The Golden Syrian hamster is a well-characterized rodent model for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-associated pneumonia. We sought to characterize the pulmonary disease course during SARS-CoV-2 infection (strain USA-WA1/2020) in the hamster model using micro-computed tomography (micro-CT) and compare radiologic observations with histopathologic findings. We observed a range of radiologic abnormalities, including ground glass opacities (GGOs), consolidations, air bronchograms, and pneumomediastinum.
View Article and Find Full Text PDFTumor-associated macrophages (TAMs) are a heterogeneous population of cells whose phenotypes and functions are shaped by factors that are incompletely understood. Herein, we asked when and where TAMs arise from blood monocytes and how they evolve during tumor development. We initiated pancreatic ductal adenocarcinoma (PDAC) in inducible monocyte fate-mapping mice and combined single-cell transcriptomics and high-dimensional flow cytometry to profile the monocyte-to-TAM transition.
View Article and Find Full Text PDFNeutrophils are increasingly recognized as key players in the tumor immune response and are associated with poor clinical outcomes. Despite recent advances characterizing the diversity of neutrophil states in cancer, common trajectories and mechanisms governing the ontogeny and relationship between these neutrophil states remain undefined. Here, we demonstrate that immature and mature neutrophils that enter tumors undergo irreversible epigenetic, transcriptional, and proteomic modifications to converge into a distinct, terminally differentiated dcTRAIL-R1 state.
View Article and Find Full Text PDFOnco-fetal reprogramming of the tumor ecosystem induces fetal developmental signatures in the tumor microenvironment, leading to immunosuppressive features. Here, we employed single-cell RNA sequencing, spatial transcriptomics and bulk RNA sequencing to delineate specific cell subsets involved in hepatocellular carcinoma (HCC) relapse and response to immunotherapy. We identified POSTN extracellular matrix cancer-associated fibroblasts (EM CAFs) as a prominent onco-fetal interacting hub, promoting tumor progression.
View Article and Find Full Text PDFObjective: The objective for this study was to evaluate the effects of short chain fatty acids (SCFAs) on arthritic bone remodeling.
Methods: We treated a recently described preclinical murine model of psoriatic arthritis (PsA), R26STAT3C CD4Cre mice, with SCFA-supplemented water. We also performed in vitro osteoclast differentiation assays in the presence of serum-level SCFAs to evaluate the direct impact of these microbial metabolites on maturation and function of osteoclasts.
Brain macrophage populations include parenchymal microglia, border-associated macrophages, and recruited monocyte-derived cells; together, they control brain development and homeostasis but are also implicated in aging pathogenesis and neurodegeneration. The phenotypes, localization, and functions of each population in different contexts have yet to be resolved. We generated a murine brain myeloid scRNA-seq integration to systematically delineate brain macrophage populations.
View Article and Find Full Text PDFMacrophages are an essential part of tissue development and physiology. Perivascular macrophages have been described in tissues and appear to play a role in development and disease processes, although it remains unclear what the key features of these cells are. Here, we identify a subpopulation of perivascular macrophages in several organs, characterized by their dependence on the transcription factor c-MAF and displaying nonconventional macrophage markers including LYVE1, folate receptor 2, and CD38.
View Article and Find Full Text PDFMethamphetamine-associated cardiomyopathy (MACM) in an increasingly prevalent disease yet presenting clinical characteristics have not been well studied. We studied consecutive patients with MACM presenting between June 2018 and March 2020 who were interviewed for drug use and medical history. We retrospectively identified an age- and gender-matched cohort of Non-MACM (NMACM) patients and compared clinical characteristics.
View Article and Find Full Text PDFSpondyloarthritis (SpA) is a group of chronic, immune-mediated, inflammatory diseases affecting the bone, synovium, and enthesis. Microbiome, the community of microorganisms that has co-evolved with human hosts, plays a pivotal role in human health and disease. This invisible "essential organ" supplies the host with a myriad of chemicals and molecules.
View Article and Find Full Text PDFBackground: Studies have revealed an association between hospitalization of breastfed infants and weaning posthospitalization. It is unknown what steps inpatient providers at children's hospitals are currently taking to support breastfeeding mothers of hospitalized infants, their comfort providing breastfeeding counseling, and what training they receive.
Methods: We conducted a multicenter survey study of pediatric providers who care for infants hospitalized at 3 urban, tertiary-care children's hospitals over a 12-month period.
Background: In most cases of community-acquired pneumonia (CAP), an etiologic agent is not determined; the most common report from the microbiological evaluation of sputum cites "normal respiratory flora." Non-diphtheria spp. a component of this flora, is commonly viewed as a contaminant, but it may be the cause of pneumonia and the frequency with which it causes CAP may be underestimated.
View Article and Find Full Text PDFEarly HIV detection and treatment decreases morbidity and mortality and reduces high-risk behaviors. Many Emergency Departments (EDs) have HIV screening programs as recommended by the Centers for Disease Control and Prevention. Recent federal legislation includes incentives for electronic health record (EHR) adoption.
View Article and Find Full Text PDF