysis. A significance threshold of 0.05 was adopted for all of the statistical analyses. RESULTS: We retrospectively analysed the records of 516 Public Sector employees. Two hundred and ninety-three subjects (57% of the population) had a low access to psychiatric care as part of their regular clinical follow-up, even the 81% who were identified has having had psychiatric antecedents (55% with 'mood disorders', and 17% with 'neurotic, stress-related and somatoform disorders'). Moreover, psychiatric expertise found a psychiatric diagnostic in 96 % of cases, mostly 'mood disorders', 'neurotic, stress-related and somatoform disorders' and 'personality disorders'. For mood disorders, clinical characteristics of episodes were defined as 'severe' or 'with psychotic symptoms' in many cases. Suicidal thoughts were found in 96 subjects (18%) during the expertise. Fewer than half of the subjects (43%) had a specialized psychiatric care (mostly subjects with 'mood disorders' and 'psychotic disorders') and 41% only had care by a general practitioner (mostly subjects with 'neurotic, stress-related and somatoform disorders'). In most of the cases, psychotropic drugs were insufficiently and inadequately prescribed. Using multivariate analysis, we found a significant association between low access to psychiatric care and: being masculine, having had more than two children, having had personal life events (in particular chronic somatic diseases), and having had no history of mental illness or of psychiatric hospitalization. It appears that chronic somatic diseases are frequently associated with psychiatric diseases, and the association worsens the prognosis of the two disorders. However, even if employees with mental disorders associated with chronic somatic diseases are unfit for work, many of them do not have access to mental health care and only have care by a general practitioner. CONCLUSION: More than half of French Public Sector employees referred to the Departmental Medical Board of Martinique for a medico-administrative decision relevant to sick leave due to mental diseases, had low access to specialized psychiatric care. By identifying barriers to care and reasons for not seeking specialized mental health care, we would be able to prevent disability claims and days off work (predicting malaise in the workplace and health-related limitations). Our results demonstrate the need to strengthen existing partnerships, and thus enhancing cooperation between public psychiatric sectors and primary healthcare players, facilitating access to mental healthcare and decreasing the stigma about mental disorders.

[Predictive factors of seclusion duration in patients hospitalized in psychiatry settings. A prospective multisite study in the DTRF Paris-Sud]. / Facteurs prédictifs de la durée d'isolement chez les patients hospitalisés en psychiatrie. Une étude prospective multicentrique au sein du DTRF Paris-Sud.

INTRODUCTION: In psychiatric inpatient settings seclusion is a last resort to ensure the safety of the patient, other patients, and staff from disturbed behaviors. Despite its major interest for patients, seclusion could negatively impact treatment adherence and patient/staff relationships. Indeed, some secluded patients report a feeling of guilt during the measure and do not consider seclusion to be a healthcare intervention. To be more beneficial and to reduce the feeling by patients of being forced, seclusions should be as short and rare as possible. In other words, measures to reduce seclusion are available and have been clearly identified. Such measures could be applied, in the first instance, in patients with longer duration. In this way, the aim of this study was to investigate predictive factors of a seclusion of long duration. METHODS: Our study was based on the dataset of the EPIC study, an observational prospective French multicenter study of seclusion and restraint. The EPIC study occurred in seven French psychiatric hospitals in the southern region of Paris. Inclusions were realized for 73days and allowed a data collection of 302 seclusion measures. Of these measures 236 were effectively a seclusion in a standardized room. Because the median duration was 7days, we defined two groups of patients: duration<7days and duration ≥ 7 days. Our variable to be explicated was duration ≥ 7 days. Explicative variables available in EPIC study were age, sex, forced hospitalization, autoagressivity, heteroagressivity, use of sedative treatment (oral or intramuscular), history of seclusion and patient diagnoses. We used bivariate and multivariate analyses to explore the association between a seclusion duration ≥ 7 days and explicative variables. Diagnoses were classified as psychotic disorders, mood disorders and others diagnoses. To be included in multivariate logistic regressions, diagnoses were treated as dummy variables (mood disorder vs psychotic disorders; psychotic disorders vs others; mood disorders vs others). Statistical analyses were performed using SPSS software 20.0 and R 3.4.0. RESULTS: Of the 236 measures of seclusion the mean age was 38.2 (±12.8), 196 (83%) patients were forcibly hospitalized prior to their seclusion, 147 (62%) had a diagnosis of psychotic disorder, 43 (18%) a diagnosis of mood disorder and 33 (14%) an "other diagnosis". Mean duration was 10.2 (1.5) days and median was 7.1 days. One hundred and thirty-five (47%) patients were in the group of duration ≥ 7 days. In bivariate analyses, variables associated with a duration ≥ 7 days were: being in forced hospitalization prior to the seclusion (P=0.04), administration of a sedative treatment (P=0.01) and against the group of others diagnoses the diagnosis of mood disorders (P<0.0005) and psychotic disorders (P=0.001). Multivariate analyses showed that, against the group of other diagnoses, the group of psychotic disorders [OR=3.3, CI 95% (1.3-8.4), P=0.01], the group of mood disorder [OR=2.7, CI 95% (1.4-4.9), P=0.002] and administration of sedative treatment [OR=8.1, CI 95% (2.0-32.5), P=0.003] were significantly associated with a duration ≥ 7 days. These results were independent from other confusion variables. Considering the hospitalization status, psychotic disorders was the only diagnosis which showed an association between duration ≥ 7 days and forced hospitalization [OR=2.9 CI 95% (1.1-7.8), P=0.03]. CONCLUSION: Our study highlighted two profiles of higher risk to remain ≥ 7days in seclusion. The first one is patients with a diagnosis of mood disorder who needed sedative treatment. The second one is patients with a diagnosis of psychotic disorder who needed sedative treatment and forced hospitalized before seclusion. Thus, these two profiles could be a good target to practice, in the first instance, measures to reduce seclusion duration in psychiatry settings.

