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ObjectiveThe purpose of this study was to evaluate long-term outcomes of sphincter pharyngoplasties, including speech outcomes, revision surgeries, and postoperative incidence of obstructive sleep apnea (OSA).DesignRetrospective matched-cohort study SETTING: Two craniofacial centers in Los Angeles, CA PATIENTS: Patients (n = 166) with cleft lip and palate (CLP) or isolated cleft palate (iCP) who underwent sphincter pharyngoplasty from 1992 to 2022 were identified. An age- and diagnosis-matched control group of 67 patients with CLP/iCP without velopharyngeal insufficiency (VPI) was also identified.InterventionsThe pharyngoplasty group underwent sphincter pharyngoplasty, whereas the non-VPI group had no history of VPI surgery or sphincter pharyngoplasty.Main outcome measuresPostoperative speech outcomes, revision surgeries, and incidence of OSA were evaluated. Multivariable regression was used to evaluate independent predictors of OSA.ResultsAmong the patients in the pharyngoplasty cohort, 63.9% demonstrated improved and sustained speech outcomes after a single pharyngoplasty, with a median postoperative follow-up of 8.8 years (interquartile range [IQR], 3.6-12.0 years). One-third of the patients who underwent pharyngoplasty required a revision surgery, with a median time to primary revision of 3.9 years (IQR, 1.9-7.0 years). OSA rates increased significantly among the pharyngoplasty cohort, from 3% before surgery to 14.5% after surgery (p < 0.001). The average time from sphincter pharyngoplasty to OSA diagnosis was 4.4 ± 2.4 years. Multivariable analysis results indicated that sphincter pharyngoplasty surgery was independently associated with a fourfold increase in OSA (p = 0.03).ConclusionsAlthough sphincter pharyngoplasty remains successful in improving long-term speech outcomes, persistent OSA is a sequela that should be monitored beyond the immediate postoperative period.

Acanthodes has long been the primary source of information on the pharyngeal skeleton of ‘acanthodians’. Because of this its anatomy has played a disproportionate role in attempts to understand the evolution of the jawed vertebrate pharynx and the clade as a whole. However, the anatomy of the pharynx of Acanthodes, now understood to be a stem-group chondrichthyan, remains poorly characterized and subject to several com- peting interpretations. We used computed tomography to image the articulated pharyngeal skeletons of three specimens of Acanthodes confusus from Lebach, Germany. Acanthodes has a mélange of osteichthyan-like and chondrichthyan-like morphologies in its pharyngeal skeleton. Like many other chondrichthyans, Acanthodes lacked hypohyals, and had four pairs of posteriorly oriented pharyngobranchials. Like osteichthyans, Acanthodes possessed an interhyal, but lacked the separate infra- and supra-pharyngobranchial elements present in osteichthyans and the crown- chondrichthyan Ozarcus. Using these new data we built and animated a digital 3D model of the pharyngeal endoskeleton in Acanthodes, showing that the jaws could have swung outwards during the opening cycle, increasing the anteriorly facing area of the gape for suspension feeding. These new data provide a more definitive picture of the anatomy of a taxon that has long been of great significance in early vertebrate palaeontology.

Salt (NaCl), is an essential nutrient for survival, while excessive salt can be detrimental. In the fruit fly, Drosophila melanogaster, internal taste organs in the pharynx are critical gatekeepers impacting the decision to accept or reject a food. Currently, our understanding of the mechanism through which pharyngeal gustatory receptor neurons (GRNs) sense high salt are rudimentary. Here, we found that a member of the ionotropic receptor family, Ir60b, is expressed exclusively in a pair of GRNs activated by high salt. Using a two-way choice assay (DrosoX) to measure ingestion volume, we demonstrate that IR60b and two co-receptors IR25a and IR76b are required to prevent high salt consumption. Mutants lacking external taste organs but retaining the internal taste organs in the pharynx exhibit much higher salt avoidance than flies with all taste organs but missing the three IRs. Our findings highlight the vital role for IRs in a pharyngeal GRN to control ingestion of high salt.

Objective: The aim of this study was to clarify whether antireflux surgery prevents laryngeal and pharyngeal squamous cell carcinoma. Summary Background Data: Gastroesophageal reflux disease (GERD) seems to increase the risk of laryngeal and pharyngeal squamous cell carcinoma. Methods: All-Nordic (Denmark, Finland, Iceland, Norway, and Sweden) population-based cohort study of adults with documented GERD in 1980 to 2014. First, cancer risk after antireflux surgery was compared to the expected risk in the corresponding background population by calculating standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). Second, cancer risk among antireflux surgery patients was compared to nonoperated GERD patients using multivariable Cox regression, providing hazard ratios (HR) with 95% CIs, adjusted for sex, age, calendar period, and diagnoses related to tobacco smoking, obesity, and alcohol overconsumption. Results: Among 814,230 GERD patients, 47,016 (5.8%) underwent antireflux surgery. The overall SIRs and HRs of the combined outcome laryngeal or pharyngeal squamous cell carcinoma (n=39) were decreased after antireflux surgery [SIR=0.62 (95% CI 0.44-0.85) and HR=0.55 (95% CI 0.38-0.80)]. The point estimates were further decreased >10 years after antireflux surgery [SIR=0.48 (95% CI 0.26-0.80) and HR=0.47 (95% CI 0.26-0.85)]. The risk estimates of laryngeal squamous cell carcinoma were particularly decreased >10 years after antireflux surgery [SIR=0.28 (95% CI 0.08-0.72) and HR=0.23 (95% CI 0.08-0.69)], whereas no such decrease over time after surgery was found for pharyngeal squamous cell carcinoma. Analyses of patients with severe GERD (reflux esophagitis or Barrett esophagus) showed similar results. Conclusion: Antireflux surgery may decrease the risk of laryngeal squamous cell carcinoma and possibly also of pharyngeal squamous cell carcinoma.

Tobacco smoking-related diseases are estimated to kill more than 8 million people/year and most smokers are willing to stop smoking. The pharmacological approach to aid smoking cessation comprises nicotine replacement therapy (NRT) and inhibitors of the nicotinic acetylcholine receptor, which is activated by nicotine. Common side effects of oral NRT products include hiccoughs, gastrointestinal disturbances and, most notably, irritation, burning and pain in the mouth and throat, which are the most common reasons for premature discontinuation of NRT and termination of cessation efforts. Attempts to reduce the unwanted sensory side effects are warranted, and research discovering the most optimal masking procedures is urgently needed. This requires a firm mechanistic understanding of the neurobiology behind the activation of sensory nerves and their receptors by nicotine. The sensory nerves in the oral cavity and throat express the so-called transient receptor potential (TRP) channels, which are responsible for mediating the nicotine-evoked irritation, burning and pain sensations. Targeting the TRP channels is one way to modulate the unwanted sensory side effects. A variety of natural (Generally Recognized As Safe [GRAS]) compounds interact with the TRP channels, thus making them interesting candidates as safe additives to oral NRT products. The present narrative review will discuss (1) current evidence on how nicotine contributes to irritation, burning and pain in the oral cavity and throat, and (2) options to modulate these unwanted side-effects with the purpose of increasing adherence to NRT. Nicotine provokes irritation, burning and pain in the oral cavity and throat. Managing these side effects will ensure better compliance to oral NRT products and hence increase the success of smoking cessation. A specific class of sensory receptors (TRP channels) are involved in mediating nicotine's sensory side effects, making them to potential treatment targets. Many natural (G

