Homeless drug users' awareness and risk perception of peer "Take Home Naloxone" use – a qualitative study

BACKGROUND Peer use of take home naloxone has the potential to reduce drug related deaths. There appears to be a paucity of research amongst homeless drug users on the topic. This study explores the acceptability and potential risk of peer use of naloxone amongst homeless drug users. From the findings the most feasible model for future treatment provision is suggested. METHODS In depth face-to-face interviews conducted in one primary care centre and two voluntary organisation centres providing services to homeless drug users in a large UK cosmopolitan city. Interviews recorded, transcribed and analysed thematically by framework techniques. RESULTS Homeless people recognise signs of a heroin overdose and many are prepared to take responsibility to give naloxone, providing prior training and support is provided. Previous reports of the theoretical potential for abuse and malicious use may have been overplayed. CONCLUSION There is insufficient evidence to recommend providing "over the counter" take home naloxone" to UK homeless injecting drug users. However a programme of peer use of take home naloxone amongst homeless drug users could be feasible providing prior training is provided. Peer education within a health promotion framework will optimise success as current professionally led health promotion initiatives are failing to have a positive impact amongst homeless drug users

High-Content Chemical and RNAi Screens for Suppressors of Neurotoxicity in a Huntington's Disease Model

To identify Huntington's Disease therapeutics, we conducted high-content small molecule and RNAi suppressor screens using a Drosophila primary neural culture Huntingtin model. Drosophila primary neurons offer a sensitive readout for neurotoxicty, as their neurites develop dysmorphic features in the presence of mutant polyglutamine-expanded Huntingtin compared to nonpathogenic Huntingtin. By tracking the subcellular distribution of mRFP-tagged pathogenic Huntingtin and assaying neurite branch morphology via live-imaging, we identified suppressors that could reduce Huntingtin aggregation and/or prevent the formation of dystrophic neurites. The custom algorithms we used to quantify neurite morphologies in complex cultures provide a useful tool for future high-content screening approaches focused on neurodegenerative disease models. Compounds previously found to be effective aggregation inhibitors in mammalian systems were also effective in Drosophila primary cultures, suggesting translational capacity between these models. However, we did not observe a direct correlation between the ability of a compound or gene knockdown to suppress aggregate formation and its ability to rescue dysmorphic neurites. Only a subset of aggregation inhibitors could revert dysmorphic cellular profiles. We identified lkb1, an upstream kinase in the mTOR/Insulin pathway, and four novel drugs, Camptothecin, OH-Camptothecin, 18β-Glycyrrhetinic acid, and Carbenoxolone, that were strong suppressors of mutant Huntingtin-induced neurotoxicity. Huntingtin neurotoxicity suppressors identified through our screen also restored viability in an in vivo Drosophila Huntington's Disease model, making them attractive candidates for further therapeutic evaluation.National Institutes of Health (U.S.) (grant R01 EB007042)National Institutes of Health (U.S.

Effect of long-term fertilisation on the weed community of a winter wheat field

Abstract Effects of fertilisation and other management techniques on a weed community were evaluated during wheat growth in a rice-wheat cropping system. Fertiliser treatments were C0 (C means chemical, C0 means zero chemical fertiliser.), CN (N fertiliser), CNK (N plus K fertiliser), CNPK (N plus P and K fertiliser), CNP (N plus P fertiliser), and CPK (P plus K fertiliser). Weed density, biomass, and bio-diversity were determined. Redundancy analysis (RDA) was used to investigate the relationship between fertiliser management, weed species, and weed density. The overall weed densities in the C0 and CPK treatments were the greatest during wheat seeding and ripening periods and were significantly greater than densities in the other treatments. N, P and organic matter in soil were highly correlated with weed species and density, whereas K in soil was not significantly correlated with weed species and weed density. N fertiliser significantly reduced weed density. Balanced fertilisation maintained weed species richness and resulting in a high yield of wheat. CNPK application reduced weed damage and improved the productivity and stability of the farmland ecosystem

Mutual Mistrust in the Medical Care of Drug Users: The Keys to the “Narc” Cabinet

OBJECTIVE: Caring for patients who are active drug users is challenging. To better understand the often difficult relationships between illicit drug–using patients and their physicians, we sought to identify major issues that emerge during their interactions in a teaching hospital. DESIGN: Exploratory qualitative analysis of data from direct observation of patient care interactions and interviews with drug-using patients and their physicians. SETTING: The inpatient internal medicine service of an urban public teaching hospital. PARTICIPANTS: Nineteen patients with recent active drug use, primarily opiate use, and their 8 physician teams. RESULTS: Four major themes emerged. First, physicians feared being deceived by drug-using patients. In particular, they questioned whether patients' requests for opiates to treat pain or withdrawal might result from addictive behavior rather than from “medically indicated” need. Second, they lacked a standard approach to commonly encountered clinical issues, especially the assessment and treatment of pain and opiate withdrawal. Because patients' subjective report of symptoms is suspect, physicians struggled to find criteria for appropriate opiate prescription. Third, physicians avoided engaging patients regarding key complaints, and expressed discomfort and uncertainty in their approach to these patients. Fourth, drug-using patients were sensitive to the possibility of poor medical care, often interpreting physician inconsistency or hospital inefficiency as signs of intentional mistreatment. CONCLUSION: Physicians and drug-using patients in the teaching hospital setting display mutual mistrust, especially concerning opiate prescription. Physicians' fear of deception, inconsistency and avoidance interacts with patients' concern that they are mistreated and stigmatized. Medical education should focus greater attention on addiction medicine and pain management

Structural basis of the Axin–adenomatous polyposis coli interaction

Axin and the adenomatous polyposis coli (APC) tumor suppressor protein are components of the Wnt/Wingless growth factor signaling pathway. In the absence of Wnt signal, Axin and APC regulate cytoplasmic levels of the proto-oncogene β-catenin through the formation of a large complex containing these three proteins, glycogen synthase kinase 3β (GSK3β) and several other proteins. Both Axin and APC are known to be critical for β-catenin regulation, and truncations in APC that eliminate the Axin-binding site result in human cancers. A protease-resistant domain of Axin that contains the APC-binding site is a member of the regulators of G-protein signaling (RGS) superfamily. The crystal structures of this domain alone and in complex with an Axin-binding sequence from APC reveal that the Axin–APC interaction occurs at a conserved groove on a face of the protein that is distinct from the G-protein interface of classical RGS proteins. The molecular interactions observed in the Axin–APC complex provide a rationale for the evolutionary conservation seen in both proteins