Pre-hospital stroke screening and notification of patients with reperfusion-eligible acute ischaemic stroke using modified Face Arm Speech Time test.

OBJECTIVES: To investigate the effects of pre-hospital stroke screening and notification on reperfusion therapy for patients with acute ischaemic stroke. METHODS: Pre-hospital stroke screening criteria were established based on a modified version of the Face Arm Speech Time (FAST) test. Screening was performed during ambulance transport by emergency medical service (EMS) personnel who completed a 2-hour training session on stroke screening. Temporal trends affecting acute ischaemic stroke investigation and intervention were compared before and after implementation of the pre-hospital screening. RESULTS: From July 2018 to October 2019, 298 patients with suspected stroke were screened by EMS personnel during ambulance transport prior to hospital arrival. Of these 298 patients, 213 fulfilled the screening criteria, 166 were diagnosed with acute stroke, and 32 received reperfusion therapy. The onset-to-door time was shortened by more than 1.5 hours (100.6 min vs 197.6 min, P<0.001). The door-to-computed tomography time (25.6 min vs 32.0 min, P=0.021), door-to-needle time (49.2 min vs 70.1 min, P=0.003), and door-to-groin puncture time for intra-arterial mechanical thrombectomy (126.7 min vs 168.6 min, P=0.04) were significantly shortened after implementation of the pre-hospital screening and notification, compared with historical control data of patients admitted from January 2018 to June 2018, before implementation of the screening system. CONCLUSION: Implementation of pre-hospital stroke screening using criteria based on a modified version of the FAST test, together with pre-arrival notification, significantly shortened the door-to-reperfusion therapy time for patients with ischaemic stroke. Pre-hospital stroke screening during ambulance transport by EMS personnel who complete a 2-hour focused training session is effective for identifying reperfusion-eligible patients with stroke.

The small molecule indirubin-3'-oxime activates Wnt/ß-catenin signaling and inhibits adipocyte differentiation and obesity.

OBJECTIVES: Activation of the Wnt/ß-catenin signaling pathway inhibits adipogenesis by maintaining preadipocytes in an undifferentiated state. We investigated the effect of indirubin-3'-oxime (I3O), which was screened as an activator of the Wnt/ß-catenin signaling, on inhibiting the preadipocyte differentiation in vitro and in vivo. METHODS: 3T3L1 preadipocytes were differentiated with 0, 4 or 20 µM of I3O. The I3O effect on adipocyte differentiation was observed by Oil-red-O staining. Activation of Wnt/ß-catenin signaling in I3O-treated 3T3L1 cells was shown using immunocytochemical and immunoblotting analyses for ß-catenin. The regulation of adipogenic markers was analyzed via real-time reverse transcription-PCR (RT-PCR) and immunoblotting analyses. For the in vivo study, mice were divided into five different dietary groups: chow diet, high-fat diet (HFD), HFD supplemented with I3O at 5, 25 and 100 mg kg(-1). After 8 weeks, adipose and liver tissues were excised from the mice and subject to morphometry, real-time RT-PCR, immunoblotting and histological or immunohistochemical analyses. In addition, adipokine and insulin concentrations in serum of the mice were accessed by enzyme-linked immunosorbent assay. RESULTS: Using a cell-based approach to screen a library of pharmacologically active small molecules, we identified I3O as a Wnt/ß-catenin pathway activator. I3O inhibited the differentiation of 3T3-L1 cells into mature adipocytes and decreased the expression of adipocyte markers, CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor γ, at both mRNA and protein levels. In vivo, I3O inhibited the development of obesity in HFD-fed mice by attenuating HFD-induced body weight gain and visceral fat accumulation without showing any significant toxicity. Factors associated with metabolic disorders such as hyperlipidemia and hyperglycemia were also improved by treatment of I3O. CONCLUSION: Activation of the Wnt/ß-catenin signaling pathway can be used as a therapeutic strategy for the treatment of obesity and metabolic syndrome and implicates I3O as a candidate anti-obesity agent.