Objective: The aim of this study was to clarify whether antireflux surgery prevents laryngeal and pharyngeal squamous cell carcinoma. Summary Background Data: Gastroesophageal reflux disease (GERD) seems to increase the risk of laryngeal and pharyngeal squamous cell carcinoma. Methods: All-Nordic (Denmark, Finland, Iceland, Norway, and Sweden) population-based cohort study of adults with documented GERD in 1980 to 2014. First, cancer risk after antireflux surgery was compared to the expected risk in the corresponding background population by calculating standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). Second, cancer risk among antireflux surgery patients was compared to nonoperated GERD patients using multivariable Cox regression, providing hazard ratios (HR) with 95% CIs, adjusted for sex, age, calendar period, and diagnoses related to tobacco smoking, obesity, and alcohol overconsumption. Results: Among 814,230 GERD patients, 47,016 (5.8%) underwent antireflux surgery. The overall SIRs and HRs of the combined outcome laryngeal or pharyngeal squamous cell carcinoma (n=39) were decreased after antireflux surgery [SIR=0.62 (95% CI 0.44-0.85) and HR=0.55 (95% CI 0.38-0.80)]. The point estimates were further decreased >10 years after antireflux surgery [SIR=0.48 (95% CI 0.26-0.80) and HR=0.47 (95% CI 0.26-0.85)]. The risk estimates of laryngeal squamous cell carcinoma were particularly decreased >10 years after antireflux surgery [SIR=0.28 (95% CI 0.08-0.72) and HR=0.23 (95% CI 0.08-0.69)], whereas no such decrease over time after surgery was found for pharyngeal squamous cell carcinoma. Analyses of patients with severe GERD (reflux esophagitis or Barrett esophagus) showed similar results. Conclusion: Antireflux surgery may decrease the risk of laryngeal squamous cell carcinoma and possibly also of pharyngeal squamous cell carcinoma.

OBJECTIVES/HYPOTHESIS: Modulation of the pharyngeal swallow to bolus volume and viscosity is important for safe swallowing and is commonly studied using high-resolution pharyngeal manometry (HRPM). Use of unidirectional pressure sensor technology may, however, introduce variability in swallow measures and a fixed bolus administration protocol may induce time and order effects. We aimed to overcome these limitations and to investigate the effect of time by repeating randomized measurements using circumferential pressure sensor technology. STUDY DESIGN: Sub-set analysis of data from the placebo arm of a randomized, repeated measures trial. METHODS: HRPM with impedance was recorded using a solid-state catheter with 36 circumferential pressure sensors and 18 impedance segments straddling from hypopharynx to stomach. Testing included triplicates of 5, 10, and 20 ml thin liquid and 10 ml thick liquid boluses, the order of the thin liquid boluses was randomized. The swallow challenges were repeated approximately 10 minutes after finishing the baseline measurement. RESULTS: We included 19 healthy adults (10/9 male/female; age 24.5 ± 4.1 year). Intrabolus pressure, all upper esophageal sphincter (UES) opening and relaxation metrics, and flow timing metrics increased with larger volumes. A thicker viscosity decreased UES relaxation time, UES basal pressure, and flow timing metrics, whereas UES opening extent increased. Pre-swallow UES basal pressure and post-swallow UES contractile integral decreased over time. CONCLUSION: Using circumferential pressure sensor technology, the effects of volume and viscosity were largely consistent with previous reports. UES contractile pressures reduced over time. The growing body of literature offers a benchmark for recognizing aberrant pharyngo-esophageal motor responses. LEVEL OF EVIDENCE: 3 Laryngoscope, 2021., Funding agency:College of Medicine and Public Health, Flinders University

Twang-like vocal qualities have been related to a megaphone-like shape of the vocal tract (epilaryngeal tube and pharyngeal narrowing, and a wider mouth opening), low-frequency spectral changes, and tighter and/or increased vocal fold adduction. Previous studies have focused mainly on loud and high-pitched singing, comfortable low-pitched spoken vowels, or are based on modeling and simulation. There is no data available related to twang-like voices in loud, low-pitched singing. Purpose: This study investigates the possible contribution of the lower and upper vocal tract configurations during loud twang-like singing on high and low pitches in a real subject. Methods: One male contemporary commercial music singer produced a sustained vowel [a:] in his habitual speaking pitch (B2) and loudness. The same vowel was also produced in a loud twang-like singing voice on high (G4) and low pitches (B2). Computerized tomography, acoustic analysis, inverse filtering, and audio-perceptual assessments were performed. Results: Both loud twang-like voices showed a megaphone-like shape of the vocal tract, being more notable on the low pitch. Also, low-frequency spectral changes, a peak of sound energy around 3 kHz and increased vocal fold adduction were found. Results agreed with audio-perceptual evaluation. Conclusions: Loud twang-like phonation seems to be mainly related to low-frequency spectral changes (under 2 kHz) and a more compact formant structure. Twang-like qualities seem to require different degrees of twang-related vocal tract adjustments while phonating in different pitches. A wider mouth opening, pharyngeal constriction, and epilaryngeal tube narrowing may be helpful strategies for maximum power transfer and improved vocal economy in loud contemporary commercial music singing and potentially in loud speech. Further studies should focus on vocal efficiency and vocal economy measurements using modeling and simulation, based on real-singers’ data., QC 20211011

BackgroundNorwich terriers are affected by an upper airway syndrome (NTUAS) but little is known about outcome in affected dogs.ObjectiveTo determine outcome in dogs with NTUAS using owner questionnaires.AnimalsThirty-four client-owned dogs.MethodsAt initial assessment, owners were questioned about respiratory noises and exercise tolerance. A NTUAS score was prospectively constructed based on the number and severity of obstructive lesions detected endoscopically (range, 0-25). Owner questionnaires on respiratory noises, exercise tolerance, and quality of life (QOL) were obtained 2.2-9.3 years (median, 4.2 years) after endoscopy.ResultsDogs ranged from 0.5 to 10.7 years of age (median, 4.75 years) at initial examination and no correlation was found between age and NTUAS score (median, 13; range, 1-25). Of 5 possible laryngeal abnormalities, 7 dogs had 1-2, 10 dogs had 3, and 17 dogs had 4-5 abnormalities (median, 3.5). Surgery was performed in 15 dogs, which had higher NTUAS scores (18.5 ± 6.3) than dogs that did not have surgery (7.7 ± 4.7, P < .0001). Scores for QOL ranged from 0 to 31 out of 40, with higher scores indicating worse QOL. Owner surveys resulted in QOL scores of ≤3 in 25/31 dogs (81%), with worse scores in dogs that had surgery performed (median 5, vs 0; P = .003). No correlation was noted between NTUAS and QOL scores, but age at follow-up was weakly associated with worse QOL.Conclusions and clinical importanceDespite variable severity of NTUAS scores, owners reported excellent QOL for most Norwich terriers examined.

BackgroundThe COVID-19 pandemic illuminated the benefits of telemedicine. Self-collected specimens are a promising alternative to clinician-collected specimens when in-person testing is not feasible. In this study, we assessed the adequacy of self-collected pharyngeal and rectal specimens for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae among individuals undergoing chlamydia and gonorrhea screening.MethodsWe used data from a large cohort study that included male and female adolescents between the ages of 12-24 years. We considered self-collected specimens adequate for clinical use if the human synthase gene (a control target of the assay) was detected in the specimen.ResultsIn total, 2,458 specimens were included in the analysis. The human synthase gene was detected in 99.2% (2,439/2,458) of all self-collected specimens, 99.5% (1,108/1,114) of the pharyngeal specimens, and 99.0% (1,331/1,344) of the rectal specimens.ConclusionSelf-collected pharyngeal and rectal specimens demonstrated a very high proportion of human gene presence, suggesting that self-collection was accurate. A limitation of this study is that the sample adequacy control detects the presence or absence of the human hydroxymethylbilane synthase gene, but it does not indicate the specific anatomic origin of the human hydroxymethylbilane synthase gene. Self-collected specimens may be an appropriate alternative to clinician-collected specimens.

