BackgroundNeural network synchrony is a critical factor in regulating information transmission through the nervous system. Improperly regulated neural network synchrony is implicated in pathophysiological conditions such as epilepsy. Despite the awareness of its importance, the molecular signaling underlying the regulation of neural network synchrony, especially after stimulation, remains largely unknown.ResultsIn this study, we show that elevation of neuronal activity by the GABA(A) receptor antagonist, Picrotoxin, increases neural network synchrony in primary mouse cortical neuron cultures. The elevation of neuronal activity triggers Mdm2-dependent degradation of the tumor suppressor p53. We show here that blocking the degradation of p53 further enhances Picrotoxin-induced neural network synchrony, while promoting the inhibition of p53 with a p53 inhibitor reduces Picrotoxin-induced neural network synchrony. These data suggest that Mdm2-p53 signaling mediates a feedback mechanism to fine-tune neural network synchrony after activity stimulation. Furthermore, genetically reducing the expression of a direct target gene of p53, Nedd4-2, elevates neural network synchrony basally and occludes the effect of Picrotoxin. Finally, using a kainic acid-induced seizure model in mice, we show that alterations of Mdm2-p53-Nedd4-2 signaling affect seizure susceptibility.ConclusionTogether, our findings elucidate a critical role of Mdm2-p53-Nedd4-2 signaling underlying the regulation of neural network synchrony and seizure susceptibility and reveal potential therapeutic targets for hyperexcitability-associated neurological disorders.Electronic supplementary materialThe online version of this article (doi:10.1186/s13041-016-0214-6) contains supplementary material, which is available to authorized users.

Minimally invasive aesthetic procedures with hyaluronic acid filler have increased drastically since their development in 1989. Patients' desires to avoid surgery and achieve rapid results with minimal recovery led to a transformation in facial plastic surgery, demanding that aesthetic surgeons become proficient in nonsurgical augmentation. Over the years, new hyaluronic acid filler products were developed with different intrinsic properties, allowing clinicians to better treat different deficiencies of the face, reduce postprocedural pain, and optimize outcomes. The purpose of this article is to review the current state of nonsurgical facial plastic surgery with the superficial dermal filler, hyaluronic acid.

Objective: Acute complications in orthognathic surgery are reported in single-institution studies with small sample sizes. We aimed to analyze risk factors for acute complications using a national data set to better inform surgical decision-making. Methods: 2005-2015 National Surgical Quality Improvement Program (NSQIP) data sets were analyzed for patients undergoing Le Fort 1 and/or bilateral sagittal split osteotomies (BSSO) for nontraumatic indications. Demographics, comorbidities, medical, and surgical 30-day complications were tabulated. A logistic regression model was used to determine predictors of complications. Results: Five hundred eight patients met the inclusion criteria: 228 underwent Le Fort I osteotomies, 152 BSSO, and 128 patients underwent both during a single surgical encounter. Overall complication rate was 4.5% (23/508). Superficial infection was the most common complication (11 in BSSO and 2 in Le Fort I cohorts). Increasing age and undergoing BSSO alone were associated with higher overall complication rates (P < .05) and surgical complications specifically (P < .05). Patients undergoing the combined procedure had shorter operative time (208 minutes) than the times for Le Fort I osteotomies alone (177 minutes) and BSSO alone (155 minutes) added together and did not have a longer hospital stay (P = .608) or increased need for transfusion (P = 1.0) compared to the surgeries being done separately. Conclusion: This is the first complication risk factor analysis for Le Fort I osteotomy and BSSO using the multi-institutional NSQIP data set. Combining BSSO and Le Fort I osteotomy leads to a shorter overall operative time and does not increase hospital stay duration or 30-day complication rate when compared to the 2 procedures being done separately.

Small-particle hyaluronic acid filler treatment for perioral rejuvenation is an effective method for improving physical appearance as well as first impressions. Larger studies are necessary to verify whether perioral rejuvenation with hyaluronic acid offers enhanced self-perception of mood.