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Vanderbilt University Medical Center (VUMC) launched a new electronic health record (EHR) in a “big bang” implementation that saw the new software go live across multiple hospitals, clinics and geographic locations in a single morning. The organization rightly focused most of its energy on preparing its nearly 25,000 employees for the impacts of the transition, but it also considered the effects that would be felt by its patients and families. Survey data indicate that patient satisfaction scores demonstrably dip before, during and after an EHR implementation, and take approximately a year to recover. A team at DMC employed a seven-step approach to preparing patients for the impacts of the transition, which led to a return to pre-implementation patient satisfaction scores in about half the time of its peer institutions. The article explores these seven steps in detail and offers recommendations for how healthcare organizations facing large-scale change can use a similar structured approach to mitigate negative impacts to patients. Experience Framework This article is associated with the Culture & Leadership lens of The Beryl Institute Experience Framework. (http://bit.ly/ExperienceFramework) Access other PXJ articles related to this lens. Access other resources related to this lens

Purpose: Trauma-exposed persons often experience difficulties accessing medical care, remaining engaged in treatment plans, and feeling psychologically safe when receiving care. Trauma-informed care (TIC) is an established framework for health care professionals, but best practices for TIC education remain unclear. To remedy this, the authors conducted a multidisciplinary scoping literature review to discern best practices for the design, implementation, and evaluation of TIC curricula for health care professionals., Method: The research team searched Ovid MEDLINE, Cochrane Library, Elsevier's Scopus, Elsevier's Embase, Web of Science, and the PTSDpubs database from the database inception date until May 14, 2021. Worldwide English language studies on previously implemented TIC curricula for trainees or professionals in health care were included in this review., Results: Fifty-five studies met the inclusion criteria, with medicine being the most common discipline represented. The most prevalent learning objectives were cultivating skills in screening for trauma and responding to subsequent disclosures (41 studies [74.5%]), defining trauma (34 studies [61.8%]), and understanding trauma's impact on health (33 studies [60.0%]). Fifty-one of the studies included curricular evaluations, with the most common survey items being confidence in TIC skills (38 studies [74.5%]), training content knowledge assessment (25 studies [49.0%]), participant demographic characteristics (21 studies [41.2%]), and attitudes regarding the importance of TIC (19 studies [37.3%])., Conclusions: Future curricula should be rooted in cultural humility and an understanding of the impacts of marginalization and oppression on individual and collective experiences of trauma. Moreover, curricula are needed for clinicians in more diverse specialties and across different cadres of care teams. Additional considerations include mandated reporting, medical record documentation, and vicarious trauma experienced by health care professionals., (Copyright © 2022 by the Association of American Medical Colleges.)

Exercise confers protection against obesity, type 2 diabetes and other cardiometabolic diseases 1-5 . However, the molecular and cellular mechanisms that mediate the metabolic benefits of physical activity remain unclear 6 . Here we show that exercise stimulates the production of N-lactoyl-phenylalanine (Lac-Phe), a blood-borne signalling metabolite that suppresses feeding and obesity. The biosynthesis of Lac-Phe from lactate and phenylalanine occurs in CNDP2 + cells, including macrophages, monocytes and other immune and epithelial cells localized to diverse organs. In diet-induced obese mice, pharmacological-mediated increases in Lac-Phe reduces food intake without affecting movement or energy expenditure. Chronic administration of Lac-Phe decreases adiposity and body weight and improves glucose homeostasis. Conversely, genetic ablation of Lac-Phe biosynthesis in mice increases food intake and obesity following exercise training. Last, large activity-inducible increases in circulating Lac-Phe are also observed in humans and racehorses, establishing this metabolite as a molecular effector associated with physical activity across multiple activity modalities and mammalian species. These data define a conserved exercise-inducible metabolite that controls food intake and influences systemic energy balance., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

