Alice Zhao Maxfield

MethodsEthmoid sinus EpCs from 19 adults with CRS were sorted into subsets (basal, transitional, differentiated), bulk RNA-sequenced, and analyzed for differentially expressed genes and pathways. Single cell RNA-seq (scRNA-seq) datasets of CRSwNP [GSE202100, HRA000772] and a bulk RNA-seq dataset from mild-to-moderate and severe asthmatic epithelium [GSE158752] were also assessed. Immunofluorescent staining and ex vivo analysis of sinus EpCs were used to validate findings.ResultsExpression of the Hallmark glycolysis gene set was enriched in CRSwNP throughout all EpC subsets (padj< 0.05). Spearman correlation analysis identified mammalian target of rapamycin complex 1 (mTORC1) as a potential regulator of enhanced glycolysis (p< 0.05) and identified expression of wound healing genes and EpC cytokines as potential sequelae. Phospho-6SRP staining demonstrated that mTORC1 …

BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) causes nasal obstruction and olfactory dysfunction. Aspirin-exacerbated respiratory disease (AERD) is the triad of CRSwNP, asthma, and respiratory reactions to COX-1 inhibitors. Patients with AERD have elevated nasal IL-5 levels and high numbers of antibody-secreting cells (ASCs), including plasma cells and plasmablasts, in their polyp tissue; in addition, their nasal polyp (NP) IgE levels are correlated with disease severity and recurrence of nasal polyposis.ObjectiveWe sought to explore differences in the transcriptomic profile, activation markers, and IL-5Rα expression and function of NP ASCs from patients with AERD and CRSwNP.MethodsNP tissue was collected from patients with AERD and CRSwNP and digested into single-cell suspensions. NP cells were analyzed for protein expression by mass cytometry. For IL-5Rα functional studies …

Brain organoids are three‐dimensional aggregates of self‐organized differentiated stem cells that mimic the structure and function of human brain regions. Organoids bridge the gaps between conventional drug screening models such as planar mammalian cell culture, animal studies, and clinical trials. They can revolutionize the fields of developmental biology, neuroscience, toxicology, and computer engineering. Conventional microinstrumentation for conventional cellular engineering, such as planar microfluidic chips; microelectrode arrays (MEAs); and optical, magnetic, and acoustic techniques, has limitations when applied to three‐dimensional (3D) organoids, primarily due to their limits with inherently two‐dimensional geometry and interfacing. Hence, there is an urgent need to develop new instrumentation compatible with live cell culture techniques and with scalable 3D formats relevant to organoids. This …

IL-5, CCL2, and CXCL8 in sinus mucous are higher in patients with AERD relative to aspirin-tolerant patients with CRS These mediators are pleiotropic, leading to widescale inflammatory processes contributing to AERD AERD is not only a T2 disease but heterogeneous: this may explain the refractory nature of AERD.

Key points Mast cell numbers were reduced in samples cryopreserved as whole tissue chunks. Thawed epithelial cells had reduced proliferation rates when preserved as dissociated cell suspensions. The right cryopreservation method to choose may depend on the goals and cell‐type focus of the project.

Elevated IL-5, IL-13, IL-33, and CCL2 correlate with lower UPSIT scores in CRS and AERD patients. Elevated IL-5, IL-13, TNF-α, CCL2, and CXCL-8 correlate with higher SNOT-22 scores in CRS and AERD patients.

The olfactory neuroepithelium serves as a sensory organ for odors and forms part of the nasal mucosal barrier. Olfactory sensory neurons are surrounded and supported by epithelial cells. Among them, microvillous cells (MVCs) are strategically positioned at the apical surface, but their specific functions are enigmatic, and their relationship to the other specialized epithelial cells is unclear. Here, we establish that the family of MVCs comprises tuft cells and ionocytes in both mice and humans. Integrating analysis of the respiratory and olfactory epithelia, we define the distinct receptor expression of TRPM5+ tuft-MVCs compared with Gɑ-gustducinhigh respiratory tuft cells and characterize a previously undescribed population of glandular DCLK1+ tuft cells. To establish how allergen sensing by tuft-MVCs might direct olfactory mucosal responses, we used an integrated single-cell transcriptional and protein analysis …

BackgroundThe airway epithelium plays a central role in the pathogenesis of chronic respiratory diseases such as asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), but the mechanisms by which airway epithelial cells (EpCs) maintain inflammation are poorly understood.ObjectiveWe hypothesized that transcriptomic assessment of sorted airway EpCs across the spectrum of differentiation would allow us to define mechanisms by which EpCs perpetuate airway inflammation.MethodsEthmoid sinus EpCs from adult patients with CRS were sorted into 3 subsets, bulk RNA sequenced, and analyzed for differentially expressed genes and pathways. Single cell RNA-seq (scRNA-seq) datasets from eosinophilic and non-eosinophilic CRSwNP and bulk RNA-seq of EpCs from mild/moderate and severe asthma were assessed. Immunofluorescent staining and ex vivo functional analysis of sinus EpCs were used …

