| 1. |
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| 2. |
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| 3. |
- Brantsæter, A. L., et al.
(författare)
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Diet matters, particularly in pregnancy – Results from MoBa studies of maternal diet and pregnancy outcomes
- 2014
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Ingår i: Norsk Epidemiologi. - 0803-2491. ; 24:1-2, s. 63-77
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Forskningsöversikt (refereegranskat)abstract
- Awareness that maternal diet may influence the outcome of pregnancy as well as the long-term health of mother and child has increased in recent years. A new food frequency questionnaire (FFQ) was developed and validated specifically for the Norwegian Mother and Child Cohort Study (MoBa). The MoBa FFQ is a semi-quantitative tool which covers the average intake of food, beverages and dietary supplements during the first 4 to 5 months of pregnancy. It includes questions about intakes of 255 foods and dishes and was used from 2002 onwards. Data assessed by the MoBa FFQ is available for 87,700 pregnancies. Numerous sub-studies have examined associations between dietary factors and health outcomes in MoBa. The aim of this paper is to summarize the results from 19 studies of maternal diet and pregnancy outcomes, which is the complete collection of studies based on the MoBa FFQ and published before September 2014. The overall research question is whether maternal diet – from single substances to dietary patterns – matters for pregnancy outcome. The pregnancy outcomes studied till now include birth size measures, infants being small and large for gestational age, pregnancy duration, preterm delivery, preeclampsia, as well as maternal gestational weight gain and postpartum weight retention. As a whole, the results from these studies corroborate that the current dietary recommendations to pregnant women are sound and that maternal diet during pregnancy is likely to contribute to reduce the risk of pregnancy complications including preterm birth, preeclampsia, and reduced foetal growth. The results provide supporting evidence for recommending pregnant women to consume vegetables, fruit, whole grain, fish, dairy, and water regularly and lower the intake of sugar sweetened beverages, processed meat products and salty snacks. The results showing negative impact of even low levels of environmental contaminants support the precautionary advice on consumption of foods containing these. New findings are that particularly lean fish explained the positive association between seafood intake and foetal growth, and the indications of a protective effect of probiotic and antimicrobial foods on pregnancy outcomes. This points to the importance of diet composition for a healthy gut flora and the body’s immune response. Although these studies are observational and cannot infer causality, the results identify diet as an important modifiable lifestyle factor, suggesting that healthy eating, defined as following the official recommendations, is particularly important in pregnancy.
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| 4. |
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| 5. |
- Green, L, et al.
(författare)
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Data supporting: Invader at the edge - genomic origins and physiological differences of round gobies across a steep urban salinity gradient
- 2022
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Annan publikationabstract
- Species invasions are a global problem of increasing concern, especially in highly connected aquatic environments. Despite this, salinity conditions can pose physiological barriers to their spread and understanding them is important for management. In Scandinavia’s largest cargo port, the invasive round goby (Neogobius melanostomus), is established across a steep salinity gradient. We used 12 937 SNPs to identify the genetic origin and diversity of three sites along the salinity gradient and round goby from western, central and northern Baltic Sea, as well as north European rivers. Fish from two sites from the extreme ends of the gradient were also acclimated to freshwater and seawater, and tested for respiratory and osmoregulatory physiology. Fish from the high salinity environment in the outer port showed higher genetic diversity, and closer relatedness to the other regions, compared to fish from lower salinity upstream the river. Fish from the high salinity site also had higher maximum metabolic rate, fewer blood cells and lower blood Ca2+. Despite these genotypic and phenotypic differences, salinity acclimation affected fish from both sites in the same way: seawater increased the blood osmolality and Na+ levels, and freshwater increased the levels of the stress hormone cortisol. Our results show genotypic and phenotypic differences over short spatial scales across this steep salinity gradient. These patterns of the physiologically robust round goby are likely driven by multiple introductions into the high salinity site, and a process of sorting, likely based on behaviour or selection, along the gradient. Since this euryhaline fish risks spreading from this area, seascape genomics and phenotypic characterisation can inform management strategies even within an area as small as a coastal harbour inlet.
