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Despite signs of infection-including taste loss, dry mouth and mucosal lesions such as ulcerations, enanthema and macules-the involvement of the oral cavity in coronavirus disease 2019 (COVID-19) is poorly understood. To address this, we generated and analyzed two single-cell RNA sequencing datasets of the human minor salivary glands and gingiva (9 samples, 13,824 cells), identifying 50 cell clusters. Using integrated cell normalization and annotation, we classified 34 unique cell subpopulations between glands and gingiva. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral entry factors such as ACE2 and TMPRSS members were broadly enriched in epithelial cells of the glands and oral mucosae. Using orthogonal RNA and protein expression assessments, we confirmed SARS-CoV-2 infection in the glands and mucosae. Saliva from SARS-CoV-2-infected individuals harbored epithelial cells exhibiting ACE2 and TMPRSS expression and sustained SARS-CoV-2 infection. Acellular and cellular salivary fractions from asymptomatic individuals were found to transmit SARS-CoV-2 ex vivo. Matched nasopharyngeal and saliva samples displayed distinct viral shedding dynamics, and salivary viral burden correlated with COVID-19 symptoms, including taste loss. Upon recovery, this asymptomatic cohort exhibited sustained salivary IgG antibodies against SARS-CoV-2. Collectively, these data show that the oral cavity is an important site for SARS-CoV-2 infection and implicate saliva as a potential route of SARS-CoV-2 transmission.

Introduction: Cystic fibrosis (CF) is commonly complicated by chronic rhinosinusitis (CRS). Despite highly effective management options, CRS in people with CF (PwCF+CRS) may be refractory to medical therapy, eventually requiring endoscopic sinus surgery. The impact of sinus surgery on pulmonary, quality of life (QOL), and other outcomes in PwCF+CRS in the expanding era of highly effective modulator therapy has not been fully elucidated. This study aims to determine if endoscopic sinus surgery can offer superior outcomes for PwCF+CRS when compared to continued medical treatment of CRS. Methods and analysis: This multi-institutional, observational, prospective cohort study will enroll 150 adults with PwCF+CRS across nine US CF Centers who failed initial medical therapy for CRS and elected to pursue either endoscopic sinus surgery or continue medical treatment. To determine if sinus surgery outperforms continued medical therapy in different outcomes, we will assess changes in pulmonary, CF-specific QOL, CRS-specific QOL, sleep quality, depression, headache, cognition, olfaction, productivity loss, and health utility value after treatment. The influence of highly effective modulator therapy on these outcomes will also be evaluated. This study will provide crucial insights into the impact of endoscopic sinus surgery for PwCF+CRS and aid with development of future treatment pathways and guidelines. Ethics and dissemination: This study has been approved by each institution's internal review board, and study enrollment began August 2019. Results will be disseminated in conferences and peer-reviewed journals. Trial registration: This study was registered on ClinicalTrials.gov (NCT04469439). [ABSTRACT FROM AUTHOR]

The vast majority of people with cystic fibrosis (CF) are now eligible for CF transmembrane regulator (CFTR) modulator therapy. The remaining individuals with CF harbor premature termination codons (PTCs) or rare CFTR variants with limited treatment options. Although the clinical modulator response can be reliably predicted using primary airway epithelial cells, primary cells carrying rare CFTR variants are scarce. To overcome this obstacle, cell lines can be created by overexpression of mouse Bmi-1 and human TERT (hTERT). Using this approach, we developed 2 non-CF and 6 CF airway epithelial cell lines, 3 of which were homozygous for the W1282X PTC variant. The Bmi-1/hTERT cell lines recapitulated primary cell morphology and ion transport function. The 2 F508del-CFTR cell lines responded robustly to CFTR modulators, which was mirrored in the parent primary cells and in the cell donors' clinical response. Cereblon E3 ligase modulators targeting eukaryotic release factor 3a (eRF3a) rescued W1282X-CFTR function to approximately 20% of WT levels and, when paired with G418, rescued G542XCFTR function to approximately 50% of WT levels. Intriguingly, eRF3a degraders also diminished epithelial sodium channel (ENaC) function. These studies demonstrate that Bmi-1/hTERT cell lines faithfully mirrored primary cell responses to CFTR modulators and illustrate a therapeutic approach to rescue CFTR nonsense mutations., Introduction Cystic fibrosis (CF) is a life-limiting genetic disease affecting approximately 70,000 people worldwide (1). Severe pathology develops in the lungs, where absent or dysfunctional CF transmembrane regulator (CFTR) protein [...]

