Post-discharge complications and follow-up timing after hospitalization for traumatic rib fractures.

Purpose: To evaluate frequency and timing of post-discharge complications in patients with traumatic rib fractures undergoing operative or nonoperative management.

Methods: We retrospectively reviewed adult patients with rib fractures admitted to a Level 1 trauma center from 1/2020 to 12/2021. Outcomes included rib-related complications, pneumonia within 1 month, new diagnosis of opioid- or alcohol-use disorder, and all-cause mortality.

High-efficiency transgene integration by homology-directed repair in human primary cells using DNA-PKcs inhibition.

Therapeutic applications of nuclease-based genome editing would benefit from improved methods for transgene integration via homology-directed repair (HDR). To improve HDR efficiency, we screened six small-molecule inhibitors of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a key protein in the alternative repair pathway of non-homologous end joining (NHEJ), which generates genomic insertions/deletions (INDELs). From this screen, we identified AZD7648 as the most potent compound.

Microfluidic Organ-Chips and Stem Cell Models in the Fight Against COVID-19.

SARS-CoV-2, the virus underlying COVID-19, has now been recognized to cause multiorgan disease with a systemic effect on the host. To effectively combat SARS-CoV-2 and the subsequent development of COVID-19, it is critical to detect, monitor, and model viral pathogenesis. In this review, we discuss recent advancements in microfluidics, organ-on-a-chip, and human stem cell-derived models to study SARS-CoV-2 infection in the physiological organ microenvironment, together with their limitations.

Modeling Cardiac SARS-CoV-2 Infection with Human Pluripotent Stem Cells.

Although SARS-CoV-2, the causative virus of the global COVID-19 pandemic, primarily affects the respiratory tract, it is now recognized to have broad multi-organ tropism and systemic effects. Early reports indicated that SARS-CoV-2 infection could lead to cardiac damage, suggesting the virus may directly impact the heart. Cardiac cell types derived from human pluripotent stem cells (hPSCs) enable mechanistic interrogation of SARS-CoV-2 infection in human cardiac tissue.

SARS-CoV-2 infection of human iPSC-derived cardiac cells reflects cytopathic features in hearts of patients with COVID-19.

Although coronavirus disease 2019 (COVID-19) causes cardiac dysfunction in up to 25% of patients, its pathogenesis remains unclear. Exposure of human induced pluripotent stem cell (iPSC)-derived heart cells to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revealed productive infection and robust transcriptomic and morphological signatures of damage, particularly in cardiomyocytes. Transcriptomic disruption of structural genes corroborates adverse morphologic features, which included a distinct pattern of myofibrillar fragmentation and nuclear disruption.

BRD2 inhibition blocks SARS-CoV-2 infection by reducing transcription of the host cell receptor ACE2.

SARS-CoV-2 infection of human cells is initiated by the binding of the viral Spike protein to its cell-surface receptor ACE2. We conducted a targeted CRISPRi screen to uncover druggable pathways controlling Spike protein binding to human cells. We found that the protein BRD2 is required for transcription in human lung epithelial cells and cardiomyocytes, and BRD2 inhibitors currently evaluated in clinical trials potently block endogenous expression and SARS-CoV-2 infection of human cells, including those of human nasal epithelia.

SARS-CoV-2 infection of human iPSC-derived cardiac cells predicts novel cytopathic features in hearts of COVID-19 patients.

Although COVID-19 causes cardiac dysfunction in up to 25% of patients, its pathogenesis remains unclear. Exposure of human iPSC-derived heart cells to SARS-CoV-2 revealed productive infection and robust transcriptomic and morphological signatures of damage, particularly in cardiomyocytes. Transcriptomic disruption of structural proteins corroborated adverse morphologic features, which included a distinct pattern of myofibrillar fragmentation and numerous iPSC-cardiomyocytes lacking nuclear DNA.