Characterisation of plasmids conferring ampicillin resistance in South African isolates of haemophilus ducreyi

A dissertation submitted to the Faculty of Medicine, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master of Science (medicine).' Johannesburg 1996Fifty-two strains of Haemophilus ducreyi from various geographic regions of southern Africa (Botswana, Lesotho, Namibia, Gauteng, Natal and Transkei) isolated between 1988 to 1994 were tested for susceptibilities to five antimicrobial agents and characterized according to their plasmid content and ampicillin- resistance genes.IT201

Short-hairpin RNA library: identification of therapeutic partners for gefitinib-resistant non-small cell lung cancer.

Somatic mutations of the epidermal growth factor receptor often cause resistance to therapy with tyrosine kinase inhibitor in non-small cell lung cancer (NSCLC). In this study, we aimed to identify partner drugs and pathways that can induce cell death in combination with gefitinib in NSCLC cells. We undertook a genome-wide RNAi screen to identify synthetic lethality with gefitinib in tyrosine kinase inhibitor resistant cells. The screening data were utilized in different approaches. Firstly, we identified PRKCSH as a candidate gene, silencing of which induces apoptosis of NSCLC cells treated with gefitinib. Next, in an in silico gene signature pathway analysis of shRNA library data, a strong correlation of genes involved in the CD27 signaling cascade was observed. We showed that the combination of dasatinib (NF-κB pathway inhibitor) with gefitinib synergistically inhibited the growth of NSCLC cells. Lastly, utilizing the Connectivity Map, thioridazine was identified as a top pharmaceutical perturbagen. In our experiments, it synergized with gefitinib to reduce p-Akt levels and to induce apoptosis in NSCLC cells. Taken together, a pooled short-hairpin library screen identified several potential pathways and drugs that can be therapeutic targets for gefitinib resistant NSCLC

Belinostat and panobinostat (HDACI): in vitro and in vivo studies in thyroid cancer

PurposeAdvanced thyroid cancer responds poorly to most therapies. New therapies and combinations are needed. The aim of this study was to examine both in vitro and in vivo activity of two relatively new histone deacetylase inhibitors (HDACIs), belinostat and panobinostat, and a variety of tyrosine kinase inhibitors (TKIs) against a panel of nine human thyroid cancer cell lines.MethodsThe anti-proliferative activity and the effects of HDACIs, TKIs and their combinations on thyroid cancer cells were determined by cytotoxicity assays, microarray and immunoblot analyses. Synergism between HDACIs and TKIs was assessed by the median effects model of Chou-Talalay (Calcusyn(®)).ResultsBelinostat and panobinostat were active against the thyroid cancer cell lines irrespective of their mutational composition, and belinostat was effective in preventing growth of human thyroid cancer xenografts in immunodeficient mice. Further studies showed that both HDACIs induced apoptosis. HDACI also elevated acetylated histone 3, p21(Waf), and PARP, and decreased levels of phosphorylated ERK and AKT (Ser473). RNA assay analysis suggested both HDACIs modulated genes associated with the cell cycle, DNA damage and apoptosis. Most of the TKI (pazopanib, motesanib, sorafenib and dasatinib) were either inactive in vitro or were active only at high doses. However, the novel combinations of either pazopanib or dasatinib TKIs with either belinostat or panobinostat synergistically inhibited cell growth of thyroid cancer cells in vitro.ConclusionsIn summary, these HDACIs either alone or combined with selected TKIs may have a role in treatment of aggressive thyroid cancer

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Students’ response to feedback : an exploratory study

Much research work on teacher feedback has concentrated on the perceptions of students and teachers on feedback, but few studies have addressed the extent to which students respond to their teachers’ written feedback, particularly at the tertiary level. This study analysed the extent to which students made appropriate revisions based on the feedback they received. Forty-one sets of drafts and final papers written by first-year undergraduates were compared. The analysis focused on the main components of the grading criteria for the assignment: language and style, rhetorical structure, and format. The findings showed that the students paid more attention to feedback on the rhetorical structure of their writing. There was no statistically significant difference in the students’ revisions of language/style and format. The results suggest that the students were more concerned with macro issues concerning the clarity of their thesis/topic statements and the logical development of ideas, than with the mechanical aspects of writing. This study serves as a useful guide to teachers when providing feedback, and also serves to encourage further research involving different groups of students in different contexts

Do genitourinary physicians report notifiable diseases? A survey in South East England

Genitourinary medicine work requires public health actions. Notifiable infections may be seen in genitourinary medicine, but concerns over confidentiality could delay public health actions and outbreak management. To assess genitourinary medicine clinicians’ awareness of notification of infectious disease, reporting practices and liaison with Health Protection Units, we sent postal surveys to 140 genitourinary medicine clinicians (SE HPA region) that explored prior public health training, Health Protection Unit liaison and management of possible clinical scenarios. Fifty-seven respondents reported median genitourinary medicine experience of 12 years; 29% had prior public health training, nine on the British Association for Sexual Health and HIV course. A total of 90% had heard of Health Protection Units and understood their role. Approximately one-third would not report key diseases at all, most reporting only on laboratory confirmation. In all, 83% would only notify acute hepatitis on lab confirmation; 50% would report suspected measles immediately (44% awaiting lab confirmation) and 40% would not pass on any patient details without consent. Clinicians have good knowledge of notification of infectious disease conditions but responses suggest it is not always used in clinical context. Reporting delays occur waiting for lab confirmation and liaison with local Health Protection Units may be hindered by confidentiality concerns, potentially delaying public health action. Doctors with prior public health training are more likely to report appropriately

Investigating teacher perceptions of feedback

In writing classes, teacher feedback is important in helping students with their writing. While research has generally focused on the purpose, nature, and form of teacher feedback, attention to teachers’ views regarding their own feedback practices has been modest. Yet, it is important to understand why and how teachers provide feedback, as practice is often guided by beliefs. This study, therefore, investigated the factors that shape teacher feedback. Writing teachers at a Singaporean university were interviewed regarding their beliefs about feedback and their feedback practices. The findings revealed that the respondents’ feedback practices were shaped by their beliefs about the needs and capabilities of their students, but that contextual constraints created tensions between ideal and actual practice. Practical suggestions are offered to facilitate feedback practice. This study highlights the need for further work in this area in order to inform teachers’ practices in providing feedback to their students

Investigating teacher perceptions of feedback

In writing classes, teacher feedback is important in helping students with their writing. While research has generally focused on the purpose, nature, and form of teacher feedback, attention to teachers’ views regarding their own feedback practices has been modest. Yet, it is important to understand why and how teachers provide feedback, as practice is often guided by beliefs. This study, therefore, investigated the factors that shape teacher feedback. Writing teachers at a Singaporean university were interviewed regarding their beliefs about feedback and their feedback practices. The findings revealed that the respondents’ feedback practices were shaped by their beliefs about the needs and capabilities of their students, but that contextual constraints created tensions between ideal and actual practice. Practical suggestions are offered to facilitate feedback practice. This study highlights the need for further work in this area in order to inform teachers’ practices in providing feedback to their students