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Enones are widely utilized linchpin functional groups in chemical synthesis and molecular biology. We herein report the direct conversion of boronic esters into enones using commercially available methoxyallene as a three-carbon building block. Following boronate complex formation by reaction of the boronic ester with lithiated-methoxyallene, protonation triggers a stereospecific 1,2-migration before oxidation generates the enone. The protocol shows broad substrate scope and complete enantiospecificity is observed with chiral migrating groups. In addition, various electrophiles could be used to induce 1,2-migration and give a much broader range of α-functionalized enones. Finally, the methodology was applied to a 14-step synthesis of the enone-containing polyketide 10-deoxymethynolide., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Objective  To investigate the incidence and degree of contralateral sinus disease following treatment of sinonasal malignancy (SNM) using radiological findings as an outcome measure. Study Design  Retrospective case series. Setting  Tertiary referral academic center. Participants  Patients with SNM treated with surgical and adjuvant radiotherapy with or without concurrent chemotherapy. Main Outcome Measures  Pre- and posttreatment computed tomography and magnetic resonance imaging scans, Lund-Mackay (LM) score, date of diagnosis, chemotherapy, and dosage of radiation therapy (RT). Results  There was a significant difference between pre- and posttreatment LM scores ( p  < 0.001) of the contralateral paranasal sinuses. There was no statistical significance between the change in pre- and posttreatment LM scores and patient age, gender, chemotherapy, RT dosage, and time lapse between diagnosis and when we performed this study in the univariate and the multivariable analyses. Conclusions  Following treatment of SNM with surgical resection and RT, there was a significant increase in incidence and degree of mucosal thickening of the contralateral sinus by LM grading that persisted after the completion of treatment. This indicates the need for long-term follow-up to monitor for chronic rhinosinusitis as a delayed complication following treatment of SNM.

Objectives/hypothesis: The hypoglossal nerve (XII) has been used as a donor nerve in facial and laryngeal reinnervation. The purpose of this study was to investigate the neuromuscular changes that occur within the tongue following partial or complete transection of XII using a canine model., Study Design: Histopathological comparison of tongue denervation following two types of XII resection in a canine model., Methods: Ten adult canines underwent complete unilateral resection of XII or resection of only the medial terminal branch of the hypoglossal nerve (mXII). After 6 months of recovery, tongue specimens were analyzed histopathologically using whole cross-sections. Routine histologic sections were assessed by two neuropathologists blinded to the type of denervation. The cross-sectional area was calculated of both sides of the tongue, and the amount of myosin was quantified morphometrically using immunohistochemistry for myosin (antimyosin heavy chain, fast isotype). Statistical comparison between partial and complete denervation was performed using the Student t test., Results: Six months following XII transection, quantitative measures of the cross-sectional area of the tongue and content of myosin demonstrated severe muscle atrophy on the operated side of the tongue for both groups, compared to the nonoperated side. For partial transection involving only mXII, the degree of atrophy was less severe (P < .05)., Conclusions: This study provides new histological information demonstrating that partial resection of the hypoglossal nerve, sacrificing only the proximal medial branch of the hypoglossal nerve (mXII), results in less severe atrophy of the tongue than complete transection of the entire hypoglossal nerve., Level of Evidence: NA Laryngoscope, 126:2689-2693, 2016., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To characterize our experience with the surgical management of anterior skull base malignancy, and to propose an algorithm for surgical approach to anterior skull base malignancies., Design: Retrospective review., Setting: Academic cranial base center., Participants: Sixty-seven patients who underwent resection of paranasal sinus or anterior skull base malignancy with an endoscopic, cranioendoscopic, or traditional anterior craniofacial approach., Outcome Measures: Complications, recurrence, and survival., Results: There were 48 males and 19 females, ranging from 6 to 88 years old. There were three groups: endonasal endoscopic resection (n = 10), cranioendoscopic resection (n = 12), and traditional craniofacial resection (n = 45). The most common tumor pathologies included esthesioneuroblastoma, squamous cell carcinoma, and sinonasal undifferentiated carcinoma. Patients with T3/T4 disease were less likely to undergo endoscopic resection (p = 0.007). The 5-year disease-free survival was 82.1% overall, with no statistically significant differences among approaches. There were no differences in orbital complications, meningitis, or cerebrospinal fluid leak. Use of a transfacial incisions predisposed patients to surgical site infection and sinocutaneous fistulae. An algorithm for surgical approach was developed based on these results., Conclusion: Sinonasal and skull base malignancies can be safely surgically addressed via several approaches. Surgical approach should be selected algorithmically based on preoperative clinical assessment of the tumor and known postoperative complication rates.

