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- Olive, M, et al.
(författare)
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Myoglobinopathy is an adult-onset autosomal dominant myopathy with characteristic sarcoplasmic inclusions
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1396-
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Tidskriftsartikel (refereegranskat)abstract
- Myoglobin, encoded by MB, is a small cytoplasmic globular hemoprotein highly expressed in cardiac myocytes and oxidative skeletal myofibers. Myoglobin binds O2, facilitates its intracellular transport and serves as a controller of nitric oxide and reactive oxygen species. Here, we identify a recurrent c.292C>T (p.His98Tyr) substitution in MB in fourteen members of six European families suffering from an autosomal dominant progressive myopathy with highly characteristic sarcoplasmic inclusions in skeletal and cardiac muscle. Myoglobinopathy manifests in adulthood with proximal and axial weakness that progresses to involve distal muscles and causes respiratory and cardiac failure. Biochemical characterization reveals that the mutant myoglobin has altered O2 binding, exhibits a faster heme dissociation rate and has a lower reduction potential compared to wild-type myoglobin. Preliminary studies show that mutant myoglobin may result in elevated superoxide levels at the cellular level. These data define a recognizable muscle disease associated with MB mutation.
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| 7. |
- Pettersson-Segerlind, J, et al.
(författare)
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Long-Term Follow-Up and Predictors of Functional Outcome after Surgery for Spinal Meningiomas: A Population-Based Cohort Study
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:13
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Tidskriftsartikel (refereegranskat)abstract
- Spinal meningiomas are the most common adult primary spinal tumor, constituting 24–45% of spinal intradural tumors and 2% of all meningiomas. The aim of this study was to assess postoperative complications, long-term outcomes, predictors of functional improvement and differences between elderly (≥70 years) and non-elderly (18–69 years) patients surgically treated for spinal meningiomas. Variables were retrospectively collected from patient charts and magnetic resonance images. Baseline comparisons, paired testing and regression analyses were used. In conclusion, 129 patients were included, with a median follow-up time of 8.2 years. Motor deficit was the most common presenting symptom (66%). The median time between diagnosis and surgery was 1.3 months. A postoperative complication occurred in 10 (7.8%) and tumor growth or recurrence in 6 (4.7%) patients. Surgery was associated with significant improvement of motor and sensory deficit, gait disturbance, bladder dysfunction and pain. Time to surgery, tumor area and the degree of spinal cord compression significantly predicted postoperative improvement in a modified McCormick scale (mMCs) in the univariable regression analysis, and spinal cord compression showed independent risk association in multivariable analysis. There was no difference in improvement, complications or tumor control between elderly and non-elderly patients. We concluded that surgery of spinal meningiomas was associated with significant long-term neurological improvement, which could be predicted by time to surgery, tumor size and spinal cord compression.
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| 9. |
- Björk-Eriksson, Thomas, 1960, et al.
(författare)
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The lack of correlation between proliferation (Ki-67, PCNA, LI, Tpot), p53 expression and radiosensitivity for head and neck cancers
- 1999
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Ingår i: Br J Cancer. - 0007-0920. ; 80:9, s. 1400-4
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Tidskriftsartikel (refereegranskat)abstract
- A study was made of the relationship between measurements of radiosensitivity versus proliferation and p53 status in head and neck cancers. Inherent tumour radiosensitivity was assessed as surviving fraction at 2 Gy (SF2) using a clonogenic soft agar assay (n = 77). The results were compared to data on proliferation obtained by both flow cytometry (labelling index (LI), the potential doubling time (Tpot) n = 55) and immunohistochemistry (Ki-67 and PCNA; n = 68), together with immunohistochemical p53 expression (n = 68). There were no overall significant differences in the median values of the various parameters analysed for the different sites within the head and neck region, disease stages, grades of tumour differentiation or nodal states. A subgroup analysis showed that oropharyngeal (n = 22) versus oral cavity (n = 35) tumours were more radiosensitive (P = 0.056) and had a higher Ki-67 index (P = 0.001). Node-positive tumours had higher LI (P = 0.021) and a trend towards lower Tpot (P = 0.067) values than node-negative ones. No correlations were seen between SF2 and any of the parameters studied. The long-standing dogma of an increased radiosensitivity of rapidly proliferating cells in contrast to slowly proliferating cells was not confirmed. The study shows that parallel measurements of different biological markers can be obtained for a large number of patients with head and neck cancers. The independence of the various parameters studied suggests that there may be potential for their combined use as prognostic factors for the outcome of radiotherapy.
