Diffusion tensor imaging tractography in the one-humped camel (Camelus dromedarius) brain.

Introduction: Tractography is a technique used to trace the pathways of the brain using noninvasive diffusion tensor imaging (DTI) data. It is becoming increasingly popular for investigating the brains of domestic mammals and other animals with myelinated fibers but the principle of DTI can also apply for those with unmyelinated fibers. In the case of camels, DTI tractography is a promising method for enhancing current knowledge of the brain's structural connectivity and identifying white-matter tract changes potentially linked to neurodegenerative pathologies. The present study was therefore designed to describe representative white-matter tracts in the one-humped camel DTI tractography. Methods: Post mortem DTI was used to obtain images of two one-humped camel brains using a 3 Tesla system. T2-weighted images were also acquired to identify regions of interest for each fiber tract and a fiber dissection technique was used to complement the DT images. The main association, commissural, and projection fibers were reconstructed and superimposed on T2-weighted images or fractional anisotropy maps. Results: The results of the present study show the reconstruction of the most representative tracts, ie the cingulum, the corpus callosum and the internal capsule, in the one-humped camel brain using DTI data acquired post mortem. These DTI results were compared to those from fiber dissection. Discussion: Anatomy of the cingulum, corpus callosum and internal capsule correlates well with the description in anatomical textbooks and appears to be similar to fibers describe in large animals. Further research will be required to improve and validate these findings and to generate a tractography atlas based on MRI and histological data, as such an atlas would be a valuable resource for future neuroimaging research.

Between zero risk and harm reduction: An ethnography of Montreal supervised injection services as a public policy instrument.

BACKGROUND: While much has been written about the positive individual and collective effects of Supervised injection services (SIS), notably on health and drug-related harm, little research focuses on their operational context and constraints. Building on Lascoumes and Le Gales's "public policy instrument and instrumentation" framework (2007), this article analyzes the implementation of Montreal SIS and discusses how the organizational aspects of SIS produce the contexts for drug injection. METHODS: Using an ethnographic approach, this article draws on three types of data: 10 months of participant observation in a SIS (700 h); 19 semi-structured interviews with staff members (social workers, peers, heads of staff, management); and analysis of organizational documents (protocols, staff notebooks). RESULTS: First, this article examines how political context and advocacy coalitions produced Montreal SIS as a public policy instrument, affecting both the philosophy and the implementation of the service. It shows that Montreal SIS were developed under a health care network blueprint rather than a community organization harm reduction framework. Then, it analyzes how SIS as a policy instrument defines what constitutes appropriate injection practices, trying to supervise injection as an individual and technical act, rather than a broader social practice composed of pleasure, rituals, routines, and group dynamics. CONCLUSION: Montreal SIS were conceptualized under a "health banner" and through alliances between regional public health administration and local well-known community organizations. They were then developed mostly under a health care administration blueprint, although operated at a ground-level by local community organizations. It created tensions between the logics of "zero risk" and "harm reduction", and ambiguity about how injection should be supervised and what parts of drug use could be managed.

Escaping from Flatland: Substituted Bridged Pyrrolidine Fragments with Inherent Three-Dimensional Character.

The pressure to deliver new medicines to the patient continues to grow along with increases in compound failure rate, thus putting the current R&D model at risk. Analysis has shown that increasing the three-dimensionality of potential drug candidates decreases the risk of failure and improves binding selectivity and frequency. For this reason many workers have taken a new look at the power of photochemistry as a means to generate novel sp3 rich scaffolds for use in drug discovery programs. Here we report the design, synthesis, and computational structural analysis of a series of 2,4-methanoprolines having inherent 3D character (PMI and PBF scores) significantly higher than that of the broader AbbVie Rule of 3 (Ro3) collection.

The Synthesis of Waltherione F and Its Analogues with Modifications at the 2- and 3-Positions as Potential Antitrypanosomal Agents.

Chagas disease also know as American Trypanosomiasis (AT) is a tropical parasitic disease endemic in South America, is caused by Trypanosoma cruzi, which is transmitted by the blood-sucking insect vectors called triatomine bugs. Quinoline alkaloids from the root extract of Waltheria indica are known to possess antitrypanosomal activity. Waltherione F, one of those alkaloids, was synthesised in 5 steps in 11 % overall yield. We report here the first X-ray crystallographic confirmation of the structure of Waltherione F 3. A key step in the sequence utilised the Conrad-Limpach synthesis for the formation of the quinolin-4(1H)-one ring system. Our synthetic strategy was designed to enable the modification of the 2- and 3-positions of the scaffold, allowing the generation of a diverse library of analogues to support our on-going medicinal chemistry program that is looking for new agents to tackle this devastating disease.