Objective: To collect data on skull base surgery training experiences and practice patterns of otolaryngologists that recently completed fellowship training., Design: A 24-item survey was disseminated to physicians who completed otolaryngology fellowships in rhinology, head and neck oncology, or neurotology between 2010 and 2014., Results: During a typical year, 50% of rhinologists performed more than 20 endoscopic anterior skull base cases, 83% performed fewer than 20 open cases, and were more confident performing advanced transplanum (p = 0.02) and transclival (p = 0.03) endoscopic approaches than head and neck surgeons. Head and neck surgeons performed fewer than 20 endoscopic and fewer than 20 open cases in 100% of respondents and were more confident with open approaches than rhinologists (p = 0.02). Neurotologists performed more than 20 lateral skull base cases in 45% of respondents during a typical year, fewer than 20 endoscopic ear cases in 95%, and were very comfortable performing lateral skull base approaches., Conclusion: Many recent otolaryngology fellowship graduates are integrating skull base surgery into their practices. Respondents reported high confidence levels performing a range of cranial base approaches. Exposure to endoscopic ear techniques is minimal in neurotology training, and rhinology training appears to offer increased exposure to skull base surgery compared with head and neck training.

Importance: Patients with a septal deviation and concerns about nasal obstruction often undergo septoplasty to improve nasal airflow. Following primary septoplasty, however, some patients have persistent symptoms due to nasal valve dysfunction and may require nasal valve surgery., Objectives: To evaluate the change in disease-specific quality of life for patients who undergo nasal valve correction after failed septoplasty using the Nasal Obstruction Symptom Evaluation (NOSE) survey and to determine whether identifiable anatomical risk factors are more common in patients with a history of failed septoplasty., Design, Setting, and Participants: Prospective observational outcomes study conducted at a tertiary care medical center. Forty patients who underwent nasal valve correction through an open approach from January 1, 2012, through December 31, 2014, with a history of septoplasty for nasal obstruction were included. Data analysis was conducted from January 1, 2013, through May 1, 2015. [corrected]., Interventions: Demographic information, a standardized nasal examination, and preoperative and postoperative NOSE scores were collected and reviewed., Main Outcomes and Measures: Comparison between preoperative and postoperative NOSE scores at 2, 4, and more than 6 months after surgery., Results: Forty patients were included in the study; 23 (57%) were male and 17 (43%) were female. The mean age was 39.3 years. Findings from preoperative nasal examination demonstrated moderate or severe internal nasal valve narrowing in 38 (95%) patients, internal nasal valve collapse in 19 (48%), external nasal valve narrowing in 18 (45%), or external nasal valve collapse in 16 (40%). The most common anatomical cause of obstruction was internal nasal valve narrowing in 38 (95%) patients, dorsal septum deflection in 26 (65%), and narrowed middle vault in 16 (40%). The mean (SD) preoperative NOSE score was 75.7 (20.1). Mean (SD) postoperative NOSE scores at 2, 4, and greater than 6 months were 31.4 (27.2), 34.0 (19.8), and 22.1 (18.8), respectively, with significantly improved NOSE scores at each time point compared with before surgery (P < .001)., Conclusions and Relevance: Nasal valve dysfunction remains an underdiagnosed entity and should be considered in all patients with septal deviation before septoplasty, especially in patients with a severe dorsal deflection and a narrow middle vault. In this study, surgical nasal valve correction demonstrated a significant reduction in nasal obstruction, as measured by a validated outcome measure, in patients for whom a previous septoplasty had failed., Level of Evidence: 4.

