Pharyngeal Tissue Research Articles

Equine upper airway laser surgery generates plumes containing hazardous components

Abstract Objective To evaluate plume composition during simulated diode laser equine upper airway surgery. Methods A 980-nm diode laser fiber was applied in continuous-wave mode in contact with laryngeal and pharyngeal tissues of 6 equine cadaver heads, and resultant plumes were collected for analysis. Measured parameters included the real-time concentration of particulate matter under the size of 2.5 μm (PM2.5), organic carbon (OC), elemental carbon (EC), and volatile organic compounds (VOCs). Results Visible smoke was encountered during surgical laser application and plume collection. Diode laser median activation time was 326 seconds (IQR, 116 to 387 seconds), and median energy was 8,099 J (IQR, 2,721 to 9,110 J). Mean real-time PM2.5 concentrations during laser procedures exceeded 5 mg/m3 throughout. Organic carbon concentrations were much higher than EC concentrations in the surgical plume, with a median OC/EC ratio of 422. Fifty-five individual VOCs were identified. All measured surgical plume components were higher than control samples. Conclusions The evaluation of surgical plumes collected during simulated upper airway diode laser surgery revealed high levels of harmful fine particulate matter PM2.5 exceeding Occupational Safety and Health Administration standards. Increased OC and OC/EC ratio were also observed. Surgical plumes contained VOCs, including the known carcinogenic compounds benzene and toluene. Clinical Relevance These data suggest the need for mitigation strategies, such as specialized masks or local exhaust ventilation, to decrease the exposure of personnel to plumes generated during equine upper airway laser surgery.

Integration of transcriptomics and metabolomics reveals the mechanism of Glycyrrhizae Radix Et Rhizoma extract inhibiting CCL5 in the treatment of acute pharyngitis.

Acute pharyngitis (AP) is a common condition marked by inflammation of the oropharynx, which can lead to severe throat swelling, breathing difficulties, and even suffocation, significantly impacting quality of life. Despite the beneficial anti-inflammatory activity of Glycyrrhizae Radix Et Rhizoma (GRER) and Isoliquiritigenin (ISL), their pharmacological mechanisms against AP remain unclear. This study explores the mechanisms by which GRER treats AP, utilizing both transcriptomics and metabolomics approaches. We identified the chemical components of GRER and those that enter the bloodstream using UPLC-MS/MS. Based on15 % ammonia-induced AP model, this study integrates transcriptomics and metabolomics to investigate the mechanism of GRER and ISL in the AP treatment. The results indicated that GRER has significantly protective and anti-inflammatory effects against AP. Our analysis identified 144 components of GRER in vitro and 17 components in vivo. Network pharmacology and quantitative analysis highlighted ISL as a key active ingredient responsible for GRER's anti-AP effects. Transcriptomics and metabolomics results indicate that GRER and its active ingredient ISL exert therapeutic effects on AP by inhibiting the expression of CCL5 in pharyngeal tissue, thereby downregulating the levels of pro-inflammatory metabolites malic acid and fumaric acid in the tricarboxylic acid (TCA) cycle pathway. The data in this article demonstrated that GRER and ISL has significantly anti-inflammatory effects and protective effects for AP by regulating CCL5 expression to reduce the levels of pro-inflammatory metabolites within TCA cycle pathway. It provides a scientific basis for prevention and treatment of AP.

Research Progress of TCM Treatment of Chronic Pharyngitis

Chronic pharyngitis is a chronic inflammation of the pharyngeal mucosa, submucosa and lymphoid tissue. The main clinical symptoms are dry pharynx, itching, foreign body sensation in pharynx, cough, nausea and retching. It has the characteristics of long course of disease, easy recurrence, prolonged and difficult to cure. The etiology of chronic pharyngitis is complex and the symptoms are stubborn. At present, Western medicine treatment includes oral or nebulized inhalation of antibiotics to fight infection, nebulized inhalation of hormones, a large amount of vitamin supplement and comprehensive dietary intervention. Although there are many western medical treatment methods, they are mainly to improve local symptoms, with unstable conditions, more adverse reactions, and patients' compliance is not high. The treatment of traditional Chinese medicine is based on the fundamental and holistic treatment, which has considerable advantages in improving the symptoms of chronic pharyngitis, reducing recurrence and improving the quality of life of patients.

