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Background: Sodium oxybate (SMO) has been shown to be effective in the maintenance of abstinence (MoA) in alcohol-dependent patients in a series of small randomized controlled trials (RCTs). These results needed to be confirmed by a large trial investigating the treatment effect and its sustainability after medication discontinuation. Aims: To confirm the SMO effect on (sustained) MoA in detoxified alcohol-dependent patients. Methods: Large double-blind, randomized, placebo-controlled trial in detoxified adult alcohol-dependent outpatients (80% men) from 11 sites in four European countries. Patients were randomized to 6 months SMO (3.3–3.9 g/day) or placebo followed by a 6-month medication-free period. Primary outcome was the cumulative abstinence duration (CAD) during the 6-month treatment period defined as the number of days with no alcohol use. Secondary outcomes included CAD during the 12-month study period. Results: Of the 314 alcohol-dependent patients randomized, 154 received SMO and 160 received placebo. Based on the pre-specified fixed-effect two-way analysis of variance including the treatment-by-site interaction, SMO showed efficacy in CAD during the 6-month treatment period: mean difference +43.1 days, 95% confidence interval (17.6–68.5; p = 0.001). Since significant heterogeneity of effect across sites and unequal sample sizes among sites ( n = 3–66) were identified, a site-level random meta-analysis was performed with results supporting the pre-specified analysis: mean difference +32.4 days, p = 0.014. The SMO effect was sustained during the medication-free follow-up period. SMO was well-tolerated. Conclusions: Results of this large RCT in alcohol-dependent patients demonstrated a significant and clinically relevant sustained effect of SMO on CAD. Trial registration: ClinicalTrials.gov Identifier: NCT04648423

International audience; BACKGROUND and AIMS: Only a minority of excess alcohol drinkers develop cirrhosis. We developed and evaluated risk stratification scores to identify those at highest risk. METHODS: Three cohorts (GenomALC-1: n=1690, GenomALC-2: n=3037, UK Biobank: relevant n=6898) with a history of heavy alcohol consumption (≥80 g/day (men), ≥50 g/day (women), for ≥10 years) were included. Cases were participants with alcohol-related cirrhosis. Controls had a history of similar alcohol consumption but no evidence of liver disease. Risk scores were computed from up to eight genetic loci identified previously as associated with alcohol-related cirrhosis and three clinical risk factors. Score performance for the stratification of alcohol-related cirrhosis risk was assessed and compared across the alcohol-related liver disease spectrum, including hepatocellular carcinoma (HCC). RESULTS: A combination of three single nucleotide polymorphisms (SNPs) (PNPLA3:rs738409, SUGP1-TM6SF2:rs10401969, HSD17B13:rs6834314) and diabetes status best discriminated for cirrhosis risk. The odds ratio (OR) and 95% confidence intervals (CI) for the extreme score quintiles (Q1-Q5) of the 3-SNP score, based on independent allelic effect size estimates, were 5.99 (4.18;8.60) (GenomALC-1); 2.81 (2.03;3.89) (GenomALC-2); and 3.10 (2.32;4.14) (UK Biobank). Patients with diabetes and high-risk score, compared to those without diabetes and a low-risk score, had ORs increased to 14.7 (7.69;28.1) (GenomALC-1) and 17.1 (11.3;25.7) (UK Biobank). Patients with cirrhosis and HCC had significantly higher mean risk scores than patients with cirrhosis alone (0.76±0.06 versus 0.61±0.02, p=0.007). Score performance was not significantly enhanced by information on additional genetic risk variants, body mass index or coffee consumption. CONCLUSIONS: A risk score based on three genetic risk variants and diabetes status can provide meaningful risk stratification for cirrhosis in excess drinkers, allowing earlier prevention planning including intensive intervention. LAY SUMMARY: Excessive chronic drinking leads to liver cirrhosis in some people, but so far there is no way to identify those at high risk of developing this debilitating disease. Our study has developed a genetic risk score (GRS) test that can identify patients at high risk and shows that the risk of cirrhosis is increased >10-fold with just two risk factors - diabetes and high GRS. Risk assessment using this test has potential for early and personalised management of this disease in high-risk patients.