Importance: Vocal fold immobility following injury to the recurrent laryngeal nerve (RLN) may lead to substantial morbidity. A reinnervation treatment strategy offers several theoretical benefits over static treatment options. This study evaluates the robustness of reinnervation of the larynx using a split-hypoglossal nerve graft in an animal model, with outcomes assessed by independent blinded review., Objectives: To assess whether a full-hypoglossal nerve graft to the RLN after RLN section can provide return of dynamic vocal fold motion in a canine model, and to validate that a split-hypoglossal nerve graft to the RLN may also provide dynamic vocal fold motion to rehabilitate laryngeal function in a canine model., Design, Setting, and Subjects: A pilot animal study to assess the feasibility and morbidity of laryngeal reinnervation following RLN injury with an end-to-end full-hypoglossal or split-hypoglossal nerve graft was performed at an animal care and research facility in 10 adult female dogs. The study dates were January to July 2013., Interventions: We performed full-hypoglossal (full XII group [n = 5]) and split-hypoglossal (split XII group [n = 5]) nerve grafts to the RLN in a canine model following RLN section., Main Outcomes and Measures: Morbidity was evaluated through scored feeding observation. Laryngeal function was assessed by video laryngoscopy and evoked laryngeal electromyography was performed at baseline and 6 months after surgery. Video laryngoscopy was graded by independent reviewers blinded to study intervention., Results: No clinically significant morbidity was identified after surgery. On review of video laryngoscopy, all 5 animals in the full XII group and all 5 animals in the split XII group demonstrated vocal fold motion by at least 1 independent reviewer. All 3 reviewers agreed on motion in 1 of 5 animals in the full XII group and in 1 of 5 animals in the split XII group. Stimulation of the hypoglossal nerve demonstrated neural connection on evoked laryngeal electromyography in all animals at 6 months., Conclusions and Relevance: This study confirms that a full-hypoglossal or split-hypoglossal nerve graft may restore vocal fold motion, without significant functional morbidity, following RLN section in a canine model.

Objectives/hypothesis: Determine trends in global health-related publication in otolaryngology., Study Design: A review of research databases., Methods: A search of publications available on PubMed and nine additional databases was undertaken reviewing two time periods 10 years apart for the timeframes 1998 to 2002 (early time period) and 2008 to 2012 (recent time period) using specific search terms to identify global health-related publications in otolaryngology. Publications were examined for region of origin, subspecialty, type of publication, and evidence of international collaboration. χ and t test analyses were used to identify trends., Results: In the 1998 to 2002 time period, a total of 26 publications met inclusion criteria for the study, with a mean of 5.2 ± 2.8 publications per year. In the 2008 to 2012 time period, a total of 61 publications met inclusion criteria, with a mean of 12.3 ± 5.6 publications per year. The 235% increase in global health-related publications identified between the two study periods was statistically significant (P = .02). The absolute number of publications in which collaboration occurred between countries increased from three in the early time period to nine the recent time period., Conclusions: There has been a significant increase in the volume of global health-related publications in English language otolaryngology journals over the past decade, providing strong evidence of the increasing trend of global health as an academic pursuit within the field of otolaryngology., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To determine the value of a collaborative course for advanced head and neck surgery in East Africa., Study Design: Survey of participants., Methods: A 3-day course in head and neck surgery was designed for otolaryngologists and trainees from Kenya and surrounding countries through a collaborative effort between Kenyatta National Hospital, the University of Nairobi, and the Head and Neck Divisions from the Vanderbilt Bill Wilkerson Center and the Massachusetts Eye and Ear Infirmary. Topics included neck dissection, parotidectomy, total laryngectomy, parapharyngeal space tumors excision, and pectoralis myocutaneous flaps. A pre- and postcourse self-evaluation survey was administered to measure course impact., Results: Eighteen otolaryngologists and trainees participated in the course, with 17 completing course surveys. The majority of participants (72%) were from Kenya. Prior to the start of the course, 41%, 71%, 23%, 12%, and 0% of participants indicated they could complete a neck dissection, parotidectomy, parapharyngeal space mass excision, total laryngectomy, and pectoralis myocutaneous flap, respectively. Following the course, 50%, 94%, 69%, 25%, and 38% of participants indicated they could complete a neck dissection, parotidectomy, total laryngectomy, parapharyngeal space tumors excision, respectively, with a statistically significant increase identified for pectoralis myocutaneous flaps (P < .001) and total laryngectomy (P = .009). There was also a trend toward an increase in the number of participants indicating an ability to complete parotidectomy following the course (P = .085)., Conclusions: This survey demonstrates the potential value of a collaborative course in advanced head and neck surgery as one useful model for increasing the number of well-trained head and neck surgeons in East Africa., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To characterize patterns of utilization and outcomes following transfusion in head and neck patients undergoing free flap reconstruction., Study Design: Case series with chart review., Setting: Tertiary academic medical center., Subjects and Methods: Two hundred eighty-two head and neck patients undergoing free flap reconstruction from 2011 to 2013. Outcome parameters included post-transfusion hematocrit increase, length of stay (LOS), flap survival, and perioperative complications., Results: Of all head and neck free flap patients, 48.9% received blood transfusions. Average pretransfusion hametocrit (Hct) was 24.7%±0.2% with 2.5±0.1 units of blood transfused. Transfused patients were more likely to have been taken back to the operating room. Rates of transfusion were similar between flap types, although anterolateral thigh (ALT) and fibular free flap (FFF) patients had higher transfusion requirements compared to radial forearm free flap (RFFF) patients. Further, FFF patients trended toward receiving transfusions earlier. Transfusion did not influence flap survival but was associated with wound dehiscence, myocardial infarction, congestive heart failure, respiratory distress, and pneumonia. Subset analyses by flap type revealed that differences were significant among the RFFF and FFF cohorts but not ALT patients. When comparing patients who were transfused for Hct<21 to those transfused for Hct<27, there were no differences in LOS, flap survival, or postsurgical complications., Conclusions: Among the different types of flaps, FFF and ALT are associated with higher transfusion requirements. Transfusion in patients undergoing free flap reconstruction does not significantly affect flap survival but was associated with perioperative complications. Our data support consideration of a restrictive transfusion policy in free flap patients., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.)

