Granting access: Development of a formal course to demystify and promote predoctoral fellowship applications for graduate students.

Strong scientific writing skills are the foundation of a successful research career and require training and practice. Although these skills are critical for completing a PhD, most students receive little formal writing instruction prior to joining a graduate program. In 2015, the University of Iowa Medical Scientist Training Program (MSTP) addressed this issue by developing the scientific writing course Grant Writing Basics (GWB). Here we describe the structure of this course and its effectiveness. GWB is an interactive, workshop-based course that uses a National Institutes of Health (NIH) F30 predoctoral fellowship proposal as a platform for building writing expertise. GWB incorporates established pedagogical principles of adult learning, including flipped classrooms, peer teaching, and reiterative evaluation. Time spent in class centers on active student analysis of previously submitted fellowship applications, discussion of writing resources, active writing, facilitated small group discussion of critiques of student writing samples, revision, and a discussion with a panel of experienced study section members and a student who completed a fellowship submission. Outcomes of GWB include a substantial increase in the number of applications submitted and fellowships awarded. Rigorous evaluation provides evidence that learning objectives were met and that students gained confidence in both their scientific writing skills and their ability to give constructive feedback. Our findings show that investment in formal training in written scientific communication provides a foundation for good writing habits, and the knowledge and skills needed to succeed in this vital aspect of a scientific research career. Furthermore, they highlight that evaluation is valuable in guiding course evolution. Strategies embedded in GWB can be adapted for use in any graduate program to advance scientific writing skills among its trainees.

Guidelines for organizing accessible and inclusive research retreats.

Research retreats are elements of scientific graduate training programs. Although expected to provide strong educational value, some students are reluctant to attend. Here, we identify participation barriers and provide guidelines for retreat design that minimize obstacles and establish an inclusive environment to improve attendance and enrichment for all attendees.

Massage and Medicine: An Interprofessional Approach to Learning Musculoskeletal Anatomy and Enhancing Personal Wellness.

PURPOSE: To investigate the impact of a unique curriculum combining learning of surface anatomy and massage therapy for medical and physician assistant students. METHOD: The authors conducted a randomized controlled trial in 2014 at University of Iowa Carver College of Medicine with 20 first-year students who viewed 4 hours of educational videos and participated in 11 hours of hands-on massage practice and 20 first-year students who only viewed the educational videos. Participants completed pre- and postcourse assessments of knowledge, attitudes, and personal wellness and completed a validated assessment of four dimensions of personal wellness. RESULTS: Hands-on group participants outscored the online-only group in postcourse knowledge assessments of surface anatomy and massage therapy principles (P < .05). Students in the hands-on group reported higher agreement with statements about perceived knowledge and beliefs about referrals and advising patients regarding massage therapy (P < .05). Students also frequently reported greater comfort administering physical examinations. Hands-on group participants had statistically significant improvements in psychological wellness during the study (P = .03), whereas online-only participants had a slight decrease (P = .09). Physical wellness was also slightly improved in the hands-on group (P = .06). CONCLUSIONS: Findings show that integrating surface anatomy and massage therapy in an experiential course resulted in significant gains in knowledge of anatomy, understanding about interprofessional health care roles, increased confidence in clinical practice, and improved wellness. Accordingly, further development of learning experiences that incorporate basic science, interprofessional education, and techniques that promote student wellness should be encouraged.

Application of flipped classroom pedagogy to the human gross anatomy laboratory: Student preferences and learning outcomes.

To improve student preparedness for anatomy laboratory dissection, the dental gross anatomy laboratory was transformed using flipped classroom pedagogy. Instead of spending class time explaining the procedures and anatomical structures for each laboratory, students were provided online materials to prepare for laboratory on their own. Eliminating in-class preparation provided the opportunity to end each period with integrative group activities that connected laboratory and lecture material and explored clinical correlations. Materials provided for prelaboratory preparation included: custom-made, three-dimensional (3D) anatomy videos, abbreviated dissection instructions, key atlas figures, and dissection videos. Data from three years of the course (n = 241 students) allowed for analysis of students' preferences for these materials and detailed tracking of usage of 3D anatomy videos. Students reported spending an average of 27:22 (±17:56) minutes preparing for laboratory, similar to the 30 minutes previously allocated for in-class dissection preparation. The 3D anatomy videos and key atlas figures were rated the most helpful resources. Scores on laboratory examinations were compared for the three years before the curriculum change (2011-2013; n = 242) and three years after (2014-2016; n = 241). There was no change in average grades on the first and second laboratory examinations. However, on the final semi-cumulative laboratory examination, scores were significantly higher in the post-flip classes (P = 0.04). These results demonstrate an effective model for applying flipped classroom pedagogy to the gross anatomy laboratory and illustrate a meaningful role for 3D anatomy visualizations in a dissection-based course. Anat Sci Educ 11: 385-396. © 2017 American Association of Anatomists.

Dissection and dissection-associated required experiences improve student performance in gross anatomy: Differences among quartiles.

To promote student learning, educational strategies should provide multiple levels of engagement with the subject matter. This study investigated examination data from five first year medical gross anatomy class cohorts (692 students) to determine if enhanced student performance was correlated with learning through dissection in a course that used a rotating dissection schedule coupled with peer teaching and other associated experiences. When students performed two of five weekly dissections for a given unit, their average scores on both laboratory and written examinations tended to increase as compared to when they had completed only one week of dissection (P < 0.01). However, these performance gains differed across the class strata and were related to the amount of dissection completed. Students in the upper quartile (UQS) of the class benefited when they had dissected once (92.8%) or twice (92.4%), and these scores were significantly higher than those attained when learning from peers (90.3%, P < 0.01). Students in the lower quartile (LQS) benefited most from the dissection experiences, where practical examination performance was better (77.8% and 80.5%) than when these students learned material from their peers (73.7%, P < 0.01). Although UQS benefited from dissection, LQS benefited to a greater extent in both the practical and written examinations with dissection. Although limited, these data suggest that dissection, coupled with associated educational activities, is an effective pedagogical strategy for learning. Further investigation is required to evaluate the concomitant benefits of peer teaching that are associated with the dissection experience. Anat Sci Educ 9: 238-246. © 2015 American Association of Anatomists.

Adenoviral delivery of VEGF121 early in pregnancy prevents spontaneous development of preeclampsia in BPH/5 mice.

An imbalance in circulating proangiogenic and antiangiogenic factors is postulated to play a causal role in preeclampsia (PE). We have described an inbred mouse strain, BPH/5, which spontaneously develops a PE-like syndrome including late-gestational hypertension, proteinuria, and poor feto-placental outcomes. Here we tested the hypothesis that an angiogenic imbalance during pregnancy in BPH/5 mice leads to the development of PE-like phenotypes in this model. Similar to clinical findings, plasma from pregnant BPH/5 showed reduced levels of free vascular endothelial growth factor (VEGF) and placental growth factor (PGF) compared to C57BL/6 controls. This was paralleled by a marked decrease in VEGF protein and Pgf mRNA in BPH/5 placentae. Surprisingly, antagonism by the soluble form of the FLT1 receptor (sFLT1) did not appear to be the cause of this reduction, as sFLT1 levels were unchanged or even reduced in BPH/5 compared to controls. Adenoviral-mediated delivery of VEGF(121) (Ad-VEGF) via tail vein at embryonic day 7.5 normalized both the plasma-free VEGF levels in BPH/5 and restored the in vitro angiogenic capacity of serum from these mice. Ad-VEGF also reduced the incidence of fetal resorptions and prevented the late-gestational spike in blood pressure and proteinuria observed in BPH/5. These data underscore the importance of dysregulation of angiogenic factors in the pathogenesis of PE and suggest the potential utility of early proangiogenic therapies in treating this disease.

Chronic tempol prevents hypertension, proteinuria, and poor feto-placental outcomes in BPH/5 mouse model of preeclampsia.

Recently we described a mouse model, BPH/5, that spontaneously develops the hallmark clinical features of preeclampsia. BPH/5 exhibit impaired placentation before the onset of hypertension and proteinuria, supporting a causal role for the placenta in the pathogenesis of preeclampsia. Here we tested the hypothesis that an increase in reactive oxygen species (ROS) early in pregnancy results in placental abnormalities leading to the maternal symptoms of preeclampsia. We further hypothesized that chronic antioxidant therapy would ameliorate both feto-placental abnormalities and maternal symptoms. ROS levels measured by dihydroethidium revealed significant increases in oxidative stress in BPH/5 placentas at midgestation compared with C57 controls. This increase in ROS was correlated with reduced expression and activity of cytoplasmic superoxide dismutase in early and midgestation BPH/5 placentas. These abnormalities in placental oxidant factors occurred before the onset of maternal symptoms, suggesting a possible causal link between increased ROS and maternal and feto-placental pathology in this model. In support of this, chronic treatment of BPH/5 with the superoxide dismutase-mimetic Tempol throughout gestation significantly improved fetal growth and survival. Furthermore, Tempol ameliorated pregnancy-induced increases in blood pressure and proteinuria in BPH/5 mothers. We confirmed that Tempol radical was present in plasma, and it normalized ROS levels in all placental zones in BPH/5. These data for the first time demonstrate an important causative role for increased ROS in the placenta in the pathogenesis of preeclampsia in a model that spontaneously develops the disease. The results also strongly suggest the potential utility of antioxidant therapy in treating preeclampsia.

