The aims of this review are to demonstrate that the changes in coagulation and fibrinolysis observed in cardiac arrest and resuscitation can be recognized as disseminated intravascular coagulation ...(DIC), and to discuss the probability of DIC being a therapeutic target. The appearance of triggers of DIC, such as damage‐associated molecular patterns, inflammatory cytokines, and adrenaline, is associated with platelet activation, marked thrombin generation and fibrin formation, insufficient anticoagulation pathways, and increased fibrinolysis by tissue‐type plasminogen activator, followed by the suppression of fibrinolysis by plasminogen activator inhibitor‐1, in patients with cardiac arrest and resuscitation. Simultaneous neutrophil activation and endothelial injury associated with glycocalyx perturbation have been observed in these patients. The degree of these changes is more severe in patients with prolonged precardiac arrest hypoxia and long no‐flow and low‐flow times, patients without return of spontaneous circulation, and non‐survivors. Animal and clinical studies have confirmed decreased cerebral blood flow and microvascular fibrin thrombosis in vital organs, including the brain. The clinical diagnosis of DIC in patients with cardiac arrest and resuscitation is associated with multiple organ dysfunction, as assessed with the sequential organ failure assessment score, and increased mortality. This review confirms that the coagulofibrinolytic changes in cardiac arrest and resuscitation meet the definition of DIC proposed by the ISTH, and that DIC is associated with organ dysfunction and poor patient outcomes. This evidence implies that established DIC should be considered to be one of the main therapeutic targets in post–cardiac arrest syndrome.
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FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Thromboplasminflammation in coronavirus disease 2019 (COVID-19) coagulopathy consists of angiotensin II (Ang II)-induced coagulopathy, activated factor XII (FXIIa)- and kallikrein, kinin ...system-enhanced fibrinolysis, and disseminated intravascular coagulation (DIC). All three conditions induce systemic inflammation
each pathomechanism-developed production of inflammatory cytokines. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) downregulates angiotensin-converting enzyme 2, leading to an increase in Ang II levels. Ang II-induced coagulopathy comprising platelet activation, thrombin generation, plasminogen activator inhibitor-1 expression and endothelial injury causes thrombosis
the angiotensin II type 1 receptor. SARS-CoV-2 RNA and neutrophil extracellular trap (NET) DNA activate FXII, resulting in plasmin generation through FXIIa- and kallikrein-mediated plasminogen conversion to plasmin and bradykinin-induced tissue-type plasminogen activator release from the endothelium
the kinin B2 receptor. NETs induce immunothrombosis at the site of infection (lungs), through histone- and DNA-mediated thrombin generation, insufficient anticoagulation control, and inhibition of fibrinolysis. However, if the infection is sufficiently severe, immunothrombosis disseminates into the systemic circulation, and DIC, which is associated with the endothelial injury, occurs. Inflammation, and serine protease networks of coagulation and fibrinolysis, militate each other through complement pathways, which exacerbates three pathologies of COVID-19 coagulopathy. COVID-19 coagulopathy causes microvascular thrombosis and bleeding, resulting in multiple organ dysfunction and death in critically ill patients. Treatment targets for improving the prognosis of COVID-19 coagulopathy include thrombin, plasmin, and inflammation, and SARS-CoV-2 infection. Several drugs are candidates for controlling these conditions; however, further advances are required to establish robust treatments based on a clear understanding of molecular mechanisms of COVID-19 coagulopathy.
Glass transition is one of the unresolved critical issues in solid-state physics and materials science, during which a viscous liquid is frozen into a solid or structurally arrested state. On account ...of the uniform arrested mechanism, the calorimetric glass transition temperature (T
) always follows the same trend as the dynamical glass transition (or α-relaxation) temperature (T
) determined by dynamic mechanical analysis (DMA). Here, we explored the correlations between the calorimetric and dynamical glass transitions of three prototypical high-entropy metallic glasses (HEMGs) systems. We found that the HEMGs present a depressed dynamical glass transition phenomenon, i.e., HEMGs with moderate calorimetric T
represent the highest T
and the maximum activation energy of α-relaxation. These decoupled glass transitions from thermal and mechanical measurements reveal the effect of high configurational entropy on the structure and dynamics of supercooled liquids and metallic glasses, which are associated with sluggish diffusion and decreased dynamic and spatial heterogeneities from high mixing entropy. The results have important implications in understanding the entropy effect on the structure and properties of metallic glasses for designing new materials with plenteous physical and mechanical performances.
