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Atrial-ventricular differences in voltage-gated Na

currents might be exploited for atrial-selective antiarrhythmic drug action for the suppression of atrial fibrillation without risk of ventricular tachyarrhythmia. Eleclazine (GS-6615) is a putative antiarrhythmic drug with properties similar to the prototypical atrial-selective Na

channel blocker ranolazine that has been shown to be safe and well tolerated in patients.

The present study investigated atrial-ventricular differences in the biophysical properties and inhibition by eleclazine of voltage-gated Na

currents.

The fast and late components of whole-cell voltage-gated Na

currents (respectively,



and



) were recorded at room temperature (∼22°C) from rat isolated atrial and ventricular myocytes.

Atrial



activated at command potentials ∼5.5 mV more negative and inactivated at conditioning potentials ∼7 mV more negative than ventricular



. There was no difference between atrial and ventricular myocytes in the eleclazine inhibites differences between the 2 cell types in the voltage dependence of instantaneous inhibition by eleclazine. Eleclazine warrants further investigation as an atrial-selective antiarrhythmic drug.In a recent issue of Cancer Cell, Carrot-Zhang et al. identified ancestry-specific molecular variants and expression changes among patients from The Cancer Genome Atlas (TCGA).1 Their study findings and limitations highlight the critical need to diversify populations represented in cancer genomics research.Development of effective prevention and treatment strategies for pre-eclampsia is limited by the lack of accurate methods for identification of at-risk pregnancies. We performed small RNA sequencing (RNA-seq) of maternal serum extracellular RNAs (exRNAs) to discover and verify microRNAs (miRNAs) differentially expressed in patients who later developed pre-eclampsia. Sera collected from 73 pre-eclampsia cases and 139 controls between 17 and 28 weeks gestational age (GA), divided into separate discovery and verification cohorts, are analyzed by small RNA-seq. Discovery and verification of univariate and bivariate miRNA biomarkers reveal that bivariate biomarkers verify at a markedly higher rate than univariate biomarkers. The majority of verified biomarkers contain miR-155-5p, which has been reported to mediate the pre-eclampsia-associated repression of endothelial nitric oxide synthase (eNOS) by tumor necrosis factor alpha (TNF-α). Deconvolution analysis reveals that several verified miRNA biomarkers come from the placenta and are likely carried by placenta-specific extracellular vesicles.Follicular helper T cells (TFH) are critical for vaccine and infection elicitation of long-lived humoral immunity, but exaggerated TFH responses can promote autoimmunity and other pathologies. It is unfortunate that no clinical interventions exist for the selective depletion of follicular T cells to alleviate these diseases. We engineered a chimeric antigen receptor (CAR) facilitating the specific targeting of cells with high expression levels of human programmed cell death protein 1 (PD-1), a cardinal feature of follicular T cells. CAR-expressing human natural killer (NK) cells robustly and discriminately eliminated PD-1high follicular human T cells in vitro and in a humanized mouse model of lupus-like disease while sparing B cells and other PD-1low T cell subsets, including regulatory T cells. These results establish a strategy for specific targeting of PD-1high T cells that can be advanced as a clinical tool for the selective depletion of pathogenic follicular T cells or other PD-1high target cells in certain disease states.

Research examining RNs' experiences during the COVID-19 pandemic is lacking, thus inhibiting efforts to optimize nursing care delivery and patient outcomes during the current pandemic and future public health emergencies.

To explore the experience of being a registered nurse caring for patients with COVID-19 at an urban academic medical center during the early stages of the pandemic.

Qualitative descriptive study, guided by Donabedian's Quality Framework for Evaluation of Healthcare Delivery which focuses on structures, processes, and outcomes of care delivery.

Urban academic medical center in the northeast United States.

Registered nurses cared for or caring for patients with COVID-19, age ≥18 years old, and English-speaking.

Participants were recruited for individual in-person semi-structured interviews. Trastuzumab ic50 Interviews occurred during March and April 2020 and were recorded and transcribed. Transcripts were analyzed by two researchers using emergent qualitative content analysis to identify themes.

to optimize healthcare structures, nursing care processes, and patient outcomes. Our study can inform strategies for providing registered nurses with adequate communication, protection, and resources during the COVID-19 pandemic and future similar public health emergencies.

Roles and nursing practice processes evolved to meet the demand for care despite challenges. Registered nurses require adequate protection for their frontline role which may consist of increased patient exposure compared to clinical colleagues, emotional support, and clear clinical guidance. A deeper understanding of how a public health emergency, such as the COVID-19 pandemic, affects nursing practice can guide future efforts to optimize healthcare structures, nursing care processes, and patient outcomes. Our study can inform strategies for providing registered nurses with adequate communication, protection, and resources during the COVID-19 pandemic and future similar public health emergencies.We present the characteristics and outcomes of the first 2 cases of catheter-directed thrombolysis performed in patients presenting with coronavirus disease-2019 (COVID-19)-related iliocaval thrombosis. (Level of Difficulty Beginner.).

A subset of patients with severe COVID-19 develop a hyperinflammatory syndrome, which might contribute to morbidity and mortality. This study explores a specific phenotype of COVID-19-associated hyperinflammation (COV-HI), and its associations with escalation of respiratory support and survival.

In this retrospective cohort study, we enrolled consecutive inpatients (aged ≥18 years) admitted to University College London Hospitals and Newcastle upon Tyne Hospitals in the UK with PCR-confirmed COVID-19 during the first wave of community-acquired infection. Demographic data, laboratory tests, and clinical status were recorded from the day of admission until death or discharge, with a minimum follow-up time of 28 days. We defined COV-HI as a C-reactive protein concentration greater than 150 mg/L or doubling within 24 h from greater than 50 mg/L, or a ferritin concentration greater than 1500 μg/L. Respiratory support was categorised as oxygen only, non-invasive ventilation, and intubation. Initial and repeated measures of hyperinflammation were evaluated in relation to the next-day risk of death or need for escalation of respiratory support (as a combined endpoint), using a multi-level logistic regression model.