| 1. |
- Einarsdottir, E., et al.
(author)
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CELSR2 is a candidate susceptibility gene in idiopathic scoliosis
- 2017
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:12
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Journal article (peer-reviewed)abstract
- A Swedish pedigree with an autosomal dominant inheritance of idiopathic scoliosis was initially studied by genetic linkage analysis, prioritising genomic regions for further analysis. This revealed a locus on chromosome 1 with a putative risk haplotype shared by all affected individuals. Two affected individuals were subsequently exome-sequenced, identifying a rare, non-synonymous variant in the CELSR2 gene. This variant is rs141489111, a c. G6859A change in exon 21 (NM_001408), leading to a predicted p. V2287I (NP_001399.1) change. This variant was found in all affected members of the pedigree, but showed reduced penetrance. Analysis of tagging variants in CELSR1-3 in a set of 1739 Swedish-Danish scoliosis cases and 1812 controls revealed significant association (p = 0.0001) to rs2281894, a common synonymous variant in CELSR2. This association was not replicated in case-control cohorts from Japan and the US. No association was found to variants in CELSR1 or CELSR3. Our findings suggest a rare variant in CELSR2 as causative for idiopathic scoliosis in a family with dominant segregation and further highlight common variation in CELSR2 in general susceptibility to idiopathic scoliosis in the Swedish-Danish population. Both variants are located in the highly conserved GAIN protein domain, which is necessary for the auto-proteolysis of CELSR2, suggesting its functional importance.
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| 2. |
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| 3. |
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| 4. |
- Kou, I, et al.
(author)
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A multi-ethnic meta-analysis confirms the association of rs6570507 with adolescent idiopathic scoliosis
- 2018
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 11575-
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Journal article (peer-reviewed)abstract
- Adolescent idiopathic scoliosis (AIS) is the most common type of spinal deformity and has a significant genetic background. Genome-wide association studies (GWASs) identified several susceptibility loci associated with AIS. Among them is a locus on chromosome 6q24.1 that we identified by a GWAS in a Japanese cohort. The locus is represented by rs6570507 located within GPR126. To ensure the association of rs6570507 with AIS, we conducted a meta-analysis using eight cohorts from East Asia, Northern Europe and USA. The analysis included a total of 6,873 cases and 38,916 controls and yielded significant association (combined P = 2.95 × 10−20; odds ratio = 1.22), providing convincing evidence of the worldwide association between rs6570507 and AIS susceptibility. In silico analyses strongly suggested that GPR126 is a susceptibility gene at this locus.
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| 5. |
- Ogura, Y, et al.
(author)
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An international meta-analysis confirms the association of BNC2 with adolescent idiopathic scoliosis
- 2018
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 4730-
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Journal article (peer-reviewed)abstract
- Adolescent idiopathic scoliosis (AIS) is a common spinal deformity with the prevalence of approximately 3%. We previously conducted a genome-wide association study (GWAS) using a Japanese cohort and identified a novel locus on chromosome 9p22.2. However, a replication study using multi-population cohorts has not been conducted. To confirm the association of 9p22.2 locus with AIS in multi-ethnic populations, we conducted international meta-analysis using eight cohorts. In total, we analyzed 8,756 cases and 27,822 controls. The analysis showed a convincing evidence of association between rs3904778 and AIS. Seven out of eight cohorts had significant P value, and remaining one cohort also had the same trend as the seven. The combined P was 3.28 × 10−18 (odds ratio = 1.19, 95% confidence interval = 1.14–1.24). In silico analyses suggested that BNC2 is the AIS susceptibility gene in this locus.
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| 8. |
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| 9. |
- Diarbakerli, E., et al.