BackgroundPublic health organizations have inconsistent recommendations for screening adolescents and young adults for Chlamydia trachomatis and Neisseria gonorrhoeae infections. Guidelines suggest different combinations of anorectal, pharyngeal, and urogenital testing based on age, sex, and sexual activity. Further evaluation of how identity and behaviors impact the anatomic distribution of C. trachomatis and N. gonorrhoeae infection is needed to optimize future screening practices.MethodsWe assessed the positivity of C. trachomatis and N. gonorrhoeae infections at different anatomic sites in a cohort of at-risk sexually active adolescents and young adults aged 12-24 years in New Orleans, Louisiana and Los Angeles, California. Participants were tested for C. trachomatis and N. gonorrhoeae at 3 sites (anorectum, pharynx, and urethral/cervix) every 4 months using self-collected swabs. We stratified anatomic distributions of infection into 4 gender and sexual behavior categories: (1) cisgender men who have sex with men and transgender women (MSMTW); (2) cisgender heterosexual males; (3) cisgender heterosexual females; and (4) gender minorities assigned female at birth.ResultsWhile three-site testing detected all infections, two-site (anorectum and urethra/cervix) testing identified 92%-100% of C. trachomatis or N. gonorrhoeae infections in participants assigned female at birth and cisgender heterosexual males. For MSMTW, two-site anorectal and pharyngeal testing vs single-site anorectal testing increased the proportion of individuals with either infection from 74% to 93%.ConclusionsSexual behavior and gender identity may influence detection of C. trachomatis and N. gonorrhoeae infections at specific anatomic testing sites. Testing guidelines should incorporate sexual behavior and gender identity.Clinical trials registrationNCT03134833.

BackgroundThe COVID-19 pandemic illuminated the benefits of telemedicine. Self-collected specimens are a promising alternative to clinician-collected specimens when in-person testing is not feasible. In this study, we assessed the adequacy of self-collected pharyngeal and rectal specimens for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae among individuals undergoing chlamydia and gonorrhea screening.MethodsWe used data from a large cohort study that included male and female adolescents between the ages of 12-24 years. We considered self-collected specimens adequate for clinical use if the human synthase gene (a control target of the assay) was detected in the specimen.ResultsIn total, 2,458 specimens were included in the analysis. The human synthase gene was detected in 99.2% (2,439/2,458) of all self-collected specimens, 99.5% (1,108/1,114) of the pharyngeal specimens, and 99.0% (1,331/1,344) of the rectal specimens.ConclusionSelf-collected pharyngeal and rectal specimens demonstrated a very high proportion of human gene presence, suggesting that self-collection was accurate. A limitation of this study is that the sample adequacy control detects the presence or absence of the human hydroxymethylbilane synthase gene, but it does not indicate the specific anatomic origin of the human hydroxymethylbilane synthase gene. Self-collected specimens may be an appropriate alternative to clinician-collected specimens.

Study Objectives: Oral appliance therapy is an increasingly common option for treating obstructive sleep apnea (OSA) in patients who are intolerant to continuous positive airway pressure (CPAP). Clinically applicable tools to identify patients who could respond to oral appliance therapy are limited. Method(s): Data from three studies (N = 81) were compiled, which included two sleep study nights, on and off oral appliance treatment. Along with clinical variables, airflow features were computed that included the average drop in airflow during respiratory events (event depth) and flow shape features, which, from previous work, indicates the mechanism of pharyngeal collapse. A model was developed to predict oral appliance treatment response (>50% reduction in apnea-hypopnea index [AHI] from baseline plus a treatment AHI <10 events/h). Model performance was quantified using (1) accuracy and (2) the difference in oral appliance treatment efficacy (percent reduction in AHI) and treatment AHI between predicted responders and nonresponders. Result(s): In addition to age and body mass index (BMI), event depth and expiratory "pinching" (validated to reflect palatal prolapse) were the airflow features selected by the model. Nonresponders had deeper events, "pinched" expiratory flow shape (i.e. associated with palatal collapse), were older, and had a higher BMI. Prediction accuracy was 74% and treatment AHI was lower in predicted responders compared to nonresponders by a clinically meaningful margin (8.0 [5.1 to 11.6] vs. 20.0 [12.2 to 29.5] events/h, p < 0.001). Conclusion(s): A model developed with airflow features calculated from routine polysomnography, combined with age and BMI, identified oral appliance treatment responders from nonresponders. This research represents an important application of phenotyping to identify alternative treatments for personalized OSA management.Copyright © Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep

Introduction: Quantification of upper airway collapsibility in obstructive sleep apnoea (OSA) could help inform targeted therapy decisions. However, current techniques are not clinically feasible. The primary aim of this study was to assess if a simple, novel technique could be implemented as part of a continuous positive airway pressure (CPAP) titration study to estimate pharyngeal collapsibility. Method(s): 35 participants (15 female) with OSA (apnoea-hypopnoea index [mean +/- SD]=35 +/- 19 events/hr) were studied. Participants first completed a simple clinical intervention during a routine CPAP titration in which CPAP was transiently turned off from the therapeutic pressure for up to 5 breaths/efforts on >= 5 occasions during stable non-REM sleep. Participants were then invited to a second physiology study to determine the pharyngeal critical closing pressure (Pcrit) and repeat transient drops to zero CPAP to assess reproducibility. Result(s): Mean peak inspiratory flow (PIF) of breaths 3-5 during zero CPAP on the simple clinical intervention versus the physiology night were similar (34 +/- 29 vs. 28 +/- 30% baseline on therapeutic CPAP, p = 0.2; range 0-90 vs. 0-95%). Pcrit was-0.95 +/- 2.5 cm H2O (range-6 to + 5 cm H2O). Mean PIF during zero CPAP quantified during the simple clinical intervention and the physiology night correlated with Pcrit (r = 0.7 and 0.9 respectively, p < 0.05). Receiver operating characteristic analysis indicates 'good' and 'excellent' diagnostic potential for the simple intervention to predict Pcrit <-2 and < 0cmH2O (AUC = 0.81 and 0.92, respectively). Conclusion(s): This simple CPAP intervention performed well in identifying people with mild-moderately collapsible pharyngeal airways. This approach may help select individuals who are more likely to respond to non-CPAP therapies for OSA.

In this article, we discuss the properties of styrene, the organic substances derived from it, and the chemistry and technology of polymers.

In this article, we discuss the properties of styrene, the organic substances derived from it, and the chemistry and technology of polymers.

In this article, we discuss the properties of styrene, the organic substances derived from it, and the chemistry and technology of polymers.

In this article, we discuss the properties of styrene, the organic substances derived from it, and the chemistry and technology of polymers.

In this article, we discuss the properties of styrene, the organic substances derived from it, and the chemistry and technology of polymers.

In this article, we discuss the properties of styrene, the organic substances derived from it, and the chemistry and technology of polymers.

Study Objectives: Oral appliance therapy is an increasingly common option for treating obstructive sleep apnea (OSA) in patients who are intolerant to continuous positive airway pressure (CPAP). Clinically applicable tools to identify patients who could respond to oral appliance therapy are limited. Method(s): Data from three studies (N = 81) were compiled, which included two sleep study nights, on and off oral appliance treatment. Along with clinical variables, airflow features were computed that included the average drop in airflow during respiratory events (event depth) and flow shape features, which, from previous work, indicates the mechanism of pharyngeal collapse. A model was developed to predict oral appliance treatment response (>50% reduction in apnea-hypopnea index [AHI] from baseline plus a treatment AHI <10 events/h). Model performance was quantified using (1) accuracy and (2) the difference in oral appliance treatment efficacy (percent reduction in AHI) and treatment AHI between predicted responders and nonresponders. Result(s): In addition to age and body mass index (BMI), event depth and expiratory "pinching" (validated to reflect palatal prolapse) were the airflow features selected by the model. Nonresponders had deeper events, "pinched" expiratory flow shape (i.e. associated with palatal collapse), were older, and had a higher BMI. Prediction accuracy was 74% and treatment AHI was lower in predicted responders compared to nonresponders by a clinically meaningful margin (8.0 [5.1 to 11.6] vs. 20.0 [12.2 to 29.5] events/h, p < 0.001). Conclusion(s): A model developed with airflow features calculated from routine polysomnography, combined with age and BMI, identified oral appliance treatment responders from nonresponders. This research represents an important application of phenotyping to identify alternative treatments for personalized OSA management.Copyright © Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep

Introduction: Quantification of upper airway collapsibility in obstructive sleep apnoea (OSA) could help inform targeted therapy decisions. However, current techniques are not clinically feasible. The primary aim of this study was to assess if a simple, novel technique could be implemented as part of a continuous positive airway pressure (CPAP) titration study to estimate pharyngeal collapsibility. Method(s): 35 participants (15 female) with OSA (apnoea-hypopnoea index [mean +/- SD]=35 +/- 19 events/hr) were studied. Participants first completed a simple clinical intervention during a routine CPAP titration in which CPAP was transiently turned off from the therapeutic pressure for up to 5 breaths/efforts on >= 5 occasions during stable non-REM sleep. Participants were then invited to a second physiology study to determine the pharyngeal critical closing pressure (Pcrit) and repeat transient drops to zero CPAP to assess reproducibility. Result(s): Mean peak inspiratory flow (PIF) of breaths 3-5 during zero CPAP on the simple clinical intervention versus the physiology night were similar (34 +/- 29 vs. 28 +/- 30% baseline on therapeutic CPAP, p = 0.2; range 0-90 vs. 0-95%). Pcrit was-0.95 +/- 2.5 cm H2O (range-6 to + 5 cm H2O). Mean PIF during zero CPAP quantified during the simple clinical intervention and the physiology night correlated with Pcrit (r = 0.7 and 0.9 respectively, p < 0.05). Receiver operating characteristic analysis indicates 'good' and 'excellent' diagnostic potential for the simple intervention to predict Pcrit <-2 and < 0cmH2O (AUC = 0.81 and 0.92, respectively). Conclusion(s): This simple CPAP intervention performed well in identifying people with mild-moderately collapsible pharyngeal airways. This approach may help select individuals who are more likely to respond to non-CPAP therapies for OSA.

OBJECTIVES/HYPOTHESIS: Modulation of the pharyngeal swallow to bolus volume and viscosity is important for safe swallowing and is commonly studied using high-resolution pharyngeal manometry (HRPM). Use of unidirectional pressure sensor technology may, however, introduce variability in swallow measures and a fixed bolus administration protocol may induce time and order effects. We aimed to overcome these limitations and to investigate the effect of time by repeating randomized measurements using circumferential pressure sensor technology. STUDY DESIGN: Sub-set analysis of data from the placebo arm of a randomized, repeated measures trial. METHODS: HRPM with impedance was recorded using a solid-state catheter with 36 circumferential pressure sensors and 18 impedance segments straddling from hypopharynx to stomach. Testing included triplicates of 5, 10, and 20 ml thin liquid and 10 ml thick liquid boluses, the order of the thin liquid boluses was randomized. The swallow challenges were repeated approximately 10 minutes after finishing the baseline measurement. RESULTS: We included 19 healthy adults (10/9 male/female; age 24.5 ± 4.1 year). Intrabolus pressure, all upper esophageal sphincter (UES) opening and relaxation metrics, and flow timing metrics increased with larger volumes. A thicker viscosity decreased UES relaxation time, UES basal pressure, and flow timing metrics, whereas UES opening extent increased. Pre-swallow UES basal pressure and post-swallow UES contractile integral decreased over time. CONCLUSION: Using circumferential pressure sensor technology, the effects of volume and viscosity were largely consistent with previous reports. UES contractile pressures reduced over time. The growing body of literature offers a benchmark for recognizing aberrant pharyngo-esophageal motor responses. LEVEL OF EVIDENCE: 3 Laryngoscope, 2021., Funding agency:College of Medicine and Public Health, Flinders University

BackgroundPublic health organizations have inconsistent recommendations for screening adolescents and young adults for Chlamydia trachomatis and Neisseria gonorrhoeae infections. Guidelines suggest different combinations of anorectal, pharyngeal, and urogenital testing based on age, sex, and sexual activity. Further evaluation of how identity and behaviors impact the anatomic distribution of C. trachomatis and N. gonorrhoeae infection is needed to optimize future screening practices.MethodsWe assessed the positivity of C. trachomatis and N. gonorrhoeae infections at different anatomic sites in a cohort of at-risk sexually active adolescents and young adults aged 12-24 years in New Orleans, Louisiana and Los Angeles, California. Participants were tested for C. trachomatis and N. gonorrhoeae at 3 sites (anorectum, pharynx, and urethral/cervix) every 4 months using self-collected swabs. We stratified anatomic distributions of infection into 4 gender and sexual behavior categories: (1) cisgender men who have sex with men and transgender women (MSMTW); (2) cisgender heterosexual males; (3) cisgender heterosexual females; and (4) gender minorities assigned female at birth.ResultsWhile three-site testing detected all infections, two-site (anorectum and urethra/cervix) testing identified 92%-100% of C. trachomatis or N. gonorrhoeae infections in participants assigned female at birth and cisgender heterosexual males. For MSMTW, two-site anorectal and pharyngeal testing vs single-site anorectal testing increased the proportion of individuals with either infection from 74% to 93%.ConclusionsSexual behavior and gender identity may influence detection of C. trachomatis and N. gonorrhoeae infections at specific anatomic testing sites. Testing guidelines should incorporate sexual behavior and gender identity.Clinical trials registrationNCT03134833.

BackgroundNorwich terriers are affected by an upper airway syndrome (NTUAS) but little is known about outcome in affected dogs.ObjectiveTo determine outcome in dogs with NTUAS using owner questionnaires.AnimalsThirty-four client-owned dogs.MethodsAt initial assessment, owners were questioned about respiratory noises and exercise tolerance. A NTUAS score was prospectively constructed based on the number and severity of obstructive lesions detected endoscopically (range, 0-25). Owner questionnaires on respiratory noises, exercise tolerance, and quality of life (QOL) were obtained 2.2-9.3 years (median, 4.2 years) after endoscopy.ResultsDogs ranged from 0.5 to 10.7 years of age (median, 4.75 years) at initial examination and no correlation was found between age and NTUAS score (median, 13; range, 1-25). Of 5 possible laryngeal abnormalities, 7 dogs had 1-2, 10 dogs had 3, and 17 dogs had 4-5 abnormalities (median, 3.5). Surgery was performed in 15 dogs, which had higher NTUAS scores (18.5 ± 6.3) than dogs that did not have surgery (7.7 ± 4.7, P < .0001). Scores for QOL ranged from 0 to 31 out of 40, with higher scores indicating worse QOL. Owner surveys resulted in QOL scores of ≤3 in 25/31 dogs (81%), with worse scores in dogs that had surgery performed (median 5, vs 0; P = .003). No correlation was noted between NTUAS and QOL scores, but age at follow-up was weakly associated with worse QOL.Conclusions and clinical importanceDespite variable severity of NTUAS scores, owners reported excellent QOL for most Norwich terriers examined.

BackgroundThe COVID-19 pandemic illuminated the benefits of telemedicine. Self-collected specimens are a promising alternative to clinician-collected specimens when in-person testing is not feasible. In this study, we assessed the adequacy of self-collected pharyngeal and rectal specimens for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae among individuals undergoing chlamydia and gonorrhea screening.MethodsWe used data from a large cohort study that included male and female adolescents between the ages of 12-24 years. We considered self-collected specimens adequate for clinical use if the human synthase gene (a control target of the assay) was detected in the specimen.ResultsIn total, 2,458 specimens were included in the analysis. The human synthase gene was detected in 99.2% (2,439/2,458) of all self-collected specimens, 99.5% (1,108/1,114) of the pharyngeal specimens, and 99.0% (1,331/1,344) of the rectal specimens.ConclusionSelf-collected pharyngeal and rectal specimens demonstrated a very high proportion of human gene presence, suggesting that self-collection was accurate. A limitation of this study is that the sample adequacy control detects the presence or absence of the human hydroxymethylbilane synthase gene, but it does not indicate the specific anatomic origin of the human hydroxymethylbilane synthase gene. Self-collected specimens may be an appropriate alternative to clinician-collected specimens.

In this article, we discuss the properties of styrene, the organic substances derived from it, and the chemistry and technology of polymers.

