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Goals of pediatric mandibular reconstruction are restoring form, function, and esthetics while providing platforms for dental restoration. Though many techniques recreate the inferior mandibular border, most fail to address form and function in a manner that optimizes dental rehabilitation. We describe a surgical technique using a novel custom endoprosthesis that recapitulates the native mandibular contour while supporting the bone construct in a cephalad direction with a medial ledge facilitating implant placement and oral rehabilitation. This multi-institutional retrospective review at high-volume pediatric craniofacial surgery departments features patients with large mandibular resections warranting custom constructs. Thirteen patients underwent mandibular resection and endoprosthesis reconstruction with either free fibula osteocutaneous flaps (n = 9), soft tissue free flaps without bone graft (n = 2), rib graft (n = 1), or iliac crest bone graft (n = 1). Five patients required revisions for distal flap necrosis, intraoral granuloma, and orocutaneous fistulas; one endoprosthesis required removal. Excellent esthetic and reconstructive outcomes were achieved; however, only 2 patients completed dental restoration given financial constraints. A custom endoprosthesis represents an untapped avenue toward comprehensive pediatric mandibular reconstruction. It shows compatibility with microvascular flaps while optimizing facial contour and bone height for implant placement. Given these advantages, substantial financial barriers to dental restoration should be addressed.

The diversity of patients pursuing facial aesthetic and facial gender-affirming surgery (FGAS) is increasing, yet there is a paucity of objective guidelines to facilitate surgical decision-making in patients of color. We conducted a quantitative analysis of black celebrities using standardized frontal photos of 21 female and 21 male celebrities. Celebrities were chosen from popular entertainment magazines and websites, including People Magazine, the Internet Movie Database (IMDb), Cosmopolitan, and Essence. For each celebrity, 100 facial landmarks were detected through a facial analysis artificial intelligence (AI) program. Black males had greater facial height, bizygomatic width, lower facial height, and bigonial width than females. However, the facial height to bigonial width ratio was similar between genders and approximated the golden ratio (1.618). Female faces demonstrated a greater mid-face height to total facial height proportion, and males had a greater lower facial height proportion. Females exhibited an upward-slanted medial brow and shorter total eyebrow length, nose height, and alar width. Forehead height above the lateral brow was greater in males, while central forehead height was similar to females. This is the first study that has utilized AI to provide ethnicity-specific facial morphometrics relevant to facial rejuvenation and FGAS in the black population.

von Willebrand factor (VWF) plays a key role in normal hemostasis, and deficiencies of VWF lead to clinically significant bleeding. We sought to identify novel modifiers of VWF levels in endothelial colony-forming cells (ECFCs) using single-cell RNA sequencing (scRNA-seq). ECFCs were isolated from patients with low VWF levels (plasma VWF antigen levels between 30 and 50 IU/dL) and from healthy controls. Human umbilical vein endothelial cells were used as an additional control cell line. Cells were characterized for their Weibel Palade body (WPB) content and VWF release. scRNA-seq of all cell lines was performed to evaluate for gene expression heterogeneity and for candidate modifiers of VWF regulation. Candidate modifiers identified by scRNA-seq were further characterized with small-interfering RNA (siRNA) experiments to evaluate for effects on VWF. We observed that ECFCs derived from patients with low VWF demonstrated alterations in baseline WPB metrics and exhibit impaired VWF release. scRNA-seq analyses of these endothelial cells revealed overall decreased VWF transcription, mosaicism of VWF expression, and genes that are differentially expressed in low VWF ECFCs and control endothelial cells (control ECs). An siRNA screen of potential VWF modifiers provided further evidence of regulatory candidates, and 1 such candidate, FLI1, alters the transcriptional activity of VWF. In conclusion, ECFCs from individuals with low VWF demonstrate alterations in their baseline VWF packaging and release compared with control ECs. scRNA-seq revealed alterations in VWF transcription, and siRNA screening identified multiple candidate regulators of VWF.