Objective To determine trends in sinonasal undifferentiated carcinoma (SNUC) survival patterns in the United States. Design Retrospective review of national database. Participants All cases of SNUC in the National Cancer Institute's Surveillance Epidemiology and End Results program from 1973 to 2010 were examined. Main Outcome Measures Age-adjusted incidence and survival rates were calculated and stratified by demographic information and treatment modality. Cohort analysis was performed to analyze survival patterns over time. Results A total of 318 SNUC cases were identified. Age-adjusted incidence rate (IR) was 0.02 per 100,000. Incidence was greater in males (IR: 0.03) than females (IR: 0.01; p = 0.03). Overall 5- and 10-year relative survival rate was 34.9% and 31.3%, respectively. Overall median survival was 22.1 months. Median survival following surgery combined with radiation was 41.9 months. Five-year relative survival rate following surgery, radiation, or surgery combined with radiation was 38.7%, 36.0%, and 39.1%, respectively. Median survival from 1973-1986 and 1987-2010 was 14.5 and 23.5 months, respectively. Conclusions This study provides new data regarding survival patterns of SNUC in the United States, confirming survival benefit with surgery and radiation as well as identifying a trend toward improved survival in recent decades.

Objectives/hypothesis: To identify histopathologic features associated with poor correlation of frozen and permanent pathology margins following wide local excision for advanced cutaneous squamous cell carcinomas of the head and neck., Study Design: Retrospective review., Methods: A retrospective review of patients undergoing excision of advanced head and neck squamous cell carcinomas between the years 2010 AND 2013 was performed. Demographic, operative, and pathology data were collected. Overall correlation between frozen section margins and final margins on permanent section results was calculated. Positive and negative predictive values of several histopathologic features were determined., Results: Forty-one cases were identified from the database. Perineural invasion, lymphovascular invasion, and a component of poorly differentiated carcinoma were identified in 61.3%, 34.5%, and 17.1% of cases, respectively. Discrepancy between frozen section margins and permanent margins was identified in eight cases (19.5%). The false-negative rate for poorly differentiated carcinoma, lymphovascular invasion, and perineural invasion was 14%, 36%, 26%, respectively. The positive and negative predictive value of poorly differentiated carcinoma, lymphovascular invasion, and perineural invasion in predicting discrepancy between frozen and permanent margins was 14% and 80%, 36% and 84%, and 26% and 92%, respectively., Conclusions: This study demonstrated a moderate rate of discrepancy between frozen and permanent section analysis of operative margins from high-risk cutaneous squamous cell carcinomas of the head and neck. The presence or absence of certain histopathologic features appears to be associated with a higher rate of frozen section discrepancy. Evaluation of these features in a preoperative biopsy or staging excision may be useful in planning definitive excision and reconstruction., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Intra-operative nerve monitoring (IONM) of the recurrent laryngeal nerve (RLN) during thyroid and parathyroid surgery is thought to aid in identification and dissection of the RLN. While utilization of IONM is increasing, one area of variability in its application is the assessment of adequate endotracheal tube electrode placement for IONM during the case. The main objective of this study is to assess the overall success of utilizing respiratory variation to confirm proper endotracheal tube placement for RLN monitoring., Methods: A prospective study of RLN monitoring during thyroid and parathyroid surgery at an academic referral center., Results: Fifty-five cases were included. Fifty (91 %) achieved optimal respiratory variation during