Survey of pharyngeal foreign bodies in Japan: An ecological study using the nationwide claims data.

OBJECTIVE: Pharyngeal foreign bodies (PFBs) are a prevalent disease affected by food culture and dietary habits, with fish bones as the leading cause. Most studies were limited to specific regions, and a nationwide survey was not conducted in Japan. In this ecological study, we aimed to conduct a nationwide analysis of outpatient PFB cases in Japan over three years, focusing on seasonal trends, sex- and age-stratified cases, and regional differences. METHODS: We used the National Database of Health Insurance Claims and Specific Health Checkups of Japan open data from April 2019 to March 2022. The case data were analyzed by month, age, sex, and prefecture. Additionally, we calculated the standardized claim ratios (SCRs) for each prefecture and investigated the association between dietary habits, food culture, and SCR of PFBs using a two-level linear regression model. RESULTS: We analyzed a total of 164,337 outpatient PFB cases in Japan, revealing an average incidence rate of 45.6 per 100,000 persons. The seasonal trend revealed a peak in July each year from 2019 to 2021, confirming seasonality in PFB incidents. Children reported a higher incidence rate. Living west of Japan and expenditure on fish and shellfish had a strongly positive association with the SCR of PFBs. CONCLUSION: Our nationwide survey reveals that, even within Japan, there were regional variations influenced by food culture and dietary habits. The data showed that PFB incidence was higher among children, highlighting the need for preventive education. LEVEL OF EVIDENCE: Level 3.

A 3-month-old male infant with Goldenhar syndrome: A clinical case report from Woldia, Northeast Ethiopia.

Goldenhar syndrome is a multifactorial congenital anomaly that involves structures that develop from the first and second pharyngeal arches. In this report, we present a clinical case of a 3-month-old male infant diagnosed with Goldenhar syndrome, born to a known retro-viral infected mother who was receiving antiretroviral therapy. The baby was brought to the hospital with complaints related to upper respiratory system. On examination, he had typical signs and symptoms of Goldenhar syndrome: an asymmetrical face with small left facial bones, a low-set ear, left anophthalmia, an atretic left ear with only small ear appendages, and a complete cleft lip and palate. His family had no history of birth defects or exposure to the known causes of birth defects. The baby was treated for severe community-acquired pneumonia, the diagnosis for his current presentation to our hospital, and he is now on multidisciplinary follow-up for possible medical and surgical management of the Goldenhar syndrome.

The safety and efficacy of endoscopic approaches for the management of Zenker's diverticulum: a multicentre retrospective study.

INTRODUCTION: Minimally invasive endoscopic options are safe and effective alternatives to surgery for the treatment of symptomatic Zenker's diverticulum (ZD). However, there is no consensus on the gold-standard approach. We compared the safety and efficacy of Zenker's peroral endoscopic myotomy (Z-POEM), flexible diverticulotomy (FD), and rigid diverticulotomy (RD) for the management of ZD. METHODS: Patients undergoing treatment for ZD at three UK tertiary referral centres were identified and analysed between 2013 and 2023. Patient demographics, procedural details, clinical success, and 30-day adverse events (AE) were recorded. The primary outcomes were technical and clinical success defined as a fall in Dakkak and Bennett dysphagia score to ≤ 1 without re-intervention. RESULTS: There was no difference in baseline characteristics amongst 126 patients undergoing intervention (50 RD, 31 FD, 45 Z-POEM). Technical success for RD, FD, and Z-POEM was 80%, 100%, and 100%, respectively (p < 0.001). Over a mean follow-up of 11.0 months (95% CI 8.2-13.9), clinical success amongst those treated was 85.3% (RD), 74.1% (FD), and 83.7% (Z-POEM; p = 0.48) with recurrence in 17.2% (RD), 20.0% (FD), and 8.3% (Z-POEM; p = 0.50). AEs were equivalent between groups (p = 0.98). During this time, 11 patients underwent surgical myotomy with low clinical success (36.4%) and high morbidity. CONCLUSION: Endoscopic options for the treatment of ZD show equivalent rates of success, but failed RD often led to open myotomy with worse outcomes. Flexible endoscopic modalities are both safe and highly effective treatments that may be considered first-line in experienced centres and should be offered before surgery.

