Reanimation of the Lower Lip with the Anterior Belly of Digastric Transfer: A Systematic Review.

Background: Dynamic reanimation of the lower lip is a challenging issue for patients, with depressor asymmetry commonly addressed with chemodenervation, selective neurectomy, or myectomy. Objective: To determine whether the anterior belly of digastric transfer is an effective method of lower-lip reanimation for patients with either isolated marginal mandibular branch weakness or inadequate depressor function after hemifacial reanimation, as measured by patient satisfaction and objective symmetry evaluation. Method: Systematic review of the literature was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Abstracts and full texts were reviewed. A Risk of Bias assessment was performed. Results: Nine studies with 164 patients were included. Anterior belly of digastric transfer was successfully performed in 162 patients. Most patients (52%) underwent one-staged reanimation innervated by the native nerve to the mylohyoid. A two-staged approach after placement of a cross face nerve graft was performed in 46%. Patient satisfaction was excellent (90.6%), with minimal complications including revision (4/162), infection (4/162), and lipofilling (8/162). Conclusion: In patients seeking a permanent outcome, use of an anterior belly of digastric transfer in either a one-stage or two-stage approach appears to be a safe and effective method to restore symmetry and dynamic function.

Deformity, etiology, solution, sequence (DESS): Facial analysis in rhinoplasty.

PURPOSE: Rhinoplasty is amongst the most challenging surgeries to perfect and can take decades. This process begins during residency; however, residents often have limited exposure to rhinoplasty during their training and lack a standardized method for systematically analyzing and formulating a surgical plan. The DESS (Deformity, Etiology, Solution, Sequence) is a novel educational format for residents that serves to increase their pre-operative comfort with the surgical evaluation and intraoperative planning for a rhinoplasty. MATERIALS AND METHODS: A qualitative study performed at a tertiary academic institution with an otolaryngology residency program evaluating three consecutive residency classes comprised of four residents per class. A 9-item questionnaire was distributed to measure change in resident comfort after utilizing the DESS during their facial plastics rotation. Questionnaire responses highlighted resident comfort with facial nasal analysis, identifying deformities, suggesting surgical maneuvers, and synthesizing a comprehensive surgical plan. RESULTS: Ten of the twelve residents surveyed responded. Of those that responded, comfort in facial nasal analysis, identification of common nasal deformities, surgical planning, and development of an overall surgical plan were significantly improved after completion of the facial plastic rotation. These residents largely attributed their success to the systematic educational format, with an average score of 4.8/5.0 (SD 0.42). CONCLUSION: While rhinoplasty is a challenging artform to master, systematic approaches to analysis and operative planning are vital for teaching and guiding residents. Through this novel methodology, residents display significant improvement in their comfort with facial nasal analysis and overall surgical preparation.

Correction of the Nasal Ala.

The alar-columellar relationship is an important concept for the rhinoplasty surgeon to master. The alar rim in particular is a critical component of the nasal tip, contributing to both overall symmetry and proportion of the nasal base. The retracted ala creates a displeasing aesthetic to the tip complex, distorts the nostril openings, and may have functional implications of the external nasal valve. While alar retraction can occur naturally or as the result of trauma, the majority of cases are post-surgical in nature. Many techniques have been described for correction of alar retraction, most of which require open rhinoplasty and many fail to add the soft tissue within the vestibule necessary to properly lower the alar margin. Herein, we present our experience with the auricular chondrocutaneous composite graft-a simple, reliable, and effective technique to correct moderate to severe alar retraction via either open or endonasal rhinoplasty.

Nasolacrimal Duct Management During Endoscopic Sinus and Skull Base Surgery.

