Summary
The inflammatory response and the activation of coagulation are two important responses in a host's defense against infection. These mechanisms do not work independently, but cooperate in a ...complex and synchronous manner. Recent research has also shed light on the critical role of thrombus formation, which prevents the dissemination of microorganisms. The cellular components of blood vessels, i.e. leukocytes, platelets, erythrocytes, and vascular endothelial cells, play significant roles in the development of thrombi in combination with activation of the coagulation system. In addition to the cellular components, alarmins such as histones and high‐mobility group box 1, microparticles and secreted granule proteins are all important for clot formation. In this summary, we review the pathophysiology of sepsis‐induced coagulopathy and the role of cellular components and critical factors released from damaged cells. In addition, we review important therapeutic approaches that have been developed, are under investigation and are currently available in certain countries, including antithrombin, recombinant thrombomodulin, anti‐Toll‐like receptor 4 therapy, anti‐damage associated molecular pattern therapy, and hemoadsorption with a polymyxin B‐immobilized fiber column.
Summary
The vascular endothelial surface is coated by the glycocalyx, a ubiquitous gel‐like layer composed of a membrane‐binding domain that contains proteoglycans, glycosaminoglycan side‐chains, and ...plasma proteins such as albumin and antithrombin. The endothelial glycocalyx plays a critical role in maintaining vascular homeostasis. However, this component is highly vulnerable to damage and is also difficult to examine. Recent advances in analytical techniques have enabled biochemical, visual and computational investigation of this vascular component. The glycocalyx modulates leukocyte–endothelial interactions, thrombus formation and other processes that lead to microcirculatory dysfunction and critical organ injury in sepsis. It also acts as a regulator of vascular permeability and contains mechanosensors as well as receptors for growth factors and anticoagulants. During the initial onset of sepsis, the glycocalyx is damaged and circulating levels of glycocalyx components, including syndecans, heparan sulfate and hyaluronic acid, can be measured and are reportedly useful as biomarkers for sepsis. Also, a new methodology using side‐stream dark‐field imaging is now clinically available for assessing the glycocalyx. Multiple factors including hypervolemia and hyperglycemia are toxic to the glycocalyx, and several agents have been proposed as therapeutic modalities, although no single treatment has been proven to be clinically effective. In this article, we review the derangement of the glycocalyx in sepsis. Despite the accumulated knowledge regarding the important roles of the glycocalyx, the relationship between derangement of the endothelial glycocalyx and severity of sepsis or disseminated intravascular coagulation has not been adequately elucidated and further work is needed.
Highlights ► Economic theories suggest that it is as if values of rewards are mapped on a common scale for comparison. ► A few brain areas appear to encode values on a neural common scale. ► A new ...meta-analysis suggests that the main area representing value on a common scale is a subregion of the vmPFC/OFC. ► We review a neurobiological foundation for standard economic theory. ► This suggests a tool for measuring preferences.
Perioperative management of the bleeding patient Ghadimi, K; Levy, J.H.; Welsby, I.J.
British journal of anaesthesia : BJA,
December 2016, 20161201, 2016-Dec, 2016-12-00, Volume:
117, Issue:
suppl_3
Journal Article
Peer reviewed
Open access
Perioperative bleeding remains a major complication during and after surgery, resulting in increased morbidity and mortality. The principal causes of non-vascular sources of haemostatic perioperative ...bleeding are a preexisting undetected bleeding disorder, the nature of the operation itself, or acquired coagulation abnormalities secondary to haemorrhage, haemodilution, or haemostatic factor consumption. In the bleeding patient, standard therapeutic approaches include allogeneic blood product administration, concomitant pharmacologic agents, and increasing application of purified and recombinant haemostatic factors. Multiple haemostatic changes occur perioperatively after trauma and complex surgical procedures including cardiac surgery and liver transplantation. Novel strategies for both prophylaxis and therapy of perioperative bleeding include tranexamic acid, desmopressin, fibrinogen and prothrombin complex concentrates. Point-of-care patient testing using thromboelastography, rotational thromboelastometry, and platelet function assays has allowed for more detailed assessment of specific targeted therapy for haemostasis. Strategic multimodal management is needed to improve management, reduce allogeneic blood product administration, and minimize associated risks related to transfusion.
