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INTRODUCTION: Uncertainty is an inevitable part of medical practice. An ability to tolerate uncertainty is viewed as a key competency across many health-care systems. Poor uncertainty tolerance (UT) has been linked to negative outcomes including reduced psychological well-being in medical students. A variety of medical education interventions have been developed with the intention of increasing medical students' UT. However, there is no synthesis of these studies available to inform education and research practice. Our aim was to conduct a scoping review of medical education interventions that evaluate their impact on UT. METHODS: Medline, PsycInfo, Embase and ERIC databases were searched for articles published from inception to December 2020. An extensive supplementary search was conducted and both quantitative and qualitative evaluations were included. For each intervention, we categorised the stimulus of uncertainty (ambiguity, complexity and/or probability) and mapped the students' reported cognitive, behavioural, and/or emotional response(s) to uncertainty onto an existing conceptual framework. RESULTS: Twenty-two of 24 included studies reported a positive impact on medical student UT in at least one domain (cognitive, behavioural or emotional). Interventions included problem based learning-based curricula, medical humanities, simulation, reflection and assessment. We found in four studies that a negative response in the emotional domain was reported despite positive responses also being reported in the cognitive and/or behavioural domains. CONCLUSION: We identified a range of medical education interventions which report a positive impact on medical student UT. Further research is required to understand why a single intervention may stimulate a negative emotional response alongside a positive cognitive or behavioural response. In turn, this could support stakeholders such as policymakers and institutions to adapt the medical curriculum to better prepare their medical students for practice by enhancing their UT.

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Recent advances in three-dimensional (3-D) printing offer an excellent opportunity to address critical challenges faced by current tissue engineering approaches. Alginate hydrogels have been used extensively as bioinks for 3-D bioprinting. However, most previous research has focused on native alginates with limited degradation. The application of oxidized alginates with controlled degradation in bioprinting has not been explored. Here, a collection of 30 different alginate hydrogels with varied oxidation percentages and concentrations was prepared to develop a bioink platform that can be applied to a multitude of tissue engineering applications. The authors systematically investigated the effects of two key material properties (i.e. viscosity and density) of alginate solutions on their printabilities to identify a suitable range of material properties of alginates to be applied to bioprinting. Further, four alginate solutions with varied biodegradability were printed with human adipose-derived stem cells (hADSCs) into lattice-structured, cell-laden hydrogels with high accuracy. Notably, these alginate-based bioinks were shown to be capable of modulating proliferation and spreading of hADSCs without affecting the structure integrity of the lattice structures (except the highly degradable one) after 8days in culture. This research lays a foundation for the development of alginate-based bioink for tissue-specific tissue engineering applications.

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Current chemotherapy treatments are limited by poor drug solubility, rapid drug clearance and systemic side effects. Additionally, drug penetration into solid tumors is limited by physical diffusion barriers [e.g., extracellular matrix (ECM)]. Nanoparticle (NP) blood circulation half-life, biodistribution and ability to cross extracellular and cellular barriers will be dictated by NP composition, size, shape and surface functionality. Here, we investigated the effect of surface charge of poly(lactide)-poly(ethylene glycol) NPs on mediating cellular interaction. Polymeric NPs of equal sizes were used that had two different surface functionalities: negatively charged carboxyl (COOH) and neutral charged methoxy (OCH3). Cellular uptake studies showed significantly higher uptake in human brain cancer cells compared to noncancerous human brain cells, and negatively charged COOH NPs were uptaken more than neutral OCH3 NPs in 2D culture. NPs were also able to load and control the release of paclitaxel (PTX) over 19 days. Toxicity studies in U-87 glioblastoma cells showed that PTX-loaded NPs were effective drug delivery vehicles. Effect of surface charge on NP interaction with the ECM was investigated using collagen in a 3D cellular uptake model, as collagen content varies with the type of cancer and the stage of the disease compared to normal tissues. Results demonstrated that NPs can effectively diffuse across an ECM barrier and into cells, but NP mobility is dictated by surface charge. In vivo biodistribution of OCH3 NPs in intracranial tumor xenografts showed that NPs more easily accumulated in tumors with less collagen. These results indicate that a robust understanding of NP interaction with various tumor environments can lead to more effective patient-tailored therapies.

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It is important to determine the enabling mechanisms that underlie locomotor performance to explain the evolutionary patterns and ecological success of animals. Our aim was to determine the extent to which calcium (Ca(2+)) handling dynamics modulate the contractile properties of isolated skeletal muscle, and whether the effects of changing Ca(2+) handling dynamics in skeletal muscle are paralleled by changes in whole-animal sprint and sustained swimming performance. Carp (Cyprinus carpio) increased swimming speed by concomitant increases in tail-beat amplitude and frequency. Reducing Ca(2+) release from the sarcoplasmic reticulum (SR) by blocking ryanodine receptors with dantrolene decreased isolated peak muscle force and was paralleled by a decrease in tail-beat frequency and whole-animal sprint performance. An increase in fatigue resistance following dantrolene treatment may reflect the reduced depletion of Ca(2+) stores in the SR associated with lower ryanodine receptor (RyR) activity. Blocking RyRs may be detrimental by reducing force production and beneficial by reducing SR Ca(2+) depletion so that there was no net effect on critical sustained swimming speed (U(crit)). In isolated muscle, there was no negative effect on force production of blocking Ca(2+) release via dihydropyridine receptors (DHPRs) with nifedipine. Nifedipine decreased fatigue resistance of isolated muscle, which was paralleled by decreases in tail-beat frequency and U(crit). However, sprint performance also decreased with DHPR inhibition, which may indicate a role in muscle contraction of the Ca(2+) released by DHPR into the myocyte. Inhibiting sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) activity with thapsigargin decreased fatigue resistance, suggesting that SERCA activity is important in avoiding Ca(2+) store depletion and fatigue. We have shown that different molecular mechanisms modulate the same muscle and whole-animal traits, which provides an explanatory model for the observed variations in locomotor performance within and between species.

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