Loss of Meaning at Work Associated with Burnout Risk in Academic Medicine.

OBJECTIVES: Meaning at work has been proposed as one of the key drivers of professional burnout in healthcare, but few studies have simultaneously measured this relation. METHODS: In this cross-sectional analysis of 1637 individuals at the University of Arkansas for Medical Sciences, burnout was measured using the Copenhagen Burnout Inventory work-related subscale. RESULTS: Meaningful work was measured using items adapted from the Work as Meaning Inventory. The prevalence of work-related burnout increased with each level of diminished meaning at work. From the highest ("always") to the lowest ("never") level of meaning at work, the prevalence of burnout was: 13, 26, 57, 84, and 94%, respectively. CONCLUSIONS: Work-related burnout was inversely proportional to reported meaning at work in an academic medical center.

A One-Year Institutional View of Resident Physician Burnout.

OBJECTIVES: This prospective study explores the prevalence, associated characteristics, and trajectory of burnout over one academic year in a multidisciplinary sample of resident physicians using a relatively new burnout survey instrument. METHODS: All residents from a U.S. academic health center (n = 633) were invited to complete the Copenhagen Burnout Inventory (CBI) three times, with 4-month time lags between invitations. A total of 281 (44%) provided complete CBI survey responses at least once, and 43 (7%) did at all three times. Descriptive statistics, cross-sectional analyses, correlations, and multivariable linear regression analyses were computed, as well as repeated measures ANOVAs and paired t tests, as appropriate, for each CBI domain (personal, work, patient-related burnout). RESULTS: About half had CBI scores indicating moderate-to-high levels of personal burnout (49-52%) and work-related burnout (45-49%), whereas patient-related burnout was less common (14-24%). However, patient-related burnout increased significantly from the beginning to the end of the year. Regression analyses indicated patient-related burnout was significantly higher for postgraduate year 1-2 residents compared to PGY 4+ residents, but was not significantly different by gender. Personal and work burnout scores were significantly higher for females. Persistently high burnout was observed in only 6% of respondents. CONCLUSIONS: In this study of resident physicians using the CBI, burnout was prevalent and higher levels of burnout were observed for females on the personal and work burnout domains, while junior residents had higher patient-related burnout. Persistently, high burnout was rare. The CBI demonstrated high reliability, was practical to administer, and produced similar results with existing burnout research.

Differences in burnout prevalence between clinical professionals and biomedical scientists in an academic medical centre: a cross-sectional survey.

OBJECTIVE: To determine the prevalence and associated factors for personal, work-related and patient/client-related burnout in clinical professionals and biomedical scientists in academic medicine. DESIGN: Prevalence survey using the Copenhagen Burnout Inventory. SETTING: Mid-size academic health centre. PARTICIPANTS: Clinical providers (n=6489) and biomedical scientists (n=248) were invited to complete the survey. 1646 completed responses (response rate 24.4%) were analysed. PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalence estimates and adjusted ORs (AOR) were stratified for gender, age and professional category. RESULTS: Type of burnout varies across professional categories, with significant differences between clinicians and scientists. The prevalence of personal burnout was 52.7% (95%CI 50% to 55%), work-related burnout 47.5% (95%CI 45% to 49%) and patient/client-related burnout 20.3% (95%CI 18% to 22%). The prevalence of personal and work-related burnout was higher among women, while those aged 20-30 had a higher prevalence of all three burnout categories. Overall, clinical professionals had higher personal and work-related burnout, while biomedical scientists had higher client-related burnout. Accounting for the effects of gender and age, a significantly higher risk for personal burnout was found for physicians (AOR 1.64; 95%CI 1.3 to 2.1) and nurses (AOR 1.5; 95%CI 1.03 to 2.2). Significantly higher odds of work-related burnout were found for nurses (AOR 1.5; 95%CI 1.2 to 1.9) and residents (AOR 1.9; 95%CI 1.04 to 3.6). Basic scientists (AOR 10.0; 95%CI 5.7 to 17.6), physicians (AOR 2.8; 95%CI 1.9 to 4.1) and nurses (AOR 2.1; 95%CI 1.3 to 3.5) had higher odds of patient/client-related burnout. CONCLUSIONS: Types of burnout are unevenly distributed in academic medical centres. Physicians have higher risk of personal and patient/client-related burnout, residents have higher risk of work-related burnout, basic scientists are at higher risk of client-related burnout and nurses have higher odds of all three types of burnout. Interventions addressing the problem of burnout in clinical environments may be inadequate to support biomedical scientists.

A miRNA181a/NFAT5 axis links impaired T cell tolerance induction with autoimmune type 1 diabetes.

