Medical School Rankings-Bad for the Health of the Profession and the Public.

This Viewpoint discusses the limitations of medical school ranking in attracting a diverse student population and urges administrators to holistically communicate their mission, goals, and learning environment as an alternative strategy.

Ferrichrome Has Found Its Match: Biomimetic Analogues with Diversified Activity Map Discrete Microbial Targets.

Siderophores provide an established platform for studying molecular recognition principles in biological systems. Herein, the preparation of ferrichrome (FC) biomimetic analogues varying in length and polarity of the amino acid chain separating between the tripodal scaffold and the pendent FeIII chelating hydroxamic acid groups was reported. Spectroscopic and potentiometric titrations determined their iron affinity to be within the range of efficient chelators. Microbial growth promotion and iron uptake studies were conducted on E. coli, P. putida and U. maydis. A wide range of siderophore activity was observed in the current series: from a rare case of a species-specific growth promotor in P. putida to an analogue matching FC in cross-phylum activity and uptake pathway. A fluorescent conjugate of the broad-range analogue visualized siderophore destination in bacteria (periplasmic space) vs. fungi (cytosol) mapping new therapeutic targets. Quantum dots (QDs) decorated with the most potent FC analogue provided a tool for immobilization of FC-recognizing bacteria. Bacterial clusters formed around QDs may provide a platform for their selection and concentration.

Limits of Versatility of Versatile Peroxidase.

UNLABELLED: Although Mn(2+) is the most abundant substrate of versatile peroxidases (VPs), repression of Pleurotus ostreatus vp1 expression occurred in Mn(2+)-sufficient medium. This seems to be a biological contradiction. The aim of this study was to explore the mechanism of direct oxidation by VP1 under Mn(2+)-deficient conditions, as it was found to be the predominant enzyme during fungal growth in the presence of synthetic and natural substrates. The native VP1 was purified and characterized using three substrates, Mn(2+), Orange II (OII), and Reactive Black 5 (RB5), each oxidized by a different active site in the enzyme. While the pH optimum for Mn(2+) oxidation is 5, the optimum pH for direct oxidation of both dyes was found to be 3. Indeed, effective in vivo decolorization occurred in media without addition of Mn(2+) only under acidic conditions. We have determined that Mn(2+) inhibits in vitro the direct oxidation of both OII and RB5 while RB5 stabilizes both Mn(2+) and OII oxidation. Furthermore, OII was found to inhibit the oxidation of both Mn(2+) and RB5. In addition, we could demonstrate that VP1 can cleave OII in two different modes. Under Mn(2+)-mediated oxidation conditions, VP1 was able to cleave the azo bond only in asymmetric mode, while under the optimum conditions for direct oxidation (absence of Mn(2+) at pH 3) both symmetric and asymmetric cleavages occurred. We concluded that the oxidation mechanism of aromatic compounds by VP1 is controlled by Mn(2+) and pH levels both in the growth medium and in the reaction mixture. IMPORTANCE: VP1 is a member of the ligninolytic heme peroxidase gene family of the white rot fungus Pleurotus ostreatus and plays a fundamental role in biodegradation. This enzyme exhibits a versatile nature, as it can oxidize different substrates under altered environmental conditions. VPs are highly interesting enzymes due to the fact that they contain unique active sites that are responsible for direct oxidation of various aromatic compounds, including lignin, in addition to the well-known Mn(2+) binding active site. This study demonstrates the limits of versatility of P. ostreatus VP1, which harbors multiple active sites, exhibiting a broad range of enzymatic activities, but they perform differently under distinct conditions. The versatility of P. ostreatus and its enzymes is an advantageous factor in the fungal ability to adapt to changing environments. This trait expands the possibilities for the potential utilization of P. ostreatus and other white rot fungi.

Inactivation of a Pleurotus ostreatus versatile peroxidase-encoding gene (mnp2) results in reduced lignin degradation.