Insect gustatory systems comprise multiple taste organs for detecting chemicals that signal palatable or noxious quality. Although much is known about how taste neurons sense various chemicals, many questions remain about how individual taste neurons in each taste organ control feeding. Here, we use the Drosophila pharynx as a model to investigate how taste information is encoded at the cellular level to regulate consumption of sugars and amino acids. We first generate taste-blind animals and establish a critical role for pharyngeal input in food selection. We then investigate feeding behavior of both male and female flies in which only selected classes of pharyngeal neurons are restored via binary choice feeding preference assays as well as Fly Liquid-Food Interaction Counter (FLIC) assays. We find instances of integration as well as redundancy in how pharyngeal neurons control behavioral responses to sugars and amino acids. Additionally, we find that pharyngeal neurons drive sugar feeding preference based on sweet taste but not on nutritional value. Finally, we demonstrate functional specialization of pharyngeal and external neurons using optogenetic activation. Overall, our genetic taste neuron protection system in a taste-blind background provides a powerful approach to elucidate principles of pharyngeal taste coding and demonstrates functional overlap and subdivision among taste neurons.SIGNIFICANCE STATEMENTDietary intake of nutritious chemicals such as sugars and amino acids is essential for an animal's survival. In insects, distinct classes of taste neurons control acceptance or rejection of food sources. Here we develop a genetic system to investigate how individual taste neurons in the Drosophila pharynx encode specific tastants, focusing on sugars and amino acids. By examining flies in which only a single class of taste neurons is active, we find evidence for functional overlap as well as redundancy in responses to sugars and amino acids. We also uncover

The ability to predict invasive fungal infections (IFI) in patients with hematological malignancies is fundamental for successful therapy. Although gut dysbiosis is known to occur in hematological patients, whether airway dysbiosis also contributes to the risk of IFI has not been investigated. Nasal and oropharyngeal swabs were collected for functional microbiota characterization in 173 patients with hematological malignancies recruited in a multicenter, prospective, observational study and stratified according to the risk of developing IFI. A lower microbial richness and evenness were found in the pharyngeal microbiota of high-risk patients that were associated with a distinct taxonomic and metabolic profile. A murine model of IFI provided biologic plausibility for the finding that loss of protective anaerobes, such as Clostridiales and Bacteroidetes, along with an apparent restricted availability of tryptophan, is causally linked to the risk of IFI in hematologic patients and indicates avenues for antimicrobial stewardship and metabolic reequilibrium in IFI.

Chlamydia trachomatis and Neisseria gonorrhoeae infections in the rectum and pharynx are important extragenital reservoirs of infection. Few assays approved by the US Food and Drug Administration are commercially available to diagnose pharyngeal or rectal infections. The current study reports on the analytical performance of the Abbott RealTime CT/NG assay, including the limit of detection, inclusivity, and analytical specificity for C. trachomatis and N. gonorrhoeae in rectal and pharyngeal specimens. The limit of detection was performed using known concentrations of organisms, elementary bodies per milliliter (EB/mL) for C. trachomatis and colony-forming units per milliliter (CFU/mL) for N. gonorrhoeae, in clinical rectal and pharyngeal swab matrices. Inclusivity was performed against 12 serovars of C. trachomatis and seven strains of N. gonorrhoeae. The analytical specificity was performed using 28 different bacteria and viruses. The limit of detection for C. trachomatis was 2.56 EB/mL in pharyngeal specimens and 12.8 EB/mL in rectal specimens. The limit of detection for N. gonorrhoeae was 0.0256 CFU/mL for both pharyngeal and rectal specimens. The inclusivity and analytical specificity were 100% for both rectal and pharyngeal specimens. These analytical performance data demonstrate that the Abbott CT/NG RealTime assay is an accurate, sensitive, and specific assay in rectal and pharyngeal specimens, supporting the potential of the assay for detection of rectal and pharyngeal C. trachomatis and N. gonorrhoeae infections.

RATIONALE:Upper airway surgery (UAS) is an established treatment for obstructive sleep apnea (OSA) and is reported to lead to a ~40% improvement in OSA severity. UAS has been suggested to improve OSA by increasing the volume of the pharyngeal airway, however the mechanisms of anatomical improvement following UAS have not been well defined. We therefore aimed to compare and quantify pharyngeal airway and anatomical structures before and after UAS using Magnetic Resonance Imaging (MRI) based analysis. METHOD(S):In a prospective study, 18 patients with moderate-severe OSA suitable for UAS (uvulopalatopharyngoplasty +/- nasal surgery +/- tongue channelling) underwent upper airway MRI imaging paired with diagnostic polysomnography at baseline and at least three months after UAS. Volume of the pharyngeal airway and surrounding soft-tissue structures were determined through segmentation using image analysis software (Slicer3D) performed by one investigator blinded to the operative status of the patient (pre-UAS vs. post-UAS). We also compared the differences in baseline volumes between responders (defined by a reduction in apnea-hypopnea index (AHI) >=50% from baseline) and non-responders. RESULT(S):Completed data analysis is available in 15 patients to date. Pre-operative AHI (mean+/-SD) of was not significantly changed after surgery: 37.67+/-26.90 events/hr to 28.37+/-28.37 events/hr (p=0.29). Total pharyngeal airway volume after UAS did not change significantly from baseline: median pre-UAS volume of 15.42 cm3 [IQR 10.90-19.86] vs. post-UAS 13.17 cm3 [IQR 11.44-23.85] (p>0.99). Velopharyngeal airway volume was significantly reduced after UAS in all but three patients: median pre-UAS volume 3.50cm3 [IQR 2.44-4.73] vs. post-UAS volume 2.70cm3 [IQR 2.12-3.80] (p=0.010). We observed a trend for an association between the percentage changes in total airway volume and AHI (r2= 0.22, p= 0.076). Near-significant increases in volume of the parapharyngeal fat pads 7.51 cm3 [IQR 5

RATIONALE:Upper airway surgery (UAS) is an established treatment for obstructive sleep apnea (OSA) and is reported to lead to a ~40% improvement in OSA severity. UAS has been suggested to improve OSA by increasing the volume of the pharyngeal airway, however the mechanisms of anatomical improvement following UAS have not been well defined. We therefore aimed to compare and quantify pharyngeal airway and anatomical structures before and after UAS using Magnetic Resonance Imaging (MRI) based analysis. METHOD(S):In a prospective study, 18 patients with moderate-severe OSA suitable for UAS (uvulopalatopharyngoplasty +/- nasal surgery +/- tongue channelling) underwent upper airway MRI imaging paired with diagnostic polysomnography at baseline and at least three months after UAS. Volume of the pharyngeal airway and surrounding soft-tissue structures were determined through segmentation using image analysis software (Slicer3D) performed by one investigator blinded to the operative status of the patient (pre-UAS vs. post-UAS). We also compared the differences in baseline volumes between responders (defined by a reduction in apnea-hypopnea index (AHI) >=50% from baseline) and non-responders. RESULT(S):Completed data analysis is available in 15 patients to date. Pre-operative AHI (mean+/-SD) of was not significantly changed after surgery: 37.67+/-26.90 events/hr to 28.37+/-28.37 events/hr (p=0.29). Total pharyngeal airway volume after UAS did not change significantly from baseline: median pre-UAS volume of 15.42 cm3 [IQR 10.90-19.86] vs. post-UAS 13.17 cm3 [IQR 11.44-23.85] (p>0.99). Velopharyngeal airway volume was significantly reduced after UAS in all but three patients: median pre-UAS volume 3.50cm3 [IQR 2.44-4.73] vs. post-UAS volume 2.70cm3 [IQR 2.12-3.80] (p=0.010). We observed a trend for an association between the percentage changes in total airway volume and AHI (r2= 0.22, p= 0.076). Near-significant increases in volume of the parapharyngeal fat pads 7.51 cm3 [IQR 5

Chlamydia trachomatis and Neisseria gonorrhoeae infections in the rectum and pharynx are important extragenital reservoirs of infection. Few assays approved by the US Food and Drug Administration are commercially available to diagnose pharyngeal or rectal infections. The current study reports on the analytical performance of the Abbott RealTime CT/NG assay, including the limit of detection, inclusivity, and analytical specificity for C. trachomatis and N. gonorrhoeae in rectal and pharyngeal specimens. The limit of detection was performed using known concentrations of organisms, elementary bodies per milliliter (EB/mL) for C. trachomatis and colony-forming units per milliliter (CFU/mL) for N. gonorrhoeae, in clinical rectal and pharyngeal swab matrices. Inclusivity was performed against 12 serovars of C. trachomatis and seven strains of N. gonorrhoeae. The analytical specificity was performed using 28 different bacteria and viruses. The limit of detection for C. trachomatis was 2.56 EB/mL in pharyngeal specimens and 12.8 EB/mL in rectal specimens. The limit of detection for N. gonorrhoeae was 0.0256 CFU/mL for both pharyngeal and rectal specimens. The inclusivity and analytical specificity were 100% for both rectal and pharyngeal specimens. These analytical performance data demonstrate that the Abbott CT/NG RealTime assay is an accurate, sensitive, and specific assay in rectal and pharyngeal specimens, supporting the potential of the assay for detection of rectal and pharyngeal C. trachomatis and N. gonorrhoeae infections.

