A Common Trajectory Toward a Professional Identity as a Faculty Developer.

BACKGROUND AND OBJECTIVES: Professional identity formation is a complex construct that continually evolves in relation to an individual's experiences. The literature on educators identifying as faculty developers is limited and incompletely addresses how that identify affects other identities, careers, and influences on teaching. Twenty-six health professionals were trained to serve as faculty developers within our educational system. We sought to examine the factors that influence the professional identity of these faculty developers and to determine whether a common trajectory existed. METHODS: We employed a constructivist thematic analysis methodology using an inductive approach to understand the experiences of faculty developers. We conducted semistructured recorded interviews. Coding and thematic analysis were completed iteratively. RESULTS: We identified eight primary themes: (1) initial invitation, (2) discovery of faculty development as a professional activity, (3) discovery of educational theory, skills, and need for more education, (4) process of time and experience, (5) fostering relationships and community, (6) transfer of skills to professional and personal roles, (7) experiences that lead to credibility, and (8) sense of greater impact. CONCLUSIONS: An individual's journey to a faculty developer identity is variable, with several shared pivotal experiences that help foster the emergence of this identity. Consideration of specific programmatic elements to support the themes identified might allow for a strategic approach to faculty development efforts in health professions education.

A Faculty Development Model for Academic Leadership Education Across A Health Care Organization.

Academic leadership in undergraduate and graduate medical education requires a specific set of leadership and managerial skills that are unique to academic leadership positions. While leadership development training programs exist for traditional leadership roles such as department chairs, executives, and deans, there are fewer models of leadership training specifically geared for academic leadership positions such as program and clerkship directors, and designated institutional officials. There are academic programs at the national level, but there is sparse literature on the specific decisions required to create such programs locally. With growing regulatory and accreditation requirements as well as the challenges of balancing the clinical and educational missions, effective leadership is needed across the spectrum of academic medicine. To meet this need for the military health care system in the United States, we used Kern's six-step framework for curriculum development to create a 1-week academic leadership course. This paper describes the process of development, implementation, outcomes, and lessons learned following the initial 3 years of courses. Specific discussions regarding who to train, which faculty to use, content, and other elements of course design are reviewed. The course and process outlined in the paper offer a model for other organizations desiring to establish an academic leadership course.

The Ripple Effect: A Train-the-Trainer Model to Exponentially Increase Organizational Faculty Development.

This article was migrated. The article was marked as recommended. INTRODUCTION: Faculty development is a key component of undergraduate and graduate medical education and is required for accreditation. Many institutions face the challenges of training large numbers of faculty at multiple locations on a recurring basis. In order to meet the faculty development demands of our organization, we implemented a train-the trainer model of faculty development. METHODS: A train-the-trainer program was created using deliberate practice as the theoretical framework. The primary goals of the program were to enhance content knowledge and develop facilitation skills of the participants (called faculty trainers). Two separate cohorts received 40 hours of in-person training consisting of attending the faculty development workshops as a learner, providing feedback to course faculty, facilitating and participating in journal club sessions on relevant content, and practicing facilitation and receiving feedback on the workshops. Cohorts 1 and 2 were trained on how to deliver 6 and 7 workshops, respectively. An additional 16 hours of training and further feedback occurred when faculty trainers delivered the workshops at outside institutions. RESULTS: Twenty-nine faculty trainers from 15 specialties and subspecialties were trained, including 18 in the first cohort (January 2018) and 14 in the second cohort (February 2019) with 3 who participated in both cohorts. From January 2018 to January 2020, faculty trainers delivered 298 workshops to 3742 attendees at 25 locations. For the faculty trainers, 1477 evaluations were completed with 1031 (88.1%) rated as excellent, 141 (9.5%) rated as good, and 8 (0.5%) as average. There were no fair or poor ratings. DISCUSSION: Our train-the-trainer program effectively developed a community of national faculty developers. Faculty trainer output was substantial and early evaluations of performance were positive. The model outlined in this paper serves as a potential sustainable model for other institutions desiring to train a cadre of faculty developers for their organization.

