The Inflammatory Prequel of Pediatric Appendicitis

AbstractBackground: Appendicitis is the most common disease requiring acute abdominal surgery in children, yet the pathogenesis of appendicitis is not fully understood. It can be challenging to diagnose appendicitis clinically, especially in young children, leading to high rates of initial misdiagnosis. It is not clear why some children are affected by a complicated disease course while others recover spontaneously. It has been proposed that different immune responses in different individuals propel the inflammation towards an uncomplicated or a complicated disease course. To date, there is no reliable measure to distinguish between patients with uncomplicated appendicitis and those with complicated appendicitis.Aims: To increase the knowledge of how the inflammatory processes anteceding pediatric appendicitis can be categorized, modulated, and detected.Methods: Papers I, IV and V were prospective clinical institution-based studies. Paper II was a retrospective institutionbased cohort study and Paper III a nationwide cohort study. In Paper I the diagnostic performances of four different clinical prediction scores for pediatric appendicitis were evaluated. In Papers II and III the associations of immunoglobulin E (IgE)-mediated allergy and complicated appendicitis in children were evaluated. In Paper IV we assessed the associations of biological stress, measured as hair cortisol concentrations (HCC) and pediatric appendicitis. In Paper V the associations of serum concentrations of IgE and T helper cell 2 (Th2)-associated cytokines with complicated appendicitis were evaluated.Results: The clinical prediction scores appendicitis inflammatory response (AIR) score and pediatric appendicitis risk calculator (pARC) displayed significantly higher specificity and positive predictive value and lower rates of negative appendectomies compared to the pediatric appendicitis score (PAS) and Alvarado score (I). Children with IgE-mediated allergy had a significantly reduced odds of complicated appendicitis (aOR 0.33 [95% CI 0.18-0.59], p<0.001 (II), and aOR 0.80 [95% CI 0.67-0.96], p=0.021 (III)). The risk of complicated appendicitis among allergic children was reduced by one-third compared to that in non-allergic children (IR 0.13 vs 0.20 per 1000 person-years, HR 0.68 [95% CI 0.58-0.81], p<0.001), while the risk of uncomplicated appendicitis did not vary with allergy status (IR 0.91 vs 0.91, HR 1.00 [95% CI 0.94-1.07], p=0.932). Seasonal antigen exposure was a protective factor for complicated appendicitis (aOR 0.82 [95% CI 0.71-0.94], p=0.004), and ongoing antihistamine medication was a risk factor (aOR 2.28 [95% CI 1.21-4.28], p=0.012) (III). An increase in HCC was associated with an increased risk of appendicitis (aOR 10.76 [95% CI 2.50-46.28], p=0.001) and complicated appendicitis (aOR 7.86 [95% CI 1.20-51.63], p=0.03) (IV). High concentrations of IL-13 were associated with an increased risk of complicated appendicitis (aOR 1.02 [95% CI 1.01-1.04], p=0.011). Serum concentrations of IgE, IL-4, and IL-9 were not significantly associated with the risk of complicated appendicitis (V).Conclusions: AIR score and pARC are superior to the PAS and Alvarado score for diagnosing appendicitis in children. Children with allergy have a lower risk of complicated appendicitis, but the same risk of uncomplicated appendicitis, compared to non-allergic children. Increased stress, measured as an increase in HCC, is associated with an increased risk of appendicitis and complicated appendicitis in children. High levels of IL-13 seem to be associated with an increased risk of complicated appendicitis in children

Comparison of Models for Calculation of the Thermodynamic Properties of NH3-CO2-H2O Mixture

Couple of models have been developed to calculate thermodynamic properties of NH3-CO2-H2O systems. These models are typically an equation of state for the vapor phase and an activity coefficient model for the liquid phase (Que & Chen, 2011). The activity coefficient models can be divided into three groups based on previous studies, Pitzer model, electrolyte Non Random Two Liquid (e-NRTL) model and extended UNIQUAC model. Que & Chen (2011) deem the e-NRTL model the model the most suitable for process modelling and simulations since it requires only binary interaction parameters and makes use of mole fraction concentration scale consistently for both the short range local compositions interactions and the long range Debey-Huckel expression. Darde (2011) compared the built in e-NRTL model from Aspen Plus to an upgraded version of the extended UNIQUAC model developed by Thomsen et al. (1996). His findings were that the extended UNIQUAC model is significantly more accurate than the e-NRTL model from Aspen. He does mention that if the binary interaction parameters were better fitted to experimental data for NH3-CO2-H2O mixture, the e-NRTL model might become more competitive with the extended UNIQUAC model. Since then the e-NRTL model has been modified in this way by couple of authors, included Que & Chen (2011) and Niu et al. (2013). Both of their adjusted models have then been used by other authors for process modelling, for example Zhang & Guo (2014) used the model with adjusted parameters from Niu et al. (2013) and Liu et al. (2015) used the modified model from Que & Chen (2011). In this paper the extended UNIQUAC model is compared with the e-NRTL thermodynamic model that is built into the most recent version of Aspen Plus, and two modified e-NRTL models; the one developed by Que and Chen (2011) and a new fit. This is done to confirm if the modified models can reach similar accuracy as the extended UNIQUAC model and how much more accurate they are compared to the built in model in Aspen Plus

Kompetanseløft for åpne barnehager (KOMÅP)

publishedVersionLe 70 S

Evaluation of bioactivity of fucoidan from laminaria with in vitro human cell cultures (THP-1)

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesBackground: Seaweeds represent one of the few remaining food sources available globally which are not being fully utilized or even over utilized. Kelps (Laminaria spp.) are one of the numerous species of brown seaweeds, a popular marine vegetable, which has been used as a source of iodine and minerals for centuries. Kelps contain anionic polysaccharides called fucoidans heteroglycans with L-fucose units. Their monosaccharide composition, physicochemical and bioactive properties vary between seaweed species. The objective of this work was to evaluate the bioactive properties of laminaria fucoidan (L. digitata and L. hyperborea) toward THP-1 macrophages, a human macrophage like cell line, and investigate its potential antioxidant and immunomodulatory characteristics. Methods: THP-1 macrophages were incubated with five fucoidan concentrations. The Oxygen Radical Absorbance Capacity (ORAC) assay was determined for cell lysates and for the fucoidan extract, in addition to Total Polyphenol Content (TPC). Cytotoxicity of fucoidan was assessed by light microscopy, followed by XTT proliferation assay. Enzyme-linked immunosorbant assays (ELISA) were performed to determine concentrations of the secreted tumor necrosis factor a (TNF-a), interleukin 6 (IL-6), and interleukin 10 (IL-10). Results: Fucoidan did not affect macrophage ability to scavenge oxygen radicals (ORAC) confirming its antioxidant properties toward activated macrophages. The laminaria fucoidan extract at 100 mu g/ml concentration lowered macrophage viability. Lower concentrations of laminaria fucoidan did not have impact on cell viability. Very low concentration of fucoidan at 0.1 mu g/ml triggered secretion of TNF-alpha. However, IL-6 and interleukin IL-10 were expressed when concentration of applied fucoidan was 10 mu g/ml indicating bioactivity of laminaria fucoidan through immunomodulatory actions. Conclusions: The study demonstrated how laminaria fucoidan may have bioactive properties towards THP-1 macrophages. Changes in cytokine secretion between pro-inflammatory (TNF-alpha, and IL-6) and anti-inflammatory (IL-10) cytokines confirmed bioactivity of the laminaria fucoidan extracts.University of Iceland Research Fun

Validity of histology for the diagnosis of paediatric coeliac disease: a Swedish multicentre study.

Objective Histological evaluation of intestinal biopsies for the diagnosis of coeliac disease can be challenging and compatible with risk of misdiagnosis. The aim was to evaluate the agreement of pathological diagnosis for coeliac disease in children investigated at four major paediatric university hospitals in Sweden. Materials and methods Intestinal duodenal biopsies were collected from 402 children at median 9.7 years (1.4-18.3 years). A pathologist at each hospital performed the primary evaluation. A designated pathologist, blinded to the primary evaluation, performed a second Marsh classification of biopsies (M0 to M3c) taken from the bulb and duodenum separately. Kappa (κ) scores between first and second evaluation determined the agreement. Plasma samples were collected at the day of intestinal biopsy and analysed for tissue transglutaminase autoantibodies (tTGA) using radioligand-binding assays. Results Marsh scores were concordant in 229/356 biopsies (64%, κ = 0.52, p < 0.0001). Among discordant results, 15/127 (12%) showed M0 in distal duodenum but ≥ M2 in the bulb, whereas the opposite was true for 8/127 (6%) of the biopsies. There were fewer collected duodenal biopsies, more missing bulb biopsies and missing CD3 staining among discordant evaluations. The second evaluation revealed a Marsh score compliant with coeliac disease in 22 children of whom seven children were tTGA positive. Conclusions The variation between university hospitals on the pathological evaluation of biopsies may lead to misdiagnosis of coeliac disease in paediatric patients. Access to clinical and endoscopic information as well as tTGA levels may be useful for the pathologist to complement the evaluation in dubious cases

