Psychometric properties of the transaddiction craving triggers questionnaire in alcohol use disorder.

We aimed to develop the transaddiction craving triggers questionnaire (TCTQ), which assesses the propensity of specific situations and contexts to trigger craving and to test its psychometric properties in alcohol use disorder (AUD). This study included a sample of 111 AUD outpatients. We performed exploratory factor analysis (EFA) and calculated item-dimension correlations. Internal consistency was measured with Cronbach's alpha coefficient. Construct validity was assessed through Spearman correlations with craving, emotional symptoms, impulsivity, mindfulness, and drinking characteristics. The EFA suggested a 3-factor solution: unpleasant affect, pleasant affect, and cues and related thoughts. Cronbach's coefficient alpha ranged from .80 to .95 for the three factors and the total score. Weak positive correlations were identified between the TCTQ and drinking outcomes, and moderate correlation were found between the TCTQ and craving strength, impulsivity, anxiety, depression, and impact of alcohol on quality of life. The 3-factor structure is congruent with the well-established propensity of emotions and cues to trigger craving. Construct validity is supported by close relations between the TCTQ and psychological well-being rather than between the TCTQ and drinking behaviors. Longitudinal validation is warranted to assess sensitivity to change of the TCTQ and to explore its psychometric properties in other addictive disorders

Giving room to subjectivity in understanding and assessing problem gambling: A patient-centered approach focused on quality of life

Background and aims: Problem gambling is characterized by high stigma and self-stigma, making relevant measurement of the burden of the disorder complex. The aim of our qualitative study was to describe health-related quality of life (HRQOL) impacted by problem gambling from the patients’ perspective. Methods: We conducted 6 focus groups with 25 current or lifetime at-risk problem gamblers to identify key domains of quality of life impacted by problem gambling. A content analysis from the focus groups data was conducted using Alceste© software, using descendant hierarchical classification analysis, to obtain stable classes and the significant presences of reduced forms. The class of interest, detailing the core of impacted quality of life, was described using a cluster analysis. Results: Thematic content analysis identified three stable classes. Class 1 contained the interviewers’ speech. Class 3 was composed of the vocabulary related to gambling practice, games and gambling venues (casino, horse betting, etc.). Class 2 described the core of impact of gambling on quality of life and corresponded to 43% of the analyzed elementary context units. This analysis revealed seven key domains of impact of problem gambling: loneliness, financial pressure, relationships deterioration, feeling of incomprehension, preoccupation with gambling, negative emotions, and avoidance of helping relationships. Conclusions: We identified, beyond objective damage, the subjective distress felt by problem gamblers over the course of the disorder and in the helping process, marked in particular by stigma and self-stigma. Four impacted HRQOL areas were new and gambling-specific: loneliness, feeling of incomprehension, avoidance of helping relationships, and preoccupation with gambling. These results support the relevance of developing, in a next step, a specific HRQOL scale in the context of gambling

Regulation of differentiation of nitrogen-fixing bacteria by microsymbiont targeting of plant thioredoxin s1

Legumes associate with rhizobia to form nitrogen (N2)-fixing nodules, which is important for plant fitness [1, 2]. Medicago truncatula controls the terminal differentiation of Sinorhizobium meliloti into N2-fixing bacteroids by producing defensin-like nodule-specific cysteine-rich peptides (NCRs) [3, 4]. The redox state of NCRs influences some biological activities in free-living bacteria, but the relevance of redox regulation of NCRs in planta is unknown [5, 6], although redox regulation plays a crucial role in symbiotic nitrogen fixation [7, 8]. Two thioredoxins (Trx), Trx s1 and s2, define a new type of Trx and are expressed principally in nodules [9]. Here, we show that there are four Trx s genes, two of which, Trx s1 and s3, are induced in the nodule infection zone where bacterial differentiation occurs. Trx s1 is targeted to the symbiosomes, the N2-fixing organelles. Trx s1 interacted with NCR247 and NCR335 and increased the cytotoxic effect of NCR335 in S. meliloti. We show that Trx s silencing impairs bacteroid growth and endoreduplication, two features of terminal bacteroid differentiation, and that the ectopic expression of Trx s1 in S. meliloti partially complements the silencing phenotype. Thus, our findings show that Trx s1 is targeted to the bacterial endosymbiont, where it controls NCR activity and bacteroid terminal differentiation. Similarly, Trxs are critical for the activation of defensins produced against infectious microbes in mammalian hosts. Therefore, our results suggest the Trx-mediated regulation of host peptides as a conserved mechanism among symbiotic and pathogenic interactions

