The History of Neurosurgical Management of Ischemic Stroke

Stroke remains a major public health issue and the second leading cause of death worldwide. The Hippocratic Corpus used the word apoplexy to describe a person collapsing while retaining pulse and respiration. This is believed to be the first written description of stroke. The theories of what caused stroke evolved over the years. When autopsies were performed stroke was attributed to emboli and thrombi formation. Carotid endarterectomies (CEA) were then performed for the treatment of stroke. Originally CEA were seen with skepticism but the North American Symptomatic Carotid Endarterectomy trial (NASCET) and the European Carotid Surgery trial (ECS) helped restore their efficacy in the management of ischemic stroke. A milestone in the management of ischemic stroke was the use of intravenous tissue plasminogen activator (tPA). Secondary to the limitations of the use of tPA other avenues were sought which included intraarterial recombinant prourokinase and mechanical thrombectomy. The field of mechanical thrombectomy continues to be rapidly changing and evolving. Various randomized controlled trials and meta-analysis have been conducted in order to evaluate who will benefit from mechanical thrombectomies, the timing, the best device to use and the role of combining this intervention with the administration of intravenous tPA

Unsaturated glycoceramides as molecular carriers for mucosal drug delivery of GLP-1

The incretin hormone Glucagon-like peptide 1 (GLP-1) requires delivery by injection for the treatment of Type 2 diabetes mellitus. Here, we test if the properties of glycosphingolipid trafficking in epithelial cells can be applied to convert GLP-1 into a molecule suitable for mucosal absorption. GLP-1 was coupled to the extracellular oligosaccharide domain of GM1 species containing ceramides with different fatty acids and with minimal loss of incretin bioactivity. When applied to apical surfaces of polarized epithelial cells in monolayer culture, only GLP-1 coupled to GM1-ceramides with short- or cis-unsaturated fatty acids trafficked efficiently across the cell to the basolateral membrane by transcytosis. In vivo studies showed mucosal absorption after nasal administration. The results substantiate our recently reported dependence on ceramide structure for trafficking the GM1 across polarized epithelial cells and support the idea that specific glycosphingolipids can be harnessed as molecular vehicles for mucosal delivery of therapeutic peptides

Unsaturated glycoceramides as molecular carriers for mucosal drug delivery of GLP-1

The incretin hormone Glucagon-like peptide 1 (GLP-1) requires delivery by injection for the treatment of Type 2 diabetes mellitus. Here, we test if the properties of glycosphingolipid trafficking in epithelial cells can be applied to convert GLP-1 into a molecule suitable for mucosal absorption. GLP-1 was coupled to the extracellular oligosaccharide domain of GM1 species containing ceramides with different fatty acids and with minimal loss of incretin bioactivity. When applied to apical surfaces of polarized epithelial cells in monolayer culture, only GLP-1 coupled to GM1-ceramides with short-or cis-unsaturated fatty acids trafficked efficiently across the cell to the basolateral membrane by transcytosis. In vivo studies showed mucosal absorption after nasal administration. The results substantiate our recently reported dependence on ceramide structure for trafficking the GM1 across polarized epithelial cells and support the idea that specific glycosphingolipids can be harnessed as molecular vehicles for mucosal delivery of therapeutic peptides

MicroRNA-338-3p and microRNA-451 contribute to the formation of basolateral polarity in epithelial cells

MicroRNAs are small noncoding RNA species, some of which are playing important roles in cell differentiation. However, the level of participations of microRNAs in epithelial cell differentiation is largely unknown. Here, utilizing an epithelial differentiation model with T84 cells, we demonstrate that miR-338-3p and miR-451 contribute to the formation of epithelial basolateral polarity by facilitating translocalization of β1 integrin to the basolateral membrane. Among 250 microRNAs screened in this study, the expression levels of four microRNAs (miR-33a, 210, 338-3p and 451) were significantly elevated in the differentiated stage of T84 cells, when epithelial cell polarity was established. To investigate the involvement of these microRNAs in terms of epithelial cell polarity, we executed loss-of- and gain-of-function analyses of these microRNAs. The blockade of endogenous miR-338-3p or miR-451 via each microRNA-specific antisense oligonucleotides inhibited the translocalization of β1 integrin to the basolateral membrane, whereas inhibition of miR-210 or miR-33a had no effect on it. On the other hand, simultaneous transfection of synthetic miR-338-3p and miR-451 accelerated the translocalization of β1 integrin to the basolateral membrane, although the introduction of individual synthetic microRNAs exhibited no effect. Therefore, we concluded that both miR-338-3p and miR-451 are necessary for the development of epithelial cell polarity

For a While

For the Grossman ensembleCommissioned and premiered by the Chicago Center for Contemporary Composition For a While is a reflection on my five years as a graduate student at the University of Chicago—a reflection on the moments, friendships, difficulties, and sounds that have shaped me and made my time here unique and special. In the early stages of this composition, the music that I was imagining was quiet, delicate, fragile... After the first workshop with the Grossman ensemble, I understood that the thought of leaving the place and the people who make it what it is made me emotional. After all, members of the ensemble are some of the first musicians I met when I arrived here or people who taught me early on. It feels as if we have watched one another grow. While there are remnants of that in the piece, there is much more than fragility and quietness. The shadow of a Cypriot folk song symbolizes home because that is what those around me made this foreign space into. There is rhythm, dance... color. After all, my time here was fun. It was loud, nervous...weird. My time here was made of bright and dark moments that are now valuable memories I will forever cherish. It was made of music and teachings that changed me forever. Finally, my time here was made of friends and colleagues who are now family members who will always be by my side. It is to them that I dedicate this piece