Recent advances in microfluidic cell cultures enable the construction of in vitro human skin models that can be used for drug toxicity testing, disease study. However, current in vitro skin model have limitations to emulate real human skin due to the simplicity of model. In this paper, we describe the development of ‘skin-on-a-chip’ to mimic the structures and functional responses of the human skin. The proposed model consists of 3 layers, on which epidermal, dermal and endothelial components originated from human, were cultured. The microfluidic device was designed for co-culture of human skin cells and each layer was separated by using porous membranes to allow interlayer communication. Skin inflammation and edema were induced by applying tumor necrosis factor alpha on dermal layer to demonstrate the functionality of the system. The expression levels of proinflammatory cytokines were analyzed to illustrate the feasibility. In addition, we evaluated the efficacy of therapeutic drug testing model using our skin chip. The function of skin barrier was evaluated by staining tight junctions and measuring a permeability of endothelium. Our results suggest that the skin-on-a-chip model can potentially be used for constructing in vitro skin disease models or for testing the toxicity of cosmetics or drugs.

RS was independently associated with good outcomes without increasing symptomatic intracranial hemorrhage or mortality. RS seemed considered in MT-failed internal carotid artery or middle cerebral artery M1 occlusion.

Background and Purpose— Stent retriever (SR) thrombectomy has become the mainstay of treatment of acute intracranial large artery occlusion. However, it is still not much known about the optimal limit of SR attempts for favorable outcome. We evaluated whether a specific number of SR passes for futile recanalization can be determined. Methods— Patients who were treated with a SR as the first endovascular modality for their intracranial large artery occlusion in anterior circulation were retrospectively reviewed. The recanalization rate for each SR pass was calculated. The association between the number of SR passes and a patient’s functional outcome was analyzed. Results— A total of 467 patients were included. Successful recanalization by SR alone was achieved in 82.2% of patients. Recanalization rates got sequentially lower as the number of passes increased, and the recanalization rate achievable by ≥5 passes of the SR was 5.5%. In a multivariable analysis, functional outcomes were more favorable in patients with 1 to 4 passes of the SR than in patients without recanalization (odds ratio [OR] was 8.06 for 1 pass; OR 7.78 for 2 passes; OR 6.10 for 3 passes; OR 6.57 for 4 passes; all P <0.001). However, the functional outcomes of patients with ≥5 passes were not significantly more favorable than found among patients without recanalization (OR 1.70 with 95% CI, 0.42–6.90 for 5 passes, P =0.455; OR 0.33 with 0.02–5.70, P =0.445 for ≥6 passes). Conclusions— The likelihood of successful recanalization got sequentially lower as the number of SR passes increased. Five or more passes of the SR became futile in terms of the recanalization rate and functional outcomes.

Background and Purpose— Based on its mechanism, the use of balloon guide catheters (BGCs) may be beneficial during endovascular treatment, regardless of the type of mechanical recanalization modality used—stent retriever thrombectomy or thrombaspiration. We evaluated whether the use of BGCs can be beneficial regardless of the first-line mechanical endovascular modality used. Methods— We retrospectively reviewed consecutive acute stroke patients who underwent stent retriever thrombectomy or thrombaspiration from the prospectively maintained registries of 17 stroke centers nationwide. Patients were assigned to the BGC or non-BGC group based on the use of BGCs during procedures. Endovascular and clinical outcomes were compared between the BGC and non-BGC groups. To adjust the influence of the type of first-line endovascular modality on successful recanalization and favorable outcome, multivariable analyses were also performed. Results— This study included a total of 955 patients. Stent retriever thrombectomy was used as the first-line modality in 526 patients (55.1%) and thrombaspiration in 429 (44.9%). BGC was used in 516 patients (54.0%; 61.2% of stent retriever thrombectomy patients; 45.2% of thrombaspiration patients). The successful recanalization rate was significantly higher in the BGC group compared with the non-BGC group (86.8% versus 74.7%, respectively; P <0.001). Furthermore, the first-pass recanalization rate was more frequent (37.0% versus 14.1%; P <0.001), and the number of device passes was fewer in the BGC group (2.5±1.9 versus 3.3±2.1; P <0.001). The procedural time was also shorter in the BGC group (54.3±27.4 versus 67.6±38.2; P <0.001). The use of BGC was an independent factor for successful recanalization (odds ratio, 2.18; 95% CI, 1.54–3.10; P <0.001) irrespective of the type of first-line endovascular modality used. The use of BGC was also an independent factor for a favorable outcome (odds ratio, 1.40; 95% CI, 1.02–1.92; P =0.038) irrespective of the type of first-line endovascular modality used. Conclusions— Regardless of the first-line mechanical endovascular modality used, the use of BGC in endovascular treatment was beneficial in terms of both recanalization success and functional outcome.

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We report here a stereodivergent method for the Michael addition of aryl acetic acid esters to α,β-unsaturated aldehydes catalyzed by a combination of a chiral pyrrolidine and a chiral Lewis base. This reaction proceeds through a synergistic catalytic cycle which consists of one cycle leading to a chiral iminium electrophile and a second cycle generating a nucleophilic chiral enolate for the construction of a carbon−carbon bond. By varying the combinations of catalyst enantiomers, all four stereoisomers of the products with two vicinal stereocenters are accessible with high enantio-and diastereoselectivity. The products of the Michael addition, 1,5-aldehyde esters, can be readily transformed into a variety of other valuable enantioenriched structures, including those bearing three contiguous stereocenters in an acyclic system, thus providing an efficient route to an array of structural and stereochemical diversity.

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