Type IV Pili Can Mediate Bacterial Motility within Epithelial Cells.

Pseudomonas aeruginosa is among bacterial pathogens capable of twitching motility, a form of surface-associated movement dependent on type IV pili (T4P). Previously, we showed that T4P and twitching were required for P. aeruginosa to cause disease in a murine model of corneal infection, to traverse human corneal epithelial multilayers, and to efficiently exit invaded epithelial cells. Here, we used live wide-field fluorescent imaging combined with quantitative image analysis to explore how twitching contributes to epithelial cell egress. Results using time-lapse imaging of cells infected with wild-type PAO1 showed that cytoplasmic bacteria slowly disseminated throughout the cytosol at a median speed of >0.05 μm s-1 while dividing intracellularly. Similar results were obtained with flagellin (fliC) and flagellum assembly (flhA) mutants, thereby excluding swimming, swarming, and sliding as mechanisms. In contrast, pilA mutants (lacking T4P) and pilT mutants (twitching motility defective) appeared stationary and accumulated in expanding aggregates during intracellular division. Transmission electron microscopy confirmed that these mutants were not trapped within membrane-bound cytosolic compartments. For the wild type, dissemination in the cytosol was not prevented by the depolymerization of actin filaments using latrunculin A and/or the disruption of microtubules using nocodazole. Together, these findings illustrate a novel form of intracellular bacterial motility differing from previously described mechanisms in being directly driven by bacterial motility appendages (T4P) and not depending on polymerized host actin or microtubules.IMPORTANCE Host cell invasion can contribute to disease pathogenesis by the opportunistic pathogen Pseudomonas aeruginosa Previously, we showed that the type III secretion system (T3SS) of invasive P. aeruginosa strains modulates cell entry and subsequent escape from vacuolar trafficking to host lysosomes. However, we also showed that mutants lacking either type IV pili (T4P) or T4P-dependent twitching motility (i) were defective in traversing cell multilayers, (ii) caused less pathology in vivo, and (iii) had a reduced capacity to exit invaded cells. Here, we report that after vacuolar escape, intracellular P. aeruginosa can use T4P-dependent twitching motility to disseminate throughout the host cell cytoplasm. We further show that this strategy for intracellular dissemination does not depend on flagellin and resists both host actin and host microtubule disruption. This differs from mechanisms used by previously studied pathogens that utilize either host actin or microtubules for intracellular dissemination independently of microbe motility appendages

Use of Non-Steroidal Anti-Inflammatory Drugs That Elevate Cardiovascular Risk: An Examination of Sales and Essential Medicines Lists in Low-, Middle-, and High-Income Countries

PMCID: PMC3570554This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Self-directed learning research and its impact on educational practice

This scholarly book is the third volume in an NWU book series on self-directed learning and is devoted to self-directed learning research and its impact on educational practice. The importance of self-directed learning for learners in the 21st century to equip themselves with the necessary skills to take responsibility for their own learning for life cannot be over emphasised. The target audience does not only consist of scholars in the field of self-directed learning in Higher Education and the Schooling sector but includes all scholars in the field of teaching and learning in all education and training sectors. The book contributes to the discourse on creating dispositions towards self-directed learning among all learners and adds to the latest body of scholarship in terms of self-directed learning. Although from different perspectives, all chapters in the book are closely linked together around self-directed learning as a central theme, following on the work done in Volume 1 of this series (Self-Directed Learning for the 21st Century: Implications for Higher Education) to form a rich knowledge bank of work on self-directed learning

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

New perspectives on learning

No abstract available

Critical thinking: are the ideals of OBE failing us or are we failing the ideals of OBE?

One of the cornerstones of the Outcomes-based approach adopted by the South African education and training sector is the so-called Critical Outcomes. Included as one of these outcomes is the ability of learners to identify and solve problems, using creative and critical thinking. Underpinned by the Critical Outcomes, Outcomes-based Education (OBE) was introduced in South African schools in 1997. It can therefore be argued that the critical thinking abilities of the cohort of first-year students who entered higher education institutions in 2006 were challenged somewhere in their school careers. Based on this assumption, a group of first-year education students were required to complete the Watson Glaser Critical Thinking Appraisal (WGCTA) to gauge their critical thinking abilities. The results obtained by this means are discussed and some suggestions made to address the way forward with regard to development of learners' critical thinking abilities

Creative thinking in prospective teachers: the status quo and the impact of contextual factors

To create unique and appropriate learning opportunities and environments and to nurture the development of creative thinking abilities among learners are some of the demands for creative thinking currently expected of teachers globally and also in South Africa. Creative thinking in academic context assumes, among other things, the ability to generate a variety of original ideas, to see different viewpoints and elaborate on ideas. We report on the findings of a quantitative pilot investigation by means of experimental research utilizing an ex post facto design to determine the status quo regarding the creative thinking abilities of a hetrogeneous group of 207 pre-service teachers studying at a South African university, using the Abbreviated Torrance Test for Adults (ATTA) and a Partial Least Squares (PLS) exploration into the relationship between contextual factors and the students' creative thinking abilities. Strong correlations were found among a variety of contextual factors such as the type of school model and culture and creative thinking abilities and also between specific contextual factors such as the choice of role model and socio economic and acculturation factors and certain creative thinking abilities. This research explores a largely unknown field, namely, the creative thinking abilities of a group of South African pre-service teachers of different cultural groups and creates an awareness of the need for the development of creative thinking abilities among these prospective teachers

The relationship between the critical thinking skills and the academic language proficiency of prospective teachers

We report on the relationships that exist between the critical thinking skills and the academic language proficiency of a group of first-year prospective teachers at a South African university (n = 89). The results revealed the nature of the critical thinking skills as well as the academic language proficiency of the students. Significant correlations between academic language proficiency and making inferences, as well as between academic language proficiency and critical thinking as a general competency, were noted. The article concludes with recommendations on how to enhance critical thinking and language proficiency in the teacher-training curriculum.http://www.scielo.org.za/pdf/saje/v33n2/06.pd

Enhancing social skills through cooperative learning

The National Curriculum Statement of South Africa envisages qualified and competent teachers to deal with the diversity of learners and their needs in the classroom. One of the needs refers to all learners (Gr R-12) who need to acquire the necessary social skills to enable them to work effectively with others as members of a team, group, organization and community. These skills refer inter alia to: learning to work with others, listening to others, giving attention, asking clarifying questions, learning how to evaluate, and to praise others, handling conflict, reflecting on group work and allowing all group members to participate. The most obvious place to deal purposefully with the development of social skills is the classroom. This implies that alternative ways and methods of teaching must be introduced to develop the necessary social skills. This article reports on the findings obtained from a combined quantitative and qualitative study that set out to determine the levels of social competence achieved by a group of Grade 2 learners, and the possible association of a cooperative teaching and learning intervention programme for enhancing the social skills of these learners. The results revealed the latent potential of cooperative learning to enhance the social skills of Grade 2 learners. The significance of this research lies in the contribution it makes to establish the social competence of a group of Grade 2 learners and to determine the possibilities for enhancing their social skills through cooperative learning