A composition of ursolic acid derivatives from Ludwigia hyssopifolia induces apoptosis in throat cancer cells via the Akt/mTOR and mitochondrial signaling pathways and by modulating endoplasmic reticulum stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Ludwigia hyssopifolia (LH), an ethnopharmacological herb used in Guangxi Zhuang medicine, is known for its extensive therapeutic use in treating throat disorders. The anti-laryngeal-cancer benefits of the ethyl acetate and petroleum ether fractions of the ethanolic extracts of LH have been shown in our prior cell-based research. Nevertheless, the specific impacts and underlying processes by which LH combats throat cancer effects have not been fully understood. AIM OF THE STUDY: This study involved the extraction of a composition containing two derivatives of ursolic acid from LH (LH-CUAD). The present study aimed to assess the anti-throat-cancer effects of these derivatives and the underlying mechanisms through in vitro and in vivo experiments. MATERIALS AND METHODS: Solvent extraction, fractionation, chromatography, and semipreparative high-performance liquid chromatography were used for the extraction, purification, and analysis of LH-CUAD. The in vitro and in vivo anti-throat-cancer effects of LH-CUAD were investigated using the throat cancer cell lines Hep-2 and FaDu as well as Hep-2 tumor-bearing nude mice. RESULTS: LH-CUAD significantly inhibited the proliferation and migration of throat cancer cells without any prominent toxicity. The Hoechst 33258 staining, Annexin V-FITC/PI double-staining assays, and flow cytometry confirmed that LH-CUAD could induce throat cancer cell death from early to late apoptosis in vitro. LH-CUAD exhibited significant antitumor activity and low toxicity in a xenograft model, and induced throat cancer cells apoptosis in vivo. The apoptotic effects of LH-CUAD therapy were validated using Western blotting, which demonstrated the activation of a caspase cascade response triggered by an imbalance between the endoplasmic reticulum and mitochondria. In addition, it was observed that LH-CUAD exhibited inhibitory effects on Akt and mTOR phosphorylation, hence promoting apoptosis. CONCLUSIONS: LH-CUAD induces apoptosis in both in vivo and in vitro models of throat cancer. This effect is achieved by activating the mitochondrial pathway, inhibiting the Akt/mTOR pathway and initiating endoplasmic reticulum stress. The findings of this study suggest that LH-CUAD has the potential to offer a novel approach to the clinical management of throat cancer.

CT-based diagnosis in patients presenting with throat pain: A single institutional review.

RATIONALE AND OBJECTIVE: To determine if patient demographic data, medical history, physical examination, and laboratory tests will help predict likelihood of imaging-based diagnosis using CT of the neck performed in the ED for a chief complaint of throat pain. MATERIAL AND METHODS: Single institutional, retrospective review of 367 CT scans of the neck performed for the evaluation of throat pain in the ED from August 2013 to September 2019. Patients' clinical history, physical exams, lab findings, and imaging results were recorded. RESULTS: A total of 367 CT scans of the neck performed for the evaluation of throat pain included a recorded exam and clinical history. Of these cases, we noted that the presence of cervical lymphadenopathy (OR = 2.69; 95% CI, 1.37-5.49), tonsillar findings (OR = 2.94; 95% CI, 1.4-6.57), increased white blood cell count (OR = 1.08; 95% CI, 1.02-1.15), and temperature (OR = 1.94; 95% CI, 1.1-3.6) were associated with increased likelihood of obtaining a diagnostic CT scan. CONCLUSION: Consideration of tonsillar abnormalities, lymphadenopathy, body temperature, and measured leukocyte count prior to ordering CT scans of the neck for throat pain may increase the diagnostic yield of such exams and decrease CT utilization in the ED.

Effect of SEC III protocol on upper airway dimensions in growing class III patients: a retrospective study.