International audience; This dataset complement a previously published dataset [1] and corresponds to the physico-chemical parameters data series produced during the MESOLAC experimental project [2]. The presented dataset is composed of: 1. In situ profiles (0–3m) of temperature, conductivity, pH, dissolved oxygen (concentration and saturation). 2. In situ measurements of light spectral UV/VIS/IR irradiance (300–950 nm wavelength range) taken at 0, 0.25, 0.5, 1, 1.5, 2 and 2.5m. 3. Laboratory chemical analysis of samples collected at 0 and 2 m (conductivity, pH, total alkalinity, NH4, NO2, NO3, total and particulate nitrogen (Ntot, Npart), PO4, total and particulate phosphorus (Ptot, Ppart), total, organic particulate and total particulate carbon (Ctot, Cpart-org, Cpart-tot), Cl, SO4, SiO2. 4. Laboratory analysis of pigments extracted from samples collected at 0 and 2 m (Chla, Chlc, carotenoids, phaeopigments).The experimental design is the same as in Tran-Khac et al [1]. Briefly, it consisted of nine pelagic mesocosms (about 3000 L, 3m depth) deployed in July 2019 in Lake Geneva near the shore of Thonon les Bains (France) aiming to simulate predicted climate scenarios (i.e. extreme events) and assess the response of planktonic communities, ecosystem functioning and resilience.During the experiment, physical parameters were measured twice a week. At the same time, samples were collected at 0 and 2m of depth for subsequent chemical laboratory analyses. These data are presented in the dataset file, ordered by sampling event (numbered from S1 to S8), treatment (Control-C, High-H and Medium-M) and replicates (1 to 3). For each sampling point the measured parameters are listed in columns, missing data and values below the detection limit are marked as NA (not available).This data set aims to contribute to the understanding of the effect of environmental forcing on lake physico-chemical characteristics (such as temperature, oxygen and nutrient concentration) under simulated intense weather events. To a broader extent, the presented data can be used for a wide variety of applications, including monitoring of a large peri-alpine lake functioning under environmental stress and being included in further meta-analysis to generalise the effect of climate change on large lakes. The two complementary dataset differ in the acquired data and methods, temporal and spatial resolution. They complete each other in terms of physico-chemical characterization of the experimental treatments and together can allow comparison of the two different monitoring strategies (continuous vs punctual) during in situ experimental manipulations.

International audience; Background and aims - Only a minority of heavy drinkers progress to alcohol-associated cirrhosis (ALC). The aim of this study was to identify common genetic variants that underlie risk for ALC. Approach and results - We analyzed data from 1,128 subjects of European ancestry with ALC and 614 heavy-drinking subjects without known liver disease from Australia, the United States, the United Kingdom, and three countries in Europe. A genome-wide association study (GWAS) was performed, adjusting for principal components and clinical covariates (alcohol use, age, sex, body mass index, and diabetes). We validated our GWAS findings using UK Biobank. We then performed a meta-analysis combining data from our study, the UK Biobank, and a previously published GWAS. Our GWAS found genome-wide significant risk association of rs738409 in patatin-like phospholipase domain containing 3 (PNPLA3) (odds ratio [OR] = 2.19 [G allele], P = 4.93 × 10 ) and rs4607179 near HSD17B13 (OR = 0.57 [C allele], P = 1.09 × 10 ) with ALC. Conditional analysis accounting for the PNPLA3 and HSD17B13 loci identified a protective association at rs374702773 in Fas-associated factor family member 2 (FAF2) (OR = 0.61 [del(T) allele], P = 2.56 × 10 ) for ALC. This association was replicated in the UK Biobank using conditional analysis (OR = 0.79, P = 0.001). Meta-analysis (without conditioning) confirmed genome-wide significance for the identified FAF2 locus as well as PNPLA3 and HSD17B13. Two other previously known loci (SERPINA1 and SUGP1/TM6SF2) were also genome-wide significant in the meta-analysis. GeneOntology pathway analysis identified lipid droplets as the target for several identified genes. In conclusion, our GWAS identified a locus at FAF2 associated with reduced risk of ALC among heavy drinkers. Like the PNPLA3 and HSD17B13 gene products, the FAF2 product has been localized to fat droplets in hepatocytes. Conclusions - Our genetic findings implicate lipid droplets in the biological pathway(s) underlying ALC.