The effect of different functional appliances on the sagittal pharyngeal airway dimension in skeletal class II: a retrospective study.

The aim of this study was to compare the changes in the sagittal pharyngeal airway dimension (SPAD) in adolescents with Class II mandibular retrusion treated with Invisalign Mandibular Advancement (IMA), prefabricated Myobrace (MB), and Twin block (TB). For this retrospective study, the pre-treatment and post-treatment lateral cephalograms of 60 patients who underwent myofunctional treatment, using either one of the tested appliances were gathered from the files of treated patients. Changes in the SPAD were measured in each group, and comparisons were carried out between the three study groups. Additionally, sagittal skeletal measurements were carried out. Comparisons of the study variables at T0 and T1 between the three groups were performed using one-way ANOVA, while comparisons of the difference (T1-T0) were performed using Kruskal Wallis test. A significant SPAD increase has been reported using the three tested appliances (p < 0.05), with the least change documented with MB use (p < 0.05). Significant antero-posterior improvements have been found with IMA, MB, and TB with an increase in the SNB°, and a decrease in ANB° and Wits appraisal (p < 0.05). Non-significant FMA° changes have been observed post-treatment in the three test groups (p > 0.05). The IMA, MB, and TB generated significant SPAD and sagittal changes, with both IMA and TB surpassing MB in the airway area improvement post-treatment. Moreover, the three tested Class II functional appliances did not affect the vertical dimension.

Malignant Abrikossoff's Tumour of the Tonsil - A Case Report of a Rare Entity.

Rationale: This study aimed to report an uncommon site of origin of a rare head-and-neck cancer, namely malignant granular cell tumour. Patient Concerns: An 89-year-old female patient complained of persistent pharyngodynia and odynophagia for two months. Diagnosis: Upon clinical examination, the right palatine tonsil was larger and palpably firmer than the contralateral. An incisional biopsy of the lesion was performed under local anaesthesia revealing malignant granular cell tumour. A contrast-enhanced computed tomography (CECT) scan of the head and neck and an 18F-fluoro-2-deoxy-D-glucose positron emission tomography (PET) scan confirmed the presence of a pathologic appearance of the right palatine tonsil without nodal or distant metastasis. Treatment: Following a multidisciplinary consultation and the patient's informed permission, a right tonsillectomy extended to the constrictor muscle fibres of the upper pharynx was performed. Outcomes: The tumour was staged as pT2 R0 cN0 M0, according to the AJCC 8th edition for soft-tissue tumours of the head and neck. Due to the early stage and the radicality of surgery, no further adjuvant treatments were provided. The patient is currently followed up with no evidence of disease one year post-operatively. Take-away Lessons: Granular cell tumours are rare mesenchymal tumours, firstly described by the pathologist Abrikossoff in 1926. This type of tumour constitutes approximately 0.5% of all soft-tissue tumours, and can affect any part of the body, with the head and neck being the most frequently involved site. The tonsil is an extremely rare localisation of this cancer. The differential diagnosis of unilateral tonsillar enlargement should also include this histological entity.

Effectiveness and outcomes of endoscopic resection for superficial pharyngeal squamous cell carcinomas.

BACKGROUND: With the development of endoscopic imaging, superficial pharyngeal squamous cell carcinoma can now be detected during routine endoscopy. Recently, the effectiveness of endoscopic resection for superficial pharyngeal squamous cell carcinoma have been reported. METHODS: This study had a retrospective single-center design that included patients with superficial pharyngeal squamous cell carcinoma who underwent endoscopic resection. A total 47 patients with 53 lesions were analyzed. RESULTS: En bloc and R0 resection rates were 83.0% and 56.6%. Local recurrence and cervical lymph node metastasis (CLNM) were detected in 1 and 3 patients during follow-up. The macroscopic type 0-I was an independent factor for CLNM. The 3-year cumulative incidence of metachronous pharyngeal squamous cell carcinoma following endoscopic resection was 33.0%, and the 5-year overall survival rate was 89.2%. CONCLUSIONS: Endoscopic resection is an effective treatment for superficial pharyngeal squamous cell carcinomas, and the macroscopic type 0-I is a useful predictor of CLNM.