BACKGROUND: The primary objective of the study was to evaluate the effects of SEC III (Splints, Class III Elastics, and Chin cup) protocol on the upper airway dimensions using lateral cephalometric radiographs. The secondary objectives were to evaluate the skeletal and dental effects of the SEC III protocol using lateral cephalometric radiographs. METHODS: The pre- and post-treatment lateral cephalometric radiographs of 24 patients treated using the SEC III protocol were used to address the aim of the study. Children in the pre-pubertal (CS-1 or CS-2) or circumpubertal (CS-3 or CS-4) skeletal maturation stage and having class III dentoskeletal malocclusion were included in the study. Patients with a history of previous orthodontic treatment, maxillofacial surgery or trauma, tonsillectomy, adenoidectomy, or craniofacial malformations were excluded. The pre-treatment and post-treatment lateral cephalometric radiographs were traced, then airway measurements, skeletal measurements, and dental measurements were performed. The results were analysed using paired samples t-test or Wilcoxon signed rank test according to the data normality. RESULTS: Data of 6 males and 18 females were analysed (Mean age = 11.21 ± 1.02 years). Duration of active treatment was 5.75 ± 1.03 months. Treatment using SEC III protocol resulted in a significant increase in ANB angle (2.92 ± 1.50 degrees, p < 0.001) and Wits appraisal (3.31 ± 1.99 mm) (p < 0.001). The increase in the mandibular plane angle (0.75 ± 1.42 degrees, p = 0.02) and the maxillary length (2.29 ± 2.69 mm, p < 0.001) was statistically significant. Contrarily, the mandibular length did not change significantly (p = 0.10). The maxillary incisors were significantly proclined (4.38 ± 4.28 degrees; p < 0.001), while the mandibular incisors were significantly retroclined (-5.79 ± 6.21 degrees; p < 0.001) following treatment. The change in the nasopharyngeal airway and the retropalatal airway was not statistically significant. The middle and inferior pharyngeal space (retroglossal airway) significantly decreased by 1.33 ± 1.97 mm (p = 0.003) and 1.96 ± 2.48 mm (p = 0.001), respectively. CONCLUSIONS: Early class III correction using SEC III protocol reduced the retroglossal airway dimensions but did not affect the nasopharyngeal and retropalatal airway dimensions. Correction of the class III dentoskeletal relationship was obtained through both skeletal and dental changes.

Identification of a pharyngeal mucosal lymphoid organ in zebrafish and other teleosts: Tonsils in fish?

The constant exposure of the fish branchial cavity to aquatic pathogens causes local mucosal immune responses to be extremely important for their survival. Here, we used a marker for T lymphocytes/natural killer (NK) cells (ZAP70) and advanced imaging techniques to investigate the lymphoid architecture of the zebrafish branchial cavity. We identified a sub-pharyngeal lymphoid organ, which we tentatively named "Nemausean lymphoid organ" (NELO). NELO is enriched in T/NK cells, plasma/B cells, and antigen-presenting cells embedded in a network of reticulated epithelial cells. The presence of activated T cells and lymphocyte proliferation, but not V(D)J recombination or hematopoiesis, suggests that NELO is a secondary lymphoid organ. In response to infection, NELO displays structural changes including the formation of T/NK cell clusters. NELO and gill lymphoid tissues form a cohesive unit within a large mucosal lymphoid network. Collectively, we reveal an unreported mucosal lymphoid organ reminiscent of mammalian tonsils that evolved in multiple teleost fish families.

Clinical Profile and Outcome Analysis of Ear-Nose-Throat Symptoms in SARS-CoV-2 Omicron Subvariant Infections.

Objective: This study aimed to investigate the clinical characteristics and outcomes of ear-nose-throat (ENT) symptoms in SARS-CoV-2 Omicron infected patients resulting from local transmission. Methods: A convenience sampling network survey was conducted among individuals infected with SARS-CoV-2 to examine the characteristics and progression of ENT symptoms associated with local transmission. The survey comprised 52 questions, and univariable and multivariable logistic regression analyses were employed to assess the rate, severity, and outcome of ENT symptoms across different genders and age groups. Results: Among the 1,366 individuals included in the investigation, a peak in new infections occurred on 20th December, and the majority (78.4%) were female. The most common symptoms reported were coughing (90.6%), nasal congestion (77.2%), and runny nose (74.3%). Otologic symptoms were predominantly represented by tinnitus (29.7%). Conclusion: The rate of specific symptoms showed a significant correlation with age and gender. It is crucial to provide timely medical intervention, especially for female patients. This study offers a comprehensive understanding of the symptom spectrum in individuals infected with the virus, providing valuable insights for the development of targeted symptom management strategies.

