Loss of developmentally derived Irf8+ macrophages promotes hyperinnervation and arrhythmia in the adult zebrafish heart.

Recent developments in cardiac macrophage biology have broadened our understanding of the critical functions of macrophages in the heart. As a result, there is further interest in understanding the independent contributions of distinct subsets of macrophage to cardiac development and function. Here, we demonstrate that genetic loss of interferon regulatory factor 8 (Irf8)-positive embryonic-derived macrophages significantly disrupts cardiac conduction, chamber function, and innervation in adult zebrafish.

On the rise: Development of a multi-tiered, indoor duckweed cultivation system.

Duckweed species (Lemnaceae) are suitable for remediation and valorization of agri-feed industry wastewaters and therefore can contribute to a more sustainable, circular economy where waste is a resource. Industrial applications will, however, require space efficient cultivation methods that are not affected by prevailing weather conditions. Here, the development and operation of a multi-tiered duckweed bioreactor is described.

Attitudes towards and engagement in self-directed learning among paramedics in New South Wales, Australia: a cross sectional study.

Background: Australian paramedics must engage in continuing professional development (CPD), including self-directed learning (SDL). This study aimed to examine paramedics' attitudes towards training and learning activities and perceptions about what could increase engagement in self-directed CPD.

Methods: A cross-sectional survey was conducted with New South Wales Ambulance paramedics.

Long-term statin therapy is associated with severe coronary artery calcification.

Background: Atherosclerosis and consequent risk of cardiovascular events or mortality can be accurately assessed by quantifying coronary artery calcium score (CACS) derived from computed tomography. HMG-CoA-reductase inhibitors (statins) are the primary pharmacotherapy used to reduce cardiovascular events, yet there is growing data that support statin use may increase coronary calcification. We set out to determine the likelihood of severe CACS in the context of chronic statin therapy.

Role of innovation in pharmaceutical regulation: A proposal for principles to evaluate EU General Pharmaceutical Legislation from the innovator perspective.

Because the EU General Pharmaceutical Legislation is under review, the EFPIA Innovation Board developed evaluation principles for the policy proposals and key considerations on how the regulatory framework can support innovation while ensuring only safe, efficacious and quality medicines are authorized. The evaluation principles are anchored on actions to promote: agile adoption of new methodologies with soft law tools; continued emphasis on regulatory science to inform policies; a cost/benefit assessment of the new regulation to ensure they have an overall positive impact; and mitigation of any negative externalities or unintended effects for any type of innovation or products. The evaluation principles are intended to guide the impact assessment of the pharmaceutical legislation in the EU but the principles can be applied globally.

NLRP3 inflammasome activation in cigarette smoke priming for Pseudomonas aeruginosa-induced acute lung injury.

It is increasingly recognized that cigarette smoke (CS) exposure increases the incidence and severity of acute respiratory distress syndrome (ARDS) in critical ill humans and animals. However, the mechanism(s) is not well understood. This study aims to investigate mechanism underlying the priming effect of CS on Pseudomonas aeruginosa-triggered acute lung injury, by using pre-clinic animal models and genetically modified mice.

Association Between Periodontal Disease and Cardiovascular Disease (from the NHANES).

As observational studies support the association between periodontal disease (PD) and cardiovascular diseases (CVDs), we examined this relationship using the National Health and Nutrition Examination Survey 2013 to 2014 data. This cross-sectional study involved 2,830 adult participants, aged ≥30 years who underwent a home interview, followed by a standardized assessment at a mobile examination center from 2013 to 2014. PD was defined using the new classification scheme issued by American Academy of Periodontology Workshop on the Classification of Periodontal and Peri-implant Diseases and Conditions in 2017, and CVD was defined as the composite of coronary artery disease and stroke.

Macrophage IL-1β promotes arteriogenesis by autocrine STAT3- and NF-κB-mediated transcription of pro-angiogenic VEGF-A.

Peripheral artery disease (PAD) leads to considerable morbidity, yet strategies for therapeutic angiogenesis fall short of being impactful. Inflammatory macrophage subsets play an important role in orchestrating post-developmental angiogenesis, but the underlying mechanisms are unclear. Here, we find that macrophage VEGF-A expression is dependent upon the potent inflammatory cytokine, IL-1β.

Rac GTPase Signaling in Immune-Mediated Mechanisms of Atherosclerosis.

Coronary artery disease caused by atherosclerosis is a major cause of morbidity and mortality around the world. Data from preclinical and clinical studies support the belief that atherosclerosis is an inflammatory disease that is mediated by innate and adaptive immune signaling mechanisms. This review sought to highlight the role of Rac-mediated inflammatory signaling in the mechanisms driving atherosclerotic calcification.

Coronary Artery Calcification and Plaque Characteristics in People Living With HIV: A Systematic Review and Meta-Analysis.

Background Studies have reported that people living with HIV have higher burden of subclinical cardiovascular disease, but the data are not adequately synthesized. We performed meta-analyses of studies of coronary artery calcium and coronary plaque in people living with HIV. Methods and Results We performed systematic search in electronic databases, and data were abstracted in standardized forms.

Effect of Missed Doses on the Therapeutic Effect of Methotrexate for Rheumatoid Arthritis: A Pharmacokinetic Modeling Study.