The larval chondrocranium and its development in Smilisca phaeota with considerations of patterns characteristic for the chondrocranial development of Lalagobatrachia.

Several studies describe the development of the chondrocranium of vertebrates. The details in these studies vary a lot, which makes it hard to compare developmental patterns and identify evolutionary trends. Therefore, we aim to close this gap for anurans, which is the largest order of amphibians. We present here a detailed description of the chondrocranium morphology and development of Smilisca phaeota, the New Granada cross-banded tree frog. The anatomy was described for the larvae at or older than Gossner stage 31 and before ossification starts. Following this, we describe the development of the chondrocranium from Gossner stages 19-26. Early in Gossner stage 19 no precursors of any cartilages are visible, while later in that stage the mesodermal Anlage of Meckel's cartilage was observed. In the subsequent stages more and more mesodermal anlagen become identifiable, followed by chondrification, and final differentiation of the cartilage elements. We used serial sections to study all the developmental stages and additionally utilized cleared and stained specimens and CT scan data. The latter were also used for the 3D reconstruction of the chondrocranium. We previously studied several species and compared these developmental patterns with S. phaeota, revealing potentially characteristic patterns significant for Lalagobatrachia, a clade that includes over 7000 frog species. These include (1) the suprarostral alae develop before the suprarostral corpus, (2) the infrarostral cartilage chondrifies late, after the chondrification of ceratobranchial 1, and (3) the ceratohyal body is the first element to show chondrocytes and to chondrify. However, with only six species studied so far, our data only provide a basis for future studies and developing hypotheses about the ancestral developmental pattern in anurans.

Reliability and Confidence of Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) Rating Among Research and Clinical Speech Pathologists Before and After Implementation of a Training Manual: A Multi-site Study.

DIGEST is a validated, open-source method to grade the severity of pharyngeal dysphagia from the modified barium swallow (MBS) study. Dissemination and implementation of DIGEST is rising, making it critical to understand reliability and facilitators of accurate implementation among users. The aim was to assess reliability of the tool among speech-language pathology (SLP) raters practicing at multiple sites before and after review of a DIGEST training manual and evaluate confidence of DIGEST use pre-and post-training. Thirty-two SLPs from 5 sites participated in a blinded longitudinal DIGEST rating study. Raters were provided a standardized training set of MBS (n = 19). Initial SLP ratings (round 1, R1) were followed by a 2-4 week break before raters rated a re-keyed MBS set (round 2, R2). A minimum 4-8 week wash-out period then preceded self-study of the DIGEST training manual which was followed by a final rating (round 3, R3) and a post-manual survey afterwards. Baseline reliability (R1) of overall DIGEST was on average k = 0.70, reflecting agreement in the substantial range. Seventy-five percent of raters (24/32) demonstrated reliability ≥ 0.61 in the substantial to almost perfect range prior to training. Inter-rater reliability significantly improved from R1 to R3 after review of the DIGEST manual, with the largest change in DIGEST-Efficiency (mean change: DIGEST k = .04, p = .009, DIGEST-Safety k = .07, p = 0.03, and DIGEST-Efficiency k = .14, p = 0.009). Although DIGEST reliability at baseline was adequate in the majority of raters, self-study of the DIGEST training manual significantly improved inter-rater reliability and rater confidence using the DIGEST method, particularly when assigning DIGEST-Efficiency grade. These early data show promise that provider training may be useful to aid in fidelity of DIGEST implementation among SLP clinical users with varying DIGEST experience.

Transcriptional and epigenetic characterization of a new in vitro platform to model the formation of human pharyngeal endoderm.

