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Objectives The objective of the study was to validate PCr/ATP ratios as an in vivo marker for cardiac mitochondrial function.Background Cardiac energy status, measured as PCr/ATP ratio with 31P-MRS in vivo, was shown to be a prognostic factor in heart failure and is lowered in cardiometabolic disease. As mitochondrial function is also hampered in these diseases and oxidative phosphorylation is the major contributor to ATP synthesis, the PCr/ATP ratio might be a reflection of cardiac mitochondrial function.Methods Thirty-eight patients scheduled for open heart surgery were enrolled in this study. Before surgery, cardiac 31P-MRS was performed. During surgery, tissue specimens from the right atrial appendage were obtained for the ex vivo assessment of mitochondrial function using high-resolution respirometry.Results The patient population included was heterogenous resulting in wide ranges of PCr/ATP ratios and ADP-stimulated respiration rates (PCr/ATP ranging from 0.533 to 1.717; ADP-stimulated respiration rates ranging from 28.5 to 94.6 pmol/mg/s). Correlation analysis however showed no relationship between PCr/ATP and ADP-stimulated respiration rates fueled by various substrates (octanoylcarnitine R2 2 2 = 0.005, p = 0.71; pyruvate R2 = 0.040, p = 0.26).Conclusions Our results do not support the use of cardiac energy status (PCr/ATP) as a surrogate marker of mitochondrial function in the heart. The dissociation of the two parameters in the present study suggests that mitochondrial function is not the only determinant of cardiac energy status.Condensed abstractThis study does not support the use of in vivo cardiac energy status (PCr/ATP ratio) as a surrogate marker of ex vivo mitochondrial function (maximal oxidative respiration). Although both PCr/ATP and mitochondrial function are reduced in cardiovascular disease, the dissociation of the two parameters in the present study shows that PCr/ATP is determined by more factors than only mitochondrial function. Hence, PCr/ATP is not a good marker for mitochondrial function, but it can be a valuable marker for cardiometabolic health in cardiometabolic studies.Trial registration: https://clinicaltrials.gov (NCT03049228).

beta(2)-agonist treatment improves skeletal muscle glucose uptake and whole-body glucose homeostasis in rodents, likely via mTORC2-mediated signalling. However, human data on this topic is virtually absent. We here investigate the effects of two-weeks treatment with the beta(2)-agonist clenbuterol (40 mu g/day) on glucose control as well as energy- and substrate metabolism in healthy young men (age: 18-30 years, BMI: 20-25 kg/m(2)) in a randomised, placebo-controlled, double-blinded, cross-over study (ClinicalTrials.gov-identifier: NCT03800290). Randomisation occurred by controlled randomisation and the final allocation sequence was seven (period 1: clenbuterol, period 2: placebo) to four (period 1: placebo, period 2: clenbuterol). The primary and secondary outcome were peripheral insulin-stimulated glucose disposal and skeletal muscle GLUT4 translocation, respectively. Primary analyses were performed on eleven participants. No serious adverse events were reported. The study was performed at Maastricht University, Maastricht, The Netherlands, between August 2019 and April 2021. Clenbuterol treatment improved peripheral insulin-stimulated glucose disposal by 13% (46.6 +/- 3.5 versus 41.2 +/- 2.7 mu mol/kg/min, p = 0.032), whereas skeletal muscle GLUT4 translocation assessed in overnight fasted muscle biopsies remained unaffected. These results highlight the potential of beta(2)-agonist treatment in improving skeletal muscle glucose uptake and underscore the therapeutic value of this pathway for the treatment of type 2 diabetes. However, given the well-known (cardiovascular) side-effects of systemic beta(2)-agonist treatment, further exploration on the underlying mechanisms is needed to identify viable therapeutic targets.beta 2-agonist treatment improves skeletal muscle glucose uptake and whole-body glucose homeostasis in rodents. Here the authors report that two-weeks of treatment with the beta 2-agonist clenbuterol improves insulin-stimulated glucose disposal in healthy young men in a double-blinded, randomized cross-over trial.

Background Primary teachers' pedagogical practices (TPP) are strongly focused on supporting pupils' psychological needs, creating a safe learning climate, and encouraging pupils' developmental and learning processes. As a core motivation for teachers is the desire to interact constructively with children, pedagogical practices can be understood as central to teachers' work. A familiar problem in many international contexts is that TPP can come under pressure, typically as the result of interplay between personal and contextual factors. However, which contextual factors influence TPP, and how they do so, remains unclear. Purpose In this study, we aimed to better understand how context influences primary school teachers' pedagogical practices, within the setting of primary education in the Netherlands. We were particularly interested in which contextual factors were perceived as important and how they influenced TPP. Methods Data were collected through open questions in a survey among 215 primary school teachers in the northern part of the Netherlands. Focus group interviews were then held with 11 of the survey participants. The data were analysed qualitatively, using a framework approach with five stages of familiarisation: identifying themes, indexing, charting, and mapping and interpretation. Findings The analysis identified nine contextual factors that, according to participants, both positively and negatively affected TPP. The most frequently mentioned threats to TPP were educational accountability and standards, and organisation of work in the classroom, whilst school improvement and pupils' educational needs were regarded as the most important stimulating factors. We clustered the factors into four patterns which reflected the way that teachers appraised them: organisation of daily classroom practices, school culture, educational improvement, and contribution to pupils' development. Conclusions According to the teachers, the interplay between TPP and the context can cause pressure, frustration, and feelings of incompetence because there is insufficient time for achieving pedagogical goals. Our study draws attention to the complex challenges that teachers face in terms of balancing pedagogical practices and other educational tasks, and draws out implications for policy and practice.

Fatty acids are an important energy source during exercise. Training status and substrate availability are determinants of the relative and absolute contribution of fatty acids and glucose to total energy expenditure. Endurance-trained athletes have a high oxidative capacity, while, in insulin-resistant individuals, fat oxidation is compromised. Fatty acids that are oxidised during exercise originate from the circulation (white adipose tissue lipolysis), as well as from lipolysis of intramyocellular lipid droplets. Moreover, hepatic fat may contribute to fat oxidation during exercise. Nowadays, it is clear that myocellular lipid droplets are dynamic organelles and that number, size, subcellular distribution, lipid droplet coat proteins and mitochondrial tethering of lipid droplets are determinants of fat oxidation during exercise. This review summarises recent insights into exercise-mediated changes in lipid metabolism and insulin sensitivity in relation to lipid droplet characteristics in human liver and muscle. Graphical abstract Electronic supplementary material The online version of this article (10.1007/s00125-020-05170-z) contains a slideset of the figures for download, which is available to authorised users.