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- El-Hajj, VG, et al.
(författare)
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Current Knowledge on Spinal Meningiomas Epidemiology, Tumor Characteristics and Non-Surgical Treatment Options: A Systematic Review and Pooled Analysis (Part 1)
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:24
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Tidskriftsartikel (refereegranskat)abstract
- Background: Spinal meningiomas are the most common primary intradural spinal tumors. Although they are a separate entity, a large portion of the knowledge on spinal meningiomas is based on findings in intracranial meningiomas. Therefore, a comprehensive review of all the literature on spinal meningiomas was performed. Methods: Electronic databases were searched for all studies on spinal meningiomas dating from 2000 and onward. Findings of matching studies were pooled to strengthen the current body of evidence. Results: A total of 104 studies were included. The majority of patients were female (72.83%), elderly (peak decade: seventh), and had a world health organization (WHO) grade 1 tumor (95.7%). Interestingly, the minority of pediatric patients had a male overrepresentation (62.0% vs. 27.17%) and higher-grade tumors (33.3% vs. 4.3%). Sensory and motor dysfunction and pain were the most common presenting symptoms. Despite a handful of studies reporting promising findings associated with the use of non-surgical treatment options, the literature still suffers from contradictory results and limitations of study designs. Conclusions: Elderly females with WHO grade 1 tumors constituted the stereotypical type of patient. Compared to surgical alternatives, the evidence for the use of non-surgical treatments is still relatively weak.
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| 14. |
- El-Hajj, VG, et al.
(författare)
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Current Knowledge on Spinal Meningiomas-Surgical Treatment, Complications, and Outcomes: A Systematic Review and Meta-Analysis (Part 2)
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:24
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Tidskriftsartikel (refereegranskat)abstract
- Background: Most of the knowledge on spinal meningiomas is extrapolated from their intracranial counterparts, even though they are considered separate entities. This review aimed to systematically summarize studies covering different aspects of spinal meningiomas and their management. Methods: Databases were searched for all studies concerning spinal meningiomas dating from 2000 and onwards. When possible, a meta-analysis was performed. Results: Neurological outcomes of surgery were consistently favorable across studies, with a complication rate of 7.9% and 78.9% of the patients demonstrating good postoperative neurological function (McCormick score 1–2). The most relevant predictors of unfavorable outcomes were poor preoperative status, longer time from diagnosis to surgery, and surgery of recurrent tumors. The recurrence rate after surgery was estimated at 6%. Meta-analysis and/or survival analysis revealed that higher WHO grade (p < 0.001), higher Simpson grade (p < 0.001), ventral tumor location (p = 0.02), and male sex (p = 0.014) were all associated with higher odds of recurrence. However, the meta-analysis did not show any difference between Simpson grade 1 and grade 2 with respect to the odds of recurrence (p = 0.94). Surgery provided immediate and durable health-related quality-of-life improvement, as well as a high frequency of return to work. Conclusion: Spinal meningioma surgery is a relatively safe procedure with a low risk of tumor recurrence and high likelihood of favorable postoperative outcomes.
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| 15. |
- El-Hajj, VG, et al.
(författare)
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Unsuccessful external validation of the MAC-score for predicting increased MIB-1 index in patients with spinal meningiomas
- 2022
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Ingår i: Frontiers in oncology. - : Frontiers Media SA. - 2234-943X. ; 12, s. 1037495-
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Tidskriftsartikel (refereegranskat)abstract
- Recently, the MAC-spinal meningioma score (MAC-score) was proposed to preoperatively identify spinal meningioma patients with high MIB-1 indices. Risk factors were age ≥ 65 years, a modified McCormick score (mMCs) ≥ 2, and absence of tumor calcification. The aim of this study was to externally validate the MAC-score in an independent cohort.MethodsUsing the same inclusion and exclusion criteria as in the original study, we performed a retrospective, single-center, population-based, cohort study that included patients who had undergone surgical treatment for spinal meningiomas between 2005 – 2017. Data was collected from patient charts and radiographic images. Validation was performed by applying the MAC-score to our cohort and evaluating the area under the receiver operating characteristic curve (AUC).ResultsIn total, 108 patients were included. Baseline and outcome data were comparable to the original development study. An increased MIB-1 index (≥5%) was observed in 56 (52%) patients. AUC of the MAC-score in our validation cohort was 0.61 (95% CI: 0.51 – 0.71), which corresponds to a poor discriminative ability.ConclusionThe MAC-score showed poor discriminative ability for MIB-1 index prediction in patients with spinal meningiomas. Moreover, the MAC-score rests on a weak theoretical and statistical foundation. Consequently, we argue against its clinical implementation.