Prevalence of Mental Disorders in Martinique, French West Indies: A Community-based Epidemiological Study / Prevalencia de los trastornos mentales en Martinica, Antillas Francesas: un estudio epidemiológico comunitario

ABSTRACT Objective: This study aimed to estimate the prevalence of mental disorders in the population of Martinique, as part of the survey entitled 'Mental Health in the General Population - Images and Realities ' (Santé Mentale en Population Générale - Images et Réalités). The survey was a multicentre epidemiological study in the general population, conducted in mainland France and French overseas islands between 1997 and 2006, under the authority of the World Health Organization Collaborating Centre for Training and Research in Mental Health (Lille, France). Methods: The study took place in 2000. Participants aged 18 years or over were recruited in public places, using the quota sampling method, and interviewed using the Mini International Neuropsychiatric Interview. Results: A total of 900 participants (52.7% women) with a mean age of 43 years completed the survey. Lifetime prevalence of any mental disorder was 29%. Mood (15%) and anxiety disorders (17%) were the most frequent. The rate of suicide attempts was low (4.2% lifetime), while the frequency of suicidal thoughts was high (11% past month) and similar to the frequency in mainland France. Conclusion: Mental disorders, especially mood and anxiety disorders, were as frequent in Martinique as in mainland France. The lower rates of suicide attempts, in spite of high rates of suicidal thoughts, might deserve further investigation. Our results should strengthen the development of a system of diagnosis and care for these disorders, especially to prevent suicidal behaviours and reduce morbidity and mortality.

RESUMEN Objetivo: Este estudio tuvo por objeto estimar la prevalencia de los trastornos mentales en la población de Martinica, como parte de la encuesta intitulada 'Salud Mental en la Población General - Imágenes y Realidades ' (Santé mentale at Population Générale - Images et Réalités). La encuesta fue un estudio epidemiológico multicéntrico en la población general, realizado en Francia continental y en las islas francesas de ultramar entre 1997 y 2006, bajo la autoridad del Centro de Colaboración de la Organización Mundial de la Salud para la Formación y la Investigación de la Salud Mental (Lille, Francia). Métodos: El estudio tuvo lugar en el año 2000. Los participantes mayores de 18 años fueron reclutados en lugares públicos, utilizando el método de muestreo por cuotas, y entrevistados usando la Mini Entrevista Neuropsiquiátrica Internacional. Resultados: Un total de 900 participantes (52.7% mujeres) con edad promedio de 43 años completó la encuesta. La prevalencia de por vida de cualquier trastorno mental fue de 29%. Los estados de ánimo (15%) y los trastornos de ansiedad (17%) fueron los más frecuentes. La tasa de intentos de suicidio fue baja (4.2% por tiempo de vida), mientras que la frecuencia de los pensamientos suicidas fue alta (11% el mes pasado) y similar a la frecuencia en la Francia continental. Conclusión: Los trastornos mentales, especialmente los estados de ánimo y los trastornos de ansiedad, eran tan frecuentes en Martinica como en la Francia continental. Las tasas más bajas de intentos de suicidio, a pesar de los altos índices de pensamientos suicidas, podrían merecer investigación adicional. Nuestros resultados deben fortalecer el desarrollo de un sistema de diagnóstico y cuidado para estos trastornos, especialmente para prevenir comportamientos suicidas y reducir la morbilidad y la mortalidad.

