Nanopores map the acid-base properties of a single site in a single DNA molecule.

Nanopores are increasingly powerful tools for single molecule sensing, in particular, for sequencing DNA, RNA and peptides. This success has spurred efforts to sequence non-canonical nucleic acid bases and amino acids. While canonical DNA and RNA bases have pKas far from neutral, certain non-canonical bases, natural RNA modifications, and amino acids are known to have pKas near neutral pHs at which nanopore sequencing is typically performed. Previous reports have suggested that the nanopore signal may be sensitive to the protonation state of an individual moiety. We sequenced ion currents with the MspA nanopore using a single stranded DNA containing a single non-canonical DNA base (Z) at various pH conditions. The Z-base has a near-neutral pKa ∼ 7.8. We find that the measured ion current is remarkably sensitive to the protonation state of the Z-base. We demonstrate how nanopores can be used to localize and determine the pKa of individual moieties along a polymer. More broadly, these experiments provide a path to mapping different protonation sites along polymers and give insight in how to optimize sequencing of polymers that contain moieties with near-neutral pKas.

Assessing Readability of an 8-Letter Expanded Deoxyribonucleic Acid Alphabet with Nanopores.

Chemists have now synthesized new kinds of DNA that add nucleotides to the four standard nucleotides (guanine, adenine, cytosine, and thymine) found in standard Terran DNA. Such "artificially expanded genetic information systems" are today used in molecular diagnostics; to support directed evolution to create medically useful receptors, ligands, and catalysts; and to explore issues related to the early evolution of life. Further applications are limited by the inability to directly sequence DNA containing nonstandard nucleotides. Nanopore sequencing is well-suited for this purpose, as it does not require enzymatic synthesis, amplification, or nucleotide modification. Here, we take the first steps to realize nanopore sequencing of an 8-letter "hachimoji" expanded DNA alphabet by assessing its nanopore signal range using the MspA (Mycobacterium smegmatis porin A) nanopore. We find that hachimoji DNA exhibits a broader signal range in nanopore sequencing than standard DNA alone and that hachimoji single-base substitutions are distinguishable with high confidence. Because nanopore sequencing relies on a molecular motor to control the motion of DNA, we then assessed the compatibility of the Hel308 motor enzyme with nonstandard nucleotides by tracking the translocation of single Hel308 molecules along hachimoji DNA, monitoring the enzyme kinetics and premature enzyme dissociation from the DNA. We find that Hel308 is compatible with hachimoji DNA but dissociates more frequently when walking over C-glycoside nucleosides, compared to N-glycosides. C-glycocide nucleosides passing a particular site within Hel308 induce a higher likelihood of dissociation. This highlights the need to optimize nanopore sequencing motors to handle different glycosidic bonds. It may also inform designs of future alternative DNA systems that can be sequenced with existing motors and pores.

Is Temporomandibular Joint Arthroscopy Effective in Managing Pediatric Temporomandibular Joint Disorders in the Short- and Long-Term?

PURPOSE: Although temporomandibular joint (TMJ) arthroscopy outcomes have been well documented in the adult population, conclusive data are lacking for pediatric patients with TMJ disorders. The aim of the present study was to evaluate the early and late outcomes of TMJ arthroscopy in the pediatric population. PATIENTS AND METHODS: We performed a retrospective analysis to evaluate the short- (1-month) and long-term (1-year) improvements in the visual analog scale (VAS) scores for pain after pediatric TMJ arthroscopy from 2008 to 2016. The arthroscopic interventions varied according to the diagnostic findings and Wilkes classification. The primary outcome variable was the magnitude of VAS score for pain (0, no pain; 100, worst pain) at 1 year postoperatively. The secondary outcome variables were the short-term for the VAS score for pain and the short- and long-term outcomes for perceived jaw dysfunction (0, normal jaw function; 100, complete jaw dysfunction), mouth opening, joint loading (contralateral joint pain when biting on the canine), joint noise, and muscle pain. Univariate, bivariate, and multivariate statistical analyses were performed with the significance level set at P < .05. RESULTS: A total of 23 patients (37 joints), with a mean age of 14.1 years (range, 12.8 to 16.7 years) had undergone TMJ arthroscopic surgery with short- and long-term postoperative follow-up data available. The VAS scores for pain showed average improvements of 26% in the short-term (P < .0001) and 25% in the long-term (P < .0008). Perceived jaw dysfunction showed an average improvement of 23.8% in the short-term (P < .0001) and 19.2% in the long-term (P < .0008). The average mouth opening had improved by 5.4 mm in the short-term (P < .0016) and 8.2 mm in the long-term (P < .0001). Controlling for stage and diagnosis, the patients with Wilkes III showed the most benefit with statistically significant improvements in pain, jaw dysfunction, maximum interincisal opening, and joint loading pain. CONCLUSIONS: TMJ arthroscopy could be an effective and minimally invasive form of surgical intervention for treating Wilkes II, III, and IV TMJ disorders in the pediatric population.