Lignin biodegradation by white-rot fungi is pivotal to the earth's carbon cycle. Manganese peroxidases (MnPs), the most common extracellular ligninolytic peroxidases produced by white-rot fungi, are considered key in ligninolysis. Pleurotus ostreatus, the oyster mushroom, is a preferential lignin degrader occupying niches rich in lignocellulose such as decaying trees. Here, we provide direct, genetically based proof for the functional significance of MnP to P. ostreatus ligninolytic capacity under conditions mimicking its natural habitat. When grown on a natural lignocellulosic substrate of cotton stalks under solid-state culture conditions, gene and isoenzyme expression profiles of its short MnP and versatile peroxidase (VP)-encoding gene family revealed that mnp2 was predominately expressed. mnp2, encoding the versatile short MnP isoenzyme 2 was disrupted. Inactivation of mnp2 resulted in three interrelated phenotypes, relative to the wild-type strain: (i) reduction of 14% and 36% in lignin mineralization of stalks non-amended and amended with Mn(2+), respectively; (ii) marked reduction of the bioconverted lignocellulose sensitivity to subsequent bacterial hydrolyses; and (iii) decrease in fungal respiration rate. These results may serve as the basis to clarify the roles of the various types of fungal MnPs and VPs in their contribution to white-rot decay of wood and lignocellulose in various ecosystems.

Mn²âº-deficiency reveals a key role for the Pleurotus ostreatus versatile peroxidase (VP4) in oxidation of aromatic compounds.

The manganese peroxidase gene family (mnps) is a part of the ligninolytic system of Pleurotus ostreatus. This gene family is comprised of nine members, mnp1-9, encoding short manganese peroxidases (short-MnPs) or versatile peroxidases (VPs). We show that unlike in Mn(2+)-amended glucose-peptone (GP) medium, where redundancy among mnps was reported, in Mn(2+)-deficient GP medium mnp4 [encoding versatile peroxidase isoenzyme 4 (VP4)] has a key and nonredundant function. The abundance of mnps transcripts at time points corresponding to the tropophase (active growth), early idiophase, and idiophase indicates that mnp4 is the predominantly expressed mnp gene and that its relative predominance is dependent on the age of the culture. In this medium, azo dye, Orange II (OII) decolorization occurs only during the idiophase and a Δmnp4 strain showed a drastic reduction in this decolorization. Three degradation metabolites were identified by liquid chromatography-mass spectroscopy (LC-MS), indicating both asymmetric and symmetric enzymatic cleavage of the azo-bond. In addition, the culture filtrate of Δmnp4 showed negligible values of oxidation capability of four typical VP substrates: Mn(2+), 2,6-dimethoxyphenol, phenol red, and Reactive Black 5 (RB5), compared to the wild-type strain PC9. We concluded that under Mn(2+)-deficient GP culture, VP4 (encoded by mnp4) is the main active ligninolytic enzyme able to oxidize Mn(2+) as well as high and low redox potential aromatic substrate, including dyes. Furthermore, other VPs/MnPs do not compensate for the lack of VP4 activity.

The Next Era of Assessment: Building a Trustworthy Assessment System.

Assessment in medical education has evolved through a sequence of eras each centering on distinct views and values. These eras include measurement (e.g., knowledge exams, objective structured clinical examinations), then judgments (e.g., workplace-based assessments, entrustable professional activities), and most recently systems or programmatic assessment, where over time multiple types and sources of data are collected and combined by competency committees to ensure individual learners are ready to progress to the next stage in their training. Significantly less attention has been paid to the social context of assessment, which has led to an overall erosion of trust in assessment by a variety of stakeholders including learners and frontline assessors. To meaningfully move forward, the authors assert that the reestablishment of trust should be foundational to the next era of assessment. In our actions and interventions, it is imperative that medical education leaders address and build trust in assessment at a systems level. To that end, the authors first review tenets on the social contextualization of assessment and its linkage to trust and discuss consequences should the current state of low trust continue. The authors then posit that trusting and trustworthy relationships can exist at individual as well as organizational and systems levels. Finally, the authors propose a framework to build trust at multiple levels in a future assessment system; one that invites and supports professional and human growth and has the potential to position assessment as a fundamental component of renegotiating the social contract between medical education and the health of the public.

Redundancy among manganese peroxidases in Pleurotus ostreatus.

Manganese peroxidases (MnPs) are key players in the ligninolytic system of white rot fungi. In Pleurotus ostreatus (the oyster mushroom) these enzymes are encoded by a gene family comprising nine members, mnp1 to -9 (mnp genes). Mn(2+) amendment to P. ostreatus cultures results in enhanced degradation of recalcitrant compounds (such as the azo dye orange II) and lignin. In Mn(2+)-amended glucose-peptone medium, mnp3, mnp4, and mnp9 were the most highly expressed mnp genes. After 7 days of incubation, the time point at which the greatest capacity for orange II decolorization was observed, mnp3 expression and the presence of MnP3 in the extracellular culture fluids were predominant. To determine the significance of MnP3 for ligninolytic functionality in Mn(2+)-sufficient cultures, mnp3 was inactivated via the Δku80 strain-based P. ostreatus gene-targeting system. In Mn(2+)-sufficient medium, inactivation of mnp3 did not significantly affect expression of nontargeted MnPs or their genes, nor did it considerably diminish the fungal Mn(2+)-mediated orange II decolorization capacity, despite the significant reduction in total MnP activity. Similarly, inactivation of either mnp4 or mnp9 did not affect orange II decolorization ability. These results indicate functional redundancy within the P. ostreatus MnP gene family, enabling compensation upon deficiency of one of its members.

