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The authors report results of an analysis of nasal and throat swabs from 17 patients in Zhuhai, China, who had received a diagnosis of Covid-19. Higher viral loads soon after symptom onset indicate the need for isolation strategies different from those used for the earlier SARS epidemic.

Antibiotic administration is the standard treatment for the bacterium Helicobacter pylori, the main causative agent of peptic ulcer disease and gastric cancer. However, the long-term consequences of this treatment on the human indigenous microbiota are relatively unexplored. Here we studied short- and long-term effects of clarithromycin and metronidazole treatment, a commonly used therapy regimen against H. pylori, on the indigenous microbiota in the throat and in the lower intestine. The bacterial compositions in samples collected over a four-year period were monitored by analyzing the 16S rRNA gene using 454-based pyrosequencing and terminal-restriction fragment length polymorphism (T-RFLP). While the microbial communities of untreated control subjects were relatively stable over time, dramatic shifts were observed one week after antibiotic treatment with reduced bacterial diversity in all treated subjects in both locations. While the microbiota of the different subjects responded uniquely to the antibiotic treatment some general trends could be observed; such as a dramatic decline in Actinobacteria in both throat and feces immediately after treatment. Although the diversity of the microbiota subsequently recovered to resemble the pre treatment states, the microbiota remained perturbed in some cases for up to four years post treatment. In addition, four years after treatment high levels of the macrolide resistance gene erm(B) were found, indicating that antibiotic resistance, once selected for, can persist for longer periods of time than previously recognized. This highlights the importance of a restrictive antibiotic usage in order to prevent subsequent treatment failure and potential spread of antibiotic resistance.

This study investigated the association between tongue and hyoid position, tongue volume, and pharyngeal airway dimensions with craniofacial growth patterns in the sagittal, vertical, and transverse planes. Cone beam computed tomography was used to assess 185 non-growing subjects (mean age, 28.7 ± 9.5 years). Multivariate linear regression analyses evaluated relationships between tongue and airway variables, and cephalometric/dental arch measurements. Class III skeletal patterns-reflected by lower ANB and higher APDI-were significantly correlated with anteriorly positioned hyoids (ANB: β = 0.249; APDI: β = -0.291), and lower tongue positions at the tongue tip (ANB: β = -0.231; APDI: β = 0.166) and in the posterior area (ANB: β = -0.186; APDI: β = 0.196), and greater tongue volume (APDI: β = 0.174). Hyperdivergent vertical patterns-indicated by a lower ODI-were significantly correlated with a lower tongue tip position (β = -0.311) and posterior tongue position (β = -0.230). Regarding transverse dimensions, tongue volume showed positive correlations with upper intermolar width (β = 0.349), lower intercanine width (β = 0.130), lower intermolar width (β = 0.311), and a negative correlation with upper intercanine width (β = -0.299). Sagittal and vertical craniofacial patterns are interrelated and show associations with tongue and hyoid position, as well as tongue volume. Transverse dental arch dimensions are correlated not only with tongue position and volume but also with pharyngeal airway volume.

The comparative performance of different clinical sampling methods for diagnosis of SARS-CoV-2 infection by RT-PCR among populations with suspected infection remains unclear. This meta-analysis aims to systematically compare the diagnostic performance of different clinical specimen collection methods. In this systematic review and meta-analysis, we systematically searched PubMed, Embase, MEDLINE, Web of Science, medRxiv, bioRxiv, SSRN, and Research Square from Jan 1, 2000, to Nov 16, 2020. We included original clinical studies that examined the performance of nasopharyngeal swabs and any additional respiratory specimens for the diagnosis of SARS-CoV-2 infection among individuals presenting in ambulatory care. Studies without data on paired samples, or those that only examined different samples from confirmed SARS-CoV-2 cases were not useful for examining diagnostic performance of a test and were excluded. Diagnostic performance, including sensitivity, specificity, positive predictive value, and negative predictive value, was examined using random effects models and double arcsine transformation. Of the 5577 studies identified in our search, 23 studies including 7973 participants with 16 762 respiratory samples were included. Respiratory specimens examined in these studies included 7973 nasopharyngeal swabs, 1622 nasal swabs, 6110 saliva samples, 338 throat swabs, and 719 pooled nasal and throat swabs. Using nasopharyngeal swabs as the gold standard, pooled nasal and throat swabs gave the highest sensitivity of 97% (95% CI 93–100), whereas lower sensitivities were achieved by saliva (85%, 75–93) and nasal swabs (86%, 77–93) and a much lower sensitivity by throat swabs (68%, 35–94). A comparably high positive predictive value was obtained by pooled nasal and throat (97%, 90–100) and nasal swabs (96%, 87–100) and a slightly lower positive predictive value by saliva (93%, 88–97). Throat swabs have the lowest positive predictive value of 75% (95% CI 45–96). Comparably high specificities (range 97–99%) and negative predictive value (range 95–99%) were observed among different clinical specimens. Comparison between health-care-worker collection and self-collection for pooled nasal and throat swabs and nasal swabs showed comparable diagnostic performance. No significant heterogeneity was observed in the analysis of pooled nasal and throat swabs and throat swabs, whereas moderate to substantial heterogeneity (I2 ≥30%) was observed in studies on saliva and nasal swabs. Our review suggests that, compared with the gold standard of nasopharyngeal swabs, pooled nasal and throat swabs offered the best diagnostic performance of the alternative sampling approaches for diagnosis of SARS-CoV-2 infection in ambulatory care. Saliva and nasal swabs gave comparable and very good diagnostic performance and are clinically acceptable alternative specimen collection methods. Throat swabs gave a much lower sensitivity and positive predictive value and should not be recommended. Self-collection for pooled nasal and throat swabs and nasal swabs was not associated with any significant impairment of diagnostic accuracy. Our results also provide a useful reference framework for the proper interpretation of SARS-CoV-2 testing results using different clinical specimens. Hong Kong Research Grants Council.

