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| 5. |
- van der Steeg, H. J.J., et al.
(författare)
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High-grade Vesicoureteral Reflux in Patients With Anorectal Malformation From the ARM-Net Registry : Is Our Screening Sufficient?
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Ingår i: Journal of Pediatric Surgery. - 0022-3468.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Vesico-ureteral reflux (VUR) is a common associated urological anomaly in anorectal malformation (ARM)-patients. High-grade VUR requires antibiotic prophylaxis to prevent urinary tract infections (UTI's), renal scarring and -failure. The exact prevalence of high-grade VUR in ARM patients is unknown. Hence, the aim of this study was determining the incidence of high-grade VUR in ARM-patients, and its associated risk factors. Methods: A multicenter retrospective cohort study was performed using the ARM-Net registry, including data from 34 centers. Patient characteristics, screening for and presence of renal anomalies and VUR, sacral and spinal anomalies, and sacral ratio were registered. Phenotypes of ARM were grouped according to their complexity in complex and less complex. Multivariable analyses were performed to detect independent risk factors for high-grade (grade III-V) VUR. Results: This study included 2502 patients (50 % female). Renal screening was performed in 2250 patients (90 %), of whom 648 (29 %) had a renal anomaly documented. VUR-screening was performed in 789 patients (32 %), establishing high-grade VUR in 150 (19 %). In patients with a normal renal screening, high-grade VUR was still present in 10 % of patients. Independent risk factors for presence of high-grade VUR were a complex ARM (OR 2.6, 95 %CI 1.6–4.3), and any renal anomaly (OR 3.3, 95 %CI 2.1–5.3). Conclusions: Although renal screening is performed in the vast majority of patients, only 32 % underwent VUR-screening. Complex ARM and any renal anomaly were independent risk factors for high-grade VUR. Remarkably, 10 % had high-grade VUR despite normal renal screening. Therefore, VUR-screening seems indicated in all ARM patients regardless of renal screening results, to prevent sequelae such as UTI's, renal scarring and ultimately renal failure. Type of Study: Observational Cohort-Study. Level of Evidence: III.
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| 6. |
- Verhoeven, L. M., et al.
(författare)
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A numerical and experimental study of Polycyclic Aromatic Hydrocarbons in a laminar diffusion flame
- 2013
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Ingår i: Proceedings of the Combustion Institute. - : Elsevier BV. - 1540-7489. ; 34, s. 1819-1826
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Tidskriftsartikel (refereegranskat)abstract
- During the process of biomass gasification tars are formed which exit the gasifier in vapor phase. Tar condensation creates problems like fouling and plugging of after-treatment, conversion and end-use equipment. Gasification tars consist mainly of Polycyclic Aromatic Hydrocarbons (PAHs). Former research has shown the possibilities and difficulties of tar conversion by partial combustion. Basic studies to investigate the oxidation of tars in non-premixed combustion processes are expected to give more insight in this problem. In this paper the ability of the flamelet-generated manifold (FGM) approach to numerically model multi-dimensional, laminar, non-premixed flames with the inclusion of PAH chemistry is investigated. Modeling detailed PAH chemistry requires the employment of large reaction mechanisms which lead to expensive numerical calculations. The application of a reduction technique like FGM leads to a considerable decrease (up to two orders) in the required computation time. A 1D numerical validation shows that the improvements achieved by implementing a varying Lewis number for the progress variable Y are significant for PAH species with a large Lewis number, such as C10H8. Considerable improvements are found near the flame front and on the fuel side of the flame. A comparison has been made of FGM results with qualitative Planar Laser Induced Fluorescence (PLIF) measurements. A laminar CH4/N-2-air co-flow flame has been doped with two dopants, benzene and toluene, at three different concentrations. A set of filters was used in order to qualitatively distinguish the small (1-2 rings) and large (3 or more rings) aromatic species. The results show that the model is able to capture the major flame characteristics typical for PAH formation in multi-dimensional laminar non-premixed flames. (C) 2012 The Combustion Institute. Published by Elsevier Inc. All rights reserved.
