The hepcidin-ferroportin axis influences mitochondrial function, proliferation, and migration in pulmonary artery endothelial and smooth muscle cells.

Elevated circulating hepcidin levels have been reported in patients with pulmonary artery hypertension (PAH). Hepcidin has been shown to promote proliferation of human pulmonary artery smooth muscle cells (PASMCs) in vitro, suggesting a potential role in PAH pathogenesis. However, the role of human pulmonary artery endothelial cells (PAECs) as either a source of hepcidin, or the effect of hepcidin on PAEC function is not as well described.

Protective Behaviors Following Digital COVID-19 Exposure Notifications, Washington State, September 1, 2021, to March 1, 2022.

Context: Digital exposure notification (EN) systems were widely used to supplement public health case investigations and contact tracing during the 2019 coronavirus disease (COVID-19) pandemic. In Washington State, the state Department of Health (DOH) implemented one such system, WA Notify, which generated ENs based on smartphone Bluetooth proximity detection. However, the privacy preserving measures of this technology prevented collection of information on how users responded after seeing an EN on their device.

Evaluation of the effectiveness of Washington State's digital COVID-19 exposure notification system over one pandemic year.

Introduction: Digital exposure notifications are a novel public health intervention used during the COVID-19 pandemic to alert users of possible COVID-19 exposure. We seek to quantify the effectiveness of Washington State's digital exposure notification system, WA Notify, as measured by the number of COVID-19 cases averted during a 1-year period.

Methods: While maintaining individuals' privacy, WA Notify collected data that could be used to evaluate the system's effectiveness.

Evaluation of the Safer Use of Antipsychotics in Youth Study on Population Level Antipsychotic Initiation: An Interrupted Time Series Analysis.

Antipsychotics carry a higher-risk profile than other psychotropic medications and may be prescribed for youth with conditions in which other first-line treatments are more appropriate. This study aimed to evaluate the population-level effect of the Safer Use of Antipsychotics in Youth (SUAY) trial, which aimed to reduce person-days of antipsychotic use among participants. We conducted an interrupted time series analysis using segmented regression to measure changes in prescribing trends of antipsychotic initiation rates pre-SUAY and post-SUAY trial at four U.

Use of Digital COVID-19 Exposure Notifications at a Large Gathering: Survey Analysis of Public Health Conference Attendees.

Background: WA Notify was Washington State's smartphone-based COVID-19 digital exposure notification (EN) tool, which was used to help limit the spread of COVID-19 between November 30, 2020, and May 11, 2023. Following the 2022 Washington State Public Health Association Annual Conference, attendees who had WA Notify activated began receiving ENs alerting them to a possible COVID-19 exposure during the conference. A survey was emailed to all conference attendees to measure WA Notify adoption, mechanisms through which attendees received ENs, and self-reported engagement in protective behaviors postexposure.

Cooperative sensing of mitochondrial DNA by ZBP1 and cGAS promotes cardiotoxicity.

Mitochondrial DNA (mtDNA) is a potent agonist of the innate immune system; however, the exact immunostimulatory features of mtDNA and the kinetics of detection by cytosolic nucleic acid sensors remain poorly defined. Here, we show that mitochondrial genome instability promotes Z-form DNA accumulation. Z-DNA binding protein 1 (ZBP1) stabilizes Z-form mtDNA and nucleates a cytosolic complex containing cGAS, RIPK1, and RIPK3 to sustain STAT1 phosphorylation and type I interferon (IFN-I) signaling.

Discovery and Structure-Based Design of Inhibitors of the WD Repeat-Containing Protein 5 (WDR5)-MYC Interaction.

WDR5 is a critical chromatin cofactor of MYC. WDR5 interacts with MYC through the WBM pocket and is hypothesized to anchor MYC to chromatin through its WIN site. Blocking the interaction of WDR5 and MYC impairs the recruitment of MYC to its target genes and disrupts the oncogenic function of MYC in cancer development, thus providing a promising strategy for the treatment of MYC-dysregulated cancers.

Transient increase in atherosclerotic plaque macrophage content following pneumonia in ApoE-deficient mice.

Introduction: Despite epidemiological associations between community acquired pneumonia (CAP) and myocardial infarction, mechanisms that modify cardiovascular disease during CAP are not well defined. In particular, largely due to a lack of relevant experimental models, the effect of pneumonia on atherosclerotic plaques is unclear. We describe the development of a murine model of the commonest cause of CAP, pneumonia, on a background of established atherosclerosis.

The structural basis for high-affinity uptake of lignin-derived aromatic compounds by proteobacterial TRAP transporters.

The organic polymer lignin is a component of plant cell walls, which like (hemi)-cellulose is highly abundant in nature and relatively resistant to degradation. However, extracellular enzymes released by natural microbial consortia can cleave the β-aryl ether linkages in lignin, releasing monoaromatic phenylpropanoids that can be further catabolised by diverse species of bacteria. Biodegradation of lignin is therefore important in global carbon cycling, and its natural abundance also makes it an attractive biotechnological feedstock for the industrial production of commodity chemicals.

Elevated type I interferon responses potentiate metabolic dysfunction, inflammation, and accelerated aging in mtDNA mutator mice.

Mitochondrial dysfunction is a key driver of inflammatory responses in human disease. However, it remains unclear whether alterations in mitochondria-innate immune cross-talk contribute to the pathobiology of mitochondrial disorders and aging. Using the polymerase gamma (POLG) mutator model of mitochondrial DNA instability, we report that aberrant activation of the type I interferon (IFN-I) innate immune axis potentiates immunometabolic dysfunction, reduces health span, and accelerates aging in mutator mice.

