Implementation of team-based learning (TBL) in a second year medical school course: does prior experience with TBL improve the impact of this pedagogy?

BACKGROUND: We have shown that use of Team-based learning (TBL) in a first-year Infectious Diseases (ID) course improved final examination and course performance. Therefore, we implemented TBL in the second-year Women's Health (WH) course to improve acquisition of course content. We hypothesized that prior experience with TBL in the first-year of medical school would lead to a strong correlation between TBL performance in the first and second years. METHODS: Our study is a retrospective review of student TBL and final examination performance in the ID and WH courses. The ID course has weekly TBL exercises that cover all course material, while the WH course has one TBL that covers a small portion of the course material. Final examination and TBL individual readiness assurance test (iRAT) scores in the ID and WH courses from three classes (n = 226) were obtained with institutional review board approval. Statistical analyses were performed including comparisons of means and correlation studies. RESULTS: Average WH iRAT scores were significantly higher than ID iRAT scores (9.19 vs. 7.40,p < 0.01), and iRAT scores in both courses were highly correlated (r = 0.35,p < 0.01). When stratifying students based on WH course performance, in struggling students, iRAT but not final examination scores were higher in the WH course than the ID course (8.73 vs. 7.00,p < 0.01 and 82.45 vs. 80.51,p > 0.05, respectively). CONCLUSIONS: Our results suggest that prior experience with TBL improves TBL iRAT scores, especially in struggling students. Prior TBL experience is also associated with consistent iRAT performance between first- and second-year courses in high performing students.

Protective Adaptive Immunity Against Severe Acute Respiratory Syndrome Coronaviruses 2 (SARS-CoV-2) and Implications for Vaccines.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging human coronavirus responsible for coronavirus disease 2019 (COVID-19), a predominantly respiratory disease that has become a global pandemic. Millions of people worldwide are suffering from COVID-19, and hundreds of thousands of those infected have died. Nevertheless, many more people who have been infected with SARS-CoV-2 are asymptomatic or suffer a mild disease characterized by dry cough and mild fever. This new pandemic poses a threat to public health on a global scale, and an intervention to prevent continued spread of SARS-CoV-2 virus is of the utmost importance. To assess preventive and therapeutic strategies, it is imperative to understand the pathogenesis and immune response against SARS-CoV-2. In this review, we concentrate on the protective adaptive immune response elicited by this novel coronavirus as well as requirements for a successful vaccine inducing optimal protection.

First year medical student performance on weekly team-based learning exercises in an infectious diseases course: insights from top performers and struggling students.

BACKGROUND: In Team-Based Learning (TBL) preparation of relevant coursework during self-directed learning time is evaluated by the individual readiness assurance test (iRAT). We recently reported that student performance on iRATs is strongly correlated with final examination scores in an infectious diseases (ID) course. We now investigated how student preparation for each individual iRAT exercise relates to course performance. METHODS: Two-hundred and sixty medical students were enrolled in this three-year study. Student TBL iRAT scores were collected and correlated with final examination scores using Kruskal-Wallis One-Way ANOVA and Newman-Keul's statistical methods. RESULTS: Students performing in the upper and middle 33rd percentile on the final examination showed highly significant (p < 0.01) weekly improvements in their iRAT scores. However, students performing in the lower 33rd percentile did not show improvement in their iRAT scores until the last week of the course. Although there was a highly significant correlation between final examination and iRAT scores amongst all students participating in the study, this correlation was stronger in students performing in the lower 33rd percentile. CONCLUSIONS: Our data suggest that students who do not consistently prepare for TBL, as evidenced by low iRAT scores, exhibit poorer performance on the final examination. This lack of preparation likely interferes with the efficacy of this learning method. iRAT scores can also be used for early identification of struggling students in need of additional supports. Additionally, changes in TBL incentive structure may provide more tangible rewards for pre-class preparation in particular for struggling students.

