Influenza A viruses pose a major public health threat by causing seasonal epidemics and sporadic pandemics. Their epidemiological success relies on airborne transmission from person to person; ...however, the viral properties governing airborne transmission of influenza A viruses are complex. Influenza A virus infection is mediated via binding of the viral haemagglutinin (HA) to terminally attached α2,3 or α2,6 sialic acids on cell surface glycoproteins. Human influenza A viruses preferentially bind α2,6-linked sialic acids whereas avian influenza A viruses bind α2,3-linked sialic acids on complex glycans on airway epithelial cells. Historically, influenza A viruses with preferential association with α2,3-linked sialic acids have not been transmitted efficiently by the airborne route in ferrets. Here we observe efficient airborne transmission of a 2009 pandemic H1N1 (H1N1pdm) virus (A/California/07/2009) engineered to preferentially bind α2,3-linked sialic acids. Airborne transmission was associated with rapid selection of virus with a change at a single HA site that conferred binding to long-chain α2,6-linked sialic acids, without loss of α2,3-linked sialic acid binding. The transmissible virus emerged in experimentally infected ferrets within 24 hours after infection and was remarkably enriched in the soft palate, where long-chain α2,6-linked sialic acids predominate on the nasopharyngeal surface. Notably, presence of long-chain α2,6-linked sialic acids is conserved in ferret, pig and human soft palate. Using a loss-of-function approach with this one virus, we demonstrate that the ferret soft palate, a tissue not normally sampled in animal models of influenza, rapidly selects for transmissible influenza A viruses with human receptor (α2,6-linked sialic acids) preference.
Cleft palate is one of the most common congenital birth defects. Tremendous efforts have been made over the last decades towards understanding hard palate development. However, little is known about ...soft palate morphogenesis and myogenesis. Finding an appropriate surgical repair to restore physiological functions of the soft palate in patients with cleft palate is a major challenge for surgeons, and complete restoration is not always achievable. Here, we first analyzed the morphology, orientation and attachments of the four muscles of the murine soft palate and found that they are very similar to their counterparts in humans, validating the use of mus musculus as a model for future studies. Our data suggests that muscle differentiation extends from the lateral region to the midline following palatal fusion. We also detected an epithelial seam in the fusing soft palatal shelves, consistent with the process of fusion of the posterior palatal shelves, followed by degradation of the epithelial remnants. Innervation and vascularization are present mainly in the oral side of the soft palate, complementing the differentiated muscles. Cell lineage tracing using Wnt1-Cre;Zsgreenfl/fl mice indicated that all the tendons and mesenchyme embedding the soft palate muscles are neural crest-derived. We propose that the posterior attachment of the soft palate to the pharyngeal wall is an interface between the neural crest- and mesoderm-derived mesenchyme in the craniofacial region, and thus can serve as a potential model for the study of boundaries during development. Taken together, our study provides a comprehensive view of the development and morphology of the murine soft palate and serves as a reference for further molecular analyses.
BACKGROUND Chronic intermittent hypoxia (CIH) is a key feature of obstructive sleep apnea (OSA) syndrome. The pathogenesis of CIH-induced soft palate lesion is not well understood. Understanding the ...mechanisms of CIH-induced soft palate damage could provide new strategies for clinical treatment. MATERIAL AND METHODS Twenty male Sprague‑Dawley rats were randomized into a control group (n=10) and experimental group (n=10). The experimental group were exposed to CIH for 28 days. The control experiments were run in parallel. Morphological changes of CIH-induced soft palate were examined by hematoxylin and eosin. Peripheral nerves and vascular associated markers were analyzed by western blot and immunohistochemical staining. LC3B expression and transmission electron microscopy analysis was detected to investigate the destiny of cells in CIH-induced soft palate. RESULTS Histological studies demonstrated the thicken mucosal layer, muscular changes consistent with glands hyperplasia, and loose connective tissues of the soft palate in CIH induced rat models. CIH exposure significantly decreased the expression of annexin V but did not change argin level, suggesting that sensory nerves not motor nerves were damaged when exposed to intermittent hypoxia. Moreover, in response to CIH, the vascular vessel around the nerves and muscles became enlarged and caveolin-1 was overexpressed. Autophagy occurs in response to CIH-induced neuromuscular and vascular endothelial injury. CONCLUSIONS Sensory nerves and endothelial dysfunction contributed to the morphological damage of soft palate under intermittent hypoxia. Autophagy as a compensatory mechanism protects against CIH-induced injury. These findings have important implications for understanding mechanisms contributing to the increased soft palate lesion in patients with OSA.
