Taking the next step: How student reflective essays about difficult clinical encounters demonstrate professional identity formation.

BACKGROUND: Difficult clinical encounters pose emotional and behavioural challenges for medical students. Unless resolved, they threaten students' professional competence and well-being. Learning how to humanistically interact with patients perceived as "difficult" is an important component of the developmental process that underlies professional identity formation (PIF). METHODS: This study used thematic analysis to examine reflective essay data from the same set of students (N = 69), first in their third year and then in their fourth year of training at a US public medical school. Analysis focused on how student perceptions of patients', preceptors', and their own behaviour, attitudes, and emotions in difficult patient care situations evolved over time, and how such evolution contributed to their professional growth. FINDINGS: Students identified clinical predicaments influenced by their own emotions and behaviour, as well as those of patients and preceptors. In response to patients perceived as angry, rude, and uncooperative, students described themselves and their preceptors primarily as engaging in routine medical behaviours, followed by expressions of empathy. These encounters resulted in residual emotions as well as lessons learned. Fourth-year students reported more empathy, patient-centeredness, and patient ownership than third-year students. While student-physicians grew in professionalism and compassion, they also noted unresolved distressing emotions post-encounter. CONCLUSIONS: From third to fourth year, medical students undergo a process of professional growth that can be documented at a granular level through their perceptions of themselves, their patients, and their preceptors. Despite positive professional growth, students' lingering negative affect merits attention and support from clinical teachers.

Skeletal muscle effects of antisense oligonucleotides targeting glycogen synthase 1 in a mouse model of Pompe disease.

Pompe disease (PD) is a progressive myopathy caused by the aberrant accumulation of glycogen in skeletal and cardiac muscle resulting from the deficiency of the enzyme acid alpha-glucosidase (GAA). Administration of recombinant human GAA as enzyme replacement therapy (ERT) works well in alleviating the cardiac manifestations of PD but loses sustained benefit in ameliorating the skeletal muscle pathology. The limited efficacy of ERT in skeletal muscle is partially attributable to its inability to curb the accumulation of new glycogen produced by the muscle enzyme glycogen synthase 1 (GYS1). Substrate reduction therapies aimed at knocking down GYS1 expression represent a promising avenue to improve Pompe myopathy. However, finding specific inhibitors for GYS1 is challenging given the presence of the highly homologous GYS2 in the liver. Antisense oligonucleotides (ASOs) are chemically modified oligomers that hybridize to their complementary target RNA to induce their degradation with exquisite specificity. In the present study, we show that ASO-mediated Gys1 knockdown in the Gaa -/- mouse model of PD led to a robust reduction in glycogen accumulation in skeletal and cardiac muscle. In addition, combining Gys1 ASO with ERT further reduced glycogen content in muscle, eliminated autophagic buildup and lysosomal dysfunction, and improved motor function in Gaa -/- mice. Our results provide a strong foundation for further validation of the use of Gys1 ASO, alone or in combination with ERT, as a therapy for PD. We propose that early administration of Gys1 ASO in combination with ERT may be the key to preventative treatment options in PD.