The inferior turbinate: An autonomic organ.

The inferior turbinate has well-recognized respiratory and immune functions to provide the airway with appropriate warmth, humidification, and filtration of the inspired air while sampling the environment for pathogens. Normal functioning of the inferior turbinate relies on an intact autonomic system to maintain homeostasis within the nasal cavity. The autonomic nervous system innervates the submucosal glands and the vasculature within the inferior turbinate, resulting in control of major turbinate functions: nasal secretions, nasal patency, warmth, and humidification. This review will summarize the autonomic innervations of the turbinates, both the normal and abnormal autonomic processes that contribute to the turbinate functions, and the clinical considerations regarding optimal functioning of the turbinate autonomic system.

A Novel Surgical Landmark to Identify the Recurrent Laryngeal Nerve

Background: Although several surgical landmarks have been proposed to localize the recurrent laryngeal nerve (RLN), there is still no reliable landmark. Aims: To validate the reliability of a novel reference point at the intersection of the inferior border of the cricopharyngeal muscle and the inferior cornu of thyroid cartilage for locating the RLN. Study Design: Cadaver dissection study in the academic department of otolaryngology-head and neck surgery. Methods: Sixty-four RLNs in cadavers were assessed, and measurements of different surgical landmarks in conjunction with the proposed surgical landmark were obtained. Descriptive statistics, Pearson's chi-squared test, and Student's t-test were performed to analyze the data using GraphPad Prism (version 9.4.1; Dotmatics, Boston, Massachusetts, USA). Results: The average distance from the proposed landmark to the RLN was 2.3 ± 0.85 mm. The RLN was located just posterior to the reference point in 95.31% of the cadavers. The RLN passed under the inferior constrictor muscle in 90.63% of the cadavers. There was no statistically significant difference between right- and left-sided RLNs in terms of their relation with the reference point. Conclusion: The proposed reference point can be used as a reliable landmark to locate the RLN. This reference point may help surgeons during difficult thyroidectomy surgeries by providing an additional anatomical landmark.

Peak power output provides the most reliable measure of performance in prolonged intermittent-sprint cycling.

The aims of this study were to determine the reliability of an intermittent-sprint cycling protocol and to determine the efficacy of one practice session on main trials. Eleven men, moderately trained team-sport athletes, completed three visits to the laboratory involving a graded-exercise test and practice session and two trials of a cycling intermittent-sprint Protocol separated by three days. Data for practice and main trials were analysed using typical error of measurement, intra-class correlation and least-products regression to determine reliability. Typical error of measurement (expressed as a coefficient of variation) and intra-class correlation for peak power output from all 20 sprints for trial 1 and trial 2 were 2.9 ± 12.8% (95% confidence interval: 2.0-5.0%) and 0.96 (95% confidence interval: 0.85-0.99), respectively. Typical errors of measurement and intra-class correlation for mean power output for all 20 sprints for trials 1 and 2 were 4.2 ± 11.9% (95% confidence interval: 2.9-7.4%) and 0.90 (95% confidence interval: 0.66-0.97), respectively. The results suggest that peak power output provides a more reliable measure than mean power output. The Cycling Intermittent-Sprint Protocol provides reliable measures of intermittent-sprint performance.