Background Models based on the uniqueness of addiction processes between behavioral addictions are highly contentious, and the inclusion of gaming disorder in the addiction nosography remains controversial. An exploratory approach could clarify a hypothesized common and subjectively identifiable process in addictive behaviors and the necessarily different expressions of the disorder due to behavior specificities, in particular the sociocultural characteristics and profiles of users. Objective The aim of this study was to describe the nature of contacts to a help service by exploring commonality and specificities of burden and help-seeking for problem gambling or gaming. Methods This was an observational quantitative-qualitative study. We included all contacts (ie, online questions and contacts by phone or chat when the helper completed a summary) to a helpline for gamers, gamblers, and relatives over a 7-year period. We constituted a text corpus with online questions and summaries of contacts by phone or chat. We collected basic sociodemographic data, including the device used to contact the service (phone or internet), contacting the service for oneself (“user”) or being a relative of a user and type of relative, gambling (yes/no), gaming (yes/no), and age and sex of the gambler/gamer. We describe the corpus descriptively and report the computerized qualitative analysis of online questions, chat, and summary of phone calls. We performed a descendant hierarchical analysis on the data. Results A total of 14,564 contacts were made to the helpline, including 10,017 users and 4547 relatives. The corpus was composed of six classes: (1) gaming specificities, (2) shared psychological distress and negative emotions, (3) the procedure for being banned from gambling, (4) the provided help, (5) gambling specificities, and (6) financial problems. Conclusions Negative emotions and shared distress linked to gambling and gaming support current scientific consensus that these behaviors can produce psychological distress in se; however, meaningful differences were observed in core symptoms of addiction between gamers and gamblers, beyond specificities related to the behavior itself: loss of control was elicited in the class corresponding to gambling specificities and not by gamers and their relatives.

Background and Aim The main aim of this study was to evaluate if the binge eating disorders (BEDs) related to obesity were associated with the severity of non‐alcoholic fatty liver disease (NAFLD). Methods Severely obese patients who had been referred for bariatric surgery were included in this study at the Nice University Hospital. All patients underwent a liver biopsy at the time of surgery. Between 2008 and 2015, 388 patients had an assessable Bulimia Test (BULIT) self‐questionnaire at the time of surgery. A subgroup (n = 183), between 2011 and 2015, also responded to a Beck Depression Inventory, Hospital Anxiety and Depression Scale, and a Fatigue Impact Scale autoquestionnaire. A control group of 29 healthy people matched by age and gender was included. Results Among the 388 obese patients (median age 40 years, body mass index 41.7 kg/m2, 81% women), 14 patients had a “probable diagnosis” of BED, and 47 patients had a “high risk” of developing a BED according to the BULIT. Obese patients had significantly more severe BED, depression, anxiety, and fatigue compared to controls. Steatosis, non‐alcoholic steatohepatitis, or fibrosis was not associated with BED. Similarly, the severity of NAFLD was not associated with depression, anxiety, or fatigue. Conclusions Severely obese patients had more severe BED, depression, anxiety, and fatigue than lean subjects independent of the severity of NAFLD., Non‐alcoholic fatty liver disease, the emerging liver disease of the 21st century, is related to obesity. However, binge eating disorders, and also frequently associated psychiatric disorders (depression, anxiety, and fatigue), are not associated with the severity of liver pathology in severely obese patients.

International audience; Addiction transfer from alcohol to sugar has been demonstrated in the alcohol postdependent state model in rats. To assess whether changes in sugar intake and craving can occur during alcohol withdrawal in humans we conducted a prospective, observational study in a university hospital addictions treatment center. Recruited patients had severe alcohol use disorder, were hospitalized for 7 days in the short-stay unit for alcohol withdrawal and then for 6 weeks in the rehabilitation unit. During the hospital stay, they had no access to alcohol but had full access to sweet products and beverages in a shop and vending machines located inside the hospital. Alcohol craving was assessed using a visual analogue scale on days 1, 15 and 45. Sugar craving, sweet products stored by patients in their rooms and weight were assessed on the same days. Thirty-five patients were included. Sugar craving increased in 14 patients during the hospital stay while no change was observed in the remaining 21. Significant increases in both the amounts of sweet products stored in the patients' rooms (p

International audience; Up to 50% of liver transplantation (LT) recipients with known or clandestine alcohol-use disorder (AUD) before surgery return to alcohol use after LT. However, only severe alcohol relapse, which varies in frequency from 11% to 26% of patients, has an impact on longterm survival and significantly decreases survival rates after 10 years. Therefore, it is crucial to identify patients with the highest risk of severe relapse in order to arrange specific, standardized monitoring by an addiction team before and after LT. The aims of this study were to describe the effects of combined management of AUD on the rate of severe alcohol relapse and to determine the risk factors before LT that predict severe relapse. Patients transplanted between January 2008 and December 2014 who had met with the LT team's addiction specialist were included in the study. Patients who exhibited alcohol-related relapse risk factors received specific addiction follow-up. A total of 235 patients were enrolled in the study. Most of them were men (79%), and the mean age at the time of the LT was 55.7 years. Severe relapse occurred in only 9% of the transplant recipients. Alcohol-related factors of severe relapse were a pretransplant abstinence of 6 months and family, legal, or professional consequences of alcohol consumption, whereas the nonalcohol-related factors were being single and being eligible for a disability pension. In conclusion, the integration of an addiction team in a LT center may be beneficial. The addiction specialist can identify patients at risk of severe relapse in the pretransplantation period and hence arrange for specific follow-up.

