Professional Identity Formation of Basic Science Medical Educators: A Qualitative Study of Identity Supports and Threats.

PURPOSE: Basic science medical educators (BSME) play a vital role in the training of medical students, yet little is known about the factors that shape their professional identities. This multi-institutional qualitative study investigated factors that support and threaten the professional identity formation (PIF) of these medical educators. METHOD: A qualitative descriptive study was conducted with a purposive sample of 58 BSME from 7 allopathic medical schools in the U.S. In-depth semi-structured interviews of individual BSME were conducted between December 2020 and February 2021 to explore the facilitators and barriers shaping the PIF of BSME. Thematic analysis was conducted. RESULTS: Factors shaping PIF were grouped into 3 broad domains: personal, social, and structural. Interrelated themes described a combination of factors that pushed BSME into teaching (early or positive teaching experiences) and kept them there (satisfaction and rewards of teaching, communities of like-minded people), as well as factors that challenged their PIF (misunderstanding from medical students, clinical, and research faculty, lack of formal training programs, and lack of tenure-track educator positions). The structural environment was reported to be crucial for PIF and determined whether BSME felt that they belonged and were valued. CONCLUSIONS: This study shows that although most BSME derive a sense of fulfillment and meaning from their role as medical educators, they face considerable obstacles during their PIF. Structural change and support are needed to increase recognition, value, promotion, and belonging for BSME to improve the satisfaction and retention of this important group of faculty.

How Medical Students Apply Their Biomedical Science Knowledge to Patient Care in the Family Medicine Clerkship.

Medical students enter clerkships with the requisite biomedical science knowledge to engage in supervised patient care. While poised to apply this knowledge, students face the cognitive challenge of transfer: applying knowledge learned in one context (i.e., preclinical classroom) to solve problems in a different context (i.e., patients in the clinic). To help students navigate this challenge, a structured reflection exercise was developed using Kolb's experiential learning cycle as an organizing framework. Students selected a patient encounter (concrete experience), wrote and addressed biomedical science learning objectives related to the care of the patient (reflective observation), reflected on how addressing the learning objectives influenced patient care (abstract conceptualization), and described their attending engaging in a similar process (active experimentation). A directed content analysis of students' written reflections revealed that most students wrote clinical science learning objectives in addition to biomedical science learning objectives. When viewed through the lenses of knowledge encapsulation theory and illness script theory, some students recognized knowledge encapsulation as a process beginning to occur in their own approach and their attendings' approach to clinical reasoning. Students readily applied their biomedical science knowledge to explain the pathophysiologic basis of disease (fault illness script domain) and signs and symptoms (consequence illness script domain), with fewer addressing predisposing conditions (enabling conditions illness script domain). Instances in which students observed their attending applying biomedical science knowledge were rare. Implications for using structured reflective writing as a tool to facilitate student application of their biomedical science knowledge in clerkships are discussed. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-022-01697-5.

Correction to: IAMSE Meeting Report: Student Plenary at the 24th Annual Conference of the International Association of Medical Science Educators.

[This corrects the article DOI: 10.1007/s40670-020-01087-9.].

Correction to: "It is this very knowledge that makes us doctors": an applied thematic analysis of how medical students perceive the relevance of biomedical science knowledge to clinical medicine.

An amendment to this paper has been published and can be accessed via the original article.

"It is this very knowledge that makes us doctors": an applied thematic analysis of how medical students perceive the relevance of biomedical science knowledge to clinical medicine.

