Faculty Bibliography

Tissue homeostasis and regeneration rely on resident stem cells (SCs), whose behaviour is regulated through niche-dependent crosstalk. The mechanisms underlying SC identity are still unfolding. Here, using spatiotemporal gene ablation in murine hair follicles, we uncover a critical role for the transcription factors (TFs) nuclear factor IB (NFIB) and IX (NFIX) in maintaining SC identity. Without NFI TFs, SCs lose their hair-regenerating capability, and produce skin bearing striking resemblance to irreversible human alopecia, which also displays reduced NFIs. Through single-cell transcriptomics, ATAC-Seq and ChIP-Seq profiling, we expose a key role for NFIB and NFIX in governing super-enhancer maintenance of the key hair follicle SC-specific TF genes. When NFIB and NFIX are genetically removed, the stemness epigenetic landscape is lost. Super-enhancers driving SC identity are decommissioned, while unwanted lineages are de-repressed ectopically. Together, our findings expose NFIB and NFIX as crucial rheostats of tissue homeostasis, functioning to safeguard the SC epigenome from a breach in lineage confinement that otherwise triggers irreversible tissue degeneration.

OBJECTIVES/OBJECTIVE:to evaluate the probability of survival and failure modes of lithium-disilicate, feldspathic-ceramic, and resin-nanoceramic anterior veneers cemented on dentin analog substrates after sliding-contact step-stress accelerated life testing (SSALT). METHODS:A virtual incisor tooth preparation was produced with a reduction of 1.5mm at the incisal edge and of 0.7mm buccally. A .STL file of the preparation was generated and CAD/CAM based G10 dentin-analog material was used for testing. Laminate veneers were milled in three different materials: lithium-disilicate (LDS, E.max CAD), resin-nanoceramic (RN, Lava Ultimate), and feldspathic-ceramic (FELDS, Vita Blocks). SSALT was employed where a spherical indenter contacted the veneer, slided along its interface with G10 to lift off and start a new cycle at 2Hz in water. Qualitative fractography was performed. The probability of survival (90% confidence-bounds) was calculated for several load/cycle missions. RESULTS:The probability of survival for a mission of 50,000 cycles decreased from 50 up to 150N equally for all groups and were not different between them. At 200N, the probability of survival was significantly lower for FELDS (10%) compared to RN veneers (41%), whereas LDS presented intermediate values (22%). The characteristic strength of RN (247N) was significantly higher than LDS (149N), and FELDS (151N). In FELDS and LDS, hackles, wake hackles and twist hackles indicated the direction of crack propagation. In RN, hackles were observed. CONCLUSIONS:Differences in probability of survival were observed only at 180 and 200N between groups. Failure modes were similar with veneer fracture down to the tooth-analog substrate.

Background/Purpose: We present the first long-term outcomes analysis of the nasoalveolar molding (NAM) treatment protocol on patients with a cleft followed from birth to facial maturity. Methods/Description: Single-institution retrospective review of all patients with a cleft who underwent NAM between the years 1990 and 2000. All study patients completed cleft care treatment at the same institution and were followed by the same team members. Our institution's treatment protocol offers NAM to patients with a significant cleft nasal deformity and/or widely displaced alveolar segments. All patients underwent primary cleft lip and nasal repair prior to the age of 6 months. Gingivoperiosteoplasty (GPP) is performed, when possible, at the time of lip repair. Cleft palate repair is performed by 1 year of age. Collected data include surgical and orthodontic outcomes of cleft care such as cleft lip and palate repair, GPP, alveolar bone grafting (ABG), speech surgery for velopharyngeal insufficiency (VPI), palatal fistula repairs, orthognathic surgery, and revision surgery to the nose and/or lip.
Result(s): A total of 135 patients met the inclusion criteria. Mean length of follow-up was 18.8 years. Eighty-nine patients presented with a unilateral cleft (UNI) and 46 with a bilateral cleft (BI); 84% (113/135) of patients underwent GPP (UNI: 78% [69/89]; BI: 96% [44/46]), 43% (58/135) of patients underwent ABG (UNI: 40% [36/89]; BI: 48% [22/46]), 18% (24/135) of patients underwent speech surgery for VPI (UNI: 14% [12/89]; BI: 26% [12/46]), 3% (4/135) of patients underwent palatal fistula repair (UNI: 0% [0/89]; BI: 9% [4/46]), 31% (42/135) underwent orthognathic surgery (UNI: 22% [20/89]; BI: 48% [22/46]), and 11% (15/135) underwent revision surgery to lip, nose, or both prior to facial maturity (UNI: 9% [8/89]; BI: 15% [7/46]]. Of the patients who underwent GPP, 61% (69/113) did not require ABG (UNI: 65% [45/69]; BI: 55% [24/44]) and 42% (48/113) required neither ABG nor orthognathic surgery (UNI: 51% [35/69]; BI: 30% [13/44]).
Conclusion(s): Clinical outcomes of the NAM treatment protocol from birth to facial maturity demonstrate a low rate of revision surgery to the lip and nose, as well as a low fistula and VPI rate. The frequency of orthognathic surgery reported in this study is consistent with published data. In addition, 42% of patients who underwent NAM with GPP required neither ABG nor orthognathic surgery

Background/Purpose: Our study quantifies changes in skeletal, soft tissue profile, and globe position in patients with syndromic craniosynostosis after Le Fort I + III (LF I + III) surgery. Methods/Description: Patients with syndromic craniosynostosis who underwent LF I + III at the time of facial maturity were followed for at least 1 year. Each lateral cephalometric radiograph was traced using Dolphin Imaging software and superimposed at the sella. Changes in positions of the different landmarks at T0 (preoperatively), T1 (immediate postoperatively), and T2 (1 year postoperatively) were measured by the software. Sixty-seven soft tissue and skeletal landmarks were digitized and measured. LF III skeletal changes were measured by changes in lateral orbit and orbitale. LF I skeletal changes were measured at the A point and U1. Corresponding soft tissue profile and globe position were studied. All data were measured along the x-axis.
Result(s): Twelve patients included in our study have the following syndromes: Crouzon (n = 6), Pfeiffer (n = 2), Apert (n = 1), Antley-Bixler (n = 1), cleidocranial dysplasia (n = 1) and frontonaso dysplasia (n = 1). Nine patients had previous history of LF III distraction. Standard descriptive statistics was used. Data were analyzed using paired T test. Lateral orbit advanced 5.49 mm (T0-T1) on average, with a P value of 1.3-5, and 5.94 mm (T0-T2) on average; 0.45 mm (T1-T2) change with a P value of .96 suggests the lateral orbit is stable. Similar advancement at orbitale is observed at 5.68 mm (T0-T1) and 6.42 mm (T0-T2). The globe moved anteriorly by 1.98 mm (T0-T1) with a P value of .025 and anteriorly by 0.944mm(T0-T2). The change between T2 and T1 is 1.04 mm (P value: .26), which suggests the globe moved backward after postsurgical swelling subsided. The ratios of movement (globe to lateral orbit) between T0-T1 and T0-T2 are 31% and 16%, respectively. The decrease in ratio can be attributed to the reduction in soft tissue swelling at T2. Restoring position of the globe relative to the lateral orbit decreases the risk of exposure keratitis, keratoconjunctivitis sicca, and corneal ulceration. Anterior nasal spine and point A were advanced by 9.38 and 10.08 mm, respectively, between T0 and T1, and 9.01 mm and 8.51 mm, respectively, between T1 and T2. At the occlusal level, U1 advanced 10 mm and L1 moved back 1.45 mm between T0 and T1. Menton moved back 1.25 mm (T0-T1) but advanced by 2.48 mm (T0-T2). This change in direction is due to splint use at T1 as it rotates mandible clockwise.
Conclusion(s): In our cohort, LFI + III surgery improved both midface deficiency and proptosis in those with syndromic craniosynostosis.Combined Le Fort I + III surgery allows surgeons to perform differential corrections of the midface at the orbital and the dentition level. This is ideal for proptosis correction and establishing optimal jaw relationship

Background/Purpose: Our goal is to present to mental health professionals and craniofacial center providers a Panel Workshop on helping parents/caregivers learn how to best advocate for their school age children with craniofacial conditions who experience academic and social challenges. Information about various types of schools, choosing a school, enrollment and school placement, in-school special services, parent-teacher conferences, how to transfer to another school, at home tutoring following surgery, and other related topics will be discussed. In addition, we will address academic stress, developing a realistic schedule, bullying interventions, technology and social media guidelines, and provide families with relevant resources. Methods/Description: The panelists focused on topics including: academic advocacy, academic testing, neuropsychological and behavioral assessments, IEP's(Individual Educational Plans), optimal classroom placement, academic modifications and accommodations, in-school special services, how to ease the burden of academic stress, and providing information on available services. Social advocacy focused on issues such as how to help children feel comfortable starting school, transitions to grades and new schools, return to school after surgery, and ways to cope with social issues including bullying. Panelists included the craniofacial team psychologist, senior social worker, nurse practitioner, a nonprofit organization's director of family programs, as well as the parent of a school age child, an adult patient, a school administrator, and an educational/advocacy representative from a community organization

