Stroke is the leading cause of long term disability in developed countries and one of the top causes of mortality worldwide. The past decade has seen substantial advances in the diagnostic and treatment options available to minimize the impact of acute ischemic stroke. The key first step in stroke care is early identification of patients with stroke and triage to centers capable of delivering the appropriate treatment, as fast as possible. Here, we review the data supporting pre-hospital and emergency stroke care, including use of emergency medical services protocols for identification of patients with stroke, intravenous thrombolysis in acute ischemic stroke including updates to recommended patient eligibility criteria and treatment time windows, and advanced imaging techniques with automated interpretation to identify patients with large areas of brain at risk but without large completed infarcts who are likely to benefit from endovascular thrombectomy in extended time windows from symptom onset. We also review protocols for management of patient physiologic parameters to minimize infarct volumes and recent updates in secondary prevention recommendations including short term use of dual antiplatelet therapy to prevent recurrent stroke in the high risk period immediately after stroke. Finally, we discuss emerging therapies and questions for future research.
We report the successful transfer of a fully functional lac operator-repressor gene regulatory system to the mouse. The key component is a lac repressor transgene that resembles a typical mammalian gene both in codon usage and structure and expresses functional levels of repressor protein in the animal. We used the repressor to regulate the expression of a mammalian reporter gene consisting of the tyrosinase promoter embedded with three short lac operator sequences and the tyrosinase coding sequence. Pigmentation of the mouse was controlled by the interaction of the lac repressor with the regulatable Tyrosinase transgene in a manner that was fully reversible by the lactose analog IPTG. Direct control of mammalian promoters by the lac repressor provides tight, reversible regulation, predictable levels of de-repressed expression, and the promise of reversible control of the endogenous genome. The mouse is the most widely used experimental animal to model mammalian development and disease. In recent years, technological advances in genetic manipulation of the mouse genome have made it even more valuable as a research tool, and a great deal of information has been learned from conventional knockout and transgenic experiments. Despite this, it can be difficult to draw definite conclusions from these studies. Embryonic lethality might preclude the possibility of analyzing adult phenotype, or activation of compensatory systems confuse the analysis. Tight, reversible control of gene expression would greatly broaden the possible experimental questions that can be addressed. To gain such control, the ideal system would enable a target gene to be switched on and off repeatedly, without affecting the expression of nontargeted genes. With this ideal in mind, we have developed the lac repressor regulatory system for use in the mouse.The lac operon of Escherichia coli consists of a set of genes coordinately regulated by lactose (Jacob and Monod 1961). The regulatory components of the system are the lac repressor and its DNA-binding sequence, the lac operator. In the absence of lactose, lac repressor occupies the lac operators and prevents transcription. Lactose causes a conformational change in the repressor, and it vacates the operators, allowing RNA polymerase to gain access to the promoter and initiate transcription. Hu and Davidson (1987) were the first to use lac elements to control reporter-gene expression reversibly in mammalian cells. Their results were extended by Figge et al. (1988), who demonstrated that the lac repressor was able to gain access to the mammalian chromosome to regulate a stably integrated reporter gene.Our goal has been to adapt the lac regulatory system to control gene expression in the mouse. In an earlier paper, we reported that transgenes containing the bacterial-coding sequence for the lac repressor downstream of the -actin promoter were heavily methylated and only transcribed in the testis of transgenic mice (Scrable and Stambrook 1997). Methylation and silencing in mice also was observed by W...
Carotid webs exhibit a strong association with ischemic stroke, and their presence should be suspected in patients lacking other risk factors, particularly African American women.
Significant delays occur in treating patients with endovascular therapy in acute ischemic stroke, offering opportunities for improvements in systems of care. Ongoing prospective clinical trials can help to assess if HV centers are achieving better clinical outcomes and higher reperfusion rates.
We measured the flux of amino acids associated with sinking particles collected by sediment traps at two Pacific Ocean sites. These results were compared with results from six other sites where we and others have measured amino acid fluxes. This comparison shows that the flux of amino acids on sinking particles is related to primary productivity. This relationship exists in spite of differences in the oceanic regimes sampled and in the sediment traps, bactericides, and amino acid analysis techniques used. The amount of particulate amino acids leaving the euphotic zone in areas of higher productivity is a higher proportion of the primary production than in less productive areas. And, a larger amount of particulate amino acids reaches deeper waters in more productive areas. However, the particulate amino acids leaving the euphotic zone decompose faster with depth in more productive areas. Faster decomposition below the surface waters in areas of high productivity suggests that (I) decomposition of particulate organic matter may be mediated more by zooplankton and less by microbial processes than in areas of lower productivity, or (2) phytoplankton growing in more productive areas are more easily remineralized than those growing in less productive areas.
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