Acting on Reflection: the Effect of Reflection on Students’ Clinical Performance on a Standardized Patient Examination

BACKGROUND: Little evidence exists to support the value of reflection in the clinical setting. OBJECTIVE: To determine whether reflecting and revisiting the “patient” during a standardized patient (SP) examination improves junior medical students’ performance and to analyze students’ perceptions of its value. DESIGN: Students completed a six-encounter clinical skills examination, writing a guided assessment after each encounter to trigger reflection. SPs evaluated the students with Medical Skills and Patient Satisfaction checklists. During the last three encounters, students could opt to revisit the SP and be reevaluated with identical checklists. PARTICIPANTS: One hundred and forty-nine third year medical students. MEASUREMENTS: Changes in scores in the Medical Skills and Patient Satisfaction checklists between first visit and revisit were tested separately per case as well as across cases. RESULTS: On the medical skills and patient satisfaction checklists, mean revisit scores across cases were significantly higher than mean first visit scores [12.6 vs 12.2 (pooled SD = 2.4), P = .0001; 31.2 vs 31.0 (pooled SD = 3.5), P = .0001)]. Sixty-five percent of the time, students rated “reflect–revisit” positively, 34% neutrally, and 0.4% negatively. Five themes were identified in the positive comments: enhancement of (1) medical decision making, (2) patient education/counseling, (3) student satisfaction/confidence, (4) patient satisfaction/confidence, and (5) clinical realism. CONCLUSIONS: Offering third year medical students the option to reflect and revisit an SP during a clinical skills examination produced a small but nontrivial increase in clinical performance. Students perceived the reflect–revisit experience as enhancing patient-centered practices (counseling, education) as well as their own medical decision making and clinical confidence

The Role of ZSCAN4 in Cancer Stemness

Cancer stem cells (CSCs) represent a subset of cells within tumors that maintain the ability to self-renew, drive tumor heterogeneity, and contribute to therapeutic resistance and cancer recurrence. Over the past decade, embryonic factors have emerged as key regulators of cancer stemness and as therapeutic targets. Zscan4 is an early embryonic gene expressed in mouse embryonic and induced pluripotent stem cells where it plays critical roles in genomic stability, telomere maintenance, and pluripotency. Like other embryonic factors, ZSCAN4 is reactivated in cancer. In these studies, we define for the first time the role of ZSCAN4 in human CSCs of head and neck squamous cell carcinoma (HNSCC). We find that ZSCAN4 is enriched for in and marks the HNSCC CSC population. Induction of ZSCAN4 promotes the CSC phenotype, increases CSC factors and alters the epigenetic profile. Importantly, extreme limiting dilution analyses both in vitro and in vivo indicate that ZSCAN4 induction significantly increases the frequency of CSC. Consistently, ZSCAN4 depletion leads to loss of the CSC phenotype including CSC marker expression, the ability to form spheroids in non-adherent culture conditions, and hypersensitivity to genotoxic drugs. Furthermore, loss of ZSCAN4 severely impairs tumor growth in vivo. As our findings indicated that ZSCAN4 promotes the CSC phenotype, we next chose to study its regulation and turnover in cancer cells. Expression of Zscan4 is transient, and characterized by infrequent high expression peaks that are quickly down-regulated, suggesting its expression is tightly controlled. However, little is known about the protein degradation pathway responsible for regulating the human ZSCAN4 protein levels. We first determined the protein half-life of ZSCAN4 and elucidated the role of the ubiquitin proteasome system in ZSCAN4 degradation. Importantly, our data indicate an interaction between ZSCAN4 and the E3 ubiquitin ligase RNF20. RNF20 depletion stabilizes the ZSCAN4 protein half-life, suggesting that RNF20 negatively regulates ZSCAN4 stability. Due to the crucial cellular functions of ZSCAN4, these results have important implications in telomere regulation, stem cell biology, and cancer. Overall, our study suggests that ZSCAN4 plays a critical role in maintaining the undifferentiated state and survival of CSCs, indicating that ZSCAN4 is a potential therapeutic target in HNSCC

Harvesting multipotent progenitor cells from a small sample of tonsillar biopsy for clinical applications

Abstract Background Human adult stem cells hold the potential for the cure of numerous conditions and degenerative diseases. They possess major advantages over pluripotent stem cells as they can be derived from donors at any age, and therefore pose no ethical concerns or risk of teratoma tumor formation in vivo. Furthermore, they have a natural ability to differentiate and secrete factors that promote tissue healing without genetic manipulation. However, at present, clinical applications of adult stem cells are limited by a shortage of a reliable, standardized, and easily accessible tissue source which does not rely on specimens discarded from unrelated surgical procedures. Method Human tonsil-derived mesenchymal progenitor cells (MPCs) were isolated from a small sample of tonsillar tissue (average 0.88 cm3). Our novel procedure poses a minimal mechanical and enzymatic insult to the tissue, and therefore leads to high cell viability and yield. We characterized these MPCs and demonstrated robust multipotency in vitro. We further show that these cells can be propagated and maintained in xeno-free conditions. Results We have generated tonsillar biopsy-derived MPC (T-MPC) lines from multiple donors across a spectrum of age, sex, and race, and successfully expanded them in culture. We characterized them by cell surface markers, as well as in vitro expansion and differentiation potential. Our procedure provides a robust yield of tonsillar biopsy-derived T-MPCs. Conclusions Millions of MPCs can be harvested from a sample smaller than 1 g, which can be collected from a fully awake donor in an outpatient setting without the need for general anesthesia or hospitalization. Our study identifies tonsillar biopsy as an abundant source of adult MPCs for regenerative medicine