24 research outputs found
Transurethral Ureteroscopy: Is Local Anesthesia with Intravenous Sedation Sufficiently Effective and Safe?
Objective and Subjective Comparison of Transurethral Resection, Transurethral Incision and Balloon Dilatation of the Prostate
Human Umbilical Cord Blood Cells Protect Against Hypothalamic Apoptosis and Systemic Inflammation Response During Heatstroke in Rats
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Endocannabinoid dysfunction in neurological disease: neuro-ocular DAGLA-related syndrome
The endocannabinoid system is a highly conserved and ubiquitous signalling pathway with broad-ranging effects. Despite critical pathway functions, gene variants have not previously been conclusively linked to human disease. We identified nine children from eight families with heterozygous, de novo truncating variants in the last exon of DAGLA with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. All children displayed paroxysms of nystagmus or eye deviation accompanied by compensatory head posture and worsened incoordination most frequently after waking. RNA sequencing showed clear expression of the truncated transcript and no differences were found between mutant and wild-type DAGLA activity. Immunofluorescence staining of patient-derived fibroblasts and HEK cells expressing the mutant protein showed distinct perinuclear aggregation not detected in control samples. This report establishes truncating variants in the last DAGLA exon as the cause of a unique paediatric syndrome. Because enzymatic activity was preserved, the observed mislocalization of the truncated protein may account for the observed phenotype. Potential mechanisms include DAGLA haploinsufficiency at the plasma membrane or dominant negative effect. To our knowledge, this is the first report directly linking an endocannabinoid system component with human genetic disease and sets the stage for potential future therapeutic avenues
From Animal Models to Humans
There are currently no fully restorative therapies for human spinal cord injury (SCI). Here, we briefly review the different types of human SCI pathology as well as the most commonly used rodent and nonhuman primate models of SCI that are used to simulate these pathologies and to test potential therapies. We then discuss various high profile (sometimes controversial) experimental strategies that have reported CNS axon regeneration and functional recovery of limb movement using these animal models of SCI. We particularly focus upon strategies that have been tested both in rodents and in nonhuman primates, and highlight those which are currently transitioning to clinical tests or trials in humans. Finally we discuss ways in which animal studies might be improved and what the future may hold for physical therapists involved in rehabilitation of humans with SCI