endotracheal tube position. Five (9 %) required repeat laryngoscopy to confirm correct endotracheal tube placement following patient positioning. For the respiratory variation group, average amplitude achieved during initial vagus, maximum vagus, initial RLN, and maximal RLN was 700 (± 474) mA, 921 (± 616) mA, 887 (± 584) mA, and 1330 (± 843) mA during evoked stimulation, respectively. For the repeat laryngoscopy group, average amplitude achieved during initial vagus, maximum vagus, initial RLN, and maximal RLN evoked stimulation was 591 (± 364) mA, 959 (± 306) mA, 771 (± 424) mA, and 1462 (± 855) mA during evoked stimulation, respectively. There was no statistical difference between the two groups for average initial vagus amplitude (p = 0.62), average maximum vagus amplitude (p = 0.89), average initial RLN amplitude (p = 0.67), or average maximum RLN amplitude (p = 0.74)., Conclusion: The findings of this study support the International Neural Monitoring Study Group recommendation that confirmation of endotracheal tube electrode placement be performed either by confirmation of adequate respiratory variation or by repeat direct laryngoscopy.

Objectives/hypothesis: To determine trends in survival patterns for cranial chordoma in the United States., Study Design: A cross-sectional analysis of a national healthcare database., Methods: All cases of microscopically confirmed cranial chordoma between 1973 and 2009 from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute were examined. Age-adjusted incidence and survival rates were calculated and stratified by treatment. Additionally, in order to assess trends over time, comparisons in survival were conducted for 3 calendar year cohorts: 1975 to 1984, 1985 to 1994, and 1995 to 2004., Results: A total of 594 cases of microscopically confirmed chordoma involving cranial sites were identified, which accounted for 42% of all chordomas. Age-adjusted incidence rate (IR) of all chordomas was 0.089 per 100,000. Overall median survival time with surgery plus radiation was 9.2 years. Age and treatment modality were found to influence patient survival. Specifically, age > 50 years was associated with a significant increase in mortality rate (P < .05). Five-year survival for the 1975 to 1984, 1985 to 1994, and 1995 to 2004 cohort was 48.5%, 73.0%, and 80.7%, respectively, with improved survival in the more recent cohorts (P < 0.01)., Conclusion: This study provides new data regarding survival patterns of cranial chordoma in the United States, with a trend toward improvement in survival in recent decades., (© 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives To update the Massachusetts General Hospital (MGH) and Massachusetts Eye and Ear Infirmary (MEEI) experience in the management of esthesioneuroblastoma (ENB) with multimodality therapy and to reassess treatment outcomes and complications in a larger cohort with longer follow-up times. Design A retrospective chart review. Setting A tertiary referral center. Participants All patients presenting with ENB and managed at the MGH and MEEI from 1997 to 2013. Main Outcome Measures Disease-free and overall survival. Results Twenty-two patients were identified with an average follow-up of 73 months. Ten patients presented with Kadish stage B disease and 12 with stage C disease. A total of six patients (27%) developed regional metastases. Treatment for all patients included craniofacial resection (CFR) followed by proton beam irradiation with or without chemotherapy. The 5-year disease-free and overall survival rates were 86.4% and 95.2%, respectively, by Kaplan-Meier analysis. Negative margins were a significant factor in disease-free survival. One patient experienced severe late-radiation toxicity. Conclusions ENB is safely and effectively treated with CFR followed by proton beam irradiation. The high incidence of regional metastases warrants strong consideration for elective neck irradiation. Proton beam radiation is associated with lower rates of severe late-radiation toxicity than conventional radiotherapy.