PURPOSE: Prior studies on compressive optic neuropathy (CON) have come from large tertiary centers, which may contain referral bias toward more severe or atypical disease. To our knowledge, there are no studies to determine the population-based etiologies and clinical outcomes of compressive optic neuropathy (CON). This study aims to bridge that gap using the Rochester Epidemiology Project database. DESIGN: Retrospective, population-based cohort METHODS: Medical records of all residents living in Olmsted County, Minnesota from January 1, 2000 through December 31, 2018 were screened for CON. Demographic and clinical information were collected before and after treatment. RESULTS: 23 patients had a confirmed diagnosis of CON during our study period, which provided an overall incidence of 1.14 per 100,000 per year. Average age at onset of CON was 51 years (SD 24), and 39% were male. The most common etiologies were pituitary adenoma and meningioma. There was significant improvement in visual fields (p < 0.003) but not in visual acuity (p = 0.08) after patients underwent treatment for CON. There was also a significant relationship between the time until treatment and the degree of visual field improvement at follow-up (Pearson correlation rho = −0.58, p < 0.047). CONCLUSION: To our knowledge, this study provides the first population-based incidence of CON. The finding that earlier treatment leads to better visual outcomes stresses the importance of having CON on the differential diagnosis of patients with optic neuropathy.

Platelets from patients with myeloproliferative neoplasms (MPNs) exhibit a hyperreactive phenotype. Here, we found elevated P-selectin exposure and platelet-leukocyte aggregates indicating activation of platelets from essential thrombocythemia (ET) patients. Single cell RNA-seq analysis of primary samples revealed significant enrichment of transcripts related to platelet activation, mTOR and oxidative phosphorylation (OXPHOS) in ET patient platelets. These observations were validated via proteomic profiling. Platelet metabolomics revealed distinct metabolic phenotypes consisting of elevated ATP generation, accompanied by increases in the levels of multiple intermediates of the tricarboxylic acid (TCA) cycle, but lower alpha-ketoglutarate (α-KG) in MPN patients. Inhibition of PI3K/AKT/mTOR signaling significantly reduced metabolic responses and hyperreactivity in MPN patient platelets, while α-KG supplementation markedly reduced oxygen consumption and ATP generation.Ex vivoincubation of platelets from both MPN patients andJak2 V617Fmice with α-KG significantly reduced platelet activation responses. Oral α-KG supplementation ofJak2 V617Fmice decreased splenomegaly and reduced hematocrit, monocyte and platelet counts. Finally, α-KG incubation significantly decreased proinflammatory cytokine secretion from MPN CD14+ monocytes. Our results reveal a previously unrecognized metabolic disorder in conjunction with aberrant PI3K/AKT/mTOR signaling, contributing to platelet hyperreactivity in MPN patients.

Purpose Our study introduces a novel anesthetic protocol for neonates without using volatile agents with the goal to minimize potentially neurotoxic and pro-apoptotic agents. The authors evaluated the short-term safety and efficacy of our anesthetic protocol in patients undergoing early cleft lip repair (ECLR). Methods A retrospective review of ECLR patients who underwent repair before 2.5 months of age within the last 4.3 years was performed. This sample was comprised of 2 groups, those who received either a standard volatile gas-based regimen or a dexmedetomidine-based neonatal anesthetic protocol (DBNAP). Patient demographics, medication dosing, anesthetic time (induction to extubation), major and minor complications, and medication side effects were compared between the 2 cohorts. Results A total of 101 patients underwent ECLR. All patients were American Society of Anesthesiologists class 1 or 2. Mean age at surgery was 31 ± 13 days and mean anesthetic time was 179 ± 36 minutes. DBNAP was used in 65 patients while the standard anesthetic protocol was used in 36 patients. Patient weight was significantly lower in the DBNAP group (4.01 ± 0.61 versus 4.38 ± 0.72 kg, P = 0.007). There were no significant differences between the 2 cohorts when comparing anesthetic time, emergence time, complication rate, or medication side effects. Conclusion For patients undergoing ECLR, DBNAP is perioperatively equivalent to the anesthetic standard of care, demonstrating no major complications and acceptable rates of minor complications and medication side effects.

