186 research outputs found

    Observations on the desiccation and cracking of clay layers

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    Waterways and lakes in low-lying delta areas require regular dredging for maintenance. Often these sediments are placed on land, where they are allowed to ripen through a combination of drainage, consolidation and evaporation. When cracks develop during desiccation, the physical response of the soil is affected by changes in the overall strength, stiffness and permeability of the material. To better identify how cracks form and propagate, a series of tests was carried out in a controlled laboratory environment on samples of drying clay slurries under different initial and boundary conditions. The outcomes of this study indicate that the results from laboratory small scale models must be carefully analyzed, as they depend on the area and the thickness of the sample. However, common features from the different tests can be identified, which are mostly related to the intrinsic behavior of the material. For instance, the water content at which cracks initiate depends mostly on the drying rate and not only on the initial water content. Typically for the clayey soil investigated, the cracking water content is well above the shrinkage limit and in some instances even above the liquid limit. Cracks can form anywhere a defect is encountered, but it was observed that they propagate in horizontal directions below the soil surface. On the soil surface they tend to intersect with each other perpendicularly, suggesting that they are dominated by a tensile stress regime. Shear stresses also influence the response, but mainly near the boundaries of the samples, due to the interface friction

    Guts! Dietary modulation of innate defense

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    Necrotizing enterocolitis (NEC) is the most common gastro-intestinal emergency in the neonatal intensive care. The incidence of NEC ranges from 0.3 to 2.4 infants per 1000 live births, with nearly 70% of cases occurring in infants born at less than 36 weeks of gestation. The incidence of NEC varies, affecting 2-5% of all premature infants.[1] The overall mortality for NEC ranges from 10% to 50%.[2] Despite optimal medical and surgical management of NEC, infants that recover from the disease suffer from substantial morbidity, such as intestinal obstruction as a consequence of scarring, liver failure due to a prolonged requirement for total parenteral nutrition, short bowel syndrome with intestinal failure and associated nutritional deficiencies, and associated defects in growth and development.[3-4] Length of hospital stay in infants with surgical NEC and medically treated NEC exceeds those of controls by 60 days and 22 days respectively. Based on length of stay, the estimated total hospital charges for infants with surgical NEC in the USA averaged 186200inexcessofthoseforcontrolsand186 200 in excess of those for controls and 73 700 more for infants with medical NEC. The yearly additional hospital charges for NEC were $216 666 per survivor.[5] Hence, NEC is a significant and growing health concern for prematurely born infants. The costs in the Netherlands are not exactly known, but will not be very different. As the number of preterm births has almost doubled over the past two decades in the Netherlands (Perinatale Registratie Nederland) and the United States (National Vital Statistics Report 2003), this burden will continue to increase. In addition, recently the national policy has changed into a more liberal approach to the lower limit of viability. More very immature infants (from a gestational age of 24 weeks onwards) will be given a chance to survive, with consequently more risk of developing NEC

    Modelling desiccation cracking in a homogenous soil clay layer: comparison between different hypotheses on constitutive behaviour

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    Desiccation cracks are usually thought to start from the surface of an evaporating soil layer, and the available simplified models for crack initiation and propagation are based on this hypothesis. On the contrary, experimental results on a Dutch river clay showed that cracks in an evaporating soil layer may start and propagate below the surface, confirming earlier findings by other researchers. A simple one-dimensional model was set up to analyse the consequences of different hypotheses about the material behaviour on the crack onset in a homogenous soil layer undergoing surface drying. The results of the model show that dependence of the material behaviour on the rate of water content change is a necessary requirement for cracks to initiate below the surface. The conclusion suggests that, to properly understand cracking in an evaporating soil layer, an intrinsic time scale for the mechanical response must be accounted for, among all the other factors which were previously highlighted by other researchers. The key factor to predict crack onset below the surface is the dependence of the drying branch of the water retention curve of the compressible soil on the rate of drying, which would be justified by a rate dependent fabric evolution

    Ibuprofen treatment after the first days of life in preterm neonates with patent ductus arteriosus

