How simulated patients contribute to student learning in an authentic way:An interview study

Introduction: Simulated patients (SPs) play an instrumental role in teaching communication skills and enhancing learning outcomes. Prior research mostly focused on the SP’s contribution to students’ learning outcomes by providing feedback afterwards. A detailed understanding of the contribution of the SP during SP-student encounters is currently lacking although the majority of the interaction between SPs and students occurs during the SP-student encounter. Therefore, this study focuses on how SPs see their contribution to meaningful student learning experiences during SP-student encounters. Methods: We interviewed fifteen simulated patients from one institution. We explored their perspectives on meaningful learning experiences during SP-student encounters through in-depth, semi-structured interviews and analyzed using thematic analysis. Results: SPs view their contribution to meaningful student learning during SP-student encounters from two perspectives. A collective perspective as a member of the community of SPs and an individual perspective. From the collective perspective, SPs believe that the fact that students deal with multiple varied SP-student encounters over time is of value for meaningful learning. From the individual perspective, we noticed that SPs think, act, and react from three different positions. First, as the patient in the role description, second, as a teaching aid and third, as an individual with personal experiences, beliefs, and values. SPs mentioned that the ratio between these different positions can vary within and between encounters. Conclusions: According to SPs, we should value the variation between SPs, thereby creating meaningful variation in authentic interactions in SP-student encounters. SPs should be allowed to act and react from different positions during SP-student encounters, including their role description, as teaching aid, and based on their own experiences. In this way, SP-student encounters are optimized to contribute to meaningful student learning through authenticity.</p

Transcriptomic changes in autophagy-related genes are inversely correlated with inflammation and are associated with multiple sclerosis lesion pathology

Autophagy is a lysosomal degradative pathway essential for maintaining cellular homeostasis and is also implicated in multiple aspects of both innate and adaptive immunity. Neuroinflammation, along with demyelination and axonal loss, is an important component of multiple sclerosis (MS). Induction of autophagy ameliorated disease progression in experimental autoimmune encephalomyelitis (EAE), a mouse model for MS, underlying a possible link between autophagy and MS pathology. However, it is still unclear how autophagy is affected during different stages of MS. Here, we show a decreased expression of the autophagy-related (ATG) genes during the acute phase of EAE development in mice as well as in mixed active/inactive lesions of post-mortem human MS brain tissues. Using spatial transcriptomics, we observed that this decreased ATG gene expression is most prominent in the core of mixed active/inactive lesions. Furthermore, we observed a hyper-activation of the mammalian target of rapamycin complex 1 (mTORC1) in lesions, which could inhibit both the initiation of autophagy and the transcription factors that regulate the expression of the ATG genes. Thus, based on our data, we propose a negative regulation of autophagy in MS, possibly through persistent mTORC1 activation, which depends on the lesion stage. Our results contribute to the understanding of the role of autophagy in different stages of MS pathology and point to the mTORC1 pathway as a potential modulator that likely regulates central nervous system (CNS) homeostasis and neuroinflammation in MS

Psychosocial work characteristics associated with distress and intention to leave nursing education; a one-year follow-up study

Background: Dropout in later years of the nursing degree programme involves lost investment and is a particular problem for both students and educators. Reasons for late dropout seem to be related to the work and learning environment of the clinical placement. Objectives: The aim of this study was to investigate associations between psychosocial work characteristics and distress and intention to leave nursing education among third-year nursing students. Design: A prospective cohort study. Setting A Bachelor of Nursing programme of a University of Applied Sciences in [name country]. Participants: 363 third-year nursing students. Methods: Baseline and one-year follow-up measurements were used from a prospective cohort study. Third-year nursing students were invited annually in May between 2016 and 2018. Psychosocial work characteristics were psychological demands, supervisor and co-worker support, and acts of offensive behaviour. Logistic regression analyses were used to build multivariate models. Results: Frequent exposure to violence (OR = 2.52, 95% CI: 1.29-4.92) was univariately associated with distress. In the multivariate model for distress, psychological demands (OR = 1.63, 95% CI: 1.05-2.52) and frequent exposure to violence (OR = 3.02, 95% CI: 1.48-6.19) were associated with distress. Supervisor support (OR = 0.54, 95% CI: 0.36-0.80) and co-worker support (OR = 0.41, 95% CI: 0.24-0.72) were negatively associated with intention to leave (i.e. were protective) in the univariate model. In the adjusted multivariate model, only co-worker support (OR = 0.50, 95% CI: 0.25-0.97) was a protective factor for an intention to leave. Conclusion: Psychological demands and frequent exposure to violence are risk factors for distress, and co-worker support is a protective factor reducing the intention to leave nursing education in the last stage of the programme. Improving the psychosocial working climate of nursing students may reduce the intention to leave at a late stage in nursing education, and hence actual late dropout

Comparison of Circulating Cell-Free DNA Extraction Methods for Downstream Analysis in Cancer Patients

Circulating cell-free DNA (ccfDNA) may contain DNA originating from the tumor in plasma of cancer patients (ctDNA) and enables noninvasive cancer diagnosis, treatment predictive testing, and response monitoring. A recent multicenter evaluation of workflows by the CANCER-ID consortium using artificial spiked-in plasma showed significant differences and consequently the importance of carefully selecting ccfDNA extraction methods. Here, the quantity and integrity of extracted ccfDNA from the plasma of cancer patients were assessed. Twenty-one cancer patient-derived cell-free plasma samples were selected to compare the Qiagen CNA, Maxwell RSC ccfDNA plasma, and Zymo manual quick ccfDNA kit. High-volume citrate plasma samples collected by diagnostic leukapheresis from six cancer patients were used to compare the Qiagen CNA (2 mL) and QIAamp MinElute ccfDNA kit (8 mL). This study revealed similar integrity and similar levels of amplified short-sized fragments and tumor-specific mutants comparing the CNA and RSC kits. However, the CNA kit consistently showed the highest yield of ccfDNA and short-sized fragments, while the RSC and ME kits showed higher variant allelic frequencies (VAFs). Our study pinpoints the importance of standardizing preanalytical conditions as well as consensus on defining the input of ccfDNA to accurately detect ctDNA and be able to compare results in a clinical routine practice, within and between clinical studies

Circulating tumor DNA as a biomarker for monitoring early treatment responses of patients with advanced lung adenocarcinoma receiving immune checkpoint inhibitors

Immunotherapy for metastasized non-small-cell lung cancer (NSCLC) can show long-lasting clinical responses. Selection of patients based on programmed death-ligand 1 (PD-L1) expression shows limited predictive value for durable clinical benefit (DCB). We investigated whether early treatment effects as measured by a change in circulating tumor DNA (ctDNA) level is a proxy of early tumor response to immunotherapy according to response evaluation criteria in solid tumors v1.1 criteria, progression-free survival (PFS), DCB, and overall survival (OS). To this aim, blood tubes were collected from advanced-stage lung adenocarcinoma patients (n = 100) receiving immune checkpoint inhibitors (ICI) at baseline (t(0)) and prior to first treatment evaluation (4-6 weeks; t(1)). Nontargetable (driver) mutations detected in the pretreatment tumor biopsy were used to quantify tumor-specific ctDNA levels using droplet digital PCR. We found that changes in ctDNA levels were strongly associated with tumor response. A > 30% decrease in ctDNA at t(1) correlated with a longer PFS and OS. In total, 80% of patients with a DCB of >= 26 weeks displayed a > 30% decrease in ctDNA levels. For patients with a PD-L1 tumor proportion score of >= 1%, decreasing ctDNA levels were associated with a higher frequency a DCB (80%) and a prolonged median PFS (85 weeks) and OS (101 weeks) compared with patients with no decrease in ctDNA (34%; 11 and 39 weeks, respectively). This study shows that monitoring of ctDNA dynamics is an easy-to-use and promising tool for assessing PFS, DCB, and OS for ICI-treated NSCLC patients

Profiling Microglia From Alzheimer's Disease Donors and Non-demented Elderly in Acute Human Postmortem Cortical Tissue

Microglia are the tissue-resident macrophages of the central nervous system (CNS). Recent studies based on bulk and single-cell RNA sequencing in mice indicate high relevance of microglia with respect to risk genes and neuro-inflammation in Alzheimer's disease (AD). Here, we investigated microglia transcriptomes at bulk and single-cell levels in non-demented elderly and AD donors using acute human postmortem cortical brain samples. We identified seven human microglial subpopulations with heterogeneity in gene expression. Notably, gene expression profiles and subcluster composition of microglia did not differ between AD donors and non-demented elderly in bulk RNA sequencing nor in single-cell sequencing

Validity of the Patient Experiences and Satisfaction with Medications (PESaM) Questionnaire

Background: This study assessed the validity and reliability of the generic module of the recently developed Patient Experiences and Satisfaction with Medications (PESaM) questionnaire in a sample of patients in the Netherlands. Methods: The generic module of the PESaM questionnaire consists of 18 items related to the domains effectiveness, side effects and ease of use of medications. It assesses patients’ experiences regarding the impact of the medication on daily life, health and satisfaction. In 2017, the PESaM questionnaire was sent out to idiopathic pulmonary fibrosis patients using pirfenidone or nintedanib, atypical haemolytic uraemic syndrome patients receiving eculizumab and patients using tacrolimus after kidney transplantation. Mean scores for each domain were calculated applying a scoring algorithm. Construct validity and reliability were assessed using recommended methods. Results: 188 participants completed the generic module, of whom 48% used pirfenidone, 36% nintedanib, 11% tacrolimus and 5% eculizumab. The generic module has good structural properties. Internal consistency values of the domains were satisfactory (i.e. Cronbach’s coefficient alpha above 0.7). Confirmatory factor analysis provided further evidence for construct validity, with good convergent and discriminant validity. The PESaM questionnaire also showed different scores for patients using different medications, in line with expectations, and was therefore able to differentiate between patient groups. Test–retest reliability of the items and domains were rated as moderate to fair (i.e. intraclass coefficients ranged between 0.18 and 0.76). Conclusions: The PESaM questionnaire is a unique patient-reported outcome measure evaluating patient experiences and satisfaction with medications. It has been developed in conjunction with patients, ensuring coverage of domains and issues relevant from the patient’s perspective. This study has shown promising validity of the generic module of the PESaM questionnaire. Further research is recommended to assess reliability in greater detail as well as the responsiveness of the measure. Trial registration: The study

Mosaic of glia in multiple sclerosis: studied at the transcriptomic level

Multiple sclerosis (ms) is a common disease of the central nervous system (cns), characterized by chronic inflammation, demyelination and neuronal damage. Different lesion types develop within the cns of ms patients in both gray and white matter, resulting in a wide variety of symptoms including impaired mobility. My project aims to get a better understanding of lesion development and lesion progression in ms. My focus will be on the role of microglia in this process. Microglia are the innate immune cells of the cns and also play important roles in brain homeostasis. I will study this by using novel transcriptomic methods to identify microglia/lesion specific gene expression profiles in human post-mortem brain tissue from ms patients. Understanding the way how lesions are formed and switch to progression might lead to new insights for drug targets. Next, I will use EAE and Cuprizone ms mice models to modulate microglia specific candidate genes, which will be identified by the transcriptomic analysis

High-Resolution Transcriptomic and Proteomic Profiling of Heterogeneity of Brain-Derived Microglia in Multiple Sclerosis

Microglia are important for central nervous system (CNS) homeostasis and first to respond to tissue damage and perturbations. Microglia are heterogeneous cells; in case of pathology, microglia adopt a range of phenotypes with altered functions. However, how these different microglia subtypes are implicated in CNS disease is largely unresolved. Multiple sclerosis (MS) is a chronic demyelinating disease of the CNS, characterized by inflammation and axonal degeneration, ultimately leading to neurological decline. One way microglia are implicated in MS is through stimulation of remyelination. They facilitate efficient remyelination by phagocytosis of myelin debris. In addition, microglia recruit oligodendrocyte precursor cells (OPCs) to demyelinated areas and stimulate remyelination. The development of high-resolution technologies to profile individual cells has greatly contributed to our understanding of microglia heterogeneity and function under normal and pathological conditions. Gene expression profiling technologies have evolved from whole tissue RNA sequencing toward single-cell or nucleus sequencing. Single microglia proteomic profiles are also increasingly generated, offering another layer of high-resolution data. Here, we will review recent studies that have employed these technologies in the context of MS and their respective advantages and disadvantages. Moreover, recent developments that allow for (single) cell profiling while retaining spatial information and tissue context will be discussed

Scholen zonder kerk: De impact van ontkerkelijking op open protestants-christelijk basisonderwijs

Het aantal kerkleden en mensen dat regelmatig een kerkdienst bezoekt neemt al decennia lang gestaag af. De christelijke kerken hebben hun dominante positie in de samenleving verloren en een minderheid van de Nederlandse bevolking noemt zichzelf nog een belijdend christen. Hoe heeft het zover kunnen komen en, nog belangrijker, wat zijn eigenlijk de maatschappelijke en culturele gevolgen van deze ontwikkeling? Deze vragen staan centraal in dit speciale nummer van Religie & Samenleving, waarin de bijdragen zijn gebundeld van verschillende sprekers tijdens een symposium over ontkerkelijking dat op 31 mei 2013 plaatsvond op de Radboud Universiteit Nijmegen