Participation in Active Learning Correlates to Higher Female Performance in a Pipeline Course for Underrepresented Students in Medicine.

This study was designed to explore the relationship between participation (measured by percentage of time spoken) in team-based learning (TBL) exercises and final examination in a 4-week medical microbiology course for college students from backgrounds underrepresented in medicine (URM). A significant correlation was found between participation and examination scores in lower performing students. Although male participation was higher, a significant correlation between participation and examination scores was found only in females. These data suggest that female participation is based on knowledge of the subject under discussion and that affirmation in TBL positively reinforces self-confidence, increasing student's efficiency during peer teaching.

Implementation of Team-Based Learning: a Tale of Two New Medical Schools.

Team-based learning (TBL) is gaining popularity at medical schools transitioning from lecture-based to active learning curricula. Here, we review challenges and opportunities faced in implementing TBL at 2 new medical schools. We discuss the importance of using meaningful TBL grades as well as the role TBL plays in developing critical reasoning skills and in early identification of struggling students. We also discuss how the concurrent use of learning strategies with different incentive structures such as problem- and case-based learning could foster the development of well-rounded physicians. We hope this monograph helps and even inspires educators implementing TBL at their schools.

A Novel Grading Strategy for Team-Based Learning Exercises in a Hands-on Course in Molecular Biology for Senior Undergraduate Underrepresented Students in Medicine Resulted in Stronger Student Performance.

We developed a hands-on course in molecular biology for undergraduate underrepresented in medicine (URM) students. To incentivize student preparation for team-based learning (TBL) activities, we implemented a novel grading schema that requires a minimum individual readiness assurance test (iRAT) score to share the team group readiness assurance test (gRAT) score. Fifty-one students participated in this 2-year study and were divided in teams of five or six students that worked throughout the course on a unique, hands-on project and also participated in TBL exercises. In the laboratory sessions, students isolated RNA from cultured neuronal cells, synthesized complementary DNA (cDNA), and used gene sequencing to identify a gene relevant in human health and disease. Student participation in TBL was quantified and correlated with performance on individual iRATs and the course final examination. We found that implementation of the novel incentive structure lowered the variance of TBL scores (iRAT and gRAT) and strengthened the correlation between final examination scores and either iRAT scores or percentage participation in TBL. Subgroup analysis showed that with the new grading schema, stronger students benefited more from the gRAT exercises, while more poorly performing students were better helped by individual preparation prior to the iRAT exercise. A combination of two active learning strategies, TBL and hands-on sessions, may strengthen student acquisition of course content and promote teamwork skills. The new incentive structure seems to reduce the disparity in knowledge amongst our students as demonstrated by the reduced iRAT and gRAT score variances. © 2018 International Union of Biochemistry and Molecular Biology, 47(2): 115-123, 2019.

Evaluation of the role of incentive structure on student participation and performance in active learning strategies: A comparison of case-based and team-based learning.

BACKGROUND: Student participation is important for the success of active learning strategies, but participation is often linked to the level of preparation. At our institution, we use two types of active learning activities, a modified case-based learning exercise called active learning groups (ALG) and team-based learning (TBL). These strategies have different assessment and incentive structures for participation. Non-cognitive skills are assessed in ALG using a subjective five-point Likert scale. In TBL, assessment of individual student preparation is based on a multiple choice quiz conducted at the beginning of each session. METHODS: We studied first-year medical student participation and performance in ALG and TBL as well as performance on course final examinations. RESULTS: Student performance in TBL, but not in ALG, was strongly correlated with final examination scores. Additionally, in students who performed in the upper 33rd percentile on the final examination, there was a positive correlation between final examination performance and participation in TBL and ALG. This correlation was not seen in students who performed in the lower 33rd percentile on the final examinations. CONCLUSIONS: Our results suggest that assessments of medical knowledge during active learning exercises could supplement non-cognitive assessments and could be good predictors of performance on summative examinations.

3D printed liner for treatment of periprosthetic joint infections.

