A descriptive, cross-sectional study of medical student preferences for vodcast design, format and pedagogical approach.

BACKGROUND: Vodcasts (video podcasts) are becoming increasingly popular in medical education. At A.T. Still University School of Osteopathic Medicine in Arizona (ATSU SOMA), vodcasts are an essential component of our blended learning environment, where year 2-4 students train in a contextual setting at community health centers across the U.S. Vodcasts are used far less frequently in our year 1 residential learning environment at the main campus in Arizona, but we are considering moving to significantly more interactive educational experiences with on-demand videos followed by in-class activities. The aim of this study was to determine stakeholder (i.e. medical student) preferences for vodcast design, format, and pedagogical strategies. The overall goal was to increase opportunities for students to learn with this modality. METHODS: An interactive Qualtrics™ survey was administered to three cohorts of medical students. The survey generated quantitative and open-ended response data that addressed principles of vodcast instructional design and learning. Responses to survey items were analyzed for statistical significance using the independent samples t-test for interval data, the chi-square test for categorical data, and the Kruskal-Wallis test for ordinal data, using the post-hoc Bonferroni procedure to determine the appropriate α level. Responses to open-ended prompts were categorized using open- and axial-coding. RESULTS: The most highly valued vodcast attributes, considered essential by all three cohorts, were clear explanations, organization, conciseness, high-yield for medical board exams, and the ability to speed vodcasts up. The least helpful vodcast attributes for all three cohorts were music and objects moving on screen. The average preferred vodcast length for each cohort was 27-28 min. There were significant differences between the less experienced learners in the residential setting and the more mature learners in the blended learning environment regarding certain vodcast attribute preferences, format of included practice questions, explanations for preferred vodcast lengths, and reasons for not viewing vodcasts. CONCLUSIONS: Overall, learner preferences were in line with non-interactive, screen-capture type vodcasts, which have lower demands on institutional cost and faculty production time than Flash™-type interactive vodcasts. Students in the blended learning environment were much more focused on vodcast features that decreased their time commitment, including a preference for noninteractive vodcasts. Given the increase in distance learning in medical education, our results should be of value to other medical programs.

Evaluating medical student engagement during virtual patient simulations: a sequential, mixed methods study.

BACKGROUND: Student engagement is an important domain for medical education, however, it is difficult to quantify. The goal of this study was to investigate the utility of virtual patient simulations (VPS) for increasing medical student engagement. Our aims were specifically to investigate how and to what extent the VPS foster student engagement. This study took place at A.T. Still University School of Osteopathic Medicine in Arizona (ATSU-SOMA), in the USA. METHODS: First year medical students (n = 108) worked in teams to complete a series of four in-class virtual patient case studies. Student engagement was measured, defined as flow, interest, and relevance. These dimensions were measured using four data collection instruments: researcher observations, classroom photographs, tutor feedback, and an electronic exit survey. Qualitative data were analyzed using a grounded theory approach. RESULTS: Triangulation of findings between the four data sources indicate that VPS foster engagement in three facets: 1) Flow. In general, students enjoyed the activities, and were absorbed in the task at hand. 2) Interest. Students demonstrated interest in the activities, as evidenced by enjoyment, active discussion, and humor. Students remarked upon elements that caused cognitive dissonance: excessive text and classroom noise generated by multi-media and peer conversations. 3) Relevance. VPS were relevant, in terms of situational clinical practice, exam preparation, and obtaining concrete feedback on clinical decisions. CONCLUSIONS: Researchers successfully introduced a new learning platform into the medical school curriculum. The data collected during this study were also used to improve new learning modules and techniques associated with implementing them in the classroom. Results of this study assert that virtual patient simulations foster engagement in terms of flow, relevance, and interest.

Student perceptions of gamified audience response system interactions in large group lectures and via lecture capture technology.