A Comparison of Fresh and Frozen Lamb Meat-Differences in Technological Meat Quality and Sensory Attributes

Simple Summary Freezing is used to extend the storage time of meat and is common practice in lamb meat production, since it maintains a steady supply of seasonal meat throughout the year and allows shipping over long distances. Fresh meat may also be purchased and frozen at home, to enable longer storage of the product before consumption. Freezing is the best preservation method, apart from chilling of fresh meat. However, differences in quality parameters between fresh and frozen meat may influence consumer choice and preferences. It is thus important to evaluate these differences, and how they are affected by conditions and animal handling during primary production, slaughter method and storage conditions before retail sale. This study examined the effect of freezing on technological meat quality and sensory attributes in lamb meat samples collected at two different slaughterhouses using different slaughter methods. Several differences between fresh and frozen-thawed meat were detected in terms of technological meat quality and sensory attributes, including colour, Warner-Bratzler shear force, cooking loss, flavour attributes and juicy texture. Technological meat quality and sensory attributes of fresh and frozen lamb meat were compared. Samples were collected from two abattoirs (one small-scale, one large-scale) that use different slaughter methods in terms of chilling regime and electrical stimulation. The fresh and frozen meat samples included products from both slaughter systems. Ten twin pairs of ram lambs were used in the study, with one of each twin slaughtered at each abattoir. Fresh meat was analysed after chilling and frozen meat was stored frozen for three months and analysed after thawing. The Musculus longissimus thoracis et lumborum was analysed for colour, cooking loss, sensory attributes, Warner-Bratzler shear force (WBSF) and distribution of water and lipid within each meat sample. Meat samples analysed after frozen storage were darker, less red and more yellow than the fresh meat. Freezing and frozen storage increased fluid loss and WBSF compared with the fresh meat, due to protein denaturation. Frozen storage affected sensory attributes by increasing fatty odour, frying flavour, sour flavour, fatty flavour and liver flavour, and by reducing juicy texture and mushy texture

Автоматизированное рабочее место мастера участка тяговых подстанций КУП «Горэлектротранспорт»

Background: The elevated body swing test (EBST) is a behavioral test used to evaluate experimental stroke in rodents. The basic idea is that when the animal is suspended vertically by the tail, it will swing its head laterally to the left or right depending on lesion side. In a previous study from our lab using the EBST after middle cerebral artery occlusion (MCAo), rats swung contralateral to the infarct day 1 post-MCAo, but ipsilateral day 3 post-MCAo. This shift was unexpected and prompted us to perform the present study. First, the literature was systematically reviewed to elucidate whether a similar shift had been noticed before, and if consensus existed regarding swing direction. Secondly, an experiment was conducted to systematically investigate the suggested behavior. Eighty-three adult male and female Sprague-Dawley rats were subjected to MCAo or sham surgery and the EBST was performed up to 7 days after the lesion. Results: Both experimentally and through systematic literature review, the present study shows that the direction of biased swing activity in the EBST for rodents after cerebral ischemia can differ and even shift over time in some situations. The EBST curve for females was significantly different from that of males after the same occlusion time (p = 0.023). Conclusions: This study highlights the importance of adequate reporting of behavioral tests for lateralization and it is concluded that the EBST cannot be recommended as a test for motor asymmetry after MCAo in rats.Funding Agencies|Region Ostergotland/Linkoping University, Sweden</p

A Possible Mechanism behind Autoimmune Disorders Discovered By Genome-Wide Linkage and Association Analysis in Celiac Disease

Celiac disease is a common autoimmune disorder characterized by an intestinal inflammation triggered by gluten, a storage protein found in wheat, rye and barley. Similar to other autoimmune diseases such as type 1 diabetes, psoriasis and rheumatoid arthritis, celiac disease is the result of an immune response to self-antigens leading to tissue destruction and production of autoantibodies. Common diseases like celiac disease have a complex pattern of inheritance with inputs from both environmental as well as additive and non-additive genetic factors. In the past few years, Genome Wide Association Studies (GWAS) have been successful in finding genetic risk variants behind many common diseases and traits. To complement and add to the previous findings, we performed a GWAS including 206 trios from 97 nuclear Swedish and Norwegian families affected with celiac disease. By stratifying for HLA-DQ, we identified a new genome-wide significant risk locus covering the DUSP10 gene. To further investigate the associations from the GWAS we performed pathway analyses and two-locus interaction analyses. These analyses showed an over-representation of genes involved in type 2 diabetes and identified a set of candidate mechanisms and genes of which some were selected for mRNA expression analysis using small intestinal biopsies from 98 patients. Several genes were expressed differently in the small intestinal mucosa from patients with celiac autoimmunity compared to intestinal mucosa from control patients. From top-scoring regions we identified susceptibility genes in several categories: 1) polarity and epithelial cell functionality; 2) intestinal smooth muscle; 3) growth and energy homeostasis, including proline and glutamine metabolism; and finally 4) innate and adaptive immune system. These genes and pathways, including specific functions of DUSP10, together reveal a new potential biological mechanism that could influence the genesis of celiac disease, and possibly also other chronic disorders with an inflammatory component