Integrative network pharmacology and multi-omics to study the potential mechanism of Niuhuang Shangqing Pill on acute pharyngitis

Ethnopharmacological relevanceNiuhuang Shangqing Pill (NSP) is a renowned Chinese medicine prescription listed in the Chinese Pharmacopoeia (Edition, 2020; volume 1) and is utilized in clinical practice for treating headaches and acute pharyngitis (AP) associated with “Shanghuo". Despite its widespread use, the pharmacological mechanism and bioactive components underlying NSP in treating AP remain unclear. Aim of the studyThis study delved into evaluate the alleviation effect of NSP on AP and explore the mechanisms by analyzing multi-omics. Materials and methodsUHPLC-Q Exactive Orbitrap HRMS was employed for the chemical ingredients of NSP. Multiple compositions, targets and pathways involved in the treatment of AP with NSP were predicted by network pharmacology. Additionally, wistar rat model of AP induced by capsaicin was established to evaluate the anti-AP activity of NSP in vivo. The potential mechanism of NSP to improve AP was investigated by real-time PCR, pharyngeal transcriptome analysis, non-targeted metabolomics, immunofluorescence and Western blot. Results119 compounds were identified by UHPLC-Q Exactive Orbitrap HRMS. Both clinical data of Gene Expression Omnibus (GEO) and network pharmacology demonstrated that MAPK signaling pathway and TNF signaling pathway were the critical pathway for AP treatment. In rat model of AP induced by capsaicin, NSP demonstrated the ability to reduce the levels of IL-1β, TNF-α, IL-6, CGRP, SP, PGE2, COX-2 in serum. Moreover, Transcriptomics analysis comprehensively indicated that NSP regulated the MAPK signaling pathway, TNF signaling pathway, biosynthesis of phenylalanine, tyrosine and tryptophan, arachidonic acid metabolism in AP rats. Metabolomics analysis verified that NSP could rebalance arachidonic acid metabolism, biosynthesis of phenylalanine, tyrosine and tryptophan and regulate metabolic profiles. Multi-omics Correlation analysis exhibited that the relative expression of Tnfrsf1b was significantly negatively correlated with 12(S)-HPETE. Immunofluorescence, real-time PCR and Western blot of pharyngeal tissue revealed that NSP inhibited the TNF/p38-MAPK/NF-κB signaling pathway. Additionally, in vitro study on RAW264.7 cells confirmed that NSP counteract LPS-induced inflammatory by inhibiting the TNF/p38-MAPK/NF-κB signaling pathway. Overall, NSP effectively ameliorated capsaicin-induced AP by modulating the arachidonic acid metabolism and TNF/p38-MAPK/NF-κB signaling pathway. ConclusionNSP effectively ameliorated capsaicin-induced AP by modulating the arachidonic acid metabolism, biosynthesis of phenylalanine, tyrosine and tryptophan, as well as the TNF/p38-MAPK/NF-κB signaling pathway.

Age-group-specific associations between adenoid/tonsillar hypertrophy and craniofacial features

BackgroundAge plays an important role in the association between adenotonsillar hypertrophy and craniofacial morphology. This study aimed to analyse the association of adenoid and tonsillar hypertrophy with craniofacial features in different age groups.MethodsLateral cephalograms were obtained from 942 patients aged 6–15 years (433 boys, 509 girls). They were divided into three age groups: 6–9 years (n = 189), 9–12 years (n = 383), and 12–15 years (n = 370). According to the different sites of pharyngeal obstruction, they were classified as control group (CG), adenoid hypertrophy group (AG), tonsillar hypertrophy group (TG) and adenotonsillar hypertrophy group (ATG). Cephalometric measurements were performed on each enrolled participant. Comparisons between groups and correlations between these cephalometric variables and obstruction sites were evaluated.ResultsAt 6–9 years of age, ATG and TG correlated with increased mandibular height (B = 2.2, p = 0.029; B = 2.6, p = 0.042, respectively). At the age of 9–12 years, AG showed a steep growth direction (B = 1.5, p = 0.002), TG showed a higher probability of Class III skeletal pattern (smaller SNB, ANB and SGn/FH, larger Go-Me) and ATG manifested a higher proportion of Class III skeletal pattern. At 12–15 years of age, there was no significant association between cephalometric measurements and pharyngeal lymphoid tissue enlargement.ConclusionsChildren with isolated adenoid hypertrophy have a vertical growth direction at 9–12 years of age. Isolated adenoid hypertrophy correlated with longer mandibular body, more anterior mandible and horizontal skeletal Class III pattern at 6–12 years. Combination of obstructive adenoids and tonsils manifested similarly to children with isolated tonsil hypertrophy.

Differences in salivary microbiome among children with tonsillar hypertrophy and/or adenoid hypertrophy.

