Implicit gender bias in the diagnosis and treatment of type 2 diabetes: A randomized online study.

AIMS: Implicit gender biases (IGBs) are unconscious evaluations about a person based on gender. IGBs of healthcare providers may affect medical decision making. This study investigated whether IGBs and genders of patients and general practitioners (GPs) influence diagnostics and treatment decisions in the context of diabetes type 2. METHODS: Ninety-nine GPs participated in this randomized online study. Implicit Associations Tasks were used to measure two IGBs, related to lifestyle (women have a healthier lifestyle than men) and communication (men are less communicative than women). Clinical decisions regarding type 2 diabetes were measured with vignettes that included a fictional male or female patient case. RESULTS: Female GPs exhibited a significant lifestyle IGB (p < 0.001). GPs of both genders exhibited a significant communication IGB (p < 0.001). Several associations between IGBs and clinical decisions were found. The gender of the vignette character affected several outcomes, for example GPs were less certain in the diabetes diagnosis when the character was a woman (p < 0.001). CONCLUSION: We demonstrated that GPs have IGBs and these biases as well as patient's gender affect decisions of GP's when they are solving a diabetes vignette case. Future research is needed to understand the most important consequences of IGBs in the context of type 2 diabetes.

Patient-reported outcomes after 10-year follow-up of intensive, multifactorial treatment in individuals with screen-detected type 2 diabetes: the ADDITION-Europe trial.

AIMS: To present the longer-term impact of multifactorial treatment of type 2 diabetes on self-reported health status, diabetes-specific quality of life, and diabetes treatment satisfaction at 10-year follow up of the ADDITION-Europe trial. METHODS: The ADDITION-Europe trial enrolled 3057 individuals with screen-detected type 2 diabetes from four centres [Denmark, the UK (Cambridge and Leicester) and the Netherlands], between 2001 and 2006. Participants were randomized at general practice level to intensive treatment or to routine care . The trial ended in 2009 and a 10-year follow-up was performed at the end of 2014. We measured self-reported health status (36-item Short-Form Health Survey and EQ-5D), diabetes-specific quality of life (Audit of Diabetes-Dependent Quality of Life questionnaire), and diabetes treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire) at different time points during the study period. A mixed-effects model was applied to estimate the effect of intensive treatment (intention-to-treat analyses) on patient-reported outcome measures for each centre. Centre-specific estimates were pooled using a fixed effects meta-analysis. RESULTS: There was no difference in patient-reported outcome measures between the routine care and intensive treatment arms in this 10-year follow-up study [EQ-5D: -0.01 (95% CI -0.03, 0.01); Physical Composite Score (36-item Short-Form Health Survey): -0.27 (95% CI -1.11, 0.57), Audit of Diabetes-Dependent Quality of Life questionnaire: -0.01 (95% CI -0.11, 0.10); and Diabetes Treatment Satisfaction Questionnaire: -0.20 (95% CI -0.70, 0.29)]. CONCLUSIONS: Intensive, multifactorial treatment of individuals with screen-detected type 2 diabetes did not affect self-reported health status, diabetes-specific quality of life, or diabetes treatment satisfaction at 10-year follow-up compared to routine care.

Theory-based diabetes self-management education with pre-selection of participants: a randomized controlled trial with 2.5 years' follow-up (ELDES Study).

AIMS: To evaluate the (cost-)effectiveness of Beyond Good Intentions (BGI), a 12-week group-based, nurse-led self-management programme, in terms of cardiovascular risk factors, self-management and quality of life, after 2.5 years of follow-up in pre-selected individuals with known Type 2 diabetes of up to 5 years' duration. METHODS: A parallel randomized controlled trial comparing BGI with usual care, based on a self-management screening questionnaire, was conducted in 43 general practices after pre-selection of participants. After 2.5 years of follow-up, the between-group changes in the abovementioned variables were assessed using analysis of covariance. RESULTS: A total of 108 participants (BGI group, n =56; control group, n =52) were included. Changes over time in BMI (-0.4 vs -0.5 kg/m2 ) were similar in the two groups. Median HbA1c [BGI group 47 mmol/mol (6.5%); control group: 49 mmol/mol (6.6%)] and mean systolic blood pressure (BGI group: 132±13 mmHg; control group: 133±14 mmHg) were well controlled at baseline and no intervention effect was found. LDL cholesterol levels decreased from 2.4 to 2.2 mmol/l in the control group and remained stable at 2.6 mmol/l in the intervention group (P=0.032). No intervention effect was found for self-management or quality of life. CONCLUSION: In contrast to the first BGI study, we did not observe significant effects of the BGI intervention, despite pre-selection of individuals. In diabetes populations with target levels for HbA1c , systolic blood pressure and LDL cholesterol, no further beneficial effects can be expected from self-management programmes with regard to biomedical factors and quality of life.