This study evaluated the validity of pharyngeal 2D area measurements acquired from the lateral view for predicting the actual 3D volume in healthy adults during swallowing. Seventy-five healthy adults (39 females, 36 males; mean age 51.3 years) were examined using 320-row area detector computed tomography (320-ADCT). All participants swallowed a 10 mL honey-thick barium bolus upon command while seated in a 45° semi-reclining position. Multi-planar reconstruction images and dynamic 3D-CT images were obtained using Aquilion ONE software. Pharyngeal 2D area and 3D volume measurements were taken before swallowing and at the frame depicting maximum pharyngeal constriction. Pharyngeal volume before swallowing (PVhold) was accurately predicted by 2D area (R2 = 0.816). Adding height and sex to the model increased R2 to 0.836. Regarding pharyngeal volume during maximum constriction (PVmax), 2D area also exhibited acceptable predictive power (R2 = 0.777). However, analysis of statistical residuals and outliers revealed a greater tendency for prediction errors when there is less complete constriction of the pharynx as well as asymmetry in bolus flow or movement. Findings highlight the importance of routinely incorporating anterior–posterior views during VFSS exams. Future work is needed to determine clinical utility of pharyngeal volume measurements derived from 320-ADCT.

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstruction during sleep. OSA leads to high cardiovascular morbidity and mortality. The pathogenesis of OSA has been linked to a defect in neuromuscular control of the pharynx. There is no effective pharmacotherapy for OSA. The objective of this study was to determine whether upper airway patency can be improved using chemogenetic approach by deploying designer receptors exclusively activated by designer drug (DREADD) in the hypoglossal motorneurons. DREADD (rAAV5-hSyn-hM3(Gq)-mCherry) and control virus (rAAV5-hSyn-EGFP) were stereotactically administered to the hypoglossal nucleus of C57BL/6J mice. In 6–8 weeks genioglossus EMG and dynamic MRI of the upper airway were performed before and after administration of the DREADD ligand clozapine-N-oxide (CNO) or vehicle (saline). In DREADD-treated mice, CNO activated the genioglossus muscle and markedly dilated the pharynx, whereas saline had no effect. Control virus treated mice showed no effect of CNO. Our results suggest that chemogenetic approach can be considered as a treatment option for OSA and other motorneuron disorders.

Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 2019 1 , 2 . Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses 3 . This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung 2 , 4 ; the same receptor tropism is thought to have determined the pathogenicity—but also aided in the control—of severe acute respiratory syndrome (SARS) in 2003 5 . However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission 6 – 8 . There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 10 8  RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples—in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19. Detailed virological analysis of nine cases of coronavirus disease 2019 (COVID-19) provides proof of active replication of the SARS-CoV-2 virus in tissues of the upper respiratory tract.

Maldevelopment of the pharyngeal endoderm, an embryonic tissue critical for patterning of the pharyngeal region and ensuing organogenesis, ultimately contributes to several classes of human developmental syndromes and disorders. Such syndromes are characterized by a spectrum of phenotypes that currently cannot be fully explained by known mutations or genetic variants due to gaps in characterization of critical drivers of normal and dysfunctional development. Despite the disease-relevance of pharyngeal endoderm, we still lack a comprehensive and integrative view of the molecular basis and gene regulatory networks driving pharyngeal endoderm development. To close this gap, we apply transcriptomic and chromatin accessibility single-cell sequencing technologies to generate a multi-omic developmental resource spanning pharyngeal endoderm patterning to the emergence of organ-specific epithelia in the developing mouse embryo. We identify cell-type specific gene regulation, distill GRN models that define developing organ domains, and characterize the role of an immunodeficiency-associated forkhead box transcription factor. The molecular basis and gene regulatory networks driving pharyngeal endoderm development remain poorly understood. Here the authors report single cell transcriptomic and chromatin landscapes to delineate regulatory programs driving this process and to define the immunodeficiency-associated developmental defects resulting from Foxn1 dysfunction.

This study investigated the swallowing dynamics of jelly, thickened liquid, and thin liquid in selected stroke patients who exhibited near-normal swallowing function with screening tests. Videofluoroscopic examination compared the pharyngeal transit time (PTT), pharyngeal delay time (PDT), and laryngeal elevation delay time (LEDT). Of 175 patients (104 men, 71 women; mean age: 68.6 ± 12.0 years) evaluated, 24 (13.7%) experienced aspiration, significantly prolonging LEDT in swallowing thin liquid. PTT did not differ in swallowing jelly, thickened liquid, or thin liquid among the patients who did not aspirate. However, in two-phase analysis of PTT, performed before and after the jelly passed the epiglottis, the former was significantly prolonged, whereas the latter was significantly shortened. PDT was significantly longer with jelly than with thickened and thin liquids. LEDT was significantly longer in swallowing thin liquids. Apparently, the thin liquid reached the pyriform sinus before maximum laryngeal elevation, posing a risk of laryngeal penetration and aspiration during swallowing. A thicker liquid prolonged the time taken to reach the pyriform sinus, reducing aspiration risk. Moreover, oropharyngeal passage of jelly took longer, triggering the swallowing reflex around the vallecula and allowing the jelly to pass through the hypopharynx after laryngeal closure.