Background and aimsThe aim of this study was to gain insight in the effect of a preschool-based intervention for Early Childhood Education and Care (ECEC) teachers on promoting healthy eating and physical activity in toddlers.MethodsIn a cluster randomized controlled trial, 37 preschools of child care organization Impuls in Amsterdam Nieuw-West, the Netherlands, were randomly allocated to an intervention or control group. In total, 115 female ECEC teachers (mean age 42 ± 9 years) participated. The intervention for ECEC teachers consisted of two existing Dutch programs: ‘A Healthy Start’ and ‘PLAYgrounds’. The practices and knowledge of ECEC teachers concerning healthy eating and physical activity and the level of confidence in promoting healthy eating and physical activity in toddlers was assessed at baseline and 9 months of follow-up. To examine the effect of the intervention linear mixed models were used.ResultsPreliminary analyses of the practices indicated that Activity-related-Teaching/Autonomy-Support was increased in the intervention group (mean difference: 0.181), but not in the control group (mean difference: -0.048; p-value group*time: 0.025). Food-related-Pressure-to-Eat was decreased in the intervention group (mean difference: -0.580), but not in the control group (mean difference: -0.158; p-value group*time: 0.014). No effect of the intervention was found on knowledge (p-value group*time: 0.24) and the level of confidence (p-value group*time: 0.98) of ECEC teachers. ConclusionsThe preschool-based intervention seems to increase Activity-related-Teaching/Autonomy-Support and to decrease Food-related-Pressure-to-Eat. No effects were seen on knowledge and level of confidence of ECEC teachers in promoting healthy eating and physical activity in toddlers.
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INTRODUCTION: It is difficult to adjust fluid balance adequately in patients with severe burns due to various physical changes. B-type natriuretic peptide (BNP) is emerging as a potential marker of hydration state. Proteinuria is used as a predictor of outcome in severe illness and might correlate to systemic capillary leakage. This study investigates whether combining BNP and proteinuria can be used as a guide for individualized resuscitation and as a predictor of outcome in patients with severe burns.METHODS: From 2006 to 2009, 38 consecutive patients (age 47 ± 15 years, 74% male) with severe burns were included and followed for 20 days. All had normal kidney function at admission. BNP and proteinuria were routinely measured. Ordered and actually administered fluid resuscitation volumes were recorded. The Sequential Organ Failure Assessment (SOFA) score was used as the measure of outcome.RESULTS: BNP increased during follow-up, reaching a plateau level at Day 3. Based on median BNP levels at Day 3, patients were divided into those with low BNP and those with high BNP levels. Both groups had comparable initial SOFA scores. Patients with high BNP received less fluid from Days 3 to 10. Furthermore, patients with a high BNP at Day 3 had less morbidity, reflected by lower SOFA scores on the following days. To minimize effects of biological variability, proteinuria on Days 1 and 2 was averaged. By dividing the patients based on median BNP at Day 3 and median proteinuria, patients with high BNP and low proteinuria had significantly lower SOFA scores during the entire follow-up period compared to those patients with low BNP and high proteinuria.CONCLUSIONS: Patients with higher BNP levels received less fluid. This might be explained by a lower capillary leakage in these patients, resulting in more intravascular fluid and consequently an increase in BNP. In combination with low proteinuria, possibly reflecting minimal systemic capillary leakage, a high BNP level was associated with a better outcome. BNP and proteinuria have prognostic potential in severely burned patients and may be used to adjust individual resuscitation.
Carnitine/choline acyltransferases play diverse roles in energy metabolism and neuronal signalling. Our knowledge of their evolutionary relationships, important for functional understanding, is incomplete. Therefore, we aimed to determine the evolutionary relationships of these eukaryotic transferases. We performed extensivephylogenetic and intron position analyses. We found that mammalian intramitochondrial CPT2 is most closely related to cytosolic yeast carnitine transferases (Sc-YAT1 and 2), whereas the other members of the family are related to intraorganellar yeast Sc-CAT2. Therefore, the cytosolically active CPT1 more closely resembles intramitochondrial ancestors than CPT2. The choline acetyltransferase is closely related to carnitine acetyltransferase and shows lower evolutionary rates than long chain acyltransferases. In the CPT1 family several duplications occurred during animal radiation, leading to the isoforms CPT1A, CPT1B and CPT1C. In addition, we found five CPT1-like genes in Caenorhabditis elegans that strongly group to the CPT1 family. The long branch leading to mammalian brain isoform CPT1C suggests that either strong positive or relaxed evolution has taken place on this node. The presented evolutionary delineation of carnitine/choline acyltransferases adds to current knowledge on their functions and provides tangible leads for further experimental research.