The growing field of correlated nanoelectronics exists at the intersection of two established fields: correlated oxide electronics and semiconductor nanoelectronics. The development of quantum ...technologies that exploit quantum coherence and entanglement for the purposes of computation, simulation, and sensing will require complex material properties to be controlled at nanoscale dimensions. Heterostructures and nanostructures formed at the interface between LaAlO3 and SrTiO3 exhibit striking behavior that arises from the ability to program the conductive behavior at extreme nanoscale dimensions. The active electronic layer, SrTiO3, exhibits a wide range of gate-tunable phenomena such as ferroelectricity, ferroelasticity, magnetism, superconductivity, and spin–orbit coupling, all of which can be controlled at the nanoscale using two reversible methods: conductive atomic force microscope lithography and ultra-low-voltage electron beam lithography. Mesoscopic devices such as single-electron transistors and quasi-one-dimensional electron waveguides can be “sketched” using these techniques, and the properties of these devices differ significantly from those created from traditional semiconductors, such as Si or GaAs. The strongly correlated nature of the SrTiO3 system is evident from superconducting behavior as well as a state in which electrons are paired outside the superconducting state. A highly exotic phase was discovered in which a degenerate quantum liquid is formed from bound states of n = 2, 3, 4, … electrons. Further development of correlated nanoelectronics based on the LaAlO3/SrTiO3 system can potentially lead to a general platform for quantum simulation as well as a pathway for the development of highly entangled states of multiple photons.
Abstract Although an association between air pollution and adverse systemic health effects has been known for years, the effect of pollutants on neurodevelopment has been underappreciated. Recent ...evidence suggests a possible link between air pollution and neurocognitive impairment and behavioral disorders in children, however, the exact nature of this relationship remains poorly understood. Infants and children are uniquely vulnerable due to the potential for exposure in both the fetal and postnatal environments during critical periods in development. Carbon monoxide (CO), a common component of indoor and outdoor air pollution, can cross the placenta to gain access to the fetal circulation and the developing brain. Thus, CO is of particular interest as a known neurotoxin and a potential public health threat. Here we review overt CO toxicity and the policies regulating CO exposure, detail the evidence suggesting a potential link between CO-associated ambient air pollution, tobacco smoke, and learning and behavioral abnormalities in children, describe the effects of subclinical CO exposure on the brain during development, and provide mechanistic insight into a potential connection between CO exposure and neurodevelopmental outcome. CO can disrupt a number of critical processes in the developing brain, providing a better understanding of how this specific neurotoxin may impair neurodevelopment. However, further investigation is needed to better define the effects of perinatal CO exposure on the immature brain. Current policies regarding CO standards were established based on evidence of cardiovascular risk in adults with pre-existing comorbidities. Thus, recent and emerging data highlighted in this review regarding CO exposure in the fetus and developing child may be important to consider when the standards and guidelines are evaluated and revised in the future.
•Nature experience produced clear benefits for affect (e.g., decrease in anxiety and rumination).•Nature experience produced some benefits for cognition (complex working memory span task).•Supports ...the idea that exposure to natural greenspace can improve affect and cognition.
This study investigated the impact of nature experience on affect and cognition. We randomly assigned sixty participants to a 50-min walk in either a natural or an urban environment in and around Stanford, California. Before and after their walk, participants completed a series of psychological assessments of affective and cognitive functioning. Compared to the urban walk, the nature walk resulted in affective benefits (decreased anxiety, rumination, and negative affect, and preservation of positive affect) as well as cognitive benefits (increased working memory performance). This study extends previous research by demonstrating additional benefits of nature experience on affect and cognition through assessments of anxiety, rumination, and a complex measure of working memory (operation span task). These findings further our understanding of the influence of relatively brief nature experiences on affect and cognition, and help to lay the foundation for future research on the mechanisms underlying these effects.
Depression is a major health problem with a high prevalence and a heavy socioeconomic burden in western societies. It is associated with atrophy and impaired functioning of cortico-limbic regions ...involved in mood and emotion regulation. It has been suggested that alterations in neurotrophins underlie impaired neuroplasticity, which may be causally related to the development and course of depression. Accordingly, mounting evidence suggests that antidepressant treatment may exert its beneficial effects by enhancing trophic signaling on neuronal and synaptic plasticity. However, current antidepressants still show a delayed onset of action, as well as lack of efficacy. Hence, a deeper understanding of the molecular and cellular mechanisms involved in the pathophysiology of depression, as well as in the action of antidepressants, might provide further insight to drive the development of novel fast-acting and more effective therapies. Here, we summarize the current literature on the involvement of neurotrophic factors in the pathophysiology and treatment of depression. Further, we advocate that future development of antidepressants should be based on the neurotrophin theory.
Delineating the functional organization of the prefrontal cortex is central to advancing models of goal‐directed cognition. Considerable evidence indicates that specific forms of cognitive control ...are associated with distinct subregions of the left ventrolateral prefrontal cortex (VLPFC), but less is known about functional specialization within the right VLPFC. We report a functional MRI meta‐analysis of two prominent theories of right VLPFC function: stopping of motor responses and reflexive orienting to abrupt perceptual onsets. Along with a broader review of right VLPFC function, extant data indicate that stopping and reflexive orienting similarly recruit the inferior frontal junction (IFJ), suggesting that IFJ supports the detection of behaviorally relevant stimuli. By contrast, other right VLPFC subregions are consistently active during motor inhibition, but not reflexive reorienting tasks, with posterior‐VLPFC being active during the updating of action plans and mid‐VLPFC responding to decision uncertainty. These results highlight the rich functional heterogeneity that exists within right VLPFC.
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