BACKGROUND: Higher education students have positive attitudes about the use of audience response systems (ARS), but even technology-enhanced lessons can become tiresome if the pedagogical approach is exactly the same with each implementation. Gamification is the notion that gaming mechanics can be applied to routine activities. In this study, TurningPoint (TP) ARS interactions were gamified and implemented in 22 large group medical microbiology lectures throughout an integrated year 1 osteopathic medical school curriculum. METHODS: A 32-item questionnaire was used to measure students' perceptions of the gamified TP interactions at the end of their first year. The survey instrument generated both Likert scale and open-ended response data that addressed game design and variety, engagement and learning features, use of TP questions after class, and any value of lecture capture technology for reviewing these interactive presentations. The Chi Square Test was used to analyze grouped responses to Likert scale questions. Responses to open-ended prompts were categorized using open-coding. RESULTS: Ninety-one students out of 106 (86 %) responded to the survey. A significant majority of the respondents agreed or strongly agreed that the games were engaging, and an effective learning tool. The questionnaire investigated the degree to which specific features of these interactions were engaging (nine items) and promoted learning (seven items). The most highly ranked engagement aspects were peer competition and focus on the activity (tied for highest ranking), and the most highly ranked learning aspect was applying theoretical knowledge to clinical scenarios. Another notable item was the variety of interactions, which ranked in the top three in both the engagement and learning categories. Open-ended comments shed light on how students use TP questions for exam preparation, and revealed engaging and non-engaging attributes of these interactive sessions for students who review them via lecture capture. CONCLUSIONS: Students clearly valued the engagement and learning aspects of gamified TP interactions. The overwhelming majority of students surveyed in this study were engaged by the variety of TP games, and gained an interest in microbiology. The methods described in this study may be useful for other educators wishing to expand the utility of ARS in their classrooms.

Isolation and structures of axistatins 1-3 from the Republic of Palau marine sponge Agelas axifera Hentschel .

An investigation begun in 1979 directed at the Republic of Palau marine sponge Agelas axifera Hentschel for cancer cell growth inhibitory constituents subsequently led to the isolation of three new pyrimidine diterpenes designated axistatins 1 (1), 2 (2), and 3 (3), together with the previously reported formamides 4, 5, and agelasine F (6). The structures were elucidated by analysis of 2D-NMR spectra and by HRMS. All of the isolated compounds were found to be moderate inhibitors of cancer cell growth. Axistatins 1-3 (1-3), formamide 4, and agelasine F (6) also exhibited antimicrobial activity.

Antineoplastic agents. 548. Synthesis of iodo- and diiodocombstatin phosphate prodrugs.

Toward the objective of designing a structurally modified analogue of the combretastatin A-4 phosphate prodrug (1b) with the potential for increased specificity toward thyroid carcinoma, synthesis of a series of iodocombstatin phosphate (11a-h) and diiodocombstatin phosphate prodrugs (12a-h) has been accomplished. The diiodo series was obtained via 8a and 9c from condensation of 4 and 6, and the iodo sequence involved a parallel pathway. Both series of iodocombstatins were found to display significant to powerful inhibition of the growth of a panel of human cancer cell lines and of the murine P388 lymphocytic leukemia cell line. Of the diiodo series, 12a was also found to markedly inhibit growth of pediatric neuroblastoma, and monoiodocombstatin 9a strongly inhibited HUVEC growth. Overall, the strongest activity was found against the breast, CNS, leukemia, lung, and prostate cancer cell lines and the least activity against the pancreas and colon lines. Parallel biological investigations of tubulin interaction, antiangiogenesis, and antimicrobial effects were also conducted.

The cephalostatins. 21. Synthesis of bis-steroidal pyrazine rhamnosides (1).

The synthesis of bis-steroidal pyrazines derived from 3-oxo-11,21-dihydroxypregna-4,17(20)-diene (4) and glycosylation of a D-ring side chain with α-L-rhamnose have been summarized. Rearrangement of steroidal pyrazine 10 to 14 was found to occur with boron triflouride etherate. Glycosylation of pyrazine 10 using 2,3,4-tri-O-acetyl-α-L-rhamnose iodide led to 1,2-orthoester-α-L-rhamnose pyrazine 17b. By use of a persilylated α-L-rhamnose iodide as donor, formation of the orthoester was avoided. Bis-steroidal pyrazine 10 and rhamnosides 17b and 21c were found to significantly inhibit cancer cell growth in a murine and human cancer cell line panel. Pyrazine 9 inhibited growth of the nosocomial pathogen Enterococcus faecalis.

Temperature affects the susceptibility of Cryptococcus neoformans biofilms to antifungal agents.

