| 1. |
- Dabrowski, Michal J., et al.
(author)
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Unveiling new interdependencies between significant DNA methylation sites, gene expression profiles and glioma patients survival
- 2018
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Journal article (peer-reviewed)abstract
- In order to find clinically useful prognostic markers for glioma patients' survival, we employed Monte Carlo Feature Selection and Interdependencies Discovery (MCFS-ID) algorithm on DNA methylation (HumanMethylation450 platform) and RNA-seq datasets from The Cancer Genome Atlas (TCGA) for 88 patients observed until death. The input features were ranked according to their importance in predicting patients' longer (400+ days) or shorter (<= 400 days) survival without prior classification of the patients. Interestingly, out of the 65 most important features found, 63 are methylation sites, and only two mRNAs. Moreover, 61 out of the 63 methylation sites are among those detected by the 450 k array technology, while being absent in the HumanMethylation27. The most important methylation feature (cg15072976) overlaps with the RE1 Silencing Transcription Factor (REST) binding site, and was confirmed to intersect with the REST binding motif in human U87 glioma cells. Six additional methylation sites from the top 63 overlap with REST sites. We found that the methylation status of the cg15072976 site affects transcription factor binding in U87 cells in gel shift assay. The cg15072976 methylation status discriminates <= 400 and 400+ patients in an independent dataset from TCGA and shows positive association with survival time as evidenced by Kaplan-Meier plots.
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| 2. |
- Dramiński, Michał, et al.
(author)
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Discovering Networks of Interdependent Features in High-Dimensional Problems
- 2016
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In: Big Data Analysis. - Cham : Springer. - 9783319269894 ; , s. 285-304
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Book chapter (peer-reviewed)abstract
- The availability of very large data sets in Life Sciences provided earlier by the technological breakthroughs such as microarrays and more recently by various forms of sequencing has created both challenges in analyzing these data as well as new opportunities. A promising, yet underdeveloped approach to Big Data, not limited to Life Sciences, is the use of feature selection and classification to discover interdependent features. Traditionally, classifiers have been developed for the best quality of supervised classification. In our experience, more often than not, rather than obtaining the best possible supervised classifier, the Life Scientist needs to know which features contribute best to classifying observations (objects, samples) into distinct classes and what the interdependencies between the features that describe the observation. Our underlying hypothesis is that the interdependent features and rule networks do not only reflect some syntactical properties of the data and classifiers but also may convey meaningful clues about true interactions in the modeled biological system. In this chapter we develop further our method of Monte Carlo Feature Selection and Interdependency Discovery (MCFS and MCFS-ID, respectively), which are particularly well suited for high-dimensional problems, i.e., those where each observation is described by very many features, often many more features than the number of observations. Such problems are abundant in Life Science applications. Specifically, we define Inter-Dependency Graphs (termed, somewhat confusingly, ID Graphs) that are directed graphs of interactions between features extracted by aggregation of information from the classification trees constructed by the MCFS algorithm. We then proceed with modeling interactions on a finer level with rule networks. We discuss some of the properties of the ID graphs and make a first attempt at validating our hypothesis on a large gene expression data set for CD4+ T-cells. The MCFS-ID and ROSETTA including the Ciruvis approach offer a new methodology for analyzing Big Data from feature selection, through identification of feature interdependencies, to classification with rules according to decision classes, to construction of rule networks. Our preliminary results confirm that MCFS-ID is applicable to the identification of interacting features that are functionally relevant while rule networks offer a complementary picture with finer resolution of the interdependencies on the level of feature-value pairs.
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| 3. |
- Kowalczyk, Dorota A., et al.
