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- Borg, O. Anders, et al.
(author)
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Electron-transfer induced repair of 6-4 photoproducts in DNA : a computational study.
- 2007
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In: Journal of Physical Chemistry A. - Washington, DC : American Chemical Society. - 1089-5639 .- 1520-5215. ; 111:12, s. 2351-2361
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Journal article (peer-reviewed)abstract
- The mechanism employed by DNA photolyase to repair 6-4 photoproducts in UV-damaged DNA is explored by means of quantum chemical calculations. Considering the repair of both oxetane and azetidine lesions, it is demonstrated that reduction as well as oxidation enables a reversion reaction by creating anionic or cationic radicals that readily fragment into monomeric pyrimidines. However, on the basis of calculated reaction energies indicating that electron transfer from the enzyme to the lesion is a much more favorable process than electron transfer in the opposite direction, it is suggested that the photoenzymic repair can only occur by way of an anionic mechanism. Furthermore, it is shown that reduction of the oxetane facilitates a mechanism involving cleavage of the C−O bond followed by cleavage of the C−C bond, whereas reductive fragmentation of the azetidine may proceed with either of the intermonomeric C−N and C−C bonds cleaved as the first step. From calculations on neutral azetidine radicals, a significant increase in the free-energy barrier for the initial fragmentation step upon protonation of the carbonylic oxygens is predicted. This effect can be attributed to protonation serving to stabilize reactant complexes more than transition structures.
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- Forssten, Maximilian Peter, 1996-, et al.
(author)
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A nationwide analysis on the interaction between frailty and beta-blocker therapy in hip fracture patients
- 2023
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In: European Journal of Trauma and Emergency Surgery. - : Urban und Vogel Medien und Medizin Verlagsgesellsc. - 1863-9933 .- 1863-9941. ; 49:3, s. 1485-1497
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Hip fracture patients, who are often frail, continue to be a challenge for healthcare systems with a high postoperative mortality rate. While beta-blocker therapy (BBt) has shown a strong association with reduced postoperative mortality, its effect in frail patients has yet to be determined. This study's aim is to investigate how frailty, measured using the Orthopedic Hip Frailty Score (OFS), modifies the effect of preadmission beta-blocker therapy on mortality in hip fracture patients.METHODS: This retrospective register-based study included all adult patients in Sweden who suffered a traumatic hip fracture and subsequently underwent surgery between 2008 and 2017. Treatment effect was evaluated using the absolute risk reduction (ARR) in 30-day postoperative mortality when comparing patients with (BBt+) and without (BBt-) ongoing BBt. Inverse probability of treatment weighting (IPTW) was used to reduce potential confounding when examining the treatment effect. Patients were stratified based on their OFS (0, 1, 2, 3, 4 and 5) and the treatment effect was also assessed within each stratum.RESULTS: A total of 127,305 patients were included, of whom 39% had BBt. When IPTW was performed, there were no residual differences in observed baseline characteristics between the BBt+ and BBt- groups, across all strata. This analysis found that there was a stepwise increase in the ARRs for each additional point on the OFS. Non-frail BBt+ patients (OFS 0) exhibited an ARR of 2.2% [95% confidence interval (CI) 2.0-2.4%, p < 0.001], while the most frail BBt+ patients (OFS 5) had an ARR of 24% [95% CI 18-30%, p < 0.001], compared to BBt- patients within the same stratum.CONCLUSION: Beta-blocker therapy is associated with a reduced risk of 30-day postoperative mortality in frail hip fracture patients, with a greater effect being observed with higher Orthopedic Hip Frailty Scores.
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- Forssten, Maximilian Peter, 1996-, et al.