Children diagnosed with severe tonsillar hypertrophy display discernible craniofacial features distinct from those with adenoid hypertrophy, prompting illuminating considerations regarding microbiota regulation in this non-inflammatory condition. The present study aimed to characterize the salivary microbial profile in children with tonsillar hypertrophy and explore the potential functionality therein. A total of 112 children, with a mean age of 7.79 ± 2.41 years, were enrolled and divided into the tonsillar hypertrophy (TH) group (n = 46, 8.4 ± 2.5 years old), adenoid hypertrophy (AH) group (n = 21, 7.6 ± 2.8 years old), adenotonsillar hypertrophy (ATH) group (n = 23, 7.2 ± 2.1 years old), and control group (n = 22, 8.6 ± 2.1 years old). Unstimulated saliva samples were collected, and microbial profiles were analyzed by 16S rRNA sequencing of V3-V4 regions. Diversity and composition of salivary microbiome and the correlation with parameters of overnight polysomnography and complete blood count were investigated. As a result, children with tonsillar hypertrophy had significantly higher α-diversity indices (P＜0.05). β-diversity based on Bray-Curtis distance revealed that the salivary microbiome of the tonsillar hypertrophy group had a slight separation from the other three groups (P＜0.05). The linear discriminant analysis effect size (LEfSe) analysis indicated that Gemella was most closely related to tonsillar hypertrophy, and higher abundance of Gemella, Parvimonas, Dialister, and Lactobacillus may reflect an active state of immune regulation. Meanwhile, children with different degrees of tonsillar hypertrophy shared similar salivary microbiome diversity. This study demonstrated that the salivary microbiome in pediatric tonsillar hypertrophy patients had different signatures, highlighting that the site of upper airway obstruction primarily influences the salivary microbiome rather than hypertrophy severity.IMPORTANCETonsillar hypertrophy is the most frequent cause of upper airway obstruction and one of the primary risk factors for pediatric obstructive sleep apnea (OSA). Studies have discovered that children with isolated tonsillar hypertrophy exhibit different craniofacial morphology features compared with those with isolated adenoid hypertrophy or adenotonsillar hypertrophy. Furthermore, characteristic salivary microbiota from children with OSA compared with healthy children has been identified in our previous research. However, few studies provided insight into the relationship between the different sites of upper airway obstruction resulting from the enlargement of pharyngeal lymphoid tissue at different sites and the alterations in the microbiome. Here, to investigate the differences in the salivary microbiome of children with tonsillar hypertrophy and/or adenoid hypertrophy, we conducted a cross-sectional study and depicted the unique microbiome profile of pediatric tonsillar hypertrophy, which was mainly characterized by a significantly higher abundance of genera belonging to phyla Firmicutes and certain bacteria involving in the immune response in tonsillar hypertrophy, offering novel perspectives for future related research.

Potential active fractions and constituents in the flowers of Trollius chinensis Bunge responsible for treating acute pharyngitis

Ethnopharmacological relevanceTrollius chinensis Bunge has a long history of use in China as traditional Chinese medicine and functional tea for the treatment of respiratory infections, such as pharyngitis, tonsillitis and bronchitis. Pharyngitis can impact the entire throat and adjacent lymphoid tissues, and may lead to significant systemic complications. However, the active components and mechanism of Trollius chinensis Bunge for treating acute pharyngitis remains unclear. Aim of the studyTrollius chinensis Bunge is recognized in China both as a medicinal herb and a functional tea. Research into its properties aimed to establish its effectiveness against pharyngitis and to pinpoint the active components and mechanism. Materials and methodsA 70% ethanol extract from the herb was prepared, which was refined using chromatography through a column containing D101 macroporous resin and varying ethanol solutions. The efficacy of the initial and refined extracts was tested using a rat model of ammonia-induced acute pharyngitis. Pathological examination, HE staining and ELISA were applied to screen activity fraction. The compounds were isolated by silica gel, sephadex LH-20 column chromatography and semi-preparative HPLC chromatography from active fraction. All of the isolated compounds were assessed for anti-inflammatory activity by acting on LPS-induced RAW 264.7 macrophage cells in vitro. Cytotoxicity of compounds was detected by CCK-8 assay. The Griess reaction was applied to evaluate the inhibitory effects of isolated compounds on NO production in RAW 264.7 cells induced by LPS. TNF-α, IL-6, IL-1β and PGE2 levels in macrophage supernatant were detected by ELISA. Molecular docking and western blot analysis were applied to study the anti-inflammatory mechanism of active compound. ResultsThe fraction extracted with 30% ethanol proved particularly effective, significantly reducing pharyngitis symptoms. This was evidenced by decreased levels of cytokines (TNF-α, IL-6, IL-1β and PGE2) and visible improvements in the pharyngeal tissue histology. In pursuit of pharyngitis treatments, 23 phenolic acids and 13 flavonoids were isolated from the 30% ethanol fraction and identified using spectral analysis. Of these, three were newly discovered compounds and eight were first-time isolates from the Trollius genus. These compounds were further investigated for their ability to suppress nitric oxide production in RAW 264.7 cells triggered by lipopolysaccharide. Compounds 3, 19, and 26 exhibited strong anti-inflammatory properties. HPLC analysis of the 30% ethanol fraction revealed that orientin was the predominant component, accounting for 44.4% of this fraction. Western blot analysis demonstrated that orientin reduced the expression levels of the protein p-p65 relative to p65, p-IκBα relative to IκBα and iNOS, indicating an anti-inflammatory effect potentially through the modulation of the NF-κB signaling pathway. ConclusionThe finding of this study provided strong support for the use of T. chinensis as a potential functional food for treating pharyngitis.