BACKGROUND: Intensive study of the biomedical sciences remains a core component of undergraduate medical education with medical students often completing up to 2 years of biomedical science training prior to entering clerkships. While it is generally accepted that biomedical science knowledge is essential for clinical practice because it forms the basis of clinical reasoning and decision-making, whether medical students perceive an expanded role for their biomedical science knowledge remains to be examined. METHODS: We conducted a qualitative research study to explore how medical students in the first clerkship year perceived the relevance of biomedical science knowledge to clinical medicine during this pivotal time as they begin their transition from students to physicians. To identify previously unidentified perspectives and insights, we asked students to write brief essays in response to the prompt: How is biomedical science knowledge relevant to clinical medicine? Ten codes and four themes were interpreted through an applied thematic analysis of students' essays. RESULTS: Analysis of students' essays revealed novel perspectives previously unidentified by survey studies and focus groups. Specifically, students perceived their biomedical science knowledge as contributory to the development of adaptive expertise and professional identity formation, both viewed as essential developmental milestones for medical students. CONCLUSIONS: The results of this study have important implications for ongoing curricular reform efforts to improve the structure, content, delivery, and assessment of the undergraduate medical curriculum. Identifying the explicit and tacit elements of the formal, informal, and hidden curriculum that enable biomedical science knowledge to contribute to the development of adaptive expertise and professional identity formation will enable the purposeful design of innovations to support the acquisition of these critical educational outcomes.

Effectiveness of instructor-guided independent learning in comparison to traditional didactic lecture in the preclinical medical curriculum: A retrospective cohort study.

Introduction: To create time for learner-centered forms of active learning in the classroom, didactic lectures are being replaced with instructor-guided independent learning (IGIL) assignments that students complete on their own outside of the formal educational setting. The effectiveness of IGIL assignments in supporting learning across the preclinical medical curriculum when applied to all learners in the same class of students has not been examined. Further, we have examined this performance across three class cohorts. Methods: In this retrospective cohort study, we compared student performance on questions from both IGIL assignments and didactic lectures that were items on the end-of-course summative examinations. Data were analyzed from three classes of graduating students in each of the 14 courses that comprise our preclinical medical curriculum. Results: The results of this study suggest that IGIL assignments were as effective as didactic lectures in supporting student learning in our preclinical medical curriculum. Importantly, IGIL assignments supported learning for both low and high performing students. Conclusions: Students can effectively learn from IGIL assignments when the assignments are well-designed and their importance in the curriculum is emphasized.

HIV/AIDS: A Case-Based Learning Module for First-Year Medical Students.

In medical and healthcare-related education, case-based learning (CBL) is a teaching strategy that uses clinical cases to engage students in active learning using course concepts to solve important problems. Here we describe the design and implementation of a CBL module to teach first year medical students about the human immunodeficiency virus (HIV), acute retroviral syndrome, clinical progression to acquired immunodeficiency syndrome, HIV diagnostics, assays used to assess stage of disease and response to antiretroviral treatment, and highly active antiretroviral therapy. A team of basic science and clinical faculty in the disciplines of microbiology, immunology, infection prevention and control, clinical medicine, pharmacology, and medical ethics collaboratively designed the CBL module. The results of a questionnaire indicated that the students found the CBL case interesting, engaging, and a useful educational strategy for linking basic science concepts to important clinical problems. In our experience, the CBL promoted student synthesis of basic science concepts across disciplines and engaged learners in the application of basic science knowledge to address significant real-world clinical problems.

TB or not TB? Mycobacterium celatum mimicking Mycobacterium tuberculosis: A case of mistaken identity.

Mycobacterium celatum is a slow-growing, non-tuberculous mycobacterium (NTM) and a rare cause of infection in humans. Infection occurs primarily by inhalation or direct inoculation from environmental sources, and this pathogen has been reported to cause localized infections in the lungs and lymph nodes of both immunocompetent and immunocompromised patients, and disseminated disease in immunocompromised patients. Here, we present a case of pulmonary infection with M. celatum in an immunocompetent 68-year-old male with clinical features similar to tuberculosis. The patient initially developed palpitations, worsening fatigue, night sweats, dyspnea, productive cough, and weight loss. Computed tomography angiogram of the chest revealed a right upper lobe pulmonary artery embolus and extensive biapical fibronodular cavitary densities. Two separate sputum samples were positive for acid-fast bacilli (AFB) and sputum cultures were positive for M. celatum. The patient responded well to treatment with clarithromycin, ciprofloxacin, and ethambutol. We advise physicians to consider M. celatum infection in the differential diagnosis of patients with symptoms and radiographic and microbiologic evidence suggestive of NTM pulmonary infection.