The effectiveness of an emotion-focused educational programme in reducing diabetes distress in adults with Type 2 diabetes mellitus (VEMOFIT): a cluster randomized controlled trial.

AIMS: To evaluate the effectiveness of a brief, value-based emotion-focused educational programme (VEMOFIT) in Malay adults with Type 2 diabetes mellitus compared with a programme of active listening to participants' emotional experiences, social support and their opinion on the health clinic diabetes care services (attention control). METHODS: Malay adults with severe diabetes distress [Diabetes Distress Scale (DDS-17) mean score ≥ 3] were included. VEMOFIT consisted of four biweekly group sessions, a booster session after 3 months and a follow-up 6 months post intervention. The attention control programme consisted of three sessions over the same period. Outcomes included diabetes distress, depressive symptoms, self-efficacy and disease control. Required total sample size was 165. RESULTS: Participants (n = 124) were randomized to either VEMOFIT (n = 53) or the attention control programme (n = 71). Participants had a mean (sd) age of 55.7 (9.7) years, median diabetes duration of 7.0 (8.0) years and mean HbA1c level of 82 mmol/mol (9.7%). The mean DDS-17 level decreased significantly in both the VEMOFIT and the attention control programmes (3.4 to 2.9 vs. 3.1 to 2.7, respectively). The adjusted between-group DDS-17 difference was not significant [-0.01, 95% confidence interval (CI) -0.38, 0.35]. The proportion of individuals with severe diabetes distress decreased in both groups, from 89% to 47% vs. 69% to 39% (odds ratio 0.88; 95% CI 0.26, 2.90). Other outcomes did not differ between groups. CONCLUSIONS: Both interventions decreased diabetes distress significantly. The theory-based VEMOFIT programme was not superior to the attention control programme. The latter approach is a simpler way to decrease severe diabetes distress (Trial registration: NCT02730078; NMRR-15-1144-24803).

Effectiveness of tailored support for people with Type 2 diabetes after a first acute coronary event: a multicentre randomized controlled trial (the Diacourse-ACE study).

AIMS: To evaluate the effectiveness of a tailored, supportive intervention strategy in influencing diabetes-related distress, health status, well-being and clinical outcomes in people with Type 2 diabetes shortly after a first acute coronary event. METHODS: People with Type 2 diabetes and a recent first acute coronary event (n = 201) were randomized to the intervention group (three home visits by a diabetes nurse) or the attention control group (one telephone consultation). Outcomes were measured after discharge (baseline) and at 5 months (follow-up) using validated questionnaires for diabetes-related distress (Problem Areas in Diabetes), well-being (WHO Well-Being Index) and health status (Euroqol 5 Dimensions; Euroqol Visual Analogue Scale). ancova was used to analyse change-over-time differences between groups. RESULTS: Follow-up data were available for 81 participants in the intervention group (66.0 ± 9.3 years, 76% male) and 80 in the control group (65.6 ± 9.4 years, 75% male) participants. Mean diabetes-related distress was low after hospital discharge (intervention group: 8.2 ± 10.1; control group: 9.2 ± 12.4) and did not change after 5 months (intervention group: 9.2 ± 12.4; control group: 9.0 ± 11.2). Baseline well-being was less favourable but improved significantly in the intervention group (baseline: 58.5 ± 28.0; follow-up: 65.5 ± 23.7; P = 0.005), but not in the control group (baseline: 57.5 ± 25.2; follow-up: 59.6 ± 24.4; P = 0.481). Health status also improved in the intervention group (baseline: 69.9 ± 17.3; follow-up: 76.8 ± 15.6; P < 0.001) but not in the control group (baseline: 68.6 ± 15.9; follow-up: 69.9 ± 16.7; P = 0.470). A significant group effect was found for health status (F = 7.9; P = 0.006). CONCLUSIONS: Although the intervention had no effect on diabetes-related distress, this might be at least partially attributable to very low levels of diabetes-related distress at baseline. Interestingly, health status scores and well-being, which were less favourable at baseline, both improved after the tailored support intervention.

Diabetes-related distress over the course of illness: results from the Diacourse study.

AIMS: To investigate the relationship between diabetes duration and diabetes-related distress and to examine the impact of micro- and macrovascular complications and blood glucose-lowering treatment on this relationship. METHODS: We conducted a cross-sectional study in people with Type 2 diabetes who participated in the Dutch Diacourse study (n = 590) and completed the Problem Areas in Diabetes questionnaire. Data on diabetes duration, micro- and macrovascular complications and blood glucose-lowering treatment were collected. Multiple linear regression analysis was used to investigate the association between diabetes duration and diabetes-related distress, and to examine whether complications and treatment could explain this association. RESULTS: A significant linear and quadratic association between diabetes duration and diabetes-related distress was found (duration: ß = 0.27, P = 0.005; duration(2): ß = -0.21, P = 0.030). The association between duration and distress could be explained by microvascular complications and insulin treatment, which were both more often present in people with a longer diabetes duration, and were associated with higher levels of diabetes-related distress (ß = 0.20, P < 0.001 and ß = 0.16, P = 0.006 respectively). Duration, age, gender, complications and treatment together explained 13.1% of the variance in distress. CONCLUSIONS: Diabetes duration was associated with diabetes-related distress. This association can be explained largely by the presence of diabetes-related microvascular complications and insulin treatment. Healthcare providers should focus on distress in people with Type 2 diabetes in different stages over the course of illness, especially when complications are present or when people are on insulin treatment. As well as diabetes duration, complications and blood glucose-lowering treatment, diabetes-related distress is likely to be influenced by many other factors.

The impact of the covid-19 pandemic on diabetes care: the perspective of healthcare providers across Europe.

AIMS: Covid-19 caused changes on the delivery of diabetes care. This study aimed to explore perceptions of healthcare providers across Europe concerning 1) the impact of covid-19 on delivery of diabetes care; 2) impact of changes in diabetes care on experienced workload; 3) experiences with video consultation in diabetes care. METHODS: Cross-sectional survey among healthcare providers in the Netherlands, United Kingdom, Turkey, Ukraine and Sweden, with a focus on primary care. RESULTS: The survey was completed by 180 healthcare providers. During the COVID-19 pandemic 57.1% of respondents provided less diabetes care and 72.8% observed a negative impact on people with diabetes. More than half of respondents (61.9%) expressed worries to some extent about getting overloaded by work. Although the vast majority considered their work meaningful (85.6%). Almost half of healthcare providers (49.4%) thought that after the pandemic video-consultation could be blended with face-to-face contact. CONCLUSIONS: Less diabetes care was delivered and a negative impact on people with diabetes was observed by healthcare providers. Despite healthcare providers' feeling overloaded, mental wellbeing seemed unaffected. Video consultations were seen as having potential. Given the remaining covid-19 risks and from the interest of proactive management of people with diabetes, these findings urge for further exploration of incorporating video consultation in diabetes care.

The introduction of a data-driven population health management approach in the Netherlands since 2019: The Extramural LUMC Academic Network data infrastructure.

Improving population health and reducing inequalities through better integrated health and social care services is high up on the agenda of policymakers internationally. In recent years, regional cross-domain partnerships have emerged in several countries, which aim to achieve better population health, quality of care and a reduction in the per capita costs. These cross-domain partnerships aim to have a strong data foundation and are committed to continuous learning in which data plays an essential role. This paper describes our approach towards the development of the regional integrative population-based data infrastructure Extramural LUMC (Leiden University Medical Center) Academic Network (ELAN), in which we linked routinely collected medical, social and public health data at the patient level from the greater The Hague and Leiden area. Furthermore, we discuss the methodological issues of routine care data and the lessons learned about privacy, legislation and reciprocities. The initiative presented in this paper is relevant for international researchers and policy-makers because a unique data infrastructure has been set up that contains data across different domains, providing insights into societal issues and scientific questions that are important for data driven population health management approaches.