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| 8. |
- Chye, Yann, et al.
(författare)
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Subcortical surface morphometry in substance dependence : An ENIGMA addiction working group study
- 2020
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Ingår i: Addiction Biology. - : WILEY. - 1355-6215 .- 1369-1600. ; 25:6
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Tidskriftsartikel (refereegranskat)abstract
- While imaging studies have demonstrated volumetric differences in subcortical structures associated with dependence on various abused substances, findings to date have not been wholly consistent. Moreover, most studies have not compared brain morphology across those dependent on different substances of abuse to identify substance-specific and substance-general dependence effects. By pooling large multinational datasets from 33 imaging sites, this study examined subcortical surface morphology in 1628 nondependent controls and 2277 individuals with dependence on alcohol, nicotine, cocaine, methamphetamine, and/or cannabis. Subcortical structures were defined by FreeSurfer segmentation and converted to a mesh surface to extract two vertex-level metrics-the radial distance (RD) of the structure surface from a medial curve and the log of the Jacobian determinant (JD)-that, respectively, describe local thickness and surface area dilation/contraction. Mega-analyses were performed on measures of RD and JD to test for the main effect of substance dependence, controlling for age, sex, intracranial volume, and imaging site. Widespread differences between dependent users and nondependent controls were found across subcortical structures, driven primarily by users dependent on alcohol. Alcohol dependence was associated with localized lower RD and JD across most structures, with the strongest effects in the hippocampus, thalamus, putamen, and amygdala. Meanwhile, nicotine use was associated with greater RD and JD relative to nonsmokers in multiple regions, with the strongest effects in the bilateral hippocampus and right nucleus accumbens. By demonstrating subcortical morphological differences unique to alcohol and nicotine use, rather than dependence across all substances, results suggest substance-specific relationships with subcortical brain structures.
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| 9. |
- Goswami, Mayuri, et al.
(författare)
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The effect of elevated pressures on the laminar burning velocity of methane plus air mixtures
- 2013
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Ingår i: Combustion and Flame. - : Elsevier BV. - 0010-2180. ; 160:9, s. 1627-1635
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Tidskriftsartikel (refereegranskat)abstract
- In spite of the large amount of research spent on the evaluation of the high pressure dependence of laminar burning velocity of methane + air flame, there still exists a large uncertainty in the data for various reasons. In order to reduce the scatter to acceptable levels, the Heat Flux Method (HFM), known as a potential method with high accuracy, has been extended to higher pressures. New measurements of the laminar burning velocity of methane + air flames are presented. Non-stretched planar flames were stabilized on a perforated plate burner which was placed in a high pressure environment. The experimental results are reported for a pressure range between 1 and 5 atm. The equivalence ratio was varied from 0.8 to 1.4. Comparisons with several recent literature sources (experiments) show good agreement. An exhaustive literature survey was performed to study the numerous existing laminar burning velocity correlations for its pressure dependence. It is indicated from the literature that many of the deduced correlations use stretched laminar burning velocity results. Many used only few data points for the pressure behavior and correlations and therefore show wide discrepancies. As the heat flux method furnishes quality results with reduced errors, the results were further utilized in deducing a power-law pressure dependence. Numerical simulations were also performed using two widely used chemical reaction mechanisms, which were further involved in comparing correlations. The proposed power exponent beta(1) shows a non-monotonic behavior at equivalence ratio around 1.4 in experiments and simulations. Through species and reaction flux analysis it was observed that CH3 consumption through various reactions remain pressure dependent and show non-monotonic behavior at equivalence ratio around 1.4. (c) 2013 The Combustion Institute. Published by Elsevier Inc. All rights reserved.
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| 11. |
- Grinberg, Marianna, et al.
