To determine whether the use of mandibular distraction osteogenesis (DOG) can help to avoid tracheotomy or achieve decannulation in patients with mandibular hypoplasia and severe upper airway obstruction.Design: Retrospective medical record review (spanning a 27-month period).Setting: Tertiary care children's hospital. Subjects: Group A (n=8) was composed of infants with Pierre Robin sequence and no tracheotomy (mean age, 2.5 months); group B (n = 6), older nontracheotomized micrognathic children with obstructive sleep apnea (OSA) (mean age, 69 months); and group C (n = 12), tracheotomized children with complex congenital syndromes (mean age, 33 months).Intervention: Bilateral mandibular DOG with endoscopic (n = 24) and/or radiographic (n = 17) airway evaluation (mean follow-up, 16 months [range, 2-42 months]).Outcome Measures: Group A, tracheotomy avoidance; group B, resolution of OSA (clinically or on polysomnography); and group C, decannulation.Results: Group A, 7 patients (88%) successfully avoided tracheotomy; group B, 5 patients (83%) had resolution of OSA; and group C, 2 patients (17%) underwent decannulation.Conclusions: Mandibular DOG (1) allows tracheotomy avoidance in infants with isolated Pierre Robin sequence and (2) relieves OSA in older micrognathic children without tracheotomy. However, mandibular DOG does not frequently lead to decannulation in tracheotomized patients with complex congenital syndromes.

Mandibular distraction osteogenesis has a high rate of success in avoiding tracheotomy. Patients who required a tracheotomy before MDO had a lower success rate in achieving decannulation and a higher rate of complications. However, these patients also had a higher rate of syndromic diagnoses and associated comorbidities. Patients with Goldenhar syndrome have a decreased likelihood of surgical success.

BackgroundSebaceous glands are components of the skin essential for its normal lubrication by the production of sebum. This contributes to skin health and more importantly is crucial for the skin barrier function. A mechanistic understanding of sebaceous gland cells growth and differentiation has lagged behind that for keratinocytes, partly because of a lack of an in vitro model that can be used for experimental manipulation.MethodsWe have developed an in vitro culture model to isolate and grow primary human sebocytes without transformation that display functional characteristics of sebocytes. We used this novel method to probe the effect of Transforming Growth Factor β (TGFβ) signaling on sebocyte differentiation, by examining the expression of genes involved in lipogenesis upon treatment with TGFβ1. We also repressed TGFβ signaling through knockdown of the TGFβ Receptor II to address if the effect of TGFβ activation is mediated via canonical Smad signal transduction.ResultsWe find that activation of the TGFβ signaling pathway is necessary and sufficient for maintaining sebocytes in an undifferentiated state. The presence of TGFβ ligand triggered decreased expression in genes required for the production of characteristics sebaceous lipids and for sebocyte differentiation such as FADS2 and PPARγ, thereby decreasing lipid accumulation through the TGFβ RII-Smad2 dependent pathway.ConclusionTGFβ signaling plays an essential role in sebaceous gland regulation by maintaining sebocytes in an undifferentiated state. This data was generated using a novel method for human sebocyte culture, which is likely to prove generally useful in investigations of sebaceous gland growth and differentiation. These findings open a new paradigm in human skin biology with important implications for skin therapies.

Expanded polyglutamine (polyQ) tract in the human TATA-box-binding protein (hTBP) causes the neurodegenerative disease spinocerebellar ataxia 17 (SCA17). To investigate the pathological effects of polyQ expansion, we established a SCA17 model in Drosophila. Similar to SCA17 patients, transgenic flies expressing a mutant hTBP protein with an expanded polyQ tract (hTBP80Q) exhibit progressive neurodegeneration, late-onset locomotor impairment and shortened lifespan. Microarray analysis reveals that hTBP80Q causes widespread and time-dependent transcriptional dysregulation in Drosophila. In a candidate screen for genetic modifiers, we identified RBP-J/Su(H), a transcription factor that contains Q/N-rich domains and participates in Notch signaling. Knockdown of Su(H) by RNAi further enhances hTBP80Q-induced eye defects, whereas overexpression of Su(H) suppresses such defects. While the Su(H) transcript level is not significantly altered in hTBP80Q-expressing flies, genes that contain Su(H)-binding sites are among those that are dysregulated. We further show that hTBP80Q interacts more efficiently with Su(H) than wild-type hTBP, suggesting that a reduction in the fraction of Su(H) available for its normal cellular functions contributes to hTBP80Q-induced phenotypes. While the Notch signaling pathway has been implicated in several neurological disorders, our study suggests a possibility that the activity of its nuclear component RBP-J/Su(H) may modulate the pathological progression in SCA17 patients.

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