Advancing Health Policy and Advocacy Education in Medical School through a Student-run Elective

Introduction: Training medical students in the policy topics of healthcare economics, delivery systems, disparities, and reform helps to prepare them for the growing role of advocacy in medicine. We used a near-peer educational model to create an elective to advance learners’ policy knowledge and advocacy skills, while simultaneously offering student directors hands-on experience in educational program development. Methods: The 4-week elective for fourth year medical students included weekly readings, policy seminars, advocacy workshops, and journal clubs. Longitudinally, students prepared for a policy debate and prepared a research project or Op-Ed article on a healthcare disparity topic of their choice. The elective was designed, coordinated, and implemented by a team of first, second, third, and fourth-year medical students with faculty adviser oversight. Pre- and post-surveys were utilized to assess student learners’ knowledge of subject material and their perceptions of the effectiveness of the curriculum. Student directors self-assessed their confidence with the subject material and acquired skill in educational program development. Results: Student learners (n=6) noted significant improvement in their knowledge of health policy (P=0.0002) and advocacy (P=0.0064). They also reported improvement in several subtopics under policy and advocacy, with significant improvements seen in healthcare reform (P=0.0131) and writing skills (P=0.0099). Student directors (n=4) reported improved skills in curriculum development, educational evaluation, and leadership. Discussion: This novel student-run elective provided effective training in health policy and advocacy that extends beyond traditional curricula in medical school. Employing a near-peer model, the elective offers a sustainable system to educate interested students in these subjects and provide student directors unique experience in medical education. Further evaluation of future iterations will help determine the effectiveness of the curriculum in advancing individual policy and advocacy subtopics to guide future curricular modifications

Tools to Ease the Choice and Design of Protein Crystallisation Experiments

The process of macromolecular crystallisation almost always begins by setting up crystallisation trials using commercial or other premade screens, followed by cycles of optimisation where the crystallisation cocktails are focused towards a particular small region of chemical space. The screening process is relatively straightforward, but still requires an understanding of the plethora of commercially available screens. Optimisation is complicated by requiring both the design and preparation of the appropriate secondary screens. Software has been developed in the C3 lab to aid the process of choosing initial screens, to analyse the results of the initial trials, and to design and describe how to prepare optimisation screens

The Grizzly, February 20, 2020

UC Hosts The Vagina Monologues • Spend a Semester in Philadelphia • College Launches First Mobile App • Slavery in the Age of Memory Talk • Q&A with the Creator of High Education • Get to Know New Tech with a DLA Fellow • Opinions: The Good Place Ends in a Good Place; Marriage Story Isn\u27t Divorced from Humanity • Gymnastics Aims for First Nationals Appearance Since 2017 • Men\u27s Hoops on the Brink of Clinching CC Playoff Berthhttps://digitalcommons.ursinus.edu/grizzlynews/1599/thumbnail.jp

The C-Terminal Domain of the Arabinosyltransferase Mycobacterium tuberculosis EmbC Is a Lectin-Like Carbohydrate Binding Module

The D-arabinan-containing polymers arabinogalactan (AG) and lipoarabinomannan (LAM) are essential components of the unique cell envelope of the pathogen Mycobacterium tuberculosis. Biosynthesis of AG and LAM involves a series of membrane-embedded arabinofuranosyl (Araf) transferases whose structures are largely uncharacterised, despite the fact that several of them are pharmacological targets of ethambutol, a frontline drug in tuberculosis therapy. Herein, we present the crystal structure of the C-terminal hydrophilic domain of the ethambutol-sensitive Araf transferase M. tuberculosis EmbC, which is essential for LAM synthesis. The structure of the C-terminal domain of EmbC (EmbCCT) encompasses two sub-domains of different folds, of which subdomain II shows distinct similarity to lectin-like carbohydrate-binding modules (CBM). Co-crystallisation with a cell wall-derived di-arabinoside acceptor analogue and structural comparison with ligand-bound CBMs suggest that EmbCCT contains two separate carbohydrate binding sites, associated with subdomains I and II, respectively. Single-residue substitution of conserved tryptophan residues (Trp868, Trp985) at these respective sites inhibited EmbC-catalysed extension of LAM. The same substitutions differentially abrogated binding of di- and penta-arabinofuranoside acceptor analogues to EmbCCT, linking the loss of activity to compromised acceptor substrate binding, indicating the presence of two separate carbohydrate binding sites, and demonstrating that subdomain II indeed functions as a carbohydrate-binding module. This work provides the first step towards unravelling the structure and function of a GT-C-type glycosyltransferase that is essential in M. tuberculosis. Author Summary Top Tuberculosis (TB), an infectious disease caused by the bacillus Mycobacterium tuberculosis, burdens large swaths of the world population. Treatment of active TB typically requires administration of an antibiotic cocktail over several months that includes the drug ethambutol. This front line compound inhibits a set of arabinosyltransferase enzymes, called EmbA, EmbB and EmbC, which are critical for the synthesis of arabinan, a vital polysaccharide in the pathogen's unique cell envelope. How precisely ethambutol inhibits arabinosyltransferase activity is not clear, in part because structural information of its pharmacological targets has been elusive. Here, we report the high-resolution structure of the C-terminal domain of the ethambutol-target EmbC, a 390-amino acid fragment responsible for acceptor substrate recognition. Combining the X-ray crystallographic analysis with structural comparisons, site-directed mutagenesis, activity and ligand binding assays, we identified two regions in the C-terminal domain of EmbC that are capable of binding acceptor substrate mimics and are critical for activity of the full-length enzyme. Our results begin to define structure-function relationships in a family of structurally uncharacterised membrane-embedded glycosyltransferases, which are an important target for tuberculosis therapy