International audience; Background and aims: Completely substituting e-cigarettes (EC) for combustible tobacco cigarettes reduces exposure to toxicants and carcinogens. However, a large proportion of EC users (dual users) continue to smoke conventional cigarettes. This study aimed to compare estimated nicotine intake and e-cigarette use characteristics between exclusive EC users and dual users.Design: Web-based anonymous cross-sectional survey.Setting: France.Participants: A total of 3189 adults, current users of electronic cigarettes (EC). Data collection between 4 October 2014 and 11 November 2014.Measurements: Primary outcome: estimated nicotine intake per day (mg) from participants' reports.Secondary outcomes: duration, frequency of EC use and nicotine content of e-liquids used/day. Dual use was defined as using at least one cigarette per day while also using EC.Findings: A total of 2836 respondents reported exclusive EC use and 353 reported being dual users. Backward stepwise logistic regression showed that dual users had higher estimated combined daily nicotine intake from e-liquids and cigarettes [estimate: 2.14, standard error (SE) = 0.26, adjusted odds ratio (aOR) = 8.48, 95% confidence interval (CI) = 5.11-14.09, P < 0.001], but lower daily nicotine intake from EC (estimate: -2.14, SE = 0.26, aOR = 0.12, CI = 0.07-0.196, P < 0.001) and reported fewer months of EC use (estimate: -0.31, SE = 0.14, aOR = 0.73, CI = 0.56-0.95, P = 0.022) compared with exclusive EC users.Conclusion: Dual e-cigarette users in France may have higher nicotine intake overall than exclusive e-cigarette users, but they may take in less nicotine from their e-cigarettes.

International audience; Background: The objective was to explore the role of patient sex in cognitive recovery and to identify predictive factors for non-recovery in alcohol use disorder (AUD). Methods: All patients with AUD admitted to a residential addictions treatment center were systematically assessed at admission and after 6 weeks of abstinence in a controlled environment. The inclusion criteria were that patients were admitted for AUD with baseline alcohol-related cognitive impairment (baseline total Montreal Cognitive Assessment (MoCA) score \textless 26) and reassessed at 6 weeks (n = 395). A logistic regression model was built to determine the influence of sex on recovery status (MoCA \textless or >= 26) taking into account the interaction effect of sex with alcohol consumption on cognitive function. Results: The mean age was 50.10 years (SD = 9.79), and 27.41% were women. At baseline, the mean MoCA scores were 21.36 (SD = 3.04). Participants who did not achieve recovery (59.3% of women vs 53.8% of men) had lower total MoCA scores at baseline. The 2 factors that was significantly and independently associated with non-recovery and with a non-zero coefficient was being a woman and initial MoCA score (respective adjusted odds ratios (AOR) = 1.5 and 0.96, p-values \textless 0.05). Conclusions: These results could influence the time required in a controlled environment to maintain abstinence and the duration of in-care for women.

International audience; The effectiveness of environmental protection measures is based on the early identification and diagnosis of anthropogenic pressures. Similarly, restoration actions require precise monitoring of changes in the ecological quality of ecosystems, in order to highlight their effectiveness. Monitoring the ecological quality relies on bioindicators, which are organisms revealing the pressures exerted on the environment through the composition of their communities. Their implementation, based on the morphological identification of species, is expensive because it requires time and experts in taxonomy. Recent genomic tools should provide access to reliable and high-throughput environmental monitoring by directly inferring the composition of bioindicators' communities from their DNA (metabarcoding). The French-Swiss program SYNAQUA (INTERREG France-Switzerland 2017-2019) proposes to use and validate the tools of environmental genomic for biomonitoring and aims ultimately at their implementation in the regulatory bio-surveillance. SYNAQUA will test the metabarcoding approach focusing on two bioindicators, diatoms, and aquatic oligochaetes, which are used in freshwater biomonitoring in France and Switzerland. To go towards the renewal of current biomonitoring practices, SYNAQUA will (1) bring together different actors: scientists, environmental managers, consulting firms, and biotechnological companies, (2) apply this approach on a large scale to demonstrate its relevance, (3) propose robust and reliable tools, and (4) raise public awareness and train the various actors likely to use these new tools. Biomonitoring approaches based on such environmental genomic tools should address the European need for reliable, higher-throughput monitoring to improve the protection of aquatic environments under multiple pressures, guide their restoration , and follow their evolution.

