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Tetracyclic 6H-naphtho[2,1-c]chromenes are expeditiously synthesized through a BF3·OEt2-mediated, three-step cascade reaction, creating new central pyran and aromatic rings. The cascade involves th...

There is a growing literature on how medical education adapts to the COVID-19 pandemic. However, there is a need to examine the facilitators and barriers of these adaptations. This study explores the strengths, weaknesses, opportunities, and threats (SWOT) of how Italian medical schools adapted their curricula to the COVID −19 pandemic. The authors conducted an online survey of directors of medical curricula in Italy. Free-text responses to open-ended questions about curricular adaptations and reflections on these adaptations were analysed using qualitative thematic analysis. Twenty out of 60 Italian medical school directors completed the survey. Strengths identified were rapid responses and a spirit of cooperation. Weaknesses included dependency on clinical facilities, teachers’ limited skills to use technology, and lack of mental health support for staff. Opportunities highlighted were clear government rules, new ways of teaching and a renewed focus on underrepresented topics. Threats expressed included impaired relationships, difficulties related to online assessment, lack of IT access, and legal and insurance issues. This study, in documenting the curricular adaptations of Italian medical schools during an active global pandemic, and recording the perspectives of medical education leaders, offers important lessons for the future.

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To identify medical school factors graduates in major leadership positions perceive as contributing to their leadership development.Using a phenomenological, qualitative approach, in August-November 2015 the authors conducted semistructured interviews with 48 medical leaders who were 1976-1999 baccalaureate-MD graduates of the University of Missouri-Kansas City School of Medicine (UMKC). At UMKC, they participated in longitudinal learning communities, the centerpiece for learning professional values and behaviors plus clinical skills, knowledge, and judgment, but received no formal leadership instruction. The authors subjected interview comments to directed, largely qualitative content analysis with iterative coding cycles.Most graduates said their experiences and the people at UMKC positively influenced their leadership growth. Medical school factors that emerged as contributing to that growth were the longitudinal learning communities including docents, junior-senior partners, and team experiences; expectations set for students to achieve; a clinically oriented but integrated curriculum; admission policies seeking students with academic and nonacademic qualifications; supportive student-student and student-faculty relationships; and a positive overall learning environment. Graduates viewed a combination of factors as best preparing them for leadership and excellence in clinical medicine; together these factors enabled them to assume leadership opportunities after graduation.This study adds medical leaders' perspective to the leadership development literature and offers guidance from theory and practice for medical schools to consider in shaping leadership education: Namely, informal leadership preparation coupled with extensive longitudinal clinical education in a nurturing, authentic environment can develop students effectively for leadership in medicine.

Medical education literature has been found to lack key components of scientific reporting, including adequate descriptions of literature searches, thus preventing medical educators from replicating and building on previous scholarship. The purpose of this study was to examine the reproducibility of search strategies as reported in medical education literature reviews.The authors searched for and identified literature reviews published in 2009 in Academic Medicine, Teaching and Learning in Medicine, and Medical Education. They searched for citations whose titles included the words "meta-analysis," "systematic literature review," "systematic review," or "literature review," or whose publication type MEDLINE listed as "meta-analysis" or "review." The authors created a checklist to identify key characteristics of literature searches and of literature search reporting within the full text of the reviews. The authors deemed searches reproducible only if the review reported both a search date and Boolean operators.Of the 34 reviews meeting the inclusion criteria, 19 (56%) explicitly described a literature search and mentioned MEDLINE; however, only 14 (41%) also mentioned searches of nonmedical databases. Eighteen reviews (53%) listed search terms, but only 6 (18%) listed Medical Subject Headings, and only 2 (6%) mentioned Boolean operators. Fifteen (44%) noted the use of limits. None of the reviews included reproducible searches.According to this analysis, literature search strategies in medical education reviews are highly variable and generally not reproducible. The authors provide recommendations to facilitate future high-quality, transparent, and reproducible literature searches.