Involving a real patient in the design and implementation of case-based learning to engage learners.

Real patients offer unique opportunities to develop authentic, engaging, and transformative learning experiences for students. Patients are widely employed to teach clinical and interpersonal skills in the clerkship phase of their medical education (M3-M4), but have not been extensively included in the preclinical curriculum (M1-M2) when students are focused on acquiring foundational biomedical science knowledge. To maximize learning and help students connect foundational and clinical science concepts to real-world clinical problems, we involved a real patient in the creation and implementation of a case-based learning (CBL) activity in our preclinical curriculum. Using the patient's narrative as a framework, the CBL addressed relevant aspects of physiology, pathophysiology, anatomy, pharmacology, and nutrition, as well as clinical care decisions, health literacy, and medical ethics. The intervention was implemented with the 2019 and 2020 graduating medical school classes during the Gastrointestinal Systems course in the second year of our curriculum. The results of a survey revealed that, overall, a majority of the students agreed or strongly agreed that the activity increased engagement in class, increased the depth of discussion within their teams, increased the depth of discussion between teams, helped students to apply basic science concepts to the clinical material in the case, helped students better understand the disease processes described in the case, enhanced awareness of the complexity of patient care, provided an authentic learning experience, and elicited a feeling of empathy.

Unraveling the immunopathogenesis of glomerular disease.

Immune-mediated damage to glomerular structures is largely responsible for the pathology associated with the majority of glomerular diseases. Therefore, a detailed understanding of the basic immune mechanisms responsible for glomerular damage is needed to inform the design of novel intervention strategies. Glomerular injury of immune origin is complex and involves both inflammatory and non-inflammatory processes driven by elements of the innate and adaptive immune system. This review summarizes the basic immune mechanisms that cause glomerular injury leading to the nephritic and nephrotic syndromes. A major focus of the review is to highlight the mechanisms by which antibodies cause glomerular injury through their interactions with glomerular cells, complement proteins, phagocytes bearing complement and Fcγ receptors, and dendritic cells expressing the neonatal receptor for IgG, FcRn.

The cystine/glutamate antiporter regulates indoleamine 2,3-dioxygenase protein levels and enzymatic activity in human dendritic cells.

Indoleamine 2,3-dioxygenase (IDO) is the rate-limiting enzyme in the tryptophan-catabolizing pathway and a key regulator of peripheral immune tolerance. As the suppressive effects of IDO are predominantly mediated by dendritic cells (DCs) and IDO-competent DCs promote long-term immunologic tolerance, a detailed understanding of how IDO expression and activity is regulated in these cells is central to the rational design of therapies to induce robust immune tolerance. We previously reported that the cystine/glutamate antiporter modulates the functional expression of IDO in human monocyte-derived DCs. Specifically, we showed that blocking antiporter uptake of cystine significantly increased both IDO mRNA and IDO enzymatic activity and that this correlated with impaired DC presentation of exogenous antigen to T cells via MHC class II and the cross-presentation pathway. The antiporter regulates intracellular and extracellular redox by transporting cystine into the cell in exchange for glutamate. Intracellular cystine is reduced to cysteine to support biosynthesis of the major cellular antioxidant glutathione and cysteine is exported from the cell where it functions as an extracellular antioxidant. Here we show that antiporter control of IDO expression in DCs is reversible, independent of interferon-γ, regulated by redox, and requires active protein synthesis. These findings highlight a role for antiporter regulation of cellular redox as a critical control point for modulating IDO expression and activity in DCs. Thus, systemic disease and aging, processes that perturb redox homeostasis, may adversely affect immunity by promoting the generation of IDO-competent DCs.

The cystine/glutamate antiporter regulates dendritic cell differentiation and antigen presentation.

