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1.	Grann, Martin, et al. (författare) Methodological development : structured outcome assessment and community risk monitoring (SORM) 2005 Ingår i: International Journal of Law and Psychiatry. - : Elsevier BV. - 0160-2527 .- 1873-6386. ; 28:4, s. 442-456 Tidskriftsartikel (refereegranskat)abstract This paper describes an effort to develop a clinical tool for the continuous monitoring of risk for violence in forensic mental health clients who have left their institutions and who are dwelling in the community on a conditional release basis. The model is called Structured Outcome Assessment and Community Risk Monitoring (SORM). The SORM consists of 30 dynamic factors and each factor in SORM is assessed in two ways: The current absence, presence or partial och intermittent presence of the factors, which is an actuarial (systematized and 'objective') assessment. Secondly, the risk effect, i.e. whether the presence/absence of factors currently increases, decreases or is perceived as unrelated to violence risk, is a clinical (or impressionistic) assessment. Thus, the factors considered via the SORM can be coded as risk factors or protective factors (or as factors unimportant to risk of violence) depending on circumstances that apply in the individual case. Further, the SORM has a built-in module for gathering idiographical information about risk-affecting contextual factors. The use of the SORM and its potential as a risk monitoring instrument is illustrated via preliminary data and case vignettes from an ongoing multicenter project. In this research project, patients leaving any of the 9 participating forensic hospitals in Sweden is assessed at release on a variety of static background factors, and the SORM is then administered every 30 days for 2 years.
2.	Andersen, Peter M., 1962-, et al. (författare) Phenotype in an Infant with SOD1 Homozygous Truncating Mutation 2019 Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 381:5, s. 486-488 Tidskriftsartikel (refereegranskat)
3.	Andersson, Martin O., et al. (författare) Molecular detection of Babesia capreoli and Babesia venatorum in wild Swedish roe deer, Capreolus capreolus 2016 Ingår i: Parasites & Vectors. - : Springer Science and Business Media LLC. - 1756-3305. ; 9:1 Tidskriftsartikel (refereegranskat)abstract Background: The epidemiology of the zoonotic tick-transmitted parasite Babesia spp. and its occurrence in wild reservoir hosts in Sweden is unclear. In European deer, several parasite species, including Babesia capreoli and the zoonotic B. venatorum and B. divergens has been reported previously. The European roe deer, Capreolus capreolus, is an important and common part of the indigenous fauna in Europe, as well as an important host for Ixodes ricinus ticks, the vector of several Babesia spp. in Europe. Here, we aimed to investigate the occurrence of Babesia spp. in roe deer in Sweden. Findings: Roe deer (n = 77) were caught and sampled for blood. Babesia spp. was detected with a PCR assay targeting the 18S rRNA gene. The prevalence of Babesia spp. was 52 %, and two species were detected; B. capreoli and B. venatorum in 44 and 7.8 % of the individuals, respectively. Infection occurred both in summer and winter. Conclusions: We showed that roe deer in Sweden, close to the edge of their northern inland distributional range, are infected with Babesia spp. The occurrence of B. venatorum in roe deer imply that it is established in Sweden and the zoonotic implication of this finding should be regarded to a greater extent in future.
4.	Bejerholm, Ulrika, et al. (författare) Implementation of the Recovery Guide in inpatient mental health services in Sweden-A process evaluation study 2022 Ingår i: Health Expectations. - : Wiley. - 1369-6513 .- 1369-7625. ; 25:4, s. 1405-1417 Tidskriftsartikel (refereegranskat)abstract Background: Involving service users in inpatient care and recovery planning has gained interest worldwide. Our purpose was to evaluate the process of implementation of a coproduced Recovery Guide (RG) intervention in 22 inpatient wards in Sweden, in terms of context, implementation process and mechanisms of impact over 12 months.Methods: A mixed method design and a process evaluation framework were used to guide data collection and to deductively analyze perspectives and descriptive statistics of delivery from three stakeholder groups.Results: Results showed that although initial contextual barriers were present (e.g., lack of resources, and interest, uncertainty in the organization, a dominant illness perspective), it was possible to implement the RG in 14 wards, where 53% of admitted service users received the intervention. Legitimacy of the intervention, engaged managers and staff, capacity of staff and ward organization, coproduction and continuous support from user organization were critical mediators. Mechanisms of impact concerned (1) a new perspective on mental health, well-being and recovery, (2) capacity building of a recovery approach in inpatient settings and (3) a meaningful outlet for users' thoughts and feelings on recovery, sharing narratives and influencing care and goals.Conclusions: The RG intervention has the potential to promote a recovery approach in inpatient mental health services (MHSs). Coproduction among stakeholders created trust and a sustainable implementation that made it possible for wards to resume implementation when contextual barriers had been resolved.Patient and public contribution: The current study involved stakeholders including a service user organization, the public, first-line managers and staff (including peer support workers) in inpatient and community MHS and researchers, who greatly contributed to the implementation programme, including codesign of the RG intervention as well as coproduction of the implementation in inpatient MHS. All authors have their own lived experiences of mental health problems as a service user or as a relative.
5.	Bennmarker, Helge, et al. (författare) Workfare for the old and long-term unemployed 2013 Ingår i: Labour Economics. - : Elsevier BV. - 0927-5371 .- 1879-1034. ; 25, s. 25-34 Tidskriftsartikel (refereegranskat)abstract We estimate the effects of conditioning benefits on program participation among older long-term unemployed workers. We exploit a Swedish reform which reduced UI duration from 90 to 60 weeks for a group of older unemployed workers in a setting where workers who exhausted their benefits received unchanged transfers if they agreed to participate in a work practice program. Our results show that job finding increased as a result of the shorter duration of passive benefits. The time profile of the job-finding effects suggests that the results are due to deterrence during the program-entry phase. We find no impact on ensuing job durations or wages, suggesting that the increased job-finding rate was driven by increased search intensity rather than lower reservation wages. A crude cost-benefit analysis suggests that the reform reduced the combined cost of programs and transfers.
6.	Boman, Ulrika, et al. (författare) Alkohol och sjukskrivning : analyser på individ- och befolkningsnivå 2005 Ingår i: Den höga sjukfrånvaron - problem och lösningar. - Stockholm : Arbetslivsinstitutet. - 9170457379 ; , s. 63-111 Bokkapitel (övrigt vetenskapligt/konstnärligt)
7.	Bonagas, Nadilly, et al. (författare) Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress 2022 Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156- Tidskriftsartikel (refereegranskat)abstract The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
8.	Englund, Undis, 1957-, et al. (författare) Active commuting reduces the risk of wrist fractures in middle-aged women : the UFO study 2013 Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 24:2, s. 533-540 Tidskriftsartikel (refereegranskat)abstract Middle-aged women with active commuting had significantly lower risk for wrist fracture than women commuting by car/bus.INTRODUCTION: Our purpose was to investigate whether a physically active lifestyle in middle-aged women was associated with a reduced risk of later sustaining a low-trauma wrist fracture.METHODS: The Umeå Fracture and Osteoporosis (UFO) study is a population-based nested case-control study investigating associations between lifestyle and fragility fractures. From a cohort of ~35,000 subjects, we identified 376 female wrist fracture cases who had reported data regarding their commuting habits, occupational, and leisure physical activity, before they sustained their fracture. Each fracture case was compared with at least one control drawn from the same cohort and matched for age and week of reporting data, yielding a total of 778 subjects. Mean age at baseline was 54.3 ± 5.8 years, and mean age at fracture was 60.3 ± 5.8 years.RESULTS: Conditional logistic regression analysis with adjustments for height, body mass index, smoking, and menopausal status showed that subjects with active commuting (especially walking) were at significantly lower risk of sustaining a wrist fracture (OR 0.48; 95 % CI 0.27-0.88) compared with those who commuted by car or bus. Leisure time activities such as dancing and snow shoveling were also associated with a lower fracture risk, whereas occupational activity, training, and leisure walking or cycling were unrelated to fracture risk.CONCLUSION: This study suggests that active commuting is associated with a lower wrist fracture risk, in middle-aged women.