Altered Macrophage Polarization Induces Experimental Pulmonary Hypertension and Is Observed in Patients With Pulmonary Arterial Hypertension.

Objective: To determine whether global reduction of CD68 (cluster of differentiation) macrophages impacts the development of experimental pulmonary arterial hypertension (PAH) and whether this reduction affects the balance of pro- and anti-inflammatory macrophages within the lung. Additionally, to determine whether there is evidence of an altered macrophage polarization in patients with PAH. Approach and Results: Macrophage reduction was induced in mice via doxycycline-induced CD68-driven cytotoxic diphtheria toxin A chain expression (macrophage low [MacLow] mice).

An Evaluation of a Game-Based Treatment Package on Intraverbals in Young Children with Autism.

The purpose of the current study was to evaluate a game-based treatment package on the acquisition of intraverbals in young children with autism. The treatment package was composed of using a listener response training game (i.e.

Neutrophil microvesicles drive atherosclerosis by delivering miR-155 to atheroprone endothelium.

Neutrophils are implicated in the pathogenesis of atherosclerosis but are seldom detected in atherosclerotic plaques. We investigated whether neutrophil-derived microvesicles may influence arterial pathophysiology. Here we report that levels of circulating neutrophil microvesicles are enhanced by exposure to a high fat diet, a known risk factor for atherosclerosis.

A 72-year-old woman with periorbital swelling.

As allergists, we are frequently consulted to evaluate patients with swelling presumed to be angioedema. Patients with presumed angioedema can have multiple possible underlying triggers. We present the case of a hospitalized 72-year-old woman with a history of hypertension and metastatic chordoma who developed marked periorbital swelling that precluded eye opening 2 days after a neurosurgical operation (chordoma resection and T10-11 hardware repair).

A therapeutic antibody targeting osteoprotegerin attenuates severe experimental pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a rare but fatal disease. Current treatments increase life expectancy but have limited impact on the progressive pulmonary vascular remodelling that drives PAH. Osteoprotegerin (OPG) is increased within serum and lesions of patients with idiopathic PAH and is a mitogen and migratory stimulus for pulmonary artery smooth muscle cells (PASMCs).

The Hepcidin/Ferroportin axis modulates proliferation of pulmonary artery smooth muscle cells.

Studies were undertaken to examine any role for the hepcidin/ferroportin axis in proliferative responses of human pulmonary artery smooth muscle cells (hPASMCs). Entirely novel findings have demonstrated the presence of ferroportin in hPASMCs. Hepcidin treatment caused increased proliferation of these cells most likely by binding ferroportin resulting in internalisation and cellular iron retention.

Selective improvement of pulmonary arterial hypertension with a dual ET/ET receptors antagonist in the apolipoprotein E model of PAH and atherosclerosis.

Idiopathic pulmonary arterial hypertension (IPAH) is increasingly diagnosed in elderly patients who also have an increased risk of co-morbid atherosclerosis. Apolipoprotein E-deficient (ApoE) mice develop atherosclerosis with severe PAH when fed a high-fat diet (HFD) and have increased levels of endothelin (ET)-1. ET-1 receptor antagonists (ERAs) are used for the treatment of PAH but less is known about whether ERAs are beneficial in atherosclerosis.

Feasibility of brachytherapy as monotherapy for high-volume, low-risk prostate cancer.

Background: We sought to determine whether patients with high-volume, low-risk prostate cancer are suitable candidates for ultrasound-guided brachytherapy, monotherapy alone, without supplemental external beam radiation.

Materials And Methods: The study cohort comprised 200 consecutive patients who received ultrasound.guided monotherapy from November 02, 1998 to March 26, 2010.

Platelet P2Y12 Inhibitors Reduce Systemic Inflammation and Its Prothrombotic Effects in an Experimental Human Model.

Objective: Clinical studies suggest that platelet P2Y12 inhibitors reduce mortality from sepsis, although the underlying mechanisms have not been clearly defined in vivo. We hypothesized that P2Y12 inhibitors may improve survival from sepsis by suppressing systemic inflammation and its prothrombotic effects. We therefore determined whether clopidogrel and the novel, more potent P2Y12 inhibitor, ticagrelor, modify these responses in an experimental human model.

Ventricular ectopy in children without known heart disease.

Objective: To describe the presentation and clinical course of patients with ventricular ectopy (VE) without known heart disease seen at a single institution.

Study Design: Patients with VE were identified from the cardiology database. Patients with known hemodynamically significant heart disease or systemic diseases were excluded.

Tachycardia detection using smartphone applications in pediatric patients.

Objectives: To use smartphone applications (apps) to measure heart rates during supraventricular tachycardia (SVT) in pediatric patients and compare them with heart rates measured by standard electrocardiogram (ECG).

Study Design: Patients <18 years of age (n = 26) undergoing an electrophysiology study were enrolled. During the study, heart rates were measured at baseline and during SVT by the use of 2 smartphone apps.

Vessel wall, not platelet, P2Y12 potentiates early atherogenesis.

Aims: Platelets have a fundamental role in atherothrombosis, but their role in early atherogenesis is unclear. The P2Y12 receptor is responsible for amplifying and sustaining platelet activation and P2Y12 inhibition is crucial in modulating the vessel wall response to injury. We therefore examined the role of platelet vs.

Treatment of idiopathic immune-mediated hemolytic anemia with mycophenolate mofetil in five dogs.

Background: The optimal treatment for immune-mediated hemolytic anemia (IMHA) in dogs remains unknown. Mycophenolate mofetil (MMF) is being used with increasing frequency in veterinary medicine for immune-mediated diseases. The goal of this pilot study was to evaluate a series of dogs diagnosed with idiopathic IMHA treated with MMF and other standard therapies.