(author)
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Adults With Idiopathic Scoliosis Diagnosed at Youth Experience Similar Physical Activity and Fracture Rate as Controls
- 2017
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In: Spine. - : Ovid Technologies (Wolters Kluwer Health). - 0362-2436 .- 1528-1159. ; 42:7
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Journal article (peer-reviewed)abstract
- Study Design. Cross-sectional. Objective. To describe physical activity level and fracture rates in adults with idiopathic scoliosis, diagnosed before maturity, and to compare with a control group. Summary of Background Data. A previous study found a lower level of sporting activities in adults treated for idiopathic scoliosis compared with controls. Other studies have shown a lower bone mass in adults with idiopathic scoliosis compared with controls. Methods. One thousand two hundred seventy-eight adults (aged 18-71 yr) with idiopathic scoliosis and 214 controls (aged 18-70 yr) were included and answered the International Physical Activity Questionnaire - Short Form (IPAQ-SF) and questions about previous fractures. The three scoliosis treatment groups (untreated n=360, brace n=460, and surgically treated n=458) were compared. Furthermore, a comparison based on onset (juvenile n=169 or adolescent n=976) was performed. Achieved weekly moderate activity level and metabolic equivalent task (MET) minutes/week were assessed for patients and controls. Statistical comparisons were made with analysis of covariance with adjustments for age, body mass index, and sex. Results. The proportion achieving weekly moderate activity level was 962 out of 1278 for individuals with idiopathic scoliosis (75%) and 157 out of 214 (73%) for controls (P=0.40). The scoliosis patients reported 2016MET-minutes/week (median value) and the controls 2456 (P=0.06). Fracture rates did not differ (P=0.72). Fewer surgically treated individuals achieved moderate activity level (P=0.046) compared with the untreated and the previously braced individuals. No difference was seen regarding MET-minutes/week (P=0.86). No differences were seen between individuals with a juvenile onset compared with individuals with an adolescent onset (all P >= 0.05). Conclusion. Adults with idiopathic scoliosis have similar physical activity level and do not sustain more fractures compared with controls. Adults with surgically treated idiopathic scoliosis have slightly lower physical activity level than previously braced and untreated patients. Onset of idiopathic scoliosis does not affect physical activity level.
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| 10. |
- Diarbakerli, E., et al.
(author)
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Health-Related Quality of Life in Adulthood in Untreated and Treated Individuals with Adolescent or Juvenile Idiopathic Scoliosis
- 2018
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In: Journal of Bone and Joint Surgery-American Volume. - : Ovid Technologies (Wolters Kluwer Health). - 0021-9355 .- 1535-1386. ; 100:10, s. 811-817
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Journal article (peer-reviewed)abstract
- Background: Health-related quality of life in adults with idiopathic scoliosis diagnosed before maturity has been reported to be similar between brace-treated and surgically treated individuals. The aim of this study was to compare health-related quality of life in untreated, brace-treated, and surgically treated adults with idiopathic scoliosis diagnosed before skeletal maturity. Subgroup analyses were performed on the basis of age at the time of the study, age of onset, surgical characteristics, and curve magnitude. Methods: We included 1,187 adults with juvenile or adolescent idiopathic scoliosis with a mean age (and standard deviation) of 38.8 +/- 12.7 years. Of these, 347 were untreated, 459 had been brace-treated, and 381 had been surgically treated. The Scoliosis Research Society-22r (SRS-22r) and EuroQol 5-Dimensions (EQ-5D) were used. Statistical analyses were performed using analysis of covariance. Results: The mean SRS-22r subscore was 4.15 +/- 0.59 points for the untreated group, 4.10 +/- 0.57 points for the previously braced group, and 4.01 +/- 0.64 points for the surgically treated group (p = 0.007 adjusted for age and sex). The EQ-5D index was 0.82 +/- 0.20 for the untreated group, 0.82 +/- 0.20 for the previously brace-treated group, and 0.79 +/- 0.24 for the surgically treated group (p = 0.026, adjusted for age and sex). Brace cessation was at the mean age of 16.2 +/- 1.5 years, and the surgical procedure had been performed at the mean age of 15.3 +/- 2.1 years. A more caudal fusion was associated with a lower SRS-22r subscore and EQ-5D index. No differences were observed when comparing individuals with juvenile or adolescent onset scoliosis (all p > 0.05). Conclusions: Untreated adults with idiopathic scoliosis had similar health-related quality of life to previously brace-treated individuals, and they had marginally higher health-related quality of life compared with surgically treated individuals. Therefore, both surgical and brace treatments for idiopathic scoliosis could be considered successful from a health-related quality-of-life point of view in adulthood. The age of onset of idiopathic scoliosis does not seem to influence quality of life in adulthood.