9.	Englund, Undis, 1957- (författare) Physical activity, bone density, and fragility fractures in women 2009 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Scandinavia has among the highest incidence of fragility fractures in the world. The reasons for this are unknown, but might involve differences in genetic and/or environmental factors, such as sunlight exposure and levels of physical activity. Weight-bearing exercise is thought to have a beneficial effect on bone health in the young, but few studies have evaluated whether exercise in older subjects affects bone density and protects against fragility fractures. The initial objective of this thesis was to evaluate whether a combined weight-bearing training programme twice a week would be beneficial as regards bone mineral density (BMD) and neuromuscular function in older women. Forty-eight community living women with a mean age of 73 years were recruited for this 12-month prospective, randomised controlled trial, and were randomly assigned to an intervention group (n=24) or a control group (n=24). The intervention group displayed significant increments in BMD at the Ward’s triangle, maximum walking speed, and isometric grip strength compared to the control group. The second objective was to investigate if training effects were retained in older women five years after the cessation of training. The 40 women who completed the first study included in this thesis were invited to take part in a follow-up assessment five years later, and 34 women (~79 years) agreed to participate. During these five years both groups had sustained significant losses in hip BMD and in all neuromuscular function tests, and the previous exercise-induced intergroup differences were no longer seen. The third and fourth objective of this thesis was to investigate whether exercise and weight-bearing leisure activities in middle-aged women are associated with a decreased risk of sustaining hip or wrist fractures at a later stage. A cohort of women participating in the Umeå Fracture and Osteoporosis (UFO) study, a longitudinal, nested case-control study investigating associations between bone markers, lifestyle, and osteoporotic fractures, was used for the purpose of this investigation. Eighty-one hip fracture cases and 376 wrist fracture cases, which had reported lifestyle data before they sustained their fracture, were identified. These cases were compared with age-matched controls identified from the same cohort. Using conditional logistic regression analysis with adjustments for height, BMI, smoking, and menopausal status, results showed that moderate frequency of leisure physical activities such as gardening and berry/mushroom picking, were associated with reduced hip fracture risk (OR 0.28; 95% CI 0.12 – 0.67), whereas active commuting (especially walking) along with dancing and snow shoveling in leisure time, reduced the wrist fracture risk (OR 0.48; 95% CI 0.27 – 0.88, OR 0.42; 95% CI 0.22 – 0.80 and OR 0.50; 95% CI 0.32 – 0.79 respectively). In summary, this thesis suggests that weight-bearing physical activity is beneficial for BMD and neuromuscular functions such as muscle strength and gait in older women, and that a physically active lifestyle, with outdoor activities, in middle age is associated with reduced risk of both hip and wrist fractures. Possible mechanisms underlying this association include improved muscle strength, coordination, and balance, resulting in a decreased risk of falling and perhaps also direct skeletal benefits.
10.	Englund, Undis, 1957-, et al. (författare) Physical activity in middle-aged women and hip fracture risk : the UFO study 2011 Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 22:2, s. 499-505 Tidskriftsartikel (refereegranskat)abstract Summary: In a population-based case-control study, we demonstrate that middle-aged women who were active with walking or in different physical spare time activities were at lower risk of later sustaining a hip fracture compared to more sedentary women.Introduction: In middle-aged women participating in the Umeå Fracture and Osteoporosis (UFO) study, we investigated whether physical activity is associated with a subsequent decreased risk of sustaining a hip fracture.Methods: The UFO study is a nested case-control study investigating associations between bone markers, lifestyle, and osteoporotic fractures. We identified 81 female hip fracture cases that had reported lifestyle data before they sustained their fracture. Each case was compared with two female controls who were identified from the same cohort and matched for age and week of reporting data, yielding a total cohort of 237 subjects. Mean age at baseline was 57.2 ± 5.0 years, and mean age at fracture was 65.4 ± 6.4 years.Results: Conditional logistic regression analysis with adjustments for height, weight, smoking, and menopausal status showed that subjects who were regularly active with walking or had a moderate or high frequency of physical spare time activities (i.e. berry/mushroom picking and snow shovelling) were at reduced risk of sustaining a hip fracture (OR 0.14; 95% CI; 0.05–0.53 for walking and OR 0.19; 95% CI; 0.08–0.46, OR 0.17, 95% CI; 0.05–0.64 for moderate and high frequency of spare time activities, respectively) compared to more sedentary women.Conclusion: An active lifestyle in middle age seems to reduce the risk of future hip fracture. Possible mechanisms may include improved muscle strength, coordination, and balance resulting in a decreased risk of falling and perhaps also direct skeletal benefits.
11.	Ezer, Shlomit, et al. (författare) Infantile SOD1 deficiency syndrome caused by a homozygous SOD1 variant with absence of enzyme activity 2022 Ingår i: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 145:3, s. 872-878 Tidskriftsartikel (refereegranskat)abstract Pathogenic variants in SOD1, encoding superoxide dismutase 1, are responsible for about 20% of all familial amyotrophic lateral sclerosis cases, through a gain-of-function mechanism. Recently, two reports showed that a specific homozygous SOD1 loss-of-function variant is associated with an infantile progressive motor-neurological syndrome. Exome sequencing followed by molecular studies, including cDNA analysis, SOD1 protein levels and enzymatic activity, and plasma neurofilament light chain levels, were undertaken in an infant with severe global developmental delay, axial hypotonia and limb spasticity. We identified a homozygous 3-bp in-frame deletion in SOD1. cDNA analysis predicted the loss of a single valine residue from a tandem pair (p.Val119/Val120) in the wild-type protein, yet expression levels and splicing were preserved. Analysis of SOD1 activity and protein levels in erythrocyte lysates showed essentially no enzymatic activity and undetectable SOD1 protein in the child, whereas the parents had ∼50% protein expression and activity relative to controls. Neurofilament light chain levels in plasma were elevated, implying ongoing axonal injury and neurodegeneration. Thus, we provide confirmatory evidence of a second biallelic variant in an infant with a severe neurological syndrome and suggest that the in-frame deletion causes instability and subsequent degeneration of SOD1. We highlight the importance of the valine residues at positions V119-120, and suggest possible implications for future therapeutics research.
12.	Fedele, Valentina, et al. (författare) Neurogenesis In The R6/2 Mouse Model Of Huntington'S Disease Is Impaired At The Level Of Neurod1 2011 Ingår i: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 173, s. 76-81 Tidskriftsartikel (refereegranskat)abstract Adult neurogenesis is impaired in the hippocampus of transgenic R6 mouse models of Huntington's disease (HD). The phenotypes of R6 transgenic mice mimic several symptoms and signs of the disease (Li et al., 2005). They exhibit neurological and endocrine changes resembling some symptoms seen in humans. The reduction in neurogenesis is only apparent in the dentate gyrus as the number of newborn neurons in the subventricular zone, and olfactory bulb, is normal in R6 mice. The mechanism(s) underlying the reduction in hippocampal neurogenesis is still not fully understood. Here we show that the number of neuroblasts, but not granule neuron progenitors, is greatly reduced in 11-week old transgenic mice compared with wild-type (WT) controls. We demonstrate that NeuroD1 expression is reduced in the hippocampus. This is coupled to a decreased expression of downstream markers doublecortin and calretinin in maturing neurons. Taken together, our results suggest that mutant huntingtin (Htt) causes alterations of proteins expression in hippocampal progenitors, which might contribute to cognitive deficits in Huntington's disease. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
13.	Forsgren, Elin, et al. (författare) A Novel mutation D96Mfs*8 in SOD1 identified in a Swedish ALS patient results in a truncated and heavily aggregation-prone protein Annan publikation (populärvet., debatt m.m.)
14.	Forsgren, Elin, 1987- (författare) Using patient-derived cell models to investigate the role of misfolded SOD1 in ALS 2017 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Protein misfolding and aggregation underlie several neurodegenerative proteinopathies including amyotrophic lateral sclerosis (ALS). Superoxide dismutase 1 (SOD1) was the first gene found to be associated with familial ALS. Overexpression of human mutant or wild type SOD1 in transgenic mouse models induces motor neuron (MN) degeneration and an ALS-like phenotype. SOD1 mutations, leading to the destabilization of the SOD1 protein is associated with ALS pathogenesis. However, how misfolded SOD1 toxicity specifically affects human MNs is not clear. The aim of this thesis was to develop patient-derived, cellular models of ALS to help understand the pathogenic mechanisms underlying SOD1.To understand which cellular pathways impact on the level of misfolded SOD1 in human cells, we established a model using patient-derived fibroblasts and quantified misfolded SOD1 in relation to disturbances in several ALS-related cellular pathways. Misfolded SOD1 levels did not change following reduction in autophagy, inhibition of the mitochondrial respiratory chain, or induction of endoplasmic reticulum (ER)-stress. However, inhibition of the ubiquitin-proteasome system (UPS) lead to a dramatic increase in misfolded SOD1 levels. Hence, an age-related decline in proteasome activity might underlie the late-life onset that is typically seen in SOD1 ALS.To address whether or not SOD1 misfolding is enhanced in human MNs, we used mixed MN/astrocyte cultures (MNCs) generated in vitro from patient-specific induced pluripotent stem cells (iPSCs). Levels of soluble misfolded SOD1 were increased in MNCs as well as in pure iPSC-derived astrocytes compared to other cell types, including sensory neuron cultures. Interestingly, this was the case for both mutant and wild type human SOD1, although the increase was enhanced in SOD1 FALS MNCs. Misfolded SOD1 was also found to exist in the same form as in mouse SOD1 overexpression models and was identified as a substrate for 20S proteasome degradation. Hence, the vulnerability of motor areas to ALS could be explained by increased SOD1 misfolding, specifically in MNs and astrocytes.To investigate factors that might promote SOD1 misfolding, we focussed on the stability of SOD1 mediated by a crucial, stabilizing C57-C146 disulphide bond and its redox status. Formation of disulphide bond is dependent on oxidation by O2 and catalysed by CCS. To investigate whether low O2 tension affects the stability of SOD1 in vitro we cultured fibroblasts and iPSC-derived MNCs under different oxygen tensions. Low oxygen tension promoted disulphide-reduction, SOD1 misfolding and aggregation. This response was much greater in MNCs compared to fibroblasts, suggesting that MNs may be especially sensitive to low oxygen tension and areas with low oxygen supply could serve as foci for ALS initiation.SOD1 truncation mutations often lack C146, and cannot adopt a native fold and are rapidly degraded. We characterized soluble misfolded and aggregated SOD1 in patient-derived cells carrying a novel SOD1 D96Mfs*8 mutation as well as in cells fom an unaffected mutation carrier. The truncated protein has a C-terminal fusion of seven non-native amino acids and was found to be extremely prone to aggregation in vitro. Since not all mutation carriers develop ALS, our results suggested this novel mutation is associated with reduced penetrance.In summary, patient derived cells are useful models to study factors affecting SOD1 misfolded and aggregation. We show for the first time that misfolding of a disordered and disease associated protein is enhanced in disease-related cell types. Showing that misfolded SOD1 exists in human cells in the same form as in transgenic mouse models strengthens the translatability of results obtained in the two species. Our results demonstrate disulphide-reduction and misfolding/aggregation of SOD1 and suggest that 20S proteasome could be an important therapeutic target for early stages of disease. This model provides a great opportunity to study pathogenic mechanisms of both familial and sporadic ALS in patient-derived models of ALS.