The fungal opportunist Cryptococcus neoformans forms biofilms in vitro and in vivo. C. neoformans has an unusual ability to grow over a wide range of temperatures, and is one of only two species in the genus able to grow at 37 degrees C. The optimum growth temperature in the laboratory is 30 degrees C, but Clinical and Laboratory Standards Institute (CLSI) planktonic susceptibility testing is performed at 35 degrees C. We investigated whether these growth temperatures affected C. neoformans biofilm formation and drug resistance. Biofilms of 30 strains of C. neoformans were grown at 30 degrees C or 35 degrees C, and antifungal susceptibilities evaluated at 30 degrees C or 35 degrees C using minimum biofilm eradication endpoints. At 35 degrees C, biofilms from 40% of the strains were more susceptible to flucytosine, 30% were more susceptible to nystatin, 27% were more susceptible to amphotericin, and 20% were more susceptible to fluconazole, as compared to 30 degrees C. The reverse, that is an increased susceptibility at 30 degrees C, only occurred with a single strain using nystatin or fluconazole. For the remaining strains, biofilm susceptibility was equivalent at the two temperatures. Biofilm colony forming units (CFU)s, as measured indirectly by 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction, were greater at 35 degrees C than at 30 degrees C for the majority of the strains. Thus, growth temperature does affect C. neoformans biofilm properties, but factors other than relative biofilm CFUs/ml must be involved in the increased drug susceptibility at 35 degrees C.

Antineoplastic agents 582. Part 1: Isolation and structure of a cyclobutane-type sesquiterpene cancer cell growth inhibitor from Coprinus cinereus (Coprinaceae).

Bioassay-guided (murine P388 lymphocytic leukemia and human cancer cell lines) separation of an ethyl acetate extract prepared from the inky cap fungus Coprinus cinereus led to the isolation of three new sesquiterpenes, 7,7a-diepicoprinastatin 1 (1), 14-hydroxy-5-desoxy-2S,3S,9R-illudosin (2), and 4,5-dehydro-5-deoxyarmillol (3), together with the known armillol (4). The structure and relative configuration of 1 was determined by single-crystal X-ray diffraction experiments. The structures of compounds 2, 3, and 4 were each deduced by a combination of HRMS and 1D and 2D NMR techniques. Cyclobutane 2 led to modest inhibition of the murine P388 leukemia cell line.

Antineoplastic agents. 573. isolation and structure of papilistatin from the papilionid butterfly Byasa polyeuctes termessa.

Bioassay-guided separation of an extract of the wings from a Taiwan butterfly, Byasa polyeuctes termessa, allowed isolation of a new cancer cell growth inhibitor designated papilistatin (1a). The structure was determined by analysis of 1D and 2D NMR spectra and by HRMS. Against a panel of six human and the murine P388 leukemia cancer cell lines, papilistatin exhibited cancer cell growth inhibition with GI(50)'s of 0.093-3.5 microg/mL. Papilistatin was also found to have antibacterial activity.

Antineoplastic agents. 556. Isolation and structure of Coprinastatin 1 from Coprinus cinereus.

Cancer cell line bioassay-guided separation of an ethyl acetate extract prepared from a plant-associated fungus, Coprinus cinereus, led to the isolation of three new sesquiterpenes, coprinastatin 1 (1), coprinol (2), and the epimer (4a), of the known sesquiterpene triol (4b). The previously described sesquiterpene 3 and oxazolinone 5 were also isolated. The structure and relative configuration of coprinastatin 1 (1) were determined by HRMS and by 1D- and 2D-NMR spectroscopic analyses. The structure of terpene 2 was elucidated by single-crystal X-ray diffraction experiments. The remaining structures were similarly determined, structure 3 by spectroscopic analyses and both 4a and 5 by X-ray crystal structure determination. Coprinastatin 1 (1) was found to inhibit growth of the murine P388 lymphocytic leukemia cell line and the pathogenic bacterium Neisseria gonorrhoeae.

Isolation of human cancer cell growth inhibitory, antimicrobial lateritin from a mixed fungal culture.

The purpose of this study was to attempt the reproducible coculture of more than two fungi for biosynthesis of potential antineoplastic substances. Five different fungi were simultaneously inoculated into broth cultures and grown for two weeks. Cancer cell line bioassay-guided fractionation, NMR, and mass spectroscopy led to the isolation and characterization of lateritin. Lateritin inhibited the growth of a mini-panel of human cancer cell lines, gram-positive bacteria, and Candida albicans. Individually, the five fungi did not synthesize detectable levels of lateritin. This study adds to the small but growing body of evidence that mixed fermentation is a viable avenue for natural product drug discovery. In addition, this is the first report of the reproducible coculture of more than two microbes for natural product biosynthesis, and the first report of the human solid tumor cell line and antimicrobial activities of lateritin.

In vivo activity of anprocide alone, and in vitro activity in combination with conventional antibiotics against Staphylococcus aureus and Staphylococcus epidermidis biofilms.

The alarming spread of multiple drug resistance in Staphylococcus aureus, combined with the frequent occurrence of S. aureus and Staphylococcus epidermidis in biofilm-type infections, indicates a growing need for new therapies. The experimental steroidal amide anprocide [3beta-acetoxy-17beta-(l-prolyl)amino-5alpha-androstane] significantly reduced c.f.u. ml(-1) per suture (P <0.0001) in a murine model of topical S. aureus infection. In chequerboard assays with planktonic-grown S. aureus and S. epidermidis, anprocide was synergistic with bacitracin, oxacillin, clindamycin or ceftriaxone. Anprocide was also synergistic in combination with bacitracin or oxacillin against some isolates of biofilm-grown S. aureus and S. epidermidis.

E-Combretastatin and E-resveratrol structural modifications: antimicrobial and cancer cell growth inhibitory beta-E-nitrostyrenes.

As part of a broad-based SAR investigation of E-resveratrol (strong sirtuin activator and antineoplastic) and the anticancer vascular-targeting combretastatin-type stilbenes, a series of twenty-three beta-E-nitrostyrenes was synthesized in order to evaluate potential antineoplastic, antitubulin, and antimicrobial activities. The beta-E-nitrostyrenes evaluated ranged from monosubstituted phenols to trimethoxy and 3-methoxy-4,5-methylenedioxy derivatives. Two of the beta-nitrostyrenes were synthesized as water-soluble sodium phosphate derivatives (4t, 4v). All except four (4r, 4s, 4t, 4u) of the series significantly inhibited a minipanel of human cancer cell lines. All but eight led to an IC(50) of <10 microM for inhibition of tubulin polymerization, and all except three (4l, 4t, 4v) displayed antimicrobial activity.

Antineoplastic agents. 570. Isolation and structure elucidation of bacillistatins 1 and 2 from a marine Bacillus silvestris.

Two new cyclodepsipeptides designated bacillistatins 1 (1) and 2 (2) have been isolated from cultures of a sample of Bacillus silvestris that was obtained from a Pacific Ocean (southern Chile) crab. Each 12-unit cyclodepsipeptide strongly inhibited growth of a human cancer cell line panel, with GI(50)'s of 10(-4)-10(-5) microg/mL, and each compound was active against antibiotic-resistant Streptococcus pneumoniae. The structures were elucidated by a combination of X-ray diffraction and mass and 2D NMR spectroscopic analyses, together with chemical degradation.

Application of a high throughput Alamar blue biofilm susceptibility assay to Staphylococcus aureus biofilms.

BACKGROUND: Staphylococcus aureus and S. epidermidis biofilms differ in structure, growth and regulation, and thus the high-throughput method of evaluating biofilm susceptibility that has been published for S. epidermidis cannot be applied to S. aureus without first evaluating the assay's reproducibility and reliability with S. aureus biofilms. METHODS: Staphylococcus aureus biofilms were treated with eleven approved antibiotics, lysostaphin, or Conflikt, exposed to the oxidation reduction indicator Alamar blue, and reduction relative to untreated controls was determined visually and spectrophotometrically. The minimum biofilm inhibitory concentration (MBIC) was defined as < or = 50% Alamar blue reduction and a purple/blue well 60 min after the addition of Alamar blue. Because all of the approved antibiotics had MBICs >128 microg/ml (most >2048 microg/ml), lysostaphin and Conflikt, with relatively low MBICs, were used to correlate Alamar blue reduction with 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction and viable counts (CFU/ml) for S. aureus ATCC 29213 and three clinical isolates. Alamar blue's stability and lack of toxicity allowed CFU/ml to be determined from the same wells as Alamar blue absorbances. RESULTS: Overall, Alamar blue reduction had excellent correlation with XTT reduction and with CFU/ml. For ATCC 29213 and two clinical isolates treated with lysostaphin or Conflikt, Alamar blue reduction had excellent correlation with XTT reduction (r = 0.93-0.99) and with CFU/ml (r = 0.92-0.98). For one of the clinical isolates, the results were moderately correlated for Conflikt (r = 0.76, Alamar blue vs. XTT; r = 0.81, Alamar blue vs. CFU/ml) and had excellent correlation for lysostaphin (r = 0.95, Alamar blue vs. XTT; r = 0.97, Alamar blue vs. CFU/ml). CONCLUSION: A reliable, reproducible method for evaluating biofilm susceptibility was successfully applied to S. aureus biofilms. The described method provides researchers with a simple, nontoxic, relatively inexpensive, high throughput measure of viability after drug treatment. A standardized biofilm Alamar blue assay should greatly increase the rate of discovery of S. aureus biofilm specific agents.