(author)
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Local electronic structure of stable monolayers of α-MoO3−x grown on graphite substrate
- 2021
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In: 2D Materials. - : IOP Publishing. - 2053-1583. ; 8:2
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Journal article (peer-reviewed)abstract
- We report on van der Waals epitaxy of two-dimensional (2D) molybdenum trioxide (MoO3−x) with monolayer thickness directly grown on highly oriented pyrolytic graphite by thermal evaporation under ultrahigh vacuum. The chemical composition, electronic and crystalline lattice structures of the mono-and few-layer MoO3−x sheets are analysed. Using scanning tunnelling microscopy and spectroscopy, we investigate the electronic properties of MoO3−x as a function of the number of layers and measure the apparent energy gap to be 0.4 eV for the first three layers of MoO3−x on graphite. We carried out density functional theory calculations to shed light on the mechanism underlying the observed narrow bandgap with oxygen deficiency. Moreover, the air exposure effect on monolayer MoO3−x is investigated confirming that the apparent bandgap closes, and additionally we show the reduction of the work function from 5.7 to 4.7 eV. We prove that it is possible to synthesize the 2D, non-stoichiometric, and electrically conductive MoO3−x.
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| 4. |
- Przanowski, Piotr, et al.
(author)
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The signal transducers Stat1 and Stat3 and their novel target Jmjd3 drive the expression of inflammatory genes in microglia
- 2014
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In: Journal of Molecular Medicine. - : Springer Science and Business Media LLC. - 0946-2716 .- 1432-1440. ; 92:3, s. 239-254
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Journal article (peer-reviewed)abstract
- Most neurological diseases are associated with chronic inflammation initiated by the activation of microglia, which produce cytotoxic and inflammatory factors. Signal transducers and activators of transcription (STATs) are potent regulators of gene expression but contribution of particular STAT to inflammatory gene expression and STAT-dependent transcriptional networks underlying brain inflammation need to be identified. In the present study, we investigated the genomic distribution of Stat binding sites and the role of Stats in the gene expression in lipopolysaccharide (LPS)-activated primary microglial cultures. Integration of chromatin immunoprecipitation-promoter microarray data and transcriptome data revealed novel Stat-target genes including Jmjd3, Ccl5, Ezr, Ifih1, Irf7, Uba7, and Pim1. While knockdown of individual Stat had little effect on the expression of tested genes, knockdown of both Stat1 and Stat3 inhibited the expression of Jmjd3 and inflammatory genes. Transcriptional regulation of Jmjd3 by Stat1 and Stat3 is a novel mechanism crucial for launching inflammatory responses in microglia. The effects of Jmjd3 on inflammatory gene expression were independent of its H3K27me3 demethylase activity. Forced expression of constitutively activated Stat1 and Stat3 induced the expression of Jmjd3, inflammation-related genes, and the production of proinflammatory cytokines as potently as lipopolysacharide. Gene set enrichment and gene function analysis revealed categories linked to the inflammatory response in LPS and Stat1C + Stat3C groups. We defined upstream pathways that activate STATs in response to LPS and demonstrated contribution of Tlr4 and Il-6 and interferon-. signaling. Our findings define novel direct transcriptional targets of Stat1 and Stat3 and highlight their contribution to inflammatory gene expression.
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| 5. |
- Stepniak, Karolina, et al.
(author)
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Mapping chromatin accessibility and active regulatory elements reveals pathological mechanisms in human gliomas
- 2021
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- Chromatin structure and accessibility, and combinatorial binding of transcription factors to regulatory elements in genomic DNA control transcription. Genetic variations in genes encoding histones, epigenetics-related enzymes or modifiers affect chromatin structure/dynamics and result in alterations in gene expression contributing to cancer development or progression. Gliomas are brain tumors frequently associated with epigenetics-related gene deregulation. We perform whole-genome mapping of chromatin accessibility, histone modifications, DNA methylation patterns and transcriptome analysis simultaneously in multiple tumor samples to unravel epigenetic dysfunctions driving gliomagenesis. Based on the results of the integrative analysis of the acquired profiles, we create an atlas of active enhancers and promoters in benign and malignant gliomas. We explore these elements and intersect with Hi-C data to uncover molecular mechanisms instructing gene expression in gliomas. Gliomas are tumors often associated with epigenetics-related gene deregulation. Here the authors reveal an atlas of active enhancers and promoters in benign and malignant gliomas by performing whole-genome mapping of chromatin accessibility, histone modifications, DNA methylation patterns and transcriptome analysis simultaneously in multiple tumor samples.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
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| 10. |
- Aad, G., et al.