(författare)
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Toxicogenomics directory of chemically exposed human hepatocytes
- 2014
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 1432-0738 .- 0340-5761. ; 88:12, s. 2261-2287
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Tidskriftsartikel (refereegranskat)abstract
- A long-term goal of numerous research projects is to identify biomarkers for in vitro systems predicting toxicity in vivo. Often, transcriptomics data are used to identify candidates for further evaluation. However, a systematic directory summarizing key features of chemically influenced genes in human hepatocytes is not yet available. To bridge this gap, we used the Open TG-GATES database with Affymetrix files of cultivated human hepatocytes incubated with chemicals, further sets of gene array data with hepatocytes from human donors generated in this study, and publicly available genome-wide datasets of human liver tissue from patients with non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular cancer (HCC). After a curation procedure, expression data of 143 chemicals were included into a comprehensive biostatistical analysis. The results are summarized in the publicly available toxicotranscriptomics directory (http://wiki.toxbank.net/toxicogenomics-map/) which provides information for all genes whether they are up- or downregulated by chemicals and, if yes, by which compounds. The directory also informs about the following key features of chemically influenced genes: (1) Stereotypical stress response. When chemicals induce strong expression alterations, this usually includes a complex but highly reproducible pattern named 'stereotypical response.' On the other hand, more specific expression responses exist that are induced only by individual compounds or small numbers of compounds. The directory differentiates if the gene is part of the stereotypical stress response or if it represents a more specific reaction. (2) Liver disease-associated genes. Approximately 20 % of the genes influenced by chemicals are up- or downregulated, also in liver disease. Liver disease genes deregulated in cirrhosis, HCC, and NASH that overlap with genes of the aforementioned stereotypical chemical stress response include CYP3A7, normally expressed in fetal liver; the phase II metabolizing enzyme SULT1C2; ALDH8A1, known to generate the ligand of RXR, one of the master regulators of gene expression in the liver; and several genes involved in normal liver functions: CPS1, PCK1, SLC2A2, CYP8B1, CYP4A11, ABCA8, and ADH4. (3) Unstable baseline genes. The process of isolating and the cultivation of hepatocytes was sufficient to induce some stress leading to alterations in the expression of genes, the so-called unstable baseline genes. (4) Biological function. Although more than 2,000 genes are transcriptionally influenced by chemicals, they can be assigned to a relatively small group of biological functions, including energy and lipid metabolism, inflammation and immune response, protein modification, endogenous and xenobiotic metabolism, cytoskeletal organization, stress response, and DNA repair. In conclusion, the introduced toxicotranscriptomics directory offers a basis for a rationale choice of candidate genes for biomarker evaluation studies and represents an easy to use source of background information on chemically influenced genes.
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| 12. |
- Krais, Annette, et al.
(författare)
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Metabolic activation of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine and DNA adduct formation depends on p53: Studies in Trp53(+/+),Trp53(+/-) and Trp53(-/-) mice.
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136.
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Tidskriftsartikel (refereegranskat)abstract
- The expression of the tumor suppressor p53 can influence the bioactivation of, and DNA damage induced by, the environmental carcinogen benzo[a]pyrene, indicating a role for p53 in its cytochrome P450 (CYP)-mediated biotransformation. The carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which is formed during the cooking of food, is also metabolically activated by CYP enzymes, particularly CYP1A2. We investigated the potential role of p53 in PhIP metabolism in vivo by treating Trp53(+/+), Trp53(+/-) and Trp53(-/-) mice with a single oral dose of 50 mg/kg body weight PhIP. N-(Deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP-C8-dG) levels in DNA, measured by liquid chromatography-tandem mass spectrometry, were significantly lower in liver, colon, forestomach and glandular stomach of Trp53(-/-) mice compared to Trp53(+/+) mice. Lower PhIP-DNA adduct levels in the livers of Trp53(-/-) mice correlated with lower Cyp1a2 enzyme activity (measured by methoxyresorufin-O-demethylase activity) in these animals. Interestingly, PhIP-DNA adduct levels were significantly higher in kidney and bladder of Trp53(-/-) mice compared to Trp53(+/+) mice, which was accompanied by higher sulfotransferase (Sult) 1a1 protein levels and increased Sult1a1 enzyme activity (measured by 2-naphthylsulfate formation from 2-naphthol) in kidneys of these animals. Our study demonstrates a role for p53 in the metabolism of PhIP in vivo, extending previous results on a novel role for p53 in xenobiotic metabolism. Our results also indicate that the impact of p53 on PhIP biotransformation is tissue-dependent and that in addition to Cyp1a enzymes, Sult1a1 can contribute to PhIP-DNA adduct formation.