Enhanced Brain Disposition and Effects of Δ9-Tetrahydrocannabinol in P-Glycoprotein and Breast Cancer Resistance Protein Knockout Mice

The ABC transporters P-glycoprotein (P-gp, Abcb1) and breast cancer resistance protein (Bcrp, Abcg2) regulate the CNS disposition of many drugs. The main psychoactive constituent of cannabis Δ9-tetrahydrocannabinol (THC) has affinity for P-gp and Bcrp, however it is unknown whether these transporters modulate the brain accumulation of THC and its functional effects on the CNS. Here we aim to show that mice devoid of Abcb1 and Abcg2 retain higher brain THC levels and are more sensitive to cannabinoid-induced hypothermia than wild-type (WT) mice. Abcb1a/b (−/−), Abcg2 (−/−) and wild-type (WT) mice were injected with THC before brain and blood were collected and THC concentrations determined. Another cohort of mice was examined for THC-induced hypothermia by measuring rectal body temperature. Brain THC concentrations were higher in both Abcb1a/b (−/−) and Abcg2 (−/−) mice than WT mice. ABC transporter knockout mice exhibited delayed elimination of THC from the brain with the effect being more prominent in Abcg2 (−/−) mice. ABC transporter knockout mice were more sensitive to THC-induced hypothermia compared to WT mice. These results show P-gp and Bcrp prolong the brain disposition and hypothermic effects of THC and offer a novel mechanism for both genetic vulnerability to the psychoactive effects of cannabis and drug interactions between CNS therapies and cannabis

Decreased Reward Sensitivity in Rats from the Fischer344 Strain Compared to Wistar Rats Is Paralleled by Differences in Endocannabinoid Signaling

BACKGROUND: The aim of the present study was to examine if differences in the endocannabinoid (ECB) system might be linked to strain specific variations in reward-related behavior in Fischer344 (Fischer) and Wistar rats. METHODOLOGY/PRINCIPAL FINDINGS: Two rat strains, the Fischer and the Wistar strain, were tested for different aspects of reward sensitivity for a palatable food reward (sweetened condensed milk, SCM) in a limited-access intake test, a progressive ratio (PR) schedule and the pleasure-attenuated startle (PAS) paradigm. Additionally, basic differences in the ECB system and cannabinoid pharmacology were examined in both rat strains. Fischer rats were found to express lower reward sensitivity towards SCM compared to Wistar rats. These differences were observed for consummatory, motivational and hedonic aspects of the palatable food reward. Western blot analysis for the CB1 receptor and the ECB degrading enzyme fatty acid amide hydrolase (FAAH) revealed a lower expression of both proteins in the hippocampus (HPC) of Fischer rats compared to the Wistar strain. Furthermore, increased cannabinoid-stimulated extracellular-regulated kinase (ERK) phosphorylation was detected in Wistar rats compared to the Fischer strain, indicating alterations in ECB signaling. These findings were further supported by the pharmacological results, where Fischer rats were found to be less sensitive towards the effects of the CB1 receptor antagonist/inverse agonist SR141716 and the cannabinoid agonist WIN 55,212-2. CONCLUSIONS/SIGNIFICANCE: Our present findings indicate differences in the expression of the CB1 receptor and FAAH, as well as the activation of ECB signaling pathways between Fischer and Wistar rats. These basic differences in the ECB system might contribute to the pronounced differences observed in reward sensitivity between both rat strains

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac