Numerical Assessment of Fibre Inclusion in a Load Transfer Platform for Pile-Supported Embankments over Soft Soil

© 2016 ASCE. This study presents the results of a numerical investigation in the performance of natural fibre reinforced load transfer platform (NFRLTP) for pile supported embankment construction over soft soil. A numerical analysis based on finite element method (FEM) was carried out on an NFRLTP pile-supported embankment in a two-dimensional plane strain condition. The effects of natural fibre inclusion in the load transfer platform on the stress transfer mechanism, generation and dissipation of excess pore water pressure have been analyzed and discussed in detail. The findings indicate that natural fibre reinforced soil as a load transfer platform facilitated the load transfer process from the embankment to piles, while decreases the intensity of load transferred to soft soil, the excess pore water pressure and the overall settlement

ATP release from the human ureter on distension and P2X3 receptor expression on suburothelial sensory nerves

It is not clear how the increase in intraluminal pressure behind an obstructing ureteric calculus causes an increase in action potential frequency in ureteric sensory nerves so the pain messages are transmitted to the brain. It has been proposed that ureteric distension causes urothelial release of ATP, which activates purinoceptors on suburothelial nociceptive sensory nerves. The purpose of this study was to determine whether distension of the human ureter results in the release of ATP and whether the nociceptive P2 receptor, P2X3, is expressed on suburothelial sensory nerves in the human ureter. Human ureter segments were perfused with Krebs solution and intermittently distended to a range of pressures. Samples of perfusate were collected throughout and the ATP concentration ([ATP]) was determined using a luciferin-luciferase assay. Sections of ureter were stained using antibodies against P2X3 and capsaicin receptors (TRPV1). [ATP] rose to more than 10 times baseline levels after distension beyond a threshold of 25–30 cmH2O. Immunofluorescence studies on consecutive frozen sections showed that suburothelial nerves stained positively for P2X3 and capsaicin receptors, with no staining in controls. These findings are consistent with the hypothesis that purinergic signalling is involved in human ureteric mechanosensory transduction, leading to nociception

Prediction error and accuracy of intraocular lens power calculation in pediatric patient comparing SRK II and Pediatric IOL Calculator

<p>Abstract</p> <p>Background</p> <p>Despite growing number of intraocular lens power calculation formulas, there is no evidence that these formulas have good predictive accuracy in pediatric, whose eyes are still undergoing rapid growth and refractive changes. This study is intended to compare the prediction error and the accuracy of predictability of intraocular lens power calculation in pediatric patients at 3 month post cataract surgery with primary implantation of an intraocular lens using SRK II versus Pediatric IOL Calculator for pediatric intraocular lens calculation. Pediatric IOL Calculator is a modification of SRK II using Holladay algorithm. This program attempts to predict the refraction of a pseudophakic child as he grows, using a Holladay algorithm model. This model is based on refraction measurements of pediatric aphakic eyes. Pediatric IOL Calculator uses computer software for intraocular lens calculation.</p> <p>Methods</p> <p>This comparative study consists of 31 eyes (24 patients) that successfully underwent cataract surgery and intraocular lens implantations. All patients were 12 years old and below (range: 4 months to 12 years old). Patients were randomized into 2 groups; SRK II group and Pediatric IOL Calculator group using envelope technique sampling procedure. Intraocular lens power calculations were made using either SRK II or Pediatric IOL Calculator for pediatric intraocular lens calculation based on the printed technique selected for every patient. Thirteen patients were assigned for SRK II group and another 11 patients for Pediatric IOL Calculator group. For SRK II group, the predicted postoperative refraction is based on the patient's axial length and is aimed for emmetropic at the time of surgery. However for Pediatric IOL Calculator group, the predicted postoperative refraction is aimed for emmetropic spherical equivalent at age 2 years old. The postoperative refractive outcome was taken as the spherical equivalent of the refraction at 3 month postoperative follow-up. The data were analysed to compare the mean prediction error and the accuracy of predictability of intraocular lens power calculation between SRK II and Pediatric IOL Calculator.</p> <p>Results</p> <p>There were 16 eyes in SRK II group and 15 eyes in Pediatric IOL Calculator group. The mean prediction error in the SRK II group was 1.03 D (SD, 0.69 D) while in Pediatric IOL Calculator group was 1.14 D (SD, 1.19 D). The SRK II group showed lower prediction error of 0.11 D compared to Pediatric IOL Calculator group, but this was not statistically significant (p = 0.74). There were 3 eyes (18.75%) in SRK II group achieved acccurate predictability where the refraction postoperatively was within ± 0.5 D from predicted refraction compared to 7 eyes (46.67%) in the Pediatric IOL Calculator group. However the difference of the accuracy of predictability of postoperative refraction between the two formulas was also not statistically significant (p = 0.097).</p> <p>Conclusions</p> <p>The prediction error and the accuracy of predictability of postoperative refraction in pediatric cataract surgery are comparable between SRK II and Pediatric IOL Calculator. The existence of the Pediatric IOL Calculator provides an alternative to the ophthalmologist for intraocular lens calculation in pediatric patients. Relatively small sample size and unequal distribution of patients especially the younger children (less than 3 years) with a short time follow-up (3 months), considering spherical equivalent only.</p