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Chemo-enzymatic peptide synthesis is unique in enabling the fast and sustainable synthesis of cyclic peptides, complex peptides and functionalized mini-proteins. The starting materials are routinely obtained by solid-phase peptide synthesis. One of the starting materials requires an oxo-ester functionality for recognition by the enzymes active site. The SPPS-based synthesis of the oxo-ester functionality still suffers from significant byproduct formation and low overall synthesis yields. The solution to this is introduction of the oxo-ester functionality at the end of the SPPS via a so-called Passerini reaction. Such a process does not only result in a more efficient production of cyclic or long peptides, but also expand the scope towards proteins derived from biological synthesis (i.e. recombinant proteins). To highlight the relevance of this proposed methodology, we will demonstrate a site-selective modification of the pharmaceutically important drug insulin.
Biotherapeutic medicines such as peptides, recombinant proteins, and monoclonal antibodies have successfully entered the market for treating or providing protection against chronic and life-threatening diseases. The number of relevant commercial products is rapidly increasing. Due to degradation in the gastro-intestinal tract, protein-based drugs cannot be taken orally but need to be administered via alternative routes. The parenteral injection is still the most widely applied administration route but therapy compliance of injection-based pharmacotherapies is a concern. Long-acting injectable (LAI) sustained release dosage forms such as microparticles allow less frequent injection to maintain plasma levels within their therapeutic window. Spider Silk Protein and Poly Lactic-co-Glycolic Acid (PLGA) have been attractive candidates to fabricate devices for drug delivery applications. However, conventional microencapsulation processes to manufacture microparticles encounter drawbacks such as protein activity loss, unacceptable residual organic solvents, complex processing, and difficult scale-up. Supercritical fluids (SCF), such as supercritical carbon dioxide (scCO2), have been used to produce protein-loaded microparticles and is advantageous over conventional methods regarding adjustable fluid properties, mild operating conditions, interfacial tensionless, cheap, non-toxicity, easy downstream processing and environment-friendly. Supercritical microfluidics (SCMF) depict the idea to combine strengths of process scale reduction with unique properties of SCF. Concerning the development of long-acting microparticles for biological therapeutics, SCMF processing offers several benefits over conventionally larger-scale systems such as enhanced control on fluid flow and other critical processing parameters such as pressure and temperature, easy modulation of product properties (such as particle size, morphology, and composition), cheaper equipment build-up, and convenient parallelization for high-throughput production. The objective of this project is to develop a mild microfluidic scCO2 based process for the production of long-acting injectable protein-loaded microparticles with, for example, Spider Silk Protein or PLGA as the encapsulating materials, and to evaluate the techno-economic potential of such SCMF technology for practical & industrial production.
Biotherapeutic medicines such as peptides, recombinant proteins, and monoclonal antibodies have successfully entered the market for treating or providing protection against chronic and life-threatening diseases. The number of relevant commercial products is rapidly increasing. Due to degradation in the gastro-intestinal tract, protein-based drugs cannot be taken orally but need to be administered via alternative routes. The parenteral injection is still the most widely applied administration route but therapy compliance of injection-based pharmacotherapies is a concern. Long-acting injectable (LAI) sustained release dosage forms such as microparticles allow less frequent injection to maintain plasma levels within their therapeutic window. Spider Silk Protein and Poly Lactic-co-Glycolic Acid (PLGA) have been attractive candidates to fabricate devices for drug delivery applications. However, conventional microencapsulation processes to manufacture microparticles encounter drawbacks such as protein activity loss, unacceptable residual organic solvents, complex processing, and difficult scale-up. Supercritical fluids (SCF), such as supercritical carbon dioxide (scCO2), have been used to produce protein-loaded microparticles and is advantageous over conventional methods regarding adjustable fluid properties, mild operating conditions, interfacial tensionless, cheap, non-toxicity, easy downstream processing and environment-friendly. Supercritical microfluidics (SCMF) depict the idea to combine strengths of process scale reduction with unique properties of SCF. Concerning the development of long-acting microparticles for biological therapeutics, SCMF processing offers several benefits over conventionally larger-scale systems such as enhanced control on fluid flow and other critical processing parameters such as pressure and temperature, easy modulation of product properties (such as particle size, morphology, and composition), cheaper equipment build-up, and convenient parallelization for high-throughput production. The objective of this project is to develop a mild microfluidic scCO2 based process for the production of long-acting injectable protein-loaded microparticles with, for example, Spider Silk Protein or PLGA as the encapsulating materials, and to evaluate the techno-economic potential of such SCMF technology for practical & industrial production.