Whole-body ischemia and reperfusion due to cardiac arrest and subsequent return of spontaneous circulation constitute post-cardiac arrest syndrome (PCAS), which consists of four syndromes including ...systemic ischemia/reperfusion responses and post-cardiac arrest brain injury. The major pathophysiologies underlying systemic ischemia/reperfusion responses are systemic inflammatory response syndrome and increased coagulation, leading to disseminated intravascular coagulation (DIC), which clinically manifests as obstruction of microcirculation and multiple organ dysfunction. In particular, thrombotic occlusion in the brain due to DIC, referred to as the "no-reflow phenomenon," may be deeply involved in post-cardiac arrest brain injury, which is the leading cause of mortality in patients with PCAS. Coagulofibrinolytic changes in patients with PCAS are characterized by tissue factor-dependent coagulation, which is accelerated by impaired anticoagulant mechanisms, including antithrombin, protein C, thrombomodulin, and tissue factor pathway inhibitor. Damage-associated molecular patterns (DAMPs) accelerate not only tissue factor-dependent coagulation but also the factor XII- and factor XI-dependent activation of coagulation. Inflammatory cytokines are also involved in these changes
the expression of tissue factor on endothelial cells and monocytes, the inhibition of anticoagulant systems, and the release of neutrophil elastase from neutrophils activated by inflammatory cytokines. Hyperfibrinolysis in the early phase of PCAS is followed by inadequate endogenous fibrinolysis and fibrinolytic shutdown by plasminogen activator inhibitor-1. Moreover, cell-free DNA, which is also a DAMP, plays a pivotal role in the inhibition of fibrinolysis. DIC diagnosis criteria or fibrinolysis markers, including d-dimer and fibrin/fibrinogen degradation products, which are commonly tested in patients and easily accessible, can be used to predict the mortality or neurological outcome of PCAS patients with high accuracy. A number of studies have explored therapy for this unique pathophysiology since the first report on "no-reflow phenomenon" was published roughly 50 years ago. However, the optimum therapeutic strategy focusing on the coagulofibrinolytic changes in cardiac arrest or PCAS patients has not yet been established. The elucidation of more precise pathomechanisms of coagulofibrinolytic changes in PCAS may aid in the development of novel therapeutic targets, leading to an improvement in the outcomes of PCAS patients.
The pathomechanisms of hypoxemia and treatment strategies for type H and type L acute respiratory distress syndrome (ARDS) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced ...coronavirus disease 2019 (COVID-19) have not been elucidated.
SARS-CoV-2 mainly targets the lungs and blood, leading to ARDS, and systemic thrombosis or bleeding. Angiotensin II-induced coagulopathy, SARS-CoV-2-induced hyperfibrin(ogen)olysis, and pulmonary and/or disseminated intravascular coagulation due to immunothrombosis contribute to COVID-19-associated coagulopathy. Type H ARDS is associated with hypoxemia due to diffuse alveolar damage-induced high right-to-left shunts. Immunothrombosis occurs at the site of infection due to innate immune inflammatory and coagulofibrinolytic responses to SARS-CoV-2, resulting in microvascular occlusion with hypoperfusion of the lungs. Lung immunothrombosis in type L ARDS results from neutrophil extracellular traps containing platelets and fibrin in the lung microvasculature, leading to hypoxemia due to impaired blood flow and a high ventilation/perfusion (VA/Q) ratio. COVID-19-associated ARDS is more vascular centric than the other types of ARDS. D-dimer levels have been monitored for the progression of microvascular thrombosis in COVID-19 patients. Early anticoagulation therapy in critical patients with high D-dimer levels may improve prognosis, including the prevention and/or alleviation of ARDS.