Surgical Management of Inferior Turbinate Hypertrophy in the Era of Widespread Communicable Disease.

Inferior turbinate reduction procedures have been performed for decades. After significant evolution, turbinoplasty and other mucosal-sparing techniques have become the main method to successfully reduce turbinate hypertrophy. The debate of which technique produces the most effective and durable outcomes is ongoing. During this critical era of widespread communicable diseases, including but not limited to COVID-19, HIV, and hepatitis, additional attention is necessary to balance outcomes with a degree of generation of airborne particles when selecting a technique. This review article aims to identify the optimal method for inferior turbinate reduction that weighs both outcomes and aerosol production. The MEDLINE database was searched to discover relevant publications through August 2022. Key search terms included inferior turbinate hypertrophy, turbinate reduction surgery, turbinoplasty methods, surgical management of turbinate hypertrophy, surgical aerosol generation, COVID-19 surgery, surgery smoke plume, SARS-CoV-2 transmission during surgery, and nasal procedures COVID-19 aerosols. Surgical management of the inferior turbinates includes radiofrequency ablation (RFA), microdebrider-assisted turbinoplasty (MAIT), electrocautery, laser, and ultrasound. Piezo-assisted turbinoplasty and a turbinate-specific coblation wand are new additions to the literature. All techniques appear to improve patient symptoms of nasal obstruction. MAIT and RFA are comparable, although MAIT demonstrated better long-term outcomes in some studies and appears to generate fewer airborne particles. Studies evaluating the production of aerosols due to RFA are lacking. Ultrasound outcomes are also excellent and generate no aerosols, but the technique has not been compared against the microdebrider. Electrocautery can result in increased pain and crusting for patients and causes the highest amount of aerosols. Deficiencies of current studies, including a lack of comparison of aerosol generation, duration of follow-up, omission of outfracture, and inadequate randomized controlled trials among existing and new techniques, have limited the identification of the best inferior turbinate reduction method. Given the durability of MAIT and its minimal aerosol production, it can be reinforced as the most sensible technique until further evidence is available.

Mini Med School: why you should try a virtual, medical student-led program.

Mini Med School (MMS) programs led by medical students provide a unique opportunity for community members to access free and accurate health information while engaging with the education of medical students. Virtually delivered MMS programs reduce barriers to access. 90.3% of participants in a recent MMS enjoyed medical students delivering the seminars. 63.6% of participants preferred virtual MMS seminars, with 31.8% preferring a combination of virtual and in-person delivery. Student-led, virtually delivered MMS programs are an engaging way to support both medical student and community education while strengthening community ties with local medical schools.

Les séminaires de la mini-école de médecine (MÉM) présentés par des étudiants en médecine offrent une occasion unique aux membres de la communauté de profiter d'informations gratuites et précises en matière de santé tout en contribuant à la formation des étudiants. L'offre de séminaires MÉM en mode virtuel rend ces activités plus accessibles. Une grande majorité des participants (90,3 %) à une MÉM tenue récemment ont aimé le fait que des séminaires soient animés par des étudiants, 63,6 % d'entre eux ont préféré les séminaires MÉM virtuels et 31,8 % se sont dits favorables à une combinaison de séminaires virtuels et en personne. Les séminaires présentés virtuellement par des étudiants dans le cadre de la MÉM constituent un moyen intéressant de promouvoir aussi bien l'éducation des étudiants que celle de la communauté, tout en renforçant les liens entre cette dernière et les facultés de médecine locales.

A planning-based feasibility study of MR-Linac treatment for anal cancer radiation therapy.

