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1.
Artigo em Inglês | MEDLINE | ID: mdl-38477154

RESUMO

KEY POINTS: Silent sinus syndrome (SSS) and chronic maxillary atelectasis (CMA) represent an overlapping clinical entity, both likely lying on the spectrum of one disease process. There is widespread inconsistency of diagnosis in the literature of reported cases of SSS and CMA. We propose a novel, comprehensive staging system to simplify diagnosis and inform management.

2.
Cell Mol Gastroenterol Hepatol ; 13(5): 1449-1467, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35108658

RESUMO

BACKGROUND & AIMS: Although basal cell hyperplasia is a histologic hallmark of eosinophilic esophagitis (EoE), little is known about the capabilities of epithelial renewal and differentiation in the EoE inflammatory milieu. In murine esophageal epithelium, there are self-renewing and slowly proliferating basal stem-like cells characterized by concurrent expression of CD73 (5'-nucleotidase ecto) and CD104 (integrin ß4). Here, we investigated CD73+CD104+ cells within the basal population of human esophageal epithelium and clarified the biological significance of these cells in the EoE epithelium. METHODS: We performed flow cytometry on esophageal biopsy samples from EoE and non-EoE patients to determine the quantity of CD73+CD104+ cells in the epithelium. Simulating the EoE milieu we stimulated primary patient-derived and immortalized cell line-derived esophageal organoids with interleukin (IL)4 and IL13 and analyzed by flow cytometry, immunohistochemistry, and quantitative reverse-transcription polymerase chain reaction. We performed single-cell RNA sequencing on primary organoids in the setting of IL13 stimulation and evaluated the CD73+CD104+ population. We performed fluorescent-activated cell sorting to purify CD73+CD104+ and CD73- CD104+ populations and seeded these groups in organoid culture to evaluate the organoid formation rate and organoid size. We used RNA interference to knock down CD73 in esophageal organoids to evaluate organoid formation rates and size. We evaluated the effects of signal transducer and activator of transcription 6 (STAT6) signaling inhibition by RNA interference, a STAT6 inhibitor, AS1517499, as well as the proton pump inhibitor omeprazole. RESULTS: EoE patients showed decreased epithelial CD73+CD104+ cell content. IL4 and IL13 stimulation depleted this population in 3-dimensional organoids with a recapitulation of basal cell hyperplasia as corroborated by single-cell RNA sequencing of the organoids, which suggests depletion of CD73+CD104+ cells. The CD73+CD104+ population had enhanced organoid formation compared with the CD73-CD104+ population. Similarly, knock-down of CD73 resulted in decreased organoid formation rate. Genetic and pharmacologic inhibition of STAT6 prevented T helper 2 cytokine-induced depletion of CD73+CD104+ cells. Lastly, omeprazole treatment prevented the effects of IL4 and IL13 on the CD73+CD104+ population. CONCLUSIONS: This study addressed the role of CD73+CD104+ cells in epithelial renewal and homeostasis in the context of EoE. The depletion of the CD73+CD104+ self-renewal population by helper T cell 2 cytokines in EoE milieu may be perpetuating epithelial injury. Future therapies targeting epithelial restitution in EoE could decrease the need for immune modulation and steroid therapy.


Assuntos
Esofagite Eosinofílica , Interleucina-4 , 5'-Nucleotidase/uso terapêutico , Animais , Citocinas , Esofagite Eosinofílica/tratamento farmacológico , Esofagite Eosinofílica/patologia , Homeostase , Humanos , Hiperplasia/patologia , Interleucina-13/farmacologia , Interleucina-13/uso terapêutico , Interleucina-4/uso terapêutico , Camundongos , Omeprazol/farmacologia , Omeprazol/uso terapêutico , Células-Tronco/metabolismo
3.
Curr Cardiovasc Risk Rep ; 15(12): 23, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34900074

RESUMO

PURPOSE OF REVIEW: Telehealth is an innovative approach with great potential to bridge the healthcare delivery gap, especially for underserved communities. While minority populations represent a target audience that could benefit significantly from this modern solution, little of the existing literature speaks to its acceptability, accessibility, and overall effectiveness in underserved populations. Here, we review the various challenges and achievements of contemporary telehealth and explore its impact on care delivery as an alternative or adjunct to traditional healthcare delivery systems. RECENT FINDINGS: Given the COVID-19 pandemic, there has been a rapid acceleration in telemedicine adoption. Recent studies of telemedicine utilization during the pandemic reveal stark disparities in telemedicine modality use based on race, socioeconomic status, geography, and age. SUMMARY: While telehealth has great potential to overcome healthcare obstacles, the digital divide stands as a challenge to equitable telehealth and telemedicine adoption. Achieving health equity in telehealth will require the mobilization of resources, financial incentives, and political will among hospital systems, insurance companies, and government officials.

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