(author)
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Commissioning of the ATLAS Muon Spectrometer with cosmic rays
- 2010
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 875-916
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Journal article (peer-reviewed)abstract
- The ATLAS detector at the Large Hadron Collider has collected several hundred million cosmic ray events during 2008 and 2009. These data were used to commission the Muon Spectrometer and to study the performance of the trigger and tracking chambers, their alignment, the detector control system, the data acquisition and the analysis programs. We present the performance in the relevant parameters that determine the quality of the muon measurement. We discuss the single element efficiency, resolution and noise rates, the calibration method of the detector response and of the alignment system, the track reconstruction efficiency and the momentum measurement. The results show that the detector is close to the design performance and that the Muon Spectrometer is ready to detect muons produced in high energy proton-proton collisions.
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| 11. |
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| 12. |
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| 13. |
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| 14. |
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Aad, G., et al.
(author)
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Readiness of the ATLAS Tile Calorimeter for LHC collisions
- 2010
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:4, s. 1193-1236
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Journal article (peer-reviewed)abstract
- The Tile hadronic calorimeter of the ATLAS detector has undergone extensive testing in the experimental hall since its installation in late 2005. The readout, control and calibration systems have been fully operational since 2007 and the detector has successfully collected data from the LHC single beams in 2008 and first collisions in 2009. This paper gives an overview of the Tile Calorimeter performance as measured using random triggers, calibration data, data from cosmic ray muons and single beam data. The detector operation status, noise characteristics and performance of the calibration systems are presented, as well as the validation of the timing and energy calibration carried out with minimum ionising cosmic ray muons data. The calibration systems' precision is well below the design value of 1%. The determination of the global energy scale was performed with an uncertainty of 4%.
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| 19. |
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| 20. |
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| 21. |
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| 22. |
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| 23. |
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| 24. |
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| 25. |
- Aad, G., et al.
(author)
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Studies of the performance of the ATLAS detector using cosmic-ray muons
- 2011
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 71:3
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Journal article (peer-reviewed)abstract
- Muons from cosmic-ray interactions in the atmosphere provide a high-statistics source of particles that can be used to study the performance and calibration of the ATLAS detector. Cosmic-ray muons can penetrate to the cavern and deposit energy in all detector subsystems. Such events have played an important role in the commissioning of the detector since the start of the installation phase in 2005 and were particularly important for understanding the detector performance in the time prior to the arrival of the first LHC beams. Global cosmic-ray runs were undertaken in both 2008 and 2009 and these data have been used through to the early phases of collision data-taking as a tool for calibration, alignment and detector monitoring. These large datasets have also been used for detector performance studies, including investigations that rely on the combined performance of different subsystems. This paper presents the results of performance studies related to combined tracking, lepton identification and the reconstruction of jets and missing transverse energy. Results are compared to expectations based on a cosmic-ray event generator and a full simulation of the detector response.
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| 26. |
- Aad, G., et al.
(author)
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The ATLAS Inner Detector commissioning and calibration
- 2010
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 787-821
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Journal article (peer-reviewed)abstract
- The ATLAS Inner Detector is a composite tracking system consisting of silicon pixels, silicon strips and straw tubes in a 2 T magnetic field. Its installation was completed in August 2008 and the detector took part in data-taking with single LHC beams and cosmic rays. The initial detector operation, hardware commissioning and in-situ calibrations are described. Tracking performance has been measured with 7.6 million cosmic-ray events, collected using a tracking trigger and reconstructed with modular pattern-recognition and fitting software. The intrinsic hit efficiency and tracking trigger efficiencies are close to 100%. Lorentz angle measurements for both electrons and holes, specific energy-loss calibration and transition radiation turn-on measurements have been performed. Different alignment techniques have been used to reconstruct the detector geometry. After the initial alignment, a transverse impact parameter resolution of 22.1 +/- 0.9 mu m and a relative momentum resolution sigma (p) /p=(4.83 +/- 0.16)x10(-4) GeV(-1)xp (T) have been measured for high momentum tracks.