Mental health of jail inmates within the prison of Ducos, Martinique - a cross-sectional descriptive study.

BACKGROUND: Prisoners' sociocultural backgrounds and prison environments have an influence on detainees' psychopathology; complex judicial and public policies are also to be taken into account in the dynamics of that environment. Scientific literature shows a wide range prison inmates' profiles across the world. However, very little data about the mental health of Caribbean jail inmates has been published. Martinique is a French overseas administrative district in the Caribbean, with a population of about 400,000 inhabitants. Its only prison is located in the city of Ducos. Our study proposes a description of the psychiatric characteristics of jail inmates in Martinique with epidemiological tools. Its objectives are to highlight their specific features and compare them to mainland France's jail population. METHODS: The initial study was a multicenter cross-sectional survey conducted in 18 French prisons. The selection was done using a two-stage stratified sampling strategy. For the purpose of our study, two groups were defined and compared: the detainees from the prison of Ducos (n=100) were compared to inmates from mainland France (n=698). Current psychiatric diagnoses were rigorously collected, through clinical and semi-structured interviews. We conducted a multiple logistic regression for each assessed mental disorder. Each prisoner gave us his oral and written informed consent. RESULTS: In terms of sociodemographic characteristics, we found more children per prisoner in the Martinican group and a better educational status in the mainland France group. The inmates from Martinique had significantly more adverse experiences in their childhood and the length of incarceration at the time of the interview was longer in the Martinique sample. Major depressive disorders (aOR=0.51; 95% CI=0.26-0.95) and psychotic disorders (aOR=0.24; 95% CI=0.08-0.57) were significantly less frequent in the Martinique sample. The data concerning substance-related disorders showed significant differences in bivariate analysis but this link was no longer statistically significant in the multiple logistic regression analysis. CONCLUSION: Even if imprisonment conditions are extremely tough, the inmates carry the heavy burden of difficult family histories, and the use of cannabis seems to be a major problem, it appears that Martinique's jail inmates have lower rates of mental illness than their counterparts from mainland France. We think this could be due to the benefit of greater proximity to their relatives and a united community, both which may contribute to lower prevalence of mental disorders.

Decrease of cocaine, but not heroin, self-administration and relapse by the tyrosine kinase inhibitor masitinib in male Sprague Dawley rats.

RATIONALE: Accumulating evidence shows that cocaine, and also heroin, influence several tyrosine kinases, expressed in neurons and in non-neuronal populations such as microglia, astrocytes and mast-cells. Drug-induced activation of mast cells both triggers inflammatory processes in the brain mediated by the glial cells they activate, and facilitates histamine release which may directly influence the dopamine system. Thus, by triggering the activation and degranulation of mast cells dependent on the tyrosine kinase c-kit and Fyn, the latter being also involved in NMDA-dependent synaptic plasticity, cocaine and heroin may indirectly influence the neural mechanisms that mediate their reinforcing properties. Masitinib, a novel tyrosine kinase inhibitor with high selectivity for c-Kit, Fyn and Lyn, may alter the aberrant consequences of the activation of these tyrosine kinases by cocaine and heroin. OBJECTIVE: We investigated in rats the effect of a chronic oral treatment with masitinib (20 mg/kg) on the reinforcing and motivational properties of self-administered cocaine (250 µg/infusion) and heroin (40 µg/infusion). METHODS: Three different cohorts of rats were trained instrumentally to respond for cocaine, heroin or food under continuous reinforcement. In each group, we assessed the influence of chronic daily treatment with masitinib on the maintenance of instrumental responding and intake and the motivation for the reinforcer. Thus, masitinib and vehicle-treated rats were challenged to adapt to high behavioural demand, to respond under a progressive ratio schedule of reinforcement and to reinstate instrumental responding after extinction and/or abstinence. RESULTS: Masitinib selectively decreased cocaine intake, the motivation for cocaine and the subsequent propensity to respond for cocaine under extinction, while having no effect on instrumental responding for heroin or food. CONCLUSION: The present findings suggest masitinib, a drug with proven efficacy in CNS disorders, could represent a novel treatment for cocaine addiction provided its influence on the reinforcing and incentive properties of the drug is confirmed.