In the United States, long standing deep infections of joint arthroplasty, such as total knee and total hip replacements, are treated with two-stage exchange. This requires the removal of the prior implant, placement of an antibiotic eluting spacer block made of polymethylmethacrylate (PMMA), followed by re-implantation of a new implant after treatment with intravenous antibiotics for six to eight weeks. Unfortunately, the use of PMMA as a spacer material has limitations in terms of mechanical and drug-eluting properties. PMMA is brittle and elutes most of the antibiotics within the first few days. Furthermore, the polymerization reaction for PMMA is highly exothermic, thereby limiting the use to heat-stable antibiotics. We hypothesize that the use of a 3D printed polymeric liner made of polylactic acid (PLA) would overcome the limitations of PMMA because it is a stronger and a less brittle material than PMMA. Furthermore, the liner can also act as a controlled drug delivery vehicle by using built in reservoirs and a network of micro-channels as well as by incorporating antibiotics directly into the polymer during manufacturing stage. Finally, the liner can be 3D printed according to the anatomy of the patient and thereby has the potential to transform the manner in which periprosthetic joint infections are currently treated.

Rapid kinetics of serum IgA after vaccination with Prevnar®13 followed by Pneumovax®23.

Streptococcus pneumoniae is a causative agent of community-acquired pneumonias. The recommendations of the 2012 Advisory Committee on Immunization Practices include vaccination with Prevnar®13 (protein-polysaccharide conjugate vaccine; PCV), followed by Pneumovax®23 (polysaccharide-based vaccine; PSV) in adults 65+ or the immunocompromised. In this experiment, a group of 4 healthy volunteers were vaccinated with PCV followed by PSV 60 days later. ELISAs were optimized to study kinetics of IgA, IgM, total IgG and its four subclasses against 14 polysaccharides of the pneumococcal capsule. Although this is a small sample, results from volunteers consistently showed that rapid induction of monomeric IgA followed by rapid decline is typical for both vaccines. IgA was not detected after PSV vaccination in those serotypes present in PCV, suggesting the population of B cells secreting IgA is not renewed within 60 days of activation by PCV. In contrast to mice, human neutrophils expressed a functional receptor for the constant region of monomeric IgA. Thus, the role of IgA early in the human immune response should be further investigated.

Mouse x pig chimeric antibodies expressed in Baculovirus retain the same properties of their parent antibodies.

The development of hybridoma and recombinant DNA technologies has made it possible to use antibodies against cancer, autoimmune disorders, and infectious diseases in humans. These advances in therapy, as well as immunoprophylaxis, could also make it possible to use these technologies in agricultural species of economic importance such as pigs. Porcine reproductive and respiratory syndrome virus (PRRSV) is an arterivirus causing very important economic losses to the industry. Passive transfer of antibodies obtained by biotechnology could be used in the future to complement or replace vaccination against this and other pig pathogens. To this end, we constructed and studied the properties of chimeric mouse x pig anti-PRRSV antibodies. We cloned the constant regions of gamma-1 and gamma-2 heavy chains and the lambda light chain of pig antibodies in frame with the variable regions of heavy and light chains of mouse monoclonal antibody ISU25C1, which has neutralizing activity against PRRSV. The coding regions for chimeric IgG1 and IgG2 were expressed in a baculovirus expression system. Both chimeric antibodies recognized PRRSV in ELISA as well as in a Western-blot format and, more importantly, were able to neutralize PRRSV in the same fashion as the parent mouse monoclonal antibody ISU25C1. In addition, we show that both pig IgG1 and IgG2 antibodies could bind complement component C1q, with IgG2 being more efficient than IgG1 in binding C1q. Expressing chimeric pig antibodies with protective capabilities offers a new alternative strategy for infectious disease control in domestic pigs.

The early protective thymus-independent antibody response to foot-and-mouth disease virus is mediated by splenic CD9+ B lymphocytes.

Infection of mice with cytopathic foot-and-mouth disease virus (FMDV) induces a rapid and specific thymus-independent (TI) neutralizing antibody response that promptly clears the virus. Herein, it is shown that FMDV-infected dendritic cells (DCs) directly stimulate splenic innate-like CD9(+) B lymphocytes to rapidly (3 days) produce neutralizing anti-FMDV immunoglobulin M antibodies without T-lymphocyte collaboration. In contrast, neither follicular (CD9(-)) B lymphocytes from the spleen nor B lymphocytes from lymph nodes efficiently respond to stimulation with FMDV-infected DCs. The production of these protective neutralizing antibodies is dependent on DC-derived interleukin-6 (IL-6) and on CD9(+) cell-derived IL-10 secretion. In comparison, DCs loaded with UV-inactivated FMDV are significantly less efficient in directly stimulating B lymphocytes to secrete TI antibodies. A critical role of the spleen in the early production of anti-FMDV antibodies in infected mice was also demonstrated in vivo. Indeed, either splenectomy or functional disruption of the marginal zone of the spleen delays and reduces the magnitude of the TI anti-FMDV antibody response in infected mice. Together, these results indicate that in addition to virus localization, the FMDV-mediated modulation of DC functionality is a key parameter that collaborates in the induction of a rapid and protective TI antibody response against this virus.

Impairment of thymus-dependent responses by murine dendritic cells infected with foot-and-mouth disease virus.

Foot-and-mouth disease virus (FMDV) is a cytopathic virus that experimentally infects mice, inducing a thymus-independent neutralizing Ab response that rapidly clears the virus. In contrast, vaccination with UV-inactivated virus induces a typical thymus-dependent (TD) response. In this study we show that dendritic cells (DCs) are susceptible to infection with FMDV in vitro, although viral replication is abortive. Infected DCs down-regulate the expression of MHC class II and CD40 molecules and up-regulate the expression of CD11b. In addition, infected DCs exhibit morphological and functional changes toward a macrophage-like phenotype. FMDV-infected DCs fail to stimulate T cell proliferation in vitro and to boost an Ab response in vivo. Moreover, infection of DCs in vitro induces the secretion of IFN-gamma and the suppressive cytokine IL-10 in cocultures of DCs and splenocytes. High quantities of these cytokines are also detected in the spleens of FMDV-infected mice, but not in the spleens of vaccinated mice. The peak secretion of IFN-gamma and IL-10 is concurrent with the suppression of Con A-mediated proliferation of T cells obtained from the spleens of infected mice. Furthermore, the secretion of these cytokines correlates with the suppression of the response to OVA, a typical TD Ag. Thus, infection of DCs with FMDV induces suppression of TD responses without affecting the induction of a protective thymus-independent response. Later, T cell responses are restored, setting the stage for the development of a long-lasting protective immunity.

Genotyping of DNA using sequence-specific methyltransferases followed by immunochemical detection.

Modern molecular genetics relies on the ability to map the positions of genes on chromosomes, relative to known DNA markers. The first such DNA markers described were Restriction Fragment Length Polymorphisms, but any restriction endonuclease used for RFLP mapping is just one member of a restriction-modification pair. For each restriction endonuclease, there is a companion methyltransferase (MTase) that has the same DNA sequence specificity. Therefore, in principle, it should be possible to use MTases rather than restriction enzymes to detect polymorphic sites in DNA. We have used sequence-specific DNA MTases to detect polym orphisms in closely related viral pathogens. If at least one MTase recognition site is present in PCR-amplified DNA, then methyl groups are incorporated; if no MTase site is present, then methyl groups are not incorporated. When several different sequence-specific DNA MTase reactions are carried out, the pattern of methyl incorporation defines a DNA MTase genotype. DNA MTase Genotyping (DMG) can be used to rapidly diagnose heritable or infectious diseases, to immunochemically detect DNA at defined 2 to 8 base pair sites, or to characterize the amplicons by constructing ordered maps.