Best practices in active and student-centered learning in physiology classes.

This review article includes our analysis of the literature and our own experiences in using various types of active learning as best practices for evidence-based teaching in physiology. We have evaluated what physiology students should be expected to learn and what are specific challenges to enhancing their learning of physiology principles. We also consider how the instructor should design his or her teaching to improve buy-in from both students and other faculty members. We include a discussion of how the readers can evaluate their teaching approaches for their successes in enhancing student learning of physiology. Thus we have addressed pedagogical improvements specific to student learning of physiology, with additional suggestions from cognitive psychology approaches that can improve physiology teaching and learning.

Designing and implementing a physiology course for a new doctoral occupational therapy program with student feedback.

Recently, the Occupational Therapy Department requested a custom-designed medical physiology course for the students in the new occupational therapy doctoral program. The first author, a physiologist with extensive experience in teaching both undergraduate preprofessional and medical students in human physiology, was recruited to design and implement the course. The course was designed to be consistent with the constructivist philosophy that guides the occupational therapy curriculum. The course was offered for the first time during fall/spring 2015/2016 and included both first- and second-year occupational therapy doctoral students. A number of anonymous assessment tools were used to evaluate students' perceptions regarding the effectiveness of various pedagogies used in the course in enhancing their learning. A summative course assessment survey with comments was used at the end of the course. This paper describes the model of course design and the student feedback, which generated some suggestions for improvement of the course. This approach in designing a new course for a new disciplinary group of students should be helpful to other faculty involved in developing courses for health career programs populated by students with variable physiology backgrounds and different educational needs. The final relevant feedback from the course would be to have the students evaluate the usefulness of the course to their future careers immediately following their certification examinations in a year or two and during their subsequent clinical experiences; however, that information will likely be more difficult to obtain.

How do the Institutes on Teaching and Learning (ITLs) nurture the members of the Physiology Educators Community of Practice (PECOP)?

Do you teach physiology? Do you use best practices when you teach physiology? Have you ever thought about conducting educational research? Do you need collaborators to help with ideas for educational research or to expand your research populations? The American Physiological Society (APS) Teaching Section has developed a biennial Institute on Teaching and Learning (ITL) through the APS Conference Program to address these issues. The first institute was held in June 2014, and the second institute was held in June 2016. A Physiology Education Community of Practice (PECOP) was created to help connect the institute participants and other physiology educators and to share evidence-based teaching in physiology at all education levels. The 2018 APS ITL will be the next meeting to learn best practices, to share ideas with colleagues, and to find collaborators in improving the teaching of physiology for students. The meeting will include workshops modeling best practices, plenary talks about hot new issues in physiology and science education, and poster sessions and informal meals to discuss interests with colleagues. Even if one's primary responsibility is bench research or administration, the training from the institute will improve efficiency and effectiveness when teaching. The two prior ITLs (2014 and 2016) were highly evaluated by educators of both undergraduate and professional students who spent a week together emphasizing improvement in their teaching. This paper reports the outcomes of the 2016 ITL and encourages participation in the upcoming ITL in Madison, WI, June 18-22, 2018. Watch the APS Conference site for more information about the 2018 ITL (http://www.the-aps.org/mm/Conferences/APS-Conferences).

An evolution in student-centered teaching.

The American Physiological Society (APS) Teaching Section annually honors an educator through its Claude Bernard Distinguished Lecture at the Experimental Biology meeting. Since I knew about my selection for almost a year, I had a long time to think about what I wanted to say and how I wanted to say it. The theme of my presentation was "nothing in education makes sense except in the light of student learning." My presentation began with a video of my "And, But, Therefore" description of my educational scholarship (see Randy Olson Great Challenges Day at TEDMED 2013, Ref. 10). "Physiology is the basic foundation of all the health professions AND physiology can be hard for students to figure out BUT many physiology courses expect students to memorize a large number of facts; THEREFORE, my scholarship is to help students learn physiology better for the long-term with various types of student-centered learning opportunities." To stress the goal of student-centered learning, my brief video was followed by a 2-min video of one of my students describing her experiences with student-centered learning in one of my two-semester Advanced Human Physiology classes. Since I have been convinced that Randy Olson is an expert on science communication (11), the rest of my presentation was the story about how I have evolved from a sage-on-the-stage lecturer into a student-centered learning facilitator. I have chosen Olson's "And, But, Therefore" approach to narrative for this written version of key aspects of the presentation.

