Biomedical students' satisfaction with and engagement in laboratory e-learning support are related to their self-regulation.

Laboratory e-learning support tools can assist students' learning while preparing for laboratory classes. To successfully work in such virtual experimental environments (VEEs) outside class, students require self-regulated learning (SRL) skills. A deeper understanding of the continuous reciprocal interactions between SRL, satisfaction, and online engagement is needed to develop more effective online learning experiences. This study therefore aimed to explore the interconnection between students' satisfaction with, effort/importance and engagement in an exemplary VEE, and to relate this to their perceived SRL and learning outcomes. Based on surveys in 79 university students, SRL was related to VEE engagement, effort/importance, and satisfaction. VEE engagement and satisfaction were not related to learning outcomes, while SRL and effort were. Students with different SRL also tended to interact differently with the VEE and experienced differing degrees of procedural and feedback support by the e-environment. We conclude that, for optimal learning experience and outcomes, students' effort regulation and SRL need to be supported while interacting with the VEE, preferably by interventions that integrate personalized and adaptive features. This study has implications for designing and optimizing VEEs and indicates that future research should focus on VEEs taking students' SRL and effort regulation into account to support individual learners effectively.

Exendin-4 decreases liver inflammation and atherosclerosis development simultaneously by reducing macrophage infiltration.

BACKGROUND AND PURPOSE: The aetiology of inflammation in the liver and vessel wall, leading to non-alcoholic steatohepatitis (NASH) and atherosclerosis, respectively, shares common mechanisms including macrophage infiltration. To treat both disorders simultaneously, it is highly important to tackle the inflammatory status. Exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist, reduces hepatic steatosis and has been suggested to reduce atherosclerosis; however, its effects on liver inflammation are underexplored. Here, we tested the hypothesis that exendin-4 reduces inflammation in both the liver and vessel wall, and investigated the common underlying mechanism. EXPERIMENTAL APPROACH: Female APOE*3-Leiden.CETP mice, a model with human-like lipoprotein metabolism, were fed a cholesterol-containing Western-type diet for 5 weeks to induce atherosclerosis and subsequently treated for 4 weeks with exendin-4. KEY RESULTS: Exendin-4 modestly improved dyslipidaemia, but markedly decreased atherosclerotic lesion severity and area (-33%), accompanied by a reduction in monocyte adhesion to the vessel wall (-42%) and macrophage content in the plaque (-44%). Furthermore, exendin-4 reduced hepatic lipid content and inflammation as well as hepatic CD68⁺ (-18%) and F4/80⁺ (-25%) macrophage content. This was accompanied by less monocyte recruitment from the circulation as the Mac-1⁺ macrophage content was decreased (-36%). Finally, exendin-4 reduced hepatic chemokine expression in vivo and suppressed oxidized low-density lipoprotein accumulation in peritoneal macrophages in vitro, effects dependent on the GLP-1 receptor. CONCLUSIONS AND IMPLICATIONS: Exendin-4 reduces inflammation in both the liver and vessel wall by reducing macrophage recruitment and activation. These data suggest that exendin-4 could be a valuable strategy to treat NASH and atherosclerosis simultaneously.

The insulin sensitizing effect of topiramate involves KATP channel activation in the central nervous system.

BACKGROUND AND PURPOSE: Topiramate improves insulin sensitivity, in addition to its antiepileptic action. However, the underlying mechanism is unknown. Therefore, the present study was aimed at investigating the mechanism of the insulin-sensitizing effect of topiramate both in vivo and in vitro. EXPERIMENTAL APPROACH: Male C57Bl/6J mice were fed a run-in high-fat diet for 6 weeks, before receiving topiramate or vehicle mixed in high-fat diet for an additional 6 weeks. Insulin sensitivity was assessed by hyperinsulinaemic-euglycaemic clamp. The extent to which the insulin sensitizing effects of topiramate were mediated through the CNS were determined by concomitant i.c.v. infusion of vehicle or tolbutamide, an inhibitor of ATP-sensitive potassium channels in neurons. The direct effects of topiramate on insulin signalling and glucose uptake were assessed in vivo and in cultured muscle cells. KEY RESULTS: In hyperinsulinaemic-euglycaemic clamp conditions, therapeutic plasma concentrations of topiramate (∼4 µg·mL(-1) ) improved insulin sensitivity (glucose infusion rate + 58%). Using 2-deoxy-D-[(3) H]glucose, we established that topiramate improved the insulin-mediated glucose uptake by heart (+92%), muscle (+116%) and adipose tissue (+586%). Upon i.c.v. tolbutamide, the insulin-sensitizing effect of topiramate was completely abrogated. Topiramate did not directly affect glucose uptake or insulin signalling neither in vivo nor in cultured muscle cells. CONCLUSION AND IMPLICATIONS: In conclusion, topiramate stimulates insulin-mediated glucose uptake in vivo through the CNS. These observations illustrate the possibility of pharmacological modulation of peripheral insulin resistance through a target in the CNS.