| 1. |
- Ferreira, Catarina, et al.
(författare)
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Genetic variation in the conjugative plasmidome of a hospital effluent multidrug resistant Escherichia coli strain
- 2019
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 220, s. 748-759
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Tidskriftsartikel (refereegranskat)abstract
- Bacteria harboring conjugative plasmids have the potential for spreading antibiotic resistance through horizontal gene transfer. It is described that the selection and dissemination of antibiotic resistance is enhanced by stressors, like metals or antibiotics, which can occur as environmental contaminants. This study aimed at unveiling the composition of the conjugative plasmidome of a hospital effluent multidrug resistant Escherichia coli strain (H1FC54) under different mating conditions. To meet this objective, plasmid pulsed field gel electrophoresis, optical mapping analyses and DNA sequencing were used in combination with phenotype analysis. Strain H1FC54 was observed to harbor five plasmids, three of which were conjugative and two of these, pH1FC54_330 and pH1FC54_140, contained metal and antibiotic resistance genes. Transconjugants obtained in the absence or presence of tellurite (0.5 μM or 5 μM), arsenite (0.5 μM, 5 μM or 15 μM) or ceftazidime (10 mg/L) and selected in the presence of sodium azide (100 mg/L) and tetracycline (16 mg/L) presented distinct phenotypes, associated with the acquisition of different plasmid combinations, including two co-integrate plasmids, of 310 kbp and 517 kbp. The variable composition of the conjugative plasmidome, the formation of co-integrates during conjugation, as well as the transfer of non-transferable plasmids via co-integration, and the possible association between antibiotic, arsenite and tellurite tolerance was demonstrated. These evidences bring interesting insights into the comprehension of the molecular and physiological mechanisms that underlie antibiotic resistance propagation in the environment.
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| 2. |
- Ferreira, Catarina, et al.
(författare)
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Polyphasic characterization of carbapenemresistant Klebsiella pneumoniae clinical isolates suggests vertical transmission of the bla KPC-3 gene
- 2021
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 16:2 Febuary
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Tidskriftsartikel (refereegranskat)abstract
- Carbapenem-resistant Klebsiella pneumoniae are a major global threat in healthcare facilities. The propagation of carbapenem resistance determinants can occur through vertical transmission, with genetic elements being transmitted by the host bacterium, or by horizontal transmission, with the same genetic elements being transferred among distinct bacterial hosts. This work aimed to track carbapenem resistance transmission by K. pneumoniae in a healthcare facility. The study involved a polyphasic approach based on conjugation assays, resistance phenotype and genotype analyses, whole genome sequencing, and plasmid characterization by pulsed field gel electrophoresis and optical DNA mapping. Out of 40 K. pneumoniae clinical isolates recovered over two years, five were carbapenem- and multidrug- resistant and belonged to multilocus sequence type ST147. These isolates harboured the carbapenemase encoding blaKPC-3 gene, integrated in conjugative plasmids of 140 kbp or 55 kbp, belonging to replicon types incFIA/incFIIK or incN/incFIIK, respectively. The two distinct plasmids encoding the blaKPC-3 gene were associated with distinct genetic lineages, as confirmed by optical DNA mapping and whole genome sequence analyses. These results suggested vertical (bacterial strain-based) transmission of the carbapenem-resistance genetic elements. Determination of the mode of transmission of antibiotic resistance in healthcare facilities, only possible based on polyphasic approaches as described here, is essential to control resistance propagation.
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| 3. |
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| 4. |
- Suempelmann, R., et al.
