Current Presurgical Infant Orthopedics Practices Among American Cleft Palate Association-Approved Cleft Teams in North America.

Presurgical infant orthopedic (PSIO) therapy has evolved in both its popularity and focus of treatment since its advent. Nasoalveolar molding, nasal elevators, the Latham appliance, lip taping, and passive plates are the modern treatment options offered by cleft teams. Many cleft surgeons also employ postsurgical nasal stenting (PSNS) after the primary lip repair procedure. The purpose of this study is to examine trends in current PSIO care as well as PSNS for the management of patients with cleft lip and palate. An electronic survey was distributed to cleft team coordinators listed by the American Cleft Palate Association. The survey reported on team setting, provider availability, PSIO offerings, contraindications, and use of PSNS. Descriptive statistics and analyses were performed using MS Excel and SPSS. A total of 102 survey responses were received. The majority of settings were children's specialty hospitals (66%) or university hospitals (27%). Presurgical infant orthopedics was offered by 86% of cleft teams, and the majority of those (68%) provided nasoalveolar molding. Nasal elevators and lip taping are offered at 44% and 53% of centers, respectively. Latham and passive plates are both offered at 5.5% of centers. Most centers had an orthodontist providing treatment. The majority of centers use PSNS (86%). Nasoalveolar molding is the most popular PSIO technique in North American cleft centers followed by the nasal elevator, suggesting that the nasal molding component of PSIO is of critical influence on current treatment practices.

Reduction of the expression of the late-onset Alzheimer's disease (AD) risk-factor BIN1 does not affect amyloid pathology in an AD mouse model.

Alzheimer's disease (AD) is pathologically characterized by the deposition of the ß-amyloid (Aß) peptide in senile plaques in the brain, leading to neuronal dysfunction and eventual decline in cognitive function. Genome-wide association studies have identified the bridging integrator 1 (BIN1) gene within the second most significant susceptibility locus for late-onset AD. BIN1 is a member of the amphiphysin family of proteins and has reported roles in the generation of membrane curvature and endocytosis. Endocytic dysfunction is a pathological feature of AD, and endocytosis of the amyloid precursor protein is an important step in its subsequent cleavage by ß-secretase (BACE1). In vitro evidence implicates BIN1 in endosomal sorting of BACE1 and Aß generation in neurons, but a role for BIN1 in this process in vivo is yet to be described. Here, using biochemical and immunohistochemistry analyses we report that a 50% global reduction of BIN1 protein levels resulting from a single Bin1 allele deletion in mice does not change BACE1 levels or localization in vivo, nor does this reduction alter the production of endogenous murine Aß in nontransgenic mice. Furthermore, we found that reduction of BIN1 levels in the 5XFAD mouse model of amyloidosis does not alter Aß deposition nor behavioral deficits associated with cerebral amyloid burden. Finally, a conditional BIN1 knockout in excitatory neurons did not alter BACE1, APP, C-terminal fragments derived from BACE1 cleavage of APP, or endogenous Aß levels. These results indicate that BIN1 function does not regulate Aß generation in vivo.

Complications of Nasal Tip Stabilizing Grafts with Autologous Versus Irradiated Homologous Costal Cartilage in Septorhinoplasty: A Systematic Review.

Background: Complications associated with the use of autologous and homologous costal cartilage for nasal tip stabilizing grafts in septorhinoplasty are not well understood. Objective: The authors review current literature to evaluate complications associated with autologous and irradiated homologous costal cartilage (IHCC) used for septal extension and columellar strut grafts in rhinoplasty. Method: A comprehensive literature search was conducted in PubMed, Embase, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov. Articles that used autologous or IHCC for either septal extension or columellar strut grafts in patients undergoing septorhinoplasty were included. The primary outcomes analyzed were postoperative complications. Results: A total of 14 studies representing 1358 patients were included. The pooled complication rate was 4.7%. IHCC grafts were associated with a higher incidence of complications (n = 21, 5.0% vs. n = 44, 4.6%, p = 0.01). Resorption was the most common complication in the IHCC group and occurred significantly more frequently than in the autologous costal cartilage (ACC) group (n = 10, 2.4% vs. n = 5, 0.49%, p = 0.002). Deviation/warping was the most common complication in the ACC group (n = 16, 1.7%). Conclusion: Autologous and irradiated homologous costal rhinoplasties remain safe procedures. The increased incidence of resorption associated with IHCC grafts should be considered during preoperative planning.

Pig-to-human heart xenotransplantation in two recently deceased human recipients.

Genetically modified xenografts are one of the most promising solutions to the discrepancy between the numbers of available human organs for transplantation and potential recipients. To date, a porcine heart has been implanted into only one human recipient. Here, using 10-gene-edited pigs, we transplanted porcine hearts into two brain-dead human recipients and monitored xenograft function, hemodynamics and systemic responses over the course of 66 hours. Although both xenografts demonstrated excellent cardiac function immediately after transplantation and continued to function for the duration of the study, cardiac function declined postoperatively in one case, attributed to a size mismatch between the donor pig and the recipient. For both hearts, we confirmed transgene expression and found no evidence of cellular or antibody-mediated rejection, as assessed using histology, flow cytometry and a cytotoxic crossmatch assay. Moreover, we found no evidence of zoonotic transmission from the donor pigs to the human recipients. While substantial additional work will be needed to advance this technology to human trials, these results indicate that pig-to-human heart xenotransplantation can be performed successfully without hyperacute rejection or zoonosis.