Search

IntroductionEvidence points toward the early life being crucial for preventing nutrition-related diseases. As promotion of healthier food preferences in toddlerhood and preschool age might still modulate the trajectories of disease risk, understanding diet in these age groups is necessary. The objective was to analyze food consumption and diet quality of 1–5-year-old children living in Germany in relation to age and sex.MethodsData from 890 children, a subsample of the representative, cross-sectional Children’s Nutrition Survey to Record Food Consumption (KiESEL) conducted by the German Federal Institute for Risk Assessment in 2014–2017, were analyzed. Dietary data were collected using food records (3 consecutive plus 1 independent day). Diet quality was evaluated against the German food-based dietary guidelines (FBDG).ResultsConsumption of unfavorable foods (e.g., sweets, soft drinks) exceeded the recommended maximum of 10% of energy intake (E%) by a multiple in all age and sex groups (medians: 24.8–35.8 E%). Preschoolers consumed more unfavorable foods than toddlers and boys more than girls. More than half of the children exceeded the recommendation for meat intake (medians: 2.3–3.2% of the total food consumption (%TFC) vs. 2 %TFC), especially preschoolers. In nearly all children, vegetable consumption was too low (medians: 4.2–4.5 %TFC vs. 12 %TFC). Also, milk/milk product consumption was below recommendations, more so in preschoolers (median: 12.0 %TFC ♂, 11.9 %TFC ♀ vs. 18 %TFC) than in toddlers (median: 16.1 %TFC ♂, 19.6 %TFC ♀). In toddlers and preschoolers with overweight or obesity, adherence to dietary recommendations of these food groups was largely similar to that of the total sample. Overall, 5-year-olds showed an unhealthier dietary pattern than 1-year-olds, which already emerged at age 2 years and became more evident at age 3 years.DiscussionAn adverse dietary pattern arises and even deteriorates at a very young age, showing sex-specific aspects. High attention from public health and research needs to be given to toddlerhood and even earlier life phases, e.g., to develop more age-specific FBDGs, aiming at reducing unhealthy food consumption.

Isovaleric acidemia (IVA), an inborn error of leucine catabolism, is caused by mutations in the isovaleryl-CoA dehydrogenase (IVD) gene, resulting in the accumulation of derivatives of isovaleryl-CoA including isovaleryl (C5)-carnitine, the marker metabolite used for newborn screening (NBS). The inclusion of IVA in NBS programs in many countries has broadened knowledge of the variability of the condition, whereas prior to NBS, two distinct clinical phenotypes were known, an “acute neonatal” and a “chronic intermittent” form. An additional biochemically mild and potentially asymptomatic form of IVA and its association with a common missense mutation, c.932C>T (p.A282V), was discovered in subjects identified through NBS. Deficiency of short/branched chain specific acyl-CoA dehydrogenase (2-methylbutyryl-CoA dehydrogenase), a defect of isoleucine degradation whose clinical significance remains unclear, also results in elevated C5-carnitine, and may therefore be detected by NBS for IVA. Treatment strategies for the long-term management of symptomatic IVA comprise the prevention of catabolism, dietary restriction of natural protein or leucine intake, and supplementation with l-carnitine and/or l-glycine. Recommendations on how to counsel and manage individuals with the mild phenotype detected by NBS are required.

Introduction Cystinuria is an inherited disorder of the renal dibasic amino acid transporter and leads to increased urinary cystine, ornithine, lysine and arginine excretion. Prevalence is estimated at 1 in [...], Background Cystinuria is an inherited disorder of a renal tubular amino acid transporter and leads to increased cystine excretion with the risk of urinary stone formation. Phenotypical classification is based on urinary amino acid concentration as type I (silent), type non-I (hyper-excretors), mixed or untyped. Genotypic classification is based on mutations in SLC3A1 (type A) or SLC7A9 (type B). Case-Diagnosis/Treatment We present six family members with a complex phenotypic profile based on mutations in both genes. The index patient presents a known homozygous mutation (p.T189M) in SLC3A1 and a homozygous mutation (c.225C > T) in SLC7A9. Based on a bio-informatics analysis and published findings, we considered p.T189M to be pathogenic and initially classified c.225C > T as a silent variant. However, segregation analysis detected homozygosity for p.T189M also in non-affected individuals, whereas homozygous c.225C > T segregated with the phenotype. RNA studies confirmed c.225C > T to cause aberrant splicing. Conclusions Based on our findings, we conclude that c.225C > T in SLC7A9 determines the clinical phenotype in this family, whereas additional SLC3A1 mutations aggravate the phenotype in heterozygotes for c.225C > T in SLC7A9 without resulting in cystinuria in the homozygous state. Our results underline the need for careful biochemical characterization of family members of an index case of cystinuria. Genetic analysis of both cystinuria genes may be necessary due to the synergistic effects of mutations in two genes. Keywords Cystinuria * Digenic inheritance * SLC3A1 * SLC7A9

Classical organic acidemias (OAs) result from defective mitochondrial catabolism of branched‐chain amino acids (BCAAs). Abnormal mitochondrial function relates to oxidative stress, ectopic lipids and insulin resistance (IR). We investigated whether genetically impaired function of mitochondrial BCAA catabolism associates with cardiometabolic risk factors, altered liver and muscle energy metabolism, and IR. In this case‐control study, 31 children and young adults with propionic acidemia (PA), methylmalonic acidemia (MMA) or isovaleric acidemia (IVA) were compared with 30 healthy young humans using comprehensive metabolic phenotyping including in vivo 31P/1H magnetic resonance spectroscopy of liver and skeletal muscle. Among all OAs, patients with PA exhibited abdominal adiposity, IR, fasting hyperglycaemia and hypertriglyceridemia as well as increased liver fat accumulation, despite dietary energy intake within recommendations for age and sex. In contrast, patients with MMA more frequently featured higher energy intake than recommended and had a different phenotype including hepatomegaly and mildly lower skeletal muscle ATP content. In skeletal muscle of patients with PA, slightly lower inorganic phosphate levels were found. However, hepatic ATP and inorganic phosphate concentrations were not different between all OA patients and controls. In patients with IVA, no abnormalities were detected. Impaired BCAA catabolism in PA, but not in MMA or IVA, was associated with a previously unrecognised, metabolic syndrome‐like phenotype with abdominal adiposity potentially resulting from ectopic lipid storage. These findings suggest the need for early cardiometabolic risk factor screening in PA. [ABSTRACT FROM AUTHOR]

Background: Cystinuria is an inherited disorder of a renal tubular amino acid transporter and leads to increased cystine excretion with the risk of urinary stone formation. Phenotypical classification is based on urinary amino acid concentration as type I (silent), type non-I (hyper-excretors), mixed or untyped. Genotypic classification is based on mutations in SLC3A1 (type A) or SLC7A9 (type B). Case-Diagnosis/Treatment: We present six family members with a complex phenotypic profile based on mutations in both genes. The index patient presents a known homozygous mutation (p.T189M) in SLC3A1 and a homozygous mutation (c.225C > T) in SLC7A9. Based on a bioinformatics analysis and published findings, we considered p.T189M to be pathogenic and initially classified c.225C > T as a silent variant. However, segregation analysis detected homozygosity for p.T189M also in non-affected individuals, whereas homozygous c.225C > T segregated with the phenotype. RNA studies confirmed c.225C > T to cause aberrant splicing. Conclusions: Based on our findings, we conclude that c.225C > T in SLC7A9 determines the clinical phenotype in this family, whereas additional SLC3A1 mutations aggravate the phenotype in heterozygotes for c.225C > T in SLC7A9 without resulting in cystinuria in the homozygous state. Our results underline the need for careful biochemical characterization of family members of an index case of cystinuria. Genetic analysis of both cystinuria genes may be necessary due to the synergistic effects of mutations in two genes. [ABSTRACT FROM AUTHOR]

For realistic modelling of reinforced concrete structures, non-linear models are often inevitable, which raises the question of an appropriate safety format for non-linear analysis. This paper gives an overview of available safety formats and discusses their advantages and disadvantages. An analysis of available round robin tests and modelling competitions shows that current safety formats do not properly account for the modelling uncertainty of non-linear analysis. Based on this observation a new safety format was proposed which allows one to explicitly account for the modelling uncertainty. To avoid any interaction of the modelled response with the safety format, the mean in situ material parameters should be used in the non-linear analysis and a resistance safety factor is used to assure the intended reliability level. The application of the new safety format to beam sections loaded in bending showed that it offers a reliability level that is in good agreement with the target reliability. [ABSTRACT FROM AUTHOR]

Corrosion of reinforcement affects the bond mechanism between reinforcement and concrete, and thus the anchorage. Reliable models describing this are needed especially for assessment of the load-carrying capacity of existing structures. This paper presents an analytical one-dimensional model for bond-slip response of corroded reinforcement. The proposed model is an extension of the bond-slip model given in the CEB-FIP Model Code 1990, and is practically applicable for structural analyses to determine the load-carrying capacity of corroded structures. Furthermore, the anchorage length needed to anchor the yield force is calculated from the bond slip, using the one-dimensional bond-slip differential equation. Results of the proposed model are compared with experimental results as well as results from an advanced three-dimensional finite element model. The suggested model is shown to give results that are consistent with the physical behaviour. [ABSTRACT FROM PUBLISHER]

Throughout oogenesis, huge amounts of RNA are produced that are needed for early development. Early stages of oocyte development are characterized by high transcriptional activity whereas translation of maternal RNA dominates late stages. Nuclear pore complexes (NPCs), located in the nuclear envelope (NE), mediate bidirectional macromolecule exchange between the nuclear and cytosolic compartments including RNA export. Here, we report on structural correlates of this transport pathway at single NPC level. Using atomic force microscopy (AFM), we imaged the nucleoplasmic ("inner") surface of the NE of Xenopus laevis oocytes in different stages of development. We found that NPC frequency per nucleus increases with maturation. However, individual NPCs are more active in immature stages. In early stages, known for high transcriptional activity, we found nearly 10% of NPC central channels plugged with a 400-800 kDa mass. In contrast, the incidence of plugged NPCs was below 1% in late oocyte stages. On-site RNA digestion led to a change in plug shape from prominent to flat while plug mass decreased by almost 20%. Quantitative AFM analysis revealed that RNase exposure reduced total nucleoplasmic NPC mass by about 58 and 25% in early and late stage oocytes, respectively. We conclude: (i) NPCs of immature oocytes are more active in RNA transport, (ii) Plugs identified at the nucleoplasmic entrance of NPC central channels represent ribonucleoproteins exiting the nucleus, (iii) RNA is a structural component of the NPC nanomachine., ((c) 2006 Wiley-Liss, Inc.)