(author)
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The mortality burden of frailty in hip fracture patients : a nationwide retrospective study of cause-specific mortality
- 2023
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In: European Journal of Trauma and Emergency Surgery. - : Springer. - 1863-9933 .- 1863-9941. ; 49:3, s. 1467-1475
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Journal article (peer-reviewed)abstract
- Purpose: Frailty is a condition characterized by a reduced ability to adapt to external stressors because of a reduced physiologic reserve, which contributes to the high risk of postoperative mortality in hip fracture patients. This study aims to investigate how frailty is associated with the specific causes of mortality in hip fracture patients.Methods: All adult patients in Sweden who suffered a traumatic hip fracture and underwent surgery between 2008 and 2017 were eligible for inclusion. The Orthopedic Hip Frailty Score (OFS) was used to classify patients as non-frail (OFS 0), pre-frail (OFS 1), and frail (OFS & GE; 2). The association between the degree of frailty and both all-cause and cause-specific mortality was determined using Poisson regression models with robust standard errors and presented using incidence rate ratios (IRRs) with corresponding 95% confidence intervals (CIs), adjusted for potential sources of confounding.Results: After applying the inclusion and exclusion criteria, 127,305 patients remained for further analysis. 23.9% of patients were non-frail, 27.7% were pre-frail, and 48.3% were frail. Frail patients exhibited a 4 times as high risk of all-cause mortality 30 days [adj. IRR (95% CI): 3.80 (3.36-4.30), p < 0.001] and 90 days postoperatively [adj. IRR (95% CI): 3.88 (3.56-4.23), p < 0.001] as non-frail patients. Of the primary causes of 30-day mortality, frailty was associated with a tripling in the risk of cardiovascular [adj. IRR (95% CI): 3.24 (2.64-3.99), p < 0.001] and respiratory mortality [adj. IRR (95% CI): 2.60 (1.96-3.45), p < 0.001] as well as a five-fold increase in the risk of multiorgan failure [adj. IRR (95% CI): 4.99 (3.95-6.32), p < 0.001].Conclusion: Frailty is associated with a significantly increased risk of all-cause and cause-specific mortality at 30 and 90 days postoperatively. Across both timepoints, cardiovascular and respiratory events along with multiorgan failure were the most prevalent causes of mortality.
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- Olsson, Per-Erik, et al.
(author)
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Molecular cloning and characterization of a nuclear androgen receptor activated by 11-ketotestosterone
- 2005
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In: Reproductive Biology and Endocrinology. - London : BioMed Central (BMC). - 1477-7827. ; 3
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Journal article (peer-reviewed)abstract
- Although 11-ketotestosterone is a potent androgen and induces male secondary sex characteristics in many teleosts, androgen receptors with high binding affinity for 11-ketotestosterone or preferential activation by 11-ketotestosterone have not been identified. So, the mechanism by which 11-ketotestosterone exhibits such high potency remains unclear. Recently we cloned the cDNA of an 11-ketotestosterone regulated protein, spiggin, from three-spined stickleback renal tissue. As spiggin is the only identified gene product regulated by 11-ketotestosterone, the stickleback kidney is ideal for determination of the mechanism of 11-ketotestosterone gene regulation. A single androgen receptor gene with two splicing variants, belonging to the androgen receptor-beta subfamily was cloned from stickleback kidney. A high affinity, saturable, single class of androgen specific binding sites, with the characteristics of an androgen receptor, was identified in renal cytosolic and nuclear fractions. Measurement of ligand binding moieties in the cytosolic and nuclear fractions as well as to the recombinant receptor revealed lower affinity for 11-ketotestosterone than for dihydrotestosterone. Treatment with different androgens did not upregulate androgen receptor mRNA level or increase receptor abundance, suggesting that autoregulation is not involved in differential ligand activation. However, comparison of the transactivation potential of the stickleback androgen receptor with the human androgen receptor, in both human HepG2 cells and zebrafish ZFL cells, revealed preferential activation by 11-ketotestosterone of the stickleback receptor, but not of the human receptor. These findings demonstrate the presence of a receptor preferentially activated by 11-ketotestosterone in the three-spined stickleback, so far the only one known in any animal.
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| 6. |
- Petersson, M., et al.