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| 18. |
- Frisk, H, et al.
(författare)
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Feasibility and Accuracy of Thoracolumbar Pedicle Screw Placement Using an Augmented Reality Head Mounted Device
- 2022
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Ingår i: Sensors (Basel, Switzerland). - : MDPI AG. - 1424-8220. ; 22:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: To investigate the accuracy of augmented reality (AR) navigation using the Magic Leap head mounted device (HMD), pedicle screws were minimally invasively placed in four spine phantoms. Methods: AR navigation provided by a combination of a conventional navigation system integrated with the Magic Leap head mounted device (AR-HMD) was used. Forty-eight screws were planned and inserted into Th11-L4 of the phantoms using the AR-HMD and navigated instruments. Postprocedural CT scans were used to grade the technical (deviation from the plan) and clinical (Gertzbein grade) accuracy of the screws. The time for each screw placement was recorded. Results: The mean deviation between navigation plan and screw position was 1.9 ± 0.7 mm (1.9 [0.3–4.1] mm) at the entry point and 1.4 ± 0.8 mm (1.2 [0.1–3.9] mm) at the screw tip. The angular deviation was 3.0 ± 1.4° (2.7 [0.4–6.2]°) and the mean time for screw placement was 130 ± 55 s (108 [58–437] s). The clinical accuracy was 94% according to the Gertzbein grading scale. Conclusion: The combination of an AR-HMD with a conventional navigation system for accurate minimally invasive screw placement is feasible and can exploit the benefits of AR in the perspective of the surgeon with the reliability of a conventional navigation system.
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| 20. |
- Hackman, P, et al.
(författare)
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Welander distal myopathy: The evasive gene
- 2008
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Ingår i: NEUROMUSCULAR DISORDERS. - : Elsevier BV. - 0960-8966. ; 18:9-10, s. 767-767
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 21. |
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| 22. |
- Karlsson, M, et al.
(författare)
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Wireless system for real-time recording of heart rate variability for home nursing.
- 2005
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Ingår i: Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference. - 1557-170X. ; 4, s. 3717-9
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Tidskriftsartikel (refereegranskat)abstract
- Modern wireless communication technologies offer new possibilities for patient monitoring in hospitals, as well as at home or in outdoor environments. In this paper, we present a wireless system for ECG recordings and real-time analysis of heart rate variability (HRV). The system also makes it possible for distance consultation, for example with a specialist in cardiology, with the help of a WEB-solution.
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| 23. |
- Lange, S, et al.
(författare)
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The kinase domain of titin controls muscle gene expression and protein turnover
- 2005
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 308:5728, s. 1599-1603
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Tidskriftsartikel (refereegranskat)abstract
- The giant sarcomeric protein titin contains a protein kinase domain (TK) ideally positioned to sense mechanical load. We identified a signaling complex where TK interacts with the zinc-finger protein nbr1 through a mechanically inducible conformation. Nbr1 targets the ubiquitin-associated p62/SQSTM1 to sarcomeres, and p62 in turn interacts with MuRF2, a muscle-specific RING-B-box E3 ligase and ligand of the transactivation domain of the serum response transcription factor (SRF). Nuclear translocation of MuRF2 was induced by mechanical inactivity and caused reduction of nuclear SRF and repression of transcription. A human mutation in the titin protein kinase domain causes hereditary muscle disease by disrupting this pathway.
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| 24. |
- Manti, M., et al.