Objectives/hypothesis: To determine trends in office visits and medical specialty seen for surgical diagnoses of the thyroid gland., Study Design: A cross-sectional analysis of a national healthcare database., Methods: From the National Ambulatory Medical Care Survey (NAMCS), all cases of surgical thyroid disorders (e.g., benign neoplasm of thyroid gland, malignant neoplasm of thyroid gland, multinodular goiter) were extracted for 2 calendar year cohorts: 1995 to 1999 and 2005 to 2009. In addition to demographic information, the medical specialty of the health care provider seen was extracted. Comparisons were conducted for the proportion of surgical thyroid cases seen between general surgeons and otolaryngologists for the respective cohorts., Results: In the 1995 to 1999 cohort, there were a total of 107 ± 13 thousand outpatient visits annually to either general surgery or otolaryngology for surgical thyroid conditions. Among these, 62.7 ± 8.4 thousand visits (58.3 ± 5.6%) were seen by general surgery versus 44.8 ± 9.1 thousand (41.7 ± 5.6%) seen by otolaryngology. In comparison, in the 2005 to 2009 cohort, there were 218 ± 29 thousand visits annually for surgical thyroid conditions. Among these, 88.4 ± 17 thousand (40.5 ± 5.4%) were seen by general surgery versus 130 ± 21 thousand (59.5 ± 5.4%) seen by otolaryngology. The increase in proportion of surgical thyroid patients seen by otolaryngology in the second 5 year cohort was statistically significant (P = 0.032, chi-square)., Conclusions: There is a national trend in the United States toward otolaryngologists seeing an increasing majority proportion of increasingly prevalent surgical thyroid conditions. These data objectively confirm the perceived increasing role of otolaryngologists in the management of surgical thyroid disorders on a national level., (Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

To highlight an unusual cause of chronic cough, we present two cases of chronic cough in older children referred to a pediatric otolaryngology outpatient clinic with persistent symptoms despite extensive previous workup and treatment. Cranial neuropathy was identified in each case. As a result, magnetic resonance imaging was performed revealing Chiari type I malformation. In each case, surgical decompression provided symptom improvement. Chronic cough is a rare presenting symptom in children with Chiari type I malformation. We emphasize the significance of awareness for unusual cases of cough to aid in the correct identification and treatment in children., (Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Allergic rhinitis (AR) and chronic rhinosinusitis (CRS) are a major burden to the healthcare system. Although no causal relationship has been established, previous work has demonstrated a strong association of AR with CRS. In this study, we sought to identify risk factors that may influence speed of development of CRS in patients with AR., Methods: Retrospective review of all patients diagnosed with AR without CRS presenting to an otolaryngology clinic at a tertiary medical center as part of a multidisciplinary allergy evaluation between March 2004 and November 2011. Medical records were evaluated for clinicodemographic factors including age, gender, smoking history, medical comorbidities, categories of AR based on formal allergy testing, the presence of sinonasal anatomic variants on computed tomography as well as subsequent development of CRS., Results: Faster progression to CRS in patients with AR was associated with comorbid asthma (hazard ratio [HR] = 3.97) as well as sinonasal anatomic variants, such as infraorbital cells (HR = 7.39), and frontal intersinus cells (HR = 68.03), on multivariate survival analysis. A statistically significant but negative interaction between infraorbital cells and frontal intersinus cells suggests that concomitant presence of both leads to a less than additive increase in the rate of CRS progression., Conclusion: Sinonasal anatomical variants, infraorbital cells, and frontal intersinus cells, as well as comorbid asthma are associated with faster development of CRS in patients with AR. The presence of these clinical risk factors identifies patients who should be counseled on compliance with medical therapy for AR., (© 2013 ARS-AAOA, LLC.)