BACKGROUND: The Pharyngeal Endoderm (PE) is an extremely relevant developmental tissue, serving as the progenitor for the esophagus, parathyroids, thyroids, lungs, and thymus. While several studies have highlighted the importance of PE cells, a detailed transcriptional and epigenetic characterization of this important developmental stage is still missing, especially in humans, due to technical and ethical constraints pertaining to its early formation. RESULTS: Here we fill this knowledge gap by developing an in vitro protocol for the derivation of PE-like cells from human Embryonic Stem Cells (hESCs) and by providing an integrated multi-omics characterization. Our PE-like cells robustly express PE markers and are transcriptionally homogenous and similar to in vivo mouse PE cells. In addition, we define their epigenetic landscape and dynamic changes in response to Retinoic Acid by combining ATAC-Seq and ChIP-Seq of histone modifications. The integration of multiple high-throughput datasets leads to the identification of new putative regulatory regions and to the inference of a Retinoic Acid-centered transcription factor network orchestrating the development of PE-like cells. CONCLUSIONS: By combining hESCs differentiation with computational genomics, our work reveals the epigenetic dynamics that occur during human PE differentiation, providing a solid resource and foundation for research focused on the development of PE derivatives and the modeling of their developmental defects in genetic syndromes.

Fucoxanthin Inhibits the Proliferation and Metastasis of Human Pharyngeal Squamous Cell Carcinoma by Regulating the PI3K/Akt/mTOR Signaling Pathway.

Human pharyngeal squamous cell carcinoma (HPSCC) is the most common malignancy in the head and neck region, characterized by high mortality and a propensity for metastasis. Fucoxanthin, a carotenoid isolated from brown algae, exhibits pharmacological properties associated with the suppression of tumor proliferation and metastasis. Nevertheless, its potential to inhibit HPSCC proliferation and metastasis has not been fully elucidated. This study represents the first exploration of the inhibitory effects of fucoxanthin on two human pharyngeal squamous carcinoma cell lines (FaDu and Detroit 562), as well as the mechanisms underlying those effects. The results showed dose-dependent decreases in the proliferation, migration, and invasion of HPSCC cells after fucoxanthin treatment. Further studies indicated that fucoxanthin caused a significant reduction in the expression levels of proteins in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway, as well as the downstream proteins matrix metalloproteinase (MMP)-2 and MMP-9. Specific activators of PI3K/AKT reversed the effects of fucoxanthin on these proteins, as well as on cell proliferation and metastasis, in FaDu and Detroit 562 cells. Molecular docking assays confirmed that fucoxanthin strongly interacted with PI3K, AKT, mTOR, MMP-2, and MMP-9. Overall, fucoxanthin, a functional food component, is a potential therapeutic agent for HPSCC.

Randomized controlled trial to examine the tolerability of bronchoscopy with and without pharyngeal laryngeal anesthesia (TACOYAKI study).

BACKGROUND: The SARS-CoV-2 pandemic, pharyngeal anesthesia such as nebulizer or lidocaine pump spray is the risk of droplet transmission to health care workers from coughing due to spraying anesthesia. Absence of pharyngeal anesthesia may induce coughing and reduce patient and operator satisfaction, but the efficacy of pharyngeal anesthesia under sedation is still limited. Therefore we evaluated a prospective, randomized, single-blind trial to evaluate efficacy of pharyngeal anesthesia in patients receiving sedation. MATERIALS AND METHODS: We conducted a randomized comparison of pharyngeal anesthesia with or without bronchoalveolar lavage in patients undergoing bronchoscopy at our hospital between March and October 2022. Pharyngeal anesthesia was performed using 8％ lidocaine spray and the operators were blinded to eliminate bias. Two hundred patients were entered into the study and divided into two groups: those who received pharyngeal anesthesia(control group) and did not receive pharyngeal anesthesia(test group). The primary endpoint was the operator's satisfaction with the procedure. The secondary endpoints were the patient's cough during the examination as perceived by the operator, cough and discomfort experienced by the patient and the dose of analgesic/sedative/lidocaine administered. These scales were scored from 0 to 100. RESULT: In primary endpoint, there was no significant difference in the operator-rated procedure satisfaction between the 2 groups. The median for the discomfort score for patients in the control group was tendency higher than in the test group. There were no significant differences in other secondary endpoints. CONCLUSION: Pharyngeal anesthesia may not be recommended for flexible bronchoscopy performed under combined sedation and analgesia. TRIAL REGISTRATION: Registration number: UMIN000046975Date of registration: 2022/03/07.