(författare)
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Perioperative fasting times in children and adolescents
- 2022
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Ingår i: Anasthesiologie und Intensivmedizin. - : AKTIV DRUCK & VERLAG GMBH. - 0170-5334 .- 1439-0256. ; 63, s. 320-328
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Tidskriftsartikel (refereegranskat)abstract
- The German Scientific Working Group for Paediatric Anaesthesia (Wissenschaftlicher Arbeitskreis Kinderansthesie, WAKKA) of the German Society for Anaesthesia and Intensive Care Medicine (DGAI) has updated their current recommendations on preoperative fasting in children from 2007, along with the preoperative fasting statement of the German Association of Anaesthesiologists (Berufsverband Deutscher Anasthesisten, BDA) and DGAI from 2016 in agreement with the new evidence-based European Guideline of the European Society of Anaesthesiology and Intensive Care (ESAIC) of 2022 - and transferred it into the S1 Guideline format of the Association of the Scientific. Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgeselischaften e. V., AWMF). This revision became necessary because recent studies had shown that optimized fasting times improved hornoeostasis and well-being of the children, while the risk of regurgitation and aspiration had not increased. On the other hand, long periods of fasting might be the cause of misbehaviour, stress, iatrogenic dehydration and catabolism. The updated S1 Guideline therefore recommends shorter fasting times of 4 hours for small, light meals and/or formula or cow's milk (still 6 hours for a full meal), 3 hours for breast milk, and 1 hour for clear fluids (6-4-3-1 Rule). In addition, the new S1 Guideline contains further recommendations for children with concomitant diseases that are of relevance to anaesthesia, for the application of ultrasound to examine the stomach content prior to the induction of anaesthesia, for postoperative fasting and the implementation of the new rules in clinical practice.
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| 5. |
- Blacker, C, et al.
(författare)
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Randomized cross-over study investigating the tolerability and side effects of an intra-oral air-cooling device compared to ice in healthy volunteers
- 2023
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Ingår i: Medical Oncology. - : Springer. - 1357-0560 .- 1559-131X. ; 40
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Tidskriftsartikel (refereegranskat)abstract
- Oral cryotherapy (OC) is a common preventive treatment of oral mucositis (OM) and is recommended in international guidelines. Ice and air OC have previously been shown to result in temperature reductions of 8.1-12.9 degrees C, and 14.5 degrees C, respectively, in healthy volunteers. However, no direct comparison between these two modalities has been performed. The primary aim was to investigate the tolerability and side effects of air OC using an intra-oral air-cooling (IOAC) device compared with ice OC. The secondary aim was to evaluate the temperature reduction in the mouth for the two respective methods. Cross-over study with randomization to order of treatment, in 15 healthy volunteers. We evaluated the self-reported intensity, frequency, and discomfort for 13 pre-defined side effects used in previous studies. All participants were able to complete both OC sessions, although one participant required reduced airflow in the air OC arm. The subjects reported more discomfort from being cold, having sensitive teeth, and numbness in the ice OC group, while they reported more discomfort from swallowing when subjected to air OC. No significant difference in the median temperature reduction was detected in the two modalities, except for the dorsal posterior part of the tongue where temperature reduction was larger in the ice OC group. We found that oral cooling using a new IOAC device was tolerated and seems to be safe in healthy volunteers.
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| 6. |
- de Graaff, Jurgen C., et al.
(författare)
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Ephedrine to treat intraoperative hypotension in infants : what is the target?
- 2023
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Ingår i: British Journal of Anaesthesia. - : Elsevier. - 0007-0912 .- 1471-6771. ; 130:5, s. 510-515
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Off-label use of medications in paediatric anaesthesia is common practice, owing to the relative paucity of evidence -based dosing regimens in children. Well-performed dose-finding studies, especially in infants, are rare and urgently needed. Unanticipated effects can result when paediatric dosing is based on adult parameters or local traditions. A recent dose-finding study on ephedrine highlights the uniqueness of paediatric dosing in comparison with adult dosing. We discuss the problems of off-label medication use and the lack of evidence for various definitions of hypotension and associated treatment strategies in paediatric anaesthesia. What is the aim of treating hypotension associated with anaesthesia induction: restoring the MAP to awake baseline values or elevating it above a provisional hypotension threshold?
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| 7. |
- Dvirnas, Albertas, et al.
(författare)
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Detection of structural variations in densely-labelled optical DNA barcodes: A hidden Markov model approach
- 2021
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:11
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Tidskriftsartikel (refereegranskat)abstract
- Large-scale genomic alterations play an important role in disease, gene expression, and chromosome evolution. Optical DNA mapping (ODM), commonly categorized into sparsely-labelled ODM and densely-labelled ODM, provides sequence-specific continuous intensity profiles (DNA barcodes) along single DNA molecules and is a technique well-suited for detecting such alterations. For sparsely-labelled barcodes, the possibility to detect large genomic alterations has been investigated extensively, while densely-labelled barcodes have not received as much attention. In this work, we introduce HMMSV, a hidden Markov model (HMM) based algorithm for detecting structural variations (SVs) directly in densely-labelled barcodes without access to sequence information. We evaluate our approach using simulated data-sets with 5 different types of SVs, and combinations thereof, and demonstrate that the method reaches a true positive rate greater than 80% for randomly generated barcodes with single variations of size 25 kilobases (kb). Increasing the length of the SV further leads to larger true positive rates. For a real data-set with experimental barcodes on bacterial plasmids, we successfully detect matching barcode pairs and SVs without any particular assumption of the types of SVs present. Instead, our method effectively goes through all possible combinations of SVs. Since ODM works on length scales typically not reachable with other techniques, our methodology is a promising tool for identifying arbitrary combinations of genomic alterations.
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| 8. |
- Enblad P., Frykholm P., Valtysson J., Silander H C., Andersson J., Fasth K J., Watanabe Y., Långström B., Hillered L., Persson L.
(författare)
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Middle cerebral artery occlusion and reperfusion in primates monitored by microdialysis and sequential positron emission tomography
- 2001
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Ingår i: Stroke. ; :32 (7), s. 1574-80
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Tidskriftsartikel (refereegranskat)
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| 9. |
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| 10. |
- Johansson, J., et al.
(författare)
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Gustavson syndrome is caused by an in-frame deletion in RBMX associated with potentially disturbed SH3 domain interactions
- 2024
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Ingår i: European Journal of Human Genetics. - : SPRINGERNATURE. - 1018-4813 .- 1476-5438. ; 32:3, s. 333-341
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Tidskriftsartikel (refereegranskat)abstract
- RNA binding motif protein X-linked (RBMX) encodes the heterogeneous nuclear ribonucleoprotein G (hnRNP G) that regulates splicing, sister chromatid cohesion and genome stability. RBMX knock down experiments in various model organisms highlight the gene's importance for brain development. Deletion of the RGG/RG motif in hnRNP G has previously been associated with Shashi syndrome, however involvement of other hnRNP G domains in intellectual disability remain unknown. In the current study, we present the underlying genetic and molecular cause of Gustavson syndrome. Gustavson syndrome was first reported in 1993 in a large Swedish five-generation family presented with profound X-linked intellectual disability and an early death. Extensive genomic analyses of the family revealed hemizygosity for a novel in-frame deletion in RBMX in affected individuals (NM_002139.4; c.484_486del, p.(Pro162del)). Carrier females were asymptomatic and presented with skewed X-chromosome inactivation, indicating silencing of the pathogenic allele. Affected individuals presented minor phenotypic overlap with Shashi syndrome, indicating a different disease-causing mechanism. Investigation of the variant effect in a neuronal cell line (SH-SY5Y) revealed differentially expressed genes enriched for transcription factors involved in RNA polymerase II transcription. Prediction tools and a fluorescence polarization assay imply a novel SH3-binding motif of hnRNP G, and potentially a reduced affinity to SH3 domains caused by the deletion. In conclusion, we present a novel in-frame deletion in RBMX segregating with Gustavson syndrome, leading to disturbed RNA polymerase II transcription, and potentially reduced SH3 binding. The results indicate that disruption of different protein domains affects the severity of RBMX-associated intellectual disabilities.
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