Aims/hypothesis Physical inactivity, low mitochondrial function, increased intramyocellular lipid (IMCL) deposition and reduced insulin sensitivity are common denominators of chronic metabolic disorders, like obesity and type 2 diabetes. Yet, whether low mitochondrial function predisposes to insulin resistance in humans is still unknown. Methods Here we investigated, in an intervention study, whether muscle with low mitochondrial oxidative capacity, induced by one-legged physical inactivity, would feature stronger signs of lipid-induced insulin resistance. To this end, ten male participants (age 22.4 ± 4.2 years, BMI 21.3 ± 2.0 kg/m2) underwent a 12 day unilateral lower-limb suspension with the contralateral leg serving as an active internal control. Results In vivo, mitochondrial oxidative capacity, assessed by phosphocreatine (PCr)-recovery half-time, was lower in the inactive vs active leg. Ex vivo, palmitate oxidation to 14CO2 was lower in the suspended leg vs the active leg; however, this did not result in significantly higher [14C]palmitate incorporation into triacylglycerol. The reduced mitochondrial function in the suspended leg was, however, paralleled by augmented IMCL content in both musculus tibialis anterior and musculus vastus lateralis, and by increased membrane bound protein kinase C (PKC) θ. Finally, upon lipid infusion, insulin signalling was lower in the suspended vs active leg. Conclusions/interpretation Together, these results demonstrate, in a unique human in vivo model, that a low mitochondrial oxidative capacity due to physical inactivity directly impacts IMCL accumulation and PKCθ translocation, resulting in impaired insulin signalling upon lipid infusion. This demonstrates the importance of mitochondrial oxidative capacity and muscle fat accumulation in the development of insulin resistance in humans. Trial registration ClinicalTrial.gov NCT01576250. Funding PS was supported by a ‘VICI’ Research Grant for innovative research from the Netherlands Organization for Scientific Research (Grant 918.96.618).

OBJECTIVE: SGLT2 inhibitors increase urinary glucose excretion and have beneficial effects on cardiovascular and renal outcomes; the underlying mechanism may be metabolic adaptations due to urinary glucose loss. Here, we investigated the cellular and molecular effects of 5 weeks of dapagliflozin treatment on skeletal muscle metabolism in type 2 diabetes patients.METHODS: Twenty-six type 2 diabetes mellitus patients were randomized to a 5-week double-blind, cross-over study with 6-8-week wash-out. Skeletal muscle acetylcarnitine levels, intramyocellular lipid (IMCL) content and phosphocreatine (PCr) recovery rate were measured by magnetic resonance spectroscopy (MRS). Ex vivo mitochondrial respiration was measured in skeletal muscle fibers using high resolution respirometry. Intramyocellular lipid droplet and mitochondrial network dynamics were investigated using confocal microscopy. Skeletal muscle levels of acylcarnitines, amino acids and TCA cycle intermediates were measured. Expression of genes involved in fatty acid metabolism were investigated.RESULTS: Mitochondrial function, mitochondrial network integrity and citrate synthase and carnitine acetyltransferase activities in skeletal muscle were unaltered after dapagliflozin treatment. Dapagliflozin treatment increased intramyocellular lipid content (0.060 (0.011, 0.110) %, p = 0.019). Myocellular lipid droplets increased in size (0.03 μm2 (0.01-0.06), p < 0.05) and number (0.003 μm-2 (-0.001-0.007), p = 0.09) upon dapagliflozin treatment. CPT1A, CPT1B and malonyl CoA-decarboxylase mRNA expression was increased by dapagliflozin. Fasting acylcarnitine species and C4-OH carnitine levels (0.4704 (0.1246, 0.8162) pmoles∗mg tissue-1, p < 0.001) in skeletal muscle were higher after dapagliflozin treatment, while acetylcarnitine levels were lower (-40.0774 (-64.4766, -15.6782) pmoles∗mg tissue-1, p < 0.001). Fasting levels of several amino acids, succinate, alpha-ketoglutarate and lactate in skeletal muscle were significantly lower after dapagliflozin treatment.CONCLUSION: Dapagliflozin treatment for 5 weeks leads to adaptive changes in skeletal muscle substrate metabolism favoring metabolism of fatty acid and ketone bodies and reduced glycolytic flux. The trial is registered with ClinicalTrials.gov, number NCT03338855.

While real-time data and sophisticated Reinforcement Learning (RL) approaches are emerging, logistic organizations, in particular Small and Medium-sized Enterprises (SMEs), lack the tools and expertise to effectively identify whether (parts of) their business processes are suitable for using RL and adopt these approaches in their daily practice. This paper presents the results of our efforts to design, develop, test and implement a RL-based decision support platform based on the Open Trip Model (OTM) for the logistics industry. The main contribution of this paper is a potentially generalizable platform architecture and instantiation of the following main functional components: 1) a graphical user interface to access platform services, 2) APIs to automate the data collection based on the OTM, 3) an OTM compliant data storage, 4) a repository and tool for testing multiple algorithms and perform (hyper)parameter tuning, and 5) infrastructure provisioning to run and monitor agents. The platform is complemented with RL guidelines to transfer the platform, knowledge, and practices to SMEs. The platform architecture is validated with a panel of experts and demonstrated in use in a case study at a logistics services provider. The platform demonstration and case study contribute to increasing awareness of potential applications of RL in the logistics industry. The platform provides a foundation for empirical research and experimental development of RL approaches in logistics. Future research will focus on alternative and hybrid approaches, federated learning, and incorporating data sharing concepts as part of the envisioned federated data sharing infrastructure for the Dutch logistics industry.

Falls among older adults are often attributed to declining muscle strength with ageing. Associations between muscle strength and balance control have been reported, but the evidence for, and key mechanisms of resistance exercise in fall prevention are unclear. No studies have directly examined the relationship between muscle fibre characteristics and reactive balance control. Here, we address whether or not Type II muscle fibre characteristics associate with reactive balance during walking in young and older adults with varying muscle fibre type composition. We analyse muscle biopsy-derived fibre characteristics and stability during a treadmill-based walking perturbation (trip-like) task of healthy young adults, healthy, normally active older adults, trained older adults and physically impaired older adults. We find no significant associations between Type II muscle fibre properties and reactive balance during walking, indicating that practitioners and researchers should consider more than just the muscle tissue properties when assessing and intervening on fall risk.

Objective Storage of triglycerides in lipid droplets is governed by a set of lipid droplet-associated proteins. One of these lipid droplet-associated proteins, hypoxia-inducible lipid droplet-associated (HILPDA), was found to impair lipid droplet breakdown in macrophages and cancer cells by inhibiting adipose triglyceride lipase. Here, we aimed to better characterize the role and mechanism of action of HILPDA in hepatocytes. Methods We performed studies in HILPDA-deficient and HILPDA-overexpressing liver cells, liver slices, and mice. The functional role and physical interactions of HILPDA were investigated using a variety of biochemical and microscopic techniques, including real-time fluorescence live-cell imaging and Förster resonance energy transfer-fluorescence lifetime imaging microscopy (FRET-FLIM). Results Levels of HILPDA were markedly induced by fatty acids in several hepatoma cell lines. Hepatocyte-specific deficiency of HILPDA in mice modestly but significantly reduced hepatic triglycerides in mice with non-alcoholic steatohepatitis. Similarly, deficiency of HILPDA in mouse liver slices and primary hepatocytes reduced lipid storage and accumulation of fluorescently-labeled fatty acids in lipid droplets, respectively, which was independent of adipose triglyceride lipase. Fluorescence microscopy showed that HILPDA partly colocalizes with lipid droplets and with the endoplasmic reticulum, is especially abundant in perinuclear areas, and mainly associates with newly added fatty acids. Real-time fluorescence live-cell imaging further revealed that HILPDA preferentially localizes to lipid droplets that are being remodeled. Overexpression of HILPDA in liver cells increased the activity of diacylglycerol acyltransferases (DGAT) and DGAT1 protein levels, concurrent with increased lipid storage. Confocal microscopy coupled to FRET-FLIM analysis demonstrated that HILPDA physically interacts with DGAT1 in living liver cells. The stimulatory effect of HILPDA on lipid storage via DGAT1 was corroborated in adipocytes. Conclusions Our data indicate that HILPDA physically interacts with DGAT1 and increases DGAT activity. Our findings suggest a novel regulatory mechanism by which fatty acids promote triglyceride synthesis and storage., Graphical abstract Image 1, Highlights • HILPDA expression is induced by fatty acids in hepatoma cells. • HILPDA deficiency modestly decreases liver triglyceride storage in mice with NASH. • HILPDA preferentially associates with newly synthesized lipid droplets and active lipid droplets. • HILPDA promotes lipid storage at least in part independently of ATGL. • HILPDA physically interacts and induces DGAT1.

In many different cell types neutral lipids can be stored in lipid droplets (LDs). Nowadays, LDs are viewed as dynamic organelles, which store and release fatty acids depending on energy demand (LD dynamics). Proteins like perilipin 2 (PLIN2) and PLIN5 decorate the LD membrane and are determinants of LD lipolysis and fat oxidation, thus affecting LD dynamics. Trained athletes and type 2 diabetes (T2D) patients both have high levels of intramyocellular lipid (IMCL). While IMCL content scales negatively with insulin resistance, athletes are highly insulin sensitive in contrast to T2D patients, the so-called athlete's paradox. Differences in LD dynamics may be an underlying factor explaining the athlete's paradox. We aimed to quantify PLIN2 and PLIN5 content at individual LDs as a reflection of the ability to switch between fatty acid release and storage depending on energy demand. Thus, we developed a novel fluorescent super-resolution microscopy approach and found that PLIN2 protein abundance at the LD surface was higher in T2D patients than in athletes. Localization of adipocyte triglyceride lipase (ATGL) to the LD surface was lower in LDs abundantly decorated with PLIN2. While PLIN5 abundance at the LD surface was similar in athletes and T2D patients, we have observed previously that the number of PLIN5 decorated LDs was higher in athletes, indicating more LDs in close association with mitochondria. Thus, in athletes interaction of LDs with mitochondria was more pronounced and LDs have the protein machinery to be more dynamic, while in T2D patients the LD pool is more inert. This observation contributes to our understanding of the athlete's paradox.

Mild cold acclimation for 10 days has been previously shown to markedly improve insulin sensitivity in patients with type 2 diabetes. Here we show in a single-arm intervention study (Trialregister.nl ID: NL4469/NTR5711) in nine patients with type 2 diabetes that ten days of mild cold acclimation (16–17 °C) in which observable, overt shivering was prevented, does not result in improved insulin sensitivity, postprandial glucose and lipid metabolism or intrahepatic lipid content and only results in mild effects on overnight fasted fat oxidation, postprandial energy expenditure and aortic augmentation index. The lack of marked metabolic effects in this study is associated with a lack of self-reported shivering and a lack of upregulation of gene expression of muscle activation or muscle contraction pathways in skeletal muscle and suggests that some form of muscle contraction is needed for beneficial effects of mild cold acclimation., Cold acclimation has been shown to have beneficial metabolic effects, including improved insulin sensitivity in patients with type 2 diabetes. Here the authors show that a mild cold acclimation regiment during which overt shivering was prevented did not result in improved insulin sensitivity in a small group of patients with type 2 diabetes.

The aim of this study is to explore Dutch primary school teachers' perceptions regarding their pedagogical practices, and, specifically, whether they consider these practices under pressure. We conducted a survey among a sample of 261 primary school teachers from 115 schools, that included open and closed questions. The analyses showed that primary school teachers' perceptions of pressure varied: 75% of the teachers indicated that their pedagogical practices are under pressure and one-quarter of the teachers reported experiencing low or no pressure. Furthermore, the variety in experienced pressure is not influenced by teachers' experience or educational beliefs. The data show that a lack of coherence between teachers' personal vision and the school's vision influences the extent to which teachers experience pressure. This study builds on theoretical research into teachers' pedagogical practices by showing that pressure on teachers' pedagogical practices is a general problem in primary education.

Lipid droplets (LD) are dynamic organelles that can expand and shrink, driven by fluctuations in the rate of triglyceride synthesis and degradation. Triglyceride synthesis, storage in LD, and degradation are governed by a complex set of LD-associated proteins. One of these LD-associated proteins, hypoxia-inducible lipid droplet-associated (HILPDA), was found to impair LD breakdown by inhibiting adipose triglyceride lipase. Here we characterized the physiological role and mechanism of action of HILPDA in hepatocytes. Expression of HILPDA was induced by fatty acids in several hepatoma cell lines. Hepatocyte-specific deficiency of HILPDA in mice modestly but significantly reduced hepatic triglycerides in mice with non-alcoholic fatty liver disease. Similarly, deficiency of HILPDA in mouse precision-cut liver slices and primary hepatocytes reduced lipid storage and accumulation of fluorescently-labelled fatty acids in LD, respectively, which was independent of adipose triglyceride lipase. Fluorescence microscopy showed that HILPDA partly colocalizes with LD and with the endoplasmic reticulum, is especially abundant in perinuclear areas, and mainly associates with newly added fatty acids. Real-time fluorescence live-cell imaging further revealed that HILPDA preferentially localizes to LD that are being remodelled. Mechanistically, HILPDA overexpression increased lipid storage in human hepatoma cells concomitant with an increase in DGAT activity and DGAT1 protein levels. Finally, confocal microscopy and Förster resonance energy transfer-fluorescence lifetime imaging microscopy analysis indicated that HILPDA colocalizes and physically interacts with DGAT1. Overall, our data indicate that HILPDA physically interacts with DGAT1 and increases DGAT activity. These findings suggest a novel mechanism in hepatocytes that links elevated fatty acid levels to stimulation of triglyceride synthesis and storage.

Preservice teachers face the complex challenge of balancing the requirements of teacher education programmes and schools and developing a professional identity as a teacher. Developing the knowledge and skills to manage working as a teacher is important to prevent emotional exhaustion during teacher education and later in the teaching career. Therefore, it is important to begin building resilience during the teacher education programme. Dutch policymakers and teacher educators recognize this need; however, there are currently no structural practices in teacher education programmes to help preservice teachers build resilience. Thus, introducing the BRiTE framework and modules could be a beneficial opportunity for Dutch teacher education. This chapter focuses on describing the Dutch teacher education context and teacher educators’ perceptions of resilience. We also discuss how the BRiTE modules can be implemented in Dutch teacher education programmes.

Objective: Intramyocellular lipid droplets (LD) and their coat proteins PLIN2 and PLIN5 are involved in lipolysis, with a putative role for PLIN5 in mitochondrial tethering. Reportedly, these proteins co-localize and cover the surface of the LD. To provide the spatial basis for understanding how these proteins possess their distinct roles, we examined the precise location of PLIN2 and PLIN5 and explored PLIN5 presence at LD-mitochondria contact sites using Stimulated emission depletion (STED) microscopy and correlative light-electron microscopy (CLEM) in human skeletal muscle sections.Methods: LDs were stained by MDH together with combinations of mitochondria] proteins and PLINs. Subcellular distribution and co-localization of PLIN proteins and mitochondria was imaged by STED microscopy (Leica TCS SP8) and quantified using Pearson's correlation coefficients and intensity profile plots. CLEM was employed to examine the presence of PLIN5 on mitochondria-LD contact sites.Results: Both PLIN2 and PLIN5 localized to the LD in a dot-like, juxtaposed fashion rather than colocalizing and covering the entire LD. Both STED and CLEM revealed a high fraction of PLIN5 at the LD-mitochondria interface, but not at mitochondrial cristae, as suggested previously.Conclusion: Using two super-resolution imaging approaches, this is the first study to show that in sections of human skeletal muscle PLIN2 and PLIN5 localize to the LD at distinct sites, with abundance of PLIN5 at LD-mitochondria tethering sites. This novel spatial information uncovers that PLIN proteins do not serve as lipolytic barriers but rather are docking sites for proteins facilitating selective lipase access under a variety of lipolytic conditions.

Exercise training reduces intrahepatic lipid (IHL) content in people with elevated liver fat content. It is unclear, however, whether exercise training reduces IHL content in people with normal liver fat content. Here, we measured the effect of exercise training on IHL content in people with and people without nonalcohol fatty liver. We further measured changes in insulin sensitivity and hepatic energy metabolism. Eleven males with nonalcoholic fatty liver (NAFL) and 11 body mass index-matched individuals without nonalcoholic fatty liver (CON) completed a 12-wk supervised exercise training program. IHL content (proton magnetic resonance spectroscopy), maximal oxidative capacity (V̇o2max, spiroergometry), total muscle strength, body composition, insulin sensitivity (hyperinsulinemic-euglycemic clamp), hepatic ATP-to-total phosphorus ratio, and the hepatic phosphomonoester-to-phosphodiester (PME/PDE) ratio (phosphorus magnetic resonance spectroscopy) were determined. IHL content reduced with exercise training ( P = 0.014) in the whole study population. The relative reduction in IHL content was comparable in NAFL (−34.5 ± 54.0%) and CON (−28.3 ± 60.1%) individuals ( P = 0.800). V̇o2max ( P < 0.001), total muscle strength ( P < 0.001), and skeletal muscle insulin sensitivity ( P = 0.004) increased, whereas adipose tissue ( P = 0.246) and hepatic ( P = 0.086) insulin sensitivity did not increase significantly. Hepatic ATP-to-total phosphorus ratio ( P = 0.987) and PME/PDE ratio ( P = 0.792) did not change. Changes in IHL content correlated with changes in body weight ( r = 0.451, P = 0.035) and changes in hepatic PME/PDE ratio ( r = 0.569, P = 0.019). In conclusion, exercise training reduced intrahepatic lipid content in people with nonalcoholic fatty liver and in people with normal intrahepatic lipid content, and the percent reduction in intrahepatic lipid content was similar in both groups.

Intramyocellular lipids (IMCL) hamper insulin sensitivity albeit not in endurance-trained athletes (Trained). Compared to type 2 diabetes patients (T2DM), Trained subjects have high levels of Perilipin 5 (PLIN5). Here, we tested if the fraction of PLIN5 coated LDs is a determinant of skeletal muscle insulin sensitivity and contributes to the athlete's paradox. Muscle biopsies were taken from 8 Trained, Lean sedentary, Obese and T2DM subjects. Trained, Obese and T2DM subjects were matched for total IMCL content. Confocal images were analysed for lipid area fraction, LD size and number and PLIN5+ and PLIN5- LDs were measured. A stepwise linear regression was performed to identify factors explaining observed variance in GIR. Trained and T2DM subjects stored IMCL differently; Trained had a higher number of LDs compared to T2DM (0.037 ± 0.004 μm−2 vs. 0.023 ± 0.003 μm−2, P = 0.024), that were non-significantly smaller (0.27 ± 0.01 μm2 vs. 0.32 ± 0.02 μm2, P = 0.197, Trained vs. T2DM). Even though total PLIN5 protein content was almost double in Trained vs. T2DM (1.65 ± 0.21 AU vs. 0.89 ± 0.09 AU, P = 0.004), PLIN5 coating did not affect LD number or size significantly. Of the observed variance in GIR, the largest fraction by far (70.2%) was explained by maximal oxygen uptake, adding PLIN5 protein content or PLIN5+ LDs increased the explained variance in GIR (74.7% and 80.7% for PLIN5 protein content and PLIN5+ LDs, respectively). Thus, the putative relation between PLIN5 and insulin sensitivity is at best indirect and is apparent only in conjunction with maximal oxygen uptake. Hence, PLIN5 abundance cannot be causally linked to the athlete's paradox. This article is protected by copyright. All rights reserved

Non-alcoholic fatty liver (NAFL) is an independent risk factor for the development of type 2 diabetes (T2DM). We examined metabolic perturbations in patients with NAFL, patients with T2DM, and control (CON) subjects with normal intrahepatic lipid (IHL) content. A two-step (10 mU/m2 /min; 40 mU/m2/min) hyperinsulinemic–euglycemic clamp was performed in 11 NAFL, 13 T2DM, and 11 CON subjects, all matched for BMI, and aerobic fitness. IHL content was measured using proton magnetic resonance spectroscopy. Because of high IHL content variability in T2DM patients, this group was separated into a high IHL content group (IHL ≥ 5.0%, T2DM+NAFL) and a normal IHL content group (IHL < 5.0%, T2DM-non-NAFL) for further analysis. IHL content was increased in NAFL and T2DM+NAFL subjects (P0.05), and was lower in comparison with CON subjects (all P Individuals with NAFL suffer from metabolic perturbations to a similar degree as T2DM patients. NAFL is an important feature leading to severe insulin resistance and should be viewed as a serious health threat for the development of T2DM. ClinicalTrials.gov: NCT01317576

Nederlandse basisschoolleraren lijken spanningen te ervaren ten aanzien van hun pedagogische handelen, dat gericht is op het ondersteunen van de sociale, emotionele en morele ontwikkeling van leerlingen. Het doel van deze studie was daarom om te onderzoeken hoe de schoolcontext en het onderwijsbeleid van invloed zijn op deze spanningen. Een survey met open en gesloten vragen is ingevuld door basisschoolleraren (N = 261) en opgevolgd door focusgroepinterviews (N=12). De resultaten laten zien dat schoolcultuur en professionele ontwikkeling een positieve invloed hebben op de spanningen in het pedagogische handelen. Leraren ervaren vooral negatieve invloeden vanuit de schoolcontext door conflicterende opvattingen en vanuit het onderwijsbeleid door de toename aan administratieve taken en diversiteit aan onderwijsbehoeften.

n.v.t.

Aims/hypothesis Dissipating energy via mitochondrial uncoupling has been suggested to contribute to enhanced insulin sensitivity. We hypothesised that skeletal muscle mitochondria of endurance-trained athletes have increased sensitivity for fatty acid (FA)-induced uncoupling, which is driven by the mitochondrial protein adenine nucleotide translocase 1 (ANT1). Methods Capacity for FA-induced uncoupling was measured in endurance-trained male athletes (T) and sedentary young men (UT) in an observational study and also in isolated skeletal muscle mitochondria from Zucker diabetic fatty (ZDF) rats and C2C12 myotubes following small interfering RNA (siRNA)-mediated gene silencing of ANT1. Thus, fuelled by glutamate/succinate (fibres) or pyruvate (mitochondria and myotubes) and in the presence of oligomycin to block ATP synthesis, increasing levels of oleate (fibres) or palmitate (mitochondria and myotubes) were automatically titrated while respiration was monitored. Insulin sensitivity was measured by hyperinsulinaemic–euglycaemic clamp in humans and via insulin-stimulated glucose uptake in myotubes. Results Skeletal muscle from the T group displayed increased sensitivity to FA-induced uncoupling (p = 0.011) compared with muscle from the UT group, and this was associated with elevated insulin sensitivity (p = 0.034). ANT1 expression was increased in T (p = 0.013). Mitochondria from ZDF rats displayed decreased sensitivity for FA-induced uncoupling (p = 0.008). This difference disappeared in the presence of the adenine nucleotide translocator inhibitor carboxyatractyloside. Partial knockdown of ANT1 in C2C12 myotubes decreased sensitivity to the FA-induced uncoupling (p = 0.008) and insulin-stimulated glucose uptake (p = 0.025) compared with controls. Conclusions/interpretation Increased sensitivity to FA-induced uncoupling is associated with enhanced insulin sensitivity and is affected by ANT1 activity in skeletal muscle. FA-induced mitochondrial uncoupling may help to preserve insulin sensitivity in the face of a high supply of FAs. Trial registration www.trialregister.nl NTR2002

Objective Intramyocellular lipid (IMCL) storage negatively associates with insulin resistance, albeit not in endurance-trained athletes. We investigated the putative contribution of lipid droplet (LD) morphology and subcellular localization to the so-called athlete's paradox. Methods We performed quantitative immunofluorescent confocal imaging of muscle biopsy sections from endurance Trained, Lean sedentary, Obese, and Type 2 diabetes (T2DM) participants (n = 8/group). T2DM patients and Trained individuals were matched for IMCL content. Furthermore we performed this analysis in biopsies of T2DM patients before and after a 12-week exercise program (n = 8). Results We found marked differences in lipid storage morphology between trained subjects and T2DM: the latter group mainly store lipid in larger LDs in the subsarcolemmal (SS) region of type II fibers, whereas Trained store lipid in a higher number of LDs in the intramyofibrillar (IMF) region of type I fibers. In addition, a twelve-week combined endurance and strength exercise program resulted in a LD phenotype shift in T2DM patients partly towards an ‘athlete-like’ phenotype, accompanied by improved insulin sensitivity. Proteins involved in LD turnover were also more abundant in Trained than in T2DM and partly changed in an ‘athlete-like’ fashion in T2DM patients upon exercise training. Conclusions Our findings provide a physiological explanation for the athlete's paradox and reveal LD morphology and distribution as a major determinant of skeletal muscle insulin sensitivity., Highlights • Distinct lipid droplet morphology and distribution underlies the athletes' paradox. • Muscle lipid storage occurs in a fiber type specific manner. • Exercise training shifts LD morphology towards an athletes' phenotype.

Gemmink, M.M., Fokkens-Bruinsma, M., Pauw, I. & Van Veen, K. (2018). Pedagogisch opleiden voor een complexe beroepspraktijk. Round table, VELON Congres voor Lerarenopleiders, Roermond, March 2018.

Intramyocellular lipid (IMCL) hampers insulin sensitivity, albeit not in endurance-trained athletes (Trained). Compared to type 2 diabetes mellitus (T2DM) patients, Trained subjects have high levels of perilipin 5 (PLIN5). In the present study, we tested whether the fraction of PLIN5-coated lipid droplets (LDs) is a determinant of skeletal muscle insulin sensitivity and contributes to the athlete's paradox. Muscle biopsies were taken from eight Trained, Lean sedentary, Obese and T2DM subjects. Trained, Obese and T2DM subjects were matched for total IMCL content. Confocal images were analysed for lipid area fraction, LD size and number and PLIN5+ and PLIN5- LDs were measured. A stepwise linear regression was performed to identify factors explaining observed variance in glucose infusion rate (GIR). Trained and T2DM subjects stored IMCL differently; Trained subjects had a higher number of LDs compared to T2DM subjects (0.0370.004m(-2)vs. 0.0230.003m(-2), P=0.024) that were non-significantly smaller (0.270.01m(2)vs. 0.320.02m(2), P=0.197, Trained vs. T2DM). Even though total PLIN5 protein content was almost double in Trained vs. T2DM subjects (1.650.21AU vs. 0.89 +/- 0.09AU, P=0.004), PLIN5 coating did not affect LD number or size significantly. Of the observed variance in GIR, the largest fraction by far (70.2%) was explained by maximal oxygen uptake. Adding PLIN5 protein content or PLIN5+ LDs increased the explained variance in GIR (74.7% and 80.7% for PLIN5 protein content and PLIN5+ LDs, respectively). Thus, the putative relationship between PLIN5 and insulin sensitivity is at best indirect and is apparent only in conjunction with maximal oxygen uptake. Hence, PLIN5 abundance cannot be causally linked to the athlete's paradox.

Insulin resistance lies at the basis of type 2 diabetes. Insulin resistance is often paired with increased fat deposits in muscle tissue, which some people claim to be the cause; however, highly trained and insulin-sensitive athletes also store a lot of fat in their muscles, which serves to counter this causal relationship. This dissertation examines the distinct characteristics of fat accumulation in insulin-sensitive and insulin-resistant states using techniques such as microscopy. The most important conclusion is that normal lipid droplets that come into contact with the protein PLIN5 are associated with higher insulin sensitivity.

OBJECTIVE: Parental high-fat feeding was proposed to negatively impact metabolic health in offspring. Here, the ectopic fat storage in heart and liver in offspring was investigated, and the effects on mitochondrial function, de novo lipogenesis, and postprandial lipid metabolism were explored in detail. METHODS: Male and female mice received either a high-fat (HF) or standard chow (LF) diet during mating, gestation and lactation. All offspring animals received the HF diet. RESULTS: Abdominal visceral adipose tissue tended to be higher in HF/HF mice. Cardiac lipid content was also higher in the HF/HF mice (LF/HF vs. HF/HF: 1.03% +/- 0.08% vs. 1.33% +/- 0.07% of water signal, P = 0.01). In contrast, hepatic lipid content tended to be lower in HF/HF mice compared to LF/HF mice. A severely disturbed postprandial lipid clearance was revealed in HF/HF mice by the results from the triglyceride (TG) tolerance tests (LF/HF vs. HF/HF: 6,753 +/- 2,213 vs. 14,367 +/- 1,978 mmol l(-1) min(-1) , P = 0.01) and (13) C-fatty acid retention test (LF/HF vs. HF/HF: 2.73% +/- 0.85% vs. 0.89% +/- 0.26% retention from bolus, P = 0.04), which may underlie the lower hepatic lipid content. CONCLUSIONS: Here it is shown that HF diet negatively impacts postprandial TG clearance in offspring and results in an overall metabolic unfavorable phenotype and ectopic lipid deposition in the heart and in visceral storage sites.

Item does not contain fulltext OBJECTIVE: Parental high-fat feeding was proposed to negatively impact metabolic health in offspring. Here, the ectopic fat storage in heart and liver in offspring was investigated, and the effects on mitochondrial function, de novo lipogenesis, and postprandial lipid metabolism were explored in detail. METHODS: Male and female mice received either a high-fat (HF) or standard chow (LF) diet during mating, gestation and lactation. All offspring animals received the HF diet. RESULTS: Abdominal visceral adipose tissue tended to be higher in HF/HF mice. Cardiac lipid content was also higher in the HF/HF mice (LF/HF vs. HF/HF: 1.03% +/- 0.08% vs. 1.33% +/- 0.07% of water signal, P = 0.01). In contrast, hepatic lipid content tended to be lower in HF/HF mice compared to LF/HF mice. A severely disturbed postprandial lipid clearance was revealed in HF/HF mice by the results from the triglyceride (TG) tolerance tests (LF/HF vs. HF/HF: 6,753 +/- 2,213 vs. 14,367 +/- 1,978 mmol l(-1) min(-1) , P = 0.01) and (13) C-fatty acid retention test (LF/HF vs. HF/HF: 2.73% +/- 0.85% vs. 0.89% +/- 0.26% retention from bolus, P = 0.04), which may underlie the lower hepatic lipid content. CONCLUSIONS: Here it is shown that HF diet negatively impacts postprandial TG clearance in offspring and results in an overall metabolic unfavorable phenotype and ectopic lipid deposition in the heart and in visceral storage sites.

Skeletal muscle can store excess fat as subcellular lipid droplets (LDs). While originally viewed as uninteresting static balls of triacylglycerol, it is now clear that myocellular LDs play an active role in myocellular (patho) physiology. In this review we aim to discuss the role of LDs in muscle cell insulin sensitivity and identify parameters which appear to affect this relationship. Moreover, we discuss the application of novel tools permitting detailed examination of these parameters. This article is part of a Special Issue entitled: Recent Advances in Lipid Droplet Biology edited by Rosalind Coleman and Matthijs Hesselink.

