Control of inflammatory lung injury and repair by metabolic signaling in endothelial cells.

Purpose Of Review: Sepsis-induced inflammatory lung injury includes acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). There are currently no effective treatments for ALI/ARDS, but clinical outcomes could be improved by inhibiting lung injury and/or promoting post-sepsis vascular repair. In this review, we describe studies of endothelial cell metabolic pathways in sepsis-induced ALI/ARDS and vascular repair and identify areas of research that deserve attention in future studies.

Implementing a clinical scientist-led screening clinic for hypertrophic and dilated cardiomyopathies.

Background: The burden of screening for inherited cardiac conditions on health services grows ever larger, with each new diagnosis necessitating screening of additional family members. Screening these usually asymptomatic, low-risk individuals is currently performed by consultant cardiologists, consuming vital clinic resources that could otherwise be diverted to sicker patients requiring specialist consultant input. Clinical scientists now constitute a highly skilled and often underutilised group of individuals with training in areas such as clinical evaluation, 12-lead electrocardiography (ECG) interpretation, and echocardiography.

Variable task switching in the feeding network of is a function of differential command input.

Command systems integrate sensory information and then activate the interneurons and motor neurons that mediate behavior. Much research has established that the higher-order projection neurons that constitute these systems can play a key role in specifying the nature of the motor activity induced, or determining its parametric features. To a large extent, these insights have been obtained by contrasting activity induced by stimulating one neuron (or set of neurons) to activity induced by stimulating a different neuron (or set of neurons).

Endothelial FoxM1 reactivates aging-impaired endothelial regeneration for vascular repair and resolution of inflammatory lung injury.

Aging is a major risk factor of high incidence and increased mortality of acute respiratory distress syndrome (ARDS). Here, we demonstrated that persistent lung injury and high mortality in aged mice after sepsis challenge were attributable to impaired endothelial regeneration and vascular repair. Genetic lineage tracing study showed that endothelial regeneration after sepsis-induced vascular injury was mediated by lung resident endothelial proliferation in young adult mice, whereas this intrinsic regenerative program was impaired in aged mice.

The Unexpected Protective Role of Thrombosis in Sepsis-Induced Inflammatory Lung Injury Via Endothelial Alox15.

Background: Patients with sepsis-induced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) commonly suffer from severe pulmonary thrombosis, but clinical trials of anti-coagulant therapies in sepsis and ARDS patients have failed. ARDS patients with thrombocytopenia also exhibit increased mortality, and widespread pulmonary thrombosis is often seen in coronavirus disease 2019 (COVID-19) ARDS patients.

Methods: Employing different amounts of microbeads to induce various levels of pulmonary thrombosis.

Pulmonary Thrombosis Promotes Tumorigenesis via Myeloid Hypoxia-Inducible Factors.

Cancer patients have a greater risk of thrombosis than individuals without cancer. Conversely, thrombosis is a diagnostic predictor of cancer, but the mechanisms by which thrombosis promotes tumor propagation are incompletely understood. Our previous studies showed that hypoxia-inducible factors (HIF) 1α and HIF2α are stabilized in myeloid cells of murine thrombi.

Rabeprazole Promotes Vascular Repair and Resolution of Sepsis-Induced Inflammatory Lung Injury through HIF-1α.

There are currently no effective treatments for sepsis and acute respiratory distress syndrome (ARDS). The repositioning of existing drugs is one possible effective strategy for the treatment of sepsis and ARDS. We previously showed that vascular repair and the resolution of sepsis-induced inflammatory lung injury is dependent upon endothelial HIF-1α/FoxM1 signaling.

Silent Persistent Left Superior Vena Cava Right-to-Left Shunt as a Unique Cause of Recurrent Brain Abscesses.

We present a novel case of recurrent brain abscesses found to be the result of a silent congenital right-to-left extracardiac shunt, a persistent left superior vena cava draining into the left atrium. The patient's brain abscess was evacuated surgically and treated with antibiotics, and his shunt was subsequently repaired. The case suggests that attention should be paid to evaluation for shunt physiology allowing for bypass of the pulmonary circulation in those with recurrent brain abscesses.

Hypoxia-Inducible Factor Signaling in Inflammatory Lung Injury and Repair.

Inflammatory lung injury is characterized by lung endothelial cell (LEC) death, alveolar epithelial cell (AEC) death, LEC-LEC junction weakening, and leukocyte infiltration, which together disrupt nutrient and oxygen transport. Subsequently, lung vascular repair is characterized by LEC and AEC regeneration and LEC-LEC junction re-annealing, which restores nutrient and oxygen delivery to the injured tissue. Pulmonary hypoxia is a characteristic feature of several inflammatory lung conditions, including acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and severe coronavirus disease 2019 (COVID-19).

Examining non-technical skills for ad hoc resuscitation teams: a scoping review and taxonomy of team-related concepts.

Background: Non-technical skills (NTS) concepts from high-risk industries such as aviation have been enthusiastically applied to medical teams for decades. Yet it remains unclear whether-and how-these concepts impact resuscitation team performance. In the context of ad hoc teams in prehospital, emergency department, and trauma domains, even less is known about their relevance and impact.

