6,319 research outputs found

    Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

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    Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

    Distinct regulatory networks control toxin gene expression in elapid and viperid snakes

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    Background Venom systems are ideal models to study genetic regulatory mechanisms that underpin evolutionary novelty. Snake venom glands are thought to share a common origin, but there are major distinctions between venom toxins from the medically significant snake families Elapidae and Viperidae, and toxin gene regulatory investigations in elapid snakes have been limited. Here, we used high-throughput RNA-sequencing to profile gene expression and microRNAs between active (milked) and resting (unmilked) venom glands in an elapid (Eastern Brown Snake, Pseudonaja textilis), in addition to comparative genomics, to identify cis- and trans-acting regulation of venom production in an elapid in comparison to viperids (Crotalus viridis and C. tigris). Results Although there is conservation in high-level mechanistic pathways regulating venom production (unfolded protein response, Notch signaling and cholesterol homeostasis), there are differences in the regulation of histone methylation enzymes, transcription factors, and microRNAs in venom glands from these two snake families. Histone methyltransferases and transcription factor (TF) specificity protein 1 (Sp1) were highly upregulated in the milked elapid venom gland in comparison to the viperids, whereas nuclear factor I (NFI) TFs were upregulated after viperid venom milking. Sp1 and NFI cis-regulatory elements were common to toxin gene promoter regions, but many unique elements were also present between elapid and viperid toxins. The presence of Sp1 binding sites across multiple elapid toxin gene promoter regions that have been experimentally determined to regulate expression, in addition to upregulation of Sp1 after venom milking, suggests this transcription factor is involved in elapid toxin expression. microRNA profiles were distinctive between milked and unmilked venom glands for both snake families, and microRNAs were predicted to target a diversity of toxin transcripts in the elapid P. textilis venom gland, but only snake venom metalloproteinase transcripts in the viperid C. viridis venom gland. These results suggest differences in toxin gene posttranscriptional regulation between the elapid P. textilis and viperid C. viridis. Conclusions Our comparative transcriptomic and genomic analyses between toxin genes and isoforms in elapid and viperid snakes suggests independent toxin regulation between these two snake families, demonstrating multiple different regulatory mechanisms underpin a venomous phenotype

    Gastrointestinal delivery of codfish skin-derived collagen hydrolysates: deep eutectic solvent extraction and bioactivity analysis

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    The fishing industry produces substantial by-products, such as heads, skins, bones, and scales, rich in collagen—a prevalent protein in these materials. However, further application of deep eutectic solvent-based extraction remains unexplored. In this study, we extracted collagen with urea: propanoic acid mixture (U:PA; 1:2) with a 2.2% yield, followed by enzymatic hydrolysis with alcalase for 120 min. The resulting bioactive peptides demonstrated notable antioxidant activity (961 µmol TE) and antihypertensive properties (39.3% ACE inhibition). Subsequently, we encapsulated 39.3% of these hydrolysates in chitosan-TPP capsules, which released about 58% of their content, primarily in the intestine, as mimicked in the in vitro model of the gastrointestinal tract. Although the digestion process did not significantly alter the size of the non-encapsulated collagen peptides, it did influence their health benefits. The promising results suggest that further research could optimize the use of collagen from fish by-products, potentially offering a sustainable source for health products.N/

    Relationship between objective and perceived sugar content on consumers perceptions about breakfast cereals

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    In Portugal, about one-fourth of the adult population exceeds the recommended daily amount of free sugars intake. This excessive consumption may be due to a lack of awareness of the sugar content of commonly available processed products. In two studies, we explored this assumption by asking participants (convenient samples) to evaluate the sugar content of breakfast cereals based on the front-of-packaging images and analyzed the correspondence between subjective and objective sugar content. In Study 1 (n = 90), all the exemplars were high in sugar, whereas in Study 2 (n = 85), exemplars contained low, moderate, or high sugar content. Study 1 revealed that participants accurately perceived all exemplars as containing high sugar. Study 2 showed that participants were able to distinguish between different levels of sugar content, which impacted how they evaluated the products in other dimensions. Specifically, besides being rated as having more sugar, products with objective high (vs. moderate or low) sugar content were perceived as tastier, as having more fat and calories, but also as less healthful. Notably, participants who perceived the exemplars as containing more sugar also reported using nutritional information more often and consuming these products less frequently. These findings suggest that awareness of products' sugar content may not be sufficient to address the problem of excessive sugar intake. Intervention should also focus on building up consumers' knowledge about sugar intake guidelines and its negative health outcomes.info:eu-repo/semantics/publishedVersio

    Tidal Turbine Benchmarking Project:Stage I - Steady Flow Blind Predictions

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    This paper presents the first blind prediction stage of the Tidal Turbine Benchmarking Project being conducted and funded by the UK's EPSRC and Supergen ORE Hub. In this first stage, only steady flow conditions, at low and elevated turbulence (3.1%) levels, were considered. Prior to the blind prediction stage, a large laboratory scale experiment was conducted in which a highly instrumented 1.6m diameter tidal rotor was towed through a large towing tank in well-defined flow conditions with and without an upstream turbulence grid. Details of the test campaign and rotor design were released as part of this community blind prediction exercise. Participants were invited to use a range of engineering modelling approaches to simulate the performance and loads of the turbine. 26 submissions were received from 12 groups from across academia and industry using solution techniques ranging from blade resolved computational fluid dynamics through actuator line, boundary integral element methods, vortex methods to engineering Blade Element Momentum methods. The comparisons between experiments and blind predictions were extremely positive helping to provide validation and uncertainty estimates for the models, but also validating the experimental tests themselves. The exercise demonstrated that the experimental turbine data provides a robust data set against which researchers and design engineers can test their models and implementations to ensure robustness in their processes, helping to reduce uncertainty and provide increased confidence in engineering processes. Furthermore, the data set provides the basis by which modellers can evaluate and refine approaches

    Technologies developed in precision agriculture.

