Motor skill learning in groups: Some proposals for applying implicit learning and self-controlled feedback

Contrary to researchers' current focus on individual motor skill learning, in institutional settings such as physical education and sports motor skill learning is often taught in groups. In these settings, there is not only the interaction between teacher and learner (analogous to research), but also the many interactions between the learners in the group. In this paper, we discuss the pitfalls of applying research findings without taking into account the different dynamics that the interactions between group members bring about. To this end, we especially discuss implicit motor learning and self-controlled feedback, as these have recently been hailed as being particularly effective for increasing motor skill and self-efficacy. Proposals are provided to adopt these methods for motor skill learning in groups. This is not only relevant for practitioners in physical education and sports, but also establishes an agenda for research

Proposal for an individualized dietary strategy in patients with very long-chain acyl-CoA dehydrogenase deficiency

Background: Patients with very long chain acyl-CoA dehydrogenase deficiency (VLCADD), a long chain fatty acid oxidation disorder, are traditionally treated with a long chain triglyceride (LCT) restricted and medium chain triglyceride (MCT) supplemented diet. Introduction of VLCADD in newborn screening (NBS) programs has led to the identification of asymptomatic newborns with VLCADD, who may have a more attenuated phenotype and may not need dietary adjustments. Objective: To define dietary strategies for individuals with VLCADD based on the predicted phenotype. Method: We evaluated long-term dietary histories of a cohort of individuals diagnosed with VLCADD identified before the introduction of VLCADD in NBS and their beta-oxidation (LC-FAO) flux score (rate of oleate oxidation) in cultured skin fibroblasts in relation to the clinical outcome. Based on these results a dietary strategy is proposed. Results: Sixteen individuals with VLCADD were included. One had an LC-FAO flux score >90%, was not on a restricted diet and is asymptomatic to date. Four patients had an LC-FAO flux score <10%, and significant VLCADD related symptoms despite the use of strict diets including LCT restriction, MCT supplementation and nocturnal gastric drip feeding. Patients with an LC-FAO flux score between 10 and 90% (n = 11) showed a more heterogeneous phenotype. Conclusions: This study shows that a strict diet cannot prevent poor clinical outcome in severely affected patients and that the LC-FAO flux is a good predictor of clinical outcome in individuals with VLCADD identified before its introduction in NBS. Hereby, we propose an individualized dietary strategy based on the LC-FAO flux score

Capillary electrophoresis and hydrophilic interaction chromatography coupled to mass spectrometry for anionic metabolic profiling

Metabolomics encompasses the identification and quantification of low-molecular weight endogenous metabolites in biological samples, such as cells, tissues and body fluids. The identities, concentrations and fluxes of metabolites result from gene expression, protein expression and environmental factors (e.g. bacteria, diet, drugs), which together determine the phenotype of an organism. Therefore, profiling of metabolites present in biological samples provides information on biochemical processes and phenotypes of organisms. Various analytical techniques have been developed to analyze different classes of metabolites, including capillary electrophoresis (CE) and hydrophilic interaction chromatography (HILIC) coupled to mass spectrometry (MS), which are eminently suited for profiling highly polar compounds. This thesis describes the optimization, evaluation and comparison of CE–MS and HILIC–MS using negative electrospray ionization for the profiling of anionic metabolites. Particular attention was paid to sensitivity, reproducibility, separation selectivity and metabolite coverage. It is demonstrated that the use of triethylamine in the background electrolyte and sheath liquid in CE–MS is an effective way to improve the limits of detection of anionic metabolites significantly as compared to earlier developed CE–MS methods applying ammonium acetate. The increase in signal intensities allows the detection of low-abundant metabolites, thereby increasing the metabolite coverage. This is of utmost importance in metabolic profiling studies. The optimization of the mobile phase composition, the gradient of the mobile phase and sample solvent in HILIC–MS resulted in a large separation window with good peak shapes and low limits of detection of anionic metabolites. Detection limits obtained with HILIC–MS were up to 80 times lower compared to CE–MS, mainly due to the larger injection volume. Moreover, the migration and retention times of anionic metabolites were considerably different, demonstrating the different separation selectivities of CE–MS and HILIC–MS. The applicability of the optimal CE–MS and HILIC–MS methods has been tested by analyzing urine samples in studies on antibiotic-treated rats and patients with inborn errors of metabolism. Reproducible metabolite profiles were obtained as demonstrated by the repetitive analysis of a quality control sample. In general, more molecular features were obtained with HILIC–MS. However, CE–MS also revealed a large number of metabolite features, which were not detected with HILIC–MS. Using multivariate data analysis, different groups of urine samples could be discerned based on obtained CE–MS and HILIC–MS data, and potential biomarkers were revealed. These discriminatory compounds were putatively identified based on accurate mass and MS/MS experiments. Some of the biomarker candidates were observed with both CE–MS and HILIC–MS. Several anionic metabolites were also uniquely revealed by one of the applied techniques. This demonstrates that these analytical techniques can provide important and complementary information in metabolic profiling studies

Circulating microRNAs and other biomarkers for premature atherosclerosis

Atherosclerosis, the underlying pathological mechanisms of cardiovascular disease (CVD), is an extensively studied process. Risk factors that contribute to the origin and the progression of this process are reasonably well established and mathematical models have been built to calculate the exact risk of an individual patient to develop CVD. However, in patients who suffer their first cardiovascular event at an early age (premature CVD), traditional risk factors are usually not as pronounced and other factors seem to contribute to the development of CVD. Since early identification of an increased cardiovascular risk will enable subjects to take preventive measures early in the development of the disease, it is of utmost importance to identify new markers that can be used to predict the risk of premature CVD. It has been postulated that circulating miRNAs could be used as suitable biomarkers for CVD. In this thesis we addressed the question whether the expression of circulating miRNAs could be used to predict premature CVD in specific populations at risk. Furthermore, we investigated whether, apart from miRNAs, different markers could be used to identify specific subpopulations at risk of premature CVD

The role of capillary electrophoresis in metabolic profiling studies employing multiple analytical techniques

Capillary electrophoresis-mass spectrometry (CE-MS) is increasingly used for the targeted and untargeted analysis of metabolites in biological samples. CE-MS is particularly useful for the profiling of highly polar metabolites without the need for derivatization and/or extensive sample preparation. This overview covers reported studies in which CE or CE-MS was used with direct MS, gas chromatography (GC)-MS, liquid chromatography (LC)-MS, and/or nuclear magnetic resonance (NMR) spectroscopy for the analysis of metabolites. We include an extensive overview of comparative metabolic profiling studies involving multiple analytical techniques, including CE. Tables set out the particular conditions and the characteristics of each study. Furthermore, we discuss and compare the results of these studies using selected examples. Based on the outcomes of the comparative studies, we conclude that CE is highly complementary to the other analytical technologies and can add essential information on the metabolic profile of biological samples