Changes in Upper Airway Anatomy Following Orthodontic Treatment for Malocclusion: A Comparative Retrospective Study in 96 Patients.

BACKGROUND This retrospective study aimed to compare pharyngeal anatomical changes measured in cephalometric images before and after treatment for malocclusion Class I, II, and III in 96 patients undergoing orthodontic treatment. MATERIAL AND METHODS A total of 96 patients who underwent fixed orthodontic treatment were included in the study. The patients were divided into 3 groups according to the malocclusion (32 people in each group). The upper airway data in the lateral cephalometric images of the patients were retrospectively analyzed before starting fixed orthodontic treatment and the upper airway data taken after the end of the fixed orthodontic treatment. RESULTS According to the findings, all the upper airway data in individuals in Class I (Skeletal Class I malocclusion) group and most of the upper airway data in Class II (Skeletal Class II malocclusion) groups increased after orthodontic treatment compared to before treatment (P<0.05). Most of the upper airway data in Class III (Skeletal Class III malocclusion) group individuals decreased after orthodontic treatment compared to before treatment (P<0.05). CONCLUSIONS Orthodontic treatment should be chosen considering that an increase may be observed in individuals with Class I and Class II malocclusion. Similarly, in individuals with Class III malocclusion, orthodontic treatment can be chosen considering that there will be a decrease in the upper airways. By determining the effects of fixed orthodontic treatment on the airways, airway problems experienced at an early age can be prevented.

Sustained pharyngeal inflation in infant airway-Flexible bronchoscopy measurements.

Sustained pharyngeal inflation (SPI) with pharyngeal oxygen flow and nasal closure (PhO2-NC) technique create positive inflation pressure in the airway. This study measured the peak inflation pressure (PIP) levels and image changes with SPI-assisted flexible bronchoscopy (SPI-FB) and compared the effects in the pharyngeal space and mid-tracheal lumen. This prospective study enrolled 20 participants aged 6 months to 3 years. Each participant underwent sequential SPI-FB of four different durations (0, 1s, 3s, and 5s) for three cycles. We used a 3.8 mm OD flexible bronchoscope to measure and analyze PIP levels, images, and lumen dimension scores. A total of 480 data were collected. The mean (SD) age and body weight were 12.0 (11.5) months and 7.8 (7.5) kg, respectively. The mean (IQR) PIPs were 4.2 (2.0), 18.5 (6.1), 30.6 (13.5), and 46.1 (25.0) cmH2O in the pharynx and 5.0 (1.6), 17.5 (6.5), 28.0 (12.3), 46.0 (28.5) cmH2O in the mid-trachea at SPI durations of 0, 1s, 3s, and 5s, respectively. The PIP levels had a positive correlation (p <0.001) with different SPI durations in both pharynx and trachea, and were nearly identical (p = 0.695, 0.787, and 0.725 at 1s, 3s, and 5s, respectively) at the same duration except the 0 s (p = 0.015). Lumen dimension scores also significantly increased with increasing SPI durations (p <0.05) in both locations. The identified lesions significantly increased as PIP levels increased (p <0.001). Conclusion: SPI-FB using PhO2-NC with durations up to 3s is safe and informative technique that provides controllable PIP, dilates airway lumens, and benefits lesion detection in the pharyngeal space and mid-tracheal lumen.

[«Our whole family does not get out of the common cold¼: an ear, throat and nose disease in the conditions of S.P. Botkin]. / «Vse nashe semeistvo ne vykhodit iz nasmorka¼: zabolevaniya ukha, gorla i nosa v okruzhenii S.P. Botkina.

The article presents an epistolary insight into the history of otorhinolaringology in Russia. It shows pathology of ear, nose and throat, which S.P. Botkin faced: cases of diseases of empress Maria Aleksandrovna, grand duke Vyacheslav Konstantinovich, poet N.A. Nekrasov, publisher A.A. Kraevsky, Sergey Petrovich himself, his relatives and loved ones. The biographical singularity of the famous doctor's patients is noted. On the materials of family letters of 1855-1889 yrs., service diaries of 1872-1889 yrs. and S.P. Botkin's clinical lectures it is shown how daily cases and casuistry of otorhinolaryngology pathology formed scientific innovative ideas.