Altered peripheral amino acid profile indicate a systemic impact of active celiac disease and a possible role of amino acids in disease pathogenesis

Background: We have previously performed a Genome Wide Association and linkage study that indicated a new disease triggering mechanism involving amino acid metabolism and nutrient sensing signaling pathways. Objective: The aim of this study was to investigate if plasma amino acid levels differed among children with celiac disease compared with disease controls. Materials and methods: Fasting plasma samples from 141 children with celiac disease and 129 non-celiac disease controls, were analyzed for amino acid levels by liquid chromatography-tandem mass spectrometry (LC/MS). A general linear model using age and experimental effects as covariates was used to compare amino acid levels between children with a diagnosis of celiac disease and controls. Results: Seven out of twenty-three analyzed amino acids were elevated in children with celiac disease compared with controls (tryptophan, taurine, glutamic acid, proline, ornithine, alanine and methionine). The significance of the individual amino acids do not survive multiple correction, however, multivariate analyses of the amino acid profile showed significantly altered amino acid levels in children with celiac disease overall and after correction for age, sex and experimental effects (p = 8.4 7 10 -8 ). Conclusion: These findings support the idea that amino acids could influence systemic inflammation and play a possible role in disease pathogenesis

Effect of acute hypoxia on respiratory muscle fatigue in healthy humans

<p>Abstract</p> <p>Background</p> <p>Greater diaphragm fatigue has been reported after hypoxic versus normoxic exercise, but whether this is due to increased ventilation and therefore work of breathing or reduced blood oxygenation per se remains unclear. Hence, we assessed the effect of different blood oxygenation level on isolated hyperpnoea-induced inspiratory and expiratory muscle fatigue.</p> <p>Methods</p> <p>Twelve healthy males performed three 15-min isocapnic hyperpnoea tests (85% of maximum voluntary ventilation with controlled breathing pattern) in normoxic, hypoxic (SpO₂= 80%) and hyperoxic (FiO₂= 0.60) conditions, in a random order. Before, immediately after and 30 min after hyperpnoea, transdiaphragmatic pressure (P_di,tw) was measured during cervical magnetic stimulation to assess diaphragm contractility, and gastric pressure (P_ga,tw) was measured during thoracic magnetic stimulation to assess abdominal muscle contractility. Two-way analysis of variance (time x condition) was used to compare hyperpnoea-induced respiratory muscle fatigue between conditions.</p> <p>Results</p> <p>Hypoxia enhanced hyperpnoea-induced P_di,twand P_ga,twreductions both immediately after hyperpnoea (P_di,tw: normoxia -22 ± 7% vs hypoxia -34 ± 8% vs hyperoxia -21 ± 8%; P_ga,tw: normoxia -17 ± 7% vs hypoxia -26 ± 10% vs hyperoxia -16 ± 11%; all <it>P </it>< 0.05) and after 30 min of recovery (P_di,tw: normoxia -10 ± 7% vs hypoxia -16 ± 8% vs hyperoxia -8 ± 7%; P_ga,tw: normoxia -13 ± 6% vs hypoxia -21 ± 9% vs hyperoxia -12 ± 12%; all <it>P </it>< 0.05). No significant difference in P_di,twor P_ga,twreductions was observed between normoxic and hyperoxic conditions. Also, heart rate and blood lactate concentration during hyperpnoea were higher in hypoxia compared to normoxia and hyperoxia.</p> <p>Conclusions</p> <p>These results demonstrate that hypoxia exacerbates both diaphragm and abdominal muscle fatigability. These results emphasize the potential role of respiratory muscle fatigue in exercise performance limitation under conditions coupling increased work of breathing and reduced O₂transport as during exercise in altitude or in hypoxemic patients.</p