Mechanism of the Immediate Effect of Balloon Dilation Therapy in Spinal Muscular Atrophy With Dysphagia: A High-Resolution Manometric Study.

Balloon dilation therapy (BDT) is used to treat pharyngeal dysphagia in patients with impaired upper esophageal sphincter (UES) relaxation due to cricopharyngeal dysfunction. However, the mechanism underlying this immediate effect remains unclear. Here, we present a case in which we investigated the immediate effects of BDT on UES dysfunction using high-resolution manometry (HRM). A 67-year-old man was diagnosed with spinal muscular atrophy (SMA). He gradually developed dysphagia, and a gastrostomy was performed. Despite continuing oral intake of supplemental nutrition, the patient developed dysphagia. Videofluoroscopic (VF) examination of swallowing revealed pharyngeal residue, while HRM showed weak pharyngeal contractility and impaired UES opening. BDT was performed to address the UES dysfunction. Immediately following BDT, VF demonstrated improved pharyngeal bolus passage. As for the UES function during swallowing, HRM revealed that the UES relaxation duration was significantly longer and the UES nadir pressure was significantly decreased. The patient continued the BDT before oral intake. HRM revealed immediate and prolonged UES opening with decreased UES pressure during swallowing as an immediate effect of BDT. This suggests that these findings represent the mechanisms underlying dysphagia in this patient with SMA. BDT resulted in an immediate improvement in UES function, potentially leading to dysphagia improvement. BDT should be combined with conventional rehabilitation for impaired UES opening. However, further studies are needed to confirm the long-term effectiveness of BDT for dysphagia due to SMA.

Adapting and optimizing GCaMP8f for use in Caenorhabditis elegans.

Improved genetically-encoded calcium indicators (GECIs) are essential for capturing intracellular dynamics of both muscle and neurons. A novel set of GECIs with ultra-fast kinetics and high sensitivity was recently reported by Zhang et al. (Nature, 2023). While these indicators, called jGCaMP8, were demonstrated to work in Drosophila and mice, data for Caenorhabditis elegans were not reported. Here, we present an optimized construct for C. elegans and use this to generate several strains expressing GCaMP8f (fast variant of the indicator). Utilizing the myo-2 promoter, we compare pharyngeal muscle activity measured with GCaMP7f and GCaMP8f and find that GCaMP8f is brighter upon binding to calcium, shows faster kinetics and is not disruptive to the intrinsic contraction dynamics of the pharynx. Additionally, we validate its application for detecting neuronal activity in touch receptor neurons which reveals robust calcium transients even at small stimulus amplitudes. As such, we establish GCaMP8f as a potent tool for C. elegans research which is capable of extracting fast calcium dynamics at very low magnifications across multiple cell types.

Prevalence and Molecular Characterization of Pharyngeal Gonorrhea in Korean Men With Urethritis.

Background: Pharyngeal infection is more difficult to diagnose and treat than genital or rectal infection and can act as a reservoir for gonococcal infection. We determined the prevalence of pharyngeal gonorrhea in Korean men with urethritis and analyzed the molecular characteristics and antimicrobial susceptibility of the isolates. Methods: Seventy-two male patients with symptoms of urethritis who visited a urology clinic in Wonju, Korea, between September 2016 and March 2018 were included. Urethral and pharyngeal gonococcal cultures, antimicrobial susceptibility testing, Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST), and multiplex real-time PCR (mRT-PCR) were performed. Results: Among the 72 patients, 59 tested positive for gonococcus by mRT-PCR. Of these 59 patients, 18 (30.5%) tested positive in both the pharynx and urethra, whereas 41 tested positive only in the urethra. NG-MAST was feasible in 16 out of 18 patients and revealed that 14 patients had the same sequence types in both urethral and pharyngeal specimens, whereas two patients exhibited different sequence types between the urethra and pharynx. Of the 72 patients, 33 tested culture-positive. All patients tested positive only in urethral specimens, except for one patient who tested positive in both. All culture-positive specimens also tested positive by mRT-PCR. All isolates were susceptible to azithromycin and spectinomycin, but resistance rates to ceftriaxone and cefixime were 2.9% and 14.7%, respectively. Conclusions: The prevalence of pharyngeal gonorrhea in Korean men with gonococcal urethritis is as high as 30.5%, highlighting the need for pharyngeal screening in high-risk groups. Ceftriaxone is the recommended treatment for pharyngeal gonorrhea.