Emerging and Established Histological Techniques for the Analysis of Thrombosis in COVID-19 Lungs.

Coronavirus disease 2019 (COVID-19) is the potentially lethal disease that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with COVID-19 have an increased risk of thrombosis, but the role of thrombosis in the pathogenesis and progression of severe COVID-19 remains unclear. A better understanding of the contribution of thrombosis to the development and progression of COVID-19 could lead to the development of novel COVID-19 treatments.

Prevalence and clinical correlates of exercise-induced ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy.

Exercise has a deleterious effect on the phenotypic expression of arrhythmogenic right ventricular cardiomyopathy (ARVC) and increases the risk of sudden death. The aim of the study was to determine the prevalence and correlates of exercise-induced arrhythmias during exercise tolerance test (ETT) in patients with ARVC. Between 2010 and 2019, 30 (47% males, mean age 42 ± 12 years) consecutive patients with a definite diagnosis of ARVC underwent a full genotypic and phenotypic characterization at our center.

Native valve endocarditis and pacemaker infection with Mycobacterium fortuitum.

Endocarditis and cardiac device infection due to is a rare entity in the hospital settings. We report a case of pacemaker infection and native valve endocarditis due to , which was associated with tricuspid valve vegetation. two days after admission with fever, chills, body aches and swelling around her pacemaker, the patient's pacing system was surgically removed.

The Complement of Projection Neurons Activated Determines the Type of Feeding Motor Program in .

Multiple projection neurons are often activated to initiate behavior. A question that then arises is, what is the unique functional role of each neuron activated? We address this issue in the feeding system of . Previous experiments identified a projection neuron [cerebral buccal interneuron 2 (CBI-2)] that can trigger ingestive motor programs but only after it is repeatedly stimulated, i.

Oridonin-Loaded Nanoparticles Inhibit Breast Cancer Progression Through Regulation of ROS-Related Nrf2 Signaling Pathway.

Oridonin (ORI) has been shown to inhibit tumor cell growth and proliferation , while its optimum anti-tumor activity is limited due to the poor aqueous solubility and bioavailability. In this study, to improve the bioavailability, we developed a nanoparticle-based drug delivery system to facilitate delivery of ORI to breast tumor. ORI was encapsulated in biodegradable nanoparticles (NPs) based on poly-lactic-co-glycolic acid (PLGA) and polyethylene glycol (PEG) to form ORI NPs (ORI-NPs).

Nasal Delivery of Hesperidin/Chitosan Nanoparticles Suppresses Cytokine Storm Syndrome in a Mouse Model of Acute Lung Injury.

The cytokine storm or cytokine storm syndrome (CSS) is associated with high mortality in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), for example following sepsis or infectious diseases including COVID-19. However, there are no effective treatments for CSS-associated ALI or ALI/ARDS. Thus, there remains an urgent need to develop effective drugs and therapeutic strategies against CSS and ALI/ARDS.

Cardiac magnetic resonance in patients with ARVC and family members: the potential role of native T1 mapping.

Left ventricular (LV) involvement in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) is not evaluated in the revised Task Force Criteria, possibly leading to underdiagnosis. This study explored the diagnostic role of myocardial native T1 mapping in patients with ARVC and their first-degree relatives. Thirty ARVC patients (47% males, mean age 45 ± 27 years) and 59 first-degree relatives not meeting diagnostic criteria underwent CMR with native T1 mapping.

Endothelial cells in the pathogenesis of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a devastating disease that involves pulmonary vasoconstriction, small vessel obliteration, large vessel thickening and obstruction, and development of plexiform lesions. PAH vasculopathy leads to progressive increases in pulmonary vascular resistance, right heart failure and, ultimately, premature death. Besides other cell types that are known to be involved in PAH pathogenesis ( smooth muscle cells, fibroblasts and leukocytes), recent studies have demonstrated that endothelial cells (ECs) have a crucial role in the initiation and progression of PAH.

Surviving and thriving in thrombosis research during a global pandemic: Experiences of a vascular scientist diagnosed with COVID-19.

The 2019-2020 COVID-19 outbreak resulted in widespread suffering along with major changes in the ways that researchers carry out their work. This article profiles the experiences of an early-career investigator in thrombosis research who worked through the COVID-19 pandemic and a COVID-19 diagnosis. The aims of this article are to normalize concern regarding COVID-19 in the research community, to provide a perspective on maintaining productivity during stay-at-home periods, and to discuss how the COVID-19 pandemic might alter common research practices in the future.

Cobalt oxide nanoparticle-synergized protein degradation and phototherapy for enhanced anticancer therapeutics.

How to enable protein degradation pathways including the autophagy-lysosome pathway (ALP) and the ubiquitin-proteasome system (UPS) to enhance the efficacy of anticancer treatments remains a substantial challenge. Cobalt oxide nanoparticles (CoO NPs) have attracted interest in recent years for their potential use as a synergistic anticancer treatment, although their therapeutic mechanisms of action are still poorly understood. Here, we describe the synergistic use of CoO NPs as an autophagy inhibitor, chemosensitizer and photosensitizer, which manipulate protein degradation pathways (ALP and UPS) and photothermal therapy for enhanced anticancer treatments both in vitro and in vivo.