The authors present an overview of the educational programs, infrastructure to support them, and the assessment strategies of 128 medical schools in the United States and Canada, based on reports submitted by those schools and published in this supplement to Academic Medicine. The authors explore many important changes that have occurred since the publication of the Flexner Report in 1910 as well as the progress that is evident since a similar collection of medical school reports was published in September 2000, also as a supplement to Academic Medicine. Drawing on the reports, the authors summarize, among other topics, the advances that have taken place in the support for faculty, the funding of medical student education, changes in pedagogy and assessment, and the expansion of medical education to distributed models and regional campuses.The authors observe that the reports from the 128 schools illustrate that medical student education has undergone and continues to undergo substantive change, has advanced markedly since the reforms stimulated by the Flexner Report, and has continued to evolve during the past decade. The reports illustrate the strength of support for the educational programs, even in a time of financial constraints, and the increasing recognition of the scholarly contributions of faculty through teaching. The authors provide examples of the changes in pedagogy and new topics in the required curriculum in the past decade and describe selected highlights of the 128 educational programs.

Background Prolonged exposure to ketamine results in accelerated neurodegeneration and neurocognitive deficits in the neonatal rats. Experimental models of neurodegeneration have implicated reentry of postmitotic neurons into the cell cycle, leading to cell death. The authors hypothesize that the ketamine-induced neuroapoptosis is partially due to aberrant cycle cell reentry. To explore this hypothesis, the authors characterized the effect of ketamine on the cell cycle signaling pathway in the developing rodent brain in vivo and in vitro. Methods Postnatal day 7 rat pups and primary neurons were used for the experiments. Each rat pup received five intraperitoneal doses of either saline or ketamine (5, 10, and 20 mg/kg/dose) at 90-min intervals over 6 h. Primary neurons were exposed to varying concentrations of ketamine to determine the dose and duration effects. The expression of cell cycle proteins (cyclin D1, cyclin-dependent kinase 4, and E2F1), Bcl2-interacting mediator of cell death (Bim), and activated caspase-3 was determined. The effect of cyclin D1 knockdown by small interfering RNA was also examined in primary neurons incubated in ketamine. Results Ketamine mediated a dose- and time-dependent increase in expression of cell cycle proteins and activated caspase-3. Cyclin D1, cyclin-dependent kinase 4, E2F1, Bim, and cleaved caspase-3 expression increased at 12 h and peaked at 24 h in vitro. Knockdown of cyclin D1 by small interfering RNA attenuated Bim and cleaved caspase-3 expression. Conclusion These findings support a model in which ketamine induces aberrant cell cycle reentry, leading to apoptotic cell death in the developing rat brain.

The ability to understand and integrate new knowledge into clinical practice is a necessary quality of good physicians. Student participation in in-depth scholarship could enhance this skill in physicians while also creating a larger cadre of physician-scientists prepared to advance the field of medicine. However, because no definitive data exist demonstrating that in-depth scholarship in medical school leads to improved patient care or to productive academic careers, whether such scholarship should be required as part of the medical school curriculum is unclear. In this article, the authors present both sides of this debate. Theoretical benefits to students of a required scholarly program include closer mentorship by individual faculty, enhanced capabilities in critical interpretation of research findings, and increased confidence to investigate conundrums encountered in clinical care. Society may also benefit by having physicians available to create and apply new knowledge related to biomedicine. These theoretical benefits must be balanced, however, by pragmatic considerations of required scholarly projects including their impact on medical school applications, their effect on the medical curriculum, their costs, the availability of mentors, and their effects on the school's educational culture.

In an effort to use model fluid membranes for immunological studies, we compared the formation of planar phospholipid bilayers supported on silicon dioxide surfaces with and without incorporation of glycolipids as the antigen for in situ antibody binding. Dynamic light scattering measurements did not differentiate the hydrodynamic volumes of extruded small unilamellar vesicles (E-SUVs) containing physiologically relevant concentrations (0.5-5 mol%) of monosialoganglioside GM1 (GM1) from exclusive egg yolk L-alpha-phosphatidylcholine (egg PC) E-SUVs. However, quantifiable differences in deposition mass and dissipative energy loss emerged in the transformation of 5 mol% GM1/95 mol% egg PC E-SUVs to planar supported lipid bilayers (PSLBs) by vesicle fusion on thermally evaporated SiO2, as monitored by the quartz crystal microbalance with dissipation (QCM-D) technique. Compared to the 100 mol% egg PC bilayers on the same surface, E-SUVs containing 5 mol% GM1 reached a approximately 12% higher mass and a lower dissipative energy loss during bilayer transformation. PSLBs with 5 mol% GM1 are approximately 18% heavier than 100 mol% egg PC and approximately 11% smaller in projected area per lipid, indicating an increased rigidity and a tighter packing. Subsequent binding of polyclonal immunoglobulin G anti-GM1 to the PSLBs was performed in situ and showed specificity. The anti-GM1 to GM1 ratios at equilibrium were roughly proportional to the concentrations of anti-GM1 administered in the solution. Fluorescence recovery after photobleaching was utilized to verify the retained, albeit reduced lateral fluidity of the supported membranes. Five moles percentage of GM1 membranes (GM1 to PC ratio approximately 1:19) decorated with 1 mol% N-(Texas Red sulfonyl)-1,2-dihexadecanoyl-sn-glycerol-3-phosphoethanolamine (Texas Red DHPE) exhibited an approximately 16% lower diffusion coefficient of 1.32+/-0.06 microm2/s, compared to 1.58+/-0.04 microm2/s for egg PC membranes without GM1 (p0.01). The changes in vesicle properties and membrane lateral fluidity are attributed to the interactions of GM1 with itself and GM1 with other membrane lipids. This system allows for molecules of interest such as GM1 to exist on a more biologically relevant surface than those used in conventional methods such as ELISA. Our analysis of rabbit serum antibodies binding to GM1 demonstrates this platform can be used to test for the presence of anti-lipid antibodies in serum.