Estimating the severity of obstructive sleep apnea during wakefulness using speech: A review

Obstructive sleep apnea (OSA) is a chronic breathing disorder during sleep that affects 10-30% of adults in North America. The gold standard for diagnosing OSA is polysomnography (PSG). However, PSG has several drawbacks, for example, it is a cumbersome and expensive procedure, which can be quite inconvenient for patients. Additionally, patients often have to endure long waitlists before they can undergo PSG. As a result, other alternatives for screening OSA have gained attention. Speech, as an accessible modality, is generated by variations in the pharyngeal airway, vocal tract, and soft tissues in the pharynx, which shares similar anatomical structures that contribute to OSA. Consequently, in this study, we aim to provide a comprehensive review of the existing research on the use of speech for estimating the severity of OSA. In this regard, a total of 851 papers were initially identified from the PubMed database using a specified set of keywords defined by population, intervention, comparison and outcome (PICO) criteria, along with a concatenated graph of the 5 most cited papers in the field extracted from ConnectedPapers platform. Following a rigorous filtering process that considered the preferred reporting items for systematic reviews and meta-analyses (PRISMA) approach, 32 papers were ultimately included in this review. Among these, 28 papers primarily focused on developing methodology, while the remaining 4 papers delved into the clinical perspective of the association between OSA and speech. In the next step, we investigate the physiological similarities between OSA and speech. Subsequently, we highlight the features extracted from speech, the employed feature selection techniques, and the details of the developed models to predict OSA severity. By thoroughly discussing the current findings and limitations of studies in the field, we provide valuable insights into the gaps that need to be addressed in future research directions.

Use and evaluation of the McMurray enhanced airway - Distal pharyngeal airway for improved airway management under deep sedation in the endoscopy clinic

BackgroundThe distal pharyngeal airway (DPA) is a novel airway management tool that relieves airway obstruction. Elongated tubing extends to distal pharyngeal tissues which traditional oral and nasal airways fail to reach. This Quality Improvement initiative aimed to develop and implement a DPA guideline for improving airway management and patient safety in patients undergoing deep sedation for endoscopic procedures. MethodsA quasi-experimental design was used to evaluate the use of a commercially available DPA, the McMurray Enhanced Airway (MEA), in comparison to another new solution, nasal positive airway pressure (nPAP) (SuperNO2VA). Adult patients (n = 47) receiving deep sedation for endoscopic procedures received either a DPA or nPAP based on the preference of the anesthesia provider. During the procedure, the number of airway obstructions and manual airway maneuvers was recorded, as were any adverse events. Anesthesia providers were surveyed regarding perceptions of how well the DPA worked to improve airway management in sedated patients. ResultsThere were no statistically significant differences between the DPA and nPAP groups. A desaturation event was reported for five (20 %) patients in the DPA group and five patients (22.7 %) in the nPAP group, p = 0.999. An airway maneuver was performed for seven (29.2 %) patients in the DPA group and nine (40.9 %) in the nPAP group (p = 0.538). No serious complications were seen in either group. In a subset of patients receiving a colonoscopy, 2 of 15 (13.3 %) in the DPA and 5 of 14 (35.7 %) in the nPAP group had a desaturation event (p = 0.215). In the anesthesia provider survey, 92 % agreed the DPA was successful in relieving an upper airway obstruction. ConclusionThis project shows that the DPA was useful in managing airway obstructions and most providers expressed overall satisfaction with its function. The rate of desaturations and airway maneuvers was equivalent in the two groups despite the DPA group having substantially higher BMIs. We found the DPA to be a useful multi-functional rescue device to restore adequate ventilation quickly and easily. As a result, a guideline and a flowchart based on this study were adopted at our institution.

