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- Al-Anati, Lauy, et al.
(author)
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Hydroxyl metabolite of PCB 180 induces DNA damage signaling and enhances the DNA damaging effect of benzo[a]pyrene
- 2015
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In: Chemico-Biological Interactions. - : Elsevier. - 0009-2797 .- 1872-7786. ; 239, s. 164-173
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Journal article (peer-reviewed)abstract
- Non-dioxin-like (NDL) polychlorinated biphenyls (PCBs) and their hydroxyl metabolites (OH-PCBs) are ubiquitous environmental contaminants in human tissues and blood. The toxicological impact of these metabolites is poorly understood. In this study rats were exposed to ultrapure PCB180 (10-1000 mg/kg bw) for 28 days and induction of genotoxic stress in liver was investigated. DNA damage signaling proteins (pChk1Ser317 and gamma H2AXSer319) were increased dose dependently in female rats. This increase was paralleled by increasing levels of the metabolite 3'-OH-PCB180. pChk1 was the most sensitive marker. In in vitro studies HepG2 cells were exposed to 1 mu M of PCB180 and 3'-OH-PCB180 or the positive control benzo[a]pyrene (BaP, 5 mu M). 3'-OH-PCB180, but not PCB180, induced CYP1A1 mRNA and gamma H2AX. CYP1A1 mRNA induction was seen at 1 h, and gamma H2AX at 3 h. The anti-oxidant N-Acetyl-L-Cysteine (NAC) completely prevented, and 17 beta-estradiol amplified the gamma H2AX induction by 3'-OH-PCB180. As 3'-OH-PCB180 induced CYP1A1, a major BaP-metabolizing and activating enzyme, interactions between 3'-OH-PCB180 and BaP was also studied. The metabolite amplified the DNA damage signaling response to BaP. In conclusion, metabolism of PCB180 to its hydroxyl metabolite and the subsequent induction of CYP1A1 seem important for DNA damage induced by PCB180 in vivo. Amplification of the response with estradiol may explain why DNA damage was only seen in female rats.
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- Engberg, David L. J., 1986-, et al.
(author)
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Atom probe tomography field evaporation characteristics and compositional corrections of ZrB2
- 2019
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In: Materials Characterization. - : Elsevier BV. - 1044-5803 .- 1873-4189. ; 156
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Journal article (peer-reviewed)abstract
- The microstructure of stoichiometric ZrB2.0 and B over-stoichiometric ZrB2.5 thin films has been studied using atom probe tomography (APT), X-ray diffraction, and transmission electron microscopy. Both films consist of columnar ZrB2 grains with AlB2-type crystal structure. The narrow stoichiometry range of ZrB2 results in the presence of separate disordered B-rich boundaries even in ZrB2.0. At higher average B content, specifically ZrB2.5, the formation of a continuous network around the sides of the ZrB2 columns is promoted. In addition, the APT field evaporation characteristics of ZrB2 and its influence on the measured local composition has been studied and compared to the average composition from elastic recoil detection analysis (ERDA). Differences in the measured average compositions of the two techniques are explained by the APT detector dead-time/space. A new pile-up pairs correction procedure based on co-evaporation correlation data was thus employed here for the APT data and compared with the 10B-method (the B equivalence of the 13C-method), as well as the combination of both methods. In ZrB2.0, all of the applied compositional correction methods were found to reduce the compositional difference when appropriate isotopic abundances were used. In ZrB2.5, the inhomogeneity of the film likely increased the local APT composition to such an extent that even conservative correction procedures overestimated the B content compared to the ERDA reference. The strengths of the pile-up pairs correction compared the 10B and the combined methods are higher precision, due to it being less dependent on the accuracy of estimated isotopic abundances, and that the correction itself is not dependent on careful background correction of the mass spectrum.
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- Eriksson, Mia, et al.