Mixed fermentation for natural product drug discovery.

Natural products continue to play a major role in drug discovery and development. However, chemical redundancy is an ongoing problem. Genomic studies indicate that certain groups of bacteria and fungi have dozens of secondary metabolite pathways that are not expressed under standard laboratory growth conditions. One approach to more fully access the metabolic potential of cultivatable microbes is mixed fermentation, where the presence of neighboring microbes may induce secondary metabolite synthesis. Research to date indicates that mixed fermentation can result in increased antibiotic activity in crude extracts, increased yields of previously described metabolites, increased yields of previously undetected metabolites, analogues of known metabolites resulting from combined pathways and, importantly, induction of previously unexpressed pathways for bioactive constituents.

Ten tips to encourage student interaction with screen-capture type vodcasts.

Video podcasts (vodcasts) are gaining popularity in medical education, but they can be a passive learning modality if students do not actively engage with the content. Of the two categories of vodcast software, screen-capture (mp4 output) and Flash™ (HTML5/Flash output), screen-capture has greater potential to result in passive learning because students cannot physically interact with the content. However, screen-capture offers several advantages for the producer (often faculty) and the consumer (students). As such, this type of software is popular with medical school faculty. To encourage active learning, ten tips are presented with specific strategies that faculty can use with screen-capture type vodcasts. Many of the tips also apply to Flash-type vodcasts. By incorporating these strategies, faculty with limited technical abilities can create engaging vodcasts that stimulate active learning.

Tracking Active Learning in the Medical School Curriculum: A Learning-Centered Approach.

BACKGROUND: Medical education is moving toward active learning during large group lecture sessions. This study investigated the saturation and breadth of active learning techniques implemented in first year medical school large group sessions. METHODS: Data collection involved retrospective curriculum review and semistructured interviews with 20 faculty. The authors piloted a taxonomy of active learning techniques and mapped learning techniques to attributes of learning-centered instruction. RESULTS: Faculty implemented 25 different active learning techniques over the course of 9 first year courses. Of 646 hours of large group instruction, 476 (74%) involved at least 1 active learning component. CONCLUSIONS: The frequency and variety of active learning components integrated throughout the year 1 curriculum reflect faculty familiarity with active learning methods and their support of an active learning culture. This project has sparked reflection on teaching practices and facilitated an evolution from teacher-centered to learning-centered instruction.

What millennial medical students say about flipped learning.

Flipped instruction is gaining popularity in medical schools, but there are unanswered questions such as the optimum amount of the curriculum to flip and whether flipped sessions should be mandatory. We were in a unique position to evaluate feedback from first-year medical students who had experienced both flipped and lecture-based courses during their first semester of medical school. A key finding was that the students preferred a variety of different learning formats over an "all or nothing" learning format. Learning format preferences did not necessarily align with perceptions of which format led to better course exam performance. Nearly 70% of respondents wanted to make their own decisions regarding attendance. Candid responses to open-ended survey prompts reflected millennial preferences for choice, flexibility, efficiency, and the ability to control the pace of their learning, providing insight to guide curricular improvements.

Antineoplastic agents. 445. Synthesis and evaluation of structural modifications of (Z)- and (E)-combretastatin A-41.

A series of cis- and trans-stilbenes related to combretastatin A-4 (1a), with a variety of substituents at the 3'-position of the aryl B-ring, were synthesized and evaluated for inhibitory activity employing six human cancer cell lines (NCI-H460 lung carcinoma, BXPC-3 pancreas, SK-N-SH neuroblastoma, SW1736 thyroid, DU-145 prostate, and FADU pharynx-squamous sarcoma) as well as the P-388 murine lymphocyte leukemia cell line. Several of the cis-stilbene derivatives were significantly inhibitory against all cell lines used, with potencies comparable to that of the parent 1a. All were potent inhibitors of tubulin polymerization. The corresponding trans-stilbenes had little or no activity as tubulin polymerization inhibitors and were relatively inactive against the seven cancer cell lines. In terms of inhibition of both cancer cell growth and tubulin polymerization, the dimethylamino and bromo cis-stilbenes were the most potent of the new derivatives, the latter having biological activity approaching that of 1a. As part of the present study, the X-ray crystal structure of the 3'-O-phosphate of combretastatin A-4 (1b) was successfully elucidated. Compound 1b has been termed the "combretastatin A-4 prodrug", and it is currently undergoing clinical trials for the treatment of human cancer patients.