Patient involvement in assessment of postgraduate medical learners: A scoping review.

CONTEXT: Competency-based assessment of learners may benefit from a more holistic, inclusive, approach for determining readiness for unsupervised practice. However, despite movements towards greater patient partnership in health care generally, inclusion of patients in postgraduate medical learners' assessment is largely absent. METHODS: We conducted a scoping review to map the nature, extent and range of literature examining the inclusion (or exclusion) of patients within the assessment of postgraduate medical learners. Guided by Arskey and O'Malley's framework and informed by Levac et al. and Thomas et al., we searched two databases (MEDLINE® and Embase®) from inception until February 2021 using subheadings related to assessment, patients and postgraduate learners. Data analysis examined characteristics regarding the nature and factor influencing patient involvement in assessment. RESULTS: We identified 41 papers spanning four decades. Some literature suggests patients are willing to be engaged in assessment, however choose not to engage when, for example, language barriers may exist. When stratified by specialty or clinical setting, the influence of factors such as gender, race, ethnicity or medical condition seems to remain consistent. Patients may participate in assessment as a stand-alone group or part of a multi-source feedback process. Patients generally provided high ratings but commented on the observed professional behaviours and communication skills in comparison with physicians who focused on medical expertise. CONCLUSION: Factors that influence patient involvement in assessment are multifactorial including patients' willingness themselves, language and reading-comprehension challenges and available resources for training programmes to facilitate the integration of patient assessments. These barriers however are not insurmountable. While understudied, research examining patient involvement in assessment is increasing; however, our review suggests that the extent which the unique insights will be taken up in postgraduate medical education may be dependent on assessment systems readiness and, in particular, physician readiness to partner with patients in this way.

Mesenchymal Stromal Cell-derived Extracellular Vesicles in Preclinical Animal Models of Tumor Growth: Systematic Review and Meta-analysis.

BACKGROUND: Mesenchymal stromal cell derived extracellular vesicles (MSC-EVs) have been implicated in the regulation of tumor growth. Studies remain preclinical with effects ranging from inhibition of tumor growth to cancer progression. A systematic review and meta-analysis is needed to clarify the effect of MSC-EVs on tumor growth to facilitate potential translation to clinical trials. METHODS: A systematic search of the literature (MEDLINE, Embase, and BIOSIS databases to June 1, 2019) identified all pre-clinical controlled studies investigating the effect of MSC-EVs on tumor growth. Study selection and data extraction were performed in duplicate. Potential risk of bias was assessed using the SYRCLE tool. A random effects meta-analysis of reduction in tumor weight/volume (primary outcome) was performed. RESULTS: We identified 29 articles and 22 reported data on tumor responses that were included for meta-analysis. Studies were associated with unclear risk of bias in a large proportion of domains in accordance with the SYRCLE tool for determining risk of bias in preclinical studies. A high risk of bias was not identified in any study. MSC-EVs had a mixed response on tumor progression with some studies reporting inhibition of tumor growth and others reporting tumor progression. Overall, MSC-EVs exerted a non-significant reduction in tumor growth compared to controls (standardized mean difference (SMD) -0.80, 95 % CI -1.64 to 0.03, p = 0.06, I2 = 87 %). Some studies reported increased tumor growth which aligned with their stated hypothesis and some interrogated mechanisms in cancer biology. EVs isolated from MSCs that overexpressed anti-tumor RNAs were associated with significant tumor reduction in meta-analysis (SMD - 2.40, 95 % CI -3.36 to -1.44, p < 0.001). Heterogeneity between studies was observed and included aspects of study design such as enrichment of MSC-EVs with specific anti-tumor molecules, tissue source of MSCs, method of EV isolation, characterization of MSCs and EVs, dosage and administration schedules, and tissue type and source of tumor cells studied. CONCLUSIONS: MSC-EVs are associated with mixed effects on tumor growth in animal models of cancer. In studies where anti-tumor RNAs are packaged in EVs, a significant reduction in tumor growth was observed. Reducing heterogeneity in study design may accelerate our understanding of the potential effects of MSC-EVs on cancer. [274 words] Forest plot of MSC-EV effect on tumor growth accordinggenetic modification of EVs in animal studies identified from a systematicreview of the literature. All cohorts from studies with multiple interventiongroups are presented separately with control groups divided equally among thegroups. M, modified; H, hypoxia.