The effects of ghrelin on sleep, appetite, and memory, and its possible role in depression: A review of the literature.

OBJECTIVES: Ghrelin is an orexigenic digestive hormone that plays a role in sleep and memory. Our work aims is to synthesize the effects of ghrelin on appetite, sleep and memory, and also to evidence its role in depressive disorders. METHODS: A systematic search was carried out on PubMed with no time boundaries. The following MeSH terms were used: ghrelin AND (appetite regulation OR obesity), (sleep wake disorders OR sleep) (memory OR cognition disorders) (depression OR depressive disorder OR mood disorder). RESULTS: Ghrelin triggers appetite and alters meal patterns by making them longer and richer. This can lead to pathologies, obesity and insulin-resistance. Ghrelin seems to have a favourable effect on sleep in human beings. It tends to make sleep more efficacious and better quality. Finally, it seems to have an effect on synaptic plasticity in the zones involved in memory and it has been shown to improve memory capacity in rodents. Regarding depression, the administration of ghrelin leads to an anti-depressive effect in animals and in humans. Conversely, post anti-depressant ghrelin titrations have generally shown a decrease in ghrelin levels. Resistant patients seem to retain high levels. Finally, the seriousness of depression could be related to ghrelin levels. CONCLUSION: Ghrelin plays a probable part in depression, especially for particular endophenotypes. A better understanding of ghrelin in depression could potentially help to optimize future therapeutic treatments.

Environmental scenarii for the degradation of oxo-polymers.

The fate of oxo-polymers in nature is strongly dependent on environmental conditions, mainly on the intensity and duration of sunshine, which vary with the season and the climate. In this work, we report the effect of different scenarii on the production and the molecular composition of oligomers released from oxo-biodegradable HDPE films. Under our experimental conditions, the duration of accelerated weathering corresponded to a period of 3 months to 3 years of exposure to outside conditions under temperate climate. In addition, the oligomers were extracted in three different solvents: i) water to mimics the natural environment; ii) acetone and chloroform to identify oligomers trapped in the polymer matrix. The combination of high-resolution mass spectrometry and 1H NMR spectroscopy gives an extensive picture of the relative concentrations and the structural compositions of the extracted oligomers in the different tested conditions. In particular, the masses, the number of oxygen and carbon atoms could be determined for up to 2283 molecules. Globally the concentration and the size of oligomers increased with the duration of extraction, the level of aging of the polymer and the use of non-polar solvents. Surprisingly, the presence of highly oxidized molecules in acetone and chloroform extract, suggested an important swelling of HPDE films in these solvents and a better diffusion of these oligomers in the matrix. In nature, the biodegradability of oligomers could result from processes occurring both at the molecular (oxidation) and the macromolecular (diffusion and release) levels.

[Keratoacanthomas on recent tattoos: Two cases]. / Kératoacanthomes sur tatouages récents : deux cas.