OBJECTIVE: To evaluate rates of epiphora after transection and marsupialization of the nasolacrimal duct (NLD) during endoscopic sinus and skull base surgery. INTRODUCTION: The nasolacrimal canal forms part of the medial wall of the maxillary sinus. Transecting the NLD is sometimes necessary for tumor resection or surgical access to maxillary sinus and infratemporal fossa pathology. There is no consensus for the endoscopic management of the NLD when only the duct is transected without involving the nasolacrimal sac. METHODS: Medical records of 29 patients from 2 academic institutions who underwent endoscopic sinus and skull base surgery with transection of the NLD were retrospectively reviewed. Whether the duct was marsupialized or simply transected was recorded, and the postoperative rate of epiphora was calculated. RESULTS: Mean age was 59 years (range, 14-86 years). Mean follow-up was 10.5 months (range, 1-33 months). The NLD was marsupialized in 16 (55%) and simply transected in 13 (45%) patients. Six patients underwent postoperative radiation. No patients in the marsupialization group had epiphora postoperatively, all with Munk score of 0. One patient in the transection group developed postoperative epiphora with Munk score of 1. Pathology included inverted papilloma (8), acute on chronic inflammation (6), B-cell lymphoma (3), juvenile nasopharyngeal angiofibroma (2), squamous cell carcinoma (2), Schneiderian papilloma (2), metastatic melanoma (1), HPV-related carcinoma (1), adenocarcinoma (1), benign epithelial cyst (1), adenoid cystic carcinoma (1), and erosive chronic sinusitis without nasal polyposis (1). CONCLUSION: Management after transection of the NLD varies widely. The duct may be simply transected or marsupialized, or a formal dacryocystorhinostomy can be performed. The surgeon must also choose whether to place a stent. Based on our small series and review of the literature, marsupialization or simple transection of the NLD results in a low rate of postoperative epiphora in the setting of endoscopic sinus and skull base surgery.

Clinically significant cancer rates in incidentally discovered thyroid nodules by routine imaging.

BACKGROUND: With widespread use of diagnostic imaging modalities, incidental thyroid nodules are frequently identified in patients for unrelated reasons. If underlying thyroid cancer risk in such patients is significant, further evaluation becomes imperative. This study evaluates the malignancy rate of incidentally discovered compared to clinically apparent thyroid nodules in surgical patients. METHODS: A retrospective review of prospectively collected data of 809 patients who underwent thyroidectomy at a tertiary referral center was performed. The association between incidental discovery of thyroid nodules, malignancy rates, and clinicopathologic characteristics was assessed. RESULTS: Of 809 patients, 12% (n = 98) had incidental thyroid nodules, where malignancy was found in 65 (66%) of these patients. The overall rate of malignancy identified incidentally by routine imaging was 14% (65/466). Most common imaging modalities leading to detection were ultrasound (32%), computed tomography (29%), and magnetic resonance imaging (23%). Of patients with incidental thyroid nodules harboring malignancy, follicular variant papillary thyroid cancer (PTC) (48%), classical variant PTC (18%), tall cell variant PTC (12%), and diffuse sclerosing variant PTC (12%) were most commonly found. Patients with malignant incidental thyroid nodules had more lymphovascular invasion and positive lymph nodes compared to nonincidental malignant thyroid nodules (53% versus 41% and 47% versus 33%, P < 0.05, respectively). CONCLUSIONS: Incidentally discovered thyroid nodules by imaging represent an important group of surgical patients with clinically significant rates of underlying malignancy. Patients with incidentally discovered thyroid nodules by imaging should undergo appropriate evaluation and counseling for further surgical treatment.

Excitatory glutamate is essential for development and maintenance of the piloneural mechanoreceptor.

The piloneural collar in mammalian hairy skin comprises an intricate pattern of circumferential and longitudinal sensory afferents that innervate primary and secondary pelage hairs. The longitudinal afferents tightly associate with terminal Schwann cell processes to form encapsulated lanceolate nerve endings of rapidly adapting mechanoreceptors. The molecular basis for piloneural development, maintenance and function is poorly understood. Here, we show that Nefh-expressing glutamatergic neurons represent a major population of longitudinal and circumferential sensory afferents innervating the piloneural collar. Our findings using a VGLUT2 conditional-null mouse model indicate that glutamate is essential for innervation, patterning and differentiation of NMDAR(+) terminal Schwann cells during piloneural collar development. Similarly, treatment of adult mice with a selective NMDAR antagonist severely perturbed piloneural collar structure and reduced excitability of these mechanosensory neurons. Collectively, these results show that DRG-derived glutamate is essential for the proper development, maintenance and sensory function of the piloneural mechanoreceptor.

Replication-independent histone deposition by the HIR complex and Asf1.

The orderly deposition of histones onto DNA is mediated by conserved assembly complexes, including chromatin assembly factor-1 (CAF-1) and the Hir proteins . CAF-1 and the Hir proteins operate in distinct but functionally overlapping histone deposition pathways in vivo . The Hir proteins and CAF-1 share a common partner, the highly conserved histone H3/H4 binding protein Asf1, which binds the middle subunit of CAF-1 as well as to Hir proteins . Asf1 binds to newly synthesized histones H3/H4 , and this complex stimulates histone deposition by CAF-1 . In yeast, Asf1 is required for the contribution of the Hir proteins to gene silencing . Here, we demonstrate that Hir1, Hir2, Hir3, and Hpc2 comprise the HIR complex, which copurifies with the histone deposition protein Asf1. Together, the HIR complex and Asf1 deposit histones onto DNA in a replication-independent manner. Histone deposition by the HIR complex and Asf1 is impaired by a mutation in Asf1 that inhibits HIR binding. These data indicate that the HIR complex and Asf1 proteins function together as a conserved eukaryotic pathway for histone replacement throughout the cell cycle.