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| 14. |
- Oliveira, M. H. de Andrade, et al.
(författare)
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Soot, PAH and OH measurements in vaporized liquid fuel flames
- 2013
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Ingår i: Fuel. - : Elsevier BV. - 1873-7153 .- 0016-2361. ; 112, s. 145-152
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Tidskriftsartikel (refereegranskat)abstract
- Qualitative measurements of both OH and polycyclic aromatic hydrocarbons (PAH) as well as quantitative data of soot volume fraction f(v) have been obtained in vaporized liquid fuels, with the main goal of providing experimental data for combustion models and numerical mechanism validation. Measurements were carried out in a laminar coflow burner which was designed, built and integrated with an evaporation system, enabling the combustion of vaporized liquid fuels at pressures of up to 3.0 MPa to be studied. The fuels n-heptane and n-decane, referred to in the literature as being important surrogate fuels, were selected for measurements at atmospheric pressure that were carried out in the experimental setup described, making use of a combination of the Laser Induced Fluorescence (LIF) and Laser Induced Incandescence (LII) techniques. Partially premixed flames of n-heptane and n-decane showed similar combustion characteristics in the range of 1.9 < phi < 3.7. For both of the fuels the threshold for soot formation was found to be at about phi similar to 3.3. Comparison of the LIF and LII measurements for the n-heptane flames within the range of 3.7 <= phi <= 8.5 indicated the maximum PAH LIF signal to be a good predictor of f(vmax) obtained from LII. Excitation at 266 nm using delayed detection was found to result in the signals obtained showing a close linear correlation with the soot volume fraction obtained from LII when prompt detection at 1064 nm excitation was used. Neither the effects of any additional photo-chemical processes making use of high laser power at 266 nm nor the effects of particle size on the delayed gate times appeared to be of any significance for the flame conditions studied here. (C) 2013 Elsevier Ltd. All rights reserved.
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| 15. |
- van Veluw, Susanne J, et al.
(författare)
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Hippocampal T2 hyperintensities on 7 Tesla MRI
- 2013
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Ingår i: NeuroImage: Clinical. - : Elsevier BV. - 2213-1582. ; 3, s. 196-201
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Tidskriftsartikel (refereegranskat)abstract
- Hippocampal focal T2 hyperintensities (HT2Hs), also referred to as hippocampal sulcal cavities, are a common finding on Magnetic Resonance (MR) images. There is uncertainty about their etiology and clinical significance. In this study we aimed to describe these HT2Hs in more detail using high resolution 7 Tesla MR imaging, addressing 1) the MR signal characteristics of HT2Hs, 2) their occurrence frequency, 3) their location within the hippocampus, and 4) their relation with age. We also performed an explorative post-mortem study to examine the histology of HT2Hs. Fifty-eight persons without a history of invalidating neurological or psychiatric disease (mean age 64 ± 8 years; range 43-78 years), recruited through their general practitioners, were included in this study. They all underwent 7 Tesla MRI, including a T1, T2, and FLAIR image. MR signal characteristics of the HT2Hs were assessed on these images by two raters. Also, the location and number of the HT2Hs were assessed. In addition, four formalin-fixed brain slices from two subjects were scanned overnight. HT2Hs identified in these slices were subjected to histopathological analysis. HT2Hs were present in 97% of the subjects (median number per person 10; range 0-20). All HT2Hs detected on the T2 sequence were hypointense on T1 weighted images. Of all HT2Hs, 94% was hypointense and 6% hyperintense on FLAIR. FLAIR hypointense HT2Hs were all located in the vestigial sulcus of the hippocampus, FLAIR hyperintense HT2Hs in the hippocampal sulcus or the gray matter. Post-mortem MRI and histopathological analysis suggested that the hypointense HT2Hs on FLAIR were cavities filled with cerebrospinal fluid. A hyperintense HT2H on FLAIR proved to be a microinfarct upon microscopy. In conclusion, hippocampal T2Hs are extremely common and unrelated to age. They can be divided into two types (hypo- and hyperintense on FLAIR), probably with different etiology.