The hybrid magnetic resonance image (MRI) scanner and radiation therapy linear accelerator (MR-Linac) has the potential to enhance clinical outcomes for anal cancer (AC) patients with improved soft tissue visualization and daily plan adaption but has planning and delivery limitations due to the incorporation of MRI. We aimed to identify if Elekta Unity MR-Linac-based radiation therapy is feasible for anal cancer. Ten prospectively enrolled AC patients treated with radical chemoradiotherapy were replanned for MR-Linac treatment using departmental planning criteria. For comparison, and to reduce interobserver variability, volumetric modulated arc radiation therapy (VMAT) plans were also created for each patient by the same single senior radiation therapist. Plans were compared using departmental dosimetric plan criteria, as well as conformity and homogeneity indices, monitor units (MUs) and measured plan delivery (beam-on) time. Results were deemed clinically acceptable. Target and organ at risk (OAR) doses were comparable between MR-Linac plans and VMAT plans, although PTV45Gy D98% coverage was compromised in 3 of 10 MR-Linac plans due to caudocranial length exceeding the limits of the MR-Linac. MR-Linac plans had lower MUs, median of 689.1 vs 849.65 (p = 0.002), but took over twice as long to deliver, 529.5s vs 224s (p = <0.0001) as VMAT plans. MR-Linac planning and treatment of AC is feasible for a subset of patients. The current physical limitations of the Elekta Unity system mean patients with large caudocranial elective PTV45Gy target volumes may not be covered dosimetrically to the required clinical standard. Longer image verification and treatment delivery times of the MR-Linac also mean patient selection and intrafractional IGRT are likely to be integral to ensuring high quality clinical outcomes in this rare cancer.

Geographic Distribution of Otolaryngology Training Programs and Potential Opportunities for Strategic Program Growth.

OBJECTIVE: To characterize the geographic distribution of US otolaryngology residents based on geographical population density to determine current status and identify potential opportunities for otolaryngology residency program expansion. METHODS: The locoregional population of otolaryngology residency programs was analyzed (as defined by the US Census) and the number of resident trainees per 100,000 people in each region was calculated. Otolaryngology residency program location was determined by mailing address, and program size was determined by AAMC public data. RESULTS: The average metropolitan city in the United States contained 2.07 otolaryngology trainees per 100,000 people. Cities with low trainee numbers per population included Phoenix, AZ (0.20 trainees per 100,000 people); Las Vegas, NV (0.26 per 100,000); Dallas, TX (0.26 per 100,000), Atlanta, GA (0.33 per 100,000); and Miami, FL (0.34 per 100,000). Comparing otolaryngology to other surgical subspecialties demonstrated similar distributions. Metropolitan centers with a population over 1 million without full academic representation in otolaryngology were also identified and included Charlotte, NC; Orlando, FL; Austin, TX; Providence, RI; Jacksonville, FL; Raleigh, NC; and Grand Rapids, MI. CONCLUSION: Strategic residency training program expansion should be considered in cities that exhibit a low trainee to population ratio. Although many factors ultimately determine program expansion or development of new training programs, this study provides substantiated population data describing where expansion could be prioritized. LEVEL OF EVIDENCE: NA Laryngoscope, 133:1600-1605, 2023.

Association between ethnicity and hypertension in Northern Colombia in 2015.

BACKGROUND: Studies in the United States have shown a genetic predisposition to hypertension in individuals of African descent. However, studies on the associations between ethnic groups and hypertension in Latin America are lacking and the limited results have been inconsistent. The objective of this study is to determine whether Afro-Colombian ethnicity increases the risk of hypertension. METHODS: This study is a secondary data analysis of a cross sectional study from five provinces in Northern Colombia. Randomly selected individuals (N = 2613; age-range 18-74 years) enrolled in a health care insurance company underwent physical examinations and completed questionnaires regarding ethnicity, lifestyle, and other risk factors. Hypertension in these patients was determined. Unadjusted and adjusted logistic regression analysis were calculated to determine the association between ethnicity and hypertension. RESULTS: No association between Afro-Colombian ethnicity and hypertension was found (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.66-1.09). As expected, people with a body mass index (BMI) of 30 or higher were at a greater risk of having hypertension (OR, 3.12; 95% CI, 2.35-4.16) compared with those with a normal BMI. CONCLUSIONS: Findings from this study suggest no independent association between Afro-Colombian ethnicity and hypertension. Further research should focus on genotyping or socioeconomic factors such as income level.