Tensin is a focal adhesion molecule that is known to regulate cell adhesion, migration, and proliferation. Although there are four tensin homologs (TNS1, TNS2, TNS3, and CTEN/TNS4) in mammals, only one tensin gene is found in Caenorhabditis elegans. Sequence analysis suggests that Caenorhabditis elegans tensin is slightly closer aligned with human TNS1 than with other human tensins. To establish the role of TNS1 in Caenorhabditis elegans, we have generated TNS1 knockout (KO) worms by CRISPR-Cas9 and homologous recombination directed repair approaches. Lack of TNS1 does not appear to affect the development or gross morphology of the worms. Nonetheless, defecation cycles are significantly longer in TNS1 KO worms. In addition, their pharyngeal pumping rate is markedly faster, which is likely due to a shorter pump duration in the KO worms. These findings indicate that TNS1 is not required for the development and survival of Caenorhabditis elegans but point to a critical role in modulating defecation and pharyngeal pumping rates.

Coronavirus disease 19 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this scenario, managing acute medical conditions, such as stroke, requires a timely treatment together with proper strategies that minimize the risk of infection spreading to health care workers and other patients. We report the case of a 79-year-old woman, who was admitted for a wake-up stroke due to occlusion of the left middle cerebral artery. She was treated outside the COVID-19-dedicated track of the hospital because she had no concomitant signs or symptoms suggestive of SARS-CoV-2 infection nor recent contact with other infected individuals. Post-mortem nasal and pharyngeal swab was positive for SARS-CoV-2 infection. We propose that hyperacute stroke patients should be tested for SARS-CoV-2 infection at admission and then managed as having COVID-19 until cleared by a negative result. We are aware that such measure results in some delay of the acute treatment of stroke, which could be minimal using well-exercised containment protocols.

Feeding behaviors, guided by the taste system, serve universal and essential functions in animals. The availability of molecular genetic tools and assays to measure behavioral outcomes at high resolution in real time have made the fly, Drosophila melanogaster, an invaluable model to identify molecular components and dissect circuit logic of how the quality and quantity of ingested food is controlled. However, most investigations of taste responses have focused on neurons residing in external taste hairs in the labellum, legs, and wing margins. There remains a complex repertoire of pharyngeal taste neurons lying in an anatomical position to control food intake, which has been largely overlooked. This comparatively limited knowledge of the molecular or functional nature of internal taste neurons in the pharynx represents a critical missing link between taste sensory input and feeding behavior output. Notably, taste-guided feeding behaviors of insect disease vectors and pests impose a substantial economic and health burden in the world. An understanding of taste circuits that regulate feeding may lead to the development of behavior-modifying strategies for insect control. In this dissertation, I present a receptor-to-neuron map for all pharyngeal organs, comprising in a genetic toolkit that allows manipulation of specific cell types in the pharynx, and genetic dissection experiments to assess the roles of selected classes of pharyngeal taste neurons in food selection and intake. The results uncover mechanisms of combinatorial taste coding in pharyngeal taste neurons that mediate feeding avoidance of aversive compounds such as bitter compounds, acids, and high salts. I then report the development of a taste-blind system to examine function of individual classes of pharyngeal taste neurons in controlling food intake of appetitive tastants, such as sugars and amino acids. Finally, I describe efforts to identify potential higher-order brain neurons that control feeding beh

Taste drives appropriate food preference and intake. In Drosophila, taste neurons are housed in both external and internal organs, but the latter have been relatively underexplored. Here, we report that Poxn mutants with a minimal taste system of pharyngeal neurons can avoid many aversive tastants, including bitter compounds, acid, and salt, suggesting that pharyngeal taste is sufficient for rejecting intake of aversive compounds. Optogenetic activation of selected pharyngeal bitter neurons during feeding events elicits changes in feeding parameters that can suppress intake. Functional dissection experiments indicate that multiple classes of pharyngeal neurons are involved in achieving behavioral avoidance, by virtue of being inhibited or activated by aversive tastants. Tracing second-order pharyngeal circuits reveals two main relay centers for processing pharyngeal taste inputs. Together, our results suggest that the pharynx can control the ingestion of harmful compounds by integrating taste input from different classes of pharyngeal neurons.

Introduction: We recently demonstrated that patients with "deep" respiratory events (i.e., complete apneas, suggesting a more collapsible pharynx) were less likely to respond to oral appliance therapy. However, event depth, which requires accurate airflow measurements, can be difficult to determine due to movement of the nasal cannula or oral breathing. Oxygen saturation is an alternative signal for potentially characterizing respiratory event depth that is not impacted by these challenges in airflow measurement. In general, the reduction in ventilation during a respiratory event is proportional to the rate of change in oxygen saturation; deeper events cause a more rapid drop in oxygen saturation per unit time. Therefore, the aim of this abstract was to demonstrate that the slope of the oxygen desaturation curve is proportional to event depth and can be similarly associated with oral appliance treatment efficacy. Method(s): Eighty-one OSA patients (AHI>10 events/hr) were assessed via polysomnography during one night off and one night on treatment with oral appliance. Event depth and desaturation slope were measured from the "average" ventilatory and saturation profiles, respectively, as follows. The time-series signal (e.g. oxygen saturation) from all respiratory events were aligned at event termination and ensemble averaged to output a signal profile of the average respiratory event. Event depth was calculated as the mean reduction in ventilation from the ventilatory profile of the average respiratory event. Desaturation slope was measured as the change in oxygen saturation from the 10th (i.e. event start) to the 90th (i.e. event end) percentile of the saturation profile of the average respiratory event, divided by time between these points. Correlation between event depth and desaturation slope was assessed using Pearson's correlation. Bivariate logistic regression tested differences in both variables between oral appliance responders (>50% reduction in AHI from b

Rationale: Oral appliance therapy is an increasingly prescribed non-PAP alternative for treating OSA, but its efficacy is challenging to predict in individual patients, limiting its application as a first-line therapy. In small physiological studies, we have shown that pathophysiological (endotype) traits causing OSA can predict patient response to oral appliance therapy. These traits include upper airway collapsibility, arousal threshold, and ventilatory control instability (loop gain, response to arousal). Estimating these traits require invasive measurement during sleep or complex model-fitting to full in-lab polysomnographic data. Here we apply a novel, simplified method for estimating the traits causing OSA in individual patients using the ventilation-profile of the average respiratory event. We aimed to determine if PSG-derived traits were associated with oral appliance efficacy (percent reduction in total AHI from baseline). Method(s): Forty-three subjects with total AHI >= 20 hr-1 were available for analysis. The ventilation-profile of the average respiratory event was determined using the following approach: First, all scored respiratory events (apneas, hypopneas) were identified. Second, the ventilation signal for each event was calculated (uncalibrated volume x respiratory rate, expressed as percentage of eupneic [mean] ventilation) and ensemble-averaged with event-termination set to time zero for all events (Figure 1a). Surrogate measures of the endotype traits were calculated from this average respiratory event ventilation-profile as follows: mean event depth was the reduction from eupnea of the mean ventilation during the events, and considered a surrogate of pharyngeal collapsibility; the ventilatory overshoot was the peak ventilation following events as a surrogate of the arousal threshold, and the disturbance was the area under the curve (below eupnea) during the events, which were both utilized used to calculate a surrogate of loop gain (overshoot