KEY POINTS: Intramyocellular lipid storage is negatively associated with insulin sensitivity. However, endurance trained athletes and type 2 diabetes mellitus (T2DM) patients store similar amounts of lipids in their muscle; the so‐called athlete's paradox. Compared to T2DM, trained athletes possess higher levels of perilipin 5 (PLIN5), a lipid droplet (LD) coating protein. We examined whether coating LD with PLIN5 affects the pattern of muscle lipid (LD size and number) in relation to the athlete's paradox. Despite differences in PLIN5 protein content, we observed that coating the LD with PLIN5 could not explain the observed differences in LD size and number between athletes and T2DM. PLIN5‐coated LDs were positively associated with oxidative capacity but not with insulin sensitivity. We conclude that coating of LDs with PLIN5 cannot causally explain the athlete's paradox. ABSTRACT: Intramyocellular lipid (IMCL) hampers insulin sensitivity, albeit not in endurance‐trained athletes (Trained). Compared to type 2 diabetes mellitus (T2DM) patients, Trained subjects have high levels of perilipin 5 (PLIN5). In the present study, we tested whether the fraction of PLIN5‐coated lipid droplets (LDs) is a determinant of skeletal muscle insulin sensitivity and contributes to the athlete's paradox. Muscle biopsies were taken from eight Trained, Lean sedentary, Obese and T2DM subjects. Trained, Obese and T2DM subjects were matched for total IMCL content. Confocal images were analysed for lipid area fraction, LD size and number and PLIN5+ and PLIN5– LDs were measured. A stepwise linear regression was performed to identify factors explaining observed variance in glucose infusion rate (GIR). Trained and T2DM subjects stored IMCL differently; Trained subjects had a higher number of LDs compared to T2DM subjects (0.037 ± 0.004 μm(−2) vs. 0.023 ± 0.003 μm(−2), P = 0.024) that were non‐significantly smaller (0.27 ± 0.01 μm(2) vs. 0.32 ± 0.02 μm(2), P = 0.197, Trained vs. T2DM). Even though total PLIN5 protein content was almost double in Trained vs. T2DM subjects (1.65 ± 0.21 AU vs. 0.89 ± 0.09 AU, P = 0.004), PLIN5 coating did not affect LD number or size significantly. Of the observed variance in GIR, the largest fraction by far (70.2%) was explained by maximal oxygen uptake. Adding PLIN5 protein content or PLIN5+ LDs increased the explained variance in GIR (74.7% and 80.7% for PLIN5 protein content and PLIN5+ LDs, respectively). Thus, the putative relationship between PLIN5 and insulin sensitivity is at best indirect and is apparent only in conjunction with maximal oxygen uptake. Hence, PLIN5 abundance cannot be causally linked to the athlete's paradox.

Today’s CD-SEM metrology is challenged when it comes to measuring complex features found in patterning hotspots (like tip to tip, tip to side, necking and bridging). Metrology analysis tools allow us to extract SEM contours of a feature and convert them into a GDS format from which dimensional data can be extracted. While the CD-SEM is being used to take images, the actual measurement and the choice of what needs to be measured is done offline. Most of the time this method is used for OPC model creation but barely for process variability analysis at nominal process conditions. We showed in a previous paper [1] that it is possible to study lithography to etch transfer behavior of a hotspot using SEM contours. The goal of the current paper is to go extend this methodology to quantify process variability of 2D features using a new tooling to measure contour data.

A 5-day High-Fat High-Calorie diet (HFHC-diet) reduces insulin-stimulated glucose disposal (Rd) in South Asian, but not Caucasian healthy lean males. We aimed to investigate if differences in myocellular lipid handling are underlying this differential response. A two-step hyperinsulinemic-euglycemic clamp and muscle biopsies were performed in 12 healthy lean Caucasian and South Asian males (BMI 2, 19–25 years) before and after a 5-day HFHC-diet (regular diet + 375 mL cream/day; 1275 kcal/day; 94% fat). Triglyceride extractions and Western Blots for lipid droplet and mitochondrial proteins were performed. Intramyocellular lipid content and HFHC-diet response were similar between ethnicities (group effect: P = 0.094; diet effect: +~30%, P = 0.044). PLIN5 protein content increased upon the HFHC-diet (P = 0.031) and tended to be higher in South Asians (0.87 ± 0.42 AU vs. 1.35 ± 0.58 AU, P = 0.07). 4-HNE tended to increase in South Asians upon the HFHC-diet (interaction effect: P = 0.057). In Caucasians ΔPLIN5 content correlated with ΔRd (Caucasians: r = 0.756, P = 0.011; South Asians: r = −0.085, P = 0.816), while in South Asians Δ4-HNE associated with ΔPLIN5 content (Caucasians: r = 0.312, P = 0.380; South Asians: r = 0.771, P = 0.003). These data indicate that in Caucasians, PLIN5 may be protective against HFHC-diet induced insulin resistance, which for reasons not yet understood is not observed in South Asians, who possess increased lipid peroxidation levels.

In Dutch primary schools, pedagogical actions seem to receive much less attention than content knowledge. This is the consequence of several developments and innovations that aimed at enhancing pupils’ learning outcomes and at improving teachers’ content knowledge and didactic actions. This results in a multitude of tasks and responsibilities for teachers around didactics and seems to constrain time and attention for pedagogical actions. This research explores whether the pedagogical actions of primary school teachers are indeed under pressure in the current educational climate. The goals of this study were threefold; (1) to examine teachers’ perceptions regarding their pedagogical actions, (2) to examine how teaching experience, age of the students and the specific school context influence these perceptions, (3) to determine which needs for professionalisation teachers have to increase their pedagogical actions in the classroom. A survey was conducted among a sample of 261 Dutch mainstream primary education teachers in the northern part of the Netherlands. Data were collected with a questionnaire, which consisted of fifteen open and closed questions. Teachers were asked about their perceptions of pedagogical actions in the classroom, the school’s vision of pedagogy, their personal vision of pedagogy and background variables of the respondents. Half of the responding teachers (47.5%) indicate that pedagogical actions of primary schools are under pressure. Over 60% of teachers indicated that they would like to pay more attention to this issue. Pedagogical actions of primary school teachers are indeed under pressure in the current educational climate.

Developing fluency in arithmetic facts is instrumental to mathematics learning. This study compares the effects of two practice conditions on children’s fluency in simple multiplication facts. Third and fourth graders in the Netherlands (N = 282) practised in either a conventional recall condition where they produced answers to problems, or a choice condition where they had to choose between competing answers that included common multiplication errors. Practice in the choice condition was faster and as accurate as recall practice but was not more beneficial to performance on speed tests of practised facts. For more experienced students, recall practice led to greater improvement on a conventional recall fluency test. Differential effects of practice conditions on test performance are explained in terms of practice-to-test transfer demands. The relative merits of recall and choice tasks in multiplication fact learning are discussed.