A pilot study investigating the role of 18 F-FDG-PET in the early identification of chemoradiotherapy response in anal cancer.

INTRODUCTION: Anal cancer (AC) is 18 F-FDG-PET avid and has been used to evaluate treatment response several months after chemoradiotherapy. This pilot study aimed to assess the utility of semi-automated contouring methods and quantitative measures of treatment response using 18 F-FDG-PET imaging at the early time point of 1-month post-chemoradiotherapy. METHODS: Eleven patients with AC referred for chemoradiotherapy were prospectively enrolled into this study, with 10 meeting eligibility requirements. 18 F-FDG-PET imaging was obtained pre-chemoradiotherapy (TP1), and then 1-month (TP2), 3-6 months (TP3) and 9-12 months (TP4) post-chemoradiotherapy. Manual and semi-automated (Threshold) contouring methods were used to define the primary tumour on all 18 F-FDG-PET images. Resultant contours from each method were interrogated using quantitative measures, including volume, response index (RI), total lesion glycolysis (TLG), SUVmax , SUVmedian and SUVmean . Response was assessed quantitatively as reductions in these measures and also qualitatively against established criteria. RESULTS: Nine patients were qualitatively classified as complete metabolic responders at TP2 and all 10 at TP3. All quantitative measures demonstrated significant (P < 0.05) reductions at TP2 for both Manual and Threshold methods. All reduced further at TP3 and again at TP4 for Threshold methods. TLG showed the highest reduction at all post-chemoradiotherapy time points and classified the most responders for each method at each time point. All patients are recurrence-free at minimum 4-year follow-up. CONCLUSION: Based on our small sample size, semi-automated methods of disease definition using 18 F-FDG-PET imaging are feasible and appear to facilitate quantitative response classification of AC as early as 1-month post-chemoradiotherapy. Early identification of treatment response may potentially improve disease management.

Cystic fibrosis exacerbations treated with medical therapy with and without concurrent sinus surgery.

OBJECTIVE: This analysis investigates any potential differences in pulmonary function test (PFT) outcomes among pediatric patients with cystic fibrosis (CF) receiving both medical management (MM) and functional endoscopic sinus surgery (FESS) versus MM alone for CF exacerbation. STUDY DESIGN: Prospective cohort. SETTING: Pediatric tertiary care facility. METHODS: The data was prospectively collected from July 2011 to March 2020. Diagnosis of CF and age ≤ to 18 were required. All patients were hospitalized and treated for CF exacerbations with both FESS with MM and MM alone at variable time intervals, although the order of initial treatment received differed. Two-way ANOVA with repeated measures were used to determine the effect of receiving FESS with MM versus MM alone on PFT outcomes over time (during admission, at discharge, at 3 months, at 6 months, and at 12 months). RESULTS: 13 pediatric patients, 7 of which had FESS with MM initially and 6 who had MM alone initially, and 20 events of both FESS and MM were included for analysis. For PFT outcomes, there was no statistically significant two-way interaction between treatment type and time following treatment, p = 0.492. The main effect of treatment did not show a statistically significant difference in FEV1 between treatment types, p = 0.737. There was no statistically significant association between treatment type and time between hospital readmission in months, p = 0.111. CONCLUSION: There was no significant difference between PFT outcomes in pediatric patients hospitalized for CF exacerbation treated with MM with or without FESS at any time interval.

A clinical study comparing polymer and gold fiducials for prostate cancer radiotherapy.