Recent studies suggest that increased T-cell and autoantibody reactivity to lipids may be present in the autoimmune demyelinating disease multiple sclerosis. To perform large-scale multiplex analysis of antibody responses to lipids in multiple sclerosis, we developed microarrays composed of lipids present in the myelin sheath, including ganglioside, sulfatide, cerebroside, sphingomyelin and total brain lipid fractions. Lipid-array analysis showed lipid-specific antibodies against sulfatide, sphingomyelin and oxidized lipids in cerebrospinal fluid (CSF) derived from individuals with multiple sclerosis. Sulfatide-specific antibodies were also detected in SJL/J mice with acute experimental autoimmune encephalomyelitis (EAE). Immunization of mice with sulfatide plus myelin peptide resulted in a more severe disease course of EAE, and administration of sulfatide-specific antibody exacerbated EAE. Thus, autoimmune responses to sulfatide and other lipids are present in individuals with multiple sclerosis and in EAE, and may contribute to the pathogenesis of autoimmune demyelination.

Many U.S. medical schools offer students the opportunity to undertake laboratory or clinical research or another form of scholarly project over the summer months, yet few require this as a prerequisite for graduation, and even fewer provide comprehensive didactic material in preparation for the performance of such a project as an integrated component of their curricula. The authors describe the Scholarly Project Initiative of the University of Pittsburgh School of Medicine, a novel, longitudinal, and required program. The program will aim to provide all students with structured preparatory coursework, foster critical analytical and communication skills, and introduce the breadth and depth of the research and scholarly enterprise engendered by modern academic medicine in the contexts of both the classroom and an individual, mentored experience. The initiative has two goals: encouraging an interest in academic medicine in an era marked by the continuing decline in the number of physician-investigators, and fostering the development of physicians who have confidence in their abilities to practice medicine with creativity, original and analytical thought, and relentless attention to the scientific method. Planning for the Scholarly Project Initiative began officially at the University of Pittsburgh School of Medicine's Curriculum Colloquium in May 2003. The initiative was implemented with the first-year class of July 2004 as part of the new "Scientific Reasoning and Medicine" block of the School of Medicine's curriculum. The block as a whole includes traditional lectures, small-group laboratory and problem-based sessions, and mentored independent study components.

This article was migrated. The article was marked as recommended. Brazilian educator Paulo Freire argues that the purpose of education is to liberate human potential and, thus, is much more than a teacher simply depositing information into the mind of a learner. His ideas are important to medical education because 1) they strengthen the philosophical underpinning of practices in medical education (for example, Freire's dialogical approach to learning vis-à-vis the banking model of education adds philosophic strength to the use of problem-based learning as a primary learning modality); 2) they encourage medical educators to confront directly the tension between teaching for conformity, which many would argue is key to performing a good and reliable physical examination, and teaching to liberate human potential, which is critical to preparing physicians to question current assumptions, practices, and knowledge; and 3) they encourage expanded thought about approaches to medical education, for example in the choice of pedagogical method, defining the role of the educator, and the use of experiences like service learning.

