An Educational Workshop to Improve Neurology Resident Understanding of Burnout, Substance Abuse, and Mood Disorders.

Introduction: Burnout, substance abuse, and mood disorders are prevalent among neurology residents. Increased recognition of concerning behaviors might encourage more access to mental health resources and reduce burnout. Methods: We created an educational resource reviewing burnout, substance abuse, and mood disorders for neurology residents. This resource included an online module (control) and a role-play scenario offered only to one cohort (intervention). Online surveys assessed knowledge as well as confidence in the ability to recognize concerning behaviors. A practical assessment using a previously published "Stressed Resident" video was also conducted among resident cohorts. Results: Of neurology residents, 18 participated in the activity, with nine in the control group and nine in the intervention group. In the postvideo survey, the residents who participated in a role-play activity outperformed a control cohort of their peers when identifying signs of burnout, mood disorders, and substance abuse portrayed in the video (84% vs. 72%; t test, p = .01). Residents indicated increased confidence in the ability to recognize symptoms of maladaptive stress as well as identify resources for themselves and peers. Participants demonstrated no difference in knowledge-based questions scores on pre- and postactivity assessments. Discussion: Our educational resource improved resident ability to recognize signs of maladaptive stress and to identify residents that are a risk to patient safety. The activity is easy to implement and can be easily adapted outside neurology. Limited sample sizes may limit the ability to demonstrate this tool's impact on knowledge of burnout, substance abuse, and mood disorders.

Mycobacterium tuberculosis pellicles express unique proteins recognized by the host humoral response.

Mycobacterium tuberculosis (MTB) causes both acute and chronic infections in humans characterized by tolerance to antibiotics and reactivation to cause secondary tuberculosis. These characteristics have led to renewed interest in the in vitro pellicle, or biofilm mode of growth, where bacteria grow to produce a thick aggregate at the air-liquid interface and exhibit increased phenotypic resistance to antibiotics. We infected guinea pigs with the virulent H37Rv strain of MTB for 60 days at which point we collected blood. To identify antigenic proteins, membrane protein extracts of MTB H37Ra pellicles and shaken cultures grown for 3, 5, or 7 weeks were probed with the infected animals' sera after the proteins were separated by two-dimensional gel electrophoresis (2DGE). Antigenic proteins were then identified using MALDI-TOF/TOF mass spectrometry peptide mass fingerprinting. Antigenic pellicle proteins were compared across the three timepoints to identify those that were produced consistently during pellicle growth. They were also compared to those membrane proteins identified from harvested shaken cultures to determine pellicle-specific vs. universally expressed proteins. Using this technique, we identified 44 distinct antigenic proteins, nine of which were pellicle-specific. The sequence of antigenic pellicle-specific proteins was checked for sequence conservation across 15 sequenced MTB clinical isolates, three other members of the MTB complex, as well as M. avium and M. smegmatis. The antigenic pellicle-specific protein Rv0097 was found to have very high sequence conservation within the MTB complex but not with related mycobacteria, while FabG4 was highly conserved in all mycobacteria analyzed. These conserved pellicle-specific proteins represent targets for the development of future diagnostic tests and vaccines.

Vaccine development in Staphylococcus aureus: taking the biofilm phenotype into consideration.

Vaccine development against pathogenic bacteria is an imperative initiative as bacteria are gaining resistance to current antimicrobial therapies and few novel antibiotics are being developed. Candidate antigens for vaccine development can be identified by a multitude of high-throughput technologies that were accelerated by access to complete genomes. While considerable success has been achieved in vaccine development against bacterial pathogens, many species with multiple virulence factors and modes of infection have provided reasonable challenges in identifying protective antigens. In particular, vaccine candidates should be evaluated in the context of the complex disease properties, whether planktonic (e.g. sepsis and pneumonia) and/or biofilm associated (e.g. indwelling medical device infections). Because of the phenotypic differences between these modes of growth, those vaccine candidates chosen only for their efficacy in one disease state may fail against other infections. This review will summarize the history and types of bacterial vaccines and adjuvants as well as present an overview of modern antigen discovery and complications brought about by polymicrobial infections. Finally, we will also use one of the better studied microbial species that uses differential, multifactorial protein profiles to mediate an array of diseases, Staphylococcus aureus, to outline some of the more recently identified problematic issues in vaccine development in this biofilm-forming species.

Early epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-azacytidine and entinostat in patients with myeloid malignancies.

Sequential administration of DNA methyltransferase (DNMT) inhibitors and histone deacetylase (HDAC) inhibitors has demonstrated clinical efficacy in patients with hematologic malignancies. However, the mechanism behind their clinical efficacy remains controversial. In this study, the methylation dynamics of 4 TSGs (p15(INK4B), CDH-1, DAPK-1, and SOCS-1) were studied in sequential bone marrow samples from 30 patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) who completed a minimum of 4 cycles of therapy with 5-azacytidine and entinostat. Reversal of promoter methylation after therapy was observed in both clinical responders and nonresponders across all genes. There was no association between clinical response and either baseline methylation or methylation reversal in the bone marrow or purified CD34(+) population, nor was there an association with change in gene expression. Transient global hypomethylation was observed in samples after treatment but was not associated with clinical response. Induction of histone H3/H4 acetylation and the DNA damage-associated variant histone gamma-H2AX was observed in peripheral blood samples across all dose cohorts. In conclusion, methylation reversal of candidate TSGs during cycle 1 of therapy was not predictive of clinical response to combination "epigenetic" therapy. This trial is registered with http://www.clinicaltrials.gov under NCT00101179.