Introduction: Image guidance with gold fiducials improves outcomes of prostate radiotherapy. However, gold produces artefact on CT imaging, interfering with contouring and verification. The purpose of this study was to compare polymer to standard gold fiducials using radiotherapy imaging modalities to assess the visibility and artefact. Methods: Twenty eight patients with locally advanced prostate cancer were enrolled, half had three polymer fiducials implanted into the prostate and half underwent insertion of gold fiducials. Patients were imaged with CT, T2 weighted MRI, cone-beam CT (CBCT) and planar KV images. Fiducials were scored for visibility and assessed for CT artefact in surrounding prostate tissue. The artefact was quantified from Hounsfield number histograms and separated into percentile ranges and proportion of voxels in HU normal tissue range of a 2cm sphere surrounding the fiducial. Results: Gold and polymer fiducials were sufficiently visible for CT and CBCT verification. The gold fiducials could be visualized well on KV planar imaging; however, the polymer markers were obscured by pelvic bones. Neither polymer nor gold fiducials could be visualized on MRI. The polymer fiducial produced less artefact than gold on CT, having less voxel spread for the HU percentile ranges and a greater proportion of voxels in the normal tissue range. Conclusions: Polymer fiducials are a more suitable fiducial than gold for CT/CBCT in prostate cancer radiotherapy, demonstrating minimal artefact and good visibility on CT. However, they were not well seen on MRI or KV imaging and thus not suitable for co-registration or planar KV verification.

Green Salad Intake Is Associated with Improved Oral Cancer Survival and Lower Soluble CD44 Levels.

Deficiencies in fruit and vegetable intake have been associated with oral cancer (oral cavity and oropharyngeal). Salivary rinses contain measurable biomarkers including soluble CD44 (solCD44) and total protein, which are known markers of oral cancer risk. This study investigates the effect of nutritional factors on solCD44 and protein levels to evaluate oral cancer risk and survival. We evaluated solCD44 and protein levels from 150 patients with oral and oropharyngeal squamous cell carcinoma and 150 frequency-matched controls. We subsequently characterized the effect of food group consumption and these biomarkers on progression-free survival (PFS) and overall survival (OS). Patients reported eating fewer servings of salad (p = 0.015), while controls reported eating fewer servings of potatoes (p < 0.001). Oral cancer patients who consumed at least one serving per week of green salad were found to have significantly lower CD44 levels than those who ate salad less frequently (mean of log2[solCD44]1.73 versus 2.25, p = 0.014). Patients who consumed at least one serving per week of "salad or other vegetables" had significantly longer PFS (median 43.5 versus 9.1 months, p = 0.003, adjusted hazard ratio (HR) = 0.39 p = 0.014) and OS (median 83.6 versus 10 months, p = 0.008, adjusted HR = 0.04 p = 0.029). These findings suggest that dietary factors, namely greater green salad and vegetable intake, may be associated with lower CD44 levels and better prognosis in oral cancer patients.

Decreased Levels of Soluble CD44 in a High-Risk Population following a Smoking Cessation Program.

Tobacco is a risk factor of head and neck cancer (HNC) and smoking cessation alone may reduce HNC risk by 70%. Soluble CD44 (solCD44), a cell surface receptor linked to cell proliferation and migration, and total protein (TP) levels can detect early HNC. This study aims to determine whether salivary solCD44 and TP levels in oral rinses change following a smoking cessation program. 150 smokers provided oral rinse samples at baseline and at a 12-month follow-up after participation in a smoking cessation program. Assays to measure levels of solCD44, TP, and cotinine, a metabolite used as a biomarker of tobacco exposure, were completed. A paired-samples t-test was used to determine whether there was a statistically significant (p < 0.05) mean difference in biomarker levels before and after the program. Baseline and at 12-month follow-up data were available for 88 subjects, 21 of whom quit smoking entirely. Mean levels of solCD44 significantly decreased by 0.412 ng/mL from baseline to the 12-month follow-up, p = 0.010. There was no significant difference in mean TP levels, p = 0.975. Mean cotinine levels decreased significantly by 74.7 ng/mL, p = 0.035. This is the first work demonstrating an association between smoking cessation and decreased solCD44 levels in oral rinses. Decreased expression of the tumorigenic CD44 may be one mechanism by which smoking cessation lowers cancer risk.

Current salivary biomarkers for detection of human papilloma virus-induced oropharyngeal squamous cell carcinoma.