Migratory behavior of cells generated in ganglionic eminence cultures.

Migration of cells is a common process that leads to the development and maturation of the vertebrate central nervous system (Hatten, '99). The cerebral cortex consists of two basic neuronal types: excitatory and inhibitory. These cells arise in distinct areas and migrate into the cortex along different routes (Pearlman et al., '98). Inhibitory interneurons migrate tangentially from subcortical sources, mostly from different regions of the ganglionic eminences (Gelman et al., '09; Xu et al., '04). Their movement requires precise spatiotemporal control imposed by environmental cues, to allow for the establishment of proper cytoarchitecture and connectivity in the cerebral cortex (Caviness & Rakic, '78; Hatten, '90; Rakic, '90). To study the migratory behavior of cells generated in proliferative zones of the ganglionic eminences (GE) in newborn ferrets in vitro we used a 3 dimensional culture arrangement in a BD Matrigel Matrix. The culture setup consisted of two GE explants and a source of tested proteins extracted from the cerebral cortex and adsorbed on fluorescent latex Retrobeads IX positioned between the explants (Hasling et al., '03; Riddle et al., '97). After 2-3 days of culture, the cells start to appear at the edge of the explant showing a propensity to leave the tissue in a radial direction. Live imaging allowed observation of migratory patterns without the necessity of labeling or marking the cells. When exposed to fractions of the protein extract obtained from isochronic ferret cortex, the GE cells displayed different behaviors as judged by quantitative kinetic analysis of individual moving cells.

Phosphorylation status of pyruvate dehydrogenase distinguishes metabolic phenotypes of cultured rat brain astrocytes and neurons.

Glucose metabolism in nervous tissue has been proposed to occur in a compartmentalized manner with astrocytes contributing largely to glycolysis and neurons being the primary site of glucose oxidation. However, mammalian astrocytes and neurons both contain mitochondria, and it remains unclear why in culture neurons oxidize glucose, lactate, and pyruvate to a much larger extent than astrocytes. The objective of this study was to determine whether pyruvate metabolism is differentially regulated in cultured neurons versus astrocytes. Expression of all components of the pyruvate dehydrogenase complex (PDC), the rate-limiting step for pyruvate entry into the Krebs cycle, was determined in cultured astrocytes and neurons. In addition, regulation of PDC enzymatic activity in the two cell types via protein phosphorylation was examined. We show that all components of the PDC are expressed in both cell types in culture, but that PDC activity is kept strongly inhibited in astrocytes through phosphorylation of the pyruvate dehydrogenase alpha subunit (PDH alpha). In contrast, neuronal PDC operates close to maximal levels with much lower levels of phosphorylated PDH alpha. Dephosphorylation of astrocytic PDH alpha restores PDC activity and lowers lactate production. Our findings suggest that the glucose metabolism of astrocytes and neurons may be far more flexible than previously believed.

Chronic pain disorders and headache chronification.

It is estimated that nearly half of the global adult population suffers from an active headache disorder, most of whom experience attacks on an episodic basis. The transition from episodic to chronic headache is a poorly understood process. Epidemiological findings demonstrating comorbidity and common risk factors suggest that headache progression or prognosis may be related to the presence of other chronic pain disorders. This review highlights findings from population-based studies on headache and other pain disorders and how they relate to each other, with a focus on understanding headache chronification. We also consider the limitations and methodological challenges in understanding how two different chronic pain disorders may be related.

Mitochondrial mutations contribute to HIF1alpha accumulation via increased reactive oxygen species and up-regulated pyruvate dehydrogenease kinase 2 in head and neck squamous cell carcinoma.

