Therefore, many of these PRs including A2BR, A3R, P2X3R, P2X4R, P2X7R, P2Y1R, P2Y4R, P2Y6R, and P2Y11R can be considered as therapeutic targets. However, the multitude of PR subtypes expressed in different cells of the cardiovascular system may constitute a challenge whether single or multiple receptors should be targeted at the same time for the best efficacy. The present review discusses the promising purinergic drugs used in clinical studies for the treatment of cardiovascular disease. We also update experimental evidence for many other PRs that can be considered as therapeutic targets for future drug development.Ubiquitylation is a key event that regulates protein turnover, and induction of the ubiquitin ligase E3 WWP1 has been associated with age. Left ventricular hypertrophy (LVH) commonly occurs as a function of age and can cause heart failure (HF) with a preserved ejection fraction (EF; HFpEF). We hypothesized that overexpression (O/E) of WWP1 in the heart would cause LVH as well as functional and structural changes consistent with the aging HFpEF phenotype. Global WWP1 O/E was achieved in mice (n = 11) and echocardiography (40 MHz) performed to measure LV mass, EF, Doppler velocities (early E, late/atrial A), myocardial relaxation (E'), and isovolumetric relaxation time (IVRT) at 4, 6, and 8 wk. Age-matched wild-type animals (n = 15) were included as referent controls. LV EF was identical (60 ± 1 vs. 60 ± 1%, P > 0.90) with no difference in LV mass (67 ± 3 vs. 75 ± 5, P > 0.25) at 4 wk. However, at 8 wk of age, LV mass increased over twofold, E/A fell (impaired passive filling), and E/E' was lower and IVRT prolof WWP1 in mice induced LV hypertrophy, diastolic dysfunction, and ECM accumulation, consistent with the HFpEF phenotype, and thus may identify a new therapeutic pathway.The efficacy of an anthracycline antibiotic doxorubicin (DOX) as a chemotherapeutic agent is limited by dose-dependent cardiotoxicity. DOX is associated with activation of intracellular stress signaling pathways including p38 MAPKs. While previous studies have implicated p38 MAPK signaling in DOX-induced cardiac injury, the roles of the individual p38 isoforms, specifically, of the alternative isoforms p38γ and p38δ, remain uncharacterized. We aimed to determine the potential cardioprotective effects of p38γ and p38δ genetic deletion in mice subjected to acute DOX treatment. Male and female wild-type (WT), p38γ-/-, p38δ-/-, and p38γ-/-δ-/- mice were injected with 30 mg/kg DOX and their survival was tracked for 10 days. During this period, cardiac function was assessed by echocardiography and electrocardiography and fibrosis by Picro Sirius Red staining. Immunoblotting was performed to assess the expression of signaling proteins and markers linked to autophagy. Significantly improved survival was observed in protective in female but not in male mice. Cardiac structure and function were preserved in DOX-treated p38δ-/- females and autophagy marker was increased.Rationale Aerosol generation with modes of oxygen therapy such as high-flow nasal cannula and noninvasive positive-pressure ventilation is a concern for healthcare workers during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The amount of aerosol generation from the respiratory tract with these various oxygen modalities is unknown.Objectives To measure the size and number concentration of particles and droplets generated from the respiratory tract of humans exposed to various oxygen delivery modalities.Methods Ten healthy participants with no active pulmonary disease were enrolled. Oxygen modalities tested included nonhumidified nasal cannula, face mask, heated and humidified high-flow nasal cannula, and noninvasive positive-pressure ventilation. this website Aerosol generation was measured with each oxygen mode while participants performed maneuvers of normal breathing, talking, deep breathing, and coughing. Testing was conducted in a negative-pressure room. Particles with a diameter between 0.37 and 20 μm were measured using an aerodynamic particle spectrometer.Measurements and Main Results Median particle concentration ranged from 0.041 to 0.168 particles/cm3. Median diameter ranged from 1.01 to 1.53 μm. Cough significantly increased the number of particles measured. Measured aerosol concentration did not significantly increase with the use of either humidified high-flow nasal cannula or noninvasive positive-pressure ventilation. This was the case during normal breathing, talking, deep breathing, and coughing.Conclusions Oxygen delivery modalities of humidified high-flow nasal cannula and noninvasive positive-pressure ventilation do not increase aerosol generation from the respiratory tract in healthy human participants with no active pulmonary disease measured in a negative-pressure room.Previous pandemics have seen high psychiatric morbidity among health care workers. Protecting clinician mental health in the aftermath of coronavirus disease 2019 (COVID-19) requires an evidence-based approach to developing and deploying comprehensive clinician mental health support. In a narrative review of 96 articles addressing clinician mental health in COVID-19 and prior pandemics, 7 themes emerged 1) the need for resilience and stress reduction training; 2) providing for clinicians' basic needs (food, drink, adequate rest, quarantine-appropriate housing, transportation, child care, personal protective equipment); 3) the importance of specialized training for pandemic-induced changes in job roles; 4) recognition and clear communication from leadership; 5) acknowledgment of and strategies for addressing moral injury; 6) the need for peer and social support interventions; and 7) normalization and provision of mental health support programs. In addition to the literature review, in collaboration with the Collaborative for Healing and Renewal in Medicine (CHARM) network, the authors gathered practice guidelines and resources from health care organizations and professional societies worldwide to synthesize a list of resources deemed high-yield by well-being leaders. Studies of previous pandemics demonstrate heightened distress in health care workers years after the event. The COVID-19 pandemic presents unique challenges that surpass those of previous pandemics, suggesting a significant mental health toll on clinicians. Long-term, proactive individual, organizational, and societal infrastructures for clinician mental health support are needed to mitigate the psychological costs of providing care during the COVID-19 pandemic.