Metabolic alterations during the growth of tumour spheroids

Solid tumours undergo considerable alterations in their metabolism of nutrients in order to generate sufficient energy and biomass for sustained growth and proliferation. During growth, the tumour microenvironment exerts a number of influences (e.g. hypoxia and acidity) that affect cellular biology and the flux or utilisation of fuels including glucose. The tumour spheroid model was used to characterise the utilisation of glucose and describe alterations to the activity and expression of key glycolytic enzymes during the tissue growth curve. Glucose was avidly consumed and associated with the production of lactate and an acidified medium, confirming the reliance on glycolytic pathways and a diminution of oxidative phosphorylation. The expression levels and activities of hexokinase, phosphofructokinase-1, pyruvate kinase and lactate dehydrogenase in the glycolytic pathway were measured to assess glycolytic capacity. Similar measurements were made for glucose-6-phosphate dehydrogenase, the entry point and regulatory step of the pentose-phosphate pathway (PPP) and for cytosolic malate dehydrogenase, a key link to TCA cycle intermediates. The parameters for these key enzymes were shown to undergo considerable variation during the growth curve of tumour spheroids. In addition, they revealed that the dynamic alterations were influenced by both transcriptional and posttranslational mechanisms

Metabolic alterations during the growth of tumour spheroids

Solid tumours undergo considerable alterations in their metabolism of nutrients in order to generate sufficient energy and biomass for sustained growth and proliferation. During growth, the tumour microenvironment exerts a number of influences (e.g. hypoxia and acidity) that affect cellular biology and the flux or utilisation of fuels including glucose. The tumour spheroid model was used to characterise the utilisation of glucose and describe alterations to the activity and expression of key glycolytic enzymes during the tissue growth curve. Glucose was avidly consumed and associated with the production of lactate and an acidified medium, confirming the reliance on glycolytic pathways and a diminution of oxidative phosphorylation. The expression levels and activities of hexokinase, phosphofructokinase-1, pyruvate kinase and lactate dehydrogenase in the glycolytic pathway were measured to assess glycolytic capacity. Similar measurements were made for glucose-6-phosphate dehydrogenase, the entry point and regulatory step of the pentose-phosphate pathway (PPP) and for cytosolic malate dehydrogenase, a key link to TCA cycle intermediates. The parameters for these key enzymes were shown to undergo considerable variation during the growth curve of tumour spheroids. In addition, they revealed that the dynamic alterations were influenced by both transcriptional and posttranslational mechanisms

In silico transcriptional regulation and functional analysis of dengue shock syndrome associated SNPs in PLCE1 and MICB genes

YesSingle nucleotide polymorphisms (SNPs) in PLCE1 and MICB genes increase risk for the development of dengue shock syndrome (DSS). We used Bioinformatics tools to predict alterations at the transcriptional and posttranslational levels driven by PLCE1 and MICB SNPs associated with DSS. Functional and phenotypic analysis conducted to determine deleterious SNPs and impact of amino acid substitution on the structure and function of proteins identified rs2274223 (H1619R) as deleterious to protein coding as it induces structural change in the C2 domain of PLCε, with the mutant residue more positively charged than the wild-type residue (RMSD score, 1.75 Å).Moreover, rs2274223 condenses the chromatinrepressing PLCε expression in DSS. Briefly, this study presents the impact of a single nucleotide transition at SNPs associated with DSS on differential protein binding patterns with PLCE1 and MICB genes and on protein structure modification and their possible role in the pathogenesis of DSS

Differential cell line susceptibility to the emerging Zika virus: implications for disease pathogenesis, non-vector-borne human transmission and animal reservoirs

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Experimental Gastric Carcinogenesis in Cebus apella Nonhuman Primates

The evolution of gastric carcinogenesis remains largely unknown. We established two gastric carcinogenesis models in New-World nonhuman primates. In the first model, ACP03 gastric cancer cell line was inoculated in 18 animals. In the second model, we treated 6 animals with N-methyl-nitrosourea (MNU). Animals with gastric cancer were also treated with Canova immunomodulator. Clinical, hematologic, and biochemical, including C-reactive protein, folic acid, and homocysteine, analyses were performed in this study. MYC expression and copy number was also evaluated. We observed that all animals inoculated with ACP03 developed gastric cancer on the 9th day though on the 14th day presented total tumor remission. In the second model, all animals developed pre-neoplastic lesions and five died of drug intoxication before the development of cancer. The last surviving MNU-treated animal developed intestinal-type gastric adenocarcinoma observed by endoscopy on the 940th day. The level of C-reactive protein level and homocysteine concentration increased while the level of folic acid decreased with the presence of tumors in ACP03-inoculated animals and MNU treatment. ACP03 inoculation also led to anemia and leukocytosis. The hematologic and biochemical results corroborate those observed in patients with gastric cancer, supporting that our in vivo models are potentially useful to study this neoplasia. In cell line inoculated animals, we detected MYC immunoreactivity, mRNA overexpression, and amplification, as previously observed in vitro. In MNU-treated animals, mRNA expression and MYC copy number increased during the sequential steps of intestinal-type gastric carcinogenesis and immunoreactivity was only observed in intestinal metaplasia and gastric cancer. Thus, MYC deregulation supports the gastric carcinogenesis process. Canova immunomodulator restored several hematologic measurements and therefore, can be applied during/after chemotherapy to increase the tolerability and duration of anticancer treatments