Fractal analysis of amyloid plaques in Alzheimer's disease patients and mouse models

The varied morphological and biochemical forms in which amyloid deposits in brain of Alzheimer's disease (AD) patients are complex and their mechanisms of formation are not completely understood. Here we investigated the ability of fractal dimension (FD) to differentiate between the textures of commonly observed amyloid plaques in sporadic and familial AD patients and aged-control individuals as well as in transgenic mouse models of amyloidosis. Studying more than 6000 amyloid plaques immunostained for total Aβ (Aβt), Aβ40 or Aβ42, we show here that Aβ40 FD could efficiently differentiate between (i) AD patients and aged-control individuals (P < 0.001); (ii) sporadic and familial AD due to presenilin-1 or APP (A692G) mutations (P < 0.001); and (iii) three transgenic mouse models of different genotypes (P < 0.001). Furthermore, while diffuse and dense-core plaques present in humans and transgenic mice had comparable FDs, both Aβt and Aβ42 FD could also differentiate diffuse plaques from other plaque types in both species (P < 0.001). Our data suggest that plaque FD could be a valuable tool for objective, computer-oriented AD diagnosis as well as for genotype-phenotype correlations of AD.     

The choice between deceased‐ vs living‐donor renal transplantation in children: Analysis of data from a Belgian tertiary center

Pediatric renal transplantation with a living donor (LD) has superior outcome, but there is a paucity of studies analyzing the reasons for not undertaking living donation in West‐European countries. The aim of this study was to retrospectively review the choice of donor source in our center. We also aimed to identify factors which prevented transplantation with a LD. This retrospective study was performed including children aged 2‐19 years who underwent kidney transplantation (KT) at the Ghent University Hospital between 1996 and 2016. Relevant data were collected from medical files to identify the main medical, psychological, and socio‐economic factors influencing the choice of the donor source. There were 48 patients (boys n = 33) who underwent KT. Thirty‐nine patients received a deceased donor (DD) kidney and nine patients received a LD kidney. Sixteen of 48 transplantations were preemptive. The reasons for DD KT included socio‐economic factors such as single caregiver families, one or both parents with a criminal record or convictions and religious or cultural constraints (n = 15), medical considerations (n = 13), refusal of the close relatives/parents to donate (n = 7), and acceptance of an organ from a DD while prospective donor was undergoing medical screening (n = 4). The low incidence of living kidney donation can be explained by socio‐economic and medical factors. Refusal to donate is a potentially modifiable factor and strategies aimed at education and guidance of the families might contribute to a higher incidence of living donation in our setting.     

The impact of a teacher-led structured physical activity session on preschoolers’ sedentary and physical activity levels

ObjectivesThe purpose of this observational study was to examine differences in preschoolers’ sedentary time and physical activity (PA) participation between preschool-attending weekdays with and without a teacher-led structured PA session.DesignA sample of 200 preschoolers (5.3 ± 0.4 y; 113 boys) from 26 preschools in Flanders, Belgium were included in data analysis.MethodsParticipants wore a GT1M ActiGraph accelerometer on one preschool-attending weekday with and on one preschool-attending weekday without the provision of a teacher-led structured PA session. Preschoolers’ sedentary time, light PA, and moderate-to-vigorous physical activity (MVPA) during the time in preschool (08:00–16:00 h) and after preschool (16:00–20:00 h) were estimated. To assess differences in the outcome measures between both days, multi-level linear regression models were conducted.ResultsDuring the time at preschool, lower sedentary levels (β = 13.0 min; SE = 1.6; p < 0.001) and higher light PA (β = 2.9 min; SE = 0.7 p < 0.001) and MVPA levels (β = 10.1 min; SE = 1.1; p < 0.001) were prevalent on days with a structured PA session compared to days without a structured PA session in both boys and girls. After preschool, no differences were found between both days in sedentary time (β = 0.7; SE = 1.4; p > 0.05), light PA (β = 0.3; SE = 0.5; p > 0.05), and MVPA (β = 0.3; SE = 0.9; p > 0.05).ConclusionsThe results demonstrate that no compensatory changes were found after preschool for the structured PA session during the preschool hours. Therefore, a teacher-led structured PA session integrated in the preschool curriculum is a promising mean to decrease sedentary time and to increase PA in preschool-aged boys and girls.     

The use of the activated clotting time for monitoring heparin therapy in critically ill patients

OBJECTIVE: To determine the correlation between activated clotting time (ACT) and activated partial thromboplastin time (aPTT) in patients receiving intravenous unfractionated heparin therapy, and the accuracy of the ACT in predicting the level of anticoagulation. DESIGN: Paired aPTT and ACT measurements were obtained from a convenience sample of critically ill patients requiring intravenous unfractionated heparin. The aPTT was determined in the hospital laboratory and ACT measurements were performed with a portable device. SETTING: The intensive care unit of Ghent University Hospital, a tertiary care facility with 54 beds. PATIENTS AND PARTICIPANTS: Twenty-eight patients were studied prospectively; a total of 105 paired samples were obtained. The indication for heparin therapy was cerebral ischemia in 8, various cardiac conditions in 10, pulmonary embolism in 3, continuous hemofiltration in 3, and peripheral arterial thrombosis in 4. RESULTS: There was a significant correlation between aPTT and ACT. Analysis of variance showed a significant difference in ACT between different levels of anticoagulation, aPTT shorter than 60 s (group 1), aPTT 60-90 s (group 2), and aPTT longer than 90 s (group 3): 142+/-16.7 s in group 1 vs. 155+/-29.6 and 192+/-39.1 in groups 2 and 3. CONCLUSIONS: The correlation between the aPTT and the ACT in this ICU setting is poor; ACT cannot differentiate between low and therapeutic levels of anticoagulation. The use of the ACT for monitoring low to moderate doses of heparin in ICU patients cannot be recommended.     

Activated oxazaphosphorines are transported predominantly by erythrocytes

Purpose: Oxazaphosphorines are metabolised by a variety of pathways, one of which leads to activation and the formation of alkylating compounds. However, the transport forms conveying activated oxazaphosphorines to the tumour cell have not been fully characterised. There is increasing recognition of the importance of the erythrocyte as a carrier of compounds in the circulation, and we have recently described higher concentrations of 4-hydroxycyclophosphamide within the erythrocyte compartment compared to plasma. We have now determined the concentrations of ifosfamide and seven of its metabolites in the plasma and erythrocytes of patients receiving a six-hour intravenous infusion of ifosfamide.Patients and methods: Red cells from five patients, receiving a total of eight cycles of ifosfamide, were separated from plasma using the MESED instrument, and analysis of red cells and plasma performed using Gas Chromatography-Mass Spectrometry (GC/MS).Results: The concentration of all compounds in the erythrocyte compartment was higher than or equal to those in plasma, and isophosphoramide mustard and carboxyifosfamide showed a particular affinity for the erythrocyte. The red cell fraction can contain as much as 77% of the total blood concentration of isophosphoramide mustard.Conclusions: Erythrocyte associated isophosphoramide mustard is an important transport form of activated ifosfamide. Red cells may have a role in the delivery of activated oxazaphosphorines to tissues.     

Simultaneous determination of the peptide-mitomycin KW-2149 and its metabolites in plasma by high-performance liquid chromatography

A gradient high-performance liquid chromatographic (HPLC) method is described for the quantification of KW-2149 and its two major metabolites in plasma. The method involves a sample clean-up by solid-phase extraction on C18 columns, separation of the respective compounds by HPLC on a YMC ODS-AQ column (5-microm particle size, 150x6 mm I.D.), using a methanol-water gradient system as an eluent, and measurement by UV absorbance detection at 375 nm. The limits of quantitation were 10 ng/ml for KW-2149 and M-16, and 15 ng/ml for M-18. Recoveries from plasma were higher than 92% on C18 extraction columns. Intra-day precision, expressed as %C.V., was between 1.4 and 6.5%. Intra-day accuracy ranged from 94 to 107%. Precision and accuracy of variability of inter-assays increased somewhat; however, were still within acceptable ranges. The ability of the method to quantify KW-2149 and two major metabolites simultaneously, with precision, accuracy and sensitivity, make it useful in monitoring the fate of this new mitomycin in cancer patients.     

School‐based interventions promoting both physical activity and healthy eating in Europe: a systematic review within the HOPE project

It is the purpose of this study to systematically review the evidence of school‐based interventions targeting dietary and physical activity behaviour in primary (6–12 years old) and secondary school (12–18 years old) children in Europe. Eleven studies (reported in 27 articles) met the inclusion criteria, six in primary school and five in secondary school children. Interventions were evaluated in terms of behavioural determinants, behaviour (diet and physical activity) and weight‐related outcomes (body mass index [BMI] or other indicators of obesity). The results suggest that combining educational and environmental components that focus on both sides of the energy balance give better and more relevant effects. Furthermore, computer‐tailored personalized education in the classroom showed better results than a generic classroom curriculum. Environmental interventions might include organized physical activities during breaks, or before and after school; improved availability of physical activity opportunities in and around the school environment; increased physical education lesson time; improved availability or accessibility of healthy food options; and restricted availability and accessibility of unhealthy food options. More high‐quality studies are needed to assess obesity‐related interventions in Europe.     

The validity of the masseteric post-stimulus electromyographic complex: a twin study.

The twin model was used to assess the validity of an electromyographically recorded, masseter muscle reflex by measuring the sensitivity and specificity. Results were satisfying, implying that in future studies this reflex could be used to calculate heritability estimates between monozygotic and dizygotic twins.     

Genetic association of CR1 with Alzheimer's disease: A tentative disease mechanism

CR1 is a novel Alzheimer's disease (AD) gene identified by genome-wide association studies (GWAS). Recently, we showed that AD risk could be explained by an 18-kilobase insertion responsible for the complement component (3b/4b) receptor 1 (CR1)-S isoform. We investigated the relevance of the CR1 isoforms to AD in a Canadian dataset. Also, we genotyped rs4844610 tagging the GWAS-significant CR1 single nucleotide polymorphisms. Individuals with F/S genotype had a 1.8 times increased risk for AD compared with F/F genotype (p-adjusted = 0.003), while rs4844610 was only marginally significant (p-adjusted = 0.024). The analyses of brain samples demonstrated that the CR1-S isoform is expressed at lower protein levels than CR1-F (p < 0.0001) hence likely associated with increased complement activation. Intriguingly, our neuropathological results show that the pattern of CR1 expression in neurons is different between the F/F and F/S genotypes (filiform vs. vesicular-like profiles). Furthermore, double labeling studies supported a differential distribution of CR1 in neurons (endoplasmic reticulum intermediate compartment vs. lysosomes). These observations indicate that the CR1-S and CR1-F isoforms could be processed in different ways in neurons. In conclusion, our results support that the CR1-S isoform explains the GWAS signals and open a novel prospect for the investigation of CR1-related disease mechanisms.