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| 6. |
- Majounie, Elisa, et al.
(författare)
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Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study
- 2012
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Ingår i: Lancet Neurology. - 1474-4465. ; 11:4, s. 323-330
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Tidskriftsartikel (refereegranskat)abstract
- Background We aimed to accurately estimate the frequency of a hexanucleotide repeat expansion in C9orf72 that has been associated with a large proportion of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Methods We screened 4448 patients diagnosed with ALS (El Escorial criteria) and 1425 patients with FTD (Lund-Manchester criteria) from 17 regions worldwide for the GGGGCC hexanucleotide expansion using a repeat-primed PCR assay. We assessed familial disease status on the basis of self-reported family history of similar neurodegenerative diseases at the time of sample collection. We compared haplotype data for 262 patients carrying the expansion with the known Finnish founder risk haplotype across the chromosomal locus. We calculated age-related penetrance using the Kaplan-Meier method with data for 603 individuals with the expansion. Findings In patients with sporadic ALS, we identified the repeat expansion in 236 (7.0%) of 3377 white individuals from the USA, Europe, and Australia, two (4.1%) of 49 black individuals from the USA, and six (8.3%) of 72 Hispanic individuals from the USA. The mutation was present in 217 (39.3%) of 552 white individuals with familial MS from Europe and the USA. 59 (6.0%) of 981 white Europeans with sporadic FTD had the mutation, as did 99 (24.8%) of 400 white Europeans with familial FTD. Data for other ethnic groups were sparse, but we identified one Asian patient with familial ALS (from 20 assessed) and two with familial FTD (from three assessed) who carried the mutation. The mutation was not carried by the three Native Americans or 360 patients from Asia or the Pacific Islands with sporadic MS who were tested, or by 41 Asian patients with sporadic FTD. All patients with the repeat expansion had (partly or fully) the founder haplotype, suggesting a one-off expansion occurring about 1500 years ago. The pathogenic expansion was non-penetrant in individuals younger than 35 years, 50% penetrant by 58 years, and almost fully penetrant by 80 years. Interpretation A common Mendelian genetic lesion in C9472 is implicated in many cases of sporadic and familial ALS and FTD. Testing for this pathogenic expansion should be considered in the management and genetic counselling of patients with these fatal neurodegenerative diseases.
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| 7. |
- Plymale, Andrew E., et al.
(författare)
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Niche Partitioning of Microbial Communities at an Ancient Vitrified Hillfort : Implications for Vitrified Radioactive Waste Disposal
- 2021
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Ingår i: Geomicrobiology Journal. - : Taylor & Francis. - 0149-0451 .- 1521-0529. ; 38:1, s. 36-56
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Tidskriftsartikel (refereegranskat)abstract
- Because microbes cannot be eliminated from radioactive waste disposal facilities, the consequences of bio-colonization must be understood. At a pre-Viking era vitrified hillfort, Broborg, Sweden, anthropogenic glass has been subjected to bio-colonization for over 1,500 years. Broborg is used as a habitat analogue for disposed radioactive waste glass to inform how microbial processes might influence long-term glass durability. Electron microscopy and DNA sequencing of surficial material from the Broborg vitrified wall, adjacent soil, and general topsoil show that the ancient glass supports a niche microbial community of bacteria, fungi, and protists potentially involved in glass alteration. Communities associated with the vitrified wall are distinct and less diverse than soil communities. The vitrified niche of the wall and adjacent soil are dominated by lichens, lichen-associated microbes, and other epilithic, endolithic, and epigeic organisms. These organisms exhibit potential bio-corrosive properties, including silicate dissolution, extraction of essential elements, and secretion of geochemically reactive organic acids, that could be detrimental to glass durability. However, long-term biofilms can also possess a homeostatic function that could limit glass alteration. This study documents potential impacts that microbial colonization and niche partitioning can have on glass alteration, and subsequent release of radionuclides from a disposal facility for vitrified radioactive waste.