Nasal and maxillary sinus volume change in patients with obstructive sleep apnea after bimaxillary advancement surgery.

The airway complex is modified by bimaxillary advancement surgery performed in patients suffering from obstructive sleep apnea (OSA). The aim of the present study is to analyse the volume of nasal and maxillary sinus after bimaxillary advancement surgery in patients suffering from OSA. The maxillary sinus and nasal complex of eighteen patients with OSA was measured through cone-beam computed tomography (CBCT) before and after they were treated with bimaxillary advancement surgery. Digital planning software was used to effectively measure the upper volume changes, as well as, statistical analysis of the results was performed.Methods Eighteen patients were diagnosed with OSA the severity of which was measured by the apnea hypopnea index and were selected and submitted to preoperative and postoperative CBCT scans. Afterwards, datasets were uploaded into therapeutic digital planning software (Dolphin Imaging) to measure the volume of the right and left maxillary sinus and nasal and maxillary sinus complex. Statistically analysis between preoperative and postoperative measures was performed by Student t-test statistical analysis.Results The paired t-test showed statistically significant volumetric reductions in the left maxillary sinus (p = 0.0004), right maxillary sinus (p < 0.0001) and nasal and maxillary sinus complex (p = 0.0009) after bimaxillary advancement surgery performed in patients suffering from OSA.Conclusion The results showed that bimaxillary advancement surgery reduces the maxillary sinus volume as well as, the fossa nasal and sinus complex volume.

Maintenance of appropriate size scaling of the C. elegans pharynx by YAP-1.

Even slight imbalance between the growth rate of different organs can accumulate to a large deviation from their appropriate size during development. Here, we use live imaging of the pharynx of C. elegans to ask if and how organ size scaling nevertheless remains uniform among individuals. Growth trajectories of hundreds of individuals reveal that pharynxes grow by a near constant volume per larval stage that is independent of their initial size, such that undersized pharynxes catch-up in size during development. Tissue-specific depletion of RAGA-1, an activator of mTOR and growth, shows that maintaining correct pharynx-to-body size proportions involves a bi-directional coupling between pharynx size and body growth. In simulations, this coupling cannot be explained by limitation of food uptake alone, and genetic experiments reveal an involvement of the mechanotransducing transcriptional co-regulator yap-1. Our data suggests that mechanotransduction coordinates pharynx growth with other tissues, ensuring body plan uniformity among individuals.

Practical multidisciplinary framework for the assessment and management of patients with unexplained chronic aerodigestive symptoms.

OBJECTIVE: Patients experiencing unexplained chronic throat symptoms (UCTS) are frequently referred to gastroenterology and otolaryngology outpatient departments for investigation. Often despite extensive investigations, an identifiable structural abnormality to account for the symptoms is not found. The objective of this article is to provide a concise appraisal of the evidence-base for current approaches to the assessment and management of UCTS, their clinical outcomes, and related healthcare utilisation. DESIGN: This multidisciplinary review critically examines the current understanding of aetiological theories and pathophysiological drivers in UCTS and summarises the evidence base underpinning various diagnostic and management approaches. RESULTS: The evidence gathered from the review suggests that single-specialty approaches to UCTS inadequately capture the substantial heterogeneity and pervasive overlaps among clinical features and biopsychosocial factors and suggests a more unified approach is needed. CONCLUSION: Drawing on contemporary insights from the gastrointestinal literature for disorders of gut-brain interaction, this article proposes a refreshed interdisciplinary approach characterised by a positive diagnosis framework and patient-centred therapeutic model. The overarching aim of this approach is to improve patient outcomes and foster collaborative research efforts.

Understanding the effects of inhaler resistance on particle deposition behaviour - A computational modelling study.