What is the American Physiological Society's ITL and who are the members of PECOP?

The American Physiological Society Teaching Section has developed a biennial Institute on Teaching and Learning (ITL) through the APS Conference Program. The first ITL was held in June 2014, and the second ITL will be in June 2016. A Physiology Education Community of Practice was created to help connect the institute participants and other physiology educators to share evidence-based teaching in physiology at all education levels and ideas for the Scholarship of Teaching and Learning and Discipline-Based Education Research in physiology. This editorial describes the origins and outcomes of the ITL and the advantages of joining the Physiology Education Community of Practice.

The development and implementation of a new medical biology major including physiology.

In response to the Howard Hughes Medical Institute/Association of American Medical Colleges Scientific Foundations for Future Physicians (SFFP) report and a concern for better preparing undergraduates for future doctoral programs in the health professions, the deans of the College of Arts and Sciences and Division of Basic Biomedical Sciences of Sanford School of Medicine of the University of South Dakota formed an ad hoc Premedical Curriculum Review Committee with representatives from the science departments and medical school. The Committee began by reviewing the university's suggested premedical curriculum and matching it to the proposed competencies from the SFFP to document duplications and deficiencies. The proposed changes in the Medical College Admission Test for 2015 were also evaluated. The Committee proposed a stronger premedical curriculum, with the development of some new courses, including an inquiry-based physiology course with team-based learning, to more fully address SFFP competencies. These analyses convinced the university that a new major would best help students achieve the competencies and prepare them for admission exams. Thus, a new Medical Biology major was proposed to the South Dakota Board of Regents and accepted for its initial offering in 2012. The new major has been broadly advertised to future students and is successful as a recruiting tool for the university. This article details the process of evaluating the curriculum and designing the new major, describes some of the difficulties in its implementation, and reviews outcomes from the new major to date.

Myeloid neoplasms secondary to plasma cell myeloma: an intrinsic predisposition or therapy-related phenomenon? A clinicopathologic study of 41 cases and correlation of cytogenetic features with treatment regimens.

We describe 41 cases of myeloid neoplasms (MNs) secondary to plasma cell myeloma (PCM). The types of MN included myelodysplastic syndrome (MDS) in 34 (82.9%), acute myeloid leukemia (AML) in 4 (9.8%), and myeloproliferative neoplasm (MPN) or MDS/MPN in 3 (7.3%) cases. The latency from treatment to diagnosis of MN ranged from 9 to 384 months, with a median of 60 months. Of 37 cases with cytogenetic studies, complex abnormalities were detected in 22 (59.5%), -5(q)/-7(q) in 4 (10.8%), other abnormalities in 8 (21.6%), and normal karyotype in 3 (8.1%) cases. Complex abnormalities and -5(q)/-7(q) correlated directly with multiple chemotherapeutic regimens, particularly with combined melphalan/cyclophosphamide. Moreover, the features of cytogenetic abnormalities in our series were significantly different from those with concomitant PCM/MN who had significantly lower complex abnormalities. The latency, skewed proportion of MDS, and bias toward complex cytogenetic abnormalities/unbalanced aberrations of chromosomes 5/7 suggested an alkylating mutagenic effect on pathogenesis of secondary MN. Kaplan-Meier survival analysis demonstrated a median survival of 19 months, which was better than that for therapy-related (t)-MDS/AML. In contrast to t-MDS, the survival in our patients appeared to depend on subtypes of MDS as seen in de novo diseases.

MLL duplication in a pediatric patient with B-cell lymphoblastic lymphoma.

Lymphoblastic lymphoma is the second most common type of non-Hodgkin lymphoma seen in children. Approximately, 90% of lymphoblastic lymphomas arise from T cells, with the remaining 10% being B-cell-lineage derived. Although T-cell lymphoblastic lymphoma most frequently occurs in the anterior mediastinum (thymus), B-cell lymphoblastic lymphoma (B-LBL) predominates in extranodal sites such as skin and bone. Here, we describe a pediatric B-LBL patient who presented with extensive abdominal involvement and whose lymphoma cells displayed segmental duplication of the mixed lineage leukemia (MLL) gene. MLL duplication/amplification has been described primarily in acute myeloid leukemia and myelodysplastic syndrome with no published reports of discrete MLL duplication/amplification events in B-LBL. The MLL gene duplication noted in this case may represent a novel mechanism for tumorigenesis in B-LBL.