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    Aim: Patent ductus arteriosus (PDA) is treated with ibuprofen and it is known that the clearance of ibuprofen increases with postnatal age. We aimed to study whether postnatal age-adjusted ibuprofen dosages improve the effectiveness of treatment compared to standard ibuprofen dosages after the first days of life. Methods: A historical cohort of 207 preterm neonates treated with standard ibuprofen dosages (Group A; 2011–2015) was compared to a prospective cohort of 66 preterm neonates treated with postnatal age-adjusted ibuprofen dosages (Group B; 2015–2016). Results: Both groups had comparable background characteristics. Treatment was started after median 6 (25–75th percentile: 4–11) and 5 (25–75th percentile: 4–11) days and effectiveness was 33.2 and 44.7% (p =.17) in groups A and B, respectively. No hemodynamically significant PDA was found in 23/49 (46.9%) of the patients born before 28 weeks after adjusted ibuprofen dosages compared to 48/162 (29.6%) after standard ibuprofen dosages (p =.04). There were significantly more reversible side effects with the postnatal age-adjusted ibuprofen dosages (p =.04). Conclusions: There seems to be a trend to higher effectiveness with the adjusted ibuprofen dosages in preterm neonates before 28 weeks, but it is associated with more reversible side effects

    High-level integration of murine intestinal transcriptomics data highlights the importance of the complement system in mucosal homeostasis.

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    BACKGROUND: The mammalian intestine is a complex biological system that exhibits functional plasticity in its response to diverse stimuli to maintain homeostasis. To improve our understanding of this plasticity, we performed a high-level data integration of 14 whole-genome transcriptomics datasets from samples of intestinal mouse mucosa. We used the tool Centrality based Pathway Analysis (CePa), along with information from the Reactome database. RESULTS: The results show an integrated response of the mouse intestinal mucosa to challenges with agents introduced orally that were expected to perturb homeostasis. We observed that a common set of pathways respond to different stimuli, of which the most reactive was the Regulation of Complement Cascade pathway. Altered expression of the Regulation of Complement Cascade pathway was verified in mouse organoids challenged with different stimuli in vitro. CONCLUSIONS: Results of the integrated transcriptomics analysis and data driven experiment suggest an important role of epithelial production of complement and host complement defence factors in the maintenance of homeostasis

    Gut Microbiota, Probiotics and Diabetes

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    Diabetes is a condition of multifactorial origin, involving several molecular mechanisms related to the intestinal microbiota for its development. In type 2 diabetes, receptor activation and recognition by microorganisms from the intestinal lumen may trigger inflammatory responses, inducing the phosphorylation of serine residues in insulin receptor substrate-1, reducing insulin sensitivity. In type 1 diabetes, the lowered expression of adhesion proteins within the intestinal epithelium favours a greater immune response that may result in destruction of pancreatic β cells by CD8+ T-lymphocytes, and increased expression of interleukin-17, related to autoimmunity. Research in animal models and humans has hypothesized whether the administration of probiotics may improve the prognosis of diabetes through modulation of gut microbiota. We have shown in this review that a large body of evidence suggests probiotics reduce the inflammatory response and oxidative stress, as well as increase the expression of adhesion proteins within the intestinal epithelium, reducing intestinal permeability. Such effects increase insulin sensitivity and reduce autoimmune response. However, further investigations are required to clarify whether the administration of probiotics can be efficiently used for the prevention and management of diabetes

    Cloning, annotation and developmental expression of the chicken intestinal MUC2 gene

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    Intestinal mucin 2 (MUC2) encodes a heavily glycosylated, gel-forming mucin, which creates an important protective mucosal layer along the gastrointestinal tract in humans and other species. This first line of defense guards against attacks from microorganisms and is integral to the innate immune system. As a first step towards characterizing the innate immune response of MUC2 in different species, we report the cloning of a full-length, 11,359 bp chicken MUC2cDNA, and describe the genomic organization and functional annotation of this complex, 74.5 kb locus. MUC2 contains 64 exons and demonstrates distinct spatiotemporal expression profiles throughout development in the gastrointestinal tract; expression increases with gestational age and from anterior to posterior along the gut. The chicken protein has a similar domain organization as the human orthologue, with a signal peptide and several von Willebrand domains in the N-terminus and the characteristic cystine knot at the C-terminus. The PTS domain of the chicken MUC2 protein spans ~1600 amino acids and is interspersed with four CysD motifs. However, the PTS domain in the chicken diverges significantly from the human orthologue; although the chicken domain is shorter, the repetitive unit is 69 amino acids in length, which is three times longer than the human. The amino acid composition shows very little similarity to the human motif, which potentially contributes to differences in the innate immune response between species, as glycosylation across this rapidly evolving domain provides much of the musical barrier. Future studies of the function of MUC2 in the innate immune response system in chicken could provide an important model organism to increase our understanding of the biological significance of MUC2 in host defense and highlight the potential of the chicken for creating new immune-based therapies

    Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

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    OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies
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