BACKGROUND: Increasing numbers of reports of rapidly arising, isolated or eruptive keratoacanthomas (KA) and squamous cell carcinomas (CSC) on the red part of tattoos tend to suggest a non-fortuitous link with the procedure. We report herein two different presentations of KAs on tattoos: one patient with multiple eruptive KAs on sun-exposed areas of a recent red tattoo and another with a solitary lesion on a recent tattoo. We discuss the issues related to the distinction between KAs and CSCs in this particular context. PATIENTS AND METHODS: Case No. 1: A 55-year-old heavily tattooed man presented multiple round keratotic verrucous-like lesions restricted to a red tattoo. The tattoo had been performed by a professional tattooist in summer 2016, a week before the onset of the symptoms. The patient did not protect a part of his tattoo from sun-exposure during the healing phase and lesions developed only on the sun-exposed tattooed parts. In January 2017, he consulted with about ten lesions. The histologic study by shaving of a lesion militated in favor of a CSC, KA type. The physical examination was unremarkable. He had no previous history of skin cancer. Two weeks later, most of the lesions regressed spontaneously. Based on the clinical history and progression of the lesions, a diagnosis was made of eruptive KA on a red tattoo. Residual lesions were treated by cryotherapy or excision. Case No. 2: A 72-year-old woman developed a 1-cm painful dome-shaped nodule with a central crust three weeks after tattooing. Full excision confirmed the diagnosis of KA. DISCUSSION: To date, we have found 31 case reports and series (17 men, median age: 50.5 years) of KA and CSC on tattoos. Lesions usually develop rapidly after completion of the tattoo, after between one week and several months. Exceptional cases have been described in old tattoos. Red tattoo ink is most commonly the culprit. The main difficulty lies in distinguishing between KA and CSC. Nowadays pathologists agree that a KA should be considered as a variant of CSC. Eruptive forms of KA present a peculiar situation. They may sometimes be inherited, and KA on recent traumatized areas or drug-induced have been described. Like other authors, we believe that cases of CSC on red tattoos belong rather to the KA type. The physiopathogenesis of tattoo-associated eruptive KA and CSC is not clearly understood, but could be multifactorial, involving: the trauma induced by tattooing, local inflammatory reaction, a component of the red ink, external factors such UV exposure, and a possible genetic predisposition. Rapidly arising KA and eruptive KA on top of recent (red) tattoos are not fortuitous. The lesions should be excised and the patient monitored. Additional studies on tumor specimens are warranted to identify the possible causative agents in tattoo ink that may be responsible for such reactions.

The anterior insula bidirectionally modulates cost-benefit decision-making on a rodent gambling task.

Deficits in cost-benefit decision-making, as assessed in the Iowa Gambling Task (IGT), are commonly observed in neuropsychiatric disorders such as addiction. There is considerable variation in the maximization of rewards on such tasks, both in the general population and in rodent models, suggesting individual differences in decision-making may represent a key endophenotype for vulnerability to neuropsychiatric disorders. Increasing evidence suggests that the insular cortex, which is involved in interoception and emotional processes in humans, may be a key neural locus in the control of decision-making processes. However, the extent to which the insula contributes to individual differences in cost-benefit decision-making remains unknown. Using male Sprague Dawley rats, we first assessed individual differences in the performance over the course of a single session on a rodent analogue of the IGT (rGT). Rats were matched for their ability to maximize reward and received bilateral excitotoxic or sham lesions of the anterior insula cortex (AIC). Animals were subsequently challenged on a second rGT session with altered contingencies. Finally, animals were also assessed for instrumental conditioning and reversal learning. AIC lesions produced bidirectional alterations on rGT performance; rats that had performed optimally prior to surgery subsequently showed impairments, and animals that had performed poorly showed improvements in comparison with sham-operated controls. These bidirectional effects were not attributable to alterations in behavioural flexibility or in motivation. These data suggest that the recruitment of the AIC during decision-making may be state-dependent and help guide response selection towards subjectively favourable options.

Characterization of oxidized oligomers from polyethylene films by mass spectrometry and NMR spectroscopy before and after biodegradation by a Rhodococcus rhodochrous strain.