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| 11. |
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| 12. |
- Gerdhem, P., et al.
(author)
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Serum level of cartilage oligomeric matrix protein is lower in children with idiopathic scoliosis than in non-scoliotic controls
- 2015
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In: European Spine Journal. - : Springer Science and Business Media LLC. - 0940-6719 .- 1432-0932. ; 24:2, s. 256-261
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Journal article (peer-reviewed)abstract
- The etiology of idiopathic scoliosis remains unknown, but growth is a risk factor for progression. Growth pattern differs in children with and without scoliosis. Cartilage oligomeric matrix protein (COMP) may be associated with scoliosis and growth. We, therefore, studied COMP in children with and without idiopathic scoliosis. We included 105 children, with mean age 14.4 years (range 10-16), under observation or treatment for idiopathic scoliosis, and 103 children from an age-matched population-based cohort. COMP was measured in serum at the time of inclusion. Growth velocity was estimated from repeated height measurements. T tests, analysis of covariance or linear regression were used for statistical comparisons. COMP was mean (SD) 11 (5) units/liter (U/L) in children with scoliosis and 13 (5) U/L in the control cohort (p = 0.005, adjusted for sex and sampling time of the day). When patients and controls were analyzed together, high COMP was correlated with high growth velocity (beta = 0.19, p = 0.003). When patients and controls were analyzed separately, COMP was correlated with growth velocity in children with scoliosis (beta = 0.27, p = 0.007), but not in children without scoliosis (beta = 0.02, p = 0.83) (all analyses adjusted for age, sex and sampling time). Low COMP was significantly correlated with large curve size in children with scoliosis (beta = -0.29, p = 0.003), but not after adjustment for age, sex and sampling time (beta = -0.16; p = 0.14). COMP was lower in children with idiopathic scoliosis than in a control cohort. In children with scoliosis, high COMP was modestly correlated with high growth velocity, but not with curve severity.
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| 13. |
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| 14. |
- Grauers, A, et al.
(author)
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Heritability of scoliosis
- 2012
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In: European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. - : Springer Science and Business Media LLC. - 1432-0932. ; 21:6, s. 1069-1074
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Journal article (peer-reviewed)
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| 15. |
- Grauers, A, et al.
(author)
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Prevalence of Back Problems in 1069 Adults With Idiopathic Scoliosis and 158 Adults Without Scoliosis.
- 2014
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In: Spine. - 1528-1159 .- 0362-2436. ; 39:11, s. 886-892
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Journal article (peer-reviewed)abstract
- Study Design. Multi-center case-control studyObjective. To investigate the prevalence of back problems in adults with idiopathic scoliosis.Summary of Background Data. Information on the prevalence of back problems in adults with idiopathic scoliosis is scarce, especially in untreated individuals, males and individuals with an age at onset of the scoliosis of less than 10 years.Methods. 1069 individuals with idiopathic scoliosis and 158 individuals without scoliosis, all aged 20-65 years, answered a questionnaire on back problems. Individuals with scoliosis were diagnosed between ages 4 and 20 years and any treatment was terminated before age 20. Logistic regression or ANCOVA was used for group comparisons.Results. Mean (SD) age at the time of investigation in individuals with scoliosis (123 men and 946 women) was 41 (9) years, and in individuals without scoliosis (75 men and 83 women) 45 (13) years. 374 individuals with scoliosis were untreated, 451 had been brace treated and 244 surgically treated. The mean prevalence of back problems was 64% in the individuals with scoliosis and 29% in the individuals without scoliosis (p<0.001). Among the untreated individuals with scoliosis, 69% reported back problems, among the brace treated 61%, and among the surgically treated 64% (p = 0.06). When comparing females and males with scoliosis, and individuals with juvenile and adolescent scoliosis, there were no statistically significant differences in the prevalence of back problems (p = 0.10 and p = 0.23, respectively).Conclusion. Adults with idiopathic scoliosis have a higher prevalence of back problems than individuals without scoliosis. Treatment, gender and juvenile or adolescent onset of diagnosis was not related to the prevalence of back problems in adulthood.