(author)
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Natural history and surgical outcome of Rathke's cleft cysts-A study from the Swedish Pituitary Registry
- 2022
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In: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 96:1, s. 54-61
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Journal article (peer-reviewed)abstract
- Objective Rathke's cleft cysts are benign, embryological remnants in the pituitary gland. The majority of them are small and asymptomatic but a few may become large, and cause mass effects, pituitary hormone deficiencies and visual impairment. Recommendations for the follow-up of Rathke's cleft cysts vary since data on the natural history are sparse. Patients and Design Data at diagnosis and at 1, 5 and 10 years for patients with a Rathke's cleft cyst (434 at diagnosis, 317 females) were retrieved from the Swedish Pituitary Registry. Cysts <= 3 mm in diameter were excluded from the study. Measurements Data included demographics, cyst size, pituitary function, visual defects and surgery. Results The mean age at diagnosis was 45 years. In patients with cysts <10 mm in diameter (n = 204) 2.9% had pituitary hormone deficiencies and 2% had visual field impairments. Cyst size did not progress during the 5 years. Cysts with a diameter of >= 10 mm that were not operated (n = 174) decreased in size over the years (p < .01). Pituitary hormone deficiencies and visual impairments were more frequent (18% and 5.7%, respectively) but were stable over time. Transphenoidal surgery was performed in 56 patients of whom 51 underwent surgery before the 1-year follow-up. The mean cyst diameter at diagnosis was 18 mm (range: 930 mm), 36% had pituitary hormone deficiency, 45% had visual field defects and 20% had impaired visual acuity. One year after surgery 60% had no cyst remnants, 50% had a pituitary deficiency, 26% had visual field defects and 12% had impaired visual acuity. No major changes were observed after 5 years. Twelve of the operated patients had a follow-up at 10 years, in eight the cyst remnants or recurrences increased in size over time (p < .05). Conclusions Rathke's cleft cysts with a size less than 10 mm rarely grow and our results indicate that radiological follow-up can be restricted to 5 years. In contrast, progression of postoperative remnants or recurrent cysts is more likely and require long-term follow-up.
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| 7. |
- Smith, Roger O., et al.
(author)
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Assistive technology products : a position paper from the first global research, innovation, and education on assistive technology (GREAT) summit
- 2018
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In: Disability and Rehabilitation. - : Informa Healthcare. - 1748-3107 .- 1748-3115. ; 13:5, s. 473-485
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Journal article (peer-reviewed)abstract
- This paper is based on work from the Global Research, Innovation, and Education on Assistive Technology (GREAT) Summit that was coordinated by WHO's Global Cooperation on Assistive Technology (GATE). The purpose of this paper is to describe the needs and opportunities embedded in the assistive product lifecycle as well as issues relating to the various stages of assistive product mobilization worldwide. The paper discusses assistive technology product terminology and the dangers of focusing on products outside the context and rolling out products without a plan. Additionally, the paper reviews concepts and issues around technology transfer, particularly in relation to meeting global needs and among countries with limited resources. Several opportunities are highlighted including technology advancement and the world nearing a state of readiness through a developing capacity of nations across the world to successfully adopt and support the assistive technology products and applications. The paper is optimistic about the future of assistive technology products reaching the people that can use it the most and the excitement across large and small nations in increasing their own capacities for implementing assistive technology. This is expressed as hope in future students as they innovate and in modern engineering that will enable assistive technology to pervade all corners of current and potential marketplaces. Importantly, the paper poses numerous topics where discussions are just superficially opened. The hope is that a set of sequels will follow to continue this critical dialog.Implications for RehabilitationSuccessful assistive technology product interventions are complex and include much more than the simple selection of the right product.Assistive technology product use is highly context sensitive in terms of an individual user's environment.The development of assistive technology products is tricky as it must be contextually sensitive to the development environment and market as well.As a field we have much to study and develop around assistive technology product interventions from a global perspective.
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