Strength and ductility loss of Magnesium-Gadolinium due to corrosion in physiological environment: Experiments and modeling.

We propose a computational framework to study the effect of corrosion on the mechanical strength of magnesium (Mg) samples. Our work is motivated by the need to predict the residual strength of biomedical Mg implants after a given period of degradation in a physiological environment. To model corrosion, a mass-diffusion type model is used that accounts for localised corrosion using Weibull statistics. The overall mass loss is prescribed (e.g., based on experimental data). The mechanical behaviour of the Mg samples is modeled by a state-of-the-art Cazacu-Plunkett-Barlat plasticity model with a coupled damage model. This allowed us to study how Mg degradation in immersed samples reduces the mechanical strength over time. We performed a large number of in vitro corrosion experiments and mechanical tests to validate our computational framework. Our framework could predict both the experimentally observed loss of mechanical strength and the ductility due to corrosion for both tension and compression tests.

Effect of Various Heat Treatments on the Microstructure of 316L Austenitic Stainless Steel Coatings Obtained by Cold Spray.

Industries developing cold spray aim at dense and resistant coatings for component repair. However, as-sprayed 316L coatings display non-equilibrium microstructure and brittle fracture behavior. Improving their mechanical properties requires controlling their microstructure; post-spraying heat treatment is a promising approach. The recovery and recrystallization of coatings were little studied, and heat treatments reported in literature mostly used holding for long time in furnaces, not adapted to on-site repairs. This study aimed at gaining insights into recovery and recrystallization mechanisms of 316L coatings, for a broader range of heat treatment kinetics. A study of powders and as-sprayed coatings was conducted to characterize the initial state. In situ XRD measurements provided input for heat treatment definition. Microscopy, room temperature XRD and hardness measurements allowed to better understand the microstructural evolutions and to select treatments leading to original microstructures. In this work, a variety of microstructures were produced by adapting heat treatment conditions for a given set of spraying parameters. The recrystallization path of the heterogeneous skin-core microstructure of deposited particles, as well as the interaction between grain growth and precipitation was revealed. A novel, optimized fast heat treatment led to a fully recrystallized, fine-grained coating and significantly reduced hardness.

[Addictions]. / Addictions.

This year, the actuality for addictions in this edition addresses four points. The disease model of addiction is criticized by the cognitive neurosciences which need to consider the agentivity of the persons. Regarding the societal actuality, clinical pharmacology review of cannabidiol presents an update on legal cannabis. The suicidality of excessive gamblers may be prevented specifically. Addiction and first psychotic episodes need an integrated care.

Cette année, l'actualité des addictions pour ce numéro concerne quatre points. Le modèle de la maladie de l'addiction est critiqué par les neurosciences cognitives qui demandent de reconnaître l'agentivité des personnes. Au vu de l'actualité sociétale, une revue pharmacologique clinique du cannabidiol vient mettre à jour nos connaissances sur le cannabis légal. La suicidalité des joueurs excessifs peut faire l'objet de prévention spécifique. L'addiction et le premier épisode psychotique nécessitent une prise en charge intégrée.

[Addictions]. / Addictions.

In 2016, the actuality for addictions in this edition addresses four points. Social neurosciences of addiction are of great importance regarding the vulnerabilities for addiction and for the recovery. Deep brain stimulation is emerging in the therapeutic panel coming from the clinical neurosciences for the addictions. Novelties in opioid agonists for the treatment of opiates dependence, with the apparition in the Swiss market of release morphine and of levomethadone. Cannabis and prison, a pilot study for the maintenance of abstinence in prison.

En 2016, l'actualité des addictions pour ce numéro concerne quatre points. Les neurosciences sociales de l'addiction, qui ont une grande importance en termes de vulnérabilité pour l'addiction mais aussi pour le rétablissement. La stimulation cérébrale profonde qui fait son apparition dans l'éventail thérapeutique issu des neurosciences cliniques pour les addictions. Les nouveautés du traitement agoniste opioïde de la dépendance aux opiacés avec l'apparition dans le marché suisse de la morphine retard puis de la lévométhadone. Des algorithmes sont proposés pour orienter le prescripteur. Cannabis et prison, une étude pilote pour le maintien de l'abstinence en prison.

