Neuroinflammatory signals drive spinal curve formation in zebrafish models of idiopathic scoliosis.

The etiopathogenesis of idiopathic scoliosis (IS), a highly prevalent spinal deformity that occurs in the absence of obvious congenital or physiological abnormalities, is poorly understood. Although recent zebrafish genetic studies have linked cilia motility and cerebrospinal fluid (CSF) flow defects with scoliosis progression, underlying mechanisms were not identified. Here, we use next-generation sequencing and conditional genetic methodologies to define the spatial and biological origins of spinal curve formation in ptk7 mutant zebrafish, a faithful IS model. We demonstrate that focal activation of proinflammatory signals within the spinal cord is associated with, and sufficient for, induction of spinal curvatures. Furthermore, administration of acetylsalicylic acid (aspirin) or N-acetylcysteine (NAC) to juvenile ptk7 mutants significantly reduces the incidence and/or severity of scoliosis phenotypes. Together, our results implicate neuroinflammation, downstream of CSF defects, in spinal curve formation and provide intriguing evidence that simple immunomodulating therapies might prove effective in managing idiopathic-like spinal deformities.

Mucoadhesive films inside the colonic tube: performance in a three-dimensional world.

A self-propelling colonoscopic device moving inside the colonic tube should be able to periodically grip safely to the colonic wall as well as to manipulate the generated friction. The feasibility of achieving high grip and friction manipulation by covering the device with mucoadhesive films is experimentally tested. More precisely, the frictional behaviour of mucoadhesive films inside the colonic tube is tested in vitro in porcine colon. It appears that mucoadhesive films generate significantly higher friction than conventional materials (ANOVA p=0, 95% CIs=-3.04, -2.14). The geometry of the film plays a role as well. When holes are, for instance, present in the film geometry and are large enough so that the colonic tissue can wrap their borders, friction can be significantly increased (ANOVA p=0, 95% CIs=-2.53, -1.26). By altering the contact area or the film geometry, friction manipulation can be achieved. Moreover, a simple theoretical model is developed and experimentally verified (R=0.92). The model can be used to estimate the level of the friction generated by three-dimensional configurations of mucoadhesive films as a function of their geometric characteristics and the material properties of the colon.