Results (Scientific Abstract)/Collaborative Partners (Programmatic Abstract): We initially identified 33 EV indictors grouped in six categories: 1) geographic setting (eight, e.g., urban vs. rural); 2) study population (seven, e.g., gender); 3) implementation characteristics (six, e.g., adherence efforts); 4) institutional and legal context (three e.g., stigma); 5) ability to scale with quality (two e.g., implementation scale); and 6) HTC-specific indicator (seven, e.g., service delivery mode). After the first round of expert elicitation, we added one indicator and dropped one. Four (12%) indicators were excluded due to lack of variability (>90% studies reported the same characteristics) and four (12%) due to excessive (>70%) missing data, cumulatively comprising 27% of total weights. Seventeen of 25 (68%) remaining indicators comprised the top 80% of the total renormalized weights. The bottom five least weighted indicators were: 1) WHO region 0.4 %; 2) WHO subregion 0.8%; 3) country 0.8%; 4) national per capita government health spending 1.5%; and 5) country-level income 1.7%, and the top most weighted indicators: 1) target age group 6.4%; 2) service delivery mode 5.7%; 3) type of post-test counseling 5.5%; 4) stigma for intervention 5.5%; and 5) HIV epidemic type 5.4%. Summary/Conclusion: More attention should be given to EV for translation of evidence to real-world global health practice. Our study proposes a target-specific definition for EV: The likelihood that intervention effects observed in a set of studies will be replicated if implemented in a different target setting. Intervetion-specific indicators should be carefully explored for other EV tools. Validation of our tool is underway.

Two dissimilar U.S. medical schools—the University of Pittsburgh School of Medicine and the University of Texas Medical Branch at Galveston—changed their curricula for the first two years of medical education from ones that were lecture-dominated and departmentally run to ones that are centrally governed, multi-modal, goaloriented, and fully integrated, with mechanisms to continue curricular change into the last two years of medical education. The change at each school was in response to national education philosophy, the recommendations of the Liaison Committee for Medical Education after the most recent site visit, and faculty’s and students’ concerns and interests. The change process took place over a three- to fouryear period at each school, involved students, faculty, and administration, and utilized task forces and retreats as communication vehicles. The barriers encountered (e.g., belief by some that the curriculum needed no change; concern over loss of departments’ control) and the processes employed to overcome them and to radically change the curricula (e.g., commitment of the central administration and dean to the change, involvement of all segments of the school in the change process, appointment of department chairs on task forces, and creation of a strong curriculum committee that gave authority to faculty and students) were essentially identical. The resulting curricula were also largely similar in their main characteristics, but there were notable differences, based on the goals and concerns of the two institutions. Acad. Med. 2000;75:595‐601.

Lipids comprise 70% of the myelin sheath, and autoantibodies against lipids may contribute to the demyelination that characterizes multiple sclerosis (MS). We used lipid antigen microarrays and lipid mass spectrometry to identify bona fide lipid targets of the autoimmune response in MS brain, and an animal model of MS to explore the role of the identified lipids in autoimmune demyelination. We found that autoantibodies in MS target a phosphate group in phosphatidylserine and oxidized phosphatidylcholine derivatives. Administration of these lipids ameliorated experimental autoimmune encephalomyelitis by suppressing activation and inducing apoptosis of autoreactive T cells, effects mediated by the lipids’ saturated fatty-acid side chains. Thus, phospholipids represent a natural anti-inflammatory class of compounds that have potential as novel therapeutics for MS.

PURPOSE To identify sucessful teaching techniques in the operating room environment through examining the teaching of the midurethral sling (MUS) surgery. METHOD The authors distributed questionnaires with open-ended questions about teaching and learning MUS to 5 urogynecology attendings and 16 obstetrics-gynecology residents in spring 2010. In an effort to identify qualities of an effective sling teacher, the authors used grounded theory to determine common themes and to code participant responses for examples. RESULTS Of 21 potential respondents, 14 (67%) returned questionnaires. The authors analyzed these and identified seven commonalities among effective sling teachers: they (1) emphasize anatomical landmarks (as determined by 64 total comments); (2) use perceptual-motor teaching (PMT; 38 comments); (3) encourage repetition (28); (4) promote early independence (34); (5) demonstrate confident competence (23); (6) maintain a calm demeanor in the operating room (20); and (7) exhibit a willingness to accept responsibility for mistakes and consequences (9). The second-most common attribute, using PMT, requires the teaching attending to emphasize the motor and tactile aspects of operating and involves incorporating not only what learners see but also what they feel. CONCLUSIONS The authors report seven qualities or techniques fundamental to good teaching practice in a high-stress, high-technology surgical environment, and they have identified the use of PMT, which to their knowledge has not been previously described. Teachers and learners in this study characterized PMT, which is likely generalizable to surgical procedures other than the MUS, as important. Future research should focus on exploring this technique in other surgeries.