PURPOSE: Mitochondrial mutations have been identified in head and neck squamous cell carcinoma (HNSCC), but the pathways by which phenotypic effects of these mutations are exerted remain unclear. Previously, we found that mitochondrial ND2 mutations in primary HNSCC increased reactive oxygen species (ROS) and conferred an aerobic, glycolytic phenotype with HIF1alpha accumulation and increased cell growth. The purpose of the present study was to examine the pathways relating these alterations. EXPERIMENTAL DESIGN: Mitochondrial mutant and wild-type ND2 constructs were transfected into oral keratinocyte immortal cell line OKF6 and head and neck cancer cell line JHU-O19 and established transfectants. The protein levels of HIF1alpha, pyruvate dehydrogenease (PDH), phosphorylated PDH, and pyruvate dehydrogenease kinase 2 (PDK2), together with ROS generation, were compared between the mutant and the wild type. Meanwhile, the effects of small molecule inhibitors targeting PDK2 and mitochondria-targeted catalase were evaluated on the ND2 mutant transfectants. RESULTS: We determined that ND2 mutant down-regulated PDH expression via up-regulated PDK2, with an increase in phosphorylated PDH. Inhibition of PDK2 with dichloroacetate decreased HIF1alpha accumulation and reduced cell growth. Extracellular treatment with hydrogen peroxide, a ROS mimic, increased PDK2 expression and HIF1alpha expression, and introduction of mitochondria-targeted catalase decreased mitochondrial mutation-mediated PDK2 and HIF1alpha expression and suppressed cell growth. CONCLUSIONS: Our findings suggest that mitochondrial ND2 mutation contributes to HIF1alpha accumulation via increased ROS production, up-regulation of PDK2, attenuating PDH activity, thereby increasing pyruvate, resulting in HIF1alpha stabilization. This may provide insight into a potential mechanism, by which mitochondrial mutations contribute to HNSCC development.

Pyruvate dehydrogenase complex activity controls metabolic and malignant phenotype in cancer cells.

High lactate generation and low glucose oxidation, despite normal oxygen conditions, are commonly seen in cancer cells and tumors. Historically known as the Warburg effect, this altered metabolic phenotype has long been correlated with malignant progression and poor clinical outcome. However, the mechanistic relationship between altered glucose metabolism and malignancy remains poorly understood. Here we show that inhibition of pyruvate dehydrogenase complex (PDC) activity contributes to the Warburg metabolic and malignant phenotype in human head and neck squamous cell carcinoma. PDC inhibition occurs via enhanced expression of pyruvate dehydrogenase kinase-1 (PDK-1), which results in inhibitory phosphorylation of the pyruvate dehydrogenase alpha (PDHalpha) subunit. We also demonstrate that PDC inhibition in cancer cells is associated with normoxic stabilization of the malignancy-promoting transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha) by glycolytic metabolites. Knockdown of PDK-1 via short hairpin RNA lowers PDHalpha phosphorylation, restores PDC activity, reverts the Warburg metabolic phenotype, decreases normoxic HIF-1alpha expression, lowers hypoxic cell survival, decreases invasiveness, and inhibits tumor growth. PDK-1 is an HIF-1-regulated gene, and these data suggest that the buildup of glycolytic metabolites, resulting from high PDK-1 expression, may in turn promote HIF-1 activation, thus sustaining a feed-forward loop for malignant progression. In addition to providing anabolic support for cancer cells, altered fuel metabolism thus supports a malignant phenotype. Correction of metabolic abnormalities offers unique opportunities for cancer treatment and may potentially synergize with other cancer therapies.

Survival and invasiveness of astrocytomas promoted by erythropoietin.