Linking empathy to visuospatial perspective-taking in gambling addiction.

It has been demonstrated that people suffering from substance-related addictions are less empathic than their non-addicted counterparts. Our first aim was to verify if this is also true for behavioral addictions. We hypothesized that problem gamblers are less empathic than healthy controls. Our second aim was to identify a cognitive marker of empathy that could be targeted in cognitive rehabilitation strategies. We propose that a potential cognitive marker of empathy could be visuospatial perspective-taking. Specifically, we hypothesized that visuospatial perspective-taking performances are lower in problem gamblers compared to healthy controls and that these visuospatial performances predict empathy. Thirty-one non-gamblers, 24 healthy gamblers, and 21 problem gamblers performed a visuospatial perspective-taking task before completing the Interpersonal Reactivity Index (IRI; Davis, 1980; Davis, 1983). Problem gamblers had decreased empathy and lower performance at the visuospatial perspective-taking task than non-gamblers and healthy gamblers. Furthermore, we confirmed that visuospatial perspective-taking abilities predict empathy on the IRI dimensions of interpersonal perspective-taking and personal distress. The present study provides new evidence that reduced empathy is not limited to subjects with substance-related addictions; rather, it extends to behavioral addictions. Visuospatial perspective-taking may be a viable cognitive marker for use as a rehabilitation target of empathy.

[Addiction]. / Addictions.

This year, the actuality about addiction is on psychopharmacology, in the controversy about the prescription of baclofene to reduce the craving for alcohol. More results from controlled studies are expected. The development of smartphones to access toe-Health skills is questionable, especially in matterofevaluation of these programs. Despite of encouraging results, open questions are remaining for clinicians, to be compared with clinical practice. Finally, it is necessary to keep in touch with translational neurosciences; in fact, research is showing that populations of addicts present a deficit in matter of empathy. This is the cause of a handicap in the social relationships. At a lower level, a difficulty to take the other's place could be the cause of this deficit at a higher level. Rehabilitation perspectives could come out of this discovery.

[Addiction]. / Addictions.

The news in addiction medicine in 2013 are presented according to the new version of the DSM (DSM-5); new data on cannabinoid, highlight hypotheses on self-medication; a current status about treatment of the addiction via the internet is shown; and new therapeutic perspectives emerge from the knowledge on traumatic antecedents in addictive populations.

Usefulness of methadone plasma concentration measurement in patients receiving nevirapine or efavirenz.

OBJECTIVE: To determine methadone plasma trough and peak concentrations in patients presenting opiate withdrawal symptoms after introduction of nevirapine or efavirenz. To describe the disappearance of these symptoms after methadone titration based on plasma concentrations rather than on the symptoms. METHODS: Nine patients undergoing highly active antiretroviral therapy (HAART) and either nevirapine or efavirenz treatment were monitored daily for opiate withdrawal in a specialized drug addiction center. Methadone dose was titrated daily, and plasma concentrations were measured. The data are retrospective (case series). RESULTS: Several patients complained of symptoms such as nausea, vomiting, accelerated intestinal transit, or insomnia. Even after methadone titration based on clinical symptoms, patients and health-care providers trained in infectious disease did not classify these as withdrawal symptoms and considered them as the side effects of HAART or anxiety. Methadone plasma trough concentration showed low levels of (R)- and (R,S)-methadone. Further methadone dose adjustment according to plasma level resulted in the disappearance of these withdrawal symptoms. The daily methadone dose was split when the peak/trough (R)-methadone ratio was more than 2. CONCLUSIONS: When introducing efavirenz or nevirapine to patients undergoing methadone treatment, withdrawal symptoms should be monitored, especially those such as insomnia, vomiting, or nausea. Methadone plasma trough and peak measurements can be of value in preventing unnecessary side effects of HAART.

Motivational intervention to reduce cannabis use in young people with psychosis: a randomized controlled trial.

BACKGROUND: Cannabis use has a negative impact on psychosis. Studies are needed to explore the efficacy of psychological interventions to reduce cannabis use in psychosis. Our aim is to study the efficacy of a specific motivational intervention on young cannabis users suffering from psychosis. METHODS: Participants (aged less than 35 years) were randomly assigned to treatment as usual (TAU) alone, or treatment as usual plus motivational intervention (MI + TAU). TAU was comprehensive and included case management, early intervention and mobile team when needed. Assessments were completed at baseline and at 3, 6 and 12 months follow-up. RESULTS: Sixty-two participants (32 TAU and 30 MI + TAU) were included in the study. Cannabis use decreased in both groups at follow-up. Participants who received MI in addition to TAU displayed both a greater reduction in number of joints smoked per week and greater confidence to change cannabis use at 3 and 6 months follow-up, but differences between groups were nonsignificant at 12 months. CONCLUSIONS: MI is well accepted by patients suffering from psychosis and has a short-term impact on cannabis use when added to standard care. However, the differential effect was not maintained at 1-year follow-up. MI appears to be a useful active component to reduce cannabis use which should be integrated in routine clinical practice.

[Addiction]. / Dépendances.

The 2009 news in medicine regarding dependence confirm the bio-psycho-social field of addiction medicine and psychiatry. First a statement is made about the risk of cardiac arythmy in opioid substitution treatments. Then a review of the treatment of C hepatitis shows its importance in an addicted population. In the field of cognitive neuroscience, progress has been made in the knowledge of "craving" and of its endophenotypical components. Electronic medias related disorders are on the border of addiction: a case study is exploring this new domain. At last, recent datas are presented on the relationship between cannabis and psychosis.

Cannabis and benzodiazepines as determinants of methadone trough plasma concentration variability in maintenance treatment: a transnational study.

PURPOSE: To assess tobacco, alcohol, cannabis and benzodiazepine use in methadone maintenance treatment (MMT) as potential sources of variability in methadone pharmacokinetics. METHODS: Trough plasma (R)- and (S)-methadone concentrations were measured on 77 Australian and 74 Swiss MMT patients with no additional medications other than benzodiazepines. Simple and multiple regression analyses were performed for the primary metric, plasma methadone concentration/dose. RESULTS: Cannabis and methadone dose were significantly associated with lower 24-h plasma (R)- and (S)-methadone concentrations/dose. The models containing these variables explained 14-16% and 17-25% of the variation in (R)- and (S)-methadone concentration/dose, respectively. Analysis of 61 patients using only CYP3A4 metabolised benzodiazepines showed this class to be associated with higher (R)-concentration/dose, which is consistent with a potential competitive inhibition of CYP3A4. CONCLUSION: Cannabis use and higher methadone doses in MMT could in part be a response to-or a cause of-more rapid methadone clearance. The effects of cannabis and benzodiazepines should be controlled for in future studies on methadone pharmacokinetics in MMT.

Association of dopamine and opioid receptor genetic polymorphisms with response to methadone maintenance treatment.

BACKGROUND: Genetic variations of the dopamine and opioid receptors could influence the response to methadone maintenance treatment (MMT). METHODS: We included 238 MMT patients according to their response to treatment and methadone dosing, along with 217 subjects without substance dependence. All were genotyped for polymorphisms of the dopamine D1, D2, micro-opioid and delta-opioid receptor genes. RESULTS: The polymorphisms of the micro-opioid (118A>G), delta-opioid (921T>C), dopamine D1 (DdeI) and D2 (TaqI A) receptor genes were not associated with response to MMT and methadone dosing, whereas an association was found with the dopamine D2 receptor (DRD2) 957C>T polymorphism. The 957CC carriers were more frequently non-responders to treatment (OR=2.4; p=0.02) and presented a fourfold shorter period of negative urine screening (p=0.02). No significant differences in allele frequencies were observed between the MMT patients and the control group, suggesting no association of the analyzed polymorphisms with opioid dependence. CONCLUSIONS: These results suggest that DRD2 genotype may contribute to the understanding of the interindividual variability to the response to MMT.

Methadone maintenance treatment (MMT) in general practice or in specialized centers: profile of patients in the Swiss Canton of Vaud.

We studied profile of patients (n=1782) treated in specialized centers and general practice (GP) enrolled in methadone maintenance treatment (MMT) programs during 2001 in the Swiss Canton of Vaud. We found that GPs treated the majority of patients (76%). Specialized centers treated a higher proportion of patients with uncontrolled intravenous use of cocaine and heroin, and prescribed neuroleptics as concomitant medication three times more frequently than GPs. Patients treated in specialized centers were more likely to undergo screening for HIV, HBV, HCV, and receive complete HBV immunization. In conclusion, specialized centers are more likely to treat severely addicted patients and patients with a poor global assessment (physical, psychiatric, and social).

["Epinephrine-addiction" and risk-seeking behaviour in athletes: what realities?]. / "Adrénaline-addiction" et comportements de prises de risques chez les sportifs: quelles réalités?

This article resumes the psychobiologic mechanisms involved in risk-seeking behaviour. The question is discussed whether some forms of high risk sports meet the diagnostic criteria of dependency. The intensive activation of the adrenocorticotropic pathway may yield to addiction: according to the model of emotion-focussed coping of stress, unpleasant emotion is "overwritten" by intense stress and hence better tolerated emotionally, leading to an addictive repetition of risk-seeking behaviour. In addition, pharmacologic mimicry seems possible as the perception of effects of catecholamines may imitate some of the effects of stimulating drugs. Finally, the current concept of risk and harm reduction is transferred to sports. This would mean to apply appropriate preventive interventions for a large variety of possibly dangerous activities.

Naltrexone-assisted rapid methadone discontinuation: a pilot study.

Slow downtitration as a methadone discontinuation method is time-consuming and associated to high dropout rates. Whereas ultra-rapid opiate detoxification methods have recently gained some popularity, they are expensive and may be associated with particular problems in methadone patients. In the present study, a 3-day detoxification procedure accelerated with a unique dose of naltrexone was used in 10 methadone-substituted patients. Whereas the treatment resulted in a shortened withdrawal syndrome, which was satisfactorily controlled by the drugs used, a two-phase course was observed, some symptoms reappearing between the end of day 2 and the beginning of day 3. The first phase of withdrawal symptoms was attributed to the antagonistic effect of naltrexone, which possibly also improved under the weakening of naltrexone. The second phase of withdrawal symptoms may be related to falling methadone plasma levels.

ABCB1 and cytochrome P450 genotypes and phenotypes: influence on methadone plasma levels and response to treatment.

BACKGROUND AND OBJECTIVE: The in vivo implication of various cytochrome P450 (CYP) isoforms and of P-glycoprotein on methadone kinetics is unclear. We aimed to thoroughly examine the genetic factors influencing methadone kinetics and response to treatment. METHODS: Genotyping for CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, ABCB1, and UGT2B7 polymorphisms was performed in 245 patients undergoing methadone maintenance treatment. To assess CYP3A activity, the patients were phenotyped with midazolam. RESULTS: The patients with lower CYP3A activity presented higher steady-state trough (R,S)-methadone plasma levels (4.3, 3.0, and 2.3 ng/mL x mg for low, medium, and high activity, respectively; P = .0002). As previously reported, CYP2B6*6/*6 carriers had significantly higher trough (S)-methadone plasma levels (P = .0001) and a trend toward higher (R)-methadone plasma levels (P = .07). CYP2D6 ultrarapid metabolizers presented lower trough (R,S)-methadone plasma levels compared with the extensive or intermediate metabolizers (2.4 and 3.3 ng/mL x mg, respectively; P = .04), whereas CYP2D6 poor metabolizer status showed no influence. ABCB1 3435TT carriers presented lower trough (R,S)-methadone plasma levels (2.7 and 3.4 ng/mL . mg for 3435TT and 3435CC carriers, respectively; P = .01). The CYP1A2, CYP2C9, CYP2C19, CYP3A5, and UGT2B7 genotypes did not influence methadone plasma levels. Only CYP2B6 displayed a stereoselectivity in its activity. CONCLUSION: In vivo, CYP3A4 and CYP2B6 are the major CYP isoforms involved in methadone metabolism, with CYP2D6 contributing to a minor extent. ABCB1 genetic polymorphisms also contribute slightly to the interindividual variability of methadone kinetics. The genetic polymorphisms of these 4 proteins had no influence on the response to treatment and only a small influence on the dose requirement of methadone.