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| 32. |
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| 33. |
- Forman, Ruth, et al.
(författare)
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Eosinophils may play regionally disparate roles in influencing IgA+ plasma cell numbers during large and small intestinal inflammation
- 2016
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Ingår i: BMC Immunology. - : Springer Science and Business Media LLC. - 1471-2172. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Eosinophils are innate immune cells present in the intestine during steady state conditions. An intestinal eosinophilia is a hallmark of many infections and an accumulation of eosinophils is also observed in the intestine during inflammatory disorders. Classically the function of eosinophils has been associated with tissue destruction, due to the release of cytotoxic granule contents. However, recent evidence has demonstrated that the eosinophil plays a more diverse role in the immune system than previously acknowledged, including shaping adaptive immune responses and providing plasma cell survival factors during the steady state. Importantly, it is known that there are regional differences in the underlying immunology of the small and large intestine, but whether there are differences in context of the intestinal eosinophil in the steady state or inflammation is not known. Results: Our data demonstrates that there are fewer IgA+ plasma cells in the small intestine of eosinophil-deficient ΔdblGATA-1 mice compared to eosinophil-sufficient wild-type mice, with the difference becoming significant post-infection with Toxoplasma gondii. Remarkably, and in complete contrast, the absence of eosinophils in the inflamed large intestine does not impact on IgA+ cell numbers during steady state, and is associated with a significant increase in IgA+ cells post-infection with Trichuris muris compared to wild-type mice. Thus, the intestinal eosinophil appears to be less important in sustaining the IgA+ cell pool in the large intestine compared to the small intestine, and in fact, our data suggests eosinophils play an inhibitory role. The dichotomy in the influence of the eosinophil over small and large intestinal IgA+ cells did not depend on differences in plasma cell growth factors, recruitment potential or proliferation within the different regions of the gastrointestinal tract (GIT). Conclusions: We demonstrate for the first time that there are regional differences in the requirement of eosinophils for maintaining IgA+ cells between the large and small intestine, which are more pronounced during inflammation. This is an important step towards further delineation of the enigmatic functions of gut-resident eosinophils.
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| 34. |
- Gepner, B. D., et al.
(författare)
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Comparison of human body models in frontal crashes with reclined seatback
- 2019
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Ingår i: Conference proceedings International Research Council on the Biomechanics of Injury, IRCOBI. - 2235-3151. ; , s. 293-307
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Konferensbidrag (refereegranskat)abstract
- Reclined seating configurations, relevant to the future of Autonomous Driving Systems is likely to challenge the current state-of-the-art restraint systems. Human body models (HBM) offer an attractive tool to support the design process, however their validity in the reclined scenario remains questionable. The goal of this study is to compare the response of selected HBMs in the frontal, reclined scenario, while utilizing a new prototype restraint system. A sled model with a generic seat, 50 deg seatback recline angle and a prototype 3-point belt system was used in this study. Four different male HBMs were compared, the Global Human Body Model Consortium (GHBMC) simplified occupant model (GHBMC-S), the GHBMC detailed model (GHBMC-D), Total Human Model for Safety SAFER (THUMS-S) model, and THUMS-v5 model. All HBMs showed good pelvis engagement, except GHBMC-D that submarined under the lap belt. Additionally, large differences were observed in pelvis and lumbar spine response between GHBMC and THUMS family models. Since no relevant PMHS data is currently available, it is impossible to evaluate the biofidelity of these models in the reclined scenarios. Evaluating the relative biofidelity of these models can only be accomplished with experimental data capturing detailed 3D skeletal kinematics and all the boundary forces necessary for model evaluation.
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| 35. |
- Gepner, B. D., et al.
(författare)
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Evaluation of GHBMC, THUMS and SAFER Human Body Models in Frontal Impacts in Reclined Postures
- 2022
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Ingår i: Conference proceedings International Research Council on the Biomechanics of Injury, IRCOBI. - 2235-3151. ; 2022-September, s. 116-143
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Konferensbidrag (refereegranskat)abstract
- Virtual tools, such as human body models (HBMs), can support advances in vehicle development and restraint system design. The goal of this study is to evaluate selected HBMs against data from recent reclined post-mortem human subject (PMHS) tests. Three HBMs - the Global Human Body Modelling Consortium detailed model v.6.0, Total Human Model for Safety v.6.0, and SAFER HBM v.10 - were used in this study. The models were positioned with respect to the average PMHS position and utlised a previously developed environment model. The HBMs were evaluated comparing belt engagement, boundary forces and displacements (in the seat and belt), and the trajectories of the head, T1, T8, T11, L1, L3, and pelvis. The HBMs' belt engagement, boundary forces and displacements, and X-direction (fore-aft) trajectories were all generally consistent with the PMHS. All HBMs predicted more downward motion of the head and T1 compared to the PMHS. The HBMs also showed rearward pelvis pitch at peak lap belt force, opposite to the PMHS. Some of these differences were associated with differences in flexion of the lumbar spine. This is the first study to provide an in-depth evaluation of multiple reclined HBMs in frontal crashes compared to reclined PMHS.
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| 36. |
- Hegedus, Csaba, et al.
(författare)
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Redox control of cancer cell destruction
- 2018
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Ingår i: Redox Biology. - : Elsevier BV. - 2213-2317. ; 16, s. 59-74
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Tidskriftsartikel (refereegranskat)abstract
- Redox regulation has been proposed to control various aspects of carcinogenesis, cancer cell growth, metabolism, migration, invasion, metastasis and cancer vascularization. As cancer has many faces, the role of redox control in different cancers and in the numerous cancer-related processes often point in different directions. In this review, we focus on the redox control mechanisms of tumor cell destruction. The review covers the tumor intrinsic role of oxidants derived from the reduction of oxygen and nitrogen in the control of tumor cell proliferation as well as the roles of oxidants and antioxidant systems in cancer cell death caused by traditional anticancer weapons (chemotherapeutic agents, radiotherapy, photodynamic therapy). Emphasis is also put on the role of oxidants and redox status in the outcome following interactions between cancer cells, cytotoxic lymphocytes and tumor infiltrating macrophages.
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| 37. |
- Henningsen, A. A., et al.
(författare)
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Imprinting disorders in children born after ART: a Nordic study from the CoNARTaS group
- 2020
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 35:5, s. 1178-1184
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION: Is the risk of imprinting disorders increased in children conceived after ART? SUMMARY ANSWER: We found an adjusted odds ratio (AOR) of 2.84 [95% CI: 1.34-6.01] for Beckwith-Wiedemann syndrome in ART children, while the risk of Prader-Willi syndrome, Silver-Russell syndrome or Angelman syndrome was not increased in children conceived after ART. WHAT IS KNOWN ALREADY: Earlier studies, most of them small, have suggested an association between ART and imprinting disorders. STUDY DESIGN, SIZE, DURATION: This was a binational register-based cohort study. All children conceived by ART in Denmark (n = 45 393, born between 1994 and 2014) and in Finland (n = 29 244, born between 1990 and 2014) were identified. The full background populations born during the same time periods in the two countries were included as controls. Odds ratios of imprinting disorders in ART children compared with naturally conceived (NC) children were calculated. The median follow-up time was 8 years and 9 months for ART children and 11 years and 9 months for NC children. PARTICIPANTS/MATERIALS, SETTING, METHODS: From the national health registries in Denmark and Finland, we identified all children diagnosed with Prader-Willi syndrome (n = 143), Silver-Russell syndrome (n = 69), Beckwith-Wiedemann syndrome (n = 105) and Angelman syndrome (n = 72) born between 1994/1990 and 2014, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: We identified a total of 388 children diagnosed with imprinting disorders; 16 of these were conceived after ART. The overall AOR for the four imprinting disorders in ART children compared with NC children was 1.35 [95% CI: 0.80-2.29], but since eight ART children were diagnosed with Beckwith-Wiedemann syndrome, the AOR for this specific imprinting disorder was 2.84 [95% CI: 1.34-6.01]. The absolute risk of Beckwith-Wiedemann syndrome in children conceived after ART was still low: 10.7 out of 100 000 newborns. The risks of Prader-Willi syndrome, Silver-Russell syndrome and Angelman syndrome were not increased in children conceived after ART. LIMITATIONS, REASONS FOR CAUTION: Imprinting disorders are rare events and our results are based on few ART children with imprinting disorders. The aetiology is complex and only partly clarified, and the clinical diagnoses are challenged by a broad phenotypic spectrum. WIDER IMPLICATIONS OF THE FINDINGS: In the existing studies, results on the risk of imprinting disorders in children conceived after ART are ambiguous. This study adds that the risk of imprinting disorders in ART children is very small and perhaps restricted to Beckwith-Wiedemann syndrome.
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| 38. |
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| 39. |
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| 40. |
- Henningsen, A. K. A., et al.
(författare)
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Risk of congenital malformations in live-born singletons conceived after intracytoplasmic sperm injection: a Nordic study from the CoNARTaS group
- 2023
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Ingår i: Fertility and Sterility. - 0015-0282 .- 1556-5653. ; 120:5, s. 1033-1041
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate whether the risk of major congenital malformations is higher in live-born singletons conceived with intracytoplasmic sperm injection (ICSI) compared with in vitro fertilization (IVF)?Design: Nordic register-based cohort study.Setting: Cross-linked data from Medical Birth Registers and National ART and Patient Registers in Denmark, Norway and Sweden. Data were included from the year the first child conceived using ICSI was born: Sweden, 1992; Denmark, 1994; and Norway, 1996. Data were included until 2014 for Denmark and 2015 for Norway and Sweden. Patient(s): All live-born singletons conceived using fresh ICSI (n = 32,484); fresh IVF (n = 47,178); without medical assistance (n = 4,804,844); and cryo-ICSI (n = 7,200) during the study period. Intervention(s): Different in vitro conception methods, and cryopreservation of embryos.Main Outcome Measure(s): Risk of major congenital malformations on the basis of International Classification of Diseases codes. The European Concerted Action on Congenital Anomalies and Twins was used to differentiate between major and minor malformations. Result(s): Among singletons conceived using fresh ICSI, 6.0% had a major malformation, compared with 5.3% of children conceived using fresh IVF; 4.2% of children conceived without medical assistance; and 4.9% of children conceived using cryoICSI; adjusted odds ratio (AOR) 1.07 (95% confidence interval [CI] 1.01-1.14) in ICSI vs. IVF; and AOR 1.28 (95% CI, 1.23- 1.35) in ICSI vs. no medical assistance; and AOR 1.11 (95% CI, 0.99-1.26) in ICSI fresh vs. cryo-ICSI. When malformations were grouped by different organ systems, children conceived using ICSI had a higher risk of respiratory and chromosomal malformations compared with children conceived using IVF, but there were very few cases in each group. When categorizing children conceived using ICSI according to treatment indication (male factor infertility only vs. other indications), we found a higher risk of hypospadias when ICSI was performed because of male factor infertility only (AOR 1.85 [95% CI 1.03-332]). The indications for ICSI changed over time, as male factor infertility did not remain the primary indication for ICSI throughout the study period.Conclusion(s): In this large cohort study, we found the risk of major malformations in live-born singletons to be slightly higher after fresh ICSI compared with fresh IVF. These findings should be considered when choosing the assisted reproductive technology method for couples without male factor infertility. (Fertil Sterile 2023;120:1033-41. (c) 2023 by American Society for Reproductive Medicine.) El resumen esta disponible en Espanol al final del articulo.
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