• Journal articles • Diverse disciplines • Journal articles, book chapters, dissertations, abstracts • Education literature • Journal articles, book chapters, Association of American Medical Colleges reports • Nursing and allied health literature • Journal articles, book chapters, dissertations, audiovisuals • Scientific, technical, medical and social sciences literature, citation searching • Journal articles, conference papers

PURPOSE U.S. medical students will soon complete only one licensure examination sequence, given near the end of medical school. Thus, schools are challenged to identify poorly performing students before this high-stakes test and help them retain knowledge across the duration of medical school. The authors investigated whether online spaced education progress-testing (SEPT) could achieve both aims. METHOD Participants were 2,648 students from four U.S. medical schools; 120 multiple-choice questions and explanations in preclinical and clinical domains were developed and validated. For 34 weeks, students randomized to longitudinal progress-testing alone (LPTA) received four new questions (with answers/ explanations) each week. Students randomized to SEPT received the identical four questions each week, plus two-week and six-week cycled reviews of the questions/explanations. During weeks 31-34, the initial 40 questions were re-sent to students to assess longer-term retention. RESULTS Of the 1,067 students enrolled, the 120-question progress-test was completed by 446 (84%) and 392 (74%) of the LPTA and SEPT students, respectively. Cronbach alpha reliability was 0.87. Scores were 39.9%, 51.9%, 58.7%, and 58.8% for students in years 1-4, respectively. Performance correlated with Step 1 and Step 2 Clinical Knowledge scores (r = 0.52 and 0.57, respectively; P < .001) and prospectively identified students scoring below the mean on Step 1 with 75% sensitivity, 77% specificity, and 41% positive predictive value. Cycled reviews generated a 170% increase in learning retention relative to baseline (P < .001, effect size 0.95). CONCLUSIONS SEPT can identify poorly performing students and improve their longer-term knowledge retention.

The story of Abraham Flexner's role in the founding of the Institute for Advanced Study in Princeton, New Jersey, offers important insights into Flexner himself and valuable lessons for contemporary leaders in academic medicine. The authors review this remarkable achievement along with Flexner's other accomplishments in the 49 years he lived after the 1910 publication of his report on medical schools in the United States and Canada. Lessons include his approach to philanthropy, his determination and networking, his belief in the synergism between the natural sciences and the humanities, and his regard for learning as a lifelong process. Flexner's record was not unblemished, however, and the cases in which he faltered also offer important lessons for today's academic leaders.

This article provides historical background on Henry S. Pritchett, first president of the Carnegie Foundation for the Advancement of Teaching (CFAT), analysis of his introduction to Abraham Flexner's 1910 report on medical education, and discussion of the major role that Pritchett played in conceiving the study on which the Flexner Report is based and his advocacy of the report's findings. The authors examine Pritchett's career as a scientist, scholar, and administrator. A textual analysis of the introduction to the Flexner Report demonstrates Pritchett's unique contributions to the report and how they complement Flexner's perspectives and conclusions. Finally, the authors discuss the significance of Pritchett's introduction, his rhetorical choices, and Pritchett's and CFAT's subsequent advocacy activities to improve medical education.

Most medical schools and postgraduate programs devote some time to teaching evidence-based medicine (EBM). EBM encompasses five essential skills, including constructing a sound clinical question, literature searching, critical appraisal, gaining a full understanding of study results, and integration of results into patient care. Gaining a full understanding of results requires understanding the statistical aspects of and terminology associated with the design, analysis, and results of original research--hereby referred to as physician numeracy. Physicians and physicians-in-training recognize the importance of these concepts but are uncomfortable with and demonstrate poor knowledge of the quantitative aspects of research. This is not surprising since few curricula include physician numeracy. Current approaches to teaching EBM rely on journal clubs, which have not been shown to improve participants' self-perceived EBM skills. In this paper we describe a novel approach to teaching EBM which makes use of five guiding principles: (1) Journal clubs have important limitations, (2) understanding the quantitative aspects of research promotes an in-depth understanding of papers, (3) physician numeracy can form the basis of an EBM course, (4) consumers of original research ought to determine what is useful about a paper rather than whether or not it is useful, and (5) numeracy should encompass only those concepts needed to accurately interpret evidence and apply it to individual patients. An EBM curriculum based on physician numeracy is described, together with the challenges inherent to this approach.