Introduction. Direct-acting antiviral medications have made hepatitis C virus (HCV) cure possible for >95% of persons with chronic HCV infection, including those coinfected with HIV. Achieving strategic HCV elimination targets requires an understanding of system, provider, and patient-level barriers to treatment. We explored such barriers among persons with HIV/HCV coinfection who remained untreated for HCV. Methods. Among four primary care HIV clinics in CT with high rates of HCV cure, 25 patients with HIV/HCV coinfection were eligible (no HCV treatment as of March 31, 2021). We conducted retrospective chart reviews of demographics, clinical practice patterns, patient-specific issues such as housing, transportation, food security, and presence of mental health and substance use problems. Results. Among untreated patients, 13 (51%) were female; 17 (68%) were Black; median age was 62 years old. The …

Not just snot: local inflammatory profiles in aerd patients differ from non-aerd chronic rhinosinusitis. - Abstract - Europe PMC Sign in | Create an account https://orcid.org Europe PMC Menu About Tools Developers Help Contact us Helpdesk Feedback Twitter Blog Tech blog Developer Forum Europe PMC plus Search life-sciences literature (42,520,059 articles, preprints and more) Search Advanced search Feedback This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy. Abstract Full text Not just snot: local inflammatory profiles in aerd patients differ from non-aerd chronic rhinosinusitis. Chiang S 1 , Yu SE 1 , Athni TS 1 , Bergmark RW 1 , Maxfield AZ 1 , Roditi RE 1 , Buchheit KM 2 , Lundberg M 3 , Mitchell MB 1 , Lee SE 1 Author information Affiliations 1. Division of Otolaryngology - …

BackgroundChronic rhinosinusitis with nasal polyposis (CRSwNP) is a type 2 (T2) inflammatory disease associated with an increased number of airway basal cells (BCs). Recent studies have identified transcriptionally distinct BCs, but the molecular pathways that support or inhibit human BC proliferation and differentiation are largely unknown.ObjectiveWe sought to determine the role of T2 cytokines in regulating airway BCs.MethodsSingle-cell and bulk RNA sequencing of sinus and lung airway epithelial cells was analyzed. Human sinus BCs were stimulated with IL-4 and IL-13 in the presence and absence of inhibitors of IL-4R signaling. Confocal analysis of human sinus tissue and murine airway was performed. Murine BC subsets were sorted for RNA sequencing and functional assays. Fate labeling was performed in a murine model of tracheal injury and regeneration.ResultsTwo subsets of BCs were found in …

TRANSCRIPTOMIC ANALYSIS OF AIRWAY EPITHELIAL CELLS FROM CHILDREN WITH CYSTIC FIBROSIS TO RHINOVIRUS INFECTION Curtin University Homepage Toggle navigation Library Help Admin Toggle navigation espace - Curtin’s institutional repository View Item espace Home espace Curtin Research Publications View Item espace Home espace Curtin Research Publications View Item TRANSCRIPTOMIC ANALYSIS OF AIRWAY EPITHELIAL CELLS FROM CHILDREN WITH CYSTIC FIBROSIS TO RHINOVIRUS INFECTION 77037.docx (16.40Kb) Access Status Open access Authors Ling, K. Garratt, LW Lassmann, T. Sutanto, EN Agudelo-Romero, P. Gill, EE Turvey, S. Hancock, RE Kicic, Anthony Stick, SM Date 2018 Type Conference Paper  Metadata Show full item record Citation Ling, K. and Garratt, LW and Lassmann, T. and Sutanto, EN and Agudelo-Romero, P. and Gill, EE and Turvey, S. et al. …

Objective While general health may be influenced by sinonasal symptoms, their effects may be overshadowed by comorbid states which may be more serious. To assess the validity of this postulate, we measured the extent to which sinonasal symptoms and concurrent conditions influenced general health. Study Design Observational outcomes study. Setting Academic medical center, community care sites. Methods Adults with sinonasal symptoms completed the 22‐item Sinonasal Outcome Test, along with the Patient‐Reported Outcomes Measurement Information System global health short form. Comorbidities were categorized with the Deyo modification of the Charlson comorbidity index. Multivariate regression analyses were utilized to determine the relative impact of sinonasal symptoms and concurrent comorbid conditions on general health. Results Data from 219 consecutive patients demonstrated that …

The olfactory neuroepithelium serves as a sensory organ for odors and is part of the nasal mucosal barrier. Olfactory sensory neurons are surrounded and supported by epithelial cells. A subset of these, microvillous cells (MVCs), are strategically positioned at the apical surface but their specific functions are still enigmatic and their relationship to the rest of the solitary chemosensory cell family is unclear. Here, we establish that the larger family of MVCs comprises tuft cells and ionocytes in both mice and humans. Olfactory TRPM5+ tuft-MVCs share a core transcriptional profile with the chemosensory tuft family, prominently including the machinery for lipid mediator generation. Integrating analysis of the respiratory and olfactory epithelium, we define the unique receptor expression of TRPM5+ tuft-MVC compared to the Gɑ-gustducin+ respiratory tuft cells and characterize a new population of glandular DCLK1+ tuft cells. To establish how allergen sensing by tuft-MVCs might direct olfactory mucosal responses, we employed an integrated single-cell transcriptional and protein analysis. We defined a remodeling olfactory epithelial switch pathway with induction of Chil4 and a distinct pathway of proliferation of the quiescent olfactory horizontal basal stem cell (HBC), both triggered in the absence of significant olfactory apoptosis. While the Chil4 pathway was dependent on STAT6 signaling and innate lymphocytes, neither were required for HBC proliferation. HBC proliferation was dependent on tuft-MVCs, establishing these specialized epithelial cells as both sensors for allergens and regulators of olfactory stem cell responses. Together our data provide …

