The knowledge of metabolic profile of synthetic cannabinoids is important for the detection of the drugs in urinalysis due to the typical absence or low abundance of parent cannabinoids in human urine. The fungus Cunninghamella elegans has been reported to be a useful tool for metabolism study and thus applicability to synthetic cannabinoids metabolism was examined. In this study, 8-quinolinyl 1-(5-fluoropentyl)-1H-indole-3-carboxylate (5F-PB-22), 8-quinolinyl 1-pentyl-1H-indole-3-carboxylate (PB-22), [1-(5-fluoropentyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone (XLR-11) and (1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone (UR-144) were incubated with Cunninghamella elegans and the metabolites were identified using liquid chromatographyquadrupole time-of-flight mass spectrometry. The obtained metabolites were compared with reported human metabolites to assess the suitability of the fungus to extrapolate human metabolism. 5F-PB-22 underwent, dihydroxylation, dihydrodiol formation, oxidative defluorination, oxidative defluorination to carboxylic acid, ester hydrolysis and glucosidation, alone and/or in combination. The metabolites of PB-22 were generated by hydroxylation, dihydroxylation, trihydroxylation, dihydrodiol formation, ketone formation, carboxylation, ester hydrolysis and glucosidation, alone and/or in combination. XLR-11 was transformed through hydroxylation, dihydroxylation, aldehyde formation, carboxylation, oxidative defluorination, oxidative defluorination to carboxylic acid and glucosidation, alone and/or in combination. UR-144 was metabolised by hydroxylation, dihydroxylation, trihydroxylation, aldehyde formation, ketone formation, carboxylation, N-dealkylation and combinations. These findings were consistent with previously reported human metabolism except for the small extent of ester hydrolysis observed and absence of glucuronidation. Despite the limitations, Cunninghamella elegans demonstrated the capacity to produce a wide variety of metabolites including some major human metabolites of XLR-11 and UR-144 at high abundance, showing the potential for metabolism of newly emerging synthetic cannabinoids.

BackgroundIn 2006, the British government launched ‘Improving Access to Psychological Therapies’ (IAPT), a low intensity cognitive behaviour therapy intervention (LiCBT) designed to manage people with symptoms of anxiety and depression in the community. The evidence of the effectiveness of IAPT has been demonstrated in multiple studies from the UK, USA, Australia and other countries. MindStep™ is the first adaptation of IAPT in Australia, delivered completely by telephone, targeting people with a recent history of a hospital admission for mental illnesses within the private health system. This paper reports on the outcome of the first 17 months of MindStep™ implemented across Australia from March 2016.MethodsThis prospective observational study investigated the MindStep™ program in a cohort of clients with a recent hospitalisation for mental illnesses. The study used quantitative methods to compare pre-post treatment clinical measures (N = 680) using Patient Health Questionnaire (PHQ-9) and the Generalised Anxiety Disorder (GAD-7). This study also included in-depth interviews with participants (N = 14) and coaches (N = 4) to determine the feasibility and acceptability of the program.ResultsOf the 867 clients referred to MindStep™, 757 had initial assessments by phone making an enrolment rate of 87.3%. Following assessment, 680 commenced treatment and of them, 427 (62.7%) completed treatment. According to ‘per-protocol’ analysis (N = 427), there was a large effect size for post-treatment PHQ-9 (d = 1.03) and GAD-7 (d = 0.99) scores; reliable recovery rate was 62% (95% CI: 57–68%). For intent-to-treat analysis using multiple imputation (N = 680), effect sizes were also large for pre-post treatment change: PHQ-9 (d = 0.78) and GAD-7 (d = 0.76). The reliable recovery rate was 49% (95% CI: 45–54%). Qualitative findings supported these claims where participants were positive about MindStep™ and found the telephone delivery and use of mental health coaches highly acceptable.ConclusionsMindStep™ has demonstrated encouraging outcomes that suggest LiCBT can be successfully delivered to people with a history of hospital admissions for anxiety and depressive disorders and achieve target recovery rates of > 50%. Other promising evaluation findings indicate the MindStep™ option is acceptable, feasible and safe within the stepped models of mental health care delivery in Australia.Electronic supplementary materialThe online version of this article (10.1186/s12888-018-1987-1) contains supplementary material, which is available to authorized users.

Objective: Some HIV+ patients, virally suppressed on ART, show occasional ‘blips’ of detectable HIV-1 plasma RNA. We used a new highly sensitive assay of cell-associated HIV-1 RNA to measure transcriptional activity in PBMCs and production of infectious virus from the viral reservoir, in patients with and without ‘blips’. Design/methods: RNA and DNA extracted from cells in 6 ml of peripheral blood, from suppressed patients with one to two ‘blip’ episodes over the past 2 years of ART ( n = 55), or no ‘blips’ ( n = 52), were assayed for HIV-1 RNA transcripts and proviral DNA targeting the highly conserved ‘R’ region of the LTR. Follow-up samples were also collected. Purified CD4 + T cells were cultured with anti-CD3/CD28/CD2 T-cell activator to amplify transcription and measure replication competent virus. Results: HIV-1 RNA transcripts ranged from 1.3 to 5415 copies/10 6 white blood cells. ‘Blip’ patients had significantly higher levels vs. without blips (median 192 vs. 49; P = 0.0007), which correlated with: higher levels of inducible transcripts after activation in vitro , sustained higher HIV-1 transcription levels in follow-up samples along with increasing HIV-1 DNA in some, and production of replication-competent HIV-1. Conclusion: Viral ‘blips’ are significant reflecting higher transcriptional activity from the reservoir and contribute to the reservoir over time. This sensitive assay can be used in monitoring the size and activity of the HIV-1 reservoir and will be useful in HIV-1 cure strategies.

Background: "Smoke-Free" legislation prohibiting smoking in all enclosed public places was introduced in March 2006. This qualitative study presents insights from bar workers about their observations of the changing social bar environment, changing patrons' behaviours and challenges bar workers have faced in managing smoke-free legislation.

No abstract