Seed storage at elevated partial pressure of oxygen, a fast method for analysing seed ageing under dry conditions.

BACKGROUND AND AIMS: Despite differences in physiology between dry and relative moist seeds, seed ageing tests most often use a temperature and seed moisture level that are higher than during dry storage used in commercial practice and gene banks. This study aimed to test whether seed ageing under dry conditions can be accelerated by storing under high-pressure oxygen. methods: Dry barley (Hordeum vulgare), cabbage (Brassica oleracea), lettuce (Lactuca sativa) and soybean (Glycine max) seeds were stored between 2 and 7 weeks in steel tanks under 18 MPa partial pressure of oxygen. Storage under high-pressure nitrogen gas or under ambient air pressure served as controls. The method was compared with storage at 45 °C after equilibration at 85 % relative humidity and long-term storage at the laboratory bench. Germination behaviour, seedling morphology and tocopherol levels were assessed. KEY RESULTS: The ageing of the dry seeds was indeed accelerated by storing under high-pressure oxygen. The morphological ageing symptoms of the stored seeds resembled those observed after ageing under long-term dry storage conditions. Barley appeared more tolerant of this storage treatment compared with lettuce and soybean. Less-mature harvested cabbage seeds were more sensitive, as was the case for primed compared with non-primed lettuce seeds. Under high-pressure oxygen storage the tocopherol levels of dry seeds decreased, in a linear way with the decline in seed germination, but remained unchanged in seeds deteriorated during storage at 45 °C after equilibration at 85 % RH. CONCLUSIONS: Seed storage under high-pressure oxygen offers a novel and relatively fast method to study the physiology and biochemistry of seed ageing at different seed moisture levels and temperatures, including those that are representative of the dry storage conditions as used in gene banks and commercial practice.

Automated procedure for candidate compound selection in GC-MS metabolomics based on prediction of Kovats retention index.

MOTIVATION: Matching both the retention index (RI) and the mass spectrum of an unknown compound against a mass spectral reference library provides strong evidence for a correct identification of that compound. Data on retention indices are, however, available for only a small fraction of the compounds in such libraries. We propose a quantitative structure-RI model that enables the ranking and filtering of putative identifications of compounds for which the predicted RI falls outside a predefined window. RESULTS: We constructed multiple linear regression and support vector regression (SVR) models using a set of descriptors obtained with a genetic algorithm as variable selection method. The SVR model is a significant improvement over previous models built for structurally diverse compounds as it covers a large range (360-4100) of RI values and gives better prediction of isomer compounds. The hit list reduction varied from 41% to 60% and depended on the size of the original hit list. Large hit lists were reduced to a greater extend compared with small hit lists. AVAILABILITY: http://appliedbioinformatics.wur.nl/GC-MS. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Risk and management of pre-diabetes.

Type 2 diabetes mellitus (T2DM) is associated with a two- to four-fold increased risk of developing cardiovascular disease (CVD) and microvascular complications, which may already be present before diagnosis. It is, therefore, important to detect people with an increased risk of T2DM at an early stage. In order to identify individuals with so-called 'pre-diabetes', comprising impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), current guidelines have developed definitions based on fasting plasma glucose, two-hour glucose concentrations and haemoglobin A1c. Subjects with pre-diabetes are at an increased risk of developing T2DM and CVD. This elevated risk seems similar according to the different criteria used to define pre-diabetes. The risk of progression to T2DM or CVD does, however, depend on other risk factors such as sex, body mass index and ethnicity. Based on the risk factors to develop T2DM, many risk assessment models have been developed to identify those at highest risk. These models perform well to identify those at risk and could be used to initiate preventive interventions. Many studies have shown that lifestyle modification and metformin are effective in preventing the development of T2DM, although lifestyle modification seems to have a more sustainable effect. In addition, lifestyle modification seems more effective in those with IGT than those with IFG. In this review, we will describe the different definitions used to define pre-diabetes, progression from pre-diabetes to T2DM or other vascular complications, risk factors associated with progressions and the management of progression to T2DM, ending with clinical recommendations.

Metabolomics meets functional assays: coupling LC-MS and microfluidic cell-based receptor-ligand analyses.

INTRODUCTION: Metabolomics has become a valuable tool in many research areas. However, generating metabolomics-based biochemical profiles without any related bioactivity is only of indirect value in understanding a biological process. Therefore, metabolomics research could greatly benefit from tools that directly determine the bioactivity of the detected compounds. OBJECTIVE: We aimed to combine LC-MS metabolomics with a cell based receptor assay. This combination could increase the understanding of biological processes and may provide novel opportunities for functional metabolomics. METHODS: We developed a flow through biosensor with human cells expressing both the TRPV1, a calcium ion channel which responds to capsaicin, and the fluorescent intracellular calcium ion reporter, YC3.6. We have analysed three contrasting Capsicum varieties. Two were selected with contrasting degrees of spiciness for characterization by HPLC coupled to high mass resolution MS. Subsequently, the biosensor was then used to link individual pepper compounds with TRPV1 activity. RESULTS: Among the compounds in the crude pepper fruit extracts, we confirmed capsaicin and also identified both nordihydrocapsaicin and dihydrocapsaicin as true agonists of the TRPV1 receptor. Furthermore, the biosensor was able to detect receptor activity in extracts of both Capsicum fruits as well as a commercial product. Sensitivity of the biosensor to this commercial product was similar to the sensory threshold of a human sensory panel. CONCLUSION: Our results demonstrate that the TRPV1 biosensor is suitable for detecting bioactive metabolites. Novel opportunities may lie in the development of a continuous functional assay, where the biosensor is directly coupled to the LC-MS.

Multi-platform metabolomics analyses of a broad collection of fragrant and non-fragrant rice varieties reveals the high complexity of grain quality characteristics.

The quality of rice in terms not only of its nutritional value but also in terms of its aroma and flavour is becoming increasingly important in modern rice breeding where global targets are focused on both yield stability and grain quality. In the present paper we have exploited advanced, multi-platform metabolomics approaches to determine the biochemical differences in 31 rice varieties from a diverse range of genetic backgrounds and origin. All were grown under the specific local conditions for which they have been bred and all aspects of varietal identification and sample purity have been guaranteed by local experts from each country. Metabolomics analyses using 6 platforms have revealed the extent of biochemical differences (and similarities) between the chosen rice genotypes. Comparison of fragrant rice varieties showed a difference in the metabolic profiles of jasmine and basmati varieties. However with no consistent separation of the germplasm class. Storage of grains had a significant effect on the metabolome of both basmati and jasmine rice varieties but changes were different for the two rice types. This shows how metabolic changes may help prove a causal relationship with developing good quality in basmati rice or incurring quality loss in jasmine rice in aged grains. Such metabolomics approaches are leading to hypotheses on the potential links between grain quality attributes, biochemical composition and genotype in the context of breeding for improvement. With this knowledge we shall establish a stronger, evidence-based foundation upon which to build targeted strategies to support breeders in their quest for improved rice varieties.

Comprehensive metabolomics to evaluate the impact of industrial processing on the phytochemical composition of vegetable purees.

The effects of conventional industrial processing steps on global phytochemical composition of broccoli, tomato and carrot purees were investigated by using a range of complementary targeted and untargeted metabolomics approaches including LC-PDA for vitamins, (1)H NMR for polar metabolites, accurate mass LC-QTOF MS for semi-polar metabolites, LC-MRM for oxylipins, and headspace GC-MS for volatile compounds. An initial exploratory experiment indicated that the order of blending and thermal treatments had the highest impact on the phytochemicals in the purees. This blending-heating order effect was investigated in more depth by performing alternate blending-heating sequences in triplicate on the same batches of broccoli, tomato and carrot. For each vegetable and particularly in broccoli, a large proportion of the metabolites detected in the purees was significantly influenced by the blending-heating order, amongst which were potential health-related phytochemicals and flavour compounds like vitamins C and E, carotenoids, flavonoids, glucosinolates and oxylipins. Our metabolomics data indicates that during processing the activity of a series of endogenous plant enzymes, such as lipoxygenases, peroxidases and glycosidases, including myrosinase in broccoli, is key to the final metabolite composition and related quality of the purees.