BACKGROUND AND OBJECTIVE: Understanding the impact of inhaler resistance on particle transport and deposition in the human upper airway is essential for optimizing inhaler designs, thereby contributing to the enhancement of the therapeutic efficacy of inhaled drug delivery. This study demonstrates the potential effects of inhaler resistance on particle deposition characteristics in an anatomically realistic human oropharynx and the United States Pharmacopeia (USP) throat using computational fluid dynamics (CFD). METHOD: Magnetic resonance (MR) imaging was performed on a healthy volunteer biting on a small mockup inhaler mouthpiece. Three-dimensional geometry of the oropharynx and mouthpiece were reconstructed from the MR images. CFD simulations coupled with discrete phase modelling were conducted. Inhaled polydisperse particles under two different transient flow profiles with peak inspiratory flow rates (PIFR) of 30 L/min and 60 L/min were investigated. The effect of inhaler mouthpiece resistance was modelled as a porous medium by varying the initial resistance (Ri) and viscous resistance (Rv). Three resistance values, 0.02 kPa0.5minL-1, 0.035 kPa0.5minL-1 and 0.05 kPa0.5 minL-1, were simulated. The inhaler outlet velocity was set to be consistent across all models for both flow rate conditions to enable a meaningful comparison of models with different inhaler resistances. RESULT: The results from this study demonstrate that investigating the effect of inhaler resistance by solely relying on the USP throat model may yield misleading results. For the geometrically realistic oropharyngeal model, both the pressure and kinetic energy profiles at the mid-sagittal plane of the airway change dramatically when connected to a higher-resistance inhaler. In addition, the geometrically realistic oropharyngeal model appears to have a resistance threshold. When this threshold is surpassed, significant changes in flow dynamics become evident, which is not observed in the USP throat model. Furthermore, this study also reveals that the impact of inhaler resistance in a geometrically realistic throat model extends beyond the oral cavity and affects particle deposition downstream of the oral cavity, including the oropharynx region. CONCLUSION: Results from this study suggest that key mechanisms underpinning the working principles of inhaler resistance are intricately connected to their complex interaction with the pharynx geometry, which affects the local pressure, local variation in velocity and kinetic energy profile in the airway.

[Characteristics performance of laryngopharyngeal reflux in narrow band imaging].

Objective:To study the application value of narrow-band imaging in the diagnosis of laryngopharyngeal reflux. Methods:A total of 275 patients admitted to the inpatient department or laryngoscopy room of the Otolaryngology Head and Neck Surgery Department of the First Affiliated Hospital of Harbin Medical University from September 2022 to April 2023 due to throat discomfort were selected as the research subjects. All of them completed RSI, RFS scoring scales and electronic laryngoscopy（including ordinary white light and NBI）. According to the expert consensus of LPRD in 2022, RSI and RFS scoring scale were used as diagnostic criteria to divide them into LPR group and non-LPR group. Chi-square test was used to analyze the differences of positive rates of characteristic manifestations under NBI among different groups. The consistency of NBI and scale diagnostic methods was analyzed by Kappa, and RSI and RFS scoring were used as diagnostic criteria, The diagnostic efficiency of NBI method was analyzed. Results:There were 190 people in the LPR group, 157 of whom showed characteristic performance under the NBI mode, with a positive rate of 82.6%（157/190）; there were 85 people in the non-LPR group, with a positive rate of 18.8%（16/85）. There was a statistically significant difference in the positive rate between the two groups（χ²=102.47, P<0.05）. The consistency rate between RSI, RFS and NBI was 82.2%（226/275）. Kappa consistency analysis was used, and Kappa=0.605（P<0.05）, indicating good consistency between the two diagnostic methods. Using RSI and RFS as diagnostic criteria for LPR, the sensitivity of NBI diagnostic method was 82.6%（157/190）, specificity 81.2%（69/85）, positive predictive value 90.8%（157/173） and negative predictive value 67.6%（69/102）. Conclusion:Narrow-band imaging, as a new endoscopic imaging technique, can show small changes in mucosal surface micro vessels and play an important role in the diagnosis of laryngopharyngeal reflux.

[Efficacy of Barbed reposition pharyngoplasty combined with Han-Uvulopalatopharyngoplasty for the treatment of OSAHS patients].