Introduction Screening of cognitive impairment is a major challenge in alcoholics seeking treatment, since cognitive dysfunction may impair the overall efficacy of rehabilitation programs and consequently increase relapse rate. We compared the performance of two screening tools: the MoCA (Montreal Cognitive Assessment), which is widely used in patients with neurological diseases and already used in patients with alcohol use disorder (AUD), and the BEARNI (Brief Evaluation of Alcohol-Related Neuropsychological Impairments), a recent test specifically developed for the alcoholic population. Methods We compared the sensitivity and specificity of the MoCA and the BEARNI in a sample of AUD patients with and without cognitive impairment assessed by a battery of neuropsychological tests. Results Ninety patients were included. There were 67 men and 23 women aged 48.9 ± 9.6 years. According to the neuropsychological tests, 51.1% of patients had no cognitive impairment, while it was mild or moderate to severe in 31.1 and 17.8%, respectively. The BEARNI sensitivity was extremely high (1.0), since all patients with cognitive impairment were identified, but its specificity was very low (0.04). The MoCA had a lower sensitivity (0.79) than the BEARNI, but its specificity was significantly better (0.65). A detailed analysis of the BEARNI scores showed a discrepancy between the qualitative and quantitative interpretation of the test which could, at least in part, explain its low specificity. Conclusion Both the MoCA and the BEARNI are screening tools which identified alcoholic patients with cognitive impairment. However, in routine use, the MoCA appeared to be more appropriate given the low specificity of the BEARNI.

International audience; BACKGROUND : The Montreal Cognitive Assessment (MoCA) score is a convenient and promising tool for estimating alcoholic patients' global cognitive functioning, a major challenge for all specialized alcohol treatment centers. However, whether or not the score should be corrected for education level and whether the proposed cutoff is relevant in patients with alcohol use disorders (AUD) should be determined.METHODS : We compared the MoCA scores in patients hospitalized for AUD with and without cognitive impairment assessed by a battery of neuropsychological (NP) tests. Sensitivity, specificity, and cutoff of the MoCA score were analyzed using receiver operating characteristic curve analysis.RESULTS : Thirty-one patients with and 25 without cognitive impairment were included in the study. There were 40 men and 16 women, with a mean age of 49.5 years. The mean uncorrected MoCA score was 23.1 ± 3.3 in those with and 27.0 ± 1.9 in those without cognitive impairment. NP tests were significantly correlated with the MoCA score. Uncorrected MoCA scores identified more than 80% of the patients with a cutoff score equal to 26, to obtain similar accuracy with the corrected score required using a cutoff score equal to 27.CONCLUSIONS : Our results confirm that the MoCA test is a convenient and reliable screening tool to measure cognition defects in alcoholic patients. As using the 1-point education adjustment increases the cutoff score by 1 point, it is suggested to use the noncorrected score and the usual cutoff, that is, 26. Being easy to administer and only moderately time-consuming, the MoCA score should be used extensively in addiction treatment centers.

Background The human intestinal microbiota exerts beneficial or harmful effects in several disorders. Many factors, including alcohol consumption, may influence its composition and trigger bacterial translocation. Excessive alcohol consumption increases gut permeability and translocation of endotoxin into peripheral circulation. Although plasma endotoxin concentrations have been measured often, quantitative changes following alcohol withdrawal have never been described in subjects with alcohol use disorder (AUD). The aim of this study was to measure microbial translocation (MT) and gut permeability markers in patients with AUD, to compare these markers to healthy controls (HC) and to monitor markers during the first 6 weeks of abstinence. Methods Sixty-five patients with AUD and hospitalized for alcohol withdrawal were included. Epidemiological, clinical, biological, and addictological data were gathered. Blood samples were collected at baseline, then 3 and 6 weeks after alcohol withdrawal. A hundred healthy volunteers were used as controls. Three markers of MT were monitored in plasma samples: sCD14 and lipopolysaccharide-binding protein (LBP) were quantified using ELISA, and 16S rDNA was quantified using real-time polymerase chain reaction. Zonulin and intestinal fatty acid binding protein (I-FABP) blood levels were also monitored as indirect markers of gut permeability, using ELISA. Results At baseline, LBP, 16S rDNA, sCD14 and I-FABP markers were significantly higher in patients with AUD than in HC. Six weeks after alcohol withdrawal plasma levels of sCD14 and LBP decreased significantly. Cannabis consumption and body mass index (BMI) before alcohol withdrawal influenced baseline MT levels and the decrease in MT markers after 6 weeks. Finally, markers of MT and gut permeability did not correlate with each other before and after alcohol withdrawal. Conclusions Before alcohol withdrawal, MT markers were higher in patients with AUD than in HC. After 6 weeks of abstinence, an improvement in MT markers was observed. Our data suggest that there is a link between MT, its improvement, BMI, and cannabis consumption.