Cleft lip and/or palate affects approximately one in 700 live births. Optimal timing for repair of cleft lip has yet to be objectively validated. Earlier repair takes advantage of a high degree of plasticity within the nasal cartilage and maxilla. The authors present patients enrolled in an early cleft lip repair protocol facilitating effective repair of the cleft lip and nostril.American Society of Anesthesiologists class I to II patients with unilateral cleft lip and/or palate undergoing repair before 3 months of age were enrolled over 5 years. Perioperative data, surgical and anesthetic complications, preoperative and postoperative nostril breadth, nostril width, nasal angle, lip length, frontal nasal breadth, and commissure length measured as ratios between the cleft and noncleft sides were abstracted. Early cleft lip repair and nasoalveolar molding patients were matched for cleft lip severity using the cleft width ratios and compared.The surgical and anesthetic complication rate for 100 early cleft lip repair patients was 2 percent. Operative and anesthetic times were 123 ± 37 minutes and 177 ± 34 minutes, respectively. Hospital length of stay was 1 ± 0 day. Age at repair between early cleft lip repair and nasoalveolar molding was 33 ± 15 days and 118 ± 33 days, respectively. After early cleft lip repair, preoperative to postoperative distance from symmetry for all anthropomorphic measurements improved ( p0.001). Comparing severity-matched early cleft lip repair to nasoalveolar molding patients, similar improvements were observed, suggesting equivalent results ( p0.05).Early cleft lip repair provides an efficacious method for correcting the cleft lip and nasal deformity that simulates nasoalveolar molding.Therapeutic, III.

Purpose The aim of the study is to conduct a meta-analysis examining the impact of motivational interviewing (MI) on hearing aid (HA) use compared with standard care. Research Design The research design is a systematic review and meta-analysis. Cochrane ENT, Central, Medline, Web of Science, ICTRP, and ClinicalTrials.gov electronic databases were searched. Inclusion criteria consisted of randomized controlled trials (RCTs) published between 1988 and 2018 that compared MI to standard care. Study Sample The study sample consists of four RCTs, investigating a total of 176 patients. Data Collection and Analysis RevMan 5.3 and a random effect model were used for analysis. Results The standardized mean difference in data-logged hours of HA use was not statistically significant (0.34 [95% confidence interval or CI: −0.10, 0.78; p = 0.13]). The mean difference for user-reported outcomes on the International Outcome Inventory—Hearing Aids of 0.41 [CI: −1.00, 1.82; p = 0.57] was also not significant. Conclusion There is no current evidence that MI significantly improves HA use or user-reported outcomes. However, there were limited studies included in this review and further research is indicated.

Hospitalized burn patients meet the criteria for Virchow’s triad (endothelial damage, hypercoagulability, and stasis), predisposing them to venous thromboembolism (VTE). Although the disease burden of VTE suggests a need for prevention in this population, unreliable reported VTE rates, costly and complicated prophylaxis regimens, and chemoprophylaxis risks have prevented the establishment of a universal protocol. This paper reviews thromboprophylaxis practices both in the literature and at our own institution. A systematic review was conducted according to PRISMA guidelines identifying studies pertaining to VTE chemoprophylaxis in burn patients. Additionally, medical records of patients admitted to an American Burn Association-verified burn center between June 2015 and June 2019 were retrospectively reviewed for demographics, chemoprophylaxis, and presence of VTE defined as either deep vein thrombosis (DVT) or pulmonary embolism (PE). Thirty-eight studies met inclusion criteria. In the 12 studies that reported VTE incidence, rates ranged widely from 0.25% to 47.1%. The two largest retrospective studies (n = 33,637 and 36,638) reported a VTE incidence of 0.61% and 0.8% in populations with unknown or inconsistently recorded chemoprophylaxis. Throughout the literature, prevention protocols were mixed, though a trend toward using dose-adjusted subcutaneous low molecular weight heparin based on serum anti-factor Xa level was noted. At our burn center, 1,068 patients met study criteria. At-risk patients received a simple chemoprophylaxis regimen of 5000U of subcutaneous unfractionated heparin every 8 hours. No routine monitoring tests were performed to limit cost. Nine cases of DVT and two cases of PE were identified with an incidence of 0.84% and 0.19%, respectively, and a total VTE incidence of 1.03%. Only one patient developed heparin-induced thrombocytopenia (HIT). No cases of other heparin-associated complications were observed. VTE incidence rates reported in the literature are wide-ranging and poorly capture the effect of any one chemoprophylaxis regimen in the burn population. Our center uses a single, safe, and cost-effective protocol effecting a low VTE rate comparable to that of large national retrospective studies.

