Naweed I. Chowdhury

CML24, Regulated in Expression by Diverse Stimuli, Encodes a Potential Ca2+ Sensor That Functions in Responses to Abscisic Acid, Daylength, and Ion Stress

Changes in intracellular calcium (Ca2+) levels serve to signal responses to diverse stimuli. Ca2+ signals are likely perceived through proteins that bind Ca2+, undergo conformation changes following Ca2+ binding, and interact with target proteins. The 50-member calmodulin-like (CML) Arabidopsis (Arabidopsis thaliana) family encodes proteins containing the predicted Ca2+-binding EF-hand motif. The functions of virtually all these proteins are unknown. CML24, also known as TCH2, shares over 40% amino acid sequence identity with calmodulin, has four EF hands, and undergoes Ca2+-dependent changes in hydrophobic interaction chromatography and migration rate through denaturing gel electrophoresis, indicating that CML24 binds Ca2+ and, as a consequence, undergoes conformational changes. CML24 expression occurs in all major organs, and transcript levels are increased from 2- to 15-fold in plants subjected to touch, darkness, heat, cold, hydrogen peroxide, abscisic acid (ABA), and indole-3-acetic acid. However, CML24 protein accumulation changes were not detectable. The putative CML24 regulatory region confers reporter expression at sites of predicted mechanical stress; in regions undergoing growth; in vascular tissues and various floral organs; and in stomata, trichomes, and hydathodes. CML24-underexpressing transgenics are resistant to ABA inhibition of germination and seedling growth, are defective in long-day induction of flowering, and have enhanced tolerance to CoCl2, molybdic acid, ZnSO4, and MgCl2. MgCl2 tolerance is not due to reduced uptake or to elevated Ca2+ accumulation. Together, these data present evidence that CML24, a gene expressed in diverse organs and responsive to diverse stimuli, encodes a potential Ca2+ sensor that may function to enable responses to ABA, daylength, and presence of various salts.

Arabidopsis potential calcium sensors regulate nitric oxide levels and the transition to flowering.

In plants, flowering is a critical developmental transition orchestrated by four regulatory pathways. Distinct alleles encoding mutant forms of the Arabidopsis potential calcium sensor CML24 cause alterations in flowering time. CML24 can act as a switch in the response to day length perception; loss-of-function cml24 mutants are late flowering under long days, whereas apparent gain of CML24 function results in early flowering. CML24 function is required for proper CONSTANS (CO) expression; components upstream of CO in the photoperiod pathway are largely unaffected in the cml24 mutants. In conjunction with CML23, a related calmodulin-like protein, CML24 also inhibits FLOWERING LOCUS C (FLC ) expression and therefore impacts the autonomous regulatory pathway of the transition to flowering. Nitric oxide (NO) levels are elevated in cml23/cml24 double mutants and are largely responsible for FLC transcript accumulation. Therefore, CML23 and CML24 are potential calcium sensors that have partially overlapping function that may act to transduce calcium signals to regulate NO accumulation. In turn, NO levels influence the transition to flowering through both the photoperiod and autonomous regulatory pathways.

Comprehensive Diagnostic Battery for Evaluating Sensorineural Hearing Loss in Children

Objective: Selection of diagnostic tests for children with sensorineural hearing loss (SNHL) is influenced by clinical suspicion. Testing results reported in the literature are similarly biased. We evaluate the usefulness of a comprehensive diagnostic battery for each child. Study Design: Retrospective review. Setting: Tertiary care university hospital. Patients: A total of 270 children referred for severe to profound SNHL between January 2002 and June 2009. Interventions: Results of the following were reviewed: magnetic resonance imaging, computed tomography, renal ultrasound, electrocardiography, fluorescent treponemal antibody absorption test, connexin 26 sequencing, genetic consultation, and ophthalmologic consultation. Main Outcome Measure: Diagnostic yield of each test was determined. Results: Each diagnostic test or consultation was completed by at least 95% of patients for whom it was ordered. Magnetic resonance imaging revealed abnormalities explaining SNHL in 24% of patients. Computed tomography showed inner ear anomalies in 18% of patients. Biallelic connexin 26 mutations were found in 15%. Renal ultrasound found anomalies in 4% of patients. Electrocardiography found 1% of patients with prolonged QT intervals. Fluorescent treponemal antibody absorption test result was positive in 0.5%. Genetic consultation found a genetic cause for hearing loss in 25%. Ophthalmologic consultation found abnormalities associated with hearing loss in 8%. Conclusion: Diagnostic radiologic imaging is the highest yielding test for evaluating children with SNHL. Connexin 26 sequencing identifies a nearly nonoverlapping subset of children compared with imaging. Specialty consultations, particularly from a clinical geneticist, can improve diagnostic yield. Other tests, although of lower diagnostic yield for SNHL, can identify important diseases that significantly affect patient health.