Influence of a rural family medicine rotation on residency selection: MS3 versus MS4.

BACKGROUND AND OBJECTIVES: Many family medicine educators feel that a required clinical rotation in family medicine has a positive influence on medical students' selection of family medicine residencies. We investigated the effect of a rural family medicine rotation on students' residency choices and examined the differences between a third-year and a fourth-year rotation. METHODS: We surveyed 1,260 students before and after they participated in a required rural family medicine rotation. RESULTS: The rotation had a small positive effect on student interest in family medicine. Over 20 years, there was a net gain of 4.7% (93 students) from before to after the rotation. Moving the rural rotation from the MS4 to the MS3 year resulted in a significant decline in the number of students who switched their preferences toward family medicine and ultimately matched to a family medicine residency. CONCLUSIONS: When the rotation occurs in the third year, there is more time following the rotation for other influences to exert an impact on a student's specialty choice, resulting in a small "bleed" away from family medicine. It might be useful to develop programs that continue to pique the interest in family medicine during their fourth year.

SET oncoprotein overexpression in B-cell chronic lymphocytic leukemia and non-Hodgkin lymphoma: a predictor of aggressive disease and a new treatment target.

B-cell chronic lymphocytic leukemia (CLL), an incurable leukemia, is characterized by defective apoptosis. We found that the SET oncoprotein, a potent inhibitor of the protein phosphatase 2A (PP2A) tumor suppressor, is overexpressed in primary CLL cells and B-cell non-Hodgkin lymphoma (NHL) cell line cells. In CLL, increased levels of SET correlated significantly with disease severity (shorter time to treatment and overall survival). We developed SET antagonist peptides that bound SET, increased cellular PP2A activity, decreased Mcl-1 expression, and displayed selective cytotoxicity for CLL and NHL cells in vitro. In addition, shRNA for SET was cytotoxic for NHL cells in vitro. The SET antagonist peptide COG449 inhibited growth of NHL tumor xenografts in mice. These data demonstrate that SET is a new treatment target in B-cell malignancies and that SET antagonists represent novel agents for treatment of CLL and NHL.

College of American Pathologists/American College of Medical Genetics proficiency testing for constitutional cytogenomic microarray analysis.

PURPOSE: To evaluate the feasibility of administering a newly established proficiency test offered through the College of American Pathologists and the American College of Medical Genetics for genomic copy number assessment by microarray analysis, and to determine the reproducibility and concordance among laboratory results from this test. METHODS: Surveys were designed through the Cytogenetic Resource Committee of the two colleges to assess the ability of testing laboratories to process DNA samples provided and interpret results. Supplemental questions were asked with each Survey to determine laboratory practice trends. RESULTS: Twelve DNA specimens, representing 2 pilot and 10 Survey challenges, were distributed to as many as 74 different laboratories, yielding 493 individual responses. The mean consensus for matching result interpretations was 95.7%. Responses to supplemental questions indicate that the number of laboratories offering this testing is increasing, methods for analysis and evaluation are becoming standardized, and array platforms used are increasing in probe density. CONCLUSION: The College of American Pathologists/American College of Medical Genetics proficiency testing program for copy number assessment by cytogenomic microarray is a successful and efficient mechanism for assessing interlaboratory reproducibility. This will provide laboratories the opportunity to evaluate their performance and assure overall accuracy of patient results. The high level of concordance in laboratory responses across all testing platforms by multiple facilities highlights the robustness of this technology.

Donor cell-derived leukemias/myelodysplastic neoplasms in allogeneic hematopoietic stem cell transplant recipients: a clinicopathologic study of 10 cases and a comprehensive review of the literature.