Introduction: We recently demonstrated that patients with "deep" respiratory events (i.e., complete apneas, suggesting a more collapsible pharynx) were less likely to respond to oral appliance therapy. However, event depth, which requires accurate airflow measurements, can be difficult to determine due to movement of the nasal cannula or oral breathing. Oxygen saturation is an alternative signal for potentially characterizing respiratory event depth that is not impacted by these challenges in airflow measurement. In general, the reduction in ventilation during a respiratory event is proportional to the rate of change in oxygen saturation; deeper events cause a more rapid drop in oxygen saturation per unit time. Therefore, the aim of this abstract was to demonstrate that the slope of the oxygen desaturation curve is proportional to event depth and can be similarly associated with oral appliance treatment efficacy. Method(s): Eighty-one OSA patients (AHI>10 events/hr) were assessed via polysomnography during one night off and one night on treatment with oral appliance. Event depth and desaturation slope were measured from the "average" ventilatory and saturation profiles, respectively, as follows. The time-series signal (e.g. oxygen saturation) from all respiratory events were aligned at event termination and ensemble averaged to output a signal profile of the average respiratory event. Event depth was calculated as the mean reduction in ventilation from the ventilatory profile of the average respiratory event. Desaturation slope was measured as the change in oxygen saturation from the 10th (i.e. event start) to the 90th (i.e. event end) percentile of the saturation profile of the average respiratory event, divided by time between these points. Correlation between event depth and desaturation slope was assessed using Pearson's correlation. Bivariate logistic regression tested differences in both variables between oral appliance responders (>50% reduction in AHI from b

Rationale: Oral appliance therapy is an increasingly prescribed non-PAP alternative for treating OSA, but its efficacy is challenging to predict in individual patients, limiting its application as a first-line therapy. In small physiological studies, we have shown that pathophysiological (endotype) traits causing OSA can predict patient response to oral appliance therapy. These traits include upper airway collapsibility, arousal threshold, and ventilatory control instability (loop gain, response to arousal). Estimating these traits require invasive measurement during sleep or complex model-fitting to full in-lab polysomnographic data. Here we apply a novel, simplified method for estimating the traits causing OSA in individual patients using the ventilation-profile of the average respiratory event. We aimed to determine if PSG-derived traits were associated with oral appliance efficacy (percent reduction in total AHI from baseline). Method(s): Forty-three subjects with total AHI >= 20 hr-1 were available for analysis. The ventilation-profile of the average respiratory event was determined using the following approach: First, all scored respiratory events (apneas, hypopneas) were identified. Second, the ventilation signal for each event was calculated (uncalibrated volume x respiratory rate, expressed as percentage of eupneic [mean] ventilation) and ensemble-averaged with event-termination set to time zero for all events (Figure 1a). Surrogate measures of the endotype traits were calculated from this average respiratory event ventilation-profile as follows: mean event depth was the reduction from eupnea of the mean ventilation during the events, and considered a surrogate of pharyngeal collapsibility; the ventilatory overshoot was the peak ventilation following events as a surrogate of the arousal threshold, and the disturbance was the area under the curve (below eupnea) during the events, which were both utilized used to calculate a surrogate of loop gain (overshoot

Feeding behaviors, guided by the taste system, serve universal and essential functions in animals. The availability of molecular genetic tools and assays to measure behavioral outcomes at high resolution in real time have made the fly, Drosophila melanogaster, an invaluable model to identify molecular components and dissect circuit logic of how the quality and quantity of ingested food is controlled. However, most investigations of taste responses have focused on neurons residing in external taste hairs in the labellum, legs, and wing margins. There remains a complex repertoire of pharyngeal taste neurons lying in an anatomical position to control food intake, which has been largely overlooked. This comparatively limited knowledge of the molecular or functional nature of internal taste neurons in the pharynx represents a critical missing link between taste sensory input and feeding behavior output. Notably, taste-guided feeding behaviors of insect disease vectors and pests impose a substantial economic and health burden in the world. An understanding of taste circuits that regulate feeding may lead to the development of behavior-modifying strategies for insect control. In this dissertation, I present a receptor-to-neuron map for all pharyngeal organs, comprising in a genetic toolkit that allows manipulation of specific cell types in the pharynx, and genetic dissection experiments to assess the roles of selected classes of pharyngeal taste neurons in food selection and intake. The results uncover mechanisms of combinatorial taste coding in pharyngeal taste neurons that mediate feeding avoidance of aversive compounds such as bitter compounds, acids, and high salts. I then report the development of a taste-blind system to examine function of individual classes of pharyngeal taste neurons in controlling food intake of appetitive tastants, such as sugars and amino acids. Finally, I describe efforts to identify potential higher-order brain neurons that control feeding beh

Taste drives appropriate food preference and intake. In Drosophila, taste neurons are housed in both external and internal organs, but the latter have been relatively underexplored. Here, we report that Poxn mutants with a minimal taste system of pharyngeal neurons can avoid many aversive tastants, including bitter compounds, acid, and salt, suggesting that pharyngeal taste is sufficient for rejecting intake of aversive compounds. Optogenetic activation of selected pharyngeal bitter neurons during feeding events elicits changes in feeding parameters that can suppress intake. Functional dissection experiments indicate that multiple classes of pharyngeal neurons are involved in achieving behavioral avoidance, by virtue of being inhibited or activated by aversive tastants. Tracing second-order pharyngeal circuits reveals two main relay centers for processing pharyngeal taste inputs. Together, our results suggest that the pharynx can control the ingestion of harmful compounds by integrating taste input from different classes of pharyngeal neurons.

Background: Diseases of the pharynx and upper esophageal sphincter can result in debilitating respiratory difficulty, dysphagia or a combination of both. An exact diagnosis is essential to properly prognosticate and guide therapy. Videofluoroscopic assessment of the pharynx and upper esophageal sphincter with or without orally administered contrast material is the diagnostic of choice for many diseases as both anatomic and functional information is gleaned. The purpose of this review is to assess for continuity in imaging protocols across institutions and to record quantitative and qualitative parameters used for analysis of videofluoroscopy of the pharynx and upper esophageal sphincter in dogs. Methods: A systematic literature search was performed including articles published in peer-reviewed veterinary journals involving the topic of videofluoroscopy of the pharynx and upper esophageal sphincter through August 1, 2018. Specifics of study acquisition technique were recorded. Quantitative and qualitative videofluoroscopic parameters were recorded and compared across institutions where appropriate using one-way ANOVA with p ≤ 0.05 being considered significant. Results: Videofluoroscopy of the pharynx and upper esophageal sphincter is performed either in right lateral or standing postures depending on the institution. Bolus size and consistency used during contrast videofluoroscopy of swallowing differs between institutions. Some institutions evaluate videofluoroscopic studies using qualitative criteria while others apply quantitative measures. Reported quantitative measures include inter-swallow interval, swallow rate, jaw cycles per swallow ratio, time to upper esophageal opening, maximal pharyngeal contraction, maximum laryngeal excursion, upper esophageal closure, epiglottic re-opening, and pharyngeal constriction ratio. Measurement outcomes are significantly different between institutions and when bolus size/consistency is variable when assessing healthy dogs. Co

We used magnetic resonance imaging (MRI) to quantify change in upper airway dimension during tidal breathing in subjects with obstructive sleep apnea (OSA, N = 7) and BMI-matched healthy controls (N = 7) during both wakefulness and natural sleep. Dynamic MR images of the upper airway were obtained on a 1.5 T MR scanner in contiguous 7.5 mm-thick axial slices from the hard palate to the epiglottis along with synchronous MRI-compatible electroencephalogram and nasal/oral flow measurements. The physiologic data were retrospectively scored to identify sleep state, and synchronized with dynamic MR images. For each image, the upper airway was characterized by its area, and linear dimensions (lateral and anterior-posterior). The dynamic behavior of the upper airway was assessed by the maximum change in these parameters over the tidal breath. Mean upper airway caliber was obtained by averaging data over the tidal breath. There was no major difference in the upper airway structure between OSA and controls except for a narrower airway at the low-retropalatal/high-retroglossal level in OSA than in controls. Changes in upper airway size over the tidal breath ((maximum - minimum)/mean) were significantly larger in the OSA than in the control group in the low retropalatal/high retroglossal region during both wakefulness and sleep. In the four OSA subjects who experienced obstructive apneas during MR imaging, the site of airway collapse during sleep corresponded to the region of the upper airway where changes in caliber during awake tidal breathing were the greatest. These observations suggest a potential role for dynamic OSA imaging during wakefulness.