Differential absorption and metabolic characteristics of organic acid components in pudilan xiaoyan oral liquid between young rats and adult rats

Ethnopharmacological relevancePudilan Xiaoyan Oral Liquid (PDL) is a proprietary Chinese medicinal preparation approved by the State for treating acute pharyngitis in both adults and children (Approval No. Z20030095). It is worth noting that children exhibit unique physiopathological characteristics compared to adults. However, the in vivo regulatory characteristics of PDL in treating acute pharyngitis in children remain incompletely understood. Aim of the studyThe differential absorption and metabolism characteristics of the main pharmacological components in PDL in young and adult rats were investigated with a view to providing a reference for preclinical data of PDL in medication for children. Materials and methodsThis study utilized UPLC-Q-TOF-MS to investigate the pharmacodynamic material basis of PDL. The focus was on the gastrointestinal digestion and absorption characteristics of organic acid components in PDL (PDL-OAC), known as the primary pharmacodynamic components in this formulation. The research combined in vitro dynamic simulation and a Quadruple single-pass intestinal perfusion model to examine these characteristics. The permeability properties of PDL-OAC were evaluated using an artificial parallel membrane model. Additionally, an acute pharyngitis model was established to evaluate the histopathological condition of the pharynx in young rats using H&E staining. The levels of IL-1β, TNF-α, IL-6, and IL-10 in blood and pharyngeal tissue homogenates of young rats were quantified using ELISA kits. ResultsA total of 91 components were identified in PDL, including 33 organic acids, 24 flavonoids, 14 alkaloids, 5 terpenoids and coumarins, 3 sugars, and 12 amino acids. The PDL-OAC exhibited a significant reduction in IL-1β, TNF-α, IL-6, and IL-10 levels in the pharyngeal tissues of young rats with acute pharyngitis. Results from dynamic simulation studies of gastrointestinal fluids revealed that the PDL-OAC (Specifically chlorogenic acid (CGA), gallic acid (GA), chicoric acid (CRA), and caffeic acid (CA)) were effectively stabilized in the gastrointestinal fluids of both children and adults in vitro. Young rats, characterized by thinner intestinal walls and higher permeability, efficiently absorbed the four organic acids across the entire intestinal segment. The absorption of CGA, GA, and CRA followed a concentration-dependent pattern, with CGA and GA absorption being influenced by exocytosis. ConclusionThe efficacy of the PDL-OAC in treating acute pharyngitis was demonstrated in young rats. The absorption rate of these components was observed to be faster in young rats compared to adult rats, underscoring the need for dedicated studies on the drug's usage in children. This research provides valuable insights for the appropriate clinical use of PDL in pediatric patients.

Leaderless foot-and-mouth disease virus serotype O did not cause clinical disease and failed to establish a persistent infection in cattle

ABSTRACT The foot-and-mouth disease virus (FMDV) Leader proteinase Lpro inhibits host mRNA translation and blocks the interferon response which promotes viral survival. Lpro is not required for viral replication in vitro but serotype A FMDV lacking Lpro has been shown to be attenuated in cattle and pigs. However, it is not known, whether leaderless viruses can cause persistent infection in vivo after simulated natural infection and whether the attenuated phenotype is the same in other serotypes. We have generated an FMDV O/FRA/1/2001 variant lacking most of the Lpro coding region (ΔLb). Cattle were inoculated intranasopharyngeally and observed for 35 days to determine if O FRA/1/2001 ΔLb is attenuated during the acute phase of infection and whether it can maintain a persistent infection in the upper respiratory tract. We found that although this leaderless virus can replicate in vitro in different cell lines, it is unable to establish an acute infection with vesicular lesions and viral shedding nor is it able to persistently infect bovine pharyngeal tissues.

Jiegeng decoction ameliorated acute pharyngitis through suppressing NF-κB and MAPK signaling pathways