We report 10 cases of donor cell leukemia (DCL). All cases except the case of chronic lymphocytic leukemia had anemia, neutropenia, and/or thrombocytopenia when DCL was diagnosed. Eight cases with sex-mismatched hematopoietic stem cell transplant (HCT) showed donor gonosomal complements, suggesting DCL. Clonal cytogenetic abnormalities were detected in 8 cases: 6 were monosomy 7/del(7q). In all 10 cases, engraftment studies confirmed donor cell origin. Retrospective fluorescence in situ hybridization in archived donor cells in 4 cases showed a low level of abnormalities in 2. Of 7 patients with clinical follow-up of 5 months or more, 1 (with acute myeloid leukemia) died of disease; 6 are alive, including 1 with myelodysplastic syndrome with spontaneous remission. Similar to reported cases, we found disproportional sex-mismatched HCTs, suggesting probable underdetection of DCL in sex-matched HCTs. The latency between HCT and DCL ranged from 1 to 193 months (median, 24 months), in keeping with the literature. Analyzing our cases, pooled with reported cases, with survival models showed much shorter latency for malignancy as primary disease, for T-cell large granular lymphocyte leukemia as type of DCL, and for umbilical cord blood as stem cell source.

Insights into digestion and absorption of major nutrients in humans.

Nutrient digestion and absorption is necessary for the survival of living organisms and has evolved into the complex and specific task of the gastrointestinal (GI) system. While most people simply assume that their GI tract will work properly to use nutrients, provide energy, and release wastes, few nonscientists know the details about how various nutrients are digested and how the breakdown products traverse the cells lining the small intestine to reach the blood stream and to be used by the other cells of the body. There have been several recent discoveries of new transporters that likely contribute to the absorption of oligopeptides and fatty acids. In addition, details are being clarified about how transporters work and in what forms nutrients can be absorbed. The enzymes that digest basic carbohydrates, proteins, and fats have been identified in various segments of the GI tract, and details are becoming clearer about what types of bonds they hydrolyze. Usually, detailed information about the digestion of basic nutrients is presented and learned in biochemistry courses and detailed information about absorption via transepithelial transport of the breakdown products of digestion is studied in physiology courses. The goal of this Staying Current article is to combine the details of the biochemistry of digestion with the updated information about the physiology of nutrient absorption into one source for teachers of physiology. Insights are included about some of the diseases and conditions that can bring about malabsorption of food in the GI tract and their consequences.

Donor cell leukemia in umbilical cord blood transplant patients: a case study and literature review highlighting the importance of molecular engraftment analysis.

Donor cell neoplasms are rare complications of treatment regimens that involve stem cell transplantation for hematological malignancies, myelodysplastic processes, or certain genetic or metabolic disorders. We report a case of donor cell leukemia in a pediatric patient with a history of acute myeloid leukemia that manifested as recurrent AML FAB type M5 fourteen months after umbilical cord blood transplantation. Although there was some immunophenotypic drift from the patient's original AML and their posttransplant presentation, the initial pathological impression was of recurrent disease. Bone marrow engraftment analysis by multiplex PCR of short tandem repeat markers performed on the patient's diagnostic specimen showed complete engraftment by donor cells, with a loss of heterozygosity in the donor alleles on chromosome 7. This led to the reinterpretation of this patient's disease as donor-derived leukemia. This interpretation was supported by a routine karyotype and fluorescence in situ hybridization analysis showing loss of chromosome 7 and a male (donor) chromosome complement in this female patient. Also noted was a loss of the patient's presenting chromosomal abnormality, t(11;19)(q23;p13). This case highlights the need for close coordination between all aspects of clinical testing for the transplant patient, including molecular engraftment studies, when distinguishing the very common complication of recurrent disease from the exceedingly rare complication of donor cell leukemia.

A single tube, four-color flow cytometry assay for evaluation of ZAP-70 and CD38 expression in chronic lymphocytic leukemia.

We describe a simple and robust flow cytometry assay for ZAP-70 and CD38 expression. The steps required to validate this assay in a clinical flow cytometry laboratory are described. Two criteria were used to characterize ZAP-70 expression into positive, negative, and indeterminate categories and applied to 111 cases of chronic lymphocytic leukemia (CLL) resulting in 29.7% positive, 56.8% negative, and 13.5% indeterminate cases. A sensitivity-specificity crossover plot between ZAP-70 and CD38 suggested a cutoff of 12.5% for defining CD38 positivity. ZAP-70+ cases were significantly more likely to be at a higher clinical stage and, together with CD38+ cases, were more likely to have unmutated IgV(H). However, for individual patients, the concordance between these markers was not perfect. It may be necessary to evaluate several prognostic markers simultaneously in CLL, and availability of convenient assays for ZAP-70 and CD38 is desirable for optimal clinical decision making.