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| 16. |
- Grauers, A, et al.
(author)
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Propofol infusion rate does not affect local pain on injection.
- 2002
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 46:4, s. 361-363
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Journal article (peer-reviewed)abstract
- BACKGROUND: Local pain at the site of an i.v. injection of propofol is a well-known problem, particularly in infants. This randomised investigator-blinded crossover study was designed to assess the effect of the i.v. bolus infusion rate on propofol-induced pain at the site of injection. METHODS: Thirty unpremedicated patients scheduled for ear-nose-throat or plastic surgery at Malmö University Hospital, Sweden, were given two consecutive 2.0 ml injections of propofol 10 mg/ml (Diprivan, AstraZeneca, Sweden/UK), at different infusion rates (0.2 or 1.0 ml/s), immediately before induction of general anesthesia. Half of the patients (n=15) received the first bolus of propofol over 2 s and the second bolus over 10 s, and the other half (n=15) had their injections in reversed order. After each injection, the patient was asked by an investigator to indicate pain intensity on a visual analog scale (VAS) and to report the times of the appearance, maximum point and disappearance of pain. The injections were given approximately 2 min apart. The investigators scoring pain intensity, as indicated by the patients on a 10-point numerical rate scale, were blinded to the order in which the injections were given, as were the patients themselves. RESULTS: There were no statistically significant differences in the incidence (both 86%) of intensity (median; 25th; 75th percentiles, in VAS units: 3.1; 1.0; 5.3 and 3.3; 1.4; 5.0, respectively) or duration (66+/-31 and 73+/-26 s, respectively) of pain between the faster (1.0 ml/s) and slower (0.2 ml/s) bolus infusion rates of propofol studied. CONCLUSIONS: We conclude that the i.v. bolus infusion rate of propofol does not influence drug-induced local pain on injection, at least not within the infusion rate interval studied. Therefore, adjusting i.v. injection speed does not seem to be a clinically useful tool for reducing the intensity or duration of propofol-induced pain at the site of administration.
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| 17. |
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| 18. |
- Jones, Stephen, et al.
(author)
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Energy-efficient cooperative adaptive cruise control strategy using V2I
- 2019
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In: 2019 6th International Conference on Control, Decision and Information Technologies, CoDIT 2019. ; , s. 1420-1425
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Conference paper (peer-reviewed)abstract
- In an increasingly connected world, this paper presents an advanced and cooperative semi-autonomous driving system which targets not only convenient and safe mobility, but also achieves noticeably enhanced energy efficiency. By utilizing V2V and V2I communication, a vehicle's energy consumption can be significantly reduced, while maintaining safety and driving comfort. A holistic control strategy is considered, which integrates features from earlier Cooperative Adaptive Cruise Control (CACC) and Traffic Light Assistant (TLA) research. This strategy incorporate s traffic light signal phase timing (SPAT), speed limits, road gradients and curves, surrounding traffic and detailed powertrain characteristics of the ego vehicle into a single Model Predictive Controller (MPC) formulation. The system's performance was evaluated using a realistic cosimulation toolchain and tested on a real conventional vehicle on a powertrain testbed with real V2I hardware. Results for a D-class diesel passenger car driven over an urban route, show energy savings up to 25%, with an unchanged journey time compared to a typical human driver. The approach is valid for both urban cities driving and highways, whilst being adaptable to commercial vehicles and other powertrains (hybrid, fully electric).
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| 19. |
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| 20. |
- Kiffin, Roberta, et al.