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    Introduction. Collecting, storing, and analyzing data in PA. Identification of soil spatial variability: Soil sampling; Electrical conductivity. Identification of crop spatial variability: Productivity mapping; Proximal sensing; Suborbital and remote sensing. Cloud data storage: Data analysis in PA: Data mining and pattern extraction; Filtering tools and data cleaning; Geostatistics and spatial interpolation; Outlining management zones; On-farm experiments, spatial correlation, and recommendations. Practical applications in precision agriculture: Characterization of the spatial variability in southern Minas Gerais specialty coffee production systems; Spatial and spectral behavior in sugarcane and its correlation to soil electrical conductivity; PA technologies in fiber and grain management systems in the state of Mato Grosso; RPA applications in different crops. Final considerations

    Common and rare genetic risk variants in age-related macular degeneration and genetic risk score in the Coimbra eye study.

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    PURPOSE: To determine the contribution of common and rare genetic variants in age-related macular degeneration (AMD) in a Portuguese population from the Coimbra Eye Study (CES), and the genetic risk score (GRS). METHODS: Participants underwent ophthalmologic examination and imaging. A centralized reading centre performed AMD staging. Genetic sequencing was carried out with the EYE-RISK assay. Sixty-nine single nucleotide polymorphisms (SNPs) were genotyped and tested for association with AMD. Case-control and progression-to-AMD analyses were performed using logistic regression to assess allelic odds ratio (OR) at a 95% confidence interval (CI) for each variant. GRS was calculated for cases/controls and progressors/non-progressors. Cumulative impact of rare variants was compared between cases/controls using logistic regression. RESULTS: In case-control analysis (237 cases/640 controls) variants associated with risk of disease were: ARMS2 rs10490924, ARMS2_HTRA1 rs3750846, CFH rs35292876, SLC16A8 rs8135665, TGFBR1 rs1626340. Major risk variants ARMS2/HTRA1 rs3750846, CFH rs570618 and C3 rs2230199 had unexpected lower allele frequency (AF), and the highest risk-conferring variant was a rare variant, CFH rs35292876 (OR, 2.668; p-value = 0.021). In progression-to-AMD analysis (137 progressors/630 non-progressors), variants associated with risk of progression were ARMS2 rs10490924, ARMS2_HTRA1 rs3750846, CFH rs35292876. GRS of cases/controls was 1.124 ± 1.187 and 0.645 ± 1.124 (p-value < 0.001), and of progressors/non-progressors was 1.190 ± 1.178 and 0.669 ± 1.141 (p-value < 0.001). Higher proportion of pathogenic rare CFH variants was observed in cases (OR, 9.661; p-value < 0.001). CONCLUSIONS: Both common and rare variants were associated with AMD, but a CFH rare variant conferred the highest risk of disease while three major risk variants had a lower-than-expected AF in our population originary from a geographic region with lower prevalence of AMD. GRS was still significantly higher in AMD patients. Damaging CFH rare variants were cumulatively more common in AMD cases

    Novel high entropy alloys as binder in cermets: From design to sintering

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    In recent years a new group of alloys has emerged breaking with the classical alloying concepts of physical metallurgy, high entropy alloys (HEA). Their main characteristic is that these alloys present 4 or 5 main elements increasing the entropy of the system and favouring the formation of a single phase. The disordered solid solution leads to develop an alloy with improved properties, in particular high thermal stability, hardness and strength. These properties make this group of alloys attractive as potential candidates for alternative binders in hard materials. In this work, two new compositions have been designed with the aim of obtaining a single BCC phase, reducing the cost and minimizing the presence of critical elements using elements that can present good potential properties for a cermet and with low toxicity and price such as Al, Cr, Mo, Ni, Fe and Ti. The design has been made based on the composition calculation applying the HEA phase formation empirical rules from literature in combination with thermodynamic simulations by Calphad method. The viability of the compositions has been studied through the processing of the compositions by casting and the study of wettability and solubility at high temperature on the hard phase of TiCN. Once the chosen compositions have been validated as competitive binders, cermets have been consolidated by spark plasma sintering (SPS) and the influence of the compositions on the mechanical properties of the compound materials has been studied

    Corncob as Carbon Source in the Production of Xanthan Gum in Different Strains Xanthomonas sp.

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    Xanthan gum (XG) is a biopolymer obtained in fermentation and used as a rheology control agent in aqueous systems and in stabilizing emulsions and suspensions. XG, together with other polysaccharides, can form soft, cohesive composite gels. The carbon source in the fermentative process is responsible for one-third of the production costs, and the search for less expensive and sustainable alternatives is ongoing. The use of agricultural residues such as the corncob is highly suggestive due to their abundance. This study aims to evaluate the use of derived hemicellulose fractions from the alkaline extraction of corncob as a carbon source in the production of XG in trials using four strains of Xanthomonas sp. (629, 1078, 254, and S6). The results indicate that strain 629 provides the higher yield (8.37 &plusmn; 5.75 g L&minus;1) while using a fermentation medium containing a carbon source of saccharose (1.25%), hemicellulose fractions (3.75%), and salts. In this same medium, the strain 629 produces gum in 3% aqueous solution, showing the higher apparent viscosity (9298 &plusmn; 31 mPa s&minus;1) at a shear rate of 10 s&minus;1 at 25 &deg;C. In conclusion, corncob is proven to be a promising sustainable alternative carbon source in the obtention of XG, improving the economic viability of the process within a biorefinery context. Saccharose must, however, also be included in the fermentation medium
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