International audience; Liver transplantation (LT) is the gold standard treatment for end-stage liver disease. Whatever the primary indication of LT, substance abuse after surgery may decrease survival rates and quality of life. Prevalence of severe alcohol relapse is between 11 and 26%, and reduces life expectancy regardless of the primary indication of LT. Many patients on waiting lists for LT are smokers and this is a major risk factor for both malignant tumors and cardiovascular events post-surgery. The aim of this review is to describe psychoactive substance consumption after LT, and to assess the impact on liver transplant recipients. This review describes data about alcohol and illicit drug use by transplant recipients and suggests guidelines for behavior management after surgery. The presence of an addiction specialist in a LT team seems to be very important.

International audience; BACKGROUND:Alcohol relapses after liver transplantation (LT) constitute a critical issue. Because there is no widely accepted definition of LT, its prevalence varies from 7 to 95% across studies. Only a severe relapse, the frequency of which is estimated to be 11 to 26%, decreases life expectancy after 5 years of LT and requires specific care. To improve the early identification of alcohol consumption among transplanted patients, liver transplant teams may be helped by input from an addiction team. Nevertheless, added benefit of involvement by addiction specialists in treating posttransplant patients has not been demonstrated. Thus, the aim of this study was to compare the evaluation of the alcohol consumption after LT performed routinely during the transplant consultation or obtained from a specific addiction consultation.METHODS:This was a prospective single-site study. Patients were seen consecutively by their hepatologist and by an addiction specialist, and they completed the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C). Thus, the patient's alcohol status was assessed using 3 different sources of information: the hepatologist's interview, the AUDIT-C score, and the addiction specialist visit.RESULTS:One hundred forty-one patients were consecutively evaluated. Alcohol consumption was identified by the hepatologist in 31 patients (21.9%), in 52 (36.8%) using the AUDIT-C questionnaire, and in 58 (41.1%) by the addiction specialist. The 31 patients concerned reported an average of 6.5 alcohol units/wk to the transplant physician, a number which was significantly greater (p = 0.001) by 8.6 units/wk when they were interviewed by the addiction specialist.CONCLUSIONS:This study highlights the clinical utility of a systematic addiction consultation among liver transplant patients, irrespective of the reason for transplantation.

Excessive alcohol consumption has a modulating effect on immune functions that may contribute to decreased immunity and host defense. It is associated with increased intestinal permeability to endotoxins that is normalized after 14 d of abstinence. Whether and how blood monocyte subsets are impaired in patients with an AUD and what their evolution is after alcohol withdrawal are the paper’s objectives. With the use of flow cytometry, blood monocyte subsets were quantified in AUDs before (n = 40) and 2 wk after (n = 33) alcohol withdrawal and compared with HC donors (n = 20). Expression of TLR2 and TLR4 on monocyte subsets was also quantified. Cytokine response of monocytes was monitored following PGN and LPS stimulation. The CD14+CD16− subset was decreased, whereas the CD14dimCD16+ subset was expanded (P < 0.001) in AUD compared with HC. The frequencies of TLR2- and TLR4-expressing monocytes were reduced in AUD compared with HC. Although the basal production of IL-1, IL-6, and TNF by monocytes in AUD was compared with HC, the PGN- and LPS-mediated IL-6 and TNF production was increased in AUD. Frequencies of IL-6-expressing monocytes were higher in AUD than HC. Alcohol withdrawal partially restored the distribution of monocyte subsets and the frequency of IL-6-producing monocytes and increased the frequency of TNF-producing cells in response to LPS and PGN stimulation to levels compared with those in HC. Our findings indicate that chronic alcohol use alters the distribution as well as the phenotypic and functional characteristics of blood monocyte subsets, which are partially restored following 2 wk of alcohol withdrawal.