An increasing number of medical schools have implemented or are considering implementing scholarly activity programs as part of their undergraduate medical curricula. The goal of these programs is to foster students' analytical skills, enhance their self-directed learning and their oral and written communication skills, and ultimately to train better physicians. In this article, the authors describe the approach to implementing scholarly activities at a school that requires this activity and at a school where it is elective. Both programs have dealt with significant challenges including orienting students to a complex activity that is fundamentally different than traditional medical school courses and clerkships, helping both students and their mentors understand how to "stay on track" and complete work, especially during the third and fourth years, and educating students and mentors about the responsible conduct of research, especially involving human participants. Both schools have found the implementation process to be evolutionary, requiring experience before faculty could significantly improve processes. A required scholarly activity has highlighted the need for information technology (IT) support, including Web-based document storage and student updates, as well as automatic e-mails alerting supervisory individuals to student activity. Directors of the elective program have found difficulty with both ensuring uniform outcomes across different areas of study and leadership changes in a process that has been largely student-driven. Both programs have found that teamwork, regular meetings, and close communication have helped with implementation. Schools considering the establishment of a scholarly activity should consider these factors when designing programs.

Electrical propagation in the normal heart occurs via intercellular transfer of current at gap junctions. Alterations in intercellular coupling in the diseased heart are critical in the pathogenesis of reentrant ventricular arrhythmias. Until recently only a single gap junction protein was known to couple cardiac myocytes. We have now identified and sequenced two additional distinct gap junction proteins (connexins) expressed in the mammalian heart. The sequences differ in their predicted cytoplasmic regulatory domains. Expression of all three connexins by canine ventricular myocytes has been confirmed by Northern blotting and by immunohistochemistry with connexin-specific antisera. Immunoelectron microscopy confirmed that all three connexins are localized to myocyte gap junctions. The presence of multiple connexins in myocyte gap junctions suggests novel mechanisms for regulating cardiac electrical coupling.

The authors celebrate the 30th anniversary of Lewis Thomas's provocative essay, "How to Fix the Premedical Curriculum," by reexamining its three central themes: the influence of medical schools on undergraduate education, the selection of students for admission to medical school, and a radical proposed reform of premedical education. At issue are fundamental questions concerning the relationship between the liberal arts and medical education--questions that are no less vital today than when Thomas first posed them: What is the purpose of undergraduate education? How closely aligned are the undergraduate and graduate phases of medical education? What do future physicians need to know that is not taught in medical school? Thomas reminds us that the undergraduate curriculum is no less vital to the future of medicine than medical school itself, and that premature specialization does not serve the best interests of future physicians or patients. Instead of treating premedical education as a mere prelude to medical school, we should encourage undergraduates to take full advantage of their college years as an opportunity to develop as human beings.

Introduction Anti-citrullinated protein antibodies have a diagnostic role in rheumatoid arthritis (RA); however, little is known about their origins and contribution to pathogenesis. Citrullination is the post-translational conversion of arginine to citrulline by peptidyl arginine deiminase, and increased citrullination of proteins is observed in the joint tissue in RA and in brain tissue in multiple sclerosis (MS). Methods We applied synovial and myelin protein arrays to examine epitope spreading of B cell responses to citrullinated epitopes in both the collagen-induced arthritis (CIA) model for RA and the experimental autoimmune encephalomyelitis (EAE) model for MS. Synovial and myelin protein arrays contain a spectrum of proteins and peptides, including native and citrullinated forms, representing candidate autoantigens in RA and MS, respectively. We applied these arrays to characterise the specificity of autoantibodies in serial serum samples derived from mice with acute and chronic stages of CIA and EAE. Results In samples from pre-disease CIA and acute-disease EAE, we observed autoantibody targeting of the immunising antigen and responses to a limited set of citrullinated epitopes. Over the course of diseases, the autoantibody responses expanded to target multiple citrullinated epitopes in both CIA and EAE. Using immunoblotting and mass spectrometry analysis, we identified citrullination of multiple polypeptides in CIA joint and EAE brain tissue that have not previously been described as citrullinated. Conclusions Our results suggest that anti-citrulline antibody responses develop in the early stages of CIA and EAE, and that autoimmune inflammation results in citrullination of joint proteins in CIA and brain proteins in EAE, thereby creating neoantigens that become additional targets in epitope spreading of autoimmune responses.