Preclinical Studies of MSC-Derived Extracellular Vesicles to Treat or Prevent Graft Versus Host Disease: a Systematic Review of the Literature.

INTRODUCTION: Treating and preventing graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplant (HCT) remains a significant challenge. The use of mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) appears promising and a systematic review of preclinical studies is needed to accelerate the design of translational studies. METHODS: We identified 4 eligible studies from a systematic review performed on December 1, 2018. In brief, eligible studies included the treatment or prevention of GVHD in animal models and the use of MSC-EVs. Study design and outcome data were extracted and reporting was evaluated using the SYRCLE tool to identify potential bias. RESULTS: Two studies assessed the efficacy of MSC-EVs in treatment of GVHD and 2 studies address prevention. Mice treated with MSC-EVs showed improved median survival, GVHD clinical scores and histology scores as compared to untreated mice with GVHD. Prophylactic treatment with MSC-EVs attenuated GVHD severity and improved median survival as compared to no treatment or saline. CONCLUSION: Our systematic review provides important insight regarding the potential of MSC-EVs to treat or prevent GVHD. Although few studies were identified, improved survival and attenuated histologic findings of GVHD were observed in mice after MSC-EV administration for the treatment and prevention of GVHD. Dosing of EVs and route of administration remain inconsistent, however, and scalability of EV isolation for clinical studies remains a challenge. Standardized outcome reporting is needed to pool results for metanalysis. Graphical abstract.

Exploiting mitochondrial and oxidative vulnerabilities with a synthetic analog of pancratistatin in combination with piperlongumine for cancer therapy.

Harsh adverse effects as a result of nonspecific targeting of chemotherapeutics currently pose obstacles in cancer therapy; thus, it would be invaluable to devise novel approaches to specifically target cancer cells. The natural compound pancratistatin (PST) has been shown to preferentially induce apoptosis in a variety of cancer cell types. Recently, several analogs of PST were shown to be efficacious in inducing apoptosis in a variety of aggressive cancer cell types via cancer cell mitochondrial targeting; it caused dissipation of mitochondrial membrane potential and decreased oxygen consumption, and with isolated mitochondria, it induced the release of apoptogenic factors. The natural compound piperlongumine has been shown to target the stress response to reactive oxygen species in cancer cells. We explored the combinatorial potential of two small molecules (SVTH-6 and piperlongumine) that target these vulnerabilities in cancer cells. Interestingly, when combined with the PST analog, SVTH-6, an increase in mitochondrial dysfunction was observed, leading to an enhanced cytotoxic effect against several human cancer cell types. Additionally, this combination treatment was effective in reducing cancer cell growth in physiologically more relevant 3-dimensional spheroid cell cultures. This enhanced effect was found to be dependent on reactive oxygen species generation because an antioxidant could rescue cancer cells from this combination treatment. Importantly, noncancerous cells were markedly less sensitive to this combination treatment. Thus, targeting mitochondrial and oxidative stress vulnerabilities of cancer cells could be an effective strategy for cancer therapy.-Ma, D., Gilbert, T., Pignanelli, C., Tarade, D., Noel, M., Mansour, F., Gupta, M., Ma, S., Ropat, J., Curran, C., Vshyvenko, S., Hudlicky, T., Pandey. S. Exploiting mitochondrial and oxidative vulnerabilities with a synthetic analog of pancratistatin in combination with piperlongumine for cancer therapy.

Assessing the impact of irrigation treatments on thiram residual trends: correspondence with numerical modelling and field-scale experiments.

The present study was undertaken to study the trends of transport of thiram, a dithiocarbamate pesticide, at different time and depth in the fields under real field conditions for wheat crop. Numerical simulations were carried out by solving the coupled soil-water content movement and mass transport equations using HYDRUS- 1D. The supplementary data used for paramaterization of HYDRUS-1D comprise of irrigation treatments, climatic conditions, and soil characteristics. Results focus on the effects and influence of irrigation treatments on pesticide persistence and mobility. Modelling results were in good agreement with the experimentally determined thiram concentrations. Application of the model to measured field data of thiram movement indicates that the modelling approach can provide reliable and useful estimates of the mass flux of water and non-volatile pesticide in vadose zone. For policy-makers and planners, some regulation strategies are suggested for controlling inappropriate pesticide application under deficit irrigation or rain-fed conditions.