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  • Munch Bugge posted an update 1 year, 3 months ago

    Mesenchymal stromal cells (MSCs) constitute a heterogeneous population of stromal cells with immunomodulatory and regenerative properties that support their therapeutic use. MSCs isolated from many tissue sources replicate vigorously in vitro and maintain their main biological properties allowing their widespread clinical application. To date, most MSC-based preclinical and clinical trials targeted immune-mediated and inflammatory diseases. Nevertheless, MSCs have antiviral properties and have been used in the treatment of various viral infections in the last years. Here, we revised in detail the biological properties of MSCs and their preclinical and clinical applications in viral diseases, including the disease caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection (COVID-19). Notably, rapidly increasing numbers of MSC-based therapies for COVID-19 have recently been reported. MSCs are theoretically capable of reducing inflammation and promote lung regeneration in severe COVID-19 patients. We critically discuss the rationale, advantages and disadvantages of MSC-based therapies for viral infections and also specifically for COVID-19 and point out some directions in this field. Finally, we argue that MSC-based therapy may be a promising therapeutic strategy for severe COVID-19 and other emergent respiratory tract viral infections, beyond the viral infection diseases in which MSCs have already been clinically applied. Graphical Abstract.There has been a rapid increase in the use of behavioural economics (BE) as a tool for policy makers to deploy, including in health-related applications. While this development has occurred over the past decade, health care systems have continued to struggle with escalating costs. We consider the potential role of BE for making improvements to health care system performance and the sustainability of publicly funded health care systems, in particular. RRx-001 We argue that the vast majority of applications in this field have been largely focussed on BE and public health, or the prevailing level of risks to health in populations, and with policy proposals to ‘nudge’ individual behaviour (e.g. in respect of dietary choices). Yet, improvements in population health may have little, if any, impact on the size, cost or efficiency of health care systems. Few applications of BE have focussed on the management, production, delivery or utilisation of health care services per se. The latter is our focus in this paper. We review the contributions on BE and health care and consider the potential for complementing the considerable work on BE and public health with a clear agenda for behavioural health care economics. This agenda should complement the work of conventional microeconomics in the health care sector.Mounting evidence suggests that the ATP-gated P2X7 receptor contributes to increased hyperexcitability in the brain. While increased expression of P2X7 in the hippocampus and cortex following status epilepticus and during epilepsy has been repeatedly demonstrated, the cell type-specific expression of P2X7 and its expression in extra-hippocampal brain structures remains incompletely explored. In this study, P2X7 expression was visualized by using a transgenic mouse model overexpressing P2X7 fused to the fluorescent protein EGFP. The results showed increased P2X7-EGFP expression after status epilepticus induced by intra-amygdala kainic acid and during epilepsy in different brain regions including the hippocampus, cortex, striatum, thalamus and cerebellum, and this was most evident in microglia and oligodendrocytes. Co-localization of P2X7-EGFP with cell type-specific markers was not detected in neurons or astrocytes. These data suggest that P2X7 activation is a common pathological hallmark across different brain structures, possibly contributing to brain inflammation and neurodegeneration following acute seizures and during epilepsy.During fictive locomotion cat lumbar motoneurons exhibit changes in membrane proprieties including a decrease in voltage threshold (Vth), afterhyperpolarization (AHP) and input resistance (Rin) and an increase in non-linear membrane property. The impact of these changes on the motoneuron recruitment remains unknown. Using modeling approach we investigated the channel mechanism regulating the motoneuron recruitment. Three types of motoneuron pools including slow (S), fatigue-resistant (FR) and fast-fatigable (FF) motoneurons were constructed based on the membrane proprieties of cat lumbar motoneurons. The transient sodium (NaT), persistent sodium (NaP), delayed-rectifier potassium [K(DR)], Ca2+-dependent K+ [K(AHP)] and L-type calcium (CaL) channels were included in the models. Simulation results showed that (1) Strengthening synaptic inputs increased the number of recruitments in all three types of motoneurons following the size principle. (2) Increasing NaT or NaP or decreasing K(DR) or K(AHP) lowered rheobase of spike generation thus increased recruitment of motoneuron pools. (3) Decreasing Rin reduced recruitment in all three types of motoneurons. (4) The FF-type motoneuron pool, followed by FR- and S-type, were the most sensitive to increase of synaptic inputs, reduction of Rin, upregulation of NaT and NaP, and downregulation of K(DR) and K(AHP). (5) Increasing CaL enhanced overall discharge rate of motoneuron pools with little effect on the recruitment. Simulation results suggested that modulation of ionic channels altered the output of motoneuron pools with either modulating the number of recruited motoneurons or regulating the overall discharge rate of motoneuron pools. Multiple channels contributed to the recruitment of motoneurons with interaction of excitatory and inhibitory synaptic inputs during walking.This study aimed to investigate whether the application of iodinated contrast agents before intravenous (IV) recombinant tissue plasminogen activator (rt-PA) reduces the efficacy in acute ischemic stroke (AIS) patients. To determine whether the application of iodinated contrast agents before intravenous rt-PA reduces the efficacy in AIS patients. We analyzed our prospectively collected data of consecutive AIS patients receiving IV rt-PA treatment in the MISSION CHINA study. Clinical outcome at 3 months was assessed with modified Rankin Scale (mRS) score and dichotomized into good outcome (0-2) and poor outcome (3-6). Symptomatic intracerebral hemorrhage (sICH) was defined as cerebral hemorrhagic transformation in combination with clinical deterioration of National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 points at 24-h. We performed logistic regression analysis and propensity score matching analysis to investigate the impact of iodinated contrast agents before IV rt-PA on poor outcome and sICH, respectively.