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The pathogenesis of sepsis involves complex interactions and a systemic inflammatory response leading eventually to multiorgan failure. Autotaxin (ATX, ENPP2) is a secreted glycoprotein largely responsible for the extracellular production of lysophosphatidic acid (LPA), which exerts multiple effects in almost all cell types through its at least six G-protein-coupled LPA receptors (LPARs). Here, we investigated a possible role of the ATX/LPA axis in sepsis in an animal model of endotoxemia as well as in septic patients. Mice with 50% reduced serum ATX levels showed improved survival upon lipopolysaccharide (LPS) stimulation compared to their littermate controls. Similarly, mice bearing the inducible inactivation of ATX and presenting with >70% decreased ATX levels were even more protected against LPS-induced endotoxemia; however, no significant effects were observed upon the chronic and systemic transgenic overexpression of ATX. Moreover, the genetic deletion of LPA receptors 1 and 2 did not significantly affect the severity of the modelled disease, suggesting that alternative receptors may mediate LPA effects upon sepsis. In translation, ATX levels were found to be elevated in the sera of critically ill patients with sepsis in comparison with their baseline levels upon ICU admission. Therefore, the results indicate a role for ATX in LPS-induced sepsis and suggest possible therapeutic benefits of pharmacologically targeting ATX in severe, systemic inflammatory disorders.

Introduction: BackgroundDuring the pandemic, health professionals had the unprecedented experience of dealing with a newdisease with high contagiousness and mortality. The workload, but also the fear of disease management, caused significant levels of stress. Each employee managed stress in his own way. This study detects the level of stress experienced by health workers during the pandemic and the coping strategies they selected accordingly.ObjectivesThe aim of this study was to investigate the coping strategies used by health professionals during the pandemic of coronavirus.MethodsThe sample comprised 180 health professionals that were working in a public hospital. The data collection tool was an anonymous questionnaire consisting of socio-demographic questions, the Toulouse Scale for coping , and a sub questionnaire to explore health professionals’ views on the pandemic.ResultsWomen (73.9%), young individuals (50.6% are up to 35 years old) and TEI graduates (53.9%) predominate in the sample. The sample consisted mainly of nurses (68.3%) and the great majority were contract workers (67%).The most frequently used dimensions were “Active focus” (Average 3.91/5.00), “Acceptance” (3.86), “Cognitive Control and Planning” (3.61) and “Social Information Support” (3.60).Also, health workers used more often the strategies of “Social support” (3.45), “Control” (3.33) and “Focus” (3.23), while they use the “Withdrawal” strategy less often (2.25). Finally, respondents used “Positive strategies” more often (3.54) than negative ones.ConclusionsThe health professionals in the present study preferred to ask for information and use cognitive and informative strategies more often and, to a lesser extent, they were overwhelmed by their emotions. The strategies of social support, control and focus were used more often, while the strategy of withdrawal was selected less often. Furthermore, positive strategies were used to a greater extent.Disclosure of InterestNone Declared

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The activation and accumulation of lung fibroblasts (LFs), resulting in aberrant deposition of collagens and other extracellular matrix (ECM) components, is a pathogenic hallmark of Idiopathic Pulmonary Fibrosis (IPF), a lethal and incurable disease. In this report, increased expression of TKS5, a scaffold protein essential for the formation of podosomes, was detected in the lung tissue of IPF patients and bleomycin (BLM)-treated mice, correlating with increased collagen type I alpha 1 chain (COL1A1) expression. The profibrotic milieu, TGFβ, as well as a stiff Col1a1-rich acellular fibrotic ECM, were found to induce TKS5 expression and the formation of prominent podosome rosettes in LFs, culminating in increased ECM invasion. Podosomes were retained ex vivo in the absence of any stimulation, indicating that the formation of TKS5-enabled podosomes is an inherent property of IPF LFs. Remarkably, haploinsufficient Tks5+/- mice were relatively resistant to BLM-induced pulmonary fibrosis. Disease protection was largely attributable to diminished podosome formation in LFs and decreased ECM invasion, thus indicating TKS5-enabled and podosome-mediated ECM invasion as a major pathogenic mechanism in pulmonary fibrosis. Expression profiling revealed an ECM-podosome cross talk, and pharmacologic connectivity map analysis suggested several inhibitors that could prevent podosome formation and thus pulmonary fibrosis. Among them, inhibition of src kinase was shown to potently attenuate podosome formation in LFs, ECM invasion, as well as pulmonary fibrosis in post BLM precision cut lung slices, suggesting that pharmacological targeting of TKS5-enabled podosome formation is a very promising therapeutic option in pulmonary fibrosis.