Regulation of surfactant protein D in the mouse female reproductive tract in vivo.

Surfactant protein D (SP-D) plays a role in innate immunity in the lung and is expressed at many other mucosal surfaces throughout the human body. In this study, we show that SP-D mRNA and protein are present in the murine female reproductive tract; i.e. in the vagina, cervix, uterus and oviduct. SP-D protein is primarily localized to epithelial cells lining the genital tract and is also present in secretory material within the lumen of the uterus and cervix. The levels of SP-D mRNA in the uterus vary by a factor of 10 during the estrous cycle with peak levels present at estrus and the lowest levels at diestrus. In contrast, SP-D mRNA levels in the lung do not change during the estrous cycle. Since SP-D is an innate host defense protein present in the mouse reproductive tract, we studied the influence of infection on SP-D levels in vivo. We found that Chlamydia muridarum infection caused an increase in the SP-D protein content of reproductive tract epithelial cells. These data are suggestive that SP-D may play a role in innate immunity in the female reproductive tract in vivo.

Severe feto-placental abnormalities precede the onset of hypertension and proteinuria in a mouse model of preeclampsia.

Preeclampsia is a prevalent and potentially devastating disorder of pregnancy. Characterized by a sudden spike in blood pressure and urinary protein levels, it is associated with significant obstetric complications. BPH/5 is an inbred mouse model of preeclampsia with borderline hypertension before pregnancy. BPH/5 mice develop hypertension, proteinuria, and endothelial dysfunction during late gestation (after E14.5). We hypothesized that BPH/5 mice might exhibit early feto-placental abnormalities before the onset of maternal disease. All placental cell lineages were present in BPH/5 mice. However, the fetal and placental weights were reduced, with abnormalities in all the placental zones observed starting early in gestation (E9.5-E12.5). The fractional area occupied by the junctional zone was significantly reduced at all gestational timepoints. Markedly fewer CDKN1C-stained trophoblasts were seen invading the proximal decidual zone, and this was accompanied by reductions in Cdkn1c gene expression. Trophoblast giant cell morphology and cytokeratin staining were not altered, although the mRNA levels of several giant cell-specific markers were significantly downregulated. The labyrinth layer displayed decreased branching morphogenesis of endothelial cells, with electron microscopy evidence of attenuated trophoblast layers. The maternal decidual arteries showed increased wall-to-lumen ratios with persistence of actin-positive smooth muscle cells. These changes translated into dramatically increased vascular resistance in the uterine arteries, as measured by pulse-wave Doppler. Collectively, these results support the hypothesis that defects at the maternal-fetal interface are primary causal events in preeclampsia, and further suggest the BPH/5 model is important for investigations of the underlying pathogenic mechanisms in preeclampsia.

Discovery of a spontaneous genetic mouse model of preeclampsia.

Preeclampsia remains a leading cause of maternal and fetal morbidity and mortality but has an unknown etiology. Women with elevated baseline blood pressure have an increased risk of this disorder. We hypothesized that BPH/5 mice, an inbred mouse strain with mildly elevated blood pressure, would develop a pregnancy-induced hypertensive syndrome. Nonpregnant female BPH/5 and C57BL/6 mice underwent thoracic aortic implantation of telemeters. After 7 days of recovery and 5 days of baseline mean arterial blood pressure (MAP) recording, strain-matched timed matings were carried out. MAP was recorded continuously during pregnancy and for 1 week after birth. In separate mice in metabolic cages, urinary protein was tracked, followed by renal histological analysis. Before pregnancy, the BPH/5 strain had elevated baseline MAP compared with the C57BL/6 strain, but both strains had similar total urinary protein levels and renal histology. MAP remained stable in both groups during the first 2 weeks of pregnancy. However, at the start of the last trimester, MAP began to rise further in the BPH/5 mice; it rose to peak levels just before delivery and returned to prepregnancy levels by 2 days after delivery. This was accompanied by late-gestational proteinuria and progressive glomerulosclerosis. No changes were observed in the C57BL/6 group except for a small decrease in MAP at mid gestation. The BPH/5 group delivered significantly smaller litters despite normal numbers of fetuses early in gestation, and longitudinal ultrasound studies documented fetal demise before the onset of hypertension and renal disease. This is the first report of an animal model that spontaneously develops a syndrome that bears close resemblance to preeclampsia, and it should have an impact on our understanding of the pathophysiology of this disorder.