Ethnopharmacological relevanceJiegeng decoction (JGD), consisting of Glycyrrhizae Radix et Rhizoma and Platycodonis Radix at the ratio of 2:1, is a classical Chinese medicine prescription firstly recorded in “Treatise on Febrile Diseases”. JGD has been extensively utilized to treat sore throat and lung diseases for thousands of years in China. However, the pharmacological effect and mechanism of JGD on acute pharyngitis (AP) remain unclear. Aim of the studyOur research aimed to reveal the pharmacological effect of JGD on AP and its potential mechanisms. Materials and methodsThe chemical components of JGD were analyzed based on the UPLC-MS analysis. The anti-inflammatory effect of JGD was evaluated by NO production using the Griess assay in RAW 264.7 cells. The mRNA expression of iNOS, IL-1β, IL-10, TNF-α, IL-6 and MCP-1 was determined by qRT-PCR in vitro. A 15% ammonia-induced AP model was established. The histopathology, the inflammatory cytokines IL-6 and MCP-1 in serum and the apoptosis-related genes caspease-8 and caspease-3 were determined by H&E staining, ELISA and qRT-PCR, respectively. The expression levels of p-p65, p65, p-JNK, JNK, p-p38, p38, p-ERK1/2, ERK1/2, and COX2 were measured through western blotting. ResultsNine compounds, including liquiritin, liquiritin apiosde, liquiritigenin, platycodin D, platycoside A, licorice saponin J2, licorice saponin G2, glycyrrhizic acid, and licochalcone A, were identified. JGD significantly inhibited NO production and regulated the mRNA expression levels of cytokines in LPS-stimulated RAW 264.7 cells. The results of in vivo experiments confirmed that JGD ameliorated AP through improving the pathological state of pharyngeal tissue, decreasing the serum levels of IL-6 and MCP-1 and preventing the tissue mRNA expression of caspease-8 and caspease-3. Furthermore, JGD also inhibited the NF-κB and MAPK pathways in the AP model. ConclusionsThis study suggested that JGD could alleviate AP through its anti-inflammation via NF-κB and MAPK pathways, which supported the traditional application of JGD for the treatment of throat diseases.

Is Tonsillolith a Protective Factor Against Covid-19 ?

Object: Tonsilloliths are the most common calcifications of the head and neck region and are also caused by inflammation of the pharyngeal lymphoid tissue. Changes that may occur in the lymphoid tissue due to tonsilloliths may affect the response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This radiological study aims to investigate the potential effect of tonsilloliths on Coronavirus disease 2019 (COVID-19). Material and Methods: This study, which has a cross-sectional retrospective design, was carried out by evaluating the digital panoramic radiographs taken before the pandemic period of the patient group (n=402) who had COVID -19, who applied to the Akdeniz University Faculty of Dentistry Oral, Dental and Maxillofacial radiology clinic, and the control group (n:400) who did not have COVID -19, in terms of the presence of tonsilloliths. All Statistical analyzes were performed with SPSS version 22.0 and P <0.05 was considered to indicate statistical significance. The Chi-square test and Student's t-test were performed. Results: The incidence of tonsillolith was significantly lower in the patient group (29.1%) than in the control group (45%) (p <0.01). Both groups were similar in terms of age, gender, and systemic disease status (p = 0.1, 0.08, and 0.08, respectively). Tonsilotiths were located both uni and bilaterally (p = 0.09), but unilateral ones were more common on the right side (p = 0.04). Conclusions: The results of this study showed that high-frequency tonsilloliths may have a protective effect against COVID -19.

Comparison of Force Distribution during Laryngoscopy with the C-MAC D-BLADE and Macintosh-Style Blades: A Randomised Controlled Clinical Trial.

Background: The geometry of a laryngoscope's blade determines the forces acting on the pharyngeal structures to a relevant degree. Knowledge about the force distribution along the blade may prospectively allow for the development of less traumatic blades. Therefore, we examined the forces along the blades experienced during laryngoscopy with the C-MAC D-BLADE and blades of the Macintosh style. We hypothesised that lower peak forces are applied to the patient's pharyngeal tissue during videolaryngoscopy with a C-MAC D-BLADE compared to videolaryngoscopy with a C-MAC Macintosh-style blade and direct laryngoscopy with a Macintosh-style blade. Beyond that, we assumed that the distribution of forces along the blade differs depending on the respective blade's geometry. Methods: After ethical approval, videolaryngoscopy with the D-BLADE or the Macintosh blade, or direct laryngoscopy with the Macintosh blade (all KARL STORZ, Tuttlingen, Germany), was performed on 164 randomly assigned patients. Forces were measured at six positions along each blade and compared with regard to mean force, peak force and spatial distribution. Furthermore, the duration of the laryngoscopy was measured. Results: Mean forces (all p < 0.011) and peak forces at each sensor position (all p < 0.019) were the lowest with the D-BLADE, whereas there were no differences between videolaryngoscopy and direct laryngoscopy with the Macintosh blades (all p > 0.128). With the D-BLADE, the forces were highest at the blade's tip. In contrast, the forces were more evenly distributed along the Macintosh blades. Videolaryngoscopy took the longest with the D-BLADE (p = 0.007). Conclusions: Laryngoscopy with the D-BLADE resulted in significantly lower forces acting on pharyngeal and laryngeal tissue compared to Macintosh-style blades. Interestingly, with the Macintosh blades, we found no advantage for videolaryngoscopy in terms of force application.