Predominance of a versatile-peroxidase-encoding gene, mnp4, as demonstrated by gene replacement via a gene targeting system for Pleurotus ostreatus.

Pleurotus ostreatus (the oyster mushroom) and other white rot filamentous basidiomycetes are key players in the global carbon cycle. P. ostreatus is also a commercially important edible fungus with medicinal properties and is important for biotechnological and environmental applications. Efficient gene targeting via homologous recombination (HR) is a fundamental tool for facilitating comprehensive gene function studies. Since the natural HR frequency in Pleurotus transformations is low (2.3%), transformed DNA is predominantly integrated ectopically. To overcome this limitation, a general gene targeting system was developed by producing a P. ostreatus PC9 homokaryon Δku80 strain, using carboxin resistance complemented by the development of a protocol for hygromycin B resistance protoplast-based DNA transformation and homokaryon isolation. The Δku80 strain exhibited exclusive (100%) HR in the integration of transforming DNA, providing a high efficiency of gene targeting. Furthermore, the Δku80 strains produced showed a phenotype similar to that of the wild-type PC9 strain, with similar growth fitness, ligninolytic functionality, and capability of mating with the incompatible strain PC15 to produce a dikaryon which retained its resistance to the corresponding selection and was capable of producing typical fruiting bodies. The applicability of this system is demonstrated by inactivation of the versatile peroxidase (VP) encoded by mnp4. This enzyme is part of the ligninolytic system of P. ostreatus, being one of the nine members of the manganese-peroxidase (MnP) gene family, and is the predominantly expressed VP in Mn(2+)-deficient media. mnp4 inactivation provided a direct proof that mnp4 encodes a key VP responsible for the Mn(2+)-dependent and Mn(2+)-independent peroxidase activity under Mn(2+)-deficient culture conditions.

Orally administered glucans from the edible mushroom Pleurotus pulmonarius reduce acute inflammation in dextran sulfate sodium-induced experimental colitis.

Polysaccharides are one of the most potent mushroom-derived substances exhibiting anti-inflammatory and immunomodulatory properties. The aims of the present study were to determine whether orally administered glucans from the edible mushroom Pleurotus pulmonarius could attenuate or prevent the development of experimental colitis in mice. Colonic inflammation was induced in mice by treatment with 3.5 % dextran sulfate sodium (DSS) for 18 d. Before or after DSS administration, mice were given hot water solubles (HWS) or mycelium extract (ME) (2 or 20 mg per mouse) daily in their food. Colonic damage was macroscopically and histologically evaluated. Inflammation was assessed by changes in colon length, TNF-alpha levels released by colonic samples in organ culture and myeloperoxidase (MPO) activity. mRNA levels of pro-inflammatory (IL-1beta) and anti-inflammatory (IL-10) cytokines in colonic samples were determined by quantitative real-time RT-PCR. P. pulmonarius glucans attenuated and prevented the development of symptoms associated with DSS-induced colitis. High doses of HWS and ME blocked colon shortening, suppressed MPO activity and improved macroscopic score in all treatment groups. In addition, histological damage from colitis was reduced by HWS and ME at all doses. The tissue levels of TNF-alpha protein were significantly decreased and correlated with degree of inflammation and macroscopic score. All treatments significantly attenuated the increased DSS-mediated expression levels of IL-1beta. We conclude that the different glucan preparations (HWS or ME) harvested from P. pulmonarius when orally administered to DSS-treated mice attenuate the development of colonic inflammation, suggesting putative clinical utility for these extracts in the treatment of colitis.

Chemical characterization, antiproliferative and antiadhesive properties of polysaccharides extracted from Pleurotus pulmonarius mycelium and fruiting bodies.