International audience; BACKGROUND:Alcoholism is known to be associated with cognitive deficits mainly concerning visuospatial capacity, executive function, memory, and attention. These impairments may affect treatment efficacy which should therefore be adapted. We evaluated the potential utility of the Montreal Cognitive Assessment (MoCA) to evaluate cognitive impairment in a large series of alcoholic patients hospitalized for withdrawal and rehabilitation.METHODS:Consecutive recruitment during a time period of patients admitted to an addiction treatment unit of a teaching hospital. Administration of the MoCA test on admission by trained staff members.RESULTS:A total of 166 patients aged 49.9 ± 9.2 years were included. Mean duration of administration was 20 minutes. The mean MoCA score was 23.5 ± 3.5 and 68.1% had an impaired value (12 years) significantly increased the likelihood of having a high MoCA score.CONCLUSIONS:Owing to their severity and frequency, screening for cognitive deficits is necessary in alcoholics during rehabilitation. MoCA is an appropriate tool for this purpose.

International audience; The author would like to update "Conflicts of Interest" section of their previous publication [1] as follows: Conflicts of Interest Georges Brousse has received sponsorship to attend scientific meetings, speaker honoraria, and consultancy fees from Lundbeck and Merck-Lipha. Patrick Bendimerad received honoraria and travel reimbursements for conferences and consultancy by Lundbeck Laboratory and participated as a coinvestigator.in the multicenter investigational drug studies of Lundbeck. [...].During many years in France, risk reduction strategies for substance abuse concerned prevention strategies in the general population or interventions near users of illicit substances. In this spirit, the reduction of consumption only concerned opiate addicts. With regard to alcohol, the prevention messages relative to controlled consumption were difficult to transmit because of the importance of this product in the culture of the country. In addition, methods of treatment of alcoholism rested on the dogma of abstinence. Several factors have recently led to an evolution in the treatment of alcohol use disorders integrating the reduction of consumption in strategies. Strategies for reducing consumption should aim for consumption below recommended thresholds (two drinks per day for women, three for the men) or, at least, in that direction. It must also be supported by pharmacotherapy and psychotherapy, which offer possibilities. Failure to manage reduction will allow the goals to be revisited and to reconsider abstinence. Finally this evolution or revolution is a new paradigm carried in particular by a pragmatic approach of the disease andnew treatments. The aims of this article are to give elements of comprehension relating to the evolution of the practices in France in prevention and treatment of alcohol use disorders and in particular with regard to the reduction of consumption.