HIC1 is a newly discovered tumor suppressor and transcriptional repressor that is frequently silenced in human tumors. HIC1 protein expression has been linked to better outcomes in breast cancers. The molecular mechanism underlying HIC1-mediated transcriptional and growth suppression, and the relevant targets of HIC1-mediated transcriptional modulation, is currently unclear. We have identified an HIC1 DNA-binding site in E2F-responsive gene promoters and demonstrate that HIC1 targets E2F-responsive genes for transcriptional regulation and growth suppression. We and others have recently discovered that Brg1, a central component of the SWI/SNF chromatin-remodeling family, is required for the transcriptional regulation of multiple cell cycle control-related genes, including E2F-responsive promoters. We studied HIC1 interactions with, and dependence upon, Brg1 activity, and found that HIC1 can recruit Brg1 to E2F-responsive promoters and that its transcriptional repression of these genes is dependent upon Brg1. These data indicate that HIC1 is a central molecule in a novel mechanism controlling cell growth and that the disruption of this HIC1-mediated pathway may lead to abnormal cell proliferation and, ultimately, cancer.

The SWI/SNF complex participates as a co-activator in the transcriptional regulation of certain genes. Conversely, we and others have recently established that Brg1 and Brm, the central components of SWI/SNF, act instead as co-repressors for E2F-mediated transcriptional repression, and for the transcription of certain other promoters. We report here that Brg-1 and Brm can switch their mode of function at same promoter between activation and repression by ligand-directed differential coordination with BAF155, BAF170, HDAC1, p300 and prohibitin. This ligand and context-dependent reprogramming of the SWI/SNF complex allows it to differentially serve as either a co-repressor or a co-activator of transcription at the same promoter.

Background: Gall bladder dyskinesia describes a clinical entity with symptoms of biliary colic but without objective evidence of gallstones. Recent work has suggested laparoscopic cholecystectomy as an effective treatment although this approach has not gained widespread acceptance in Australia., Methods: At the sole nuclear medicine facility in Mildura, Victoria, a retrospective search of patients with gallbladder ejection fractions

We have identified and cloned a cDNA encoding a new member of the monooxygenase family of enzymes. This novel enzyme, which we call MOX (monooxygenase X; unknown substrate) is a clear sequence homologue of the enzyme dopamine beta-hydroxylase (DBH). MOX maintains many of the structural features of DBH, as evidenced by the retention of most of the disulfide linkages and all of the peptidyl ligands to the active site copper atoms. Unlike DBH, MOX lacks a signal peptide sequence and therefore is unlikely to be a secreted molecule. The steady-state mRNA levels of MOX are highest in the kidney, lung, and adrenal gland, indicating that the tissue distribution of MOX is broader than that of DBH. Antisera raised to a fusion protein of MOX identifies a single band of the expected mobility by Western blot analysis. MOX mRNA levels are elevated in some fibroblast cell strains at replicative senescence, through this regulation is not apparent in all primary cell strains. The gene for MOX resides on the q arm of chromosome 6 and the corresponding mouse homolog has been identified.

Hemoccult slides have been used in an attempt to determine their usefulness as a screening method for the detection of colorectal neoplasia. Two methods have been used. In the first, 300 unprepared patients had an immediate single-stool specimen tested with Hemoccult. Only nine patients were referred for investigation after this single test, and no case of colorectal neoplasia was discovered. In the second method over 2,500 three-stool test kits were distributed to the public, of which 1,160 (46%) have been returned and tested. Positive tests were obtained in 68 patients. Follow-up of 58 of these patients has led to the detection of three cases of carcinoma of the colon and nine cases of benign polyps greater than one centimetre in diameter. The cost of screening patients with a three-stool test has been calculated to be $2.50 per patient.