Molecular checkpoints that trigger the onset of islet autoimmunity or progression to human type 1 diabetes (T1D) are incompletely understood. Using T cells from children at an early stage of islet autoimmunity without clinical T1D, we find that a microRNA181a (miRNA181a)-mediated increase in signal strength of stimulation and costimulation links nuclear factor of activated T cells 5 (NFAT5) with impaired tolerance induction and autoimmune activation. We show that enhancing miRNA181a activity increases NFAT5 expression while inhibiting FOXP3+ regulatory T cell (Treg) induction in vitro. Accordingly, Treg induction is improved using T cells from NFAT5 knockout (NFAT5ko) animals, whereas altering miRNA181a activity does not affect Treg induction in NFAT5ko T cells. Moreover, high costimulatory signals result in phosphoinositide 3-kinase (PI3K)-mediated NFAT5, which interferes with FoxP3+ Treg induction. Blocking miRNA181a or NFAT5 increases Treg induction in murine and humanized models and reduces murine islet autoimmunity in vivo. These findings suggest targeting miRNA181a and/or NFAT5 signaling for the development of innovative personalized medicines to limit islet autoimmunity.

A Stat6/Pten Axis Links Regulatory T Cells with Adipose Tissue Function.

Obesity and type 2 diabetes are associated with metabolic defects and adipose tissue inflammation. Foxp3+ regulatory T cells (Tregs) control tissue homeostasis by counteracting local inflammation. However, if and how T cells interlink environmental influences with adipocyte function remains unknown. Here, we report that enhancing sympathetic tone by cold exposure, beta3-adrenergic receptor (ADRB3) stimulation or a short-term high-calorie diet enhances Treg induction in vitro and in vivo. CD4+ T cell proteomes revealed higher expression of Foxp3 regulatory networks in response to cold or ADRB3 stimulation in vivo reflecting Treg induction. Specifically, Ragulator-interacting protein C17orf59, which limits mTORC1 activity, was upregulated in CD4+ T cells by either ADRB3 stimulation or cold exposure, suggesting contribution to Treg induction. By loss- and gain-of-function studies, including Treg depletion and transfers in vivo, we demonstrated that a T cell-specific Stat6/Pten axis links cold exposure or ADRB3 stimulation with Foxp3+ Treg induction and adipose tissue function. Our findings offer a new mechanistic model in which tissue-specific Tregs maintain adipose tissue function.

Ubiquitylation of the acetyltransferase MOF in Drosophila melanogaster.

The nuclear acetyltransferase MOF (KAT8 in mammals) is a subunit of at least two multi-component complexes involved in transcription regulation. In the context of complexes of the 'Non-Specific-Lethal' (NSL) type it controls transcription initiation of many nuclear housekeeping genes and of mitochondrial genes. While this function is conserved in metazoans, MOF has an additional, specific function in Drosophila in the context of dosage compensation. As a subunit of the male-specific-lethal dosage compensation complex (MSL-DCC) it contributes to the doubling of transcription output from the single male X chromosome by acetylating histone H4. Proper dosage compensation requires finely tuned levels of MSL-DCC and an appropriate distribution of MOF between the regulatory complexes. The amounts of DCC formed depends directly on the levels of the male-specific MSL2, which orchestrates the assembly of the DCC, including MOF recruitment. We found earlier that MSL2 is an E3 ligase that ubiquitylates most MSL proteins, including MOF, suggesting that ubiquitylation may contribute to a quality control of MOF's overall levels and folding state as well as its partitioning between the complex entities. We now used mass spectrometry to map the lysines in MOF that are ubiquitylated by MSL2 in vitro and identified in vivo ubiquitylation sites of MOF in male and female cells. MSL2-specific ubiquitylation in vivo could not be traced due to the dominance of other, sex-independent ubiquitylation events and conceivably may be rare or transient. Expressing appropriately mutated MOF derivatives we assessed the importance of the ubiquitylated lysines for dosage compensation by monitoring DCC formation and X chromosome targeting in cultured cells, and by genetic complementation of the male-specific-lethal mof2 allele in flies. Our study provides a comprehensive analysis of MOF ubiquitylation as a reference for future studies.

Cognitive operations on space and their impact on the precision of location memory.

Learning about object locations in space usually involves the summation of information from different experiences of that space and requires various cognitive operations to make this possible. These processes are poorly understood and, in the extreme, may not occur--leading to mutual exclusivity of memories (Baguley, Lansdale, Lines, & Parkin, 2006). In this article, we investigate how the precision of location memory--evident in near-miss errors in recall--is related to different transformational processes in spatial cognition. Analyzing errors and latencies in a sequential comparative judgment task, 4 experiments show that the precision with which location is represented in memory is specifically degraded by a subset of transformations in which an object location encoded in reference to 1 anchor point is recalibrated in relation to another. We discuss the general implications of this finding for spatial learning and demonstrate that, rather than being a special case, exclusivity in memory is the extreme expression of a rational trade-off between the benefit of combining spatial information from more than 1 memory and the reduced precision that follows from the transformations required.