PAX1 represses canonical Wnt signaling pathway and plays dual roles during endoderm differentiation

BackgroundPaired box 1 (PAX1) is a transcription factor and essential for the development of pharyngeal pouches-derived tissues, including thymus. PAX1 mutations are identified in Severe Combined Immunodeficiency (SCID) patients with Otofaciocervical Syndrome Type 2 (OTFCS2). However, despite the critical roles of PAX1 in embryonic development and diseases, detailed insights into its molecular mode of action are critically missing.MethodsThe repressing roles of PAX1 and SCID associated mutants on Wnt signaling pathway were investigated by luciferase reporter assays, qRT-PCR and in situ hybridization in HEK293FT, HCT116 cells and zebrafish embryos, respectively. Co-immunoprecipitation (co-IP) and western blotting assays were carried out to identify the molecular mechanisms underlying PAX1’s role on Wnt signaling pathway. hESC based endoderm differentiation, flow cytometry, high-throughput sequencing data analysis, and qRT-PCR assays were utilized to determine the roles of PAX1 during endoderm differentiation.ResultsHere, we show that PAX1 represses canonical Wnt signaling pathway in vertebrate cells. Mechanically, PAX1 competes with SUMO E3 ligase PIASy to bind to TCF7L2, thus perturbing TCF7L2 SUMOylation level, further reducing its transcriptional activity and protein stability. Moreover, we reveal that PAX1 plays dual roles in hESC-derived definitive and foregut/pharyngeal endoderm cells, which give rise to the thymus epithelium, by inhibiting Wnt signaling. Importantly, our data show PAX1 mutations found in SCID patients significantly compromise the suppressing ability of PAX1 on Wnt signaling.ConclusionsOur study presents a novel molecular mode of action of PAX1 in regulation of canonical Wnt signaling and endoderm differentiation, thus providing insights for the molecular basis of PAX1 associated SCID, offering better understanding of the behavior of PAX1 in embryogenesis.

Promoter DNA methylation patterns in oral, laryngeal and oropharyngeal anatomical regions are associated with tumor differentiation, nodal involvement and survival.

Differentially methylated regions (DMRs) can be used as head and neck squamous cell carcinoma (HNSCC) diagnostic, prognostic and therapeutic targets in precision medicine workflows. DNA from 21 HNSCC and 10 healthy oral tissue samples was hybridized to a genome-wide tiling array to identify DMRs in a discovery cohort. Downstream analyses identified differences in promoter DNA methylation patterns in oral, laryngeal and oropharyngeal anatomical regions associated with tumor differentiation, nodal involvement and survival. Genome-wide DMR analysis showed 2,565 DMRs common to the three subsites. A total of 738 DMRs were unique to laryngeal cancer (n=7), 889 DMRs were unique to oral cavity cancer (n=10) and 363 DMRs were unique to pharyngeal cancer (n=6). Based on the genome-wide analysis and a Gene Ontology analysis, 10 candidate genes were selected to test for prognostic value and association with clinicopathological features. TIMP3 was associated with tumor differentiation in oral cavity cancer (P=0.039), DAPK1 was associated with nodal involvement in pharyngeal cancer (P=0.017) and PAX1 was associated with tumor differentiation in laryngeal cancer (P=0.040). A total of five candidate genes were selected, DAPK1, CDH1, PAX1, CALCA and TIMP3, for a prevalence study in a larger validation cohort: Oral cavity cancer samples (n=42), pharyngeal cancer tissues (n=25) and laryngeal cancer samples (n=52). PAX1 hypermethylation differed across HNSCC anatomic subsites (P=0.029), and was predominantly detected in laryngeal cancer. Kaplan-Meier survival analysis (P=0.043) and Cox regression analysis of overall survival (P=0.001) showed that DAPK1 methylation is associated with better prognosis in HNSCC. The findings of the present study showed that the HNSCC subsites oral cavity, pharynx and larynx display substantial differences in aberrant DNA methylation patterns, which may serve as prognostic biomarkers and therapeutic targets.

Histopathological Tracing of HPV Genotypes 6 and 11 in Pediatric Patients in Medical City with Chronic Palatine and Pharyngeal Tonsillitis.