The major cellular antioxidant glutathione is depleted during HIV infection and in obesity. Although the consequence of glutathione depletion on immune function is starting to emerge, it is currently not known whether glutathione dysregulation influences the differentiation and maturation of dendritic cells (DCs). Moreover, the effect of glutathione depletion on DC effector functions, such as Ag presentation, is poorly understood. Glutathione synthesis depends on the cystine/glutamate antiporter, which transports the rate-limiting precursor cystine into the cell in exchange for glutamate. In this paper, we present a detailed study of antiporter function in DCs and demonstrate a role for the antiporter in DC differentiation and cross-presentation. We show that the antiporter is the major mechanism for transport of cystine and glutamate and modulates the intracellular glutathione content and glutathione efflux from DCs. Blocking antiporter-dependent cystine transport decreases intracellular glutathione levels, and these effects correlate with reduced transcription of the functional subunit of the antiporter. We further demonstrate that blocking antiporter activity interferes with DC differentiation from monocyte precursors, but antiporter activity is not required for LPS-induced phenotypic maturation. Finally, we show that inhibiting antiporter uptake of cystine interferes with presentation of exogenous Ag to class II MHC-restricted T cells and blocks cross-presentation on MHC class I. We conclude that aberrant antiporter function disrupts glutathione homeostasis in DCs and may contribute to impaired immunity in the diseased host.

Crosstalk between PKA and Epac regulates the phenotypic maturation and function of human dendritic cells.

The cAMP-dependent signaling pathways that orchestrate dendritic cell (DC) maturation remain to be defined in detail. Although cAMP was previously thought to signal exclusively through protein kinase A (PKA), it is now clear that cAMP also activates exchange protein activated by cAMP (Epac), a second major cAMP effector. Whether cAMP signaling via PKA is sufficient to drive DC maturation or whether Epac plays a role has not been examined. In this study, we used cAMP analogs to selectively activate PKA or Epac in human monocyte-derived DCs and examined the effect of these signaling pathways on several hallmarks of DC maturation. We show that PKA activation induces DC maturation as evidenced by the increased cell-surface expression of MHC class II, costimulatory molecules, and the maturation marker CD83. PKA activation also reduces DC endocytosis and stimulates chemotaxis to the lymph node-associated chemokines CXCL12 and CCL21. Although PKA signaling largely suppresses cytokine production, the net effect of PKA activation translates to enhanced DC activation of allogeneic T cells. In contrast to the stimulatory effects of PKA, Epac signaling has no effect on DC maturation or function. Rather, Epac suppresses the effects of PKA when both pathways are activated simultaneously. These data reveal a previously unrecognized crosstalk between the PKA and Epac signaling pathways in DCs and raise the possibility that therapeutics targeting PKA may generate immunogenic DCs, whereas those that activate Epac may produce tolerogenic DCs capable of attenuating allergic or autoimmune disease.

Ca2+-dependent calmodulin binding to FcRn affects immunoglobulin G transport in the transcytotic pathway.

The Fcgamma receptor FcRn transports immunoglobulin G (IgG) so as to avoid lysosomal degradation and to carry it bidirectionally across epithelial barriers to affect mucosal immunity. Here, we identify a calmodulin-binding site within the FcRn cytoplasmic tail that affects FcRn trafficking. Calmodulin binding to the FcRn tail is direct, calcium-dependent, reversible, and specific to residues comprising a putative short amphipathic alpha-helix immediately adjacent to the membrane. FcRn mutants with single residue substitutions in this motif, or FcRn mutants lacking the cytoplasmic tail completely, exhibit a shorter half-life and attenuated transcytosis. Chemical inhibitors of calmodulin phenocopy the mutant FcRn defect in transcytosis. These results suggest a novel mechanism for regulation of IgG transport by calmodulin-dependent sorting of FcRn and its cargo away from a degradative pathway and into a bidirectional transcytotic route.

Bidirectional transepithelial IgG transport by a strongly polarized basolateral membrane Fcgamma-receptor.