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| 16. |
- Yu, M., et al.
(författare)
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Survivability of thermographic phosphors (YAG:Dy) in a combustion environment
- 2010
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Ingår i: Measurement Science & Technology. - : IOP Publishing. - 0957-0233 .- 1361-6501. ; 21:3
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Tidskriftsartikel (refereegranskat)abstract
- The feasibility of applying laser-induced phosphorescence in a combustion environment was shown by testing the consistency of the emission-temperature relations of thermographic phosphor particles (YAG:Dy). The relations were calibrated before and after the phosphor particles had passed a flame front. The calibrations were performed in air and in pure oxygen. The emission-temperature relation prevails from around 300 K to 1300 K. The difference in emission-temperature relation for the two different cases is less than the experimental precision (3%).
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| 18. |
- Bonouvrie, D. S., et al.
(författare)
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Laparoscopic roux-en-Y gastric bypass versus sleeve gastrectomy for teenagers with severe obesity-TEEN-BEST: study protocol of a multicenter randomized controlled trial
- 2020
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Ingår i: Bmc Surgery. - : Springer Science and Business Media LLC. - 1471-2482. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Recent data support the use of bariatric surgery in adolescents with severe obesity following unsuccessful non-surgical treatments. Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) have demonstrated reasonably similar weight loss and reduction of obesity related comorbidities in randomized trials in adults. SG has internationally become the most commonly used procedure in adolescents, yet long-term outcome data are lacking. No randomized controlled trial comparing SG and RYGB has been performed in adolescents. Objective Determine whether SG is non-inferior to RYGB in terms of total body weight (TBW) loss in adolescents with severe obesity. Methods A multicenter randomized controlled non-inferiority trial. Two hundred sixty-four adolescents aged 13-17 (Tanner stage >= IV) with severe obesity (corrected for age and sex) will be included. Adolescents agreeing to participate will be randomized to either RYGB or SG. The primary outcome is the proportion of participants achieving 20% TBW loss at 3 years postoperatively. Secondary outcomes include (i) change in body weight, body mass index (BMI) and BMI standard deviation score, (ii) incidence of adverse health events and need for additional surgical intervention, (iii) resolution of obesity-related comorbidities, (iv) prevalence of cardio metabolic risk factor measures, (v) bone health measures and incidence of bone fractures, (vi) quality of life including psychosocial health, patient satisfaction and educational attainment and (vii) body composition. Follow-up will extend into the long term. Results Not applicable. Discussion This study will, to our knowledge, be the first randomized controlled trial comparing SG and RYGB in adolescents with severe obesity.
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| 19. |
- Krebs, Alice, et al.
(författare)
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Template for the Description of Cell-Based Toxicological Test Methods to Allow Evaluation and Regulatory Use of the Data
- 2019
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Ingår i: Altex. - : ALTEX Edition. - 1868-596X .- 1868-8551. ; 36:4, s. 682-699
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Only few cell-based test methods are described by Organisation for Economic Co-operation and Development (OECD) test guidelines or other regulatory references (e.g., the European Pharmacopoeia). The majority of toxicity tests still falls into the category of non-guideline methods. Data from these tests may nevertheless be used to support regulatory decisions or to guide strategies to assess compounds (e.g., drugs, agrochemicals) during research and development if they fulfill basic requirements concerning their relevance, reproducibility and predictivity. Only a method description of sufficient clarity and detail allows interpretation and use of the data. To guide regulators faced with increasing amounts of data from non-guideline studies, the OECD formulated Guidance Document 211 (GD211) on method documentation for the purpose of safety assessment. As GD211 is targeted mainly at regulators, it leaves scientists less familiar with regulation uncertain as to what level of detail is required and how individual questions should be answered. Moreover, little attention was given to the description of the test system (i.e., cell culture) and the steps leading to it being established in the guidance. To address these issues, an annotated toxicity test method template (ToxTemp) was developed (i) to fulfill all requirements of GD211, (ii) to guide the user concerning the types of answers and detail of information required, (iii) to include acceptance criteria for test elements, and (iv) to define the cells sufficiently and transparently. The fully annotated ToxTemp is provided here, together with reference to a database containing exemplary descriptions of more than 20 cell-based tests.