(author)
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Agonistic targeting of TLR1/TLR2 induces p38 MAPK-dependent apoptosis and NFκB-dependent differentiation of AML cells
- 2017
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In: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 1:23, s. 2046-2057
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Journal article (peer-reviewed)abstract
- Acute myeloid leukemia (AML) is associated with poor survival, and there is a strong need to identify disease vulnerabilities that might reveal new treatment opportunities. Here, we found that Toll-like receptor 1 (TLR1) and TLR2 are upregulated on primary AML CD34+CD38-cells relative to corresponding normal bone marrow cells. Activating the TLR1/TLR2 complex by the agonist Pam3CSK4 inMLL-AF9-driven human AML resulted in induction of apoptosis by p38 MAPK-dependent activation of Caspase 3 and myeloid differentiation in a NFκB-dependent manner. By using murineTrp53 -/- MLL-AF9AML cells, we demonstrate that p53 is dispensable for Pam3CSK4-induced apoptosis and differentiation. Moreover, murineAML1-ETO9a-driven AML cells also were forced into apoptosis and differentiation on TLR1/TLR2 activation, demonstrating that the antileukemic effects observed were not confined toMLL-rearranged AML. We further evaluated whether Pam3CSK4 would exhibit selective antileukemic effects. Ex vivo Pam3CSK4 treatment inhibited murine and human leukemia-initiating cells, whereas murine normal hematopoietic stem and progenitor cells (HSPCs) were relatively less affected. Consistent with these findings, primary human AML cells across several genetic subtypes of AML were more vulnerable for TLR1/TLR2 activation relative to normal human HSPCs. In theMLL-AF9AML mouse model, treatment with Pam3CSK4 provided proof of concept for in vivo therapeutic efficacy. Our results demonstrate that TLR1 and TLR2 are upregulated on primitive AML cells and that agonistic targeting of TLR1/TLR2 forces AML cells into apoptosis by p38 MAPK-dependent activation of Caspase 3, and differentiation by activating NFκB, thus revealing a new putative strategy for therapeutically targeting AML cells.
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- Myléus, Anna, MD PhD, et al.
(author)
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Questionnaire showed that Swedish paediatric clinics complied well with the revised European guidelines for diagnosing coeliac disease
- 2019
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In: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 108:6, s. 1140-1143
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Journal article (peer-reviewed)abstract
- Aim: In 2012, revised criteria for diagnosing childhood coeliac disease were published by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition and incorporated into the revised Swedish guidelines the same year. These made it possible, in certain cases, to diagnose coeliac disease without taking small bowel biopsies. This survey assessed the extent to which the new guidelines were implemented by Swedish paediatric clinics two years after their introduction.Methods: In October 2014, we distributed a paper questionnaire including five questions on diagnostic routines to the 40 paediatric clinics in university or regional hospitals in Sweden that perform small bowel biopsies.Results: All 36 (90%) clinics that responded used anti-tissue transglutaminase antibodies as the initial diagnostic test and some also used serological markers. Most clinics (81%) used endoscopy and took multiple duodenal biopsies, whereas only a few (19%) occasionally employed a suction capsule. Almost all clinics (86%) omitted taking small bowel biopsies in symptomatic children with repeatedly high coeliac serology and positive genotyping, thereby avoiding the need for invasive endoscopy under anaesthesia.Conclusion: The 2012 Swedish Paediatric Coeliac Disease Diagnostic Guidelines had been widely accepted and implemented in routine health care two years after their introduction.
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- Randmaa, Maria, et al.
(author)
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Implementing situation-background-assessment-recommendation in an anaesthetic clinic and subsequent information retention among receivers : a prospective interventional study of postoperative handovers
- 2016
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In: European Journal of Anaesthesiology. - 0265-0215 .- 1365-2346. ; 33:3, s. 172-178
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Journal article (peer-reviewed)abstract
- BACKGROUND: Communication errors cause clinical incidents and adverse events in relation to surgery. To ensure proper postoperative patient care, it is essential that personnel remember and recall information given during the handover from the operating theatre to the postanaesthesia care unit. Formalizing the handover may improve communication and aid memory, but research in this area is lacking.OBJECTIVE: The objective of this study was to evaluate whether implementing the communication tool Situation-Background-Assessment-Recommendation (SBAR) affects receivers' information retention after postoperative handover.DESIGN: A prospective intervention study with an intervention group and comparison nonintervention group, with assessments before and after the intervention.SETTING: The postanaesthesia care units of two hospitals in Sweden during 2011 and 2012.PARTICIPANTS: Staff involved in the handover between the operating theatre and the postanaesthesia care units within each hospital.INTERVENTION: Implementation of the communication tool SBAR in one hospital.MAIN OUTCOME MEASURES: The main outcome was the percentage of recalled information sequences among receivers after the handover. Data were collected using both audio-recordings and observations recorded on a study-specific protocol form.RESULTS: Preintervention, 73 handovers were observed (intervention group, n = 40; comparison group, n = 33) involving 72 personnel (intervention group, n = 40; comparison group, n = 32). Postintervention, 91 handovers were observed (intervention group, n = 44; comparison group, n = 47) involving 57 personnel (intervention group, n = 31; comparison group, n = 26). In the intervention group, the percentage of recalled information sequences by the receivers increased from 43.4% preintervention to 52.6% postintervention (P = 0.004) and the SBAR structure improved significantly (P = 0.028). In the comparison group, the corresponding figures were 51.3 and 52.6% (P = 0.725) with no difference in SBAR structure. When a linear regression generalised estimating equation model was used to account for confounding influences, we were unable to show a significant difference in the information recalled between the intervention group and the nonintervention group over time.CONCLUSION: Compared with the comparison group with no intervention, when SBAR was implemented in an anaesthetic clinic, we were unable to show any improvement in recalled information among receivers following postoperative handover.TRIAL REGISTRATION: Current controlled trials http://www.controlled-trials.com Identifier: ISRCTN37251313.
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- Wallin Lundell, Inger, et al.
(author)
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Neuroticism-related personality traits are associated with posttraumatic stress after abortion : findings from a Swedish multi-center cohort study
- 2017
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In: BMC Women's Health. - : Springer Science and Business Media LLC. - 1472-6874. ; 17:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Most women who choose to terminate a pregnancy cope well following an abortion, although some women experience severe psychological distress. The general interpretation in the field is that the most consistent predictor of mental disorders after induced abortion is the mental health issues that women present with prior to the abortion. We have previously demonstrated that few women develop posttraumatic stress disorder (PTSD) or posttraumatic stress symptoms (PTSS) after induced abortion. Neuroticism is one predictor of importance for PTSD, and may thus be relevant as a risk factor for the development of PTSD or PTSS after abortion. We therefore compared Neuroticism-related personality trait scores of women who developed PTSD or PTSS after abortion to those of women with no evidence of PTSD or PTSS before or after the abortion.METHODS: A Swedish multi-center cohort study including six Obstetrics and Gynecology Departments, where 1294 abortion-seeking women were included. The Screen Questionnaire-Posttraumatic Stress Disorder (SQ-PTSD) was used to evaluate PTSD and PTSS. Measurements were made at the first visit and at three and six month after the abortion. The Swedish universities Scales of Personality (SSP) was used for assessment of Neuroticism-related personality traits. Multiple logistic regression analyses were performed to investigate the risk factors for development of PTSD or PTSS post abortion.RESULTS: Women who developed PTSD or PTSS after the abortion had higher scores than the comparison group on several of the personality traits associated with Neuroticism, specifically Somatic Trait Anxiety, Psychic Trait Anxiety, Stress Susceptibility and Embitterment. Women who reported high, or very high, scores on Neuroticism had adjusted odds ratios for PTSD/PTSS development of 2.6 (CI 95% 1.2-5.6) and 2.9 (CI 95% 1.3-6.6), respectively.CONCLUSION: High scores on Neuroticism-related personality traits influence the risk of PTSD or PTSS post abortion. This finding supports the argument that the most consistent predictor of mental disorders after abortion is pre-existing mental health status.
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