Harrison W. Lin

Regulation of stereocilia length by myosin XVa and whirlin depends on the actin-regulatory protein Eps8.

Myosin XVa (MyoXVa) and its cargo whirlin are implicated in deafness and vestibular dysfunction and have been shown to localize at stereocilia tips and to be essential for the elongation of these actin protrusions [1-4]. Given that whirlin has no known actin-regulatory activity, it remains unclear how these proteins work together to influence stereocilia length. Here we show that the actin-regulatory protein Eps8 [5] interacts with MyoXVa and that mice lacking Eps8 show short stereocilia compared to MyoXVa- and whirlin-deficient mice. We show that Eps8 fails to accumulate at the tips of stereocilia in the absence of MyoXVa, that overexpression of MyoXVa results in both elongation of stereocilia and increased accumulation of Eps8 at stereocilia tips, and that the exogenous expression of MyoXVa in MyoXVa-deficient hair cells rescues Eps8 tip localization. We find that Eps8 also interacts with whirlin and that the expression of both Eps8 and MyoXVa at stereocilia tips is reduced in whirlin-deficient mice. We conclude that MyoXVa, whirlin, and Eps8 are integral components of the stereocilia tip complex, where Eps8 is a central actin-regulatory element for elongation of the stereocilia actin core.

Changes and consistencies in the epidemiology of pediatric adenotonsillar surgery, 1996-2006

OBJECTIVE Determine changes in rates for pediatric adenotonsillar procedures over time with attention to infectious indications. STUDY DESIGN Historical cohort study. SETTING Academic medical center. SUBJECTS AND METHODS The National Survey of Ambulatory Surgery and the National Hospital Discharge Survey 1996 and 2006 releases were examined, extracting all cases of pediatric tonsillectomy, adenotonsillectomy, and adenoidectomy. The aggregate numbers and rates of adenotonsillar procedures performed overall and specifically for chronic infectious etiologies were determined. These procedure rates were then compared to determine differences in performance rates between 1996 and 2006. RESULTS In 1996, an estimated 441,870 ± 23,315 children underwent some form of adenotonsillar surgery in the ambulatory and inpatient settings (60,034 ± 6994 tonsillectomies, 255,217 ± 18,960 adenotonsillectomies, and 126,619 ± 11,627 adenoidectomies), while in 2006, the total rose to 695,029 ± 36,979 children (58,111 ± 9645 tonsillectomies, 506,778 ± 32,054 adenotonsillectomies, and 129,540 ± 15,714 adenoidectomies). However, when examined according to infectious indications, a notable decline in the population rate of tonsillectomy from 0.62 per 1000 children in 1996 to 0.53 per 1000 in 2006 was found (P = 0.252). Moreover, the larger decline in the rate of adenotonsillectomy for infectious indications from 2.20 per 1000 to 1.46 per 1000 was significant (P = 0.003). There was no significant change adenoidectomy rates for chronic infectious etiologies (0.25 versus 0.21 per 1000, P = 0.326). CONCLUSION Although there was an overall increase in the rate of performance of adenotonsillar surgery, population adjusted performance rates of these procedures specifically for infectious indications declined from 1996 to 2006.

Distinct subdomain organization and molecular composition of a tight junction with adherens junction features

Most polarized epithelia constrain solute diffusion between luminal and interstitial compartments using tight junctions and generate mechanical strength using adherens junctions. These intercellular junctions are typically portrayed as incongruent macromolecular complexes with distinct protein components. Herein, we delineate the molecular composition and subdomain architecture of an intercellular junction between sensory and non-sensory cells of the inner ear. In this junction, claudins partition into claudin-14 and claudin-9/6 subdomains that are distinguishable by strand morphology, which contrasts with in vitro data that most claudins co-assemble into heteromeric strands. Surprisingly, canonical adherens junction proteins (p120ctn, α- and β-catenins) colocalize with the claudin-9/6 subdomain and recruit a dense cytoskeletal network. We also find that catenins colocalize with claudin-9 and claudin-6, but not claudin-14, in a heterologous system. Together, our data demonstrate that canonical tight junction and adherens junction proteins can be recruited to a single junction in which claudins partition into subdomains and form a novel hybrid tight junction with adherens junction organization.

Balance disorders in the elderly: Epidemiology and functional impact

To quantify the prevalence and determine the impact of dizziness and balance disorders in the elderly.

Clinical behavior of follicular variant of papillary thyroid carcinoma: Presentation and survival

To determine the prevalence and extent of disease characteristics of the follicular variant of papillary thyroid carcinoma (FV‐PTC) and the survival impact of this histopathological diagnosis compared to classical papillary thyroid carcinoma (C‐PTC).

Survival impact of treatment options for papillary microcarcinoma of the thyroid

Evaluate the impact of medical and surgical interventions on the survival of patients with papillary microcarcinoma (PMC) of the thyroid, a common tumor with an increasing worldwide incidence.

Differential cochlear implant outcomes in older adults

The goals of this study were to analyze whether cochlear implant (CI) users over 65 years of age have different surgical and audiological outcomes when compared to younger adult CI users and to identify reasons for these possible differences.

Staging and survival analysis for nonsquamous cell carcinomas of the larynx.

Objective: Determine staging and comparative survival for nonsquamous cell carcinoma (SCC) of the larynx.

Malignant transformation of a highly aggressive human papillomavirus type 11–associated recurrent respiratory papillomatosis

OBJECTIVE The objective is to present an uncommon case of squamous cell carcinoma (SCC) arising from extensive recurrent respiratory papillomatosis (RRP) involving the upper and lower airway and temporal bone. STUDY DESIGN This is a case report and a review of the literature. METHODS We describe a case of a 24-year-old woman with a history of human papillomavirus (HPV) type 11 since childhood originating in the larynx and trachea, then progressing to involve the distal pulmonary alveoli and right middle ear through the eustachian tube. Papillomatous growth was treated with multiple surgeries including laser cytoreduction of laryngotracheal papillomatosis and radical mastoidectomy, followed by a trial of chemotherapy. Despite this aggressive treatment regimen, papillomatous growth progressed with recurrence in the right eustachian tube, middle ear, and mastoid eventually extending to involve the calvaria and scalp. RESULTS The patient underwent a composite resection of involved tissues, including the scalp, auricle, and lateral temporal bone, with reconstruction using a latissimus dorsi free flap. Final pathologic analysis revealed an extensive infiltrative well-differentiated SCC arising from the papilloma. A review of the literature on aggressive respiratory papillomatosis suggests that malignant transformation of juvenile-onset RRP occurs exclusively in cases positive for HPV-11. CONCLUSIONS We report an unusual case of SCC originating from extensive RRP involving the airway, temporal bone, and scalp and describe the medical and surgical management. Although the incidence of juvenile-onset RRP transformation to SCC is very low, the presence of HPV-11 as a risk factor for malignant transformation of RRP is becoming evident.

Survival impact of nodal disease in hard palate and maxillary alveolus cancer

Evaluate the impact of primary site stage and cervical metastasis on the survival of patients with squamous cell carcinoma (SCC) of the hard palate or maxillary alveolus.