Contains fulltext : 117721.pdf (Publisher’s version ) (Closed access) Primary B-cell lymphoma of the testis, breast and thyroid are rare and data concerning cytogenetic aberrations at these extranodal sites are scarce. We examined the presence of extranodal marginal zone lymphoma-associated translocations, t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21), t(3;14)(p14.1;q32) and numerical aberrations of chromosomes 1, 3, 12 and 18 by fluorescence in situ hybridization in 6 extranodal marginal zone lymphomas and 24 diffuse large B-cell lymphomas with (n=9) or without (n=15) marginal zone lymphoma components, with primary localizations in the breast (n=15), testis (n=9) and thyroid (n=6). We found t(14;18)(q32;q21), with breakpoints in IGH and MALT1, in one testicular diffuse large B-cell lymphoma and in two diffuse large B-cell lymphomas of the breast. No other translocations, amplifications or deletions involving IGH, BCL-10, BCL-2, MALT1 and IAP2 were detected. Numerical aberrations occurred in 67% of the lymphomas, 67% of extranodal marginal zone lymphomas, 56% of diffuse large B-cell lymphomas with marginal zone lymphoma components and in 73% of 'de novo' diffuse large B-cell lymphomas. These included 78% of testis, 67% of thyroid and 60% of breast lymphomas, and included mainly trisomy 18 (n=16), trisomy 3 (n=8) and trisomy 1 (n=3). One testicular diffuse large B-cell lymphoma harbored both t(14;18)(q32;q21) and trisomy 3. Our results indicate that at least a few cases of diffuse large B-cell lymphoma of the testis and the breast belong to the spectrum of extranodal marginal zone lymphoma.

The concept of the multi-source focus correlation method was presented in 2015 [1, 2]. A more accurate understanding of real on-product focus can be obtained by gathering information from different sectors: design, scanner short loop monitoring, scanner leveling, on-product focus and topography. This work will show that chip topography can be predicted from reticle density and perimeter density data, including experimental proof. Different pixel sizes are used to perform the correlation in-line with the minimum resolution, correlation length of CMP effects and the spot size of the scanner level sensor. Potential applications of the topography determination will be evaluated, including optimizing scanner leveling by ignoring non-critical parts of the field, and without the need for time-consuming offline topography measurements.

Like all eukaryotic cell types, skeletal muscle can store free fatty acids (FFA) as triacylglycerol (TG) in lipid droplets (LDs), which in three dimensions can be viewed as balls of lipid ranging in size. This article is protected by copyright. All rights reserved

Parental high-fat feeding was proposed to negatively impact metabolic health in offspring. Here, the ectopic fat storage in heart and liver in offspring was investigated, and the effects on mitochondrial function, de novo lipogenesis, and postprandial lipid metabolism were explored in detail.Male and female mice received either a high-fat (HF) or standard chow (LF) diet during mating, gestation and lactation. All offspring animals received the HF diet.Abdominal visceral adipose tissue tended to be higher in HF/HF mice. Cardiac lipid content was also higher in the HF/HF mice (LF/HF vs.1.03% ± 0.08% vs. 1.33% ± 0.07% of water signal, P = 0.01). In contrast, hepatic lipid content tended to be lower in HF/HF mice compared to LF/HF mice. A severely disturbed postprandial lipid clearance was revealed in HF/HF mice by the results from the triglyceride (TG) tolerance tests (LF/HF vs.6,753 ± 2,213 vs. 14,367 ± 1,978 mmol l(-1) min(-1) , P = 0.01) and (13) C-fatty acid retention test (LF/HF vs.2.73% ± 0.85% vs. 0.89% ± 0.26% retention from bolus, P = 0.04), which may underlie the lower hepatic lipid content.Here it is shown that HF diet negatively impacts postprandial TG clearance in offspring and results in an overall metabolic unfavorable phenotype and ectopic lipid deposition in the heart and in visceral storage sites.

Tweede deel van een artikel over welke waarden zich manifesteren in het woordgebruik van derdejaarsstudenten in hun reflectieverhaal. Uit dit deel van het onderzoek is gebleken dat studenten hun professionele identiteit ook in het derde jaar nog voornamelijk framen in het kader van organisatorische en hiërarchische waarden en slechts beschikken over een beperkt aantal scripts voor hun handelen.

Human brown adipose tissue (BAT) has recently emerged as a potential target in the treatment of type 2 diabetes, owing to its capacity to actively clear glucose from the circulation—at least upon cold exposure. The effects of insulin resistance on the capacity of human BAT to take up glucose are unknown. Prolonged fasting is known to induce insulin resistance in peripheral tissues in order to spare glucose for the brain. We studied the effect of fasting-induced insulin resistance on the capacity of BAT to take up glucose during cold exposure as well as on cold-stimulated thermogenesis. BAT glucose uptake was assessed by means of cold-stimulated dynamic 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) imaging. We show that a 54 h fasting period markedly decreases both cold-induced BAT glucose uptake and nonshivering thermogenesis (NST) during cold stimulation. In vivo molecular imaging and modelling revealed that the reduction of glucose uptake in BAT was due to impaired cellular glucose uptake and not due to decreased supply. Interestingly, decreased BAT glucose uptake upon fasting was related to a decrease in core temperature during cold exposure, pointing towards a role for BAT in maintaining normothermia in humans. Cold-stimulated glucose uptake in BAT is strongly reduced upon prolonged fasting. When cold-stimulated glucose uptake in BAT is also reduced under other insulin-resistant states, such as diabetes, cold-induced activation of BAT may not be a valid way to improve glucose clearance by BAT under such conditions. Trial registration: www.trialregister.nl NTR3523 Funding: This work was supported by the EU FP7 project DIABAT (HEALTH-F2-2011-278373 to WDvML) and by the Netherlands Organization for Scientific Research (TOP 91209037 to WDvML).

In dit artikel wordt ingaan op uitspraken in verhalen die de basis vormen van een achttal narratieve essays van derdejaars. Het is een eerste verslag van een onderzoek naar waarden in studentenverhalen, uitgevoerd door het lectoraat Reflectie en Retorica. In volgende verslagen komen andere aspecten aan de orde.