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| 27. |
- Aad, G., et al.
(author)
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The ATLAS Simulation Infrastructure
- 2010
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 823-874
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Journal article (peer-reviewed)abstract
- The simulation software for the ATLAS Experiment at the Large Hadron Collider is being used for large-scale production of events on the LHC Computing Grid. This simulation requires many components, from the generators that simulate particle collisions, through packages simulating the response of the various detectors and triggers. All of these components come together under the ATLAS simulation infrastructure. In this paper, that infrastructure is discussed, including that supporting the detector description, interfacing the event generation, and combining the GEANT4 simulation of the response of the individual detectors. Also described are the tools allowing the software validation, performance testing, and the validation of the simulated output against known physics processes.
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| 28. |
- Dabrowski, Michal, et al.
(author)
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Reliability assessment of null allele detection : inconsistencies between and within different methods
- 2014
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In: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 14:2, s. 361-373
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Journal article (peer-reviewed)abstract
- Microsatellite loci are widely used in population genetic studies, but the presence of null alleles may lead to biased results. Here, we assessed five methods that indirectly detect null alleles and found large inconsistencies among them. Our analysis was based on 20 microsatellite loci genotyped in a natural population of Microtus oeconomus sampled during 8years, together with 1200 simulated populations without null alleles, but experiencing bottlenecks of varying duration and intensity, and 120 simulated populations with known null alleles. In the natural population, 29% of positive results were consistent between the methods in pairwise comparisons, and in the simulated data set, this proportion was 14%. The positive results were also inconsistent between different years in the natural population. In the null-allele-free simulated data set, the number of false positives increased with increased bottleneck intensity and duration. We also found a low concordance in null allele detection between the original simulated populations and their 20% random subsets. In the populations simulated to include null alleles, between 22% and 42% of true null alleles remained undetected, which highlighted that detection errors are not restricted to false positives. None of the evaluated methods clearly outperformed the others when both false-positive and false-negative rates were considered. Accepting only the positive results consistent between at least two methods should considerably reduce the false-positive rate, but this approach may increase the false-negative rate. Our study demonstrates the need for novel null allele detection methods that could be reliably applied to natural populations.
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| 29. |
- Diamanti, Klev, et al.
(author)
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Maps of context-dependent putative regulatory regions and genomic signal interactions
- 2016
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In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 44:19, s. 9110-9120
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Journal article (peer-reviewed)abstract
- Gene transcription is regulated mainly by transcription factors (TFs). ENCODE and Roadmap Epigenomics provide global binding profiles of TFs, which can be used to identify regulatory regions. To this end we implemented a method to systematically construct cell-type and species-specific maps of regulatory regions and TF-TF interactions. We illustrated the approach by developing maps for five human cell-lines and two other species. We detected similar to 144k putative regulatory regions among the human cell-lines, with the majority of them being similar to 300 bp. We found similar to 20k putative regulatory elements in the ENCODE heterochromatic domains suggesting a large regulatory potential in the regions presumed transcriptionally silent. Among the most significant TF interactions identified in the heterochromatic regions were CTCF and the cohesin complex, which is in agreement with previous reports. Finally, we investigated the enrichment of the obtained putative regulatory regions in the 3D chromatin domains. More than 90% of the regions were discovered in the 3D contacting domains. We found a significant enrichment of GWAS SNPs in the putative regulatory regions. These significant enrichments provide evidence that the regulatory regions play a crucial role in the genomic structural stability. Additionally, we generated maps of putative regulatory regions for prostate and colorectal cancer human cell-lines.
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| 30. |
- Kowalczyk, Dorota A., et al.