A pressing concern with the eyewitness testimony used in many criminal cases is that jurors may be swayed by the high confidence of an eyewitness and, as a result, may disregard other factors that provide more diagnostic information. Mock jurors were surveyed using a large national sample of 1,684 laypeople, selected to be representative of the U.S. population (age, race, gender, geographic region), using mock trial videos of eyewitness testimony. To explore the relationship between courtroom confidence and other factors, we used a fractional factorial design, permitting examination of the relationships among seven factors. Among these seven factors, we found that jurors gave most weight to the confidence of eyewitnesses, especially that expressed in the courtroom, irrespective of the eyewitness's testimony about confidence (low or high) at the initial police lineup. Jurors' assessments were not sensitive to the other factors or their interactions in the experiment: crime type (burglary or sexual assault), the race of the defendant and eyewitness, or information provided in judicial instructions or by expert testimony. The disproportionate importance of the eyewitness's expressed confidence has implications for the effectiveness of legal efforts to inform jurors about factors affecting eyewitness memory.

In the era of theInternet, most educators have been supported by powerful tools ranging from e-books and e-learning sites to cloud services, and students’ learning environment has been a mix between traditional study (in class) and e-learning through some kind of online learning platform. Due to the uncertainty of the rapidly changing COVID-19 situation, all colleges and universities have to shutter their physical campuses and move their courses to remote and online formats hastily. This prompted many to wonder if all of the faculty are ready and qualified to teach online courses and/or if all of the students are ready to learn in the comprehensive online environment. If not, what ultimate impact will be to our higher education during this national emergency virus pandemic since there is no choice but depend on where they sit currently, not to mention the negative reviews and concerns regarding the online education. To make this transfer seamlessly and conflict mitigation, this paper applied systems thinking for an e-Learning course and proposed a flexible grading method for an e-learning environment, which will enhance students’ grades by allowing students to control their own study paces and the amount of efforts spent in the course, which can bring a successful online learning experience.

The revenue generated by plastic surgeons assisting other surgical services is poorly captured by hospital accounting systems, which categorize solely by attending physician of record. The financial impact of reconstructive surgery is thus systematically underestimated. The authors sought to quantify the overlooked value of plastic surgeons as consultants who facilitate complex and profitable operations.Hospital billing data were reviewed for inpatient operations over a 3-year fiscal period (2015 to 2017). Cases in which a plastic surgeon assisted were identified. Case mix index, a measure of complexity that correlates with profit, and contribution margin, defined as revenue minus cost, were obtained for each case.Five hundred fifty-four cases required a reconstructive surgeon; 18,904 nonconsultation cases were identified for comparison. Average net revenue per case involving a consultation was 1.79 times greater than for control cases (p0.0001). Average contribution margin was 1.73 times greater (p0.005). The highest contribution margins stemmed from joint cases with cardiothoracic surgery and neurosurgery. Case mix index was significantly higher for consultation cases than for controls (4.5 versus 3.9; p0.0001). In 434 cases (78 percent), plastic surgery assisted with an integral aspect of the operation, meaning the surgery could not have been technically performed without reconstructive assistance.The authors' findings demonstrate that cases involving plastic surgeons have a higher profit margin than those performed by any department alone. However, this revenue is not appropriately attributed because of oversimplified financial metrics. The skill set of reconstructive surgeons is an undervalued resource for both patient care and hospital economics.

Neural circuits work together with muscles and sensory feedback to generate motor behaviors appropriate to an animal9s environment. In C. elegans, forward locomotion consists of dorsoventral undulations that propagate from anterior to posterior. How the worm9s motor circuit generates these undulations and modulates them based on external loading is largely unclear. To address this question, we performed quantitative behavioral analysis of C. elegans during free movement and during transient optogenetic muscle inhibition. Undulatory movements in the head were found to be highly asymmetric, with bending toward the ventral or dorsal directions occurring slower than straightening toward a straight posture during the locomotory cycle. Phase shifts induced by brief optogenetic inhibition of head muscles showed a sawtooth-shaped dependence on phase of inhibition. We developed a computational model based on proprioceptive postural thresholds that switch the active moment of body wall muscles. We show that our model, a type of relaxation oscillator, is in quantitative agreement with data from free movement, phase responses, and previous results for frequency and amplitude dependence on the viscosity of the external medium. Our results suggest a neuromuscular mechanism that enables C. elegans to coordinate rhythmic motor patterns within a compact circuit.

