The Ribosomal S10 Protein Is a General Target for Decreased Tigecycline Susceptibility

Tigecycline is a translational inhibitor with efficacy against a wide range of pathogens. Using experimental evolution, we adapted Acinetobacter baumannii, Enterococcus faecium, Escherichia coli, and Staphylococcus aureus to growth in elevated tigecycline concentrations. At the end of adaptation, 35 out of 47 replicate populations had clones with a mutation in rpsJ, the gene that encodes the ribosomal S10 protein. To validate the role of mutations in rpsJ in conferring tigecycline resistance, we showed that mutation of rpsJ alone in Enterococcus faecalis was sufficient to increase the tigecycline MIC to the clinical breakpoint of 0.5 μg/ml. Importantly, we also report the first identification of rpsJ mutations associated with decreased tigecycline susceptibility in A. baumannii, E. coli, and S. aureus. The identified S10 mutations across both Gram-positive and -negative species cluster in the vertex of an extended loop that is located near the tigecycline-binding pocket within the 16S rRNA. These data indicate that S10 is a general target of tigecycline adaptation and a relevant marker for detecting reduced susceptibility in both Gram-positive and -negative pathogens.     

An international study on teachers’ conceptions of learning and teaching and corresponding teacher profiles

Abstract

Introduction: Teachers’ conceptions of learning and teaching (COLT) affect their teaching behaviour. The 18 item COLT instrument has been developed in the Netherlands and comprises three scales, ‘teacher centredness’, ‘appreciation of active learning’ and ‘orientation to professional practice’. Previously we found five teacher profiles. The aim of this study was to find out if the COLT instrument can be used in an international setting.

Methods: Data were collected with the web-based COLT. Cronbach’s alphas of the three COLT scales were calculated. Subsequently a cluster analysis was conducted to identify different teacher profiles, followed by a split half validation procedure.

Results: Respondents (n?=?708) worked in 28 countries. Cronbach’s alphas were 0.67, 0.54, and 0.66. A six-cluster solution fitted best, based on meaning and explained variance. The sixth teacher profile scored high on ‘teacher centredness’, average on ‘appreciation of active learning’ and low on ‘orientation to professional practice’. The split half validation resulted in a Cohen’s kappa of 0.744.

Discussion: Cronbach’s alphas indicated acceptable reliablities for all three subscales. The new, sixth profile was labelled ‘neo-transmitter’.

Conclusion: We found evidence supporting the validity of the use of COLT in an international context and identified a new, sixth teacher profile.     

How basic psychological needs and motivation affect vitality and lifelong learning adaptability of pharmacists: a structural equation model

Insufficient professional development may lead to poor performance of healthcare professionals. Therefore, continuing education (CE) and continuing professional development (CPD) are needed to secure safe and good quality healthcare. The aim of the study was to investigate the hypothesized associations and their directions between pharmacists’ basic psychological needs in CE, their academic motivation, well-being, learning outcomes. Self-determination theory was used as a theoretical framework for this study. Data were collected through four questionnaires measuring: academic motivation, basic psychological needs (BPN), vitality and lifelong learning adaptability of pharmacists in the CE/CPD learning context. Structural equation modelling was used to analyze the data. Demographic factors like gender and working environment influenced the observed scores for frustration of BPN and factors like training status and working experience influenced the observed scores for academic motivation. A good model fit could be found only for a part of the hypothesized pathway. Frustration of BPN is positively directly related to the less desirable type of academic motivation, controlled motivation (0.88) and negatively directly related to vitality (? 1.61) and negatively indirectly related to learning outcomes in CE. Fulfillment or frustration of BPN are important predictors for well-being and learning outcomes. Further research should be conducted to discover how we can prevent these needs from being frustrated in order to design a motivating, vitalizing and sustainable CE/CPD system for pharmacists and other healthcare professionals. Basic psychological needs are very important predictors for well-being and learning outcomes. Further research should be conducted to discover how we can prevent these needs from being frustrated in order to design a motivating, vitalizing and sustainable CE/CPD system for pharmacists and other healthcare professionals.     

Occupational generalized urticaria and anaphylaxis after inhalation of cefuroxime in a nurse

We present the case of a 53 years old nonatopic female nurse who experienced repeated anaphylactic reactions at work without involvement in drug‐specific tasks such as crushing of tablets or preparation of injections. The causal allergen was not identified until a further severe anaphylactic reaction occurred after oral use of cefuroxime during a respiratory infection. Sensitization to cefuroxime was demonstrated by specific IgE, basophil activation test and skin prick test. An inhalation challenge with a dosimeter induced generalized urticaria after a cumulative dose of about 10 μg of the drug, but no asthmatic reaction. Complete exposure cessation was initiated and a 1‐year follow‐up was without further allergic reactions. We conclude that work‐related systemic allergic reactions to β‐lactam antibiotics may occur in nurses after inhalation of low doses and without perceived association with drug‐specific tasks like handling of antibiotics.