Histone deposition protein Asf1 maintains DNA replisome integrity and interacts with replication factor C.

Chromatin assembly and DNA replication are temporally coupled, and DNA replication in the absence of histone synthesis causes inviability. Here we demonstrate that chromatin assembly factor Asf1 also affects DNA replication. In budding yeast cells lacking Asf1, the amounts of several DNA replication proteins, including replication factor C (RFC), proliferating cell nuclear antigen (PCNA), and DNA polymerase epsilon (Pol epsilon), are reduced at stalled replication forks. In contrast, DNA polymerase alpha (Pol alpha) accumulates to higher than normal levels at stalled forks in asf1Delta cells. Using purified, recombinant proteins, we demonstrate that RFC directly binds Asf1 and can recruit Asf1 to DNA molecules in vitro. We conclude that histone chaperone protein Asf1 maintains a subset of replication elongation factors at stalled replication forks and directly interacts with the replication machinery.

Structure and function of the conserved core of histone deposition protein Asf1.

BACKGROUND: Asf1 is a ubiquitous eukaryotic histone binding and deposition protein that mediates nucleosome formation in vitro and is required for genome stability in vivo. Studies in a variety of organisms have defined Asf1's role as a histone chaperone during DNA replication through specific interactions with histones H3/H4 and the histone deposition factor CAF-I. In addition to its role in replication, conserved interactions with proteins involved in chromatin silencing, transcription, chromatin remodeling, and DNA repair have also established Asf1 as an important component of a number of chromatin assembly and modulation complexes. RESULTS: We demonstrate that the highly conserved N-terminal domain of S. cerevisiae Asf1 (Asf1N) is the core region that mediates all tested functions of the full-length protein. The crystal structure of this core domain, determined to 1.5 A resolution, reveals a compact immunoglobulin-like beta sandwich fold topped by three helical linkers. The surface of Asf1 displays a conserved hydrophobic groove flanked on one side by an area of strong electronegative surface potential. These regions represent potential binding sites for histones and other interacting proteins. The structural model also allowed us to interpret mutagenesis studies of the human Asf1a/HIRA interaction and to functionally define the region of Asf1 responsible for Hir1-dependent telomeric silencing in budding yeast. CONCLUSIONS: The evolutionarily conserved, N-terminal 155 amino acids of histone deposition protein Asf1 are functional in vitro and in vivo. This core region of Asf1 adopts a compact immunoglobulin-fold structure with distinct surface characteristics, including a Hir protein binding region required for gene silencing.

Defective S phase chromatin assembly causes DNA damage, activation of the S phase checkpoint, and S phase arrest.

The S phase checkpoint protects the genome from spontaneous damage during DNA replication, although the cause of damage has been unknown. We used a dominant-negative mutant of a subunit of CAF-I, a complex that assembles newly synthesized DNA into nucleosomes, to inhibit S phase chromatin assembly and found that this induced S phase arrest. Arrest was accompanied by DNA damage and S phase checkpoint activation and required ATR or ATM kinase activity. These results show that in human cells CAF-I activity is required for completion of S phase and that a defect in chromatin assembly can itself induce DNA damage. We propose that errors in chromatin assembly, occurring spontaneously or caused by genetic mutations or environmental agents, contribute to genome instability.

Chromatin assembly factor I and Hir proteins contribute to building functional kinetochores in S. cerevisiae.

Budding yeast centromeres are comprised of approximately 125-bp DNA sequences that direct formation of the kinetochore, a specialized chromatin structure that mediates spindle attachment to chromosomes. We report here a novel role for the histone deposition complex chromatin assembly factor I (CAF-I) in building centromeric chromatin. The contribution of CAF-I to kinetochore function overlaps that of the Hir proteins, which have also been implicated in nucleosome formation and heterochromatic gene silencing. cacDelta hirDelta double mutant cells lacking both CAF-I and Hir proteins are delayed in anaphase entry in a spindle assembly checkpoint-dependent manner. Further, cacDelta and hirDelta deletions together cause increased rates of chromosome missegregation, genetic synergies with mutations in kinetochore protein genes, and alterations in centromeric chromatin structure. Finally, CAF-I subunits and Hir1 are enriched at centromeres, indicating that these proteins make a direct contribution to centromeric chromatin structures.