Signaling pathways in osteogenesis and osteoclastogenesis: Lessons from cranial sutures and applications to regenerative medicine.

One of the simplest models for examining the interplay between bone formation and resorption is the junction between the cranial bones. Although only roughly a quarter of patients diagnosed with craniosynostosis have been linked to known genetic disturbances, the molecular mechanisms elucidated from these studies have provided basic knowledge of bone homeostasis. This work has translated to methods and advances in bone tissue engineering. In this review, we examine the current knowledge of cranial suture biology derived from human craniosynostosis syndromes and discuss its application to regenerative medicine

Peer mentoring: A move towards addressing inequality between PhD students

The number of students enrolling in postgraduate by research degrees has seen a large increase in recent years, a trend which is evident globally as well as within Australia. However, the rate at which PhD students are dropping out has also increased, indicating that students are not receiving adequate resources to support them throughout their candidature. We highlight that mentoring programs are effective in addressing inequality between PhD students, and describe a program that we have recently launched at UNSW Sydney

Intraoperative Indocyanine Green Laser Angiography in Pediatric Autologous Ear Reconstruction.

Skin flap vascularity is a critical determinant of aesthetic results in autologous ear reconstruction. In this study, we investigate the use of intraoperative laser-assisted indocyanine green angiography (ICGA) as an adjunctive measure of skin flap vascularity in pediatric autologous ear reconstruction. Twenty-one consecutive pediatric patients undergoing first-stage autologous total ear reconstruction were retrospectively evaluated. The first 10 patients were treated traditionally (non-ICGA), and the latter 11 patients were evaluated with ICGA intraoperatively after implantation of the cartilage construct and administration of suction. Relative and absolute perfusion units in the form of contour maps were generated. Statistical analyses were performed using independent sample Student t test. Statistically significant differences in exposure and infection were not found between the 2 groups. However, decreased numbers of surgical revisions were required in cases with ICGA versus without ICGA (P = 0.03), suggesting that greater certainty in skin flap perfusion correlated with a reduction in revision surgeries. In cases of exposure, we found an average lowest absolute perfusion unit of 14.3, whereas cases without exposure had an average of 26.1 (P = 0.02), thereby defining objective parameters for utilizing ICGA data in tailoring surgical decision making for this special population of patients. Defined quantitative parameters for utilizing ICGA in evaluating skin flap vascularity may be a useful adjunctive technique in pediatric autologous ear reconstruction

Evaluation of 4 Outcomes Measures in Microtia Treatment: Exposures, Infections, Aesthetics, and Psychosocial Ramifications.

BackgroundIn craniofacial microsomia, microtia and canal atresia pose formidable reconstructive challenges. We review our institutional experience in treating microtia and atresia to identify variables associated with 4 outcomes measures: complications, surgical revisions, aesthetic outcomes, and psychosocial function.MethodsCraniofacial microsomia patients treated at the University of California Los Angeles Craniofacial Clinic between 2008 and 2014 greater than 13 years of age (n = 68) were reviewed for microtia and atresia treatment and outcomes.ResultsIn total, 91.2% of patients diagnosed with craniofacial microsomia presented with microtia, affecting 75 ears. Both a male and right-sided predominance were observed. Fifty-six patients (90.3%) underwent autologous external ear reconstruction at an average age of 8.5 years. Age, type of incision, and size of cartilage framework did not predict total number of surgeries or complications. Severity of ear anomalies correlated with increased number of surgeries (P < 0.001) and decreased aesthetic outcomes (P < 0.001) but not complications. In total, 87.1% of patients with microtia had documented hearing loss, of which the majority were conductive and 18.5% were mixed sensorineural and conductive. Hearing deficits were addressed in 70.4% of patients with external hearing aids, bone anchored hearing aids, or canaloplasty. Of all variables, improvement of psychosocial function was correlated only to hearing loss treatment of any type (P = 0.01).ConclusionsOn evaluation of surgical and patient characteristics, severity of microtia predicted the total number of surgical revisions performed and aesthetic ratings. In addition, we found that the only factor that correlated with improved patient and parent-reported psychosocial outcomes was treatment of hearing loss

Osteoprotegerin reduces osteoclast resorption activity without affecting osteogenesis on nanoparticulate mineralized collagen scaffolds.

The instructive capabilities of extracellular matrix-inspired materials for osteoprogenitor differentiation have sparked interest in understanding modulation of other cell types within the bone regenerative microenvironment. We previously demonstrated that nanoparticulate mineralized collagen glycosaminoglycan (MC-GAG) scaffolds efficiently induced osteoprogenitor differentiation and bone healing. In this work, we combined adenovirus-mediated delivery of osteoprotegerin (AdOPG), an endogenous anti-osteoclastogenic decoy receptor, in primary human mesenchymal stem cells (hMSCs) with MC-GAG to understand the role of osteoclast inactivation in augmentation of bone regeneration. Simultaneous differentiation of osteoprogenitors on MC-GAG and osteoclast progenitors resulted in bidirectional positive regulation. AdOPG expression did not affect osteogenic differentiation alone. In the presence of both cell types, AdOPG-transduced hMSCs on MC-GAG diminished osteoclast-mediated resorption in direct contact; however, osteoclast-mediated augmentation of osteogenic differentiation was unaffected. Thus, the combination of OPG with MC-GAG may represent a method for uncoupling osteogenic and osteoclastogenic differentiation to augment bone regeneration