Exploring the future of data-driven product design

Connected devices present new opportunities to advance design through data collection in the wild, similar to the way digital services evolve through analytics. However, it is still unclear how live data transmitted by connected devices informs the design of these products, going beyond performance optimisation to support creative practices. Design can be enriched by data captured by connected devices, from usage logs to environmental sensors, and data about the devices and people around them. Through a series of workshops, this paper contributes industry and academia perspectives on the future of data-driven product design. We highlight HCI challenges, issues and implications, including sensemaking and the generation of design insight. We further challenge current notions of data-driven design and envision ways in which future HCI research can develop ways to work with data in the design process in a connected, rich, human manner

The evolution of HIV self-testing and the introduction of digital interventions to improve HIV self-testing

HIV self-testing (HIVST) complements traditional HIV testing programmes by removing barriers and increasing access to testing for key populations, and digital interventions have been developed for HIVST to improve the testing and linkage to care experience for users. The first HIVST kit was proposed in 1986, but it took 10 years for the home sample collection (HSC) HIVST to become available and another 16 years for rapid diagnostic test HIVST to be approved by the Federal Drug Administration. Since then, studies have shown high usability and performance of HIVST, which led the World Health Organization formally recommending HIVST in 2016, and currently almost 100 countries have incorporated HIVST into their national testing strategy. Despite the popularity, HIVST present challenges around pre-and post-test counselling, as well as the ability to report results and link users to care, and digital interventions for HIVST have been introduced to address these challenges. The first digital intervention for HIVST was introduced in 2014 and showed that digital interventions could be used to distribute HIVST kits, report results and link users to care. Since then, dozens of studies have been conducted, which have validated and expanded on these early findings, but many were pilot studies with small sample sizes and lacked the standardization of indicators required to aggregate data across platforms to prove impact at scale. For digital interventions for HIVST to be championed for scale-up, they must continue to show measurable impact at larger scales, while still maintaining and standardizing data security and integrity

Feasibility and Usability of Mobile Technology to Assist HIV Self-Testing in Youth in Zimbabwe: A Mixed-Methods Study

PURPOSE: Mobile technology is increasingly being used to widen access to and support the delivery of public health interventions. Human immunodeficiency viruses (HIV) self-testing (HIVST) enables individuals to have autonomy. We evaluated the feasibility of a novel application called ITHAKA to support HIVST among youth aged 16-24 years in Zimbabwe. METHODS: This study was nested within a trial of community-based delivery of integrated HIV and sexual and reproductive health services called CHIEDZA. Youth accessing CHIEDZA were offered provider-delivered HIV testing or HIVST supported by ITHAKA, either on a tablet on-site at a community centre or on their mobile phone off-site. ITHAKA incorporated pre and post-test counselling, and instructions for conducting the test and the appropriate actions to take depending on test result, including reporting HIV test results to health providers. The outcome was completion of the testing journey. Semistructured interviews with CHIEDZA providers explored the perceptions of and experiences with the application. RESULTS: Between April and September 2019, of the 2,181 youth who accepted HIV testing in CHIEDZA, 128 (5.8%) initiated HIVST (the remainder opting for provider-delivered testing) using ITHAKA. Nearly all who performed HIVST on-site (108/109 (99.1%)) compared to only 9/19 (47.4%) who tested off-site completed their testing journey. Low digital literacy, lack of agency, erratic network coverage, lack of dedicated phone ownership, the limited functionality of smartphones challenged implementation of ITHAKA. DISCUSSION: Digitally supported HIVST had low uptake among youth. The feasibility and usability of digital interventions should be carefully assessed before implementation, paying careful attention to digital literacy, network availability, and access to devices

Biochemical and structural characterization of mycobacterial aspartyl-tRNA synthetase AspS, a promising TB drug target.

The human pathogen Mycobacterium tuberculosis is the causative agent of pulmonary tuberculosis (TB), a disease with high worldwide mortality rates. Current treatment programs are under significant threat from multi-drug and extensively-drug resistant strains of M. tuberculosis, and it is essential to identify new inhibitors and their targets. We generated spontaneous resistant mutants in Mycobacterium bovis BCG in the presence of 10× the minimum inhibitory concentration (MIC) of compound 1, a previously identified potent inhibitor of mycobacterial growth in culture. Whole genome sequencing of two resistant mutants revealed in one case a single nucleotide polymorphism in the gene aspS at 535GAC>535AAC (D179N), while in the second mutant a single nucleotide polymorphism was identified upstream of the aspS promoter region. We probed whole cell target engagement by overexpressing either M. bovis BCG aspS or Mycobacterium smegmatis aspS, which resulted in a ten-fold and greater than ten-fold increase, respectively, of the MIC against compound 1. To analyse the impact of inhibitor 1 on M. tuberculosis AspS (Mt-AspS) activity we over-expressed, purified and characterised the kinetics of this enzyme using a robust tRNA-independent assay adapted to a high-throughput screening format. Finally, to aid hit-to-lead optimization, the crystal structure of apo M. smegmatis AspS was determined to a resolution of 2.4 Å

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment