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Aims: Adults with type 2 diabetes have an increased risk of cardiovascular events (CVE), the world's leading cause of mortality. The SCORE2-Diabetes model is a tool designed to estimate the 10-year risk of CVE specifically in individuals with type 2 diabetes. However, the performance of such models may vary across different demographic and socioeconomic groups, necessitating validation and assessment in diverse populations. This study aims to externally validate SCORE2-Diabetes and assess its performance across various socioeconomic and migration origins in the Netherlands., Methods: We selected adults with type 2 diabetes, aged 40-79 years and without previous CVE from the Extramural LUMC Academic Network (ELAN) primary care data cohort from 2007 to 2023. ELAN data were linked with Statistics Netherlands registry data to obtain information about the country of origin and socioeconomic status (SES). CVE was defined as myocardial infarction, stroke, or CV mortality. Non-CV mortality was considered a competing event. Analyses were stratified by sex, Dutch versus other non-Dutch countries of origin, and quintiles of SES., Results: Of the 26,544 included adults with type 2 diabetes, 2,518 developed CVE. SCORE2-Diabetes showed strong predictive accuracy for CVE in the Dutch population (observed-to-expected ratio (OE)=1.000, 95% CI=0.990-1.008 for men, and OE=1.050, 95% CI=1.042-1.057 for women). For non-Dutch individuals, the model underestimated CVE risk (OE=1.121, 95% CI=1.108-1.131 for men, and OE=1.100, 95% CI=1.092-1.111 for women). The model also underestimated the CVE risk (OE>1) in low SES groups and overestimated the risk (OE<1) in high SES groups. Discrimination was moderate across subgroups with c-indices between 0.6 and 0.7., Conclusions: SCORE2-Diabetes accurately predicted the risk of CVE in the Dutch population. However, it underpredicted the risk of CVE in the low SES groups and non-Dutch origins, while overpredicting the risk in high SES men and women. Additional clinical judgment must be considered when using SCORE2-Diabetes for different SES and countries of origin., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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.

Background: Secondary prevention is efficient in reducing morbidity and mortality after a myocardial infarction (MI). However, both short-term and long-term mortality after MI remains relativity high in type 2 diabetes patients., Objective: To evaluate repeat prescriptions of secondary prevention medication (anti-thrombotic agent, beta-blocker and statin) in type 2 diabetes patients with a previous MI., Methods: Data of 1009 type 2 diabetes patients with a previous MI were extracted from the Julius General Practitioners' Network database. The proportion of patients with recent repeat prescriptions of guideline-based medication was determined. Furthermore, repeat prescriptions was determined 6 months, 1 year, 2 years and 5 years after MI. Generalized linear models were used to examine changes over time. Multivariate logistic regression analysis was used to analyse the association between patient characteristics and prescription., Results: Only 46% of all type 2 diabetes patients with a previous MI had a recent repeat prescription for all three medicines. An increase in prescription over time was found for statins (P = 0.001). Older aged people [odds ratio (OR): 0.99, 95% confidence interval (CI): 0.98-1.00] were less likely to receive the combination of all three., Conclusion: A substantial proportion of type 2 diabetes patients with a previous MI did not receive guideline-based secondary prevention. Prescription rates were quite stable over time. This study confirms the need for a different approach to achieve an improvement of secondary prevention in type 2 diabetes patient with a previous MI. GPs can play an important role in this respect by being extra alert that prescription occurs according to the guidelines., (© The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Phenylpropanoid volatiles are responsible for the key tomato fruit (Solanum lycopersicum) aroma attribute termed "smoky." Release of these volatiles from their glycosylated precursors, rather than their biosynthesis, is the major determinant of smoky aroma in cultivated tomato. using a combinatorial omics approach, we identified the non-smoky glycosyltransferase1 (NSGT1) gene. Expression of NSGT1 is induced during fruit ripening, and the encoded enzyme converts the cleavable diglycosides of the smoky-related phenylpropanoid volatiles into noncleavable triglycosides, thereby preventing their deglycosylation and release from tomato fruit upon tissue disruption. In an nsgt1/nsgt1 background, further glycosylation of phenylpropanoid volatile diglycosides does not occur, thereby enabling their cleavage and the release of corresponding volatiles. Using reverse genetics approaches, the NSGT1-mediated glycosylation was shown to be the molecular mechanism underlying the major quantitative trait locus for smoky aroma. Sensory trials with transgenic fruits, in which the inactive nsgt1 was complemented with the functional NSGT1, showed a significant and perceivable reduction in smoky aroma. NSGT1 may be used in a precision breeding strategy toward development of tomato fruits with distinct flavor phenotypes.

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.

Apple (Malus×domestica Borkh) is among the main sources of phenolic compounds in the human diet. The genetic basis of the quantitative variations of these potentially beneficial phenolic compounds was investigated. A segregating F₁ population was used to map metabolite quantitative trait loci (mQTLs). Untargeted metabolic profiling of peel and flesh tissues of ripe fruits was performed using liquid chromatography-mass spectrometry (LC-MS), resulting in the detection of 418 metabolites in peel and 254 in flesh. In mQTL mapping using MetaNetwork, 669 significant mQTLs were detected: 488 in the peel and 181 in the flesh. Four linkage groups (LGs), LG1, LG8, LG13, and LG16, were found to contain mQTL hotspots, mainly regulating metabolites that belong to the phenylpropanoid pathway. The genetics of annotated metabolites was studied in more detail using MapQTL®. A number of quercetin conjugates had mQTLs on LG1 or LG13. The most important mQTL hotspot with the largest number of metabolites was detected on LG16: mQTLs for 33 peel-related and 17 flesh-related phenolic compounds. Structural genes involved in the phenylpropanoid biosynthetic pathway were located, using the apple genome sequence. The structural gene leucoanthocyanidin reductase (LAR1) was in the mQTL hotspot on LG16, as were seven transcription factor genes. The authors believe that this is the first time that a QTL analysis was performed on such a high number of metabolites in an outbreeding plant species.

Altering expression of transcription factors can be an effective means to coordinately modulate entire metabolic pathways in plants. It can also provide useful information concerning the identities of genes that constitute metabolic networks. Here, we used ectopic expression of a MYB transcription factor, Petunia hybrida ODORANT1, to alter Phe and phenylpropanoid metabolism in tomato (Solanum lycopersicum) fruits. Despite the importance of Phe and phenylpropanoids to plant and human health, the pathway for Phe synthesis has not been unambiguously determined. Microarray analysis of ripening fruits from transgenic and control plants permitted identification of a suite of coregulated genes involved in synthesis and further metabolism of Phe. The pattern of coregulated gene expression facilitated discovery of the tomato gene encoding prephenate aminotransferase, which converts prephenate to arogenate. The expression and biochemical data establish an arogenate pathway for Phe synthesis in tomato fruits. Metabolic profiling and ¹³C flux analysis of ripe fruits further revealed large increases in the levels of a specific subset of phenylpropanoid compounds. However, while increased levels of these human nutrition-related phenylpropanoids may be desirable, there were no increases in levels of Phe-derived flavor volatiles.

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.

Fruit maturation and tissue differentiation are important topics in plant physiology. These biological phenomena are accompanied by specific alterations in the biological system, such as differences in the type and concentration of metabolites. The secondary metabolism of tomato (Solanum lycopersicum) fruit was monitored by using liquid chromatography (LC) coupled to photo-diode array (PDA) detection, fluorescence detection (FD), and mass spectrometry (MS). Through this integrated approach different classes of compounds were analysed: carotenoids, xanthophylls, chlorophylls, tocopherols, ascorbic acid, flavonoids, phenolic acids, glycoalkaloids, saponins, and other glycosylated derivatives. Related metabolite profiles of peel and flesh were found between several commercial tomato cultivars indicating similar metabolite trends despite the genetic background. For a single tomato cultivar, metabolite profiles of different fruit tissues (vascular attachment region, columella and placenta, epidermis, pericarp, and jelly parenchyma) were examined at the green, breaker, turning, pink, and red stages of fruit development. Unrelated to the chemical nature of the metabolites, behavioural patterns could be assigned to specific ripening stages or tissues. These findings suggest spatio-temporal specificity in the accumulation of endogenous metabolites from tomato fruit.

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).