A machine-learned analysis of human gene polymorphisms modulating persisting pain points to major roles of neuroimmune processes

Background Human genetic research has implicated functional variants of more than one hundred genes in the modulation of persisting pain. Artificial intelligence and machine-learning techniques may combine this knowledge with results of genetic research gathered in any context, which permits the identification of the key biological processes involved in chronic sensitization to pain. MethodsResultsBased on published evidence, a set of 110 genes carrying variants reported to be associated with modulation of the clinical phenotype of persisting pain in eight different clinical settings was submitted to unsupervised machine-learning aimed at functional clustering. Subsequently, a mathematically supported subset of genes, comprising those most consistently involved in persisting pain, was analysed by means of computational functional genomics in the Gene Ontology knowledgebase. Clustering of genes with evidence for a modulation of persisting pain elucidated a functionally heterogeneous set. The situation cleared when the focus was narrowed to a genetic modulation consistently observed throughout several clinical settings. On this basis, two groups of biological processes, the immune system and nitric oxide signalling, emerged as major players in sensitization to persisting pain, which is biologically highly plausible and in agreement with other lines of pain research. ConclusionsSignificanceThe present computational functional genomics-based approach provided a computational systems-biology perspective on chronic sensitization to pain. Human genetic control of persisting pain points to the immune system as a source of potential future targets for drugs directed against persisting pain. Contemporary machine-learned methods provide innovative approaches to knowledge discovery from previous evidence. We show that knowledge discovery in genetic databases and contemporary machine-learned techniques can identify relevant biological processes involved in Persitent pain.Peer reviewe

Design and Synthesis of Fluoro Analogues of Vitamin D

The discovery of a large variety of functions of vitamin D3 and its metabolites has led to the design and synthesis of a vast amount of vitamin D3 analogues in order to increase the potency and reduce toxicity. The introduction of highly electronegative fluorine atom(s) into vitamin D3 skeletons alters their physical and chemical properties. To date, many fluorinated vitamin D3 analogues have been designed and synthesized. This review summarizes the molecular structures of fluoro-containing vitamin D3 analogues and their synthetic methodologies

Flow experience enhances the effectiveness of attentional training: A pilot randomized controlled trial of patients with attention deficits after traumatic brain injury

BACKGROUND: Flow is an optimal psychological state when people engage in a training task, and it is a theory explaining the absorbed state. OBJECTIVE: To investigate the additional effect of flow on attention deficits for chronic patients after traumatic brain injury. METHODS: Twenty patients were randomly assigned to the flow group (n = 10) or the control group. Patients performed a video game task, one inducing flow (flow group) and the other not (control group) for 4 weeks, and they were assessed with the flow state scale for occupational tasks (FSSOT) regularly and neuropsychological tests at baseline, after intervention, and at 4 weeks after intervention (follow-up). RESULTS: Although both groups significantly improved their attentional function after intervention, patients in the flow group tended to show more improvement of attention. The effect size of the neuropsychological test of attention was positive, and its value was small to medium. There was a significant positive correlation between improvement of attention and the FSSOT score. CONCLUSIONS: Attention training with induction of the flow was associated with greater improvement of attention. The results of this study may provide provisional evidence of the effectiveness of rehabilitation considering the patient's psychological state