Mushroom polysaccharides are potent substances that exhibit antitumor and immunomodulatory properties. Studies comparing the chemical composition and antitumor-related activities of polysaccharides released by fungal strains under different growth conditions are not available. Thus, the present study compared polysaccharides extracts produced by Pleurotus pulmonarius from mycelium grown in liquid culture (ME) or fruiting bodies (FBE). Polysaccharides of both ME and FBE had a relatively high molecular mass. NMR spectroscopy indicated that ME glucan is an alpha-glucan whereas FBE glucan is a mixture of both alpha- and beta-glucans. Glucose and galactose where the most prominent monosaccharide in both glucans. Treatment of several colon cancer cell lines expressing varying amounts of galectin-3 with the two fungal glucans inhibited their viability and significantly reduced their ability to adhere to the key component of the extracellular matrix, fibronectin, and to a human umbilical vein endothelial cell monolayer, in a time- and dose-dependent manner mainly in those cell lines expressing high amounts of galectin-3. We conclude that ME and FBE glucans may exert a direct antiproliferative effect on cancer cells expressing high galectin-3 concentrations and concomitantly downregulate tumor cell adherence, the latter being directly related to cancer progression and metastasis.

Supporting Inclusive Learning Environments and Professional Development in Medical Education Through an Identity and Inclusion Initiative.

In 2015, the Pritzker School of Medicine experienced increasing student interest in the changing sociopolitical landscape of the United States and the interaction of these events with student and patient identity. To address this interest, an Identity and Inclusion Steering Committee was formed and formally charged with "providing ongoing direction for programs and/or curricula at Pritzker that support an inclusive learning environment and promote respectful and effective communication with diverse patients and colleagues around issues of identity." The authors describe this committee's structure and steps taken by the committee to create an inclusive community of students at Pritzker characterized by learning through civil discourse. Initiatives were guided by a strategy of continuous quality improvement consisting of regular iterative evaluation, ongoing school-wide engagement, and responsiveness to issues and concerns as they emerged. Data collected over the committee's 4-year existence demonstrate significant improvement in students' sense of inclusion and respect for different perspectives on issues related to identity, such as access to health care, racialized medicine, safe spaces, and nursing labor strikes. The authors discuss several principles that support the development of an inclusive community of students as well as challenges to the implementation of such programming. They conclude that a strategy of continuous quality improvement guided by values of social justice, tolerance, and civil discourse can build community inclusion and enhance medical training for the care of diverse patient populations.

Effects of cre1 modification in the white-rot fungus Pleurotus ostreatus PC9: altering substrate preference during biological pretreatment.

BACKGROUND: During the process of bioethanol production, cellulose is hydrolyzed into its monomeric soluble units. For efficient hydrolysis, a chemical and/or mechanical pretreatment step is required. Such pretreatment is designed to increase enzymatic digestibility of the cellulose chains inter alia by de-crystallization of the cellulose chains and by removing barriers, such as lignin from the plant cell wall. Biological pretreatment, in which lignin is decomposed or modified by white-rot fungi, has also been considered. One disadvantage in biological pretreatment, however, is the consumption of the cellulose by the fungus. Thus, fungal species that attack lignin with only minimal cellulose loss are advantageous. The secretomes of white-rot fungi contain carbohydrate-active enzymes (CAZymes) including lignin-modifying enzymes. Thus, modification of secretome composition can alter the ratio of lignin/cellulose degradation. RESULTS: Pleurotus ostreatus PC9 was genetically modified to either overexpress or eliminate (by gene replacement) the transcriptional regulator CRE1, known to act as a repressor in the process of carbon catabolite repression. The cre1-overexpressing transformant demonstrated lower secreted cellulolytic activity and slightly increased selectivity (based on the chemical composition of pretreated wheat straw), whereas the knockout transformant demonstrated increased cellulolytic activity and significantly reduced residual cellulose, thereby displaying lower selectivity. Pretreatment of wheat straw using the wild-type PC9 resulted in 2.8-fold higher yields of soluble sugar compared to untreated wheat straw. The overexpression transformant showed similar yields (2.6-fold), but the knockout transformant exhibited lower yields (1.2-fold) of soluble sugar. Based on proteomic secretome analysis, production of numerous CAZymes was affected by modification of the expression level of cre1. CONCLUSIONS: The gene cre1 functions as a regulator for expression of fungal CAZymes active against plant cell wall lignocelluloses, hence altering the substrate preference of the fungi tested. While the cre1 knockout resulted in a less efficient biological pretreatment, i.e., less saccharification of the treated biomass, the converse manipulation of cre1 (overexpression) failed to improve efficiency. Despite the inverse nature of the two genetic alterations, the expected "mirror image" (i.e., opposite regulatory response) was not observed, indicating that the secretion level of CAZymes, was not exclusively dependent on CRE1 activity.

SEALS: an Innovative Pipeline Program Targeting Obstacles to Diversity in the Physician Workforce.

OBJECTIVE: Medical schools may find implementing pipeline programs for minority pre-medical students prohibitive due to a number of factors including the lack of well-described programs in the literature, the limited evidence for program development, and institutional financial barriers. Our goals were to (1) design a pipeline program based on educational theory; (2) deliver the program in a low cost, sustainable manner; and (3) evaluate intermediate outcomes of the program. METHODS: SEALS is a 6-week program based on an asset bundles model designed to promote: (1) socialization and professionalism, (2) education in science learning tools, (3) acquisition of finance literacy, (4) the leveraging of mentorship and networks, and (5) social expectations and resilience, among minority pre-medical students. This is a prospective mixed methods study. Students completed survey instruments pre-program, post-program, and 6 months post-program, establishing intermediate outcome measures. RESULTS: Thirteen students matriculated to SEALS. The SEALS cohort rated themselves as improved or significantly improved when asked to rate their familiarity with MCAT components (p < 0.01), ability to ask for a letter of recommendation (p = 0.04), and importance of interview skills (p = 0.04) compared with before the program. Over 90 % of students referenced the health disparities lecture series as an inspiration to advocate for minority health. Six-month surveys suggested that SEALS students acquired and applied four of the five assets at their college campuses. CONCLUSIONS: This low-cost, high-quality, program can be undertaken by medical schools interested in promoting a diverse workforce that may ultimately begin to address and reduce health care disparities.

The minority student voice at one medical school: lessons for all?

PURPOSE: Although the minority population of the United States is projected to increase, the number of minority students in medical schools remains stagnant. The University of Chicago Pritzker School of Medicine (PSOM) matriculates students underrepresented in medicine (URM) above the national average. To identify potential strategies through which medical schools can support the success of URM medical students, interviews with URM students/graduates were conducted. METHOD: Students/recent graduates (within six years) who participated in this study self-identified as URMs in medicine and were selected for participation using random quota sampling. Participants completed a semistructured, qualitative interview in 2009-2010 about their experiences at PSOM. Key themes were identified and independently analyzed by investigators to ensure intercoder agreement. RESULTS: Participants identified five facets of their medical school experiences that either facilitated or hindered their academic success. Facilitators of support clustered in three categories: the collaborative learning climate at PSOM, the required health care disparities course, and student body diversity. Inhibitors of support clustered in two categories: insufficiently diverse faculty; and expectations-from self and others-to fulfill additional responsibilities, or carry a disproportionate burden. CONCLUSIONS: Intentional cultivation of a collaborative learning climate, formal inclusion of health care disparities curriculum, and commitment to fostering student body diversity are three routes by which PSOM has supported URM students. Additionally, recognizing the importance of building a diverse faculty and extending efforts to decrease the disproportionate burden and stereotype threat felt by URM students are institutional imperatives.

Glucans from the edible mushroom Pleurotus pulmonarius inhibit colitis-associated colon carcinogenesis in mice.

BACKGROUND: We have recently demonstrated that polysaccharides from fruiting body extract (FBE) or mycelia extract (ME) of the edible mushroom Pleurotus pulmonarius exert antiproliferative effects in intestinal cells and an anti-inflammatory effect in a dextran sulfate sodium (DSS) mouse model of acute colitis. The aim of this study was to assess the role of fungal FBE and ME in colon carcinogenesis. METHODS: In vitro, human colorectal cancer cells were treated with FBE and ME and analyzed for inflammation response, for markers of apoptosis, and for cell-cycle progression. In vivo, FBE and ME were tested in a mouse model of colitis-associated colorectal carcinogenesis induced by cyclic treatments with DSS and azoxymethane. Treated mice were fed a daily diet containing 2 or 20 mg FBE or ME per mouse for 80 days. RESULTS: In vitro, FBE and ME induced apoptosis in a dose-responsive manner and modulated the expression of Bcl-2, Bax, and cytochrome c, and blocked tumor necrosis factor (TNF)-α-induced inhibitor of nuclear factor (NF) (Iκ)-Bα degradation and NF-κB nuclear translocation. In vivo, dietary administration of FBE and ME significantly reduced the formation of aberrant crypt foci, which precedes colorectal cancer, and of microadenomas. The treatments significantly lowered the expression of proliferating cell nuclear antigen and increased the number of cells undergoing apoptosis in the colon. Additionally, FBE and ME inhibited the expression of the proinflammatory cytokine TNF-α in colonic tissue. CONCLUSIONS: We conclude that P. pulmonarius FBE and ME inhibit colitis-associated colon carcinogenesis induced in mice through the modulation of cell proliferation, induction of apoptosis, and inhibition of inflammation.