The authors aimed to report a hitherto undescribed class of patients with the obvious phenotype of a novel soft palate dysplasia (SPD) combining unilateral soft palate hypoplasia with a fully ...developed uvula. The authors also aimed to investigate and evaluate the corresponding surgical approaches.
Twelve patients were clinically diagnosed with SPD. Clinical examination, including radiographic tests, was performed to characterize the congenital deformity. The effectiveness of velopharyngeal closure and speech were tested preoperatively and postoperatively.
SPD was featured with velopharyngeal insufficiency, food regurgitation, and speech disorders. It was commonly manifested as structural deformities of the soft palate, tongue palatine arch, pharyngeal palatine arch, and pterygomandibular fold, but with complete uvula shape. According to radiographic analysis, in five patients, the lateral pterygoid processes were poorly developed, and other malformations were present. Velopharyngoplasty based on the unilateral posterior pharyngeal flap can well restore the velopharyngeal closure and speech intelligibility without respiration obstruction.
SPD is characterized as congenital velopharyngeal insufficiency manifested as a primary soft palate defect. It is highly associated with other physical deformities but independent of conventionally known syndromes. The cause may be an abnormal development of the pterygoid process. Unilateral velopharyngoplasty based on the posterior pharyngeal flap is a great technique to repair SPD.
Therapeutic, IV.
Purpose: The observed sexual dimorphism of velopharyngeal structures among adult populations has not been observed in the young child (4- to 9- year-old) population. The purpose of this study was to ...examine the age at which sexual dimorphism of velopharyngeal structures become apparent and to examine how growth trends vary between boys and girls. Method: Static 3-dimensional magnetic resonance imaging velopharyngeal data were collected among 202 participants ranging from 4 to 21 years of age. Participants were divided into 3 groups based on age, including Group 1: 4-10 years of age, Group 2: 11-17 years of age, and Group 3: 18-21 years of age. Nine velopharyngeal measures were obtained and compared between groups. Results: Significant sex effects were evident for levator length (p = 0.011), origin to origin (p = 0.018), and velopharyngeal ratio (p = 0.036) for those in Group 2 (11-17 years of age). Sex effects became increasingly apparent with age, with 7 of 9 variables becoming significantly different between male and female participants in Group 3. Boys, in general, displayed a delayed growth peak in velopharyngeal growth compared to girls. Conclusion: Results from this study demonstrate the growth of velopharyngeal anatomy with sexual dimorphism becoming apparent predominantly after 18 years of age. However, velopharyngeal variables displayed variable growth trends with some variables presenting sexual dimorphism at an earlier age compared to other velopharyngeal variables.
Objectives/Hypothesis
Selective upper airway stimulation (sUAS) of the hypoglossal nerve is a useful therapy to treat patients with obstructive sleep apnea. Is it known that multiple obstructions can ...be solved by this stimulation technique, even at the retropalatal region. The aim of this study was to verify the palatoglossus coupling at the soft palate during stimulation.
Study Design
Single‐center, prospective clinical trail.
Methods
Twenty patients who received an sUAS implant from April 2015 to April 2016 were included. A drug‐induced sedated endoscopy (DISE) was performed before surgery. Six to 12 months after activation of the system, patients' tongue motions were recorded, an awake transnasal endoscopy was performed with stimulation turned on, and a DISE with stimulation off and on was done.
Results
Patients with a bilateral protrusion of the tongue base showed a significantly increased opening at the retropalatal level compared to ipsilateral protrusions. Furthermore, patients with a clear activation of the geniohyoid muscle showed a better reduction in apnea‐hypopnea index.
Conclusions
A bilateral protrusion of the tongue base during sUAS seems to be accompanied with a better opening of the soft palate. This effect can be explained by the palatoglossal coupling, due to its linkage of the muscles within the soft palate to those of the lateral tongue body.
Level of Evidence
4 Laryngoscope, 127:E378–E383, 2017
The ventral jugular foramen and the infrapetrous region are difficult to access through conventional lateral and posterolateral approaches. Endoscopic endonasal approaches to this region are ...obstructed by the eustachian tube (ET). This study presents a novel strategy for mobilizing the ET while preserving its integrity. Qualitative and quantitative comparisons with previous ET management paradigms are also presented.
Ten dry skulls were analyzed. Four ET management strategies were sequentially performed on a total of 6 sides of cadaveric head specimens. Four measurement groups were generated: in group A, the ET was intact and not mobilized; in group B, the ET was mobilized inferolaterally; in group C, the ET underwent anterolateral mobilization; and in group D, the ET was resected. ET range of mobilization, surgical exposure area, and surgical freedom were measured and compared among the groups.
Wide exposure of the infrapetrous region and jugular foramen was achieved by removing the pterygoid process, unroofing the cartilaginous ET up to the level of the posterior aspect of the foramen ovale, and detaching the ET from the skull base and soft palate. Anterolateral mobilization of the ET facilitated significantly more retraction (a 126% increase) of the ET than inferolateral mobilization (mean ± SD: 20.8 ± 11.2 mm vs 9.2 ± 3.6 mm p = 0.02). Compared with group A, groups C and D had enhanced surgical exposure (142.5% 1176.9 ± 935.7 mm2 and 155.9% 1242.0 ± 1096.2 mm2, respectively, vs 485.4 ± 377.6 mm2 for group A both p = 0.02). Furthermore, group C had a significantly larger surgical exposure area than group B (p = 0.02). No statistically significant difference was found between the area of exposure obtained by ET removal and anterolateral mobilization. Anterolateral mobilization of the ET resulted in a 39.5% increase in surgical freedom toward the exocranial jugular foramen compared with that obtained through inferolateral mobilization of the ET (67.2° ± 20.5° vs 48.1° ± 6.7° p = 0.047) and a 65.4% increase compared with that afforded by an intact ET position (67.2° ± 20.5° vs 40.6° ± 14.3° p = 0.03).
Anterolateral mobilization of the ET provides excellent access to the ventral jugular foramen and infrapetrous region. The surgical exposure obtained is superior to that achieved with other ET management strategies and is comparable to that obtained by ET resection.
Snoring is common in children and is associated with many adverse consequences. One must study the relationships between pharyngeal morphology and snoring physics to understand snoring progression. ...Although some model studies have provided fluid–structure interaction dynamic descriptions for the correlation between airway size and snoring physics, the descriptions still need to be further investigated in patient-specific airway models. Fluid-structure interaction studies using patient-specific airway structures complement the above model studies. Based on reported cephalometric measurement methods, this study quantified and preset the size of the palatopharynx airway in a patient-specific airway and investigated how the palatopharynx size affects the pharyngeal airflow fluctuation, soft palate vibration, and glossopharynx vibration with the help of a verified FSI method. The results showed that the stenosis anterior airway of the soft palate increased airway resistance and airway resistance fluctuations, which can lead to increased sleep effort and frequent snoring. Widening of the anterior airway can reduce airflow resistance and avoid obstructing the anterior airway by the soft palate vibration. The pharyngeal airflow resistance, mouth inflow proportion, and soft palate apex displacement have components at the same frequencies in all airway models, and the glossopharynx vibration and instantaneous inflow rate have components at the same frequencies, too. The mechanism of this same frequency fluctuation phenomenon can be explained by the fluid–structure interaction dynamics of an ideal coupled model consisting of a flexible plate model and a collapsible tube model. The results of this study demonstrate the potential of FSI in studying snoring physics and clarify to some degree the mechanism of airway morphology affecting airway vibration physics.
Highly compliant tissue supporting the pharynx and low muscle tone enhance the possibility of upper airway occlusion in children with obstructive sleep apnea (OSA). The present study describes ...subject-specific computational modeling of flow-induced velopharyngeal narrowing in a female child with polycystic ovarian syndrome (PCOS) with OSA and a non-OSA control. Anatomically accurate three-dimensional geometries of the upper airway and soft-palate were reconstructed for both subjects using magnetic resonance (MR) images. A fluid-structure interaction (FSI) shape registration analysis was performed using subject-specific values of flow rate to iteratively compute the biomechanical properties of the soft-palate. The optimized shear modulus for the control was 38 percent higher than the corresponding value for the OSA patient. The proposed computational FSI model was then employed for planning surgical treatment for the apneic subject. A virtual surgery comprising of a combined adenoidectomy, palatoplasty and genioglossus advancement was performed to estimate the resulting post-operative patterns of airflow and tissue displacement. Maximum flow velocity and velopharyngeal resistance decreased by 80 percent and 66 percent respectively following surgery. Post-operative flow-induced forces on the anterior and posterior faces of the soft-palate were equilibrated and the resulting magnitude of tissue displacement was 63 percent lower compared to the pre-operative case. Results from this pilot study indicate that FSI computational modeling can be employed to characterize the mechanical properties of pharyngeal tissue and evaluate the effectiveness of various upper airway surgeries prior to their application.
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