[How can an emergency department be strengthened against a pandemic?] / Was macht eine Notaufnahme schlagkräftig gegenüber einer Pandemie?

The emergency department (ED) is one of the crucial parts of the hospital infrastructure during all phases of the pandemic. The ED plays an important part in detecting an increasing number of new contagious diseases, which could potentially lead to an epidemic or pandemic.During a pandemic, the ED's main task is to detect infected individuals. These patients then need to be isolated and an adequate treatment is required. The ED must be prepared in order to perform well in such a situation. One major part for readiness is communication in an open manner to all partners within the department, as well as with emergency medical services and other departments of the hospital.The ED must be restructured to withstand the rising number of infected patients. These patients must be separated from other critically ill patients. Strategies for a diagnostic workup depending on the kind of infection have to be put in place. Pathways for the outpatient and inpatient management must be defined to avoid overcrowding in the ED. Depending on the number of patients, escalation and de-escalation strategies have to be set up within the hospital.Over the whole course of the pandemic, all staff members are the key resources for the ED and the entire hospital. The ED can only cope with a pandemic situation if staff are working together as a whole. This implies several important steps to get the staff prepared: Recurring, open conversations about fears, problems, and successes are critical for staff morale. Training must be continually provided, and protection strategies implemented. In the chronic phase of the pandemic the focus should shift more towards strategies on how to create possibilities for recuperation, domestic support measures, and mental health care for staff.

FoxP1 stimulates angiogenesis by repressing the inhibitory guidance protein semaphorin 5B in endothelial cells.

Forkhead box (Fox) transcription factors are important regulators of cardiovascular development and several Fox-proteins have recently been shown to modulate embryonic and post-natal angiogenesis. However, the role of the FoxP subfamily, which is highly expressed in cardiovascular tissue, has not been investigated so far. Here, we show that the transcription factor FoxP1 is the highest expressed FoxP-protein in endothelial cells and that it is upregulated at the site of neovascularization during hindlimb ischemia in mice. Silencing of FoxP1 results in a strong inhibition of proliferation, tube formation and migration of cultured endothelial cells. Accordingly, knockdown of FoxP1 in zebrafish was followed by a disruption of intersomitic vascular formation. Using gene expression profiling, we show that FoxP1 induces a specific change of the endothelial transcriptome and functions as a suppressor of semaphorin 5B, which has previously been described as a neuronal inhibitory factor. Our findings now demonstrate that semaphorin 5B also acts as a FoxP1- dependent suppressor of endothelial cell proliferation, migration and sprouting, mediating the effects of FoxP1. In summary, our data indicate that the transcription factor FoxP1 is essential for the angiogenic function of endothelial cells and functions as a suppressor of the inhibitory guidance cue semaphorin 5B, suggesting an important function of FoxP1 in the regulation of neovascularization.

MicroRNA-100 regulates neovascularization by suppression of mammalian target of rapamycin in endothelial and vascular smooth muscle cells.

BACKGROUND: The adaptive growth of blood vessels is an important protective mechanism in cardiovascular disease. However, the underlying regulatory mechanisms of this process are only partly understood. Recently, small endogenous RNAs (microRNAs [miRNAs]) were found to play an important role in embryonic and postnatal vascular development. Here, we used miRNA transcriptome analysis after induction of hind-limb ischemia in mice to screen for miRNAs involved in adaptive blood vessel growth following arterial occlusion. METHODS AND RESULTS: Using miRNA arrays, we explored the miRNA expression profile during adaptive neovascularization. We describe specific changes in miRNA expression patterns and show that miRNA-100 is significantly downregulated after induction of hind-limb ischemia in mice. Our data demonstrate that miR-100 modulates proliferation, tube formation, and sprouting activity of endothelial cells and migration of vascular smooth muscle cells and functions as an endogenous repressor of the serine/threonine protein kinase mammalian target of rapamycin (mTOR). Whereas miR-100 inhibition increased mTOR levels in endothelial cells, overexpression of miR-100 reduced mTOR expression and consequently attenuated cellular proliferation. Supporting this notion, overexpression of an mTOR construct lacking the miRNA binding site rescued the inhibitory effect of miR-100 on cell proliferation. Accordingly, miR-100 inhibition by specific antagomirs in vivo stimulated angiogenesis and resulted in functional improvement of perfusion after femoral artery occlusion in mice. In contrast, treatment with the mTOR inhibitor rapamycin had the opposite effect. CONCLUSIONS: Our data demonstrate that miR-100 has an antiangiogenic function and represses mTOR signaling in endothelial and vascular smooth muscle cells. Inhibition of miR-100 could be a novel approach for the modulation of blood vessel growth and other mTOR-dependent processes.

MicroRNA regulation of angiogenesis and arteriogenesis.

MicroRNAs are short, nonprotein-coding RNA molecules that play a crucial role in the post-transcriptional regulation of gene expression. By binding to specific target sequences, mostly located in the 3'-untranslated region of their target mRNA, they can induce mRNA decay or translational inhibition. Unlike siRNA, microRNAs show imperfect matching to their target mRNAs and can therefore modulate the expression of several mRNA genes at once. Although microRNAs have already been extensively studied in invertebrates, their function in mammalian organisms and in human disease is largely unknown. Several studies have shown an important regulatory function of microRNAs in embryonic and postnatal blood vessel development. Here, we provide an overview on these recent findings and summarize these so-called "angiomiRs" and their mode of action.