We report the repair of a double aortic arch, coarctation of the aorta, and left subclavian artery (LSCA) aneurysm using a hybrid procedure in a 47-year-old woman. The patient underwent repair through a median sternotomy incision to bypass the left common carotid artery and LSCA. An endovascular approach was used to repair the coarctation of the aorta and to occlude the right aortic arch. Repair of this anomaly was advised because of worsening clinical symptoms and potential for fatal rupture or dissection of the LSCA aneurysm. Hybrid repair simplified what would have required a multistage open repair.
Background: Toxoplasma gondii is a single-celled obligate intracellular parasite commonly found in cat feces and animal issues and is known to cause cerebral infections in immune- compromised individuals and neonates. Once ingested, T. gondii reaches the host's blood supply and reaches the brain, where infection ensues. However, it remains unclear how T. gondii crosses the blood-brain barrier to reach the brain. In this study, we utilize a human stem cell-derived BBB model with near in vivo properties to investigate the effects of T. gondii on critical barrier properties that permit entry into the brain parenchyma. Methods: Human-induced pluripotent stem cells (iPSCs) were used to derive brain microvascular endothelial cells (BMECs). BMECs were exposed to tachyzoites, the infectious rapid replicating stage of T. gondii, at a multiplicity of infection (MOI) of 0.1 and 1.0 for 24 hours. Following exposure, several critical barrier properties were monitored, including trans- endothelial electrical resistance (TEER) and tight junction analysis. Results: BMECs treated with both MOI of 0.1 and 1.0 showed a significant reduction in all three tight junction proteins (Claudin-5, Occludin, and ZO-1), as indicated by an increase in discontinuous junctions and a decrease in area fraction index. Barrier integrity is directly associated with tight junctional continuity and localization. Furthermore, tachyzoites at an MOI of 0.1 and 1.0 demonstrated a reduction in barrier tightness, as observed by a decrease in TEER. Conclusion and Potential Impact: These results indicate that T. gondii may, in part, have access to the brain by inducing disruption in tight junction proteins, thus increasing barrier leakiness via a para-cellular route. These data may help guide future investigations on T. gondii's ability to evoke blood-brain barrier dysfunction and reach the vulnerable brain tissue.
Background: Alcohol consumption has been directly linked to neurodegenerative diseases, including Alzheimer's disease (AD). Additionally, heavy consumption of alcohol has been shown to cause a faster cognitive decline in AD patients. A subset of studies demonstrated that alcohol can diminish BBB integrity and independently AD patients have suppressed barrier properties, but the direct effect of alcohol on barrier integrity in AD patients remains unclear. In this study, we utilize a human stem cell-derived AD BBB model with near in vivo properties to investigate the effects of alcohol on critical barrier properties. Methods: Brain microvascular endothelial cells (BMECs) were derived from healthy (IMR90) and AD (PSEN 1, PSEN 2, and APP) human induced pluripotent stem cells (iPSCs). Healthy and AD cell lines were treated with physiologically relevant concentrations of alcohol (5, 25, and 50 mM). Following exposure, several critical barrier properties were monitored for up to 5 days post-exposure, including trans-endothelial electrical resistance (TEER), sodium fluorescein permeability, and tight junction localization. Results: Moderate to severe alcohol exposure (25mM and 50mM) decreased barrier integrity in both healthy and AD-derived BMECs, as observed by an increase in sodium fluorescein permeability and a reduction in TEER. Furthermore, alcohol increased the number of discontinuous tight junctions directly contributing to the diminished barrier integrity. Interestingly, our preliminary results demonstrate that AD-derived BMECs are more susceptible to ethanol- induced barrier injury at lower concentrations of ethanol (5mM) compared to healthy-derived BMECs. Conclusion and Potential Impact: Our results indicate that alcohol can diminish critical barrier properties in healthy-derived BMECs similarly to other non-human established BBB models. For the first time, we observed an increase sensitivity to alcohol-induced BBB dysfunction in a familial AD-derived BBB model. These data suggest that mild alcohol consumption could significantly alter the BBB and contribute to the development or exacerbation of AD-induced barrier dysfunction.
Excessive blood loss in the pre-hospital setting poses a significant challenge and is one of the leading causes of death in the United States. In response, emergency medical services (EMS) have increasingly adopted the use of tranexamic acid (TXA) and calcium chloride (CaCl2) as therapeutic interventions for hemorrhagic traumas. TXA functions by inhibiting plasmin formation and restoring hemostatic balance, while calcium plays a pivotal role in the coagulation cascade, facilitating the conversion of factor X to factor Xa and prothrombin to thrombin. Despite the growing utilization of TXA and CaCl2 in both pre-hospital and hospital environments, a lack of literature exists regarding the comparative effectiveness of these agents in reducing hemorrhage and improving patient outcomes. Notably, Morgan County Indiana EMS, recently integrated the administration of TXA with CaCl2 into their treatment protocols, offering a valuable opportunity to gather insight and formulate updated guidelines based on patient-centered outcomes. This narrative review aims to comprehensively evaluate the existing evidence concerning the administration of TXA and CaCl2 in the pre-hospital management of hemorrhages, while also incorporating and analyzing data derived from the co-administration of these medications within the practices of Morgan County EMS. This represents the inaugural description of the concurrent use of both TXA and CaCl2 to manage hemorrhages in the scientific literature.
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