Background The Ryan White (RW) program funds medical and other support services for low-income persons with HIV, significantly improving progress along the HIV care continuum. Although the program has shown overall improvements in achievement of viral suppression, the relative contributions of changes in clinical practice and RW service components to the optimization of the HIV care continuum, particularly for those with new HIV diagnoses, remain unknown. Methods The target population was patients with recent HIV diagnoses who received care at RW-funded clinics in the greater New Haven area between 2009 and 2018. Client data were extracted from the RW-funded database, CAREWare, and the electronic medical record. Primary outcomes included time between HIV diagnosis and first HIV primary care (PC) visit, antiretroviral therapy (ART) initiation, and viral …

HIV pre-exposure prophylaxis (PrEP) remains underutilized in the U.S. Since greater than 85% of PrEP prescriptions are filled at commercial pharmacies, pharmacists are uniquely positioned to increase PrEP use. This scoping review explores pharmacy-based initiatives to increase PrEP use. We searched PubMed, PsycINFO, CINAHL, and Scopus for peer-reviewed studies on pharmacist-led interventions to increase PrEP use or pharmacy-based PrEP initiatives. Forty-nine articles were included in this review. Overall, studies demonstrated that patients expressed strong support for pharmacist prescription of PrEP. Three intervention designs compared changes in PrEP initiation or knowledge pre- and post-intervention. Commentary/review studies recommended PrEP training for pharmacists, policy changes to support pharmacist screening for HIV and PrEP prescription, and telemedicine to increase …

The mainstay of treatment for sinonasal and skull base malignancies includes surgical resection with or without adjuvant therapy. Depending on the extent of the tumor, surgical removal can be extremely challenging because of the proximity of the paranasal sinuses to the orbit, intracranial cavity, and major neurovascular structures. Traditionally, an open approach was used to achieve surgical resection of these malignancies. Over the last 30 years, there have been significant advances in sinonasal and skull base surgery. With improvements in anatomical knowledge, surgical technique, and skull base reconstruction, the endoscopic endonasal approach has now become an accepted surgical approach in the management of certain sinonasal malignancies. This has added to the armamentarium of options available for surgical control of these complex tumors.

The olfactory neuroepithelium serves as a sensory organ for odors and a mucosal barrier which intimately interacts with the inhaled airstream. Odorant sensing is mediated by olfactory sensory neurons (OSNs), which along with diverse accessory epithelial cell types, are continuously replenished from a basal epithelial stem cell pool. This process of ongoing OSN differentiation is so far the only definitively established site of active adult neurogenesis in mice and humans. The mediators regulating the dynamics of this unique neurogenic niche are largely unknown and how olfactory neurogenesis is regulated by the environment is unclear. Here, integrating single-cell

ObjectiveThe overall discriminatory ability of validated instrument scores for computed tomography (CT) findings of chronic rhinosinusitis has limitations and may be modified by multiple factors. To support optimal methods for assessment, we studied which factors could influence this relationship, including the concurrent impact of multiple discrete CT scoring mechanisms, colocalized imaging findings, and nasal comorbid conditions.Study DesignObservational outcomes study.SettingAcademic medical center.MethodsPatients with sinonasal complaints who completed the 22-item Sinonasal Outcome Test (SNOT-22) and underwent CT were included. Multivariate ordinal regression was utilized to assess associations. CT data were quantified with the Lund-Mackay system, Zinreich system, and a direct measure of maximal mucosal thickness. The impact of incidental findings (mucous retention cysts, periapical dental …

BackgroundThe association between sinonasal and pulmonary symptoms in aspirin-exacerbated respiratory disease is not fully established.ObjectiveTo characterize sinonasal and asthma symptomatology, and to determine whether reported sinonasal symptoms predict asthma severity.MethodsProspectively collected data from an aspirin-exacerbated respiratory disease registry cohort were included from 2013 to 2018. Sinonasal symptomatology measured by Sino-Nasal Outcomes Test (SNOT) 22-item total scores was used as the predictor variable, with Asthma Control Test (ACT) scores and percent predicted FEV1 (FEV1% predicted) as primary outcomes. All instances of paired data on the same date were used. ACT score was also evaluated with FEV1% predicted as the outcome. Mixed effects regression was completed.ResultsFrom 1065 aspirin-exacerbated respiratory disease registry subjects (mean age …