Educational Approaches Using Simulation for Psychiatric Risk Assessment: a Scoping Review.

OBJECTIVE: The ability to assess a patient's risk of harm to self or others is a core competency for mental health clinicians which can have significant patient outcomes. With the growth of simulation in medical education, there is an opportunity to enhance education outcomes for psychiatric risk assessment. The purpose of this study was to determine how simulation is used to build competency in risk assessment and map its educational outcomes. METHODS: The authors conducted a systematic scoping review using the Arksey and O'Malley framework. Electronic database searches were conducted by an academic librarian. Studies published before August 2022 which described simulation activities aimed at training clinicians in suicide, self-harm, and/or violence risk assessment were screened for eligibility. RESULTS: Of the 21,814 articles identified, 58 studies were selected for inclusion. The majority described simulations teaching suicide risk assessment, and there was a notable gap for building competency in violence risk assessment. Simulation utility was demonstrated across emergency, inpatient, and outpatient settings involving adult and pediatric care. The most common simulation modality was patient actors. A smaller subset implemented technological approaches, such as automated virtual patient avatars. Outcomes included high learner satisfaction, and increases in psychiatric risk assessment knowledge, competency, and performance. CONCLUSION: Simulation as an adjuvant to existing medical curricula can be used to teach risk assessment in mental health. Based on the results of our review, the authors provide recommendations for medical educators looking to design and implement simulation in mental health education.

Acids produced by lactobacilli inhibit the growth of commensal Lachnospiraceae and S24-7 bacteria.

The Lactobacillaceae are an intensively studied family of bacteria widely used in fermented food and probiotics, and many are native to the gut and vaginal microbiota of humans and other animals. Various studies have shown that specific Lactobacillaceae species produce metabolites that can inhibit the colonization of fungal and bacterial pathogens, but less is known about how Lactobacillaceae affect individual bacterial species in the endogenous animal microbiota. Here, we show that numerous Lactobacillaceae species inhibit the growth of the Lachnospiraceae family and the S24-7 group, two dominant clades of bacteria within the gut. We demonstrate that inhibitory activity is a property common to homofermentative Lactobacillaceae species, but not to species that use heterofermentative metabolism. We observe that homofermentative Lactobacillaceae species robustly acidify their environment, and that acidification alone is sufficient to inhibit growth of Lachnospiraceae and S24-7 growth, but not related species from the Clostridiales or Bacteroidales orders. This study represents one of the first in-depth explorations of the dynamic between Lactobacillaceae species and commensal intestinal bacteria, and contributes valuable insight toward deconvoluting their interactions within the gut microbial ecosystem.

Tryptophan-derived microbial metabolites activate the aryl hydrocarbon receptor in tumor-associated macrophages to suppress anti-tumor immunity.

The aryl hydrocarbon receptor (AhR) is a sensor of products of tryptophan metabolism and a potent modulator of immunity. Here, we examined the impact of AhR in tumor-associated macrophage (TAM) function in pancreatic ductal adenocarcinoma (PDAC). TAMs exhibited high AhR activity and Ahr-deficient macrophages developed an inflammatory phenotype. Deletion of Ahr in myeloid cells or pharmacologic inhibition of AhR reduced PDAC growth, improved efficacy of immune checkpoint blockade, and increased intra-tumoral frequencies of IFNγ+CD8+ T cells. Macrophage tryptophan metabolism was not required for this effect. Rather, macrophage AhR activity was dependent on Lactobacillus metabolization of dietary tryptophan to indoles. Removal of dietary tryptophan reduced TAM AhR activity and promoted intra-tumoral accumulation of TNFα+IFNγ+CD8+ T cells; provision of dietary indoles blocked this effect. In patients with PDAC, high AHR expression associated with rapid disease progression and mortality, as well as with an immune-suppressive TAM phenotype, suggesting conservation of this regulatory axis in human disease.

Structural Basis of the Interaction Between Ubiquitin Specific Protease 7 and Enhancer of Zeste Homolog 2.

USP7 is a deubiquitinase that regulates many diverse cellular processes, including tumor suppression, epigenetics, and genome stability. Several substrates, including GMPS, UHRF1, and ICP0, were shown to bear a specific KxxxK motif that interacts within the C-terminal region of USP7. We identified a similar motif in Enhancer of Zeste 2 (EZH2), the histone methyltransferase found within Polycomb Repressive Complex 2 (PRC2). PRC2 is responsible for the methylation of Histone 3 Lys27 (H3K27) leading to gene silencing. GST pull-down and coimmunoprecipitation experiments showed that USP7 interacts with EZH2. We determined the structural basis of interaction between USP7 and EZH2 and identified residues mediating the interaction. Mutations in these critical residues disrupted the interaction between USP7 and EZH2. Furthermore, USP7 silencing and knockout experiments showed decreased EZH2 levels in HCT116 carcinoma cells. Finally, we demonstrated decreased H3K27Me3 levels in HCT116 USP7 knockout cells. These results indicate that USP7 interacts with EZH2 and regulates both its stability and function.