15.	Freischmidt, Axel, et al. (författare) Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia 2015 Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 18:5, s. 631- Tidskriftsartikel (refereegranskat)abstract Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative syndrome hallmarked by adult-onset loss of motor neurons. We performed exome sequencing of 252 familial ALS (fALS) and 827 control individuals. Gene-based rare variant analysis identified an exome-wide significant enrichment of eight loss-of-function (LoF) mutations in TBK1 (encoding TANK-binding kinase 1) in 13 fALS pedigrees. No enrichment of LoF mutations was observed in a targeted mutation screen of 1,010 sporadic ALS and 650 additional control individuals. Linkage analysis in four families gave an aggregate LOD score of 4.6. In vitro experiments confirmed the loss of expression of TBK1 LoF mutant alleles, or loss of interaction of the C-terminal TBK1 coiled-coil domain (CCD2) mutants with the TBK1 adaptor protein optineurin, which has been shown to be involved in ALS pathogenesis. We conclude that haploinsufficiency of TBK1 causes ALS and fronto-temporal dementia.
16.	Fälth, Linda, 1973-, et al. (författare) An intervention study to prevent ‘summer reading loss’ in a socioeconomically disadvantaged area with second language learners 2019 Ingår i: Nordic Journal of Literacy Research. - : NOASP. - 2464-1596. ; 5:3, s. 10-23 Tidskriftsartikel (refereegranskat)abstract Summer reading loss is a documented reality for many students. Research has established differences in the contribution of summer reading activity between children from families with different economic status. In this study, 120 students in Grade 2 and 115 students in Grade 3 from a socioeconomically vulnerable area participated in a summer reading intervention. In addition, a control group from the same schools comprised of 106 students from Grade 2 and 94 students from Grade 3. Almost 90% of the participating students did not have Swedish as their native language. The participants were tested on reading skills, including word decoding, nonsense-word reading, word comprehension and reading comprehension, before and after the summer vacation. The intervention was planned together with teachers from three participant schools and leisure centers. Before the summer holiday the schools arranged reading weeks and library visits. The students were encouraged to read at home during the vacation and record the number of books read on a digital platform. The results showed that the largest effect sizes between groups (intervention and control) were observed for word decoding in Grade 2 and word comprehension in Grade 3 where the intervention group improved more than the control group. If summer learning loss can be avoided or limited, the treatment can be considered worth implementing
17.	Fälth, Linda, 1973-, et al. (författare) Assessment Support as Part of Teacher Duties in the Subject of Swedish at the Elementary Level 2019 Ingår i: International Journal of Learning, Teaching and Educational Research. - Flacq : Society for Research and Knowledge Management. - 1694-2493 .- 1694-2116. ; 18:4, s. 85-109 Tidskriftsartikel (refereegranskat)abstract The aim of this study was to examine and describe the use of a formative assessment support regarding reading instruction in grades 1-3, viewed from a teacher perspective. Sixty-five teachers from all parts of Sweden responded to a questionnaire, who had used the support for at least one year. Of the participant teachers, nine were interviewed for the purpose of performing an in-depth analysis of the questions. The teachers stated that the primary use of the assessment results was to identify students in need of extra support, as a basis for performance appraisals, as well as for further lesson planning. Formative assessment was, on the one hand, described as a concrete practical method and, on the other hand, as an attitude. The results also indicate a feeling of frustration that, notwithstanding the current deeper insight into what every student needs, the teaching still proceeds on some middle-ground path or level.
18.	Gerdtsson, Anna Sandström, et al. (författare) Plasma protein profiling in a stage defined pancreatic cancer cohort – Implications for early diagnosis 2016 Ingår i: Molecular Oncology. - : Wiley. - 1574-7891. ; 10:8, s. 1305-1316 Tidskriftsartikel (refereegranskat)abstract Pancreatic ductal adenocarcinoma (PDAC) is a disease where detection preceding clinical symptoms significantly increases the life expectancy of patients. In this study, a recombinant antibody microarray platform was used to analyze 213 Chinese plasma samples from PDAC patients and normal control (NC) individuals. The cohort was stratified according to disease stage, i.e. resectable disease (stage I/II), locally advanced (stage III) and metastatic disease (stage IV). Support vector machine analysis showed that all PDAC stages could be discriminated from controls and that the accuracy increased with disease progression, from stage I to IV. Patients with stage I/II PDAC could be discriminated from NC with high accuracy based on a plasma protein signature, indicating a possibility for early diagnosis and increased detection rate of surgically resectable tumors.
19.	Gustafson, Stefan, 1968-, et al. (författare) Effects of a formative assessment system on early reading development 2019 Ingår i: Education. - Mobile, AL, United States : Project Innovation. - 0013-1172. ; 140:1, s. 17-27 Tidskriftsartikel (refereegranskat)abstract We present quantitative results from the pilot-year of a large scale Swedish educational project in reading development called LegiLexi, inspired by research within the Response to intervention and Formative assessment traditions. The vision of the project is that every pupil should reach adequate reading skills at the end of grade 3 in primary school. LegiLexi contains a formative assessment tool and a teacher course, which are linked together. We describe LegiLexi and analyze quantitative effects of the pilot year regarding reading development for pupils in grade 1. The design included three conditions; full access to LegiLexi, access only to the formative assessment tool, and control. Results showed that the group with full access to LegiLexi improved their word decoding and reading comprehension the most. For language comprehension, the Formative assessment only group showed the highest improvements. Thus, the features of LegiLexi seem to help enhance critical reading skills. Some changes will be made in the project to strengthen methodological aspects and further facilitate pupils’ reading development.
20.	Janelidze, Shorena, et al. (författare) Pre-existing immunity to adeno-associated virus (AAV)2 limits transgene expression following intracerebral AAV2-based gene delivery in a 6-hydroxydopamine model of Parkinson's disease. 2014 Ingår i: Journal of Gene Medicine. - : Wiley. - 1521-2254 .- 1099-498X. ; 16:9-10, s. 300-308 Tidskriftsartikel (refereegranskat)abstract Adeno-associated virus (AAV) vectors are used to deliver potentially therapeutic genes in clinical trials in Parkinson's disease (PD). Pre-existing immunity to AAV and a local neuroinflammatory response might negatively affect the efficacy of such AAV-mediated gene delivery.
21.	Johansson, Ulrika, et al. (författare) Lustfyllda mellanmål : för svårt sjuka barn 2011 Bok (populärvet., debatt m.m.)
22.	Keskin, Isil, 1987-, et al. (författare) Low oxygen tension induces misfolding and aggregation of superoxide dismutase in ALS patient-derived motor neurons Annan publikation (övrigt vetenskapligt/konstnärligt)
23.	Keskin, Isil, 1987-, et al. (författare) Peripheral administration of SOD1 aggregates does not transmit pathogenic aggregation to the CNS of SOD1 transgenic mice 2021 Ingår i: Acta neuropathologica communications. - : BioMed Central. - 2051-5960. ; 9:1 Tidskriftsartikel (refereegranskat)abstract The deposition of aggregated proteins is a common neuropathological denominator for neurodegenerative disorders. Experimental evidence suggests that disease propagation involves prion-like mechanisms that cause the spreading of template-directed aggregation of specific disease-associated proteins. In transgenic (Tg) mouse models of superoxide dismutase-1 (SOD1)-linked amyotrophic lateral sclerosis (ALS), inoculation of minute amounts of human SOD1 (hSOD1) aggregates into the spinal cord or peripheral nerves induces premature ALS-like disease and template-directed hSOD1 aggregation that spreads along the neuroaxis. This infectious nature of spreading pathogenic aggregates might have implications for the safety of laboratory and medical staff, recipients of donated blood or tissue, or possibly close relatives and caregivers. Here we investigate whether transmission of ALS-like disease is unique to the spinal cord and peripheral nerve inoculations or if hSOD1 aggregation might spread from the periphery into the central nervous system (CNS). We inoculated hSOD1 aggregate seeds into the peritoneal cavity, hindlimb skeletal muscle or spinal cord of adult Tg mice expressing mutant hSOD1. Although we used up to 8000 times higher dose—compared to the lowest dose transmitting disease in spinal cord inoculations—the peripheral inoculations did not transmit seeded aggregation to the CNS or premature ALS-like disease in hSOD1 Tg mice. Nor was any hSOD1 aggregation detected in the liver, kidney, skeletal muscle or sciatic nerve. To explore potential reasons for the lack of disease transmission, we examined the stability of hSOD1 aggregates and found them to be highly vulnerable to both proteases and detergent. Our findings suggest that exposed individuals and personnel handling samples from ALS patients are at low risk of any potential transmission of seeded hSOD1 aggregation.