L’examen 2012 du lac du Bourget a confirmé le bon état écologique de l’écosystème pélagique et la continuité de sa progression vers un état oligotrophe. En dépit d’une augmentation marquée au cours des 4 dernières années et en particulier en 2012 des apports en Phosphore particulaire par les principaux tributaires (la Leysse et le Sierroz participant à la même hauteur avec 18-19 tonnes de Ptot transité au lac), les concentrations en Ptot et PO4 dans la colonne d’eau au milieu du lac ont continué de chuter, atteignant des niveaux « record » avec 14 et 10 μg/L, respectivement. Cette baisse de concentration en nutriments ne s’est toutefois pas accompagnée d’une baisse de la biomasse phytoplanctonique qui au contraire a augmenté significativement en 2012 (d’un peu plus de 20%). A l’exception du développement de l’espèce Scenedesmus (plutôt caractéristique des milieux riches en nutriments) en début de printemps, la composition phytoplanctonique a été dominée par des diatomées, des chrysophycées et des cryptophycées avec des espèces (notamment mixotrophes) plutôt caractéristiques de milieux oligotrophes. Pour la première fois aucune cyanobactérie filamenteuse (et susceptible d’être toxique) n’a été détectée en 2012 (en 2009 Planktothrix et Microcystis étaient présentes, en 2011 Aphanizomenom avait été détectée). Au cours des 4 dernières années, de manière concommitante à la disparition de P. rubescens, la proportion des formes nanophytoplanctoniques a augmenté de manière quasi exponentielle atteignant en 2012 la valeur de 43% (proportion comparable à ce qui est enregistré au lac d’Annecy). La proportion des formes picophytoplanctoniques (dominées par les picocyanobactéries du genre Synechococcus) est également en augmentation corroborant la réoligotrophisation marquée de l’écosystème. La biomasse du peuplement zooplanctonique a été très élevée en 2012 avec une très forte dominance des Daphnies, responsable d’une importante phase des eaux claires entre fin mai et début juin. Un événement remarquable a toutefois été constaté, l’absence du second pic de production observée généralement en fin d’été, probablement lié aux mauvaises conditions météorologiques enregistrées à cette période. Au cours des dernières années, il a été constaté que le groupe des calanides a régréssé alors qu’il est plutôt caractéristique de milieux en bonne santé. Si ce phénomène n’est pas encore complètement expliqué, il n’en reste pas moins que la dynamique zooplanctonique reste typique d’un milieu oligomésotrophe. De plus, le rapport entre les abondances zooplanctoniques et biomasses phytoplanctoniques suggère que le lac du Bourget est caractérisé par une bonne efficience trophique et ce surtout depuis la disparition, fin 2009, de P. rubescens. En lien avec (i) la restauration de l’écosystème, (ii) un changement dans la pratique de pêche (i.e. la modification de la maille des filets) et (iii) de manière concommitante à la disparition de P. rubescens, le peuplement de poissons du lac du Bourget est dans un état très satisfaisant avec la confirmation d’un stock élevé de corégones (lavarets) qui atteint en 2012 un rendement record. L’amélioration significative de l’état trophique du lac du Bourget observé depuis les 3 dernières années est donc renforcée à présent par la réponse du compartiment biologique supérieur, avec le retour emblématique du lavaret. L’ensemble des paramètres limnologiques classiques mesuré au cours de l’année 2012 (transparence, chlorophylle a, Phosphore total) mais également bon nombre d’autres descripteurs (composition et taille phytoplanctoniques, biomasse et dynamique zooplanctoniques, peuplement piscicole) permettent de confirmer que l’état et le fonctionnement pélagique du lac du Bourget est bon à très bon (ce qui est aussi corroboré par l’excellente qualité sanitaire) et qu’il peut-être classé comme étant oligo-mésotrophe. Toutefois, l’analyse du peuplement des macroinvertébrés du lac a révélé que ce dernier se caractérise encore par une quantité de matière organique trop importante, qui s’accumule dans les substrats fins de la zone littorale du lac. Cette dernière se traduit par des activités de consommation et de dégradation importantes conduisant à des conditions hypoxiques. Au fond du lac, les faibles abondances et diversité de ce peuplement benthique témoignent également d’un dysfonctionnement caractérisé par une accumulation de matière organique non transférée au sein des réseaux trophiques du lac du Bourget et dont l’hypolimnion présente encore des hypoxies voire des anoxies.

We monitored in fifty individuals with chronic hepatitis C (CHC) the expression of CCR5 and CXCR3, two chemokine receptors involved in the intra-hepatic recruitment of T cells, at the surface of circulating CD4 + T cells. The percentage of CD4 + T cells expressing CCR5 and/or CXCR3 was increased in patients. The increased percentage of CD4 + CXCR3 + T lymphocytes was linked to serum level of aspartate aminotransferase (AST) and to fibrosis METAVIR score. CD4 + T cell surface CCR5 and CXCR3 densities increased after 6 months of treatment with pegylated interferon-α and ribavirin. The pre-therapeutic percentage of CD4 + CXCR3 + T cells was correlated with alanine aminotransferase serum level at 12 months, and viral load at 24 months after treatment initiation. Thus, in CHC we observed a high CXCR3 expression on peripheral blood CD4 + T cells which correlates with AST serum level and liver fibrosis, and is predictive of the response to treatment.

International audience; Samples were collected at four depths every 6 h over a 42-h period during two contrasting seasons (June vs. December) from Lake Bourget, France, for evidence of circadian fluctuations in the concentrations and potential activities of viruses, prokaryotes and protists in relation to environmental conditions: temperature, chlorophyll a and dissolved organic carbon (DOC) concentrations. Considerable vertical and temporal fluctuations were observed for all variables. Circadian variations were noted for DOC and chlorophyll a concentrations. Despite the external abiotic forcing (light, water movements), the fluctuations of microbial variables (including viruses) in most cases were apparently linked to biotic factors and interactions. Standing stocks and activities, as well as the number and levels of correlations among the microbial components, were, surprisingly, higher in winter than in summer. We speculate that this was because trophic interactions prevailed over the seasonal forcing (i.e. temperature) in shaping the observed differences.

National audience