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| 20. |
- Luijten, Ineke H. N., et al.
(författare)
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In the absence of UCP1-mediated diet-induced thermogenesis, obesity is augmented even in the obesity-resistant 129S mouse strain
- 2019
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 316:5, s. E729-E740
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Tidskriftsartikel (refereegranskat)abstract
- The attractive tenet that recruitment and activation of brown adipose tissue (BAT) and uncoupling protein 1 (UCP1) could counteract the development of obesity and its comorbidities in humans has been experimentally corroborated mainly by experiments demonstrating that UCP1-ablated mice on a C57B1/6 background (exempt from thermal stress) become more obese when fed a high-fat diet. However, concerns may be raised that this outcome of UCP1 ablation is restricted to this very special inbred and particularly obesity-prone mouse strain. Therefore, we have examined to which degree UCP1 ablation has similar metabolic effects in a mouse strain known to be obesity resistant: the 129S strain. For this, male 129S2/sv or 129SV/Pas mice and corresponding UCP1-knockout mice were fed chow or a high-fat or a cafeteria diet for 4 w.k. The absence of UCP1 augmented obesity (weight gain, body fat mass, %body fat, fat depot size) in high-fat diet- and cafeteria-fed mice, with a similar or lower food intake, indicating that, when present, UCP1 indeed decreases metabolic efficiency. The increased obesity was due to a decrease in energy expenditure. The consumption of a high-fat or cafeteria diet increased total BAT UCP1 protein levels in wild-type mice, and correspondingly. high-fat diet and cafeteria diet-fed mice demonstrated increased norepinephrine-induced oxygen consumption. There was a positive correlation between body fat and total BAT UCP1 protein content. No evidence for diet-induced adrenergic thermogenesis was found in UCP1-ablated mice. Thus, the obesity-reducing effect of UCP1 is not restricted to a particular, and perhaps not representative, mouse strain.
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| 24. |
- Shinoda, Kosaku, et al.
(författare)
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Genetic and functional characterization of clonally derived adult human brown adipocytes
- 2015
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 21:4, s. 389-394
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Tidskriftsartikel (refereegranskat)abstract
- Brown adipose tissue (BAT) acts in mammals as a natural defense system against hypothermia, and its activation to a state of increased energy expenditure is believed to protect against the development of obesity. Even though the existence of BAT in adult humans has been widely appreciated(1-8), its cellular origin and molecular identity remain elusive largely because of high cellular heterogeneity within various adipose tissue depots. To understand the nature of adult human brown adipocytes at single cell resolution, we isolated clonally derived adipocytes from stromal vascular fractions of adult human BAT from two individuals and globally analyzed their molecular signatures. We used RNA sequencing followed by unbiased genome-wide expression analyses and found that a population of uncoupling protein 1 (UCP1)-positive human adipocytes possessed molecular signatures resembling those of a recruitable form of thermogenic adipocytes (that is, beige adipocytes). In addition, we identified molecular markers that were highly enriched in UCP1-positive human adipocytes, a set that included potassium channel K3 (KCNK3) and mitochondrial tumor suppressor 1 (MTUS1). Further, we functionally characterized these two markers using a loss-of-function approach and found that KCNK3 and MTUS1 were required for beige adipocyte differentiation and thermogenic function. The results of this study present new opportunities for human BAT research, such as facilitating cell-based disease modeling and unbiased screens for thermogenic regulators.
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