Infratemporal fossa (ITF) tumors are rare in children and may present with a variety of symptoms. Teratomas are neoplasms derived from the 3 germ layers and approximately 6% to 10% are within the head and neck. Our study discusses one of the first reported cases of teratoma in the ITF in a pediatric patient. A 3-year-old girl presents with 2 years of recurrent monthly left periorbital swelling accompanied by fevers, skin discoloration, and pain. Prior episodes were treated with antibiotics with incomplete resolution. Imaging revealed a cystic lesion centered in the ITF. She was taken for endoscopic endonasal biopsy of the lesion and had no complications. Pathology revealed a mature teratoma composed primarily of pancreatic tissue. Providers should consider masses such as teratoma in the differential for ITF tumors and periorbital edema unresponsive to typical treatment. [ABSTRACT FROM AUTHOR]

Objectives The frequency of endoscopic skull base surgery in pediatric patients is increasing. This study aims to systematically review the literature for endoscopic skull base surgery outcomes in children/adolescents aged 0 to 18 years. Design A systematic review of the literature was performed in PubMed and SCOPUS databases querying studies from 2000 to 2020 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Final inclusion criteria included: case series with more than 10 patients with pediatric patients aged ≤18 years, endoscopic or endoscopic-assisted skull base surgery, and outcomes reported. Setting This study was conducted at a tertiary care medical center. Participants Children/adolescents aged 0 to 18 years who underwent endoscopic skull base surgery were participated in this study. Main Outcome Measures Patient demographics, pathology, reconstructive technique, intraoperative findings, intraoperative, and postoperative surgical complications were measured through this study. Results Systematic literature search yielded 287 publications. Of these, 12 studies discussing a total of 399 patients aged 0 to 18 years met inclusion criteria for final analysis. Seven of the 12 studies discussed a single pathology. The most common pathology was a skull base defect causing cerebrospinal fluid (CSF) leak. The majority of skull base repairs were made with free tissue grafts. The most common postoperative complication was CSF leak (n = 40). Twelve cases of meningitis occurred postoperatively with two of these episodes resulting in death. Conclusion Endoscopic skull base surgery has been performed recently in the pediatric population in a variety of disease states. Inconsistent individual-level data and reporting standards are present in existing studies posing challenges for comparative analysis. Standardized reporting will aid future reviews and meta-analysis for rare skull base pathology. [ABSTRACT FROM AUTHOR]

Objectives  Pain management remains a point of emphasis given the ongoing opioid crisis. There are no studies in the literature interrogating opioid prescribing and use following endoscopic pituitary surgery. This study investigates provider prescribing tendency, patient utilization of analgesics, and patient outcomes regarding pain management after endoscopic pituitary surgery. Methods  We identified 100 patients undergoing endoscopic pituitary surgery at one institution from 2016 to 2018 in the electronic medical record (EMR) and state narcotic database to determine postoperative analgesic regimens. A telephone survey was used to characterize postoperative analgesic use and satisfaction with prescribed regimen. Results  Fifty-two different pain control regimens were prescribed to the study patients. Also, 93% of study patients were prescribed an opioid postoperatively. The average quantity of opioids prescribed per patient in morphine milligram equivalents (MMEs) was 625 (equivalent 83 oxycodone 5-mg tablets) with an average MME/day of 59 (equivalent 8 oxycodone 5-mg tablets). A total of 71% survey respondents who used opioids reported using <25% of their prescription. The majority of prescription narcotic users consumed >50% of their postoperative opioid intake in the first 24 to 48 hours after discharge. There were no significant differences in pain outcome between opioid users and nonopioid users. Conclusion  Vast heterogeneity exists in narcotic prescribing by providers at our institution following endoscopic pituitary surgery. Narcotic prescribing patterns exceeded most patients' analgesic needs. Opioid analgesics were not superior to nonopioids regimens in patient-reported pain outcomes in this study population. [ABSTRACT FROM AUTHOR]

