The Efficacy and Safety of Moderate-Intensity Rosuvastatin with Ezetimibe versus High-Intensity Rosuvastatin in High Atherosclerotic Cardiovascular Disease Risk Patients with Type 2 Diabetes Mellitus: A Randomized, Multicenter, Open, Parallel, Phase 4 Study.

BACKGRUOUND: To investigate the efficacy and safety of moderate-intensity rosuvastatin/ezetimibe combination compared to highintensity rosuvastatin in high atherosclerotic cardiovascular disease (ASCVD) risk patients with type 2 diabetes mellitus (T2DM). METHODS: This study was a randomized, multicenter, open, parallel phase 4 study, and enrolled T2DM subjects with an estimated 10-year ASCVD risk ≥7.5%. The primary endpoint was the low-density lipoprotein cholesterol (LDL-C) change rate after 24-week rosuvastatin 10 mg/ezetimibe 10 mg treatment was non-inferior to that of rosuvastatin 20 mg. The achievement proportion of 10-year ASCVD risk <7.5% or comprehensive lipid target (LDL-C <70 mg/dL, non-high-density lipoprotein cholesterol <100 mg/dL, and apolipoprotein B <80 mg/dL) without discontinuation, and several metabolic parameters were explored as secondary endpoints. RESULTS: A hundred and six participants were assigned to each group. Both groups showed significant reduction in % change of LDL-C from baseline at week 24 (-63.90±6.89 vs. -55.44±6.85, combination vs. monotherapy, p=0.0378; respectively), but the combination treatment was superior to high-intensity monotherapy in LDL-C change (%) from baseline (least square [LS] mean difference, -8.47; 95% confidence interval, -16.44 to -0.49; p=0.0378). The combination treatment showed a higher proportion of achieved comprehensive lipid targets rather than monotherapy (85.36% vs. 62.22% in monotherapy, p=0.015). The ezetimibe combination significantly improved homeostasis model assessment of ß-cell function even without A1c changes (LS mean difference, 17.13; p=0.0185). CONCLUSION: In high ASCVD risk patients with T2DM, the combination of moderate-intensity rosuvastatin and ezetimibe was not only non-inferior but also superior to improving dyslipidemia with additional benefits compared to high-intensity rosuvastatin monotherapy.

Optimal location selection for the installation of urban green roofs considering honeybee habitats along with socio-economic and environmental effects.

This study proposes a new framework for the selection of optimal locations for green roofs to achieve a sustainable urban ecosystem. The proposed framework selects building sites that can maximize the benefits of green roofs, based not only on the socio-economic and environmental benefits to urban residents, but also on the provision of urban foraging sites for honeybees. The framework comprises three steps. First, building candidates for green roofs are selected considering the building type. Second, the selected building candidates are ranked in terms of their expected socio-economic and environmental effects. The benefits of green roofs are improved energy efficiency and air quality, reduction of urban flood risk and infrastructure improvement costs, reuse of storm water, and creation of space for education and leisure. Furthermore, the estimated cost of installing green roofs is also considered. We employ spatial data to determine the expected effects of green roofs on each building unit, because the benefits and costs may vary depending on the location of the building. This is due to the heterogeneous spatial conditions. In the third step, the final building sites are proposed by solving the maximal covering location problem (MCLP) to determine the optimal locations for green roofs as urban honeybee foraging sites. As an illustrative example, we apply the proposed framework in Seoul, Korea. This new framework is expected to contribute to sustainable urban ecosystems.

Three-dimensional brain-on-a-chip with an interstitial level of flow and its application as an in vitro model of Alzheimer's disease.

There has been a growing need for in vitro models of neurodegenerative diseases such as Alzheimer's disease that would enable a better understanding of etiology and faster development of treatment strategies. However, meeting this demand has been held back by the limited ability to mimic the in vivo microenvironment in an in vitro system. Here, we developed a microfluidic chip based on three-dimensional (3D) neurospheroids that more closely mimics the in vivo brain microenvironment by providing a constant flow of fluid that is readily observed in the interstitial space of the brain. Uniform neurospheroids, with cell-cell interactions and contacts in all directions, were formed in concave microwell arrays, and a slow interstitial level of flow was maintained using an osmotic micropump system. Using this platform, we investigated the effect of flow on neurospheroid size, neural network, and neural differentiation. Neurospheroids cultured with flow were larger and formed more robust and complex neural networks than those cultured under static conditions, suggesting an effect of the interstitial level of slow and diffusion-dominant flow on continuous nutrient, oxygen, and cytokine transport and removal of metabolic wastes. We also tested the toxic effects of amyloid-ß, which is generally considered to be the major contributor in Alzheimer's disease. Amyloid-ß treatment via an osmotic micropump significantly reduced the viability of neurospheroids and caused a significantly more destruction of neural networks, compared to the amyloid-ß treatment under static conditions. By adding in vivo-like microenvironments, we propose this 3D culture-based microfluidic chip as an in vitro brain model for neurodegenerative disease and high-throughput drug screening.