Release of Pleurotus ostreatus versatile-peroxidase from Mn2+ repression enhances anthropogenic and natural substrate degradation.

The versatile-peroxidase (VP) encoded by mnp4 is one of the nine members of the manganese-peroxidase (MnP) gene family that constitutes part of the ligninolytic system of the white-rot basidiomycete Pleurotus ostreatus (oyster mushroom). VP enzymes exhibit dual activity on a wide range of substrates. As Mn(2+) supplement to P. ostreatus cultures results in enhanced degradation of recalcitrant compounds and lignin, we examined the effect of Mn(2+) on the expression profile of the MnP gene family. In P. ostreatus (monokaryon PC9), mnp4 was found to be the predominantly expressed mnp in Mn(2+)-deficient media, whereas strongly repressed (to approximately 1%) in Mn(2+)-supplemented media. Accordingly, in-vitro Mn(2+)-independent activity was found to be negligible. We tested whether release of mnp4 from Mn(2+) repression alters the activity of the ligninolytic system. A transformant over-expressing mnp4 (designated OEmnp4) under the control of the ß-tubulin promoter was produced. Now, despite the presence of Mn(2+) in the medium, OEmnp4 produced mnp4 transcript as well as VP activity as early as 4 days after inoculation. The level of expression was constant throughout 10 days of incubation (about 0.4-fold relative to ß-tubulin) and the activity was comparable to the typical activity of PC9 in Mn(2+)-deficient media. In-vivo decolorization of the azo dyes Orange II, Reactive Black 5, and Amaranth by OEmnp4 preceded that of PC9. OEmnp4 and PC9 were grown for 2 weeks under solid-state fermentation conditions on cotton stalks as a lignocellulosic substrate. [(14)C]-lignin mineralization, in-vitro dry matter digestibility, and neutral detergent fiber digestibility were found to be significantly higher (about 25%) in OEmnp4-fermented substrate, relative to PC9. We conclude that releasing Mn(2+) suppression of VP4 by over-expression of the mnp4 gene in P. ostreatus improved its ligninolytic functionality.

The medical school on the university campus: 20th-century legacy and 21st-century aspirations.

One of the central tenets of Abraham Flexner's seminal report of 1910 was his firm belief that the medical school should be located within a university setting. He made this recommendation in the context of his era, when universities offered the best opportunities for ensuring that medical education would be firmly grounded in science and the scientific method of inquiry. Like many of Flexner's ideas, the organization of medical schools, including the new schools being developed today, continues in the image he propounded. At the same time, over the past decade, many reports have articulated the growing challenges of integrating medical schools-and, perhaps more important, academic medical centers-within the university. Is this relationship, once considered so crucial to the quality of medical education, still a mutually beneficial and symbiotic one? On the 100th anniversary of Flexner's report, the authors of this article explore the relevance and importance of the university-medical school relationship to the quality of medical education and consider the advantages and disadvantages for both medical schools and universities. A century later, the embedding of medical schools within university settings continues to offer unique and highly relevant opportunities to reclaim the foundation on which medical education must rest and to adhere to fundamental ideals that are too often threatened by contemporary challenges.

Moving beyond nostalgia and motives: towards a complexity science view of medical professionalism.

Modern-day discourse on medical professionalism has largely been dominated by a "nostalgic" view, emphasizing individual motives and behaviors. Shaped by a defining conflict between commercialism and professionalism, this discourse has unfolded through a series of waves, the first four of which are discovery, definition, assessment, and institutionalization. They have unfolded in a series of highly interactive and overlapping sequences that extend into the present. The fifth wave-linking structure and agency-which is nascent, proposes to shift our focus on professionalism from changing individuals to modifying the underlying structural and environmental forces that shape social actors and actions. The sixth wave-complexity science-is more incubatory in nature and seeks to recast social actors, social structures, and environmental factors as interactive, adaptive, and interdependent. Moving towards such a framing is necessary if medicine is to effectively reestablish professionalism as a core principle.