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Fostering Insight and Collaboration in Long-Term Healthcare through Collection and Visualization of Qualitative Healthcare Data

The Care and Condition Monitor (CCM) is a tablet-based, networked visual analytics tool for collecting, structuring and analyzing informal and qualitative healthcare data. Building off research into application usability and best practices for communicating complex information, CCM illustrates how visual analytics tools coupled with social communication within teams of caregivers enables capturing of longitudinal informal data that would otherwise go unrecorded. This expanded scope of information can support medical decision making by making it possible to analyze informal and qualitative health care data,creating a multi-dimensional holistic picture of a person‟s health care and condition over time

PPARG SIGNALING IN THE NUCLEUS ACCUMBENS REGULATES MESOLIMBIC DOPAMINE ACTIVITY

Background: The mesolimbic dopamine system consists of dopamine neuron projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc). The NAc regulates VTA dopamine release through inhibitory GABA projections to the VTA. Hyperactive mesolimbic dopamine signaling is implicated in anxiety. Cannabidiol, a compound found in cannabis, demonstrates promising therapeutic potential for anxiety through the regulation of the mesolimbic dopamine system. Previous studies have revealed that cannabidiol infusions into the NAc decreases mesolimbic dopamine activity - potentially through the inhibitory GABA signaling to the VTA. However, the receptor mechanism in the NAc through which CBD produces its effects is unknown. Peroxisome proliferator-activated receptor gamma (PPARG) is a nuclear transcription factor that binds to CBD and colocalizes with GABA neurons. Recent evidence suggests that PPARG activation can decrease mesolimbic dopamine activity through inhibitory GABA signaling. Considering that the NAc expresses high levels of PPARG, intra-NAc CBD may regulate mesolimbic dopamine activity through PPARG activation. Hypothesis: PPARG activation in the NAc regulates mesolimbic dopamine transmission through the modulation of the GABAergic inhibition of the VTA. Methods: In-vivo electrophysiology was used to investigate the effects of intra-NAc PPARG activation on mesolimbic dopamine activity. The anxiolytic effects of intra-NAc PPARG activation was measured using the light-dark box and elevated plus maze behavioural tests. Results: We report that PPARG activation in the NAc significantly decreases mesolimbic dopamine activity whereas PPARG antagonists block this effect. Additionally, we reveal that intra-NAc PPARG activation produces anxiolytic effects as measured in the light-dark box and elevated plus maze behavioural tests

Three classes of ligands each bind to distinct sites on the orphan G protein-coupled receptor GPR84

Medium chain fatty acids can activate the pro-inflammatory receptor GPR84 but so also can molecules related to 3,3′-diindolylmethane. 3,3′-Diindolylmethane and decanoic acid acted as strong positive allosteric modulators of the function of each other and analysis showed the affinity of 3,3′-diindolylmethane to be at least 100 fold higher. Methyl decanoate was not an agonist at GPR84. This implies a key role in binding for the carboxylic acid of the fatty acid. Via homology modelling we predicted and confirmed an integral role of arginine172, located in the 2nd extracellular loop, in the action of decanoic acid but not of 3,3′-diindolylmethane. Exemplars from a patented series of GPR84 antagonists were able to block agonist actions of both decanoic acid and 3,3′-diindolylmethane at GPR84. However, although a radiolabelled form of a related antagonist, [3H]G9543, was able to bind with high affinity to GPR84, this was not competed for by increasing concentrations of either decanoic acid or 3,3′-diindolylmethane and was not affected adversely by mutation of arginine172. These studies identify three separable ligand binding sites within GPR84 and suggest that if medium chain fatty acids are true endogenous regulators then co-binding with a positive allosteric modulator would greatly enhance their function in physiological settings