Background/Purpose: Global Smile Foundation (GSF) is a nonprofit foundation that provides comprehensive cleft care to underserved patients. GSF focuses on long-term follow-up and sustainability of local health-care teams, having engaged in 32 years of follow-up in Ecuador. In 2012, GSF added presurgical nasoalveolar molding (NAM) therapy for their patients in Guayaquil, Ecuador, as part of its sustainability and empowerment initiative. We present longitudinal data on 189 patients treated with NAM and discuss the challenges/barriers to its completion. Methods/Description: Data were collected from GSF surgical and dental records including patient diagnosis, completion/incompletion, and length of NAM therapy. Surgeon, patient age, peri, intra, and postoperative procedural data were collected for primary cleft lip/nose and palate repair, and any additional surgeries. Follow-up clinical and photographic data were retrieved to document long-term outcomes.
Result(s): A total of 207 patients were treated with presurgical therapy: 189 patients received NAM therapy, while 18 patients were treated with lip tape and/or nasal elevator. Of the 189 NAM patients who received NAM, long-term follow-up was available for 96 (50.8%) patients, while 84 (44.4%) were lost to follow-up or subsequently seen by another foundation, and 9 (4.8%) are currently undergoing NAM or awaiting primary surgery. Of the 96 patients with long-term followup, 70 (72.9%) had unilateral cleft lip and palate and 26 (27.1%) had bilateral cleft lip and palate; 64 (66.67%) were male and 32 (33.3%) were female. Of those 96 patients, 58 (60.4%) completed NAM therapy, 17 (17.7%) failed to complete it, and 21 (21.8%) had incomplete NAM documentation. The average age at NAM initiation was 36.36 +/-31.39 days (range: 0-157 days) and average length of NAM therapy was 118.98 +/- 82.68 days (range: 1-222 days). Patients underwent an average of 2.13 +/- 0.93 (range: 1-5) surgeries after NAM initiation, with an average of 0.17 +/- 0.43 (0-2) cleft lip/nose revisions, 0.06 +/- 0.28 (0-2) gingivoperioplasty, 0.06 +/- 0.28 (0-1) premaxillary setbacks, 0.07 +/- 0.30 (0-2) fistula repairs, and 0.03 +/- 0.17 (0-1) velopharyngeal insufficiency corrections. Over an 8-year period, 12 NAM providers were trained in Ecuador; 7 provided treatment in Ecuador, and 5 provided treatment internationally, making Ecuador a site for information exchange. Follow-up for NAM patients was an average of 2.00 +/- 1.77 (0.22-6.67) years after NAM initiation and 1.45 +/- 1.77 (0-6.52) years after their primary cleft lip/nose repair. This includes continued long-term follow-up and comprehensive cleft care in addition to NAM therapy.
Conclusion(s): With yearly patient follow-up and year-round partnership with local professionals, our model shows successful long-term delivery of NAM therapy as part of a sustainable comprehensive cleft care strategy in outreach settings

Background/Purpose: The evolution of primary unilateral cleft lip repair represents a series of incremental modifications pioneered by a distinct group of master surgeons. It is through understanding the purpose of each evolutionary step, the limits and compromises of these steps, and the subsequent modifications which followed, can a greater understanding of the art of cleft lip repair be realized. This course will trace the conceptual development of unilateral cleft lip repair over the past 70 years using a novel, real-time computer-based cleft lip simulator. A first order accurate biophysics implementation within the simulator will be used to demonstrate the cleft lip repair techniques described to reveal the strengths and weaknesses of each stage of unilateral lip repair development. The course will begin with the Tennison Randall lower triangular lip repair, as it is still in common use today. This will be followed by Skoog, Wynn, and Mustarde adding an upper triangle to the lip repair. The various stages in the progression of the Millard repair will then be carefully traced along with the biophysics which are likely responsible for why Millard altered his original design. The modifications of the Millard design by other surgeons, and the reasons for them, will then be carefully traced. The modifications covered will be those of Noordhoff, Mohler, Cutting, Fisher, and others. The interaction between lip repair technique and primary correction of the cleft-lip nasal deformity will be discussed in detail. Simulator-based demonstrations will be augmented with patient examples from the senior author's clinical practice which illustrate the conceptual difficulties encountered at various stages in the historical development of primary unilateral cleft lip and nose repair. Methods/Description: The principal method used in this course will be real-time computer-based surgical simulation. A unilateral cleft lipnose model involving skin, mucosa, muscle, bone, cartilage, and teeth was derived from an MR scan of an adolescent with an unrepaired unilateral cleft. Alterations in the model are illustrated with first-order accurate biophysics using a new software base called projective dynamics. Surgical tools provided are scalpel, suture, hook, and undermine of both skin/mucosa and bone/cartilage. Surgical "'history" files are used to step through a succession of cleft lip repairs in the surgical eclectic. The presentation will be augmented with photographs from the senior author's long career further illustrating why successive alterations in technique were made