(author)
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Anti-Leukemic Properties of Histamine in Monocytic Leukemia: The Role of NOX2
- 2018
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In: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 8
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Journal article (peer-reviewed)abstract
- In patients with acute myeloid leukemia (AML), treatment with histamine dihydrochloride (HDC) and low-dose IL-2 (HDC/ IL-2) in the post-chemotherapy phase has been shown to reduce the incidence of leukemic relapse. The clinical benefit of HDC/ IL-2 is pronounced in monocytic forms of AML, where the leukemic cells express histamine type 2 receptors (H2R) and the NAPDH oxidase-2 (NOX2). HDC ligates to H(2)Rs to inhibit NOX2-derived formation of reactive oxygen species, but details regarding the anti-leukemic actions of HDC remain to be elucidated. Here, we report that human NOX2(+) myelomonocytic/monocytic AML cell lines showed increased expression of maturation markers along with reduced leukemic cell proliferation after exposure to HDC in vitro. These effects of HDC were absent in corresponding leukemic cells genetically depleted of NOX2 (NOX2(-/-)). We also observed that exposure to HDC altered the expression of genes involved in differentiation and cell cycle progression in AML cells and that these effects required the presence of NOX2. HDC promoted the differentiation also of primary monocytic, but not non-monocytic, AML cells in vitro. In a xenograft model, immunodeficient NOG mice were inoculated with wild-type or NOX2(-/-) human monocytic AML cells and treated with HDC in vivo. The administration of HDC reduced the in vivo expansion of NOX2(+/+), but not of NOX2(-/-) human monocytic AML cells. We propose that NOX2 may be a conceivable target in the treatment of monocytic AML.
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| 21. |
- Liljeroth, E, et al.
(author)
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Pain on injection of propofol with or without infusion of carrier fluid
- 2001
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 45:7, s. 839-841
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Journal article (peer-reviewed)abstract
- BACKGROUND: Propofol, a popular intravenous (iv) anaesthetic induction agent for brief cases or day surgery, is associated with smooth induction, pleasant sleep, rapid recovery and little postoperative nausea. A major disadvantage is pain at the site of injection. The aim of the present study was to examine the influence of simultaneous iv infusion of carrier fluid on propofol-induced local pain. METHODS: Thirty patients, scheduled for ear-nose-throat or plastic surgery under general anaesthesia, were randomly allocated into two groups. Each patient had two 2 ml iv bolus injections of propofol given at two minutes' interval. In group I (n=15) the first bolus injection was given with no iv carrier fluid and the second one given with a 10 ml iv carrier fluid infused over 10 s. Correspondingly, the patients in group II (n=15) had their first injection with and their second one without the iv carrier fluid. Following each injection of propofol the patients were asked by a blinded investigator to score their pain on a 10-point visual analogue scale, and to report the appearance, maximum and disappearance of pain. After the second assessment of pain, general anaesthesia was induced with more propofol. RESULTS: Pain intensity at the site of propofol injection was found not to be influenced by simultaneous iv infusion of carrier fluid. CONCLUSION: It seems, from the results obtained here, that simultaneous iv infusion of carrier fluid has no particular effect on local pain following iv administration of propofol.
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| 22. |
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| 23. |
- Wang, JW, et al.
(author)
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Investigation of rare and low-frequency variants using high-throughput sequencing with pooled DNA samples
- 2016
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 33256-
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Journal article (peer-reviewed)abstract
- High-throughput sequencing using pooled DNA samples can facilitate genome-wide studies on rare and low-frequency variants in a large population. Some major questions concerning the pooling sequencing strategy are whether rare and low-frequency variants can be detected reliably, and whether estimated minor allele frequencies (MAFs) can represent the actual values obtained from individually genotyped samples. In this study, we evaluated MAF estimates using three variant detection tools with two sets of pooled whole exome sequencing (WES) and one set of pooled whole genome sequencing (WGS) data. Both GATK and Freebayes displayed high sensitivity, specificity and accuracy when detecting rare or low-frequency variants. For the WGS study, 56% of the low-frequency variants in Illumina array have identical MAFs and 26% have one allele difference between sequencing and individual genotyping data. The MAF estimates from WGS correlated well (r = 0.94) with those from Illumina arrays. The MAFs from the pooled WES data also showed high concordance (r = 0.88) with those from the individual genotyping data. In conclusion, the MAFs estimated from pooled DNA sequencing data reflect the MAFs in individually genotyped samples well. The pooling strategy can thus be a rapid and cost-effective approach for the initial screening in large-scale association studies.
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