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In the Netherlands, child abuse affects about 100.000 children resulting in at least 17 child fatalities a year. General practitioners' (GPs) health care position is of vital importance for recognising and managing child abuse. In this Clinical Lesson, using three illustrating cases, we discuss how GPs' suspicion of child abuse may arise including the role of gut feelings, and what the mandatory national guideline on child abuse means for the follow-up. We also clarify the role of the Dutch Child Abuse Counselling and Reporting Centre (CACRC) in the process. A first lesson is that any doubts about child abuse should lead to action because diagnostic failure has serious consequences for vulnerable children. A second lesson is that asking CACRC for anonymous advice how to deal with a situation may certainly have added value. Finally, we advise CACRC to invest in building a relationship of trust with the collaborating partners.

Self-perceived word-finding difficulties are common in aging individuals as well as in Alzheimer's Disease (AD). Language and speech deficits are difficult to objectify with neuropsychological assessments. We therefore aimed to investigate whether amyloid, an early AD pathological hallmark, is associated with speech-derived semantic complexity. We included 63 individuals with subjective cognitive decline (age 64 ± 8, MMSE 29 ± 1), with amyloid status (positron emission tomography [PET] scans n = 59, or Aβ1-42 cerebrospinal fluid [CSF] n = 4). Spontaneous speech was recorded using three open-ended tasks (description of cookie theft picture, abstract painting and a regular Sunday), transcribed verbatim and subsequently, linguistic parameters were extracted using T-scan computational software, including specific words (content words, frequent, concrete and abstract nouns, and fillers), lexical complexity (lemma frequency, Type-Token-Ratio) and syntactic complexity (Developmental Level scale). Nineteen individuals (30%) had high levels of amyloid burden, and there were no differences between groups on conventional neuropsychological tests. Using multinomial regression with lin- guistic parameters (in tertiles), we found that high amyloid burden is associated with fewer concrete nouns (ORmiddle (95%CI): 7.6 (1.4–41.2), ORlowest: 6.7 (1.2–37.1)) and content words (ORlowest: 6.3 (1.0–38.1). In addition, we found an interaction for education between high amyloid burden and more abstract nouns. In conclusion, high amyloid burden was modestly associated with fewer specific words, but not with syntactic complexity, lexical complexity or conventional neuropsychological tests, suggesting that subtle spontaneous speech deficits might occur in preclinical AD.

Objective The folate antagonist methotrexate (MTX) is an anchor drug in the treatment of rheumatoid arthritis (RA), but its mechanism of action with regard to the impact on folate metabolism remains elusive. The aim of the present study was to investigate the cellular pharmacologic impact of MTX on peripheral blood cells, by comparing MTX-treated RA patients to MTX-naive RA patients and healthy controls. Methods Gene expression microarray data were used to investigate the expression of 17 folate pathway genes by peripheral blood cells from a cohort of 25 RA patients treated with MTX, 10 MTX-naive RA patients starting treatment with MTX, and 15 healthy controls (test cohort). Multiplex real-time polymerase chain reaction was used to validate the results in an independent cohort, consisting of 151 RA patients treated with MTX, 28 MTX-naive RA patients starting treatment with MTX, and 24 healthy controls (validation cohort). Results Multiple folate metabolism-related genes were consistently and significantly altered between the 3 groups in both cohorts. Concurrent with evidence of an immune-activation gene signature in MTX-naive RA patients, significant up-regulation of the folate-metabolizing enzymes γ-glutamyl hydrolase and dihydrofolate reductase, as well as the MTX/folate efflux transporters ABCC2 and ABCC5, was observed in the MTX-naive RA group compared to healthy controls. Strikingly, MTX treatment of RA patients normalized these differential gene expression levels to the levels observed in healthy controls. Conclusion These results suggest that under inflammatory conditions, basal folate metabolism in the peripheral blood cells of RA patients is markedly up-regulated, and treatment with MTX restores folate metabolism to normal levels. Identification of this novel gene signature provides insight into the mechanism of action of MTX, thus paving the way for development of novel folate metabolism-targeted therapies. Copyright © 2013 by the American College of Rheumatology.

Introduction: B cell depletion therapy is efficacious in rheumatoid arthritis (RA) patients failing on tumor necrosis factor (TNF) blocking agents. However, approximately 40% to 50% of rituximab (RTX) treated RA patients have a poor response. We investigated whether baseline gene expression levels can discriminate between clinical non-responders and responders to RTX.Methods: In 14 consecutive RA patients starting on RTX (test cohort), gene expression profiling on whole peripheral blood RNA was performed by Illumina

This study brings together findings from different research angles on informal feedback in the workplace. We explore the individual and joint influences of three contextual antecedents of seeking feedback: support for learning, psychological safety, and work pressure. Based on our survey of 138 employees from various organizations, hierarchical regression analyses revealed that support in the work environment positively influenced the quality of the self-initiated feedback from colleagues and (in particular( from the supervisor. Psychological safety positively related to the quality of the self-initiated feedback from colleagues. No relation was found between support, psychological safety and the frequency of feedback seeking, however, an indication for the existence of a curvilinear effect of work pressure on the frequency of feedback seeking was found. The study highlights the importance of fostering supportive and psychological safe work environments, so that employees and supervisors will look for and give constructive feedback. Learning in organizations can be stimulated by creating enough time and opportunities for informal feedback, and the results suggest several valuable and promising avenues for future research.

Medical professionals need to keep on learning as part of their everyday work to deliver high-quality health care. Although the importance of physicians learning is widely recognized, few studies have investigated how they learn in the workplace. Based on insights from deliberate practice research, this study examined the activities physicians engage in during their work that might further their professional development. As deliberate practice requires a focused effort to improve performance, the study also examined the goals underlying this behaviour. Semi-structured interviews were conducted with 50 internal medicine physicians: 19 residents, 18 internists working at a university hospital, and 13 working at a non-university hospital. The results showed that learning in medical practice was very much embedded in clinical work. Most relevant learning activities were directly related to patient care rather than motivated by competence improvement goals. Advice and feedback were sought when necessary to provide this care. Performance standards were tied to patients conditions. The patients encountered and the discussions with colleagues about patients were valued most for professional development, while teaching and updating activities were also valued in this respect. In conclusion, physicians learning is largely guided by practical experience rather than deliberately sought. When professionals interact in diagnosing and treating patients to achieve high-quality care, their experiences contribute to expertise development. However, much could be gained from managing learning opportunities more explicitly. We offer suggestions for increasing the focus on learning in medical practice and further research.