A metabolomics approach to identify factors influencing glucosinolate thermal degradation rates in Brassica vegetables.

Thermal processing of Brassica vegetables can lead to substantial loss of potential health-promoting glucosinolates (GLs). The extent of thermal degradation of a specific GL varies in different vegetables, possibly due to differences in the composition of other metabolites within the plant matrices. An untargeted metabolomics approach followed by random forest regression was applied to identify metabolites associated to thermal GL degradation in a segregating Brassica oleracea population. Out of 413 metabolites, 15 were associated with the degradation of glucobrassicin, six with that of glucoraphanin and two with both GLs. Among these 23 metabolites three were identified as flavonols (one kaempferol- and two quercetin-derivatives) and two as other GLs (4-methoxyglucobrassicin, gluconasturtiin). Twenty quantitative trait loci (QTLs) for these metabolites, which were associated with glucoraphanin and glucobrassicin degradation, were identified on linkage groups C01, C07 and C09. Two flavonols mapped on linkage groups C07 and C09 and co-localise with the QTL for GL degradation determined previously.

MSClust: a tool for unsupervised mass spectra extraction of chromatography-mass spectrometry ion-wise aligned data.

Mass peak alignment (ion-wise alignment) has recently become a popular method for unsupervised data analysis in untargeted metabolic profiling. Here we present MSClust-a software tool for analysis GC-MS and LC-MS datasets derived from untargeted profiling. MSClust performs data reduction using unsupervised clustering and extraction of putative metabolite mass spectra from ion-wise chromatographic alignment data. The algorithm is based on the subtractive fuzzy clustering method that allows unsupervised determination of a number of metabolites in a data set and can deal with uncertain memberships of mass peaks in overlapping mass spectra. This approach is based purely on the actual information present in the data and does not require any prior metabolite knowledge. MSClust can be applied for both GC-MS and LC-MS alignment data sets. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-011-0368-2) contains supplementary material, which is available to authorized users.

Gut microbial metabolism of polyphenols from black tea and red wine/grape juice is source-specific and colon-region dependent.

The colonic microbial degradation of a polyphenol-rich black tea extract (BTE) and red wine/grape juice extract (RWGE) was compared in a five-stage in vitro gastrointestinal model (TWINSHIME). Microbial metabolism of BTE and RWGE polyphenols in the TWINSHIME was studied subsequently in single- and continuous-dose experiments. A combination of liquid or gas chromatography with mass spectrometry (LC-MS or GC-MS) and NMR-based metabolic profiling was used to measure selected parent polyphenols, their microbial degradation into phenolic acids, and the production of short-chain fatty acids (SCFAs) in different colon compartments. Acetate production was increased by continuous feeding of BTE but not RWGE. During RWGE feeding, gallic acid and 4-hydroxyphenylpropionic acid remained elevated throughout the colon, while during BTE feeding, they were consumed in the distal colon, while 3-phenylpropionic acid was strongly produced. Gut microbial production of phenolics and SCFAs is dependent on colon location and polyphenol source, which may influence potential health benefits.

Long-term effect of lifestyle intervention on adiposity, metabolic parameters, inflammation and physical fitness in obese children: a randomized controlled trial.

