Cryptic splicing events in the iron transporter ABCB7 and other key target genes in SF3B1-mutant myelodysplastic syndromes.

The splicing factor SF3B1 is the most frequently mutated gene in myelodysplastic syndromes (MDS), and is strongly associated with the presence of ring sideroblasts (RS). We have performed a systematic analysis of cryptic splicing abnormalities from RNA sequencing data on hematopoietic stem cells (HSCs) of SF3B1-mutant MDS cases with RS. Aberrant splicing events in many downstream target genes were identified and cryptic 3' splice site usage was a frequent event in SF3B1-mutant MDS. The iron transporter ABCB7 is a well-recognized candidate gene showing marked downregulation in MDS with RS. Our analysis unveiled aberrant ABCB7 splicing, due to usage of an alternative 3' splice site in MDS patient samples, giving rise to a premature termination codon in the ABCB7 mRNA. Treatment of cultured SF3B1-mutant MDS erythroblasts and a CRISPR/Cas9-generated SF3B1-mutant cell line with the nonsense-mediated decay (NMD) inhibitor cycloheximide showed that the aberrantly spliced ABCB7 transcript is targeted by NMD. We describe cryptic splicing events in the HSCs of SF3B1-mutant MDS, and our data support a model in which NMD-induced downregulation of the iron exporter ABCB7 mRNA transcript resulting from aberrant splicing caused by mutant SF3B1 underlies the increased mitochondrial iron accumulation found in MDS patients with RS

BRIEF REPORT: Utilizing an Audiotape for Outpatient Preceptor Faculty Development

BACKGROUND: Faculty development for busy and geographically dispersed ambulatory preceptors is a difficult task for course directors. PURPOSE: A faculty development audiotape intended for playing in the preceptor's car was created. The feasibility of this form of faculty development was tested in this pilot study. METHODS: A short audiotape, focusing on strategies for the provision of independence to students in the office setting, was made and distributed to all preceptors of students taking a fourth-year required clerkship in ambulatory medicine. Preceptor behavior was reported by students on postclerkship evaluations before and after tape distribution. RESULTS: In the year before tape distribution, 21% of evaluations indicated a lack of independence on the part of the student, compared with 14% in the year following the intervention (P = .03). There was no regression of behavior among preceptors already providing independence. Among the preceptors initially identified as not following recommendations for student independence, the percentage of evaluations indicating a lack of independence went from 72% preintervention to 42% postintervention (P<.001). CONCLUSIONS: A short audiotape is a novel form of faculty development, which was acceptable to preceptors and may influence teaching behavior in the desired manner

Measuring Outcomes of a One-Minute Preceptor Faculty Development Workshop

BACKGROUND: Measuring outcomes of faculty development programs is difficult and infrequently attempted beyond measuring participant satisfaction with the program. Few studies have validated evaluation tools to assess the effectiveness of faculty development programs, and learners have rarely participated in assessing improvement of faculty who participate in such programs. OBJECTIVE: To develop a questionnaire to measure the effectiveness of an enhanced 1-minute preceptor (OMP) faculty development workshop via faculty self-assessment and resident assessment of faculty, and to use the questionnaire to assess an OMP faculty development workshop. DESIGN AND MEASUREMENTS: We developed and tested a questionnaire to assess the 5 “microskills” of a OMP faculty development program, and performed faculty self-assessment and resident assessment using the questionnaire 6 to 18 months before and 6 to 18 months after our experiential skills improvement workshop. PARTICIPANTS: Sixty-eight internal medicine continuity clinic preceptors (44 control and 24 intervention faculty) at a university, a veteran's affairs hospital, and 2 community internal medicine training sites. RESULTS: Twenty-two participants (92%) completed pre- and postintervention questionnaires. Residents completed 94 preintervention questionnaires and 58 postintervention questionnaires on participant faculty. Faculty reported improvement in behavior following the intervention. Residents reported no significant improvements in faculty teaching behaviors following the intervention. CONCLUSION: We attempted to rigorously evaluate a faculty development program based on the OMP. Although the intervention did not show statistically significant changes in teaching behavior, we believe that this study is an important step in extending assessment of faculty development to include resident evaluation of participating faculty