24.	Keskin, Isil, 1987-, et al. (författare) The molecular pathogenesis of superoxide dismutase 1-linked ALS is promoted by low oxygen tension 2019 Ingår i: Acta Neuropathologica. - New York : Springer. - 0001-6322 .- 1432-0533. ; 138:1, s. 85-101 Tidskriftsartikel (refereegranskat)abstract Mutations in superoxide dismutase 1 (SOD1) cause amyotrophic lateral sclerosis (ALS). Disease pathogenesis is linked to destabilization, disorder and aggregation of the SOD1 protein. However, the non-genetic factors that promote disorder and the subsequent aggregation of SOD1 have not been studied. Mainly located to the reducing cytosol, mature SOD1 contains an oxidized disulfide bond that is important for its stability. Since O2 is required for formation of the bond, we reasoned that low O2 tension might be a risk factor for the pathological changes associated with ALS development. By combining biochemical approaches in an extensive range of genetically distinct patient-derived cell lines, we show that the disulfide bond is an Achilles heel of the SOD1 protein. Culture of patient-derived fibroblasts, astrocytes, and induced pluripotent stem cell-derived mixed motor neuron and astrocyte cultures (MNACs) under low oxygen tensions caused reductive bond cleavage and increases in disordered SOD1. The effects were greatest in cells derived from patients carrying ALS-linked mutations in SOD1. However, significant increases also occurred in wild-type SOD1 in cultures derived from non-disease controls, and patients carrying mutations in other common ALS-linked genes. Compared to fibroblasts, MNACs showed far greater increases in SOD1 disorder and even aggregation of mutant SOD1s, in line with the vulnerability of the motor system to SOD1-mediated neurotoxicity. Our results show for the first time that O2 tension is a principal determinant of SOD1 stability in human patient-derived cells. Furthermore, we provide a mechanism by which non-genetic risk factors for ALS, such as aging and other conditions causing reduced vascular perfusion, could promote disease initiation and progression.
25.	Krank, Benjamin, et al. (författare) Tuning spot weld models for vehicle body structural dynamics 2012 Ingår i: Proceedings Of International Conference On Noise And Vibration Engineering (ISMA2012) / International Conference On Uncertainty In Structural Dynamics (USD2012). - : Katholieke Universiteit Leuven. - 9789073802896 ; , s. 3915-3926 Konferensbidrag (refereegranskat)abstract Efforts focussing on modelling of spot welds in typical automotive structures have been spent during the last decades resulting in a number of different modelling techniques. One of the crucial aspects common to all these approaches is the difficulties related to the local complexity of the modelling of the actual connections. In order to handle this complexity, spot weld models are often dependent on parameters tuning their characteristics. This paper discusses the tuning of two different spot weld models with respect to certain parameters; the RBE3-Hexa-RBE3 model (also known as the ACM 2) and the Spider2 model available in the pre-processor Ansa. With the current trend towards increasingly refined finite element model meshes, current guide lines need to be updated and elaborated further in order to identify the best performing models. In this paper, model studies are discussed targeting tuning of spot weld parameters together with a new proposal for an exact method for updating the Young's modulus and density of isotropic shell structures analytically using an initial FE calculation.
26.	Kurowska, Zuzanna, et al. (författare) Identification of Multiple QTLs Linked to Neuropathology in the Engrailed-1 Heterozygous Mouse Model of Parkinson's Disease 2016 Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6 Tidskriftsartikel (refereegranskat)abstract Motor symptoms in Parkinson's disease are attributed to degeneration of midbrain dopaminergic neurons (DNs). Heterozygosity for Engrailed-1 (En1), one of the key factors for programming and maintenance of DNs, results in a parkinsonian phenotype featuring progressive degeneration of DNs in substantia nigra pars compacta (SNpc), decreased striatal dopamine levels and swellings of nigro-striatal axons in the SwissOF1-En1+/- mouse strain. In contrast, C57Bl/6-En1+/- mice do not display this neurodegenerative phenotype, suggesting that susceptibility to En1 heterozygosity is genetically regulated. Our goal was to identify quantitative trait loci (QTLs) that regulate the susceptibility to PD-like neurodegenerative changes in response to loss of one En1 allele. We intercrossed SwissOF1-En1+/- and C57Bl/6 mice to obtain F2 mice with mixed genomes and analyzed number of DNs in SNpc and striatal axonal swellings in 120 F2-En1+/- 17 week-old male mice. Linkage analyses revealed 8 QTLs linked to number of DNs (p = 2.4e-09, variance explained = 74%), 7 QTLs linked to load of axonal swellings (p = 1.7e-12, variance explained = 80%) and 8 QTLs linked to size of axonal swellings (p = 7.0e-11, variance explained = 74%). These loci should be of prime interest for studies of susceptibility to Parkinson's disease-like damage in rodent disease models and considered in clinical association studies in PD.
27.	Ledning och styrning av en region : Region Dalarna & digitaliseringen #VPF11 2022 Konstnärligt arbete (film/video)abstract I den här videon beskrivs hur Region Dalarna valt att organisera ledning och styrning av uppdraget. Uppdrag och organisering i en region styrs främst av Regeringsreformen och Kommunallagen. En region är precis som en kommun, självstyrande inom ramen för lagens ramar. Videon illustrerar skillnaden mellan politisk organisation och tjänstemannaorganisation. Ledning och styrning sätts i sammanhanget av regionens digitalisering. En utvärdering visade att digitaliseringen är organiserad i en parallell beslutsstruktur med en egen uppsättning roller och arbetssätt. Det här leder till svårigheter att utkräva ansvar av ordinarie chefer, att utrymmet för utveckling och innovation är begränsat eftersom majoriteten av digitaliseringsresursen går åt till förfining och förbättring av det befintliga digitala landskapet. Region Dalarna har nu startat ett initiativ för att åtgärda problemen. Målet är att avveckla parallellstrukturen, men initialt skapas funktion i strukturen i syfte att konsolidera det digitala landskapet, samtidigt som en ny organiseringsgrund utforskas parallellt med ny teknik för att öka förmågan att genomföra Regionens kärnverksamhet.
28.	Lehmann, Manuela, et al. (författare) Aggregate-selective antibody attenuates seeded aggregation but not spontaneously evolving disease in SOD1 ALS model mice 2020 Ingår i: Acta neuropathologica communications. - : BMC. - 2051-5960. ; 8:1 Tidskriftsartikel (refereegranskat)abstract Increasing evidence suggests that propagation of the motor neuron disease amyotrophic lateral sclerosis (ALS) involves the pathogenic aggregation of disease-associated proteins that spread in a prion-like manner. We have identified two aggregate strains of human superoxide dismutase 1 (hSOD1) that arise in the CNS of transgenic mouse models of SOD1-mediated ALS. Both strains transmit template-directed aggregation and premature fatal paralysis when inoculated into the spinal cord of adult hSOD1 transgenic mice. This spread of pathogenic aggregation could be a potential target for immunotherapeutic intervention. Here we generated mouse monoclonal antibodies (mAbs) directed to exposed epitopes in hSOD1 aggregate strains and identified an aggregate selective mAb that targets the aa 143–153 C-terminal extremity of hSOD1 (αSOD1143–153). Both pre-incubation of seeds with αSOD1143–153 prior to inoculation, and weekly intraperitoneal (i.p.) administration attenuated transmission of pathogenic aggregation and prolonged the survival of seed-inoculated hSOD1G85R Tg mice. In contrast, administration of a mAb targeting aa 65–72 (αSOD165–72), which exhibits high affinity towards monomeric disordered hSOD1, had an adverse effect and aggravated seed induced premature ALS-like disease. Although the mAbs reached similar concentrations in CSF, only αSOD1143–153 was found in association with aggregated hSOD1 in spinal cord homogenates. Our results suggest that an aggregate-selective immunotherapeutic approach may suppress seeded transmission of pathogenic aggregation in ALS. However, long-term administration of αSOD1143–153 was unable to prolong the lifespan of non-inoculated hSOD1G85R Tg mice. Thus, spontaneously initiated hSOD1 aggregation in spinal motor neurons may be poorly accessible to therapeutic antibodies.