Human papilloma virus (HPV) infection is a key risk factor and etiology for oropharyngeal squamous cell carcinoma (OPSCC). HPV-induced OPSCC is rapidly increasing in incidence, with men experiencing increased mortality. When identified at an early stage, HPV-induced OPSCC can be successfully treated. Diagnosis of HPV-related OPSCC relies on an expert physical examination and invasive biopsy. Since saliva bathes the oropharyngeal mucosa and can be collected noninvasively, saliva obtained via salivary risings is an attractive body fluid for early detection of HPV-induced OPSCC. A plethora of DNA, RNA, and protein salivary biomarkers have been explored. This review discusses these markers and their robustness for detecting oncogenic HPV in OPSCC saliva samples. Methods detecting HPV DNA were more reliable than those detecting RNA, albeit both require time-consuming analyses. Salivary HPV proteomics are a new, promising focus of HPV detection research, and while more practical, lag behind nucleic acid detection methods in their development.

A phantom study to contrast and compare polymer and gold fiducial markers in radiotherapy simulation imaging.

To assess visibility and artifact characteristics of polymer fiducials compared to standard gold fiducials for radiotherapy CT and MRI simulation. Three gold and three polymer fiducials were inserted into a CT and MRI tissue-equivalent phantom that approximated the prostate cancer radiotherapy configuration. The phantom and fiducials were imaged on CT and MRI. Images were assessed in terms of fiducial visibility and artifact. ImageJ was employed to quantify the pixel gray-scale of each fiducial and artifact. Fiducial gray-scale histograms and profiles were generated for analysis. Objective measurements of the contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and artifact index (AI) were calculated. The CT images showed that the gold fiducials are visually brighter, with greater contrast than the polymer. The higher peak values illustrate this in the line profiles. However, they produce bright radiating and dark shadowing artifacts. This is depicted by the greater width of line profiles and the disruption of phantom area profiles. Quantitatively this results in greater percentile ranges of the histograms. Furthermore, for CT, gold had a higher CNR than polymer, relative to the phantom. However, the gold CNR and SNR were degraded by the greater artifact and thus AI. Both fiducials were visible on MRI and had similar histograms and profiles that were also reflected in comparable CNR, SNR and AI. Polymer fiducials were well visualized in a phantom on CT and MR and produce less artifact than the gold fiducials. Polymer markers could enhance the quality and accuracy of radiotherapy co-registration and planning but require clinical confirmation.

CD44 and associated markers in oral rinses and tissues from oral and oropharyngeal cancer patients.

OBJECTIVES: Oral and oropharyngeal squamous cell carcinoma (OOPSCC) is a debilitating disease. Salivary rinses contain soluble tumor markers including CD44 (solCD44) and total protein (TP) that may aid detection and prognosis of these aggressive tumors. Here we aim to examine the relationship between these salivary biomarkers and tissue markers p16 and CD44 and determine whether these markers can predict progression-free survival (PFS) and overall survival (OS). MATERIALS AND METHODS: Prospective study to update biomarkers using oral rinses and tissues from OOPSC patients enrolled between 2007 and 2012 at an academic tertiary referral center. 64 cases from a 300-subject case-control study with archived tissue for immunohistochemistry were included. RESULTS: 82.8% were male, 84.4% were ever smokers, 70.3% had disease stage T3-T4, and 57.8% presented with nodal disease. Nineteen patients (25%) were p16 positive. The group with strong tissue CD44 expression in membrane and cytoplasm had higher levels of solCD44 (mean 10.73 ng/ml) than other groups (5.47 ng/ml) (p = 0.033). TP levels were significantly reduced in oral rinses from subjects with p16 universal gross tumor tissue staining (mean 0.80 vs. 1.08 mg/ml; p = 0.039). On multivariate analysis, universal CD44 gross tissue staining and TP levels ≥ 1 mg/ml demonstrated poorer PFS, with the latter also affecting OS. Poorer survival was associated with soluble CD44 ≥ 5.33 ng/ml and TP ≥ 1 mg/ml. CONCLUSIONS: Direct associations were found between high solCD44 levels and strong membrane and cytoplasmic CD44 expression, and between high TP levels and peripheral/mixed p16 gross staining. Poorer PFS and OS are significantly associated with higher levels of solCD44 and protein in oral rinses.