Simulation-Based Interdisciplinary Team Learning—Pilot Study

Background: Currently, interprofessional education (IPE) is becoming widely integrated into healthcare professional education with regulating bodies including IPE as a curricular requirement. Although recent studies have concluded that students value IPE, there are a number of challenges associated with initial engagement. Many schools are unsure how to approach this interdisciplinary integration. In addition to IPE, simulation has become an important tool in the education of health professionals. As the first exercise at Wright State University involving interprofessional groups composed completely of undergraduates, interested students from the Boonshoft School of Medicine, the WSU College of Nursing and Health, and the Cedarville University School of Pharmacy collaborated to conduct a series of IPE cases in the Department of Emergency Medicine’s high-fidelity simulation lab. In order to support a continuous improvement process and identify strengths and weaknesses of the interprofessional simulation, data was collected from all participating students. Methods: This study was approved as an exempt protocol by the University IRB. Repeat surveys were conducted on an interprofessional group of students assessing their attitudes prior to and upon completion of a series of simulations. The survey included 6 Likert scale questions and a comments section. Paired t-test and frequency analysis were utilized for each of the survey questions to determine baseline status and determine any statistically significant change from baseline. Results: Students from all health professions demonstrated positive attitudes toward IPE and simulation training. Results from four of the survey questions demonstrated a statistically significant positive increase in differences between pre-simulation and post-simulation survey. Baseline responses indicate a strongly positive attitude towards IPE. In comparison to pre-simulation survey responses, post-simulation responses demonstrated significant increases in students’ experience and perceived value of high-fidelity healthcare clinical simulation. Additionally, there were statistically significant changes in students’ perceived value of interdisciplinary team training and its importance in the future of medical education. Conclusion: This study found that students from all three participating health professions demonstrated overall positive baseline attitudes toward IPE that could be further enhanced through participation in simulation-based exercises. This study provides a model of one method for integrating IPE into curricula for healthcare professionals

A SARS-CoV-2 protein interaction map reveals targets for drug repurposing

The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19

Woven Shades of Green : An Anthology of Irish Nature Literature

Woven Shades of Green is an annotated selection of literature from authors who focus on the natural world and the beauty of Ireland. The anthology begins with the Irish monks and their largely anonymous nature poetry, written at a time when Ireland was heavily forested. A section follows devoted to the changing Irish landscape, through both deforestation and famine, including the nature poetry of William Allingham, James Clarence Mangan, essays from Thomas Gainford and William Thackerary, and novel excerpts from William Carleton and Emily Lawless. The anthology then turns to the nature literature of the Irish Literary Revival, including Yeats and Synge, but also the poetry of many others, and an excerpt from George Moore’s novel The Lake. Part four of the anthology shifts to modern Irish nature poetry, beginning with Patrick Kavanaugh, and continuing with late twentieth-century, early twenty-first-century poetry of Seamus Heaney, Eavan Boland, and others. Finally, the anthology concludes with a section on various Irish naturalist writers, and the unique prose and philosophical nature writing of John Moriarty, followed by a comprehensive list of environmental organizations in Ireland, which seek to preserve the natural beauty of this unique country. Published by Bucknell University Press. Distributed worldwide by Rutgers University Press.https://digitalcommons.bucknell.edu/bucknell-press/1024/thumbnail.jp

Defining Sec61 client sensitivity using substrate-selective Sec61 modulators

One third of the human proteome relies on the Sec61 translocon for proper folding and function. Each Sec61 client has a unique signal peptide or signal anchor, which plays an essential role in promoting its translocation into the endoplasmic reticulum. Cotransins are cyclic depsipeptides that inhibit the biogenesis of a subset of secreted and membrane proteins by preventing cotranslational translocation into the endoplasmic reticulum. Sensitivity to cotransins is determined by the protein’s N-terminal signal peptide or signal anchor, which intercalates into the lateral gate of Sec61 to initiate translocation. However, it has been difficult to predict Sec61 client sensitivity to cotransins due to the large diversity of signal peptides and signal anchors and the lack of high throughput assays to effectively survey all predicted human Sec61 clients. We developed a fluorescence-based reporter system with a library of 3880 human (3212) and mouse (668) signal peptides to interrogate which Sec61 clients are most affected by cotransin analogs. This pooled-cell screening platform allowed us to profile two cotransins with distinct effects on cancer cells, KZR-9873 and KZR-8445. We identified a total of 665 sensitive signal peptides, most of which were previously not known to be sensitive to cotransins. Among several validated targets, we discovered that the oncoprotein HER3, a coreceptor for HER2, is preferentially inhibited by the more selective cotransin, KZR-9873. Comparison of the human and mouse signal peptide paralogs within the library revealed a position-dependent role for Arg and Lys in conferring cotransin sensitivity. Our screening platform revealed distinct signal peptide sequence determinants that confer sensitivity to cotransins. We used mass spectrometry to profile the effects of KZR-9873 and KZR-8445 on endogenous proteins in three cancer cell lines, CAL27, BxPC3 and SW48 cells. This approach allowed us to interrogate Sec61 client sensitivity beyond SP-containing proteins, since type II and multi-spanning membrane proteins are understudied with respect to their potential cotransin sensitivity. Of the Sec61 clients identified across the three cell lines, there were 360 KZR-9873-sensitive and 659 KZR-8445-sensitive Sec61 clients. We identified a total of 51 and 81 type II membrane proteins that were sensitive to KZR-9873 and KZR-8445, respectively. In addition, we identified 34 and 45 multi-spanning N-cyt membrane proteins that were sensitive to KZR-9873 and KZR-8445, respectively. Our proteomic approach showed that cotransins can inhibit the biogenesis of proteins that utilize the lateral gate of Sec61 to initiate cotranslational membrane insertion

Voting for the Devil You Know: Understanding Electoral Behavior in Authoritarian regimes

In countries where elections are not free or fair, and one political party consistently dominates elections, why do citizens bother to vote? If voting cannot substantively affect the balance of power, why do millions of citizens continue to vote in these elections? Until now, most answers to this question have used macro-level spending and demographic data to argue that people vote because they expect a material reward, such as patronage or a direct transfer via vote-buying. This dissertation argues, however, that autocratic regimes have social and political cleavages that give rise to variation in partisanship, which in turn create different non-economic motivations for voting behavior. Citizens with higher levels of socioeconomic status have the resources to engage more actively in politics, and are thus more likely to associate with political parties, while citizens with lower levels of socioeconomic status are more likely to be nonpartisans. Partisans, however, are further split by their political proclivities; those that support the regime are more likely to be ruling party partisans, while partisans who mistrust the regime are more likely to support opposition parties. In turn, these three groups of citizens have different expressive and social reasons for voting. This dissertation argues that ruling party partisans vote out of a sense of civic duty, opposition parties vote to improve democracy, and nonpartisans vote when they are mobilized by their communities during elections. Overall, the dissertation shows that in Cameroon, expressive and social reasons are more important to explaining the voting act than economic motivations