(author)
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Two-Dimensional Crystals as a Buffer Layer for High Work Function Applications : The Case of Monolayer MoO3
- 2022
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In: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 14:39, s. 44506-44515
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Journal article (peer-reviewed)abstract
- We propose that the crystallinity of two-dimensional (2D) materials is a crucial factor for achieving highly effective work function (WF) modification. A crystalline 2D MoO3 monolayer enhances substrate WF up to 6.4 eV for thicknesses as low as 0.7 nm. Such a high WF makes 2D MoO3 a great candidate for tuning properties of anode materials and for the future design of organic electronic devices, where accurate evaluation of the WF is crucial. We provide a detailed investigation of WF of 2D α-MoO3 directly grown on highly ordered pyrolytic graphite, by means of Kelvin probe force microscopy (KPFM) and ultraviolet photoemission spectroscopy (UPS). This study underlines the importance of a controlled environment and the resulting crystallinity to achieve high WF in MoO3. UPS is proved to be suitable for determining higher WF attributed to 2D islands on a substrate with lower WF, yet only in particular cases of sufficient coverage. KPFM remains a method of choice for nanoscale investigations, especially when conducted under ultrahigh vacuum conditions. Our experimental results are supported by density functional theory calculations of electrostatic potential, which indicate that oxygen vacancies result in anisotropy of WF at the sides of the MoO3 monolayer. These novel insights into the electronic properties of 2D-MoO3 are promising for the design of electronic devices with high WF monolayer films, preserving the transparency and flexibility of the systems.
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| 31. |
- Kruczyk, Marcin, et al.
(author)
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Integration of genome-wide of Stat3 binding and epigenetic modification mapping with transcriptome reveals novel Stat3 target genes in glioma cells
- 2014
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In: Biochimica et Biophysica Acta. - : Elsevier BV. - 0006-3002 .- 1878-2434. ; 1839:11, s. 1341-1350
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in many human tumors, including gliomas, and regulates the expression of genes implicated in proliferation, survival, apoptosis, angiogenesis and immune regulation. Only a small fraction of those genes has been proven to be direct STAT3 targets. In gliomas, STAT3 can play tumor suppressive or oncogenic roles depending on the tumor genetic background with target genes being largely unknown.RESULTS: We used chromatin immunoprecipitation, promoter microarrays and deep sequencing to assess the genome-wide occupancy of phospho (p)-Stat3 and epigenetic modifications of H3K4me3 and H3ac in C6 glioma cells. This combined assessment identified a list of 1200 genes whose promoters have both Stat3 binding sites and epigenetic marks characteristic for actively transcribed genes. The Stat3 and histone markings data were also intersected with a set of microarray data from C6 glioma cells after inhibition of Jak2/Stat3 signaling. Subsequently, we found 284 genes characterized by p-Stat3 occupancy, activating histone marks and transcriptional changes. Novel genes were screened for their potential involvement in oncogenesis, and the most interesting hits were verified by ChIP-PCR and STAT3 knockdown in human glioma cells.CONCLUSIONS: Non-random association between silent genes, histone marks and p-Stat3 binding near transcription start sites was observed, consistent with its repressive role in transcriptional regulation of target genes in glioma cells with specific genetic background.
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| 32. |
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| 33. |
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| 34. |
- Pilot, Malgorzata, et al.
(author)
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Genetic Variability of the Grey Wolf Canis lupus in the Caucasus in Comparison with Europe and the Middle East : Distinct or Intermediary Population?
- 2014
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:4, s. e93828-
-
Journal article (peer-reviewed)abstract
- Despite continuous historical distribution of the grey wolf (Canis lupus) throughout Eurasia, the species displays considerable morphological differentiation that resulted in delimitation of a number of subspecies. However, these morphological discontinuities are not always consistent with patterns of genetic differentiation. Here we assess genetic distinctiveness of grey wolves from the Caucasus (a region at the border between Europe and West Asia) that have been classified as a distinct subspecies C. l. cubanensis. We analysed their genetic variability based on mtDNA control region, microsatellite loci and genome-wide SNP genotypes (obtained for a subset of the samples), and found similar or higher levels of genetic diversity at all these types of loci as compared with other Eurasian populations. Although we found no evidence for a recent genetic bottleneck, genome-wide linkage disequilibrium patterns suggest a long-term demographic decline in the Caucasian population - a trend consistent with other Eurasian populations. Caucasian wolves share mtDNA haplotypes with both Eastern European and West Asian wolves, suggesting past or ongoing gene flow. Microsatellite data also suggest gene flow between the Caucasus and Eastern Europe. We found evidence for moderate admixture between the Caucasian wolves and domestic dogs, at a level comparable with other Eurasian populations. Taken together, our results show that Caucasian wolves are not genetically isolated from other Eurasian populations, share with them the same demographic trends, and are affected by similar conservation problems.