The increasing incidence of antibiotic-resistant Mycobacterium tuberculosis infections is a global health threat necessitating the development of new antibiotics. Serine hydrolases (SHs) are a promising class of targets because of their importance for the synthesis of the mycobacterial cell envelope. We screen a library of small molecules containing serine-reactive electrophiles and identify narrow-spectrum inhibitors of M. tuberculosis growth. Using these lead molecules, we perform competitive activity-based protein profiling and identify multiple SH targets, including enzymes with uncharacterized functions. Lipidomic analyses of compound-treated cultures reveal an accumulation of free lipids and a substantial decrease in lipooligosaccharides, linking SH inhibition to defects in cell envelope biogenesis. Mutant analysis reveals a path to resistance via the synthesis of mycocerates, but not through mutations to SH targets. Our results suggest that simultaneous inhibition of multiple SH enzymes is likely to be an effective therapeutic strategy for the treatment of M. tuberculosis infections., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The intracellular protozoan parasite Toxoplasma gondii must scavenge cholesterol and other lipids from the host to facilitate intracellular growth and replication. Enzymes responsible for neutral lipid synthesis have been identified but there is no evidence for enzymes that catalyze lipolysis of cholesterol esters and esterified lipids. Here, we characterize several T. gondii serine hydrolases with esterase and thioesterase activities that were previously thought to be depalmitoylating enzymes. We find they do not cleave palmitoyl thiol esters but rather hydrolyze short-chain lipid esters. Deletion of one of the hydrolases results in alterations in levels of multiple lipids species. We also identify small-molecule inhibitors of these hydrolases and show that treatment of parasites results in phenotypic defects reminiscent of parasites exposed to excess cholesterol or oleic acid. Together, these data characterize enzymes necessary for processing lipids critical for infection and highlight the potential for targeting parasite hydrolases for therapeutic applications., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Secreted polypeptides are a fundamental axis of intercellular and endocrine communication. However, a global understanding of the composition and dynamics of cellular secretomes in intact mammalian organisms has been lacking. Here, we introduce a proximity biotinylation strategy that enables labeling, detection and enrichment of secreted polypeptides in a cell type-selective manner in mice. We generate a proteomic atlas of hepatocyte, myocyte, pericyte and myeloid cell secretomes by direct purification of biotinylated secreted proteins from blood plasma. Our secretome dataset validates known cell type-protein pairs, reveals secreted polypeptides that distinguish between cell types and identifies new cellular sources for classical plasma proteins. Lastly, we uncover a dynamic and previously undescribed nutrient-dependent reprogramming of the hepatocyte secretome characterized by the increased unconventional secretion of the cytosolic enzyme betaine-homocysteine S-methyltransferase (BHMT). This secretome profiling strategy enables dynamic and cell type-specific dissection of the plasma proteome and the secreted polypeptides that mediate intercellular signaling.

The N-acyl amino acids are a family of bioactive lipids with pleiotropic physiologic functions, including in energy homeostasis. Their endogenous levels are regulated by an extracellular mammalian N-acyl amino acid synthase/hydrolase called PM20D1 (peptidase M20 domain containing 1). Using an activity-guided biochemical approach, we report the molecular identification of fatty acid amide hydrolase (FAAH) as a second intracellular N-acyl amino acid synthase/hydrolase. In vitro, FAAH exhibits a more restricted substrate scope compared to PM20D1. In mice, genetic ablation or selective pharmacological inhibition of FAAH bidirectionally dysregulates intracellular, but not circulating, N-acyl amino acids. Dual blockade of both PM20D1 and FAAH reveals a dramatic and non-additive biochemical engagement of these two enzymatic pathways. These data establish FAAH as a second intracellular pathway for N-acyl amino acid metabolism and underscore enzymatic division of labor as an enabling strategy for the regulation of a structurally diverse bioactive lipid family., Competing Interests: JK, ST, VL, WW, CF, JL No competing interests declared, (© 2020, Kim et al.)

Salinipostin A (Sal A) is a potent antiplasmodial marine natural product with an undefined mechanism of action. Using a Sal A-derived activity-based probe, we identify its targets in the Plasmodium falciparum parasite. All of the identified proteins contain α/β serine hydrolase domains and several are essential for parasite growth. One of the essential targets displays a high degree of homology to human monoacylglycerol lipase (MAGL) and is able to process lipid esters including a MAGL acylglyceride substrate. This Sal A target is inhibited by the anti-obesity drug Orlistat, which disrupts lipid metabolism. Resistance selections yielded parasites that showed only minor reductions in sensitivity and that acquired mutations in a PRELI domain-containing protein linked to drug resistance in Toxoplasma gondii. This inability to evolve efficient resistance mechanisms combined with the non-essentiality of human homologs makes the serine hydrolases identified here promising antimalarial targets., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Enzymes catalyze fundamental biochemical reactions that control cellular and organismal homeostasis. Here we present an approach for de novo biochemical pathway discovery across entire mammalian enzyme families using parallel viral transduction in mice and untargeted liquid chromatography-mass spectrometry. Applying this method to the M20 peptidases uncovers both known pathways of amino acid metabolism as well as a previously unknown CNDP2-regulated pathway for threonyl dipeptide catabolism. Ablation of CNDP2 in mice elevates threonyl dipeptides across multiple tissues, establishing the physiologic relevance of our biochemical assignments. Taken together, these data underscore the utility of parallel in vivo metabolomics for the family-wide discovery of enzymatic pathways., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Scientific outreach efforts traditionally involve formally trained scientists teaching the general public about the methods, significance, and excitement of science. We recently experimented with an alternative "symbiotic outreach" model that prioritizes building a reciprocal relationship between formally trained and "outsider" scientists to facilitate active two-way communication. Herein, we present the results of our outreach effort involving college students and adults with intellectual and developmental disabilities working together to make biological and multimedia art. By discussing the steps others can take to cultivate reciprocal outreach within their local communities, we hope to lower the barrier for widespread adoption of similar approaches and ultimately to decrease the gap between formally trained scientists and the general public., Competing Interests: The authors have declared that no competing interests exist.