During development, sensory hair cells (HCs) in the cochlea assemble a stereociliary hair bundle on their apical surface with planar polarized structure and orientation. We have recently identified a non-canonical, Wnt/G-protein/PI3K signaling pathway that promotes cochlear outgrowth and coordinates planar polarization of the HC apical cytoskeleton and alignment of HC orientation across the cochlear epithelium. Here, we determined the involvement of the kinase Gsk3β and the small GTPase Rac1 in non-canonical Wnt signaling and its regulation of the planar cell polarity (PCP) pathway in the cochlea. We provided the first in vivo evidence for Wnt regulation of Gsk3β activity via inhibitory Ser9 phosphorylation. Furthermore, we carried out genetic rescue experiments of cochlear defects caused by blocking Wnt secretion. We showed that cochlear outgrowth was partially rescued by genetic ablation of Gsk3β but not by expression of stabilized β-catenin; while PCP defects, including hair bundle polarity and junctional localization of the core PCP proteins Fzd6 and Dvl2, were partially rescued by either Gsk3β ablation or constitutive activation of Rac1. Our results identify Gsk3β and likely Rac1 as downstream components of non-canonical Wnt signaling and mediators of cochlear outgrowth, HC planar polarity, and localization of a subset of core PCP proteins in the cochlea.

Cell replacement therapy using mesenchymal (MSC) and other stem cells has been evaluated for diabetic retinopathy and glaucoma. This approach has significant limitations, including few cells integrated, aberrant growth, and surgical complications. Mesenchymal Stem Cell Exosomes/Extracellular Vesicles (MSC EVs), which include exosomes and microvesicles, are an emerging alternative, promoting immunomodulation, repair, and regeneration by mediating MSC’s paracrine effects. For the clinical translation of EV therapy, it is important to determine the cellular destination and time course of EV uptake in the retina following administration. Here, we tested the cellular fate of EVs using in vivo rat retinas, ex vivo retinal explant, and primary retinal cells. Intravitreally administered fluorescent EVs were rapidly cleared from the vitreous. Retinal ganglion cells (RGCs) had maximal EV fluorescence at 14 days post administration, and microglia at 7 days. Both in vivo and in the explant model, most EVs were no deeper than the inner nuclear layer. Retinal astrocytes, microglia, and mixed neurons in vitro endocytosed EVs in a dose-dependent manner. Thus, our results indicate that intravitreal EVs are suited for the treatment of retinal diseases affecting the inner retina. Modification of the EV surface should be considered for maintaining EVs in the vitreous for prolonged delivery.

Over the last 3 years a shift at our institution has taken place in which patients who would have been offered nasoalveolar molding (NAM) as an adjunct to cleft lip repair (repair after 3 months) have instead undergone early cleft lip repair (ECLR) (2-5 weeks of life) without NAM. This study sought to examine the financial and social impact of the transition away from NAM to ECLR. The efficacy of NAM is limited by patient compliance to a rigorous treatment schedule requiring weekly visits for appliance adjustments. Nasoalveolar molding patients required an average of 11 dental visits, accounting for $2132 in indirect lost income per family. Average direct charges for NAM totaled $12,290 for the hospital, physician, and appliance costs. Over the entire study period, the cumulative direct cost of NAM separate from the surgical repair of the lip was $970,910. Following the introduction of ECLR as an alternative to NAM with standard lip repair, NAM usage decreased by 48% and unilateral cleft lip patients undergoing NAM decreased by 86%. Those diverted from NAM to ECLR resulted in a decreased healthcare cost burden of $368,700 ($111,727 per year). In addition to the time burden, the financial burden of NAM is significant. Early cleft lip repair without NAM is more cost effective. Nasoalveolar molding has significantly decreased utilization since the implementation of ECLR. We believe that ECLR, with increased experience, long-term data, and increased awareness, has the potential to decrease the burden of health care costs in the United States.

Laser microsurgery has long been an important means of assessing the functions of specific cells and tissues. Most laser ablation systems use short, highly focused laser pulses to create plasma-mediated lesions with dimensions on the order of the wavelength of light. While the small size of the lesion enables ablation with high spatial resolution, it also makes it difficult to ablate larger structures. We developed an infrared laser ablation system capable of thermally lesioning tissues with spot sizes tunable by the duration and amplitude of laser pulses. We used our laser system in the roundworm C. elegans to kill single neurons and to sever the dorsal and ventral nerve cords, structures that are difficult to lesion using a plasma-based ablation system. We used these ablations to investigate the source of convulsions in a gain-of-function mutant for the acetylcholine receptor ACR-2. Severing the ventral nerve cord caused convulsions to occur independently anterior and posterior to the lesion, suggesting that convulsions can arise independently from distinct subsets of the motor circuit.