29.	Lehmann, Manuela, 1986- (författare) SOD1 misfolding and aggregation in ALS : in the light of conformation-specific antibodies 2019 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Mutations in the superoxide dismutase 1 (SOD1) gene are linked to the progressive neurodegenerative disease amyotrophic lateral sclerosis (ALS). ALS-associated mutations affect the stability of the SOD1 protein and promote its unfolding. As a consequence, disordered SOD1 species can misfold and accumulate into insoluble aggregates. Cytoplasmic inclusions containing misfolded SOD1 are a hallmark of ALS pathology in patients as well as transgenic mouse models. However, it remains unclear, which SOD1 species are pathogenic and how they arise and contribute to the disease.The aim of this thesis was to use antibodies as tools to study the role of disordered and aggregated SOD1 species in ALS. These antibodies recognize epitopes exposed in disordered SOD1 species and hence, discriminate between natively folded SOD1 and the disordered or misfolded protein.SOD1 is expressed in all cell types, but aggregates of misfolded SOD1 are predominantly found in motor neurons and associated glial cells in the spinal cord of ALS patients. To understand why misfolded SOD1 targets the motor system, we used ELISA and immunocapture methods to quantify soluble SOD1 species in patient-derived cell models of ALS. The highest levels of soluble disordered SOD1 were detected in induced pluripotent stem cell (iPSC)-derived motor neuron and astrocytes cultures (MNACs) compared to fibroblasts, iPSCs and sensory neuron cultures. These results suggest that the selective vulnerability of motor areas to SOD1-ALS could derive from an enhanced burden of disordered SOD1.To understand factors that might promote SOD1 unfolding, we focussed on the disulfide bond that is required for the stability of natively folded SOD1. Formation of the bond is oxygen-dependent and reduction of the bond promotes SOD1 unfolding. We studied the stability of SOD1 in patient-derived cells exposed to lowered oxygen tensions. This induced increases in disulfide-reduced, disordered mutant and wild-type SOD1. The response was time- and concentration-dependent and more pronounced in MNACs, where even increased aggregation of mutant SOD1 was observed. These results are consistent with the enhanced vulnerability of the motor system in ALS and suggest that conditions causing impaired oxygen perfusion could contribute to the initiation and progression of the disease.Inclusions containing aggregated misfolded wild-type SOD1 have been found in sporadic ALS (sALS) patients without SOD1 mutations and those carrying mutations in genes other than SOD1. However, other groups have reported contrasting results and the contribution of misfolded wild-type SOD1 to ALS pathology is controversial. Guidelines for preservation, storage, and analysis of tissues under standardized conditions would facilitate the comparison of results between different laboratories. We established an optimized immunohistochemistry protocol to detect misfolded wild-type SOD1 in paraffin-embedded spinal cord samples from sALS patients. We also developed a method to immunocapture disordered SOD1 from frozen post-mortem tissue. High, but variable, levels of disordered SOD1 were detected in spinal cords from sALS patients. Our data support a possible pathological role of misfolded wild-type SOD1 in sALS.Recent evidence suggests that SOD1 aggregates can induce templated aggregation of disordered SOD1 and spread from cell-to-cell via a prion-like mechanism. To test if antibodies could block this process in vivo, we conducted an immunotherapy study in a model of prion-like spread, where SOD1 aggregate seeds are inoculated into the lumbar spinal cord of SOD1G85R transgenic mice and lead to accelerated disease onset and progression. Novel monoclonal antibodies (mAb) against disordered domains of SOD1 aggregates were developed and validated for their reactivity to disordered and aggregated SOD1 species in vitro and in vivo. Immunotherapy using a mAb against the C-terminal end of SOD1 attenuated the onset and progression of prion-like SOD1 spread. However, no effect was seen on onset, duration or progression of the underlying disease. This suggests that, under the conditions tested, immunotherapy against disordered domains of SOD1 does not affect intracellular aggregation and additional strategies might be needed to reduce intracellular accumulation of misfolded SOD1 aggregation.In conclusion, we show that conformation-specific antibodies are powerful tools to investigate disordered and potentially pathogenic species of SOD1 in various biochemical, cellular and in vivo contexts. The development of the novel immunocapture strategy could facilitate future research on characterizing SOD1 aggregates from mouse tissues, patient-derived cells or post-mortem tissues with the goal of determining their role in ALS disease pathogenesis.
30.	Lindmark, Ulrika, 1965-, et al. (författare) Med en salutogen blick för att främja oral hälsa 2022 Ingår i: Aktuel Nordisk Odontologi. - : Universitetsforlaget. - 1902-3545 .- 2058-7538. ; 47:1, s. 33-47 Tidskriftsartikel (refereegranskat)abstract Tandvården är främst präglad av ett patogent synsätt med fokus på riskfaktorer och behandling. Om vi istället sätter på oss salutogena glasögon kan vi med detta synsätt se individens livssituation och dennes resurser för att främja hälsosamma vanor. Tandvårdspersonal kan stödja individen genom personcentrerade samtal och på så sätt skapa delaktighet och motivation och uppmuntra individen till att använda sin kapacitet och resurser i syfte att påverka sin orala hälsa. Tandvården är också en viktig hälsofrämjande arena som bör samverka med andra arenor utanför kliniken och integrera den orala hälsan med allmänhälsan. Att arbeta med hälsoresurser och främjande bestämningsfaktorer enligt en salutogen grundsyn för ett hälsofrämjande arbete i praktiken är en framgångsfaktor för en jämställd och god hälsa för alla.
31.	Lorentzon, Ronny, et al. (författare) The Achilles heel of exercise. 2000 Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 355:9218, s. 1909-10; author reply 1911 Tidskriftsartikel (refereegranskat)
32.	Nordström, F, et al. (författare) Decolorization of a mixture of textile dyes using Bjerkandera sp. BOL 13 2008 Ingår i: Environmental technology. - : Taylor & Francis. - 0959-3330 .- 1479-487X. ; 29:8, s. 921-929 Tidskriftsartikel (refereegranskat)abstract The white-rot fungus Bjerkandera sp. BOL 13 was evaluated regarding decolorization of four textile dyes Reactive blue 21, Reactive black 5, Reactive orange 13 and Reactive yellow 206. Experiments were performed in batch and continuous modes. The total dye concentration in all experimtents was 100 mg/l. The results of the batch experiments showed that the fungus decolorized all dyes but at different rates. There was, however, an increase in the ultraviolet (UV) absorbance when a medium with a low concentration of nitrogen was used. No increase in UV range was observed when the nitrogen concentration was increased. A continuous experiment was performed to study the decolorization of a mixture of three of the dyes Reactive blue 21, Reactive black 5 and Reactive orange 13. Scanning of inlet and outlet samples showed that the absorbance at the peaks in the visible range decreased by 60-66%. The UV absorbance of the outlet increased during the first days of operation after which it decreased again to reach the same level as the inlet. The hydraulic retention time in the reactor was 3 days. The medium containing the higher nitrogen concentration was used in the continuous experiment.
33.	Nordström, F, et al. (författare) Decolorization of a mixture of textile dyes using Bjerkandera sp. BOL-13. 2008 Ingår i: Environmental Technology. - : Informa UK Limited. - 1479-487X .- 0959-3330. ; 29:8, s. 921-929 Tidskriftsartikel (refereegranskat)abstract The white-rot fungus Bjerkandera sp. BOL-13 was evaluated regarding decolorization of four textile dyes Reactive blue 21, Reactive black 5, Reactive orange 13 and Reactive yellow 206. Experiments were performed in batch and continuous modes. The total dye concentration in all experiments was 100 mg l(-1). The results of the batch experiments showed that the fungus decolorized all dyes but at different rates. There was, however, an increase in the ultraviolet (UV) absorbance when a medium with a low concentration of nitrogen was used. No increase in UV range was observed when the nitrogen concentration was increased. A continuous experiment was performed to study the decolorization of a mixture of three of the dyes Reactive blue 21, Reactive black 5 and Reactive orange 13. Scanning of inlet and outlet samples showed that the absorbance at the peaks in the visible range decreased by 60-66%. The UV absorbance of the outlet increased during the first days of operation after which it decreased again to reach the same level as the inlet. The hydraulic retention time in the reactor was 3 days. The medium containing the higher nitrogen concentration was used in the continuous experiment.
34.	Nordström, Lena, et al. (författare) Expanded clinical and experimental use of SOX11-using a monoclonal antibody 2012 Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 12:269 Tidskriftsartikel (refereegranskat)abstract Background: The transcription factor SOX11 is of diagnostic and prognostic importance in mantle cell lymphoma (MCL) and epithelial ovarian cancer (EOC), respectively. Thus, there is an unmet clinical and experimental need for SOX11-targeting assays with low background, high specificity and robust performance in multiple applications, including immunohistochemistry (IHC-P) and flow cytometry, which until now has been lacking. Methods: We have developed SOX11-C1, a monoclonal mouse antibody targeting SOX11, and successfully evaluated its performance in western blots (WB), IHC-P, fluorescence microscopy and flow cytometry. Results: We confirm the importance of SOX11 as a diagnostic antigen in MCL as 100% of tissue micro array (TMA) cases show bright nuclear staining, using the SOX11-C1 antibody in IHC-P. We also show that previous reports of weak SOX11 immunostaining in a fraction of hairy cell leukemias (HCL) are not confirmed using SOX11-C1, which is consistent with the lack of transcription. Thus, high sensitivity and improved specificity are demonstrated using the monoclonal SOX11-C1 antibody. Furthermore, we show for the first time that flow cytometry can be used to separate SOX11 positive and negative cell lines and primary tumors. Of note, SOX11-C1 shows no nonspecific binding to primary B or T cells in blood and thus, can be used for analysis of B and T cell lymphomas from complex clinical samples. Dilution experiments showed that low frequencies of malignant cells (similar to 1%) are detectable above background using SOX11 as a discriminant antigen in flow cytometry. Conclusions: The novel monoclonal SOX11-specific antibody offers high sensitivity and improved specificity in IHC-P based detection of MCL and its expanded use in flow cytometry analysis of blood and tissue samples may allow a convenient approach to early diagnosis and follow-up of MCL patients.