The objective of this work was to develop a new approach to assess the specificity and the efficiency of biodegradation of oxidized oligomers extracted from aged HDPE polyethylene films and to bring insight on the mechanisms occurring during biodegradation. 1H NMR spectroscopy and LC Orbitrap™ mass spectrometry were combined together with data processing using Kendrick mass defect calculation and Van Krevelen Diagram. We showed that the molecular weight of extracted oligomers was lower than 850 Da with maximum chain length of 55 carbon atoms. The oligomers were divided into 11 classes of molecules with different oxidation state ranging from 0 to 10. All classes included series of chemically related compounds including up to 19 molecules. 95% of the soluble oligomers were assimilated by a strain of Rhodococcus rhodocchrous after 240 days of incubation. Large highly oxidized molecules completely disappeared while the other classes of molecules were still represented. Molecules containing 0-1 oxygen atom were less degraded. A strong shift to smaller molecules (<450 Da, 25 carbon atoms) was observed suggesting that longer molecules disappeared more rapidly than the smaller ones. It opens new perspectives on biodegradation processes as not only intracellular ß-oxidation must be considered but also extracellular mechanisms leading to chain cleavages.

[Granulomatous slack skin associated with metastatic testicular seminoma]. / Mycosis fongoïde chalazodermique associé à un séminome testiculaire métastatique.

BACKGROUND: Granulomatous slack skin (GSS) is an extremely rare subtype of T-cell lymphoma, a variant of mycosis fungoides (MF). Herein, we describe the first reported case of GSS associated with metastatic testicular seminoma. PATIENTS AND METHODS: A 28-year-old male patient presented with circumscribed erythematous loose skin masses, especially in the body folds and which had been relapsing for 4years. Skin biopsy showed a loss of elastic fibers and an atypical granulomatous T-cell infiltrate with epidermotropism, enabling a diagnosis of GSS to be made. A biopsy of a retroperitoneal lymphadenopathy showed testicular seminoma metastasis. DISCUSSION: Patients suffering from GSS have a statistically higher risk of developing a second primary cancer, especially Hodgkin's lymphoma. The association found between GSS and a lymphoproliferative malignancy requires long-term follow-up and determines the patient's prognosis. CONCLUSION: It is not possible to prove a formal link between GSS and testicular seminoma. However, this case illustrates the value of screening for a second cancer, particularly where extra-cutaneous lesions appear during GSS treatment. Lymph node biopsy should be performed routinely in the event of GSS with possible lymph node involvement.

Estimating the morbidity and mortality associated with infections due to multidrug-resistant bacteria (MDRB), France, 2012.

BACKGROUND: A study based on 2007 data estimated that 386,000 infections due to multidrug-resistant bacteria (MDRB) occurred in Europe that year and 25,000 patients died from these infections. Our objective was to estimate the morbidity and mortality associated with these infections in France. METHODS: The MDRB considered were methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide-resistant enterococci, third-generation cephalosporin-resistant (3GC-R) Escherichia coli and Klebsiella pneumoniae, carbapenem-resistant Klebsiella pneumoniae, Acinetobacter spp. and Pseudomonas aeruginosa (CR P. aeruginosa). The number of invasive infections (infections with bacteria isolated from blood or cerebrospinal fluid) due to MDRB, as reported by France to EARS-Net in 2012, was corrected for the coverage of our surveillance network and extrapolated to other body sites using ratios from the French healthcare-associated infections point prevalence survey and the literature. Mortality associated with MDRB infection was estimated using proportions from the literature. Methods and parameters were reviewed by a panel of experts. RESULTS: We estimate that 158,000 (127,000 to 245,000) infections due to MDRB occurred in 2012 in France (incidence: 1.48 to 2.85 per 1000 hospital days), including 16,000 invasive infections. MRSA, 3GC-R E. coli and K. pneumoniae were responsible for 120,000 (90,000 to 172,000) infections, i.e., 75% of the total. An estimated 12,500 (11,500 to 17,500) deaths were associated with these infections, including 2,700 associated with invasive infections. MRSA, 3GC-R E. coli and CR P. aeruginosa accounted for 88% of these deaths. CONCLUSION: These first estimates confirm that MRSA, 3GC-R Escherichia coli and Klebsiella pneumoniae account for the largest portion of the morbidity and mortality of infections due to MDRB in France. These results are not directly comparable with the European study because the methodology used differs in many respects. The differences identified between our study and previous studies underline the need to define a standardised protocol for international assessments of the morbidity and mortality of antibiotic resistance. Estimating morbidity and mortality will facilitate communication and awareness in order to reinforce adherence and support of healthcare professionals and policy-makers to MDRB prevention programs.

The role of GSK-3 in treatment-resistant depression and links with the pharmacological effects of lithium and ketamine: A review of the literature.