OBJECT: The hypoxia-inducible pleiotropic hormone, erythropoietin (EPO), has recently been found to promote the development and survival of neurons and astrocytes. Since hypoxia has been implicated in the malignant progression of some human cancers, the authors investigated whether EPO signaling influenced the malignant properties of human astrocytoma cells. METHODS: Reverse transcriptase-polymerase chain reaction, Western blot analysis, and immunohistochemical studies were used to measure EPO and its receptor (EPOR). Cell viability, Matrigel invasion assays, metalloprotease assays, EPO neutralizing antibodies, and EPOR overexpression were used to study the biological actions of EPO. Expression of both EPO and EPOR was observed in the hypoxic regions and invasive margins of glioma specimens obtained at biopsy, and expression of EPOR correlated with the stage of the tumor. The EPOR was also functionally upregulated by hypoxia in cultured glioblastoma multiforme (GBM) cells. Both hypoxia and EPO protected cultured GBM cells from cisplatin cytotoxicity and promoted the invasiveness of GBM cells through Matrigel by potentiating metalloprotease activity. Hypoxia-enhanced cell invasion was attenuated in cells that overexpressed a nonfunctional EPOR. CONCLUSIONS: Hypoxia-inducible autocrine and paracrine EPO signaling participates in the malignant progression of GBMs.

Frequency and phenotypic implications of mitochondrial DNA mutations in human squamous cell cancers of the head and neck.

Mitochondrial genomic mutations are found in a variety of human cancers; however, the frequency of mitochondrial DNA (mtDNA) mutations in coding regions remains poorly defined, and the functional effects of mitochondrial mutations found in primary human cancers are not well described. Using MitoChip, we sequenced the whole mitochondrial genome in 83 head and neck squamous cell carcinomas. Forty-one of 83 (49%) tumors contained mtDNA mutations. Mutations occurred within noncoding (D-loop) and coding regions. A nonrandom distribution of mutations was found throughout the mitochondrial enzyme complex components. Sequencing of margins with dysplasia demonstrated an identical nonconservative mitochondrial mutation (A76T in ND4L) as the tumor, suggesting a role of mtDNA mutation in tumor progression. Analysis of p53 status showed that mtDNA mutations correlated positively with p53 mutations (P < 0.002). To characterize biological function of the mtDNA mutations, we cloned NADH dehydrogenase subunit 2 (ND2) mutants based on primary tumor mutations. Expression of the nuclear-transcribed, mitochondrial-targeted ND2 mutants resulted in increased anchorage-dependent and -independent growth, which was accompanied by increased reactive oxygen species production and an aerobic glycolytic metabolic phenotype with hypoxia-inducible factor (HIF)-1alpha induction that is reversible by ascorbate. Cancer-specific mitochondrial mutations may contribute to development of a malignant phenotype by direct genotoxic effects from increased reactive oxygen species production as well as induction of aerobic glycolysis and growth promotion.

Reversible inactivation of HIF-1 prolyl hydroxylases allows cell metabolism to control basal HIF-1.

Continuous hydroxylation of the HIF-1 transcription factor alpha subunit by oxygen and 2-oxoglutarate-dependent dioxygenases promotes decay of this protein and thus prevents the transcriptional activation of many genes involved in energy metabolism, angiogenesis, cell survival, and matrix modification. Hypoxia blocks HIF-1alpha hydroxylation and thus activates HIF-1alpha-mediated gene expression. Several nonhypoxic stimuli can also activate HIF-1, although the mechanisms involved are not well known. Here we show that the glucose metabolites pyruvate and oxaloacetate inactivate HIF-1alpha decay in a manner selectively reversible by ascorbate, cysteine, histidine, and ferrous iron but not by 2-oxoglutarate or oxygen. Pyruvate and oxaloacetate bind to the 2-oxoglutarate site of HIF-1alpha prolyl hydroxylases, but their effects on HIF-1 are not mimicked by other Krebs cycle intermediates, including succinate and fumarate. We show that inactivation of HIF-1 hydroxylation by glucose-derived 2-oxoacids underlies the prominent basal HIF-1 activity commonly seen in many highly glycolytic cancer cells. Since HIF-1 itself promotes glycolytic metabolism, enhancement of HIF-1 by glucose metabolites may constitute a novel feed-forward signaling mechanism involved in malignant progression.