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| 35. |
- Torabi Moghadam, Behrooz, et al.
(author)
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Combinatorial identification of DNA methylation patterns over age in the human brain
- 2016
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In: BMC Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 17
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Journal article (peer-reviewed)abstract
- Background: DNA methylation plays a key role in developmental processes, which is reflected in changing methylation patterns at specific CpG sites over the lifetime of an individual. The underlying mechanisms are complex and possibly affect multiple genes or entire pathways. Results: We applied a multivariate approach to identify combinations of CpG sites that undergo modifications when transitioning between developmental stages. Monte Carlo feature selection produced a list of ranked and statistically significant CpG sites, while rule-based models allowed for identifying particular methylation changes in these sites. Our rule-based classifier reports combinations of CpG sites, together with changes in their methylation status in the form of easy-to-read IF-THEN rules, which allows for identification of the genes associated with the underlying sites. Conclusion: We utilized machine learning and statistical methods to discretize decision class (age) values to get a general pattern of methylation changes over the lifespan. The CpG sites present in the significant rules were annotated to genes involved in brain formation, general development, as well as genes linked to cancer and Alzheimer's disease.
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| 36. |
- Umer, Husen M., et al.
(author)
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A Significant Regulatory Mutation Burden at a High-Affinity Position of the CTCF Motif in Gastrointestinal Cancers
- 2016
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In: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 37:9, s. 904-913
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Journal article (peer-reviewed)abstract
- Somatic mutations drive cancer and there are established ways to study those in coding sequences. It has been shown that some regulatory mutations are over-represented in cancer. We develop a new strategy to find putative regulatory mutations based on experimentally established motifs for transcription factors (TFs). In total, we find 1,552 candidate regulatory mutations predicted to significantly reduce binding affinity of many TFs in hepatocellular carcinoma and affecting binding of CTCF also in esophagus, gastric, and pancreatic cancers. Near mutated motifs, there is a significant enrichment of (1) genes mutated in cancer, (2) tumor-suppressor genes, (3) genes in KEGG cancer pathways, and (4) sets of genes previously associated to cancer. Experimental and functional validations support the findings. The strategy can be applied to identify regulatory mutations in any cell type with established TF motifs and will aid identifications of genes contributing to cancer.
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| 37. |
- Weigl, Wojciech, et al.
(author)
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Analgesic efficacy of intrathecal fentanyl during the period of highest analgesic demand after cesarean section A randomized controlled study
- 2016
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In: Medicine. - 0025-7974 .- 1536-5964. ; 95:24
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Journal article (peer-reviewed)abstract
- Cesarean section (CS) is one of the most common surgical procedures in female patients. We aimed to evaluate the postoperative analgesic efficacy of intrathecal fentanyl during the period of greatest postoperative analgesic demand after CS. This period was defined by detailed analysis of patient-controlled analgesia (PCA) usage. This double-blind, placebo-controlled, parallel-group randomized trial included 60 parturients who were scheduled for elective CS. Participants received spinal anesthesia with bupivacaine supplemented with normal saline (control group) or with fentanyl 25 mg (fentanyl group). To evaluate primary endpoints, we measured total pethidine consumption over the period of greatest PCA pethidine requirement. For verification of secondary endpoints, we recorded intravenous PCA requirement in other time windows, duration of effective analgesia, pain scores assessed by visual analog scale, opioid side effects, hemodynamic changes, neonatal Apgar scores, and intraoperative pain. Detailed analysis of hour-by-hour PCA opioid requirements showed that the greatest demand for analgesics among patients in the control group occurred during the first 12 hours after surgery. Patients in the fentanyl group had significantly reduced opioid consumption compared with the controls during this period and had a prolonged duration of effective analgesia. The groups were similar in visual analog scale, incidence of analgesia-related side effects (nausea/vomiting, pruritus, oversedation, and respiratory depression), and neonatal Apgar scores. Mild respiratory depression occurred in 1 patient in each group. Fewer patients experienced intraoperative pain in the fentanyl group (3% vs 23%; relative risk 6.8, 95% confidence interval 0.9-51.6). The requirement for postoperative analgesics is greatest during the first 12hours after induction of anesthesia in patients undergoing CS. The addition of intrathecal fentanyl to spinal anesthesia is effective for intraoperative analgesia and decreases opioid consumption during the period of the highest analgesic demand after CS, without an increase in maternal or neonatal side effects. We recommend using intrathecal fentanyl for CS in medical centers not using morphine or other opioids intrathecally at present.