The human MHC class I-related neonatal Fc receptor, hFcRn, mediates bidirectional transport of IgG across mucosal barriers. Here, we find that at steady state hFcRn distributes predominantly to an apical intracellular compartment and almost exclusively to the basolateral cell surface of polarized epithelial cells. It moves only transiently to the apical membrane. Ligand binding does not redistribute the steady state location of the receptor. Removal of the cytoplasmic tail that contains di-leucine and tryptophan-based endocytosis motifs or incubation at low temperature (18 degrees C) redistributes the receptor apically. The rates of endocytosis of the full-length hFcRn from the apical or basolateral membrane domains, however, are equal. Thus, the strong cell surface polarity displayed by hFcRn results from dominant basolateral sorting by motifs in the cytoplasmic tail that nonetheless allows for a cycle of bidirectional transcytosis.

Distribution of the IgG Fc receptor, FcRn, in the human fetal intestine.

The intestinal Fc receptor, FcRn, functions in the maternofetal transfer of gamma globulin (IgG) in the neonatal rodent. In humans, most of this transfer is presumed to occur in utero via the placenta. Although the fetus swallows amniotic fluid that contains immunoglobulin, it is unknown whether this transfer also occurs via the fetal intestine. A human FcRn has been identified in the syncytiotrophoblast that mediates the maternofetal transfer of antibody. It has also been identified in human fetal intestine and is postulated to function in IgG transport. We hypothesize that the human fetal intestinal FcRn may play a role in IgG transport from the amniotic fluid into the fetal circulation. The aim of this study was to characterize the distribution of the FcRn along the human fetal intestine. Lysates prepared from human fetal intestine and from a nonmalignant human fetal intestinal epithelial cell line (H4) were subjected to Western blot analysis and probed using anti-FcRn antibodies. A 42-kD band, consistent with the known molecular weight of the FcRn, was detected along the human fetal intestine and in H4 cells. Expression of the human FcRn was confirmed with immunohistochemistry. Our study demonstrates the expression of FcRn along the human fetal intestine and in a human nonmalignant fetal intestinal epithelial cell line (H4), which by location indicates that FcRn could play a role in the uptake and transport of IgG in the human fetus.

Receptor-mediated immunoglobulin G transport across mucosal barriers in adult life: functional expression of FcRn in the mammalian lung.

Mucosal secretions of the human gastrointestinal, respiratory, and genital tracts contain the immunoglobulins (Ig)G and secretory IgA (sIgA) that function together in host defense. Exactly how IgG crosses epithelial barriers to function in mucosal immunity remains unknown. Here, we test the idea that the MHC class I-related Fc-receptor, FcRn, transports IgG across the mucosal surface of the human and mouse lung from lumen to serosa. We find that bronchial epithelial cells of the human, nonhuman primate, and mouse, express FcRn in adult-life, and demonstrate FcRn-dependent absorption of a bioactive Fc-fusion protein across the respiratory epithelium of the mouse in vivo. Thus, IgG, like dimeric IgA, can cross epithelial barriers by receptor-mediated transcytosis in adult animals. These data show that mucosal surfaces that express FcRn reabsorb IgG and explain a mechanism by which IgG may act in immune surveillance to retrieve lumenal antigens for processing in the lamina propria or systemically.

Functional reconstitution of human FcRn in Madin-Darby canine kidney cells requires co-expressed human beta 2-microglobulin.

The major histocompatibility complex class I-related neonatal Fc receptor, FcRn, assembles as a heterodimer consisting of a heavy chain and beta(2)-microglobulin (beta(2)m), which is essential for FcRn function. We observed that, in Madin-Darby canine kidney (MDCK) cells, the function of human FcRn in mediating the bidirectional transport of IgG was significantly increased upon co-expression of the human isoform of beta(2)m. In MDCK cells, the presence of human beta(2)m endowed upon human FcRn an enhanced ability to exit the endoplasmic reticulum and acquire mature carbohydrate side-chain modifications at steady state, a faster kinetics of maturation, and augmented localization at the cell surface as a mature glycoprotein able to bind IgG. Although human FcRn with immature carbohydrate side-chain modifications was capable of exhibiting pH-dependent binding of IgG, only human FcRn with mature carbohydrate side-chain modifications was detected on the cell surface. These results show that human FcRn travels to the cell surface via the normal secretory pathway and that the appropriate expression and function of human FcRn in MDCK cells depends upon the co-expression of human beta(2)m.