Using Big Data to Assess Legitimacy of Plastic Surgery Information on Social Media

Background The proliferation of social media in plastic surgery poses significant difficulties for the public in determining legitimacy of information. This work proposes a system based on social network analysis (SNA) to assess the legitimacy of information contributors within a plastic surgery community. Objectives The aim of this study was to quantify the centrality of individual or group accounts on plastic surgery social media by means of a model based on academic plastic surgery and a single social media outlet. Methods To develop the model, a high-fidelity, active, and legitimate source account in academic plastic surgery (@psrc1955, Plastic Surgery Research Council) appearing only on Instagram (Facebook, Menlo Park, CA) was chosen. All follower-followed relationships were then recorded, and Gephi (https://gephi.org/) was used to compute 5 different centrality metrics for each contributor within the network. Results In total, 64,737 unique users and 116,439 unique follower-followed relationships were identified within the academic plastic surgery community. Among the metrics assessed, the in-degree centrality metric is the gold standard for SNA, hence this metric was designated as the centrality factor. Stratification of 1000 accounts by centrality factor demonstrated that all of the top 40 accounts were affiliated with a plastic surgery residency program, a board-certified academic plastic surgeon, a professional society, or a peer-reviewed journal. None of the accounts in the top decile belonged to a non–plastic surgeon or non-physician; however, this increased significantly beyond the 50th percentile. Conclusions A data-driven approach was able to identify and successfully vet a core group of interconnected accounts within a single plastic surgery subcommunity for the purposes of determining legitimate sources of information

DEDD regulates degradation of intermediate filaments during apoptosis

Apoptosis depends critically on regulated cytoskeletal reorganization events in a cell. We demonstrate that death effector domain containing DNA binding protein (DEDD), a highly conserved and ubiquitous death effector domain containing protein, exists predominantly as mono- or diubiquitinated, and that diubiquitinated DEDD interacts with both the K8/18 intermediate filament network and pro–caspase-3. Early in apoptosis, both cytosolic DEDD and its close homologue DEDD2 formed filaments that colocalized with and depended on K8/18 and active caspase-3. Subsequently, these filamentous structures collapsed into intracellular inclusions that migrated into cytoplasmic blebs and contained DEDD, DEDD2, active caspase-3, and caspase-3–cleaved K18 late in apoptosis. Biochemical studies further confirmed that DEDD coimmunoprecipitated with both K18 and pro–caspase-3, and kinetic analyses placed apoptotic DEDD staining prior to caspase-3 activation and K18 cleavage. In addition, both caspase-3 activation and K18 cleavage was inhibited by expression of DEDDΔNLS1-3, a cytosolic form of DEDD that cannot be ubiquitinated. Finally, siRNA mediated DEDD knockdown cells exhibited inhibition of staurosporine-induced DNA degradation. Our data suggest that DEDD represents a novel scaffold protein that directs the effector caspase-3 to certain substrates facilitating their ordered degradation during apoptosis

Provider Staffing Effect on a Decision Aid Intervention

This study examined the association between Nurse Practitioner (NP) and Physician Assistant (PA) staffing in nursing homes and the effect of a decision-aid regarding feeding options in dementia on the frequency of surrogate- provider discussions and on surrogates’ decisional conflict. We compared these outcomes for facilities that had no NP/PAs, part-time only NP/PA staffing, and full-time NP/PA staffing. The sample included 256 surrogate decision-makers from 24 nursing homes. The decision aid was associated with significant increases in discussion rates in facilities with part-time or no NP/PA staffing (26% v. 51%, p <.001 and 13% v. 41%, p < .001, respectively) and decreases in decisional conflict scores (−0.08 v. −.47, p = .008 and −0.30 v. −.0.68, p = .014, respectively). Sites with full-time NP/PA staffing had high baseline rates of discussions (41%). These findings suggest that the decision aid and full-time NP/PA staffing can enhance surrogate decision-making in nursing homes

Small RNAs with 5′-Polyphosphate Termini Associate with a Piwi-Related Protein and Regulate Gene Expression in the Single-Celled Eukaryote Entamoeba histolytica

Small interfering RNAs regulate gene expression in diverse biological processes, including heterochromatin formation and DNA elimination, developmental regulation, and cell differentiation. In the single-celled eukaryote Entamoeba histolytica, we have identified a population of small RNAs of 27 nt size that (i) have 5′-polyphosphate termini, (ii) map antisense to genes, and (iii) associate with an E. histolytica Piwi-related protein. Whole genome microarray expression analysis revealed that essentially all genes to which antisense small RNAs map were not expressed under trophozoite conditions, the parasite stage from which the small RNAs were cloned. However, a number of these genes were expressed in other E. histolytica strains with an inverse correlation between small RNA and gene expression level, suggesting that these small RNAs mediate silencing of the cognate gene. Overall, our results demonstrate that E. histolytica has an abundant 27 nt small RNA population, with features similar to secondary siRNAs from C. elegans, and which appear to regulate gene expression. These data indicate that a silencing pathway mediated by 5′-polyphosphate siRNAs extends to single-celled eukaryotic organisms