Introduction: Patients rarely, if ever, take their medications exactly as prescribed. The extent to which missed doses interfere with a drug's therapeutic effect remains unclear.

Methods: After weekly oral dosing of methotrexate (MTX) for rheumatoid arthritis, its polyglutamate derivatives (MTXglu) accumulate in red blood cells, where they are markers for the drug's therapeutic effectiveness.

Aortic Valve Calcification Is Associated with Future Cognitive Impairment.

Background: While an association between atherosclerosis and dementia has been identified, few studies have assessed the longitudinal relationship between aortic valve calcification (AVC) and cognitive impairment (CI).

Objective: We sought to determine whether AVC derived from lung cancer screening CT (LCSCT) was associated with CI in a moderate-to-high atherosclerotic risk cohort.

Methods: This was a single site, retrospective analysis of 1401 U.

α7 Nicotinic acetylcholine receptor mediates right ventricular fibrosis and diastolic dysfunction in pulmonary hypertension.

Right ventricular (RV) fibrosis is a key feature of maladaptive RV hypertrophy and dysfunction and is associated with poor outcomes in pulmonary hypertension (PH). However, mechanisms and therapeutic strategies to mitigate RV fibrosis remain unrealized. Previously, we identified that cardiac fibroblast α7 nicotinic acetylcholine receptor (α7 nAChR) drives smoking-induced RV fibrosis.

Association of plasma adiponectin with pulmonary hypertension, mortality and heart failure in African Americans: Jackson Heart Study.

Background: Adiponectin is a polypeptide hormone related to obesity, and a known modulator of pulmonary vascular remodeling. Association between plasma adiponectin levels and pulmonary hypertension (PH) has not been studied in African Americans (AAs) who are disproportionately affected by obesity. The relationship between adiponectin and heart failure (HF) and mortality, outcomes associated with PH, is unclear.

Association of poor housing conditions with COVID-19 incidence and mortality across US counties.

Objective: Poor housing conditions have been linked with worse health outcomes and infectious disease spread. Since the relationship of poor housing conditions with incidence and mortality of COVID-19 is unknown, we investigated the association between poor housing condition and COVID-19 incidence and mortality in US counties.

Methods: We conducted cross-sectional analysis of county-level data from the US Centers for Disease Control, US Census Bureau and John Hopkins Coronavirus Resource Center for 3135 US counties.

Aortic valve calcification predicts all-cause mortality independent of coronary calcification and severe stenosis.

Background And Aims: Calcific aortic valve disease is highly prevalent in patients with significant smoking history and is a marker of atherosclerosis. The aim of this study was to define the prognostic value of aortic valve calcification (AVC) derived from low dose, lung cancer screening computed tomography (LCSCT) for all-cause mortality in this higher risk population.

Methods: This is a single site, retrospective analysis of 1529 moderate-to-high atherosclerotic cardiovascular risk U.

Statins Disrupt Macrophage Rac1 Regulation Leading to Increased Atherosclerotic Plaque Calcification.

Objective: Calcification of atherosclerotic plaque is traditionally associated with increased cardiovascular event risk; however, recent studies have found increased calcium density to be associated with more stable disease. 3-hydroxy-3-methylglutaryl coenzymeA reductase inhibitors or statins reduce cardiovascular events. Invasive clinical studies have found that statins alter both the lipid and calcium composition of plaque but the molecular mechanisms of statin-mediated effects on plaque calcium composition remain unclear.

Treatment of Pulmonary Hypertension With Angiotensin II Receptor Blocker and Neprilysin Inhibitor Sacubitril/Valsartan.

Background: Angiotensin II has been implicated in maladaptive right ventricular (RV) hypertrophy and fibrosis associated with pulmonary hypertension (PH). Natriuretic peptides decrease RV afterload by promoting pulmonary vasodilation and inhibiting vascular remodeling but are degraded by neprilysin. We hypothesized that angiotensin receptor blocker and neprilysin inhibitor, sacubitril/valsartan (Sac/Val, LCZ696), will attenuate PH and improve RV function by targeting both pulmonary vascular and RV remodeling.

Home-Based Cardiac Rehabilitation Alone and Hybrid With Center-Based Cardiac Rehabilitation in Heart Failure: A Systematic Review and Meta-Analysis.

Background Center-based cardiac rehabilitation (CBCR) has been shown to improve outcomes in patients with heart failure (HF). Home-based cardiac rehabilitation (HBCR) can be an alternative to increase access for patients who cannot participate in CBCR. Hybrid cardiac rehabilitation (CR) combines short-term CBCR with HBCR, potentially allowing both flexibility and rigor.

Correction to: Coronary CTA for Surveillance of Cardiac Allograft Vasculopathy.

[This corrects the article DOI: 10.1007/s12410-018-9467-z.].

Patterns of non-adherence to oral antiretroviral medication: frequencies of consecutively missed doses.

Purpose: The therapeutic effect of a once-daily oral drug will be maintained if there are no occurrences of consecutively missed doses that exceed the duration of the drug's effect. The durations of effect of antiretroviral drugs are typically in the range of 1-4 days. Here, we report the observed frequencies of ≥2, ≥3, and ≥4 consecutively missed doses for patients taking a once-daily oral antiretroviral drug for HIV infection.