Objective: To study the efficacy of Barbed reposition pharyngoplasty (BRP) combined with Han-Uvulopalatopharyngoplasty (H-UPPP) in surgical treatment of OSAHS patients. Methods: OSAHS patients admitted to our department from June 2021 to February 2022 who met the surgical enrollment criteria were divided into two groups by surgical procedure: H-UPPP operation group [Control group, 47 cases, including 42 males and 5 females, aged 18-64 (37.77±11.65)years, and H-UPPP+BRP group [Study group, 48 cases, including 45 males and 3 females, aged 23-60 (39.10±9.86) years]. The surgical efficacy 6 months after operation was retrospectively analyzed. Meanwhile, the relationship between the surgical efficacy and modified Friedman pharyngeal anatomical stages was analyzed. The postoperative pain VAS score at first 3 days and the incidence of foreign body sensation in pharynx after 6 months of operation were compared between the two groups. Statistical analysis was conducted by SPSS 23.0. Results: There were no significant differences in gender, age, BMI, Friedman pharyngeal anatomical stages, ESS score, AHI and LSpO2 between the two groups, preoperatively (P>0.05). There was significant difference between the two groups in ratio of cumulative time of oxygen saturation below 90% to total sleep time(CT90), preoperatively. Surgical efficacy of H-UPPP operation group was 48.9% (23/47), while H-UPPP+BRP operation group was 70.8% (34/48), which was statistically significant (χ2=4.74, P=0.029). H-UPPP+BRP group seemed to have a higher surgical efficacy than H-UPPP group in patients with Friedman Ⅱb (87% vs. 61.9%) and Ⅲ stage (44.4% vs. 15%), but there was no statistically significant difference (P>0.05). H-UPPP+BRP group had a higher pain VAS score in first three days (t=-3.10, P=0.003), also had higher incidence of pharyngeal foreign body sensation after 6 months of operation (χ2=4.727, P=0.030). Conclusions: In the surgical treatment of OSAHS patients, the overall efficacy of BRP combined H-UPPP surgery is higher than that of H-UPPP surgery alone. It may be more suitable for OSAHS patients with modified Friedman type Ⅱb and type Ⅲ stage.

Influence of tumor topography on clinical-morphological profile of laryngeal malignancies.

AIM: Laryngeal cancers are redoubtable because they are still diagnosed in advanced stages which results in poor survival and the decline of life quality. The authors intend to identify if the tumor topography influences clinical behavior, the morphological profile and therapeutic strategy. PATIENTS, MATERIALS AND METHODS: The study group included 188 patients with laryngeal malignancies diagnosed and treated in an Ear, Nose and Throat (ENT) Department. The patients have been divided into four groups according to the tumor topography and extension. Three categories of parameters were defined (epidemiological, clinical, and morphological) and analyzed comparatively between the four groups using filter scales and the χ² (chi-squared) correlation test. RESULTS: Epidemiological parameters (sex, age, socio-economic status) showed no significant differences between the four groups. Clinical parameters (symptoms, lymphadenopathies, surgical procedures, and hospitalization) instead registered significant differences between the four groups. Morphological parameters (longitudinal diameter, transverse diameter, shape, gross aspect, histopathological aspect, grade, local invasion - pT, lymph node invasion - pN, metastases - pM and tumor stage), excepting shape, registered too significant differences between the four groups. The analysis of the whole set of parameters in each group revealed different, distinct profiles for each of the topographic groups, especially for glottic and large tumors. Our results concerning the entire series of tumors ranged in the limits of variation of each of the parameters observed in the literature. CONCLUSIONS: Our study revealed that tumors placed in different regions of the larynx have distinct profiles from epidemiological, clinical, and morphological points of view. However, the profile of our entire group of tumors proved to be comparable with the literature data.

Namibian spitting cobra, Naja nigricincta nigricincta (Zebra snake): Antibiotic profile of bacteria cultured from the oral pharynx, venom and snakebite wounds.

This was a cross-sectional study with the aim of characterising Naja nigricincta nigricincta's oral bacterial flora as well as accompanying sensitivities and resistance towards antibiotics. Naja nigricincta nigricincta (zebra snake) is a spitting cobra indigenous to Namibia. Nasopharyngeal and venom swabs for bacterial culture and antibiotic sensitivity were taken from 37 native zebra snakes originating from the Khomas region that were captured for removal and relocation. Enterococcus faecalis, Proteus spp., Morganella morganii and Pseudomonas spp. were the organisms most often cultured. The antibiotic sensitivity profiles of these organisms suggest ciprofloxacin or a third-generation cephalosporin plus gentamicin or piperacillin-tazobactam as prophylactic antibiotics in case of Naja nigricincta nigricincta bites.

