Functional outcomes in unstable complete subaxial cervical spinal injuries with respiratory paralysis and/or hemodynamic instability.

INTRODUCTION: Subaxial cervical spine injuries (SCSI) can lead to disastrous consequences such as quadriplegia, with/without respiratory paralysis (RP) and hemodynamic instability (HDI). Till date, there is no literature available for reporting outcomes of SCSI patients specifically pertaining to those presenting with RP/HDI and ours is the first study to document the same. METHODS: Retrospective 6-year study from a tertiary trauma centre database including patients >/= 18 years of operated SCSI. Only patients with ASIA A grade with admission RP/HDI and unstable injuries (fractures, subluxations) were included. Patients with ASIA grade B and above, patients with non-osseous injuries (such as disc herniation, central cord syndrome etc.) were excluded. RESULTS: 24 cases were analysed. C5 and C6 levels were the commonest. Vertebral listhesis/subluxation was the predominant radiological finding. The mean age was 47.4 years (22-79 years) and all, except one were males. Fall from height and road traffic accident (RTA) were the most common mechanisms of injury. The most common surgery was anterior discectomy and fusion followed by corpectomy. The overall mortality rate was 22/24 (92)%. Cord edema and hemorrhage had significant association with survival. None of the grade A survivors with HDI/RP showed improvement. The mean FU duration was 18.5 months (range, 16.5-20.5 months). CONCLUSIONS: Subaxial ASIA A cervical spine injuries with pre-operative RP/HDI is an indicator for non-improvement. This is the first study documenting outcome in such patients. The mortality rate in these patients is very high and is an extremely poor prognostic factor for recovery. Hence, surgery in such patients need to be decided judiciously, especially in developing countries that has a significant financial impact on the family members.

Free volume theory explains the unusual behavior of viscosity in a non-confluent tissue during morphogenesis.

A recent experiment on zebrafish blastoderm morphogenesis showed that the viscosity (η) of a non-confluent embryonic tissue grows sharply until a critical cell packing fraction (ϕS). The increase in η up to ϕS is similar to the behavior observed in several glass-forming materials, which suggests that the cell dynamics is sluggish or glass-like. Surprisingly, η is a constant above ϕS. To determine the mechanism of this unusual dependence of η on ϕ, we performed extensive simulations using an agent-based model of a dense non-confluent two-dimensional tissue. We show that polydispersity in the cell size, and the propensity of the cells to deform, results in the saturation of the available free area per cell beyond a critical packing fraction. Saturation in the free space not only explains the viscosity plateau above ϕS but also provides a relationship between equilibrium geometrical packing to the dramatic increase in the relaxation dynamics.

3D Hydrogel Encapsulation Regulates Nephrogenesis in Kidney Organoids.

Stem cell-derived kidney organoids contain nephron segments that recapitulate morphological and functional aspects of the human kidney. However, directed differentiation protocols for kidney organoids are largely conducted using biochemical signals to control differentiation. Here, the hypothesis that mechanical signals regulate nephrogenesis is investigated in 3D culture by encapsulating kidney organoids within viscoelastic alginate hydrogels with varying rates of stress relaxation. Tubular nephron segments are significantly more convoluted in kidney organoids differentiated in encapsulating hydrogels when compared with those in suspension culture. Hydrogel viscoelasticity regulates the spatial distribution of nephron segments within the differentiating kidney organoids. Consistent with these observations, a particle-based computational model predicts that the extent of deformation of the hydrogel-organoid interface regulates the morphology of nephron segments. Elevated extracellular calcium levels in the culture medium, which can be impacted by the hydrogels, decrease the glomerulus-to-tubule ratio of nephron segments. These findings reveal that hydrogel encapsulation regulates nephron patterning and morphology and suggest that the mechanical microenvironment is an important design variable for kidney regenerative medicine.