Right-to-left shunts and high VA/Q ratios caused by lung microvascular thrombosis contribute to hypoxemia in type H and L ARDS, respectively. D-dimer monitoring-based anticoagulation therapy may prevent the progression to and/or worsening of ARDS in COVID-19 patients.
A “modular repertoire of contention” denotes prevalent forms of interaction that are used by a variety of actors against a variety of targets for a variety of issues in a variety of locations. ...Modular repertoires are important in the literature of contentious politics and social movements because of their transferability across different contentious contexts. This study addresses three limitations in the literature. First, discussion about modular repertoires to date has been framed as if some forms of contention were modular and other forms were not—thus a dichotomy is set up between modular and nonmodular forms. Second, specific dimensions of modularity (transferability across actors, targets, issues, and locations) have been mostly ignored in the literature. Third, an empirical measure has not yet been developed for the concept. By assessing how broadly a form of contention is diffused across actors, targets, issues, and locations, this study develops a new measure of modularity. Using the measure, it evaluates Charles Tilly's modular repertoire hypothesis. According to the hypothesis, public meetings, petitions, and demonstrations became a modular repertoire in Great Britain during the eighteenth and nineteenth centuries as a result of Parliament's rise as the center of British national politics. The results obtained here offer new insights. The empirical measure proposed will advance our understanding of repertoires of contention and political systems.
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BFBNIB, INZLJ, NMLJ, NUK, PNG, UL, UM, UPUK, ZRSKP
Open-cell macroporous Fe, Cr and their alloys were prepared by dealloying with a metallic melt. By immersing (Fe, Cr)30Ni70 precursors in a Mg melt, Ni selectively dissolved into the Mg and the ...remaining components formed a bicontinuous structure. Analyses of the thermal coarsening in the melt reveal that evolution of the porous structure is controlled by interfacial diffusion between the melt and precursor solid. The underlying mechanism for the nanoporous structure formation is therefore the same as that in aqueous solution.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Silicon is a promising material for negative electrode in Li-ion batteries because of high gravimetric capacity. A Si nanomaterial that can accommodate volume expansion accompanied by lithiation is ...needed for practical application in Li-ion batteries. We prepare three-dimensional nanoporous interconnected silicon material with controlled pore and ligament sizes by dealloying using an Mg–Si precursor and Bi melt. The Mg atoms in the precursor selectively dissolve into Bi, and the remaining Si atoms self-organize into a nanoporous structure with characteristic length ranging from several ten to hundred nanometer. The Li-ion battery electrodes made from nanoporous silicon exhibit higher capacities, increased cycle lives, and improved rate performances compared with those made from commercial Si nanoparticles. Measurements on the electrical resistivity and electrode thickness change by lithiation/delithiation suggest that the superior performance of nanoporous Si electrode originates from the following: (1) The nanoporous Si has much lower electrical resistivity compared with that of the nanoparticle Si owing to the n-type dopant incorporated during dealloying. (2) The nanoporous Si-based electrode has higher porosity owing to the presence of intra-particle pores, which can accommodate Si expansion up to higher levels of lithiation.
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•Nanoporous interconnected Si was prepared by dealloying in metallic melt.•Nanoporous Si electrodes outperform in capacity and rate characteristics.•Nanoporous Si has high electrical conductivity.•Nanoporous Si-based electrodes accommodate expansion of Si upon lithiation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Trauma-induced coagulopathy (TIC) is divided into primary coagulopathy caused by trauma itself and secondary coagulopathy, including anemia-, hypothermia-, and acidosis-induced coagulopathy. The main ...pathophysiology of TIC has long been considered to be disseminated intravascular coagulation (DIC), which is characterized by increased thrombin generation and subsequent consumption coagulopathy due to damage-associated molecular patterns derived from injured cells and tissues. However, trauma surgeons in Europe and the United States of America who express negative opinions about DIC have advocated the activated protein C (APC) hypothesis, which posits that the main pathophysiologies of primary coagulopathy are APC-mediated suppression of coagulation and an APC-mediated increase in fibrinolysis. The APC hypothesis is a highly questionable concept and its pathophysiological theory remains a highly controversial topic. This review summarizes the issues surrounding the TIC controversy and describes the current international consensus, suggesting future directions for readers of this article.
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