35.	Nordström, Peter, et al. (författare) Type of physical activity, muscle strength, and pubertal stage as determinants of bone mineral density and bone area in adolescent boys. 1998 Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 13:7, s. 1141-8 Tidskriftsartikel (refereegranskat)abstract The present study was conducted to evaluate the influence of different types of weight-bearing physical activity, muscle strength, and puberty on bone mineral density (BMD, g/cm2) and bone area in adolescent boys. Three different groups were investigated. The first group consisted of 12 adolescent badminton players (age 17.0 +/- 0.8 years) training for 5.2 +/- 1.9 h/week. The second group consisted of 28 ice hockey players (age 16.9 +/- 0.3 years) training for 8.5 +/- 2.2 h/week. The third group consisted of 24 controls (age 16.8 +/- 0.3 years) training for 1.4 +/- 1.4h/week. The groups were matched for age, height, and pubertal stage. BMD, bone mineral content (BMC, g), and the bone area of the total body, lumbar spine, hip, femur and tibia diaphyses, distal femur, proximal tibia, and humerus were measured using dual-energy X-absorptiometry. When adjusting for the difference in body weight between the groups, the badminton players were found to have significantly higher BMD (p < 0.05) of the trochanter and distal femur compared with the ice hockey players despite a significantly lower weekly average training. The badminton players had higher BMD compared with the control with the control group at all weight-bearing BMD sites, except at the diaphyses of the femur and tibia and lumbar spine. The independent predictors of bone density were estimated by adjusting BMC for the bone area in a multivariate analysis among all subjects (n = 64). Accordingly, the bone density of all sites except the spine was significantly related to muscle strength and height, and the bone density of the total body, neck, trochanter, distal femur, and proximal tibia was significantly related to type of physical activity (beta = 0.09-0.33, p < 0.05). The bone area values at different sites were strongly related to muscle strength and height and less strongly related to the type of physical activity and pubertal stage. In conclusion, it seems that during late puberty in adolescent boys the type of weight-bearing physical activity is an important determinant of bone density, while the bone area is largely determined by parameters related to body size. The higher BMD at weight-bearing sites in badminton players compared with ice hockey players, despite significantly less average weekly training, indicates that physical activity including jumps in unusual directions has a great osteogenic potential.
36.	Nordström, Thomas, Filosofie doktor i psykologi, 1977-, et al. (författare) Teacher inquiry of using assessments and recommendations in teaching early reading 2019 Ingår i: Studies in Educational Evaluation. - : Elsevier. - 0191-491X .- 1879-2529. ; 63, s. 9-16 Tidskriftsartikel (refereegranskat)abstract Previous research point to difficulties for teachers to interpret reading assessment data with regard to instructional decisions. This study explored Swedish primary teachers' use of assessments and recommendations, in order to be able to target individual needs. Eight teachers participated in a reading program and were interviewed in focus-group meetings. The analysis of teacher narratives stemming from assessment use resulted in three themes: Awareness of student learning, Changes in the organization of teaching, but not regarding individualized content and Strengthened teacher role, but modest professional growth. The themes indicated that the teachers had become aware of their students’ learning, had employed teaching based on informed decisions, and showed initial professional growth.However, the assessment details and the recommendations allowed for more adjustments than was evident in the teachers’ narratives. The results point to the relative difficulty of targeting individual needs in the general classroom education, and to the challenges of changing teaching practices.
37.	Nordström, Thomas, Filosofie doktor i psykologi, 1977-, et al. (författare) The potential of a forward-looking assessment and teaching system on students' reading gains 2019 Ingår i: European Dyslexia Association Autumn Seminar, Växjö, Sweden, September 27-29. Konferensbidrag (refereegranskat)abstract PurposeHow can teachers optimize reading instruction in Swedish schools? This poster presents findings from two studies investigating A) grade 1-3 teachers’ use of a forward-looking assessment and teaching system (LegiLexi) and B), its effect on student reading gains in Grade 1. The purpose of study A was to support teachers with an assessment system which included teaching recommendations for individual students and to study how that support enabled teachers to individualize instruction. The purpose of study B was to gather evidence that such support is superior in relation to “teaching as usual”.MethodIn study A, focus group meetings of eight active LegiLexi teachers were used as to answer the question of the extent teachers managed to individualize instruction in their everyday practice. In study B, we randomly assigned schools to three conditions; full access to LegiLexi (8 schools/217 students), access only to part of LegiLexi (4 schools/86 students) and control (9 schools/208 students), following estimated effects of LegiLexi across three test occasions containing reading measures. Results/conclusionsIn study A, results revealed that teachers were supported by LegiLexi, and were able to individualize instruction primarily by creating dynamic reading groups of students. However, individualizing further proved challenging. In study B, findings revealed that the group with full access to LegiLexi improved their word decoding (d=1.79 vs 1.33 and 1.20) and reading comprehension the most (d=1.75 vs 1.45 and 1.16). Thus, the findings show promising results for Swedish schools of how to improve reading instruction by focusing on students’ individual needs.
38.	Nordström, Ulrika, 1971-, et al. (författare) An early role for WNT signaling in specifying neural patterns of Cdx and Hox gene expression and motor neuron subtype identity 2006 Ingår i: PLoS biology. - : Public library of science. - 1544-9173 .- 1545-7885. ; 4:8, s. 1438-1452 Tidskriftsartikel (refereegranskat)abstract The link between extrinsic signaling, progenitor cell specification and neuronal subtype identity is central to the developmental organization of the vertebrate central nervous system. In the hindbrain and spinal cord, distinctions in the rostrocaudal identity of progenitor cells are associated with the generation of different motor neuron subtypes. Two fundamental classes of motor neurons, those with dorsal (dMN) and ventral (vMN) exit points, are generated over largely non-overlapping rostrocaudal domains of the caudal neural tube. Cdx and Hox genes are important determinants of the rostrocaudal identity of neural progenitor cells, but the link between early patterning signals, neural Cdx and Hox gene expression, and the generation of dMN and vMN subtypes, is unclear. Using an in vitro assay of neural differentiation, we provide evidence that an early Wnt-based program is required to interact with a later retinoic acid- and fibroblast growth factor–mediated mechanism to generate a pattern of Cdx and Hox profiles characteristic of hindbrain and spinal cord progenitor cells that prefigure the generation of vMNs and dMNs.
39.	Nordström, Ulrika, 1971- (författare) Early Rostrocaudal Patterning of the CNS 2005 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The transformation of an initially uniform population of epiblast cells into an intricately complex central nervous system (CNS) is one of the most fascinating processes during embryonic development. Presumptive neural cells are initially specified as cells of forebrain character. Studies in various vertebrates have indicated that cells of more caudal neural character, that will generate the brain stem and spinal cord, are generated through the reprogramming of these initial rostral cells. The initial regionalization of these neural progenitor cells is central to all further diversification of neuronal cell types and the subsequent formation of functional euronal circuits. The aim of this thesis has been to enhance our understanding of which stages of embryonic development that are critical for the initial rostrocaudal regionalization of neural precursor cells, and which signaling mechanisms that orchestrate this early diversification.Both human and chick embryos have the shape of a flat disc during gastrulation. At this early stage, the chick neural plate is already regionalized and cells positioned at distinct rostrocaudal levels are specified to generate cells exhibiting a gene expression profile characteristic of the forebrain, midbrain, rostral hindbrain and caudal spinal cord, respectively. In addition, the Isthmic organizer (IsO), a secondary signaling centre at the midbrain–hindbrain border that is required for the further development of this region, is also specified already at the gastrula stage. Caudal neural character is induced by signals from adjacent tissues - the primitive streak and the paraxial mesoderm. Wingless/Wnts, Fibroblastic growth factors (FGFs) and retinoids (RA) are signaling molecules that have been proposed to promote caudal embryonic development, and exhibit spatio- emporal expression patterns that coincide with early caudalizing activities. The caudalizing activity that emanates from the gastrula stage paraxial mesoderm is mediated by Wnt signals, and the induction of caudal neural character by Wnts results from a direct action on neural precursor cells. In the presence of FGF activity, graded Wnt signaling is sufficient to induce cells exhibiting caudal forebrain, midbrain and rostral hindbrain character. The discrimination between rostral hindbrain and caudal spinal cord character appear to depend on a gradient of both Wnt and FGF signals.At hindbrain and spinal cord levels the patterned generation of neural progenitor cells along the rostrocaudal axis controls the generation of different classes of motor neurons in response to diffusible Sonic hedgehog (Shh) signals. Gastrula stage Wnt signaling is also required for this subsequent generation of motor neuron subtypes characteristic of the hindbrain and spinal cord.Later, at the early somite stage, cells characteristic of the caudal hindbrain and rostral spinal cord are specified adjacent to RA producing paraxial mesoderm. Opponent RA and FGF signals appear to act on, and refine the rostrocaudal identity of the initial hindbrain and spinal cord cells induced by gastrula stage Wnt based signals. Consistently, combinatorial Wnt, FGF and/or RA signals are sufficient to reconstruct neural progenitor cells that differentiate into motor neurons characteristic of the caudal hindbrain, rostral spinal cord and caudal spinal cord, respectively, in response to Shh.