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| 8. |
- Rödström, E. Ygland, et al.
(författare)
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Genomic analyses of a large Swedish multi-incident kindred with autosomal dominant Parkinson’s disease with dementia
- 2023
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Ingår i: Parkinsonism & Related Disorders. - 1353-8020. ; 113:Supp, s. 28-29
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Konferensbidrag (refereegranskat)abstract
- Background:The known genetic causes for Parkinson’s disease (PD) onlyexplain a small proportion of the familial aggregation of PD. Despiteintensive efforts by researchers internationally, identifying and confirmingadditional monogenic causes for PD has been difficult.Methods:We examined 16 members of a large family with multi-incidentPD and dementia. Eight members were examined by whole exome (WES)or whole genome sequencing. Rare variants co-segregating with the disease were evaluated based on their distribution in additional familymembers and known gene functions. WES data from 843 PD cases and 885controls were screened for the two most highly ranked candidate variantsand used for gene burden analysis.Results:Clinically, all affected family members had typical PD withcognitive decline. Two affected individuals showed typical PD neuropathology. Out of nine genetic variants identified, we highlighted two as goodcandidates for causing this family’s PD. However, co-segregation with PDwas imperfect and this study was complicated by the fact that somegenotyped family members showed mild motor symptoms of uncertaincause, or cognitive decline without apparent motor dysfunction. Geneburden analysis showed no difference between cases and controls in thefrequency of potentially deleterious variants in the top-candidate genes.Nonetheless, factors that could indicate an impact of either of the two topcandidate genetic variants were found as one of the variants was identifiedin one additional familial PD proband from the case series and geneticvariants in the other top-candidate gene had previously been associatedwith an increased risk for PD in humans.Conclusions: Our study was not able to determine a single high-impactvariant as the cause of PD with cognitive decline in the family despitedetailed clinical and genetic assessments, but we nominate two potentialcandidate variants. Reduced penetrance and phenocopies may complicategenomic studies of families with PD.
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| 9. |
- Watt, F. E., et al.
(författare)
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Towards prevention of post-traumatic osteoarthritis : report from an international expert working group on considerations for the design and conduct of interventional studies following acute knee injury
- 2019
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 27:1, s. 23-33
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Tidskriftsartikel (refereegranskat)abstract
- Objective: There are few guidelines for clinical trials of interventions for prevention of post-traumatic osteoarthritis (PTOA), reflecting challenges in this area. An international multi-disciplinary expert group including patients was convened to generate points to consider for the design and conduct of interventional studies following acute knee injury. Design: An evidence review on acute knee injury interventional studies to prevent PTOA was presented to the group, alongside overviews of challenges in this area, including potential targets, biomarkers and imaging. Working groups considered pre-identified key areas: eligibility criteria and outcomes, biomarkers, injury definition and intervention timing including multi-modality interventions. Consensus agreement within the group on points to consider was generated and is reported here after iterative review by all contributors. Results: The evidence review identified 37 studies. Study duration and outcomes varied widely and 70% examined surgical interventions. Considerations were grouped into three areas: justification of inclusion criteria including the classification of injury and participant age (as people over 35 may have pre-existing OA); careful consideration in the selection and timing of outcomes or biomarkers; definition of the intervention(s)/comparator(s) and the appropriate time-window for intervention (considerations may be particular to intervention type). Areas for further research included demonstrating the utility of patient-reported outcomes, biomarkers and imaging outcomes from ancillary/cohort studies in this area, and development of surrogate clinical trial endpoints that shorten the duration of clinical trials and are acceptable to regulatory agencies. Conclusions: These considerations represent the first international consensus on the conduct of interventional studies following acute knee joint trauma.
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| 10. |
- Abella, J., et al.
(författare)
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SAFEXPLAIN : