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- van Thuijl, Hinke F., et al.
(författare)
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Evolution of DNA repair defects during malignant progression of low-grade gliomas after temozolomide treatment
- 2015
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Ingår i: Acta Neuropathologica. - : Springer Verlag (Germany). - 0001-6322 .- 1432-0533. ; 129:4, s. 597-607
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Tidskriftsartikel (refereegranskat)abstract
- Temozolomide (TMZ) increases the overall survival of patients with glioblastoma (GBM), but its role in the clinical management of diffuse low-grade gliomas (LGG) is still being defined. DNA hypermethylation of the O (6) -methylguanine-DNA methyltransferase (MGMT) promoter is associated with an improved response to TMZ treatment, while inactivation of the DNA mismatch repair (MMR) pathway is associated with therapeutic resistance and TMZ-induced mutagenesis. We previously demonstrated that TMZ treatment of LGG induces driver mutations in the RB and AKT-mTOR pathways, which may drive malignant progression to secondary GBM. To better understand the mechanisms underlying TMZ-induced mutagenesis and malignant progression, we explored the evolution of MGMT methylation and genetic alterations affecting MMR genes in a cohort of 34 treatment-na less than ve LGGs and their recurrences. Recurrences with TMZ-associated hypermutation had increased MGMT methylation compared to their untreated initial tumors and higher overall MGMT methylation compared to TMZ-treated non-hypermutated recurrences. A TMZ-associated mutation in one or more MMR genes was observed in five out of six TMZ-treated hypermutated recurrences. In two cases, pre-existing heterozygous deletions encompassing MGMT, or an MMR gene, were followed by TMZ-associated mutations in one of the genes of interest. These results suggest that tumor cells with methylated MGMT may undergo positive selection during TMZ treatment in the context of MMR deficiency.
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| 3. |
- Collins, J.W., et al.
(författare)
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Assessing intra-operative ergonomics and workload in robotic surgery using inertia measuring unit sensors and validated questionnaires
- 2016
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Ingår i: European urology. Supplement. - : Elsevier BV. - 1569-9056 .- 1878-1500. ; 15:7, s. 247-247
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION & OBJECTIVES: Robotic approaches have revolutionized radical prostatectomy surgery. The 3D vision and 10 fold magnification provide surgeons improved anatomical vision and more precise instrument control compared to open or laparoscopic techniques. However, the potential benefits of robotic techniques may have trade-offs in increased mental and physical demands for the surgeons. The assisting surgeon, also has the added workload of maintaining working postures that do not impede the robotic arms. This study implemented an innovative motion tracking tool along with validated workload questionnaires to assess the ergonomics and workload for both assisting and console surgeons during robotic surgery. MATERIAL & METHODS: Ten individual surgeons (6 console surgeons and 4 assistant surgeons) performed 15 robotic prostatectomy cases while wearing inertia measurement units (IMUs) to track neck, shoulder, and torso motion during each case. Postoperatively, participants completed a validated workload questionnaire (NASA-TLX). Analysis of variance was performed on all response variables that do not violate the assumption of normality to identify the impact of surgeon role (Console vs Assistant). RESULTS: Twenty-six questionnaires were completed from 13 assisting and 13 console surgeons over the 15 cases. Selfreported mental demand was 41% higher for surgeons at the console than assisting (p<0.05), but physical demand was not statistically different. Post-operative pain was reported highest for the right shoulder and neck and this was more frequently seen in the console surgeons. On IMU readings, the assisting surgeon experienced high neck flexion (>10 degrees) duration over 42% of the procedure compared to only 24% in the console surgeon. In general, surgeons posture on the console was primarily static resulting in fewer movements compared to assisting surgeons. Table 1 summarizes posture movements and durations of static postures. CONCLUSIONS: Postures were more ergonomic during console tasks than assisting by the operating table. However, the console constrains postures leading to static postural loads that have been associated with musculoskeletal symptoms for the neck, torso and shoulders.
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- Svenner, A., et al.
(författare)
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A simulator-based comparison of a novel 3d and a conventional 3d vision system-surgical performance and subjective ratings
- 2019
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Ingår i: Inventions. - : MDPI Multidisciplinary Digital Publishing Institute. - 2411-5134. ; 4:4
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Tidskriftsartikel (refereegranskat)abstract
- In laparoscopy, novel three-dimensional laparoscopic vision systems (3D LVS) without glasses (3D−) have been invented. While standard 3D LVS with glasses (3D+) have shown advantages over original two-dimensional systems, quantitative comparisons of surgical performance between 3D− and 3D+ systems are still lacking. The aim is to compare the systems in simulated robotic surgery tasks. In a crossover study, 18 medical students performed four basic laparoscopic tasks in the validated Simball Box simulator with authentic surgical instruments by using the 3D+ and 3D− systems. Performance was measured by the number of errors and the task’s duration. Subjective ratings of perceptions and preference were assessed after each test. There were significant, but still minor, advantages for the conventional 3D+ system regarding spatial orientation and sense of depth. Overall, ten and eight subjects preferred 3D+ and 3D− systems, respectively. No significant differences were found in performance, post-operative physicals or eye symptoms. The novel 3D− system was similar to the conventional 3D+ system regarding performance and overall preference, while there were minor advantages for the 3D+ system in the subjective ratings. Since the 3D− system is a new invention, it should have a higher potential of usability improvements.
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| 6. |
- Kastrup, Y, et al.
(författare)
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Progesterone receptor expression in the brainstem of the female rat
- 1999
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Ingår i: Neuroscience Letters. - 0304-3940 .- 1872-7972. ; 275:2, s. 85-88
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Tidskriftsartikel (refereegranskat)abstract
- By using in situ hybridization and immunohistochemistry, the presence of neurons expressing progesterone receptor mRNA (PR mRNA) and progesterone receptor-like immunoreactivity (PR-LI) was examined in the brainstem and spinal cord of female rats. Neurons expressing PR mRNA and PR-LI were seen in the ventrolateral medulla, the parvocellular reticular formation and the nucleus of the solitary tract. PR mRNA, but not PR-LI, was seen in the hypoglossal nucleus, the inferior olive, the locus coeruleus and the parabrachial nucleus. No consistent labeling was present in the spinal cord. These findings show that progesterone receptors are expressed in brainstem areas involved in various functions, including autonomic regulation and pain modulation.
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