BACKGROUND: Since the discovery of antidepressants, new treatments have emerged with fewer side effects but no greater efficacy. Glycogen synthase kinase 3 ß (GSK-3ß), a kinase known for its activity on glycogen synthesis, has in the last few years raised growing interest in biological psychiatry. Several efficient treatments in major depression have an inhibitory effect on this kinase, which could be targeted in new mood disorder treatments. METHODS: The aim of this review is to summarize findings concerning the intracellular pharmacologic effects of GSK-3ß inhibitors on mood. After a brief description of the intracellular transduction pathways implicated in both GSK-3ß and mood disorders, we reviewed the results demonstrating GSK-3ß involvement in the effects of lithium and ketamine. RESULTS: GSK-3ß can be inhibited through several mechanisms such as serine phosphorylation or binding in a proteic scaffold and others. Its inhibition is implicated in numerous cellular pathways of interest involved in neuronal growth and architecture, cell survival, neurogenesis or synaptic plasticity. This inhibition appears to be both efficient and sufficient in improving mood in animal models. In human beings, several levels of evidence show GSK-3ß inhibition with antidepressant use. Crucially, strong inhibition has been shown with lithium via the proteic scaffold PP2A/ß-arrestin/AKT, and with the rapid antidepressant effect of ketamine via p70S6K. CONCLUSION: Our review focuses on mechanisms whereby the GSK-3ß pathway has a part in the antidepressant effect of lithium and ketamine. This article highlights the importance of translational research from cell and animal models to the clinical setting in order to develop innovative therapeutic targets.

Impact of temperature on the dynamics of organic matter and on the soil-to-plant transfer of Cd, Zn and Pb in a contaminated agricultural soil.

Predicting the soil-to-plant transfer of metals in the context of global warming has become a major issue for food safety. It requires a better understanding of how the temperature alters the bioavailability of metals in cultivated soils. This study focuses on one agricultural soil contaminated by Cd, Zn and Pb. DGT measurements were performed at 10, 20 and 30 °C to assess how the bioavailability of metals was affected by a rise in soil temperature. A lettuce crop was cultivated in the same conditions to determine if the soil-to-plant transfer of metals increased with a rise in soil temperature. A gradual decline in Cd and Zn bioavailability was observed from 10 to 30 °C, which was attributed to more intense complexation of metals in the pore water at higher temperatures. Together with its aromaticity, the affinity of dissolved organic matter (DOM) for metals was indeed suspected to increase with soil temperature. One main output of the present work is a model which satisfactorily explains the thermal-induced changes in the characteristics of DOM reported in Cornu et al. (Geoderma 162:65-70, 2011) by assuming that the mineralization of initial aliphatic compounds followed a first-order reaction, increased with soil temperature according to the Arrhenius law, and due to a priming effect, led to the appearance of aromatic molecules. The soil-to-plant transfer of Cd and Zn was promoted at higher soil temperatures despite a parallel decrease in Cd and Zn bioavailability. This suggests that plant processes affect the soil-to-plant transfer of Cd and Zn the most when the soil temperature rises.

Long-term in vivo imaging of translated RNAs for gene therapy.

To determine the potential of RNA for transient expression, we followed its translational efficiency and expression kinetics in vivo in mouse skin. Three RNA species were delivered in vivo with differing 5' and 3' ends, as well as with different structures that are known to influence their translation fate, such as an internal ribosome entry site (IRES), a cap or a poly(A) tail. RNAs were transferred by electropermeabilization, and each encoded the firefly luciferase enzyme to allow monitoring of translational efficiency by in vivo bioluminescence imaging. We show that all types of naked RNAs delivered into mouse skin are efficient for transient protein expression in vivo. Expression could be achieved with some differences in efficiency and time course, using either capped/polyadenylated RNAs or RNAs containing HCV IRES structures with or without a poly(A) tail. Our data reveal expression occurring up to 2 weeks, suggesting that electroporated RNA has high stability in vivo, particularly capped and polyadenylated RNAs. Our study shows that RNA molecules are efficient tools for the transient expression of proteins in vivo and that they can be used for therapeutic purposes. Changes in RNA features may be used to modulate both expression efficiency and kinetics.