BackgroundGonorrhea (Neisseria gonorrhoeae [GC]) and chlamydia (Chlamydia trachomatis [CT]) disproportionately affect men who have sex with men (MSM), and public health implications vary by anatomic site and bacterial agent. Urethral and rectal GC and CT can increase risk of HIV transmission, whereas pharyngeal GC may be a reservoir for antimicrobial resistance. To define screening priorities in Latin America, we compare differences in the prevalence and correlates of urethral, pharyngeal, and rectal GC and CT among MSM in Peru.MethodsA cross-sectional sample of 787 MSM from Lima was screened between 2012 and 2014. We described prevalence of urethral, pharyngeal, and rectal GC and CT infection and conducted bivariate analyses of associations with social, behavioral, and biological characteristics. Poisson regression analyses assessed the correlates of each infection at each anatomic site.ResultsThe most commonly symptomatic infection (urethral GC; 42.1%) was the least prevalent (2.4%). The most prevalent infections were rectal CT (15.8%) and pharyngeal GC (9.9%). Rectal CT was the least commonly symptomatic (2.4%) infection, and was associated with younger age (adjusted prevalence ratio [95% confidence interval], 0.96 [0.94-0.98]), HIV infection (1.46 [1.06-2.02]), and pasivo (receptive; 3.59 [1.62-7.95]) and moderno (versatile; 2.63 [1.23-5.60]) sexual roles.ConclusionsResults highlight limitations of current syndromic screening strategies for sexually transmitted diseases in Peru, wherein urethral CT and rectal GC and CT may be missed due to their frequently asymptomatic presentations. Successful management of GC and CT infections among MSM in low-resource settings requires differentiating between bacterial agent, symptomatic presentation, associated risk factors, and public health implications of untreated infection at different anatomic sites.

BACKGROUND:The objective of this study was to examine the proportion of missed infections and correlates of pharyngeal gonorrhea among young people attending public sexually transmitted disease (STD) clinics. METHODS:We conducted a case-control study of 245 young men and women between April 2012 and May 2014. Participants were eligible for inclusion if they (1) were 15 to 29 years of age, (2) reported giving oral sex to a partner of the opposite sex in the past 90 days, and (3) attended 1 of 12 public STD clinics in Los Angeles County. Computer-assisted self-interviews were used to collect information on sexual behaviors and tests were conducted for pharyngeal and urogenital gonorrhea. RESULTS:Most participants were younger than 25 years (69%) and more than half were female (56%). We identified a total of 64 cases (27%) of gonorrhea, of which 29 (45%) were a urogenital only infection, 18 (28%) were a pharyngeal only, and 17 (27%) were dually infected at both sites. Pharyngeal testing increased case finding by 39% from 46 to 64 cases. After adjusting for age, sex, and number of sex partners, those who reported consistent pharyngeal exposure to ejaculate/vaginal fluids were 3 times as likely to have pharyngeal gonorrhea as compared with those without this exposure (adjusted odds ratio, 3.1; 95% confidence interval, 1.3-7.5). CONCLUSIONS:A large proportion of gonorrhea cases among young people would be missed in the absence of pharyngeal testing. These results have implications for those who provide medical care to clients at STD clinics and highlight the need for pharyngeal screening recommendations and counseling messages related to strategies to reduce exposure to infected fluids.

BACKGROUND:The objective of this study was to examine the proportion of missed infections and correlates of pharyngeal gonorrhea among young people attending public sexually transmitted disease (STD) clinics. METHODS:We conducted a case-control study of 245 young men and women between April 2012 and May 2014. Participants were eligible for inclusion if they (1) were 15 to 29 years of age, (2) reported giving oral sex to a partner of the opposite sex in the past 90 days, and (3) attended 1 of 12 public STD clinics in Los Angeles County. Computer-assisted self-interviews were used to collect information on sexual behaviors and tests were conducted for pharyngeal and urogenital gonorrhea. RESULTS:Most participants were younger than 25 years (69%) and more than half were female (56%). We identified a total of 64 cases (27%) of gonorrhea, of which 29 (45%) were a urogenital only infection, 18 (28%) were a pharyngeal only, and 17 (27%) were dually infected at both sites. Pharyngeal testing increased case finding by 39% from 46 to 64 cases. After adjusting for age, sex, and number of sex partners, those who reported consistent pharyngeal exposure to ejaculate/vaginal fluids were 3 times as likely to have pharyngeal gonorrhea as compared with those without this exposure (adjusted odds ratio, 3.1; 95% confidence interval, 1.3-7.5). CONCLUSIONS:A large proportion of gonorrhea cases among young people would be missed in the absence of pharyngeal testing. These results have implications for those who provide medical care to clients at STD clinics and highlight the need for pharyngeal screening recommendations and counseling messages related to strategies to reduce exposure to infected fluids.

We used magnetic resonance imaging (MRI) to quantify change in upper airway dimension during tidal breathing in subjects with obstructive sleep apnea (OSA, N = 7) and BMI-matched healthy controls (N = 7) during both wakefulness and natural sleep. Dynamic MR images of the upper airway were obtained on a 1.5 T MR scanner in contiguous 7.5 mm-thick axial slices from the hard palate to the epiglottis along with synchronous MRI-compatible electroencephalogram and nasal/oral flow measurements. The physiologic data were retrospectively scored to identify sleep state, and synchronized with dynamic MR images. For each image, the upper airway was characterized by its area, and linear dimensions (lateral and anterior-posterior). The dynamic behavior of the upper airway was assessed by the maximum change in these parameters over the tidal breath. Mean upper airway caliber was obtained by averaging data over the tidal breath. There was no major difference in the upper airway structure between OSA and controls except for a narrower airway at the low-retropalatal/high-retroglossal level in OSA than in controls. Changes in upper airway size over the tidal breath ((maximum - minimum)/mean) were significantly larger in the OSA than in the control group in the low retropalatal/high retroglossal region during both wakefulness and sleep. In the four OSA subjects who experienced obstructive apneas during MR imaging, the site of airway collapse during sleep corresponded to the region of the upper airway where changes in caliber during awake tidal breathing were the greatest. These observations suggest a potential role for dynamic OSA imaging during wakefulness.

Background: Deformities of the carotid artery are rare. Tortuosity, kinking and coiling of the internal carotid artery may be observed with advancing age. A tortuous internal carotid artery may cause an abnormal sensation in the throat. In the early twentieth century, there were several reported cases of fatal haemorrhage during pharyngeal surgical procedures, because this condition went undetected. Method and results: We present two cases of tortuosity of the right internal carotid artery. Both women complained of abnormal throat sensations. Endoscopic studies and radiological examinations revealed tortuous right internal carotid arteries presenting as pulsatile masses. A literature review revealed that, in most reported cases, this deformity occurred on the right side. We believe that the defect and its right-sided predominance can be attributed to anatomical influences and factors affecting blood pressure. Conclusion: In most reported cases of tortuous internal carotid artery, the defect occurred on the right side and patients complained of an abnormal sensation in the throat. This information is useful in the diagnosis of this condition. It is important for otolaryngologists to recognise this anomaly, because fatal haemorrhage can occur in patients with this condition during surgical procedures on the pharynx.