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| 38. |
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| 39. |
- Weigl, Wojciech, et al.
(author)
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Perioperative analgesia after intrathecal fentanyl and morphine or morphine alone for cesarean section : A randomized controlled study
- 2017
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In: Medicine. - : LIPPINCOTT WILLIAMS & WILKINS. - 0025-7974 .- 1536-5964. ; 96:48
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Journal article (peer-reviewed)abstract
- Objectives: Intrathecal morphine is used in the postoperative management of pain after caesarean section (CS), but might not be optimal for intraoperative analgesia. We hypothesized that intrathecal fentanyl could supplement intraoperative analgesia when added to a local anesthetic and morphine without affecting management of postoperative pain.Methods: This prospective, randomized, double-blind, parallel-group study included 60 parturients scheduled for elective CS. Spinal anesthesia consisted of bupivacaine with either morphine 100 mu g (M group), or fentanyl 25 mu g and morphine 100 mu g (FM group). The frequency of intraoperative pain and pethidine consumption in the 24 hours postoperatively was recorded.Results: Fewer patients in the FM group required additional intraoperative analgesia (P < .01, relative risk 0.06, 95% confidence interval [CI] 0.004-1.04). The FM group was noninferior to the M group for 24-hour opioid consumption (95% CI -10.0 mg to 45.7 mg, which was below the prespecified boundary of 50 mg). Pethidine consumption in postoperative hours 1 to 12 was significantly higher in the FM group (P=.02). Postoperative nausea and vomiting (PONV) were more common in the FM group (P=.01). Visual analog scale scores, effective analgesia, Apgar scores, and rates of pruritus and respiratory depression were similar between the groups.Conclusions: Intrathecal combination of fentanyl and morphine may provide better perioperative analgesia than morphine alone in CS and could be useful when the time from anesthesia to skin incision is short. However, an increase in PONV and possible acute spinal opioid tolerance after addition of intrathecal fentanyl warrants further investigation using lower doses of fentanyl.
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| 40. |
- Aad, G., et al.
(author)
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- 2011
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swepub:Mat__t (peer-reviewed)
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| 41. |
- Aad, G., et al.
(author)
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- 2011
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Journal article (peer-reviewed)
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| 42. |
- Aad, G., et al.
(author)
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- 2012
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swepub:Mat__t (peer-reviewed)
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| 43. |
- Aad, G., et al.
(author)
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- 2012
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swepub:Mat__t (peer-reviewed)
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| 44. |
- Aad, G., et al.
(author)
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- 2011
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swepub:Mat__t (peer-reviewed)
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| 45. |
- Aad, G., et al.
(author)
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- 2013
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swepub:Mat__t (peer-reviewed)
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| 46. |
- Aad, G., et al.
(author)
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- 2013
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Journal article (peer-reviewed)
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| 47. |
- Aad, G., et al.
(author)
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- 2013
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In: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 15
-
Journal article (peer-reviewed)
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| 48. |
- Aad, G., et al.
(author)
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- 2012
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swepub:Mat__t (peer-reviewed)
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| 49. |
- Aad, G., et al.
(author)
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- 2012
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swepub:Mat__t (peer-reviewed)
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| 50. |
- Aad, G., et al.
(author)
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- 2012
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swepub:Mat__t (peer-reviewed)
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