40.	Nordström, Ulrika, et al. (författare) Early Wnt Signaling is Required to Establish Hox Gene Profiles and Motor Neuron Subtypes in the Developing Hindbrain and Spinal Cord Annan publikation (övrigt vetenskapligt/konstnärligt)
41.	Nordström, Ulrika, et al. (författare) Mutant SOD1 aggregates formed in vitro and in cultured cells are polymorphic and differ from those arising in the CNS 2023 Ingår i: Journal of Neurochemistry. - : John Wiley & Sons. - 0022-3042 .- 1471-4159. ; 164:1, s. 77-93 Tidskriftsartikel (refereegranskat)abstract Mutations in the human Superoxide dismutase 1 (hSOD1) gene are well-established cause of the motor neuron disease ALS. Patients and transgenic (Tg) ALS model mice carrying mutant variants develop hSOD1 aggregates in the CNS. We have identified two hSOD1 aggregate strains, which both transmit spreading template-directed aggregation and premature fatal paralysis when inoculated into adult transgenic mice. This prion-like spread of aggregation could be a primary disease mechanism in SOD1-induced ALS. Human SOD1 aggregation has been studied extensively both in cultured cells and under various conditions in vitro. To determine how the structure of aggregates formed in these model systems related to disease-associated aggregates in the CNS, we used a binary epitope-mapping assay to examine aggregates of hSOD1 variants G93A, G85R, A4V, D90A, and G127X formed in vitro, in four different cell lines and in the CNS of Tg mice. We found considerable variability between replicate sets of in vitro-generated aggregates. In contrast, there was a high similarity between replicates of a given hSOD1 mutant in a given cell line, but pronounced variations between different hSOD1 mutants and different cell lines in both structures and amounts of aggregates formed. The aggregates formed in vitro or in cultured cells did not replicate the aggregate strains that arise in the CNS. Our findings suggest that the distinct aggregate morphologies in the CNS could result from a micro-environment with stringent quality control combined with second-order selection by spreading ability. Explorations of pathogenesis and development of therapeutics should be conducted in models that replicate aggregate structures forming in the CNS. (Figure presented.)
42.	Nordström, Ulrika, et al. (författare) Progressive induction of caudal neural character by graded Wnt signaling 2002 Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 5:6, s. 525-532 Tidskriftsartikel (refereegranskat)abstract Early in differentiation, all neural cells have a rostral character. Only later do posteriorly positioned neural cells acquire characteristics of caudal forebrain, midbrain and hindbrain cells. Caudalization of neural tissue in the chick embryo apparently involves the convergent actions of (i) fibroblast growth factor (FGF) signaling and (ii) signaling from the caudal paraxial mesoderm, or 'PMC activity', which has not yet been defined molecularly. Here we report evidence that Wnt signaling underlies PMC activity, and show that Wnt signals act directly and in a graded manner on anterior neural cells to induce their progressive differentiation into caudal forebrain, midbrain and hindbrain cells.
43.	Nordström, Ulrika, et al. (författare) Progressive nigrostriatal terminal dysfunction and degeneration in the engrailed1 heterozygous mouse model of Parkinson's disease. 2015 Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 73, s. 70-82 Tidskriftsartikel (refereegranskat)abstract Current research on Parkinson's disease (PD) pathogenesis requires relevant animal models that mimic the gradual and progressive development of neuronal dysfunction and degeneration that characterizes the disease. Polymorphisms in engrailed 1 (En1), a homeobox transcription factor that is crucial for both the development and survival of mesencephalic dopaminergic neurons, are associated with sporadic PD. This suggests that En1 mutant mice might be a promising candidate PD model. Indeed, a mouse that lacks one En1 allele exhibits decreased mitochondrial complex I activity and progressive midbrain dopamine neuron degeneration in adulthood, both features associated with PD. We aimed to further characterize the disease-like phenotype of these En1(+/-) mice with a focus on early neurodegenerative changes that can be utilized to score efficacy of future disease modifying studies. We observed early terminal defects in the dopaminergic nigrostriatal pathway in En1(+/-) mice. Several weeks before a significant loss of dopaminergic neurons in the substantia nigra could be detected, we found that striatal terminals expressing high levels of dopaminergic neuron markers TH, VMAT2, and DAT were dystrophic and swollen. Using transmission electron microscopy, we identified electron dense bodies consistent with abnormal autophagic vacuoles in these terminal swellings. In line with these findings, we detected an up-regulation of the mTOR pathway, concurrent with a downregulation of the autophagic marker LC3B, in ventral midbrain and nigral dopaminergic neurons of the En1(+/-) mice. This supports the notion that autophagic protein degradation is reduced in the absence of one En1 allele. We imaged the nigrostriatal pathway using the CLARITY technique and observed many fragmented axons in the medial forebrain bundle of the En1(+/-) mice, consistent with axonal maintenance failure. Using in vivo electrochemistry, we found that nigrostriatal terminals in the dorsal striatum were severely deficient in dopamine release and reuptake. Our findings support a progressive retrograde degeneration of En1(+/-) nigrostriatal neurons, akin to what is suggested to occur in PD. We suggest that using the En1(+/-) mice as a model will provide further key insights into PD pathogenesis, and propose that axon terminal integrity and function can be utilized to estimate dopaminergic neuron health and efficacy of experimental PD therapies.
44.	Olander, Susanne, et al. (författare) Convergent Wnt and FGF signaling at the gastrula stage induce the formation of the isthmic organizer. 2006 Ingår i: Mechanisms of Development. - : Elsevier BV. - 0925-4773 .- 1872-6356. ; 123:2, s. 166-176 Tidskriftsartikel (refereegranskat)abstract The development of the vertebrate brain depends on the formation of local organizing centres within the neural tube that express secreted signals that refine local neural progenitor identity. The isthmic organizer (IsO) forms at the isthmic constriction and is required for the growth and ordered development of mesencephalic and metencephalic structures. The formation of the IsO, which is characterized by the generation of a complex pattern of cells at the midbrain-hindbrain boundary, has been described in detail. However, when neural plate cells are initially instructed to form the IsO, the molecular nature of the inductive signals remain poorly defined. We now provide evidence that convergent Wnt and FGF signaling at the gastrula stage are required to generate the complex polarized pattern of cells characteristic of the IsO, and that Wnt and FGF signals in combination are sufficient to reconstruct, in naïve forebrain cells, an IsO-like structure that exhibits an organizing activity that mimics the endogenous IsO when transplanted into the diencephalon of chick embryos.
45.	Paré, Bastien, et al. (författare) Misfolded SOD1 pathology in sporadic Amyotrophic Lateral Sclerosis 2018 Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8 Tidskriftsartikel (refereegranskat)abstract Aggregation of mutant superoxide dismutase 1 (SOD1) is a pathological hallmark of a subset of familial ALS patients. However, the possible role of misfolded wild type SOD1 in human ALS is highly debated. To ascertain whether or not misfolded SOD1 is a common pathological feature in non-SOD1 ALS, we performed a blinded histological and biochemical analysis of post mortem brain and spinal cord tissues from 19 sporadic ALS, compared with a SOD1 A4V patient as well as Alzheimer's disease (AD) and non-neurological controls. Multiple conformation-or misfolded-specific antibodies for human SOD1 were compared. These were generated independently by different research groups and were compared using standardized conditions. Five different misSOD1 staining patterns were found consistently in tissue sections from SALS cases and the SOD1 A4V patient, but were essentially absent in AD and non-neurological controls. We have established clear experimental protocols and provide specific guidelines for working, with conformational/misfolded SOD1-specific antibodies. Adherence to these guidelines will aid in the comparison of the results of future studies and better interpretation of staining patterns. This blinded, standardized and unbiased approach provides further support for a possible pathological role of misSOD1 in SALS.
46.	Park, Julien H., et al. (författare) The motor system is exceptionally vulnerable to absence of the ubiquitously expressed superoxide dismutase-1 2023 Ingår i: Brain Communications. - : Oxford University Press. - 2632-1297. ; 5:1 Tidskriftsartikel (refereegranskat)abstract Superoxide dismutase-1 is a ubiquitously expressed antioxidant enzyme. Mutations in SOD1 can cause amyotrophic lateral sclerosis, probably via a toxic gain-of-function involving protein aggregation and prion-like mechanisms. Recently, homozygosity for loss-of-function mutations in SOD1 has been reported in patients presenting with infantile-onset motor neuron disease. We explored the bodily effects of superoxide dismutase-1 enzymatic deficiency in eight children homozygous for the p.C112Wfs∗11 truncating mutation. In addition to physical and imaging examinations, we collected blood, urine and skin fibroblast samples. We used a comprehensive panel of clinically established analyses to assess organ function and analysed oxidative stress markers, antioxidant compounds, and the characteristics of the mutant Superoxide dismutase-1. From around 8 months of age, all patients exhibited progressive signs of both upper and lower motor neuron dysfunction, cerebellar, brain stem, and frontal lobe atrophy and elevated plasma neurofilament concentration indicating ongoing axonal damage. The disease progression seemed to slow down over the following years. The p.C112Wfs∗11 gene product is unstable, rapidly degraded and no aggregates were found in fibroblast. Most laboratory tests indicated normal organ integrity and only a few modest deviations were found. The patients displayed anaemia with shortened survival of erythrocytes containing decreased levels of reduced glutathione. A variety of other antioxidants and oxidant damage markers were within normal range. In conclusion, non-neuronal organs in humans show a remarkable tolerance to absence of Superoxide dismutase-1 enzymatic activity. The study highlights the enigmatic specific vulnerability of the motor system to both gain-of-function mutations in SOD1 and loss of the enzyme as in the here depicted infantile superoxide dismutase-1 deficiency syndrome.