     

Using a multidisciplinary classification in nursing: the International Classification of Functioning Disability and Health

AIM: This paper reports a study to explore systematically the usefulness of the International Classification of Functioning, Disability and Health to nurses giving patient care. BACKGROUND: The International Classification of Functioning, Disability and Health has a history of more than 20 years. Although this World Health Organization classification offers multidisciplinary use, nurses are not familiar with it. METHODS: Applications of the International Classification for nursing practice were developed and evaluated in a multi-centre project, composed of a series of 10 projects in a variety of settings. These applications were a variety of tools, such as assessment forms, care plans and transfer forms. The study used information from 653 patients, 469 nurses and 178 others (International Classification experts; other professionals with whom nurses communicate or discuss patient data). FINDINGS: Large sections of the International Classification were used in the 10 projects, revealing a predominant focus on body functions (53% of all three-digit codes and corresponding terms used). Although large sections of the Classification were useful in practice applications, some items were identified that could be added, improved or described with more detail. Positive remarks made by nurses referred to the scope of the International Classification, which encouraged assessing beyond a patient's functional impairments. CONCLUSIONS: The International Classification of Functioning, Disability and Health can be a useful tool in classifying and communicating aspects of patient functioning by nurses. A level of moderate detail within the Classification (three-digit level) seems appropriate for most nursing purposes. Our results on items that could be added or improved can serve as input in future revisions of the Classification. Future use of the International Classification should be encouraged, because of its relevance to nursing and its potential for multidisciplinary use in patient care.     

Editor's choice: Programmed death ligand 1 expression and tumor-infiltrating lymphocytes in glioblastoma

Background

Immune checkpoint inhibitors targeting programmed cell death 1 (PD1) or its ligand (PD-L1) showed activity in several cancer types.

Methods

We performed immunohistochemistry for CD3, CD8, CD20, HLA-DR, phosphatase and tensin homolog (PTEN), PD-1, and PD-L1 and pyrosequencing for assessment of the O6-methylguanine-methyltransferase (MGMT) promoter methylation status in 135 glioblastoma specimens (117 initial resection, 18 first local recurrence). PD-L1 gene expression was analyzed in 446 cases from The Cancer Genome Atlas.

Results

Diffuse/fibrillary PD-L1 expression of variable extent, with or without interspersed epithelioid tumor cells with membranous PD-L1 expression, was observed in 103 of 117 (88.0%) newly diagnosed and 13 of 18 (72.2%) recurrent glioblastoma specimens. Sparse-to-moderate density of tumor-infiltrating lymphocytes (TILs) was found in 85 of 117 (72.6%) specimens (CD3+ 78/117, 66.7%; CD8+ 52/117, 44.4%; CD20+ 27/117, 23.1%; PD1+ 34/117, 29.1%). PD1+ TIL density correlated positively with CD3+ (P < .001), CD8+ (P < .001), CD20+ TIL density (P < .001), and PTEN expression (P = .035). Enrichment of specimens with low PD-L1 gene expression levels was observed in the proneural and G-CIMP glioblastoma subtypes and in specimens with high PD-L1 gene expression in the mesenchymal subtype (P = 5.966e-10). No significant differences in PD-L1 expression or TIL density between initial and recurrent glioblastoma specimens or correlation of PD-L1 expression or TIL density with patient age or outcome were evident.

Conclusion

TILs and PD-L1 expression are detectable in the majority of glioblastoma samples but are not related to outcome. Because the target is present, a clinical study with specific immune checkpoint inhibitors seems to be warranted in glioblastoma.     

Reforms in VUmc School of Medical Sciences Amsterdam: Student engagement,a Minor elective semester and stakeholder collaboration in improving the quality of assessments

Abstract

Background: At VUmc School of Medical Sciences, major curricular reforms occurred in 2005 and 2015, related to the introduction of a Bachelor-Master structure, a new legislation from the Ministry of Education, the changing societal context, and taking note of students’ and teachers’ needs.

Summary of work: Along with the introduction of the Bachelor-Master system, the period between 2005 and 2009 saw the movement from traditional lecture-based teaching to small group teaching in a competency-based curriculum, in which the students were responsible for their learning. Student engagement grew through students’ designing learning modules and conducting some of the teaching. In the Bachelor program, an elective “Minor”, was designed to broaden and deepen the knowledge of our students beyond the core learning outcomes, in a discipline of their choice. The examination board (EB), responsible for maintaining the quality of assessment, was split into the General EB, which handled overall strategy issues, and the Executive EB, which handled student requests and monitored the quality of assessments.

Lessons learned: Students develop a sense of what education is about if they are provided opportunities in designing teaching and conducting it. A Minor elective in the medical study can provide the students with an opportunity to learn outside the medical field. Collaborative working between different stakeholders in a medical school is crucial for safeguarding the quality of assessments. Curricular reforms need time to be accepted and integrated into the culture of the medical school. The educational vision needs to be refreshed regularly in alignment with the changing societal context.