Evaluation of pharyngeal airway volume three-dimensionally in various sagittal skeletal patterns - Systematic review.

To investigate the pharyngeal airway volume in different anteroposterior skeletal malocclusions. This study was prepared according to the Cochrane criteria for creating a systematic review and meta-analysis and confirms the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. This search was conducted to answer the patient/population, intervention, comparison and outcomes (PICO) question: To evaluate (outcome) and compare (comparison) whether there is a difference in airway volume in patients (participants) with different skeletal malocclusions diagnosed using 3D data (intervention).The first two authors extracted the data from the included studies and assessed the risk of bias in the individual studies using the Newcastle-Ottawa scale. Meta-analysis was done using STATA version 16, which compared various three-dimensional pharyngeal airway parameters in skeletal Class II and skeletal Class III malocclusions with that of skeletal class I malocclusion. Out of 370 articles from the initial search, 17 articles were included in the systematic review. Out of 17 studies, 12 eligible studies were included in the quantitative synthesis. The nasopharynx, oropharynx, hypopharynx, and total airway volume were increased in skeletal Class I malocclusion compared to that of skeletal Class II malocclusion and decreased in comparison to skeletal Class III malocclusion. The moderate quality of evidence indicates the total airway volume, oropharynx, and hypopharynx are largest in skeletal Class III compared to Class I and Class II skeletal malocclusion.

A Flexible Regression Modeling Approach Applied to Observational Laboratory Virological Data Suggests That SARS-CoV-2 Load in Upper Respiratory Tract Samples Changes with COVID-19 Epidemiology.

(1) Background. Exploring the evolution of SARS-CoV-2 load and clearance from the upper respiratory tract samples is important to improving COVID-19 control. Data were collected retrospectively from a laboratory dataset on SARS-CoV-2 load quantified in leftover nasal pharyngeal swabs (NPSs) collected from symptomatic/asymptomatic individuals who tested positive to SARS-CoV-2 RNA detection in the framework of testing activities for diagnostic/screening purpose during the 2020 and 2021 winter epidemic waves. (2) Methods. A Statistical approach (quantile regression and survival models for interval-censored data), novel for this kind of data, was applied. We included in the analysis SARS-CoV-2-positive adults >18 years old for whom at least two serial NPSs were collected. A total of 262 SARS-CoV-2-positive individuals and 784 NPSs were included: 193 (593 NPSs) during the 2020 winter wave (before COVID-19 vaccine introduction) and 69 (191 NPSs) during the 2021 winter wave (all COVID-19 vaccinated). We estimated the trend of the median value, as well as the 25th and 75th centiles of the viral load, from the index episode (i.e., first SARS-CoV-2-positive test) until the sixth week (2020 wave) and the third week (2021 wave). Interval censoring methods were used to evaluate the time to SARS-CoV-2 clearance (defined as Ct < 35). (3) Results. At the index episode, the median value of viral load in the 2021 winter wave was 6.25 log copies/mL (95% CI: 5.50-6.70), and the median value in the 2020 winter wave was 5.42 log copies/mL (95% CI: 4.95-5.90). In contrast, 14 days after the index episode, the median value of viral load was 3.40 log copies/mL (95% CI: 3.26-3.54) for individuals during the 2020 winter wave and 2.93 Log copies/mL (95% CI: 2.80-3.19) for those of the 2021 winter wave. A significant difference in viral load shapes was observed among age classes (p = 0.0302) and between symptomatic and asymptomatic participants (p = 0.0187) for the first wave only; the median viral load value is higher at the day of episode index for the youngest (18-39 years) as compared to the older (40-64 years and >64 years) individuals. In the 2021 epidemic, the estimated proportion of individuals who can be considered infectious (Ct < 35) was approximately half that of the 2020 wave. (4) Conclusions. In case of the emergence of new SARS-CoV-2 variants, the application of these statistical methods to the analysis of virological laboratory data may provide evidence with which to inform and promptly support public health decision-makers in the modification of COVID-19 control measures.