47.	Pateras, Ioannis S., et al. (författare) Short term starvation potentiates the efficacy of chemotherapy in triple negative breast cancer via metabolic reprogramming 2023 Ingår i: Journal of Translational Medicine. - : BioMed Central (BMC). - 1479-5876. ; 21:1 Tidskriftsartikel (refereegranskat)abstract Background: Chemotherapy (CT) is central to the treatment of triple negative breast cancer (TNBC), but drug toxicity and resistance place strong restrictions on treatment regimes. Fasting sensitizes cancer cells to a range of chemotherapeutic agents and also ameliorates CT-associated adverse effects. However, the molecular mechanism(s) by which fasting, or short-term starvation (STS), improves the efficacy of CT is poorly characterized.Methods: The differential responses of breast cancer or near normal cell lines to combined STS and CT were assessed by cellular viability and integrity assays (Hoechst and PI staining, MTT or H2DCFDA staining, immunofluorescence), metabolic profiling (Seahorse analysis, metabolomics), gene expression (quantitative real-time PCR) and iRNA-mediated silencing. The clinical significance of the in vitro data was evaluated by bioinformatical integration of transcriptomic data from patient data bases: The Cancer Genome Atlas (TCGA), European Genome-phenome Archive (EGA), Gene Expression Omnibus (GEO) and a TNBC cohort. We further examined the translatability of our findings in vivo by establishing a murine syngeneic orthotopic mammary tumor-bearing model.Results: We provide mechanistic insights into how preconditioning with STS enhances the susceptibility of breast cancer cells to CT. We showed that combined STS and CT enhanced cell death and increased reactive oxygen species (ROS) levels, in association with higher levels of DNA damage and decreased mRNA levels for the NRF2 targets genes NQO1 and TXNRD1 in TNBC cells compared to near normal cells. ROS enhancement was associated with compromised mitochondrial respiration and changes in the metabolic profile, which have a significant clinical prognostic and predictive value. Furthermore, we validate the safety and efficacy of combined periodic hypocaloric diet and CT in a TNBC mouse model.Conclusions: Our in vitro, in vivo and clinical findings provide a robust rationale for clinical trials on the therapeutic benefit of short-term caloric restriction as an adjuvant to CT in triple breast cancer treatment.
48.	Pettersson, Ulrika, et al. (författare) A comparison of bone mineral density and muscle strength in young male adults with different exercise level. 1999 Ingår i: Calcified Tissue International. - 0171-967X .- 1432-0827. ; 64:6, s. 490-8 Tidskriftsartikel (refereegranskat)abstract The aim of this study was to investigate any differences in bone mass at different sites between young adults subjected to a high physical activity and a group of young adults with a low level of physical activity. In addition, we compared the relationship among bone mass, muscle strength, and body constitution in these two groups. The reference group consisted of 20 men, age 24.6 +/- 2.3 years, not training for more than 3 hours per week. The ice hockey players consisted of 20 players, age 23.4 +/- 4.9 years, from an ice hockey team in the second highest national Swedish league, training for about 10 hours per week. The groups were matched according to age, height, and weight. Areal bone mineral density (BMD) was measured in total body, head, humerus, spine, pelvis, femur, femoral neck, Ward's triangle, trochanter, femur diaphysis, proximal tibia, and tibia diaphysis using dual energy X-ray absorptiometry. BMD was significantly higher in the total body (8.1%), humerus (11.4%), spine (12.7%), pelvis (12.4%), femoral neck (10.3%), femur (7.4%), proximal tibia (9.8%), and tibia diaphysis (7.5%) in the high activity group. Fat mass was significantly lower in the high activity group (18.7%). The high activity group also had a significantly higher lean body mass (5.4%) and a significantly higher isokinetic muscle strength of the quadriceps muscle compared with the reference group. In the reference group, there was a general strong independent relationship between muscle strength of the thigh and all BMD sites, except for the head, tibia diaphysis, and proximal tibia. Furthermore, in the same group, body mass index (BMI) independently predicted pelvis BMD. On the contrary, in the high activity group, muscle strength did not predict any BMD site at all. In the same group, body constitutional parameters (weight, height, and fat mass) independently predicted pelvis BMD, and BMI was shown to be an independent predictor of humerus BMD. The differences in BMD between the groups seem to be site-specific and may be associated with the type and magnitude of loading during off season training and preferentially during ice hockey. High physical activity seems to weaken the relationship between BMD and muscle strength. Hence, impact forces may be of greater importance in regulating bone mass than muscle strength in itself in highly trained athletes.
49.	Pettersson, Ulrika, et al. (författare) Bone mass in female cross-country skiers : relationship between muscle strength and different BMD sites. 2000 Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 67:3, s. 199-206 Tidskriftsartikel (refereegranskat)abstract In this cross-sectional study, bone mass and muscle strength of the thigh were investigated in 16 Caucasian female cross-country skiers, age 16.2 +/- 0.3 years, that had been ski-training for 6.4 +/- 1.8 years (range 3-9 years) and were now training for 6.3 +/- 2.4 hours/week (range 3-12 hours). They were compared with 16 nonactive females, age 16.4 +/- 0.7 years. The groups were matched according to age, weight, height, and pubertal status. Areal bone mineral density (BMD) was measured using dual energy X-ray absorptiometry, in the total body, head, both total humerus and humerus diaphyses, spine, and in the right femoral neck, greater trochanter, femoral diaphysis, distal femur, proximal tibia, and tibia diaphysis. Bone mineral apparent density (BMAD) was also calculated for the femoral neck and humerus diaphyses. Isokinetic muscle strength of the quadricep and hamstring muscles was measured in an isokinetic dynamometer. Compared with the controls, the cross-country skiing group had significantly higher BMD in the right whole humerus (6.9%), left whole humerus (9.2%), left humerus diaphysis (8.1%), femoral neck (8.9%), greater trochanter (9.3%), femur diaphysis (7.6%), and BMAD of the femoral neck (+19.4%). In the nonactive group there were significant side-to-side differences in BMD of the whole humeri, humerus diaphyses, and BMAD of the humerus diaphyses (3.1%, 5.4%, and 8.8% higher in the right arm, respectively). No such differences were found in the cross-country skiing group. Lean body mass was significantly higher in the cross-country skiers (21.7%), and fat mass (-25.5%) and body fat percent (-28.0%) were significantly lower compared with the nonactive group. There were, however, no significant differences in concentric peak torque of the thigh muscles between the two groups. Stepwise regression analyses revealed that BMI was the best predictor of several sites in the nonactive group. In the cross-country group, on the other hand, muscle strength was a strong predictor of BMD, both at adjacent and more distant BMD sites. In conclusion, it seems that this type of endurance training is associated with a site-specific higher bone mass that may be associated with the type and magnitude of loading during off-season and during the main sports activity, cross-country skiing.
50.	Pettersson, Ulrika, et al. (författare) Effect of high impact activity on bone mass and size in adolescent females : A comparative study between two different types of sports. 2000 Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 67:3, s. 207-214 Tidskriftsartikel (refereegranskat)abstract The purpose of this cross-sectional study was to investigate the influence of two different types of weight-bearing activity, muscle strength, and body composition on bone mineral density (BMD), bone mineral content (BMC), and bone area in three different groups of late adolescent girls. The first group consisted of 10 females participating in competitive rope-skipping (age 17.8 +/- 0.8 years) training for 6.7 +/- 3.1 hours/week; the second group consisted of 15 soccer players (age 17.4 +/- 0.8 years) training for 6.1 +/- 2.0 hours/week; and the third group consisted of 25 controls (age 17.6 +/- 0.8 years) with physical activity of 0.9 +/- 1.1 hours/week. The groups were matched for age, height, and weight. BMD (g/cm(2)), BMC (g), and bone area (cm(2)) of the total body, lumbar spine, hip, total femur, distal femur, diaphyses of femur and tibia, proximal tibia, and humerus were measured using dual-energy X-ray absorptiometry (DXA). Bone density was also assessed in the radial forearm site of the dominant limb in the rope skippers and in 10 matched controls. The rope skippers had 22% higher BMD at the ultradistal site (P < 0.01). Both high-activity groups had significantly higher BMD (P < 0.05) at most loaded sites compared with the control group. When adjusting for differences in lean mass and starting age of sport-specific training between the activity groups, the rope-skipping group had a higher BMD of the total body, lumbar spine, and right humerus compared with the soccer group. They also had a significantly higher bone area of the total body, total femur, and the proximal femur than both other groups, and a significantly higher bone area of the tibia diaphysis, compared with the soccer group. In a multivariate analysis among all subjects (n = 50), all BMD sites, except the femur diaphysis, distal femur, and proximal tibia, were significantly related to type of physical activity (beta = 0.25-0.43, P < 0.05). The bone area values at different sites were strongly related to muscle strength and parameters related to body size [height, weight, lean mass, fat mass, and body mass index (BMI)]. In conclusion, it appears that in late adolescent women, weight-bearing activities are an important determinant for bone density, and high impact activities such as jumping also seem to be associated with a modification of the bone geometry (hence, the bone width) at the loaded sites.

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