HPVs are considered to have high-oncogenic risk. These genotypes have been proven to have a causal link to cancers, in pediatric and youth patients, with high rates of HPV presence in the tonsillar tissues. A prospective case-control research for determining HPV 6/11 genotypes in tonsillar specimens of children who underwent operations in the otolaryngology departments of the Medical City Complex, Baghdad, Iraq, for their non-oncologic palatine and pharyngeal tonsillar hypertrophies. This study enrolled 102 tonsillar tissues, 82 from pediatric patients aged from 4 to 12 years and who underwent tonsillectomies for non-oncologic palatine and pharyngeal tonsillar hypertrophies; 38 specimens were from single operations while 22 were multiple specimens from the same pediatric patients, represented as a total of 44 tissues). In addition, trimmed nasal tissues from 20 patients, with unremarkable pathological changes, were included as the control group. For HPV 6/11 DNA detection, specific DNA probes were used for the chromogenic in situ hybridization (CISH) technique. In the palatine tonsillar hypertrophied tissue group, 26.2% of the tissues revealed positive CISH signals for HPV 6/11 DNA. Regarding the pharyngeal tonsillar hypertrophied tissues, 22.5% of the specimens expressed positive CISH reactions. Among the 22 pediatric patients who had combined pharyngeal and palatine tonsillectomies, in 22.7% both sites expressed positive signals. No positive-CISH reactions were documented in the control nasal tissues. Statistically a significant difference was seen when compared to the control group. Significant rates of HPV were observed which pointed to the spread of HPV, among other STIs, and in mothers of at least this studied pediatric group. Also, this represented a critical mark as reservoir tissue sites, allowing transmission to other mucosal tissue localizations, playing part in their pathogenesis.

Oral Microbial Profile Analysis in Patients with Oral and Pharyngeal Cancer Reveals That Tumoral Fusobacterium nucleatum Promotes Oral Cancer Progression by Activating YAP.

The incidence of oral cancer has recently been increasing worldwide, particularly among young individuals and women. The primary risk factors for head and neck cancers, including oral and pharyngeal cancers, are smoking, alcohol consumption, poor oral hygiene, and repeated exposure to mechanical stimuli. However, approximately one-third of the patients with oral and pharyngeal cancers are neither smokers nor drinkers, which points to the existence of other mechanisms. Recently, human microbes have been linked to various diseases, including cancer. Oral pathogens, especially periodontal pathobionts, are reported to play a role in the development of colon and other types of cancer. In this study, we employed a series of bioinformatics analyses to pinpoint Fusobacterium nucleatum as the predominant oral bacterial species in oral and pharyngeal cancer tissue samples. We successfully isolated Fn. polymorphum from the saliva of patients with oral cancer and demonstrated that Fn. polymorphum indeed promoted oral squamous cell carcinoma development by activating YAP in a mouse tongue cancer model. Our research offers scientific evidence for the role of the oral microbiome in oral cancer progression and provides insights that would help in devising preventative strategies against oral cancer, potentially by altering oral bacterial profiles.

The First-Line Approach in Children with Obstructive Sleep Apnea Syndrome (OSA).

Obstructive sleep apnea syndrome (OSA) is the main manifestation of sleep-disordered breathing in children. Untreated OSA can lead to a variety of complications and adverse consequences mainly due to intermittent hypoxemia. The pathogenesis of OSA is multifactorial. In children aged 2 years or older, adenoid and/or tonsil hypertrophy are the most common causes of upper airway lumen reduction; obesity becomes a major risk factor in older children and adolescents since the presence of fat in the pharyngeal soft tissue reduces the caliber of the lumen. Treatment includes surgical and non-surgical options. This narrative review summarizes the evidence available on the first-line approach in children with OSA, including clinical indications for medical therapy, its effectiveness, and possible adverse effects. Literature analysis showed that AT is the first-line treatment in most patients with adenotonsillar hypertrophy associated with OSA but medical therapy in children over 2 years old with mild OSA is a valid option. In mild OSA, a 1- to 6-month trial with intranasal steroids (INS) alone or in combination with montelukast with an appropriate follow-up can be considered. Further studies are needed to develop an algorithm that permits the selection of children with OSA who would benefit from alternatives to surgery, to define the optimal bridge therapy before surgery, to evaluate the long-term effects of INS +/- montelukast, and to compare the impact of standardized approaches for weight loss.

Sleep Apnea and Dental Implications -A Review

Obstructive sleep apnea (OSA) is an increasingly common, chronic, sleep-related breathing disorder.The prevalence of obstructive sleep apnea (OSA) continues to rise due to change in life patterns.The most common presenting symptom of OSA is excessive sleepiness and is associated with a 2- to 3-fold increased risk of cardiovascular and metabolic disease. The key contributors to OSA pathogenesis include a narrow, crowded, or collapsible upper airway “anatomical compromise” and “non-anatomical” contributors such as ineffective pharyngeal dilator muscle function during sleep, a low threshold for arousal to airway narrowing during sleep, and unstable control of breathing. Effective treatments include weight loss and exercise, positive airway pressure, oral appliances that hold the jaw forward during sleep, and surgical modification of the pharyngeal soft tissues or facial skeleton to enlarge the upper airway. This review summarizes the latest knowledge ondifferent contributors to OSA with a focus on emerging clinical tools.