(författare)
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Excess of ovarian nerve growth factor impairs embryonic development and causes reproductive and metabolic dysfunction in adult female mice
- 2020
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Ingår i: FASEB Journal. - : John Wiley & Sons. - 0892-6638 .- 1530-6860. ; 34:11, s. 14440-14457
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Tidskriftsartikel (refereegranskat)abstract
- Nerve growth factor (NGF) is critical for the development and maintenance of the peripheral sympathetic neurons. NGF is also involved in the ovarian sympathetic innervation and in the development and maintenance of folliculogenesis. Women with the endocrine disorder, polycystic ovary syndrome (PCOS), have an increased sympathetic nerve activity and increased ovarian NGF levels. The role of ovarian NGF excess in the PCOS pathophysiology and in the PCOS-related features is unclear. Here, using transgenic mice overexpressesing NGF in the ovarian theca cells (17NF mice), we assessed the female embryonic development, and the reproductive and metabolic profile in adult females. Ovarian NGF excess caused growth restriction in the female fetuses, and a delayed gonocyte and primary oocyte maturation. In adulthood, the 17NF mice displayed irregular estrous cycles and altered ovarian expression of steroidogenic and epigenetic markers. They also exhibited an increased sympathetic output with increased circulating dopamine, and metabolic dysfunction reflected by aberrant adipose tissue morphology and function, impaired glucose metabolism, decreased energy expenditure, and hepatic steatosis. These findings indicate that ovarian NGF excess leads to adverse fetal development and to reproductive and metabolic complications in adulthood, mirroring common features of PCOS. This work provides evidence that NGF excess may be implicated in the PCOS pathophysiology.
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- Pettersson-Segerlind, J, et al.
(författare)
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Long-Term Follow-Up, Treatment Strategies, Functional Outcome, and Health-Related Quality of Life after Surgery for WHO Grade 2 and 3 Intracranial Meningiomas
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:20
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Tidskriftsartikel (refereegranskat)abstract
- Progression-free survival (PFS) and overall survival (OS) for WHO grade 2 and 3 intracranial meningiomas are poorly described, and long-term results and data evaluating the routine use of supplementary fractionated radiotherapy (RT) or stereotactic radiosurgery (SRS) has been inconclusive. The aim of this study was to determine the long-term PFS and OS at a center that does not employ routine adjuvant RT. For this purpose, a retrospective population-based cohort study was conducted of all WHO grade 2 and 3 meningiomas surgically treated between 2005 and 2013. The cohort was uniformly defined according to the WHO 2007 criteria to allow comparisons to previously published reports. Patient records were reviewed, and patients were then prospectively contacted for structured quality-of-life assessments. In total, 51 consecutive patients were included, of whom 43 were WHO grade 2 and 8 were grade 3. A Simpson grade 1–2 resection was achieved in 62%. The median PFS was 31 months for grade 2 tumors, and 3.4 months for grade 3. The median OS was 13 years for grade 2, and 1.4 years for grade 3. The MIB-1-index was significantly associated with an increased risk for recurrence (p = 0.018, OR 1.12). The median PFS was significantly shorter for high-risk tumors compared to the low-risk group (10 vs. 46 months; p = 0.018). The surviving meningioma patients showed HRQoL measures comparable to that of the general population, with the exception of significantly more anxiety and depression. All patients who worked before surgery returned to work after their treatment. In conclusion, we confirm dismal prognoses in patients with grade 2 and 3 meningiomas, with tumor-related deaths resulting in severely reduced OS. However, the cohort was heterogenous, and a large subgroup of both grade 2 and 3 meningiomas was alive at 10 years follow-up, suggesting that a cure is possible. In addition, fractionated radiotherapy and chemotherapy had little benefit when introduced for recurrent and progressive diseases.
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| 29. |
- Pettersson-Segerlind, J, et al.
(författare)
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The risk of developing a meningioma during and after pregnancy
- 2021
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 9153-
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Tidskriftsartikel (refereegranskat)abstract
- Pregnancy has been associated with diagnosis or growth of meningiomas in several case reports, which has led to the hypothesis that pregnancy may be a risk factor for meningiomas. The aim of this study was to test this hypothesis in a large population-based cohort study. Women born in Sweden 1958–2000 (N = 2,204,126) were identified and matched with the Medical Birth Register and the Cancer Register. The expected number of meningioma cases and risk ratios were calculated for parous and nulliparous women and compared to the observed number of cases. Compared to parous women, meningiomas were more common among nulliparous (SIR = 1.73; 95% CI 1.52–1.95). The number of meningioma cases detected during pregnancy was lower than the expected (SIR = 0.40; 95% CI 0.20–0.72). Moreover, no increased risk was found in the first-year post-partum (SIR = 1.04; 95% CI 0.74–1.41). Contrary to our hypothesis, there was no increased risk for diagnosing a meningioma during pregnancy or 1-year post-partum. A lower detection rate during pregnancy, may reflect under-utilization of diagnostic procedures, but the actual number of meningiomas was homogenously lower among parous than nulliparous women throughout the study period, indicating that pregnancy is not a risk factor for meningioma.
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