BackgroundNewts have the remarkable ability to regenerate their spinal cords as adults. Their spinal cords regenerate with the regenerating tail after tail amputation, as well as after a gap-inducing spinal cord injury (SCI), such as a complete transection. While most studies on newt spinal cord regeneration have focused on events occurring after tail amputation, less attention has been given to events occurring after an SCI, a context that is more relevant to human SCI. Our goal was to use modern labeling and imaging techniques to observe axons regenerating across a complete transection injury and determine how cells and the extracellular matrix in the injury site might contribute to the regenerative process.ResultsWe identify stages of axon regeneration following a spinal cord transection and find that axon regrowth across the lesion appears to be enabled, in part, because meningeal cells and glia form a permissive environment for axon regeneration. Meningeal and endothelial cells regenerate into the lesion first and are associated with a loose extracellular matrix that allows axon growth cone migration. This matrix, paradoxically, consists of both permissive and inhibitory proteins. Axons grow into the injury site next and are closely associated with meningeal cells and glial processes extending from cell bodies surrounding the central canal. Later, ependymal tubes lined with glia extend into the lesion as well. Finally, the meningeal cells, axons, and glia move as a unit to close the gap in the spinal cord. After crossing the injury site, axons travel through white matter to reach synaptic targets, and though ascending axons regenerate, sensory axons do not appear to be among them. This entire regenerative process occurs even in the presence of an inflammatory response.ConclusionsThese data reveal, in detail, the cellular and extracellular events that occur during newt spinal cord regeneration after a transection injury and uncover an important role for meningeal and glial cells in facilitating axon regeneration. Given that these cell types interact to form inhibitory barriers in mammals, identifying the mechanisms underlying their permissive behaviors in the newt will provide new insights for improving spinal cord regeneration in mammals.

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We tested the hypothesis that activation of the protective arm of the renin angiotensin system, the angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis, corrects the vasoreparative dysfunction typically seen in the CD34+ cells isolated from diabetic individuals. Peripheral blood CD34+ cells from patients with diabetes were compared with those of nondiabetic controls. Ang-(1-7) restored impaired migration and nitric oxide bioavailability/cGMP in response to stromal cell–derived factor and resulted in a decrease in NADPH oxidase activity. The survival and proliferation of CD34+ cells from diabetic individuals were enhanced by Ang-(1-7) in a Mas/phosphatidylinositol 3-kinase (PI3K)/Akt-dependent manner. ACE2 expression was lower, and ACE2 activators xanthenone and diminazine aceturate were less effective in inducing the migration in cells from patients with diabetes compared with controls. Ang-(1-7) overexpression by lentiviral gene modification restored both the in vitro vasoreparative functions of diabetic cells and the in vivo homing efficiency to areas of ischemia. A cohort of patients who remained free of microvascular complications despite having a history of longstanding inadequate glycemic control had higher expression of ACE2/Mas mRNA than patients with diabetes with microvascular complications matched for age, sex, and glycemic control. Thus, ACE2/Ang-(1-7)\Mas pathway activation corrects existing diabetes-induced CD34+ cell dysfunction and also confers protection from development of this dysfunction.

Objective To evaluate the association between findings of blinded reviews of preoperative drug‐induced sleep endoscopy (DISE) examinations using the VOTE Classification and obstructive sleep apnea (OSA) surgical outcomes in a large multicenter, international cohort. Methods Retrospective, multi‐center cohort study of adults without tonsillar hypertrophy who underwent pharyngeal surgery for OSA. The study included only participants without enlarged tonsils. Four independent reviewers performed blinded review of preoperative DISE videos using the VOTE Classification system and scoring of a primary structure contributing to airway obstruction. DISE findings were examined for an association with surgical outcomes with univariate analyses and multiple regression. Results Two hundred seventy‐five study participants were included from 14 centers. Mean age was 51.4 ± 11.8 years, and body mass index was 30.1 ± 5.2 kg/m2. There was moderate interrater reliability (kappa = 0.40–0.60) for DISE findings. Oropharyngeal lateral wall‐related obstruction was associated with poorer surgical outcomes (adjusted odds ratio (AOR) 0.51; 95% CI 0.27, 0.93). Complete tongue‐related obstruction was associated with a lower odds of surgical response in moderate to severe OSA (AOR 0.52; 95% CI 0.28, 0.98), with findings that were similar but not statistically significant in other analyses. Surgical outcomes were not clearly associated with the degree and configuration of velum‐related obstruction or the degree of epiglottis‐related obstruction. Surgical response was associated with tonsil size and body mass index (inversely). Conclusion DISE findings concerning the oropharyngeal lateral walls and tongue may be the most important findings of this evaluation technique. Level of Evidence 2B Laryngoscope, 129:761–770, 2019