Cryptococcus neoformans ex vivo capsule size is associated with intracranial pressure and host immune response in HIV-associated cryptococcal meningitis

<p>Background. The Cryptococcus neoformans polysaccharide capsule is a well-characterised virulence factor with immunomodulatory properties. The organism and/or shed capsule is postulated to raise intracranial pressure(ICP) in cryptococcal meningitis(CM) by mechanical obstruction of cerebrospinal fluid(CSF) outflow. Little is known regarding capsule phenotype in human cryptococcosis. We investigated the relationship of ex vivo CSF capsular phenotype with ICP and CSF immune response, as well as in vitro phenotype.</p> <p>Methods. 134 HIV-infected Ugandan adults with CM had serial lumbar punctures with measurement of CSF opening pressures, quantitative cultures, ex vivo capsule size and shedding, viscosity, and CSF cytokines. 108 had complete data. Induced capsular size and shedding were measured in vitro for 48 C. neoformans isolates.</p> <p>Results. Cryptococcal strains producing larger ex vivo capsules in the baseline(pre-treatment) CSF correlated with higher ICP(P=.02), slower rate of fungal clearance(P=.02), and paucity of CSF inflammation, including decreased CSF white blood cell(WBC) count(P<.001), interleukin(IL)-4(P=.02), IL-6(P=.01), IL-7(P=.04), IL-8(P=.03), and interferon-gamma(P=.03). CSF capsule shedding did not correlate with ICP. On multivariable analysis, capsule size remained independently associated with ICP. Ex vivo capsular size and shedding did not correlate with that of the same isolates grown in vitro.</p> <P>Conclusions. Cryptococcal capsule size ex vivo is an important contributor to virulence in human cryptococcal meningitis.</P&gt

Breakdown mechanisms of oil-in-water emulsions stabilised with Pluronic F127 and co-surfactants

Please read abstract in the article.The University of Pretoria and the Institute of Applied Materials for a stipend to AK, the Council for Scientific and Industrial Research (CSIR) for allowing access to the surface tension instrument and to BASF for donation of the Pluronic F127 block copolymer.http://www.elsevier.com/locate/colsurfa2021-01-20hj2019Chemical Engineerin

Learning by doing in the student-run pharmacovigilance programme

Background: Pharmacovigilance, the monitoring of drug safety after marketing approval, depends highly on the adequate reporting of adverse drug reactions (ADRs). To improve pharmacovigilance awareness and future ADR reporting among medical students, we developed and evaluated a student-run pharmacovigilance programme. Methods: In this project, teams of medical students (1st-5th year) assessed real ADR-reports as submitted to the national pharmacovigi-lance centre. After assessment of causality, including identifcation of a potential pharmacological explanation for the ADR, they wrote a personalized feedback letter to the reporter and a summary for the EMA and WHO pharmacovigilance databases. This student assessment was then verifed and evaluated by Lareb staff, using an E-questionnaire. Student attitudes, intentions, skills, and knowledge of ADR reporting were evaluated with an E-questionnaire before and after participation. Results: From May 2014 to January 2015, 43 students assessed 100 different ADR reports selected by Lareb staff (n= 3). Student assess-ments were rated as useful (93%), scientifcally substantiated (90%), accurate (92%), and complete (92%), and, on average, did not cost Lareb staff extra time. Medical students were positive about ADR reporting. Their awareness of ADR reporting increased signifcantly following participation and they would be more likely to report ADRs in the future. The students' knowledge of pharmacovigilance and ADR reporting showed that they had a high overall level of pharmacological understanding. Conclusions: The student-run pharmacovigilance programme is a win-win venture. It offers students a valuable "pharmacovigilance experience", creates awareness in future doctors, and has the poten-tial to increase pharmacovigilance skills and knowledge

Learning by doing in the student-run pharmacovigilance program

Background: Medication safety is an important topic in healthcare nowadays. Pharmacovigilance, the monitoring of drug safety after approval for marketing, depends mainly on the quality and quantity of reported adverse drug reactions (ADR). To increase pharmacovigilance awareness among medical students, we developed and evaluated a Student-run Pharmacovigilance program, together with pharmacovigilance centre Lareb. Method: A pilot study was performed in which teams of (1st-4th year) medical students assessed real ADR-reports from patients/healthcare professionals reported to Lareb. After assessment on causality, students searched for a pharmacological explanation and wrote a feedback letter to the reporter and a summary for the pharmacovigilance- databases of the European Medicines Agency and WHO. This student-assessment was then verified by Lareb staff, who evaluated student-handling it in an e-questionnaire. Results: From May to December 2014, 89 different ADR-reports selected by Lareb staff were handled, with the top 3 reported ADRs being; palpitations, urinary retention and agitation. Thirty-five students and 3 Lareb staff members participated. Lareb staff rated the student assessments (very) useful (> 92%), scientifically substantiated (> 88%), complete (not lacking information) and without inaccuracies (both > 92%). Altogether the student-assessments were rated mean 8.3 (1-10; min-max). Compared to self-handling, Lareb staff indicated student-assessment cost less time in 33% assessments, neutral in 55%, and cost extra time in 11%. Conclusion: The Student-run pharmacovigilance program is a win-win venture. It offers students a valuable “pharmacovigilance experience”, creates awareness in future doctors with the potential to increase ADR-reporting, and didn't cost Lareb staff extra time overall. The learner effects need to be investigated in future studies

Student views on the student-run pharmacovigilance program

Background: Pharmacovigilance centers play a vital role in the monitoring of drug safety after approval for marketing, and depend mainly on the quantity and quality of reported adverse drug reactions (ADRs). To ensure future ADR-reporting and increase pharmacovigilance awareness among medical students, we developed and aim to evaluate student outcomes of participation in our Studentrun Pharmacovigilance program. Method: A pilot study was performed in which student attitudes, knowledge and skills on ADR-reporting were evaluated using an e-questionnaire before and after participation in the student-run pharmacovigilance program. Teams of (1st-4th year) medical students assessed real ADR-reports from healthcare-professionals/patients reported to Lareb. These student-assessments included a causality assessment, (scientific) pharmacological explanation, feedback letter to the reporter, and summary for the pharmacovigilancedatabases of the European Medicines Agency and WHO. Results: From May 2014-January 2015, 100 different ADR-reports selected by Lareb staff were handled by 43 students. Before participating in the pilot <25% knew how to report ADRs. After participation > 70% knew how to report, and were even able to name important details for ADR-reporting. Intention towards ADR-reporting was assessed using a 7-point Likert scale (1: extremely unlikely-7: extremely likely). Students indicated they intend to report serious (6.44 SD 0.73) and unknown (6.44 SD 0.63) future encountered ADRs. On a 5 point Likert scale students disagreed (2.50 SD 1.15) their current curriculum covered pharmacovigilance well, found participation educational (4.56 SD 0.63) and more interesting than fictive casuistry (4.56 SD 0.73). Furthermore besides students reported they learned how to asses ADRs, they stated to have learned skills/knowledge regarding critical appraisal of information, understanding of pharmacological mechanisms and scientific writing. Conclusion: The Student-run pharmacovigilance program is a valuable and novel educational experience. It creates awareness in future doctors with the potential to increase ADR-reporting, lets students practice in searching and writing scientifically and teaches the basics of pharmacovigilance in real life