Do Palatoplasty Procedures Resolve Hypernasality as Effectively as Pharyngoplasty Procedures in Patients with 22q11.2 Deletion Syndrome?

OBJECTIVE: Compare the effectiveness of palatoplasty and pharyngoplasty procedures at resolving hypernasality in patients with 22q11.2 deletion syndrome (22q). DESIGN: Retrospective cohort study. SETTING: Metropolitan children's hospital. PATIENTS: Fourteen patients with 22q presenting for management of velopharyngeal insufficiency. INTERVENTIONS: Palatoplasty or pharyngoplasty procedure. MAIN OUTCOME MEASURE: Resolution of hypernasality 12 months postoperatively. RESULTS: Both procedure groups had a mean preoperative velopharyngeal gap of 6.2 mm during phonation. No patient who underwent palatoplasty achieved resolution of hypernasality; 1/7 patients had worse hypernasality, 4/7 had no change, and 2/7 had improved hypernasality. In contrast, hypernasality was resolved in 6/7 patients in the pharyngoplasty group, which was significantly (P = .03) higher than the palatoplasty group. CONCLUSIONS: In patients with 22q, palatoplasty procedures may be less effective than pharyngoplasty procedures at resolving hypernasality. This may be due to underlying anatomic or physiologic differences, such as increased pharyngeal depth and hypodynamic muscles.

Validation of the European Portuguese Version of the Yale Pharyngeal Severity Rating Scale.

This study aimed to validate the Yale Pharyngeal Residue Severity Rating Scale's European Portuguese version and investigate the impact of rater experience. The scale measures the severity of residue in the vallecula and pyriform sinus. Ninety Fiberoptic Endoscopic Evaluation of Swallowing images were selected after consensus and proposed to 13 raters who were asked to assess the severity of pharyngeal residue (PR) in each image in two moments with an interval of two weeks. The raters were divided by years of experience conducting the Fiberoptic Endoscopic Evaluation of Swallowing and in experience using severity scales for residues. Construct validity, inter-rater, and intra-rater reliability were assessed by kappa statistics. The original English scale was translated into European Portuguese using a forward-backward method for validation. The scale reliability was strong, with an elevated intra-rater internal consistency for vallecula (Cronbach's alpha = 0.982) and pyriform sinus (Cronbach's alpha = 0.922). Inter-rater reliability for raters was equally significant and high for vallecula (0.613 for first assessment and 0.604 for second assessment) and pyriform sinus (0.558 for first assessment and 0.509 for second assessment) or for raters with experience using Yale Pharyngeal Severity Rating Scale (vallecula with 0.832 for first assessment and 0.717 for second assessment and pyriform sinus with 0.856 for first assessment and 0.714 for second assessment).The European Portuguese version of the Yale Pharyngeal Severity Rating Scale is a valid, reliable instrument for scoring the location and severity of pharyngeal residue in the context of fiberoptic endoscopic evaluation of swallowing.

Time-to-Treatment Delays and Their Prognostic Implications in Pharyngeal Cancer-An Exploratory Analysis in Western Romania.

