Development of Convergent Hybrid Phase Ligation for Efficient and Convenient Total Synthesis of Proteins.

Simple and efficient total synthesis of homogeneous and chemically modified protein samples remains a significant challenge. Here, we report development of a convergent hybrid phase native chemical ligation (CHP-NCL) strategy for facile preparation of proteins. In this strategy, proteins are split into ~100-residue blocks, and each block is assembled on solid support from synthetically accessible peptide fragments before ligated together into full-length protein in solution. With the new method, we increase the yield of CENP-A synthesis by 2.5-fold compared to the previous hybrid phase ligation approach. We further extend the new strategy to the total chemical synthesis of 212-residue linker histone H1.2 in unmodified, phosphorylated, and citrullinated forms, each from eight peptide segments with only one single purification. We demonstrate that fully synthetic H1.2 replicates the binding interactions of linker histones to intact mononucleosomes, as a proxy for the essential function of linker histones in the formation and regulation of higher order chromatin structure.

A Timely Problem: Parental Leave During Medical Training.

Shifting demographics and concerns about burnout prevention merit a reexamination of existing structures and policies related to leaves of absence that may be necessary during medical training. In this Invited Commentary, the authors address the issue of parental leave for medical students and residents. Discussion about parental leave for these trainees is not new. Despite decades of dialogue, leave policies throughout the undergraduate and graduate medical education continuum lack standardization and are currently ill defined and inadequate. There are a number of barriers to implementation. These include stigma, financial concerns, workforce and duty hours challenges, and the historically rigid timeline for progression from one stage of medical training to the next. Potential solutions include parent-friendly curricular innovations, competency-based medical education, and provision of short-term disability insurance. Most important, adopting more flexible approaches to graduation requirements and specialty board examination eligibility must be addressed at the national level. The authors identify cultural and practical challenges to standardizing parental leave options across the medical education continuum and issue a call to action for implementing potential solutions.

Sentinel Emotional Events: The Nature, Triggers, and Effects of Shame Experiences in Medical Residents.

PURPOSE: This study explores an under-investigated topic, how medical residents experience shame within clinical learning environments, by asking residents to reflect on (1) the nature of their shame experiences; (2) the events that triggered, and factors that contributed to, those shame experiences; and (3) the perceived effects of those shame experiences. METHOD: In this hermeneutic phenomenology study, the authors recruited 12 (self-nominated) residents from an internal medicine residency at a large teaching hospital in the United States. Data collection from each participant in 2016-2017 included (1) a written reflection about an experience during medical training in which the participant felt "flawed, deficient, or unworthy," and (2) a semi-structured interview that explored the participant's shame experience(s) in depth. The data were analyzed according to hermeneutic traditions, producing rich descriptions about participants' shame experiences. RESULTS: Participants' shame experiences ranged from debilitating emotional and physical reactions to more insidious, fleeting reactions. Participants reported shame triggers relating to patient care, learning processes, and personal goals; numerous factors contributed to their shame experiences. The effects of shame reactions included social isolation, disengagement from learning, impaired wellness, unprofessional behavior, and impaired empathy. Positive effects of shame reactions included enhanced learning, increased willingness to reach out for help, and improved relationships. CONCLUSIONS: Shame reactions can be sentinel emotional events with significant physical and/or psychological effects in medical learners. This study has implications for learners, educators, and patients, and it may pave the way toward open, honest conversations about the role shame plays in medical education.

A first step toward understanding best practices in leadership training in undergraduate medical education: a systematic review.

PURPOSE: To characterize leadership curricula in undergraduate medical education as a first step toward understanding best practices in leadership education. METHOD: The authors systematically searched the PubMed, Education Resources Information Center, Academic Search Complete, and Education Full Text databases for peer-reviewed English-language articles published 1980-2014 describing curricula with interventions to teach medical students leadership skills. They characterized educational settings, curricular format, and learner and instructor types. They assessed effectiveness and quality of evidence using five-point scales adapted from Kirkpatrick's four-level training evaluation model (scale: 0-4) and a Best Evidence Medical Education guide (scale: 1-5), respectively. They classified leadership skills taught into the five Medical Leadership Competency Framework (MLCF) domains. RESULTS: Twenty articles describing 24 curricula met inclusion criteria. The majority of curricula (17; 71%) were longitudinal, delivered over periods of one semester to four years. The most common setting was the classroom (12; 50%). Curricula were frequently provided to both preclinical and clinical students (11; 46%); many (9; 28%) employed clinical faculty as instructors. The majority (19; 79%) addressed at least three MLCF domains; most common were working with others (21; 88%) and managing services (18; 75%). The median effectiveness score was 1.5, and the median quality of evidence score was 2. CONCLUSIONS: Most studies did not demonstrate changes in student behavior or quantifiable results. Aligning leadership curricula with competency models, such as the MLCF, would create opportunities to standardize evaluation of outcomes, leading to better measurement of student competency and a better understanding of best practices.