Regulator of G protein signaling (RGS) proteins accelerate GTP hydrolysis by G[alpha] subunits and thus facilitate termination of signaling initiated by G protein-coupled receptors (GPCRs). RGS proteins hold great promise as disease intervention points, given their signature role as negative regulators of GPCRs--receptors to which the largest fraction of approved medications are currently directed. RGS proteins share a hallmark RGS domain that interacts most avidly with G[alpha] when in its transition state for GTP hydrolysis; by binding and stabilizing switch regions I and II of G[alpha], RGS domain binding consequently accelerates G[alpha]-mediated GTP hydrolysis. The human genome encodes more than three dozen RGS domain-containing proteins with varied G[alpha] substrate specificities. To facilitate their exploitation as drug-discovery targets, we have taken a systematic structural biology approach toward cataloging the structural diversity present among RGS domains and identifying molecular determinants of their differential G[alpha] selectivities. Here, we determined 14 structures derived from NMR and x-ray crystallography of members of the R4, R7, R12, and RZ subfamilies of RGS proteins, including 10 uncomplexed RGS domains and 4 RGS domain/G[alpha] complexes. Heterogeneity observed in the structural architecture of the RGS domain, as well as in engagement of switch Ill and the all-helical domain of the G[alpha] substrate, suggests that unique structural determinants specific to particular RGS protein/G[alpha] pairings exist and could be used to achieve selective inhibition by small molecules. GTPase-accelerating proteins | NMR structure | RGS proteins | x-ray crystallography

Objective  Presently, there are no standards for reporting outcomes of endoscopic endonasal skull base reconstruction (ESBR). This is problematic as a lack of consistent reporting makes synthesizing findings in systematic reviews and meta-analysis challenging. Thus, the aim of this study was to systematically review and describe the patterns of reporting outcomes in ESBR as a foundation for developing reporting guidelines. Study Design  Present study is a systematic review. Methods  Embase, PubMed, CINAHL, Cochrane Library, and Web of Science were searched for all publications with ≥25 patients and a focus on ESBR. The reporting patterns of each study's variables and outcomes were assessed. Results  A total of 112 studies were included in the review. The most commonly reported demographic variables were the number of included patients (n  = 112, 100%) and types of pathologies treated (n  = 104, 92.9%). Meanwhile, the most routinely described preoperative variable was history of prior treatment (n  = 48, 42.9%). Type of reconstruction was a commonly reported intraoperative variable (n  = 110, 98.2%), though the rate of intraoperative cerebrospinal fluid (CSF) leak was noted in only 76 studies (67.9%). With regard to postoperative outcomes, postoperative CSF leak rate was routinely provided (n  = 101, 90.2%), but reporting of other surgical complications was more inconsistent. Ultimately, of the 43 variables and outcomes reviewed, a median of 12 (range: 4–22) was reported in each study. Conclusion  There is significant heterogeneity in the outcomes reported in studies relating to ESBR. This highlights the need for the development of standard reporting guidelines to minimize bias and improve interstudy comparability. [ABSTRACT FROM AUTHOR]

The T1R and T2R families of G protein-coupled receptors (GPCRs) initiate tastant perception by signaling via guanine nucleotide exchange and hydrolysis performed by associated heterotrimeric G proteins (Gαβγ). Heterotrimeric G protein signal termination is sped up by Gα-directed GTPase-accelerating proteins (GAPs) known as the Regulators of G protein Signaling (RGS proteins). Of this family, RGS21 is highly expressed in lingual epithelial cells and we have shown it acting in vitro to decrease the potency of bitterants on cultured cells. However, constitutive RGS21 loss in mice reduces organismal response to GPCR-mediated tastants—opposite to expectations arising from observed in vitro activity of RGS21 as a GAP and inhibitor of T2R signaling. Here, we show reduced quinine aversion and reduced sucrose preference by mice lacking RGS21 does not result from post-ingestive effects, as taste-salient brief-access tests confirm the reduced bitterant aversion and reduced sweetener preference seen using two-bottle choice testing. Eliminating Rgs21 expression after chemosensory system development, via tamoxifen-induced Cre recombination in eight week-old mice, led to a reduction in quinine aversive behavior that advanced over time, suggesting that RGS21 functions as a negative regulator to sustain stable bitter tastant reception. Consistent with this notion, we observed downregulation of multiple T2R proteins in the lingual tissue of Rgs21 -deficient mice. Reduced tastant-mediated responses exhibited by mice lacking Rgs21 expression either since birth or in adulthood has highlighted the potential requirement for a GPCR GAP to maintain the full character of tastant signaling, likely at the level of mitigating receptor downregulation. [ABSTRACT FROM AUTHOR]