BACKGROUND: Diagnosis and treatment for pharyngeal cancer are decisive in determining prognosis. Diagnosis delays are frequent, representing a significant cause of avoidable mortality, and an important factor in subpar survival across the continuous HNC care delivery. METHODS: The present study represents a retrospective analysis of medical records from Western Romania, which included 180 patients, to evaluate the impact of time-to-treatment delay on patients diagnosed with pharyngeal cancer. The data analyses were performed using the Kaplan-Meier method R (version 3.6.3) packages, including tidyverse, final-fit, mcgv, survival, stringdist, janitor, and Hmisc. RESULTS: The mean days from diagnosis until the end of treatment were higher for the nasopharynx group. Cox regression analysis regarding diagnosis to treatment duration categories showed an increased risk mortality by 3.11 times (95%CI: 1.51-6.41, p = 0.0021) with a Harrell's C-index of 0.638 (95%CI: 0.552-0.723). The hypopharynx and oropharynx locations increased risk mortality by 4.59 (95%CI: 1.55-13.55) and 5.49 times (95%CI: 1.79-16.81) compared to the nasopharynx location. CONCLUSIONS: The findings of this study led to the conclusion that it seems there is a trend of mortality risk for oropharynx and hypopharynx cancers due to delays in the time to treatment over 70 days, standing as a basis for further research as there is an imperative need for prospective multicenter studies.

A Potential Role of fgf4, fgf24, and fgf17 in Pharyngeal Pouch Formation in Zebrafish.

In vertebrates, Fgf signaling is essential for the development of pharyngeal pouches, which controls facial skeletal development. Genetically, fgf3 and fgf8 are required for pouch formation in mice and zebrafish. However, loss-of-function phenotypes of fgf3 and fgf8 are milder than expected in mice and zebrafish, which suggests that an additional fgf gene(s) would be involved in pouch formation. Here, we analyzed the expression, regulation, and function of three fgfs, fgf4, fgf24, and fgf17, during pouch development in zebrafish. We find that they are expressed in the distinct regions of pharyngeal endoderm in pouch formation, with fgf4 and fgf17 also being expressed in the adjacent mesoderm, in addition to previously reported endodermal fgf3 and mesodermal fgf8 expression. The endodermal expression of fgf4, fgf24, and fgf17 and the mesodermal expression of fgf4 and fgf17 are positively regulated by Tbx1 but not by Fgf3, in pouch formation. Fgf8 is required to express the endodermal expression of fgf4 and fgf24. Interestingly, however, single mutant, all double mutant combinations, and triple mutant for fgf4, fgf24, and fgf17 do not show any defects in pouches and facial skeletons. Considering a high degree of genetic redundancy in the Fgf signaling components in craniofacial development in zebrafish, our result suggests that fgf4, fgf24, and fgf17 have a potential role for pouch formation, with a redundancy with other fgf gene(s).

A dysphagia model with denervation of the pharyngeal constrictor muscles in guinea pigs: functional evaluation of swallowing.

Introduction: Swallowing impairment is a crucial issue that can lead to aspiration, pneumonia, and malnutrition. Animal models are useful to reveal pathophysiology and to facilitate development of new treatments for dysphagia caused by many diseases. The present study aimed to develop a new dysphagia model with reduced pharyngeal constriction during pharyngeal swallowing. Methods: We analyzed the dynamics of pharyngeal swallowing over time with the pharyngeal branches of the vagus nerve (Ph-X) bilaterally or unilaterally transected, using videofluoroscopic assessment of swallowing in guinea pigs. We also evaluated the detailed anatomy of the pharyngeal constrictor muscles after the denervation. Results: Videofluoroscopic examination of swallowing showed a significant increase in the pharyngeal area during swallowing after bilateral and unilateral sectioning of the Ph-X. The videofluoroscopy also showed significantly higher pharyngeal transit duration for bilateral and unilateral section groups. The thyropharyngeal muscle on the sectioned side was significantly thinner than that on the intact side. In contrast, the thickness of the cricopharyngeal muscles on the sectioned and intact sides were not significantly different. The mean thickness of the bilateral thyropharyngeal muscles showed a linear correlation to the pharyngeal area and pharyngeal transit duration. Discussion: Data obtained in this study suggest that denervation of the Ph-X could influence the strength of pharyngeal contraction during pharyngeal swallowing in relation to thickness of the pharyngeal constrictor muscles, resulting in a decrease in bolus speed. This experimental model may provide essential information (1) for the development of treatments for pharyngeal dysphagia and (2) on the mechanisms related to the recovery process, reinnervation, and nerve regeneration following injury and swallowing impairment possibly caused by medullary stroke, neuromuscular disease, or surgical damage from head and neck cancer.