BACKGROUND: Behavioral lifestyle intervention, combined with parental involvement, is preferred over standard care or self-help in childhood obesity. The short-term results of such interventions are promising, but long-term follow-up results are equivocal. OBJECTIVE: The objective of the present study was the short (3 months) and long-term (1 and 2 years follow-up) effect evaluation of a family-based multidisciplinary cognitive behavioral lifestyle intervention on markers of adiposity, metabolism, inflammation and physical fitness compared with standard care in children with obesity. Also the association between these outcome variables was determined. METHODS: In this prospective longitudinal clinical trial, obese children were randomly assigned to a 3-month family-based cognitive behavioral multidisciplinary lifestyle treatment (n=40; body mass index-standard deviation score (BMI-SDS) 4.2±0.7; age; 13.3±2.0 years) or to a control group receiving an initial advice on physical activity and nutrition (n=39; BMI-SDS 4.3±0.6; age 13.1±1.9 years). Anthropometric data, physical fitness, metabolic parameters and inflammatory state were evaluated at baseline, after intervention (at 3 months) and at 1-year follow-up. At 2-year follow-up, anthropometric data and physical fitness were measured in the intervention group. RESULTS: An intervention effect after 1 year was found for adiposity (P=0.02 for BMI-SDS, P=0.03 for waist circumference (WC)-SDS), physical fitness (absolute measured peak value of oxygen uptake (ml min(-1)), standardized for age and gender (VO2peak-SDS), P<0.01) and insulin resistance (HOMA-SDS, P=0.04). No significant intervention effect was found for serum lipid profile, high-sensitive C-reactive protein or for adiponectin. At 2-year follow-up, BMI-SDS in the intervention group (n=31) was 3.8±1.2 SDS, significantly less than at baseline (P=0.02). CONCLUSION: A positive 1-year follow-up treatment effect was found for adiposity, physical fitness and glucose homeostasis, but not for inflammatory markers. There was a significant long-term treatment effect on adiposity, although almost all children remained obese.

Physical fitness, functional ability and quality of life in children with severe haemophilia: a pilot study.

In the Netherlands comparable levels of sports-participation between persons with haemophilia and healthy controls have been reported. This raises the question if children with haemophilia under the currently available prophylaxis do reach comparable levels of physical fitness and health-related quality of life (HRQoL) as their healthy peers. The aim of this study was to investigate the level of physical fitness, functional ability and quality of life and to determine the feasibility to safely test the exercise capacity of boys with severe haemophilia A. Thirteen subjects participated in this study. Physical fitness was determined using the measurement of maximal oxygen uptake (VO2peak) attained during a graded maximal exercise test to volitional exhaustion. Joint health, physical activity levels and health-related quality of life (Haemo-Qol) were also measured. Mean VO2peak was 1.86+/-0.77 L min-1 (Z-score: -0.39+/-1.61) which was not significantly different from reference values. Relative VO2peak was 47.42+/-8.29 mL min-1 kg-1 (Z-score: -0.52+/-1.43), which did not differ significantly from reference values either. One boy suffered a joint bleeding one day after the test. Haemo-Qol scores in parents and children ranged from 3.2% to 36.7% (100% reflects poor outcome). Relationship between the child or parent reports of Haemo-QoL and both absolute and relative VO2peak ranged from R=0.00 and R=0.4. Exercise testing in children with severe haemophilia A was a safe procedure. Patients with severe haemophilia A with good joint health and no limitations of activities have comparable physical fitness and physical active lifestyle with healthy peers and good HRQoL.

Identification of the SAAT gene involved in strawberry flavor biogenesis by use of DNA microarrays.

Fruit flavor is a result of a complex mixture of numerous compounds. The formation of these compounds is closely correlated with the metabolic changes occurring during fruit maturation. Here, we describe the use of DNA microarrays and appropriate statistical analyses to dissect a complex developmental process. In doing so, we have identified a novel strawberry alcohol acyltransferase (SAAT) gene that plays a crucial role in flavor biogenesis in ripening fruit. Volatile esters are quantitatively and qualitatively the most important compounds providing fruity odors. Biochemical evidence for involvement of the SAAT gene in formation of fruity esters is provided by characterizing the recombinant protein expressed in Escherichia coli. The SAAT enzyme showed maximum activity with aliphatic medium-chain alcohols, whose corresponding esters are major components of strawberry volatiles. The enzyme was capable of utilizing short- and medium-chain, branched, and aromatic acyl-CoA molecules as cosubstrates. The results suggest that the formation of volatile esters in fruit is subject to the availability of acyl-CoA molecules and alcohol substrates and is dictated by the temporal expression pattern of the SAAT gene(s) and substrate specificity of the SAAT enzyme(s).