Investigating the Minimal Clinically Important Difference for SNOT-22 Symptom Domains in Surgically Managed Chronic Rhinosinusitis

Prior work has described 5 domains within the 22‐item Sino‐Nasal Outcomes Test (SNOT‐22) that allow for stratification of symptoms into similar clusters and that can be used to direct therapy. Although the outcomes of various interventions on these symptom domains have been reported, minimal clinically important difference (MCID) values have not been investigated, which has limited clinical interpretation of these results.

What drives productivity loss in chronic rhinosinusitis? A SNOT-22 subdomain analysis

Previous studies have shown declines in productivity due to chronic rhinosinusitis (CRS) are correlated with disease‐specific quality‐of‐life (QOL) measures. However, it is unclear which symptom domains contribute primarily to productivity loss. This investigation sought to assess the association between CRS‐specific QOL subdomain impairment and productivity loss.

Individualized Surgical Approach Planning for Petroclival Tumors Using a 3D Printer.

Objectives To determine the utility of three-dimensional (3D) printed models in individualized petroclival tumor resection planning by measuring the fidelity of printed anatomical structures and comparing tumor exposure afforded by different approaches. Design Case series and review of the literature. Setting Tertiary care center. Participants Three patients with petroclival lesions. Main Outcome Measures Subjective opinion of access by neuro-otologists and neurosurgeons as well as surface area of tumor exposure. Results Surgeons found the 3D models of each patients skull and tumor useful for preoperative planning. Limitations of individual surgical approaches not identified through preoperative imaging were apparent after 3D models were evaluated. Significant variability in exposure was noted between models for similar or identical approaches. A notable drawback is that our printing process did not replicate mastoid air cells. Conclusions We found that 3D modeling is useful for individualized preoperative planning for approaching petroclival tumors. Our printing techniques did produce authentic replicas of the tumors in relation to bony structures.

Outcomes of HPV-related nasal squamous cell carcinoma

Human papilloma virus (HPV) infection has been shown to play an integral role in the development and prognosis of various head and neck cancers. Generational changes in sexual behavior may have led to an increased incidence of positivity in recent years. HPV positivity in both benign and malignant lesions of the sinonasal cavities has been shown in previous studies (estimates range from 20%–30% for malignancy). We intend to investigate if HPV positivity affected survival outcomes in our patient cohort.

Comparison of surgical outcomes between patients with unilateral and bilateral chronic rhinosinusitis

Although the majority of patients with chronic rhinosinusitis without nasal polyposis (CRSsNP) suffer from bilateral disease, a subset suffer from unilateral disease. Currently, outcomes following endoscopic sinus surgery (ESS) for medically recalcitrant CRS are inferred from outcomes for patients with bilateral disease. This study compares outcomes of ESS between patients with unilateral and bilateral disease.

Assessing the spectrum of germline variation in Fanconi anemia genes among patients with head and neck carcinoma before age 50

Patients with Fanconi anemia (FA) have an increased risk for head and neck squamous cell carcinoma (HNSCC). The authors sought to determine the prevalence of undiagnosed FA and FA carriers among patients with HNSCC as well as an age cutoff for FA genetic screening.

In Reply to: “Effect of Piecemeal vs En Bloc Approaches to the Lateral Temporal Bone on Survival Outcomes”

We read with great interest the article by Muelleman et al concerning piecemeal resection versus lateral temporal bone resection (LTBR) of T1-T3 squamous cell carcinoma (SCC). The authors state that piecemeal resection might be required in cases of low-lying tegmen or laterally placed vascular structures. In the >250 LTBRs performed by our group, these 2 anatomic constraints are exceedingly rare (<5%). Anatomic constraints to standard en bloc LTBR are addressed with careful surgical technique. Low-lying tegmen is handled by following the middle fossa dura medially and anteriorly until the temporomandibular joint capsule is reached. In cases where this bone is <2 mm thick, the superior bony canal is drilled away, but the remaining canal is still intact, allowing en bloc resection. The high-riding jugular bulb and the laterally placed carotid artery present their own challenges. The high-riding jugular bulb is always medial to the facial nerve, and the facial nerve is generally preserved with en bloc LTBR. Thus, staying lateral to the facial nerve and working medial to the annulus allows the surgeon to surpass the highriding jugular. The laterally placed carotid is slightly more difficult to handle and is why osteotomes are not used. Intraoperatively, the lateral carotid canal is identified in the middle ear after the hypotympanic air cells have been removed. The surgeon can then follow the carotid canal and drill between it and the annulus to complete the inferior canal cut. The authors do not adequately describe their patient population. It is unclear if all cases were primary SCC of the ear canal or if they included external ear SCC, periauricular SCC, or metastatic SCC to the parotid gland that secondarily involved the ear canal. The authors omit other confounders between the groups, such as age, bone invasion, perineural invasion, and lymph node metastases. The reason for piecemeal resection is not included. From an oncologic viewpoint, the follow-up time in this series is inadequate (median, 11 months; 40% with <4 months), given that the mean time to recurrence for SCC of the ear canal is 13 months but can be as long as 3 years. In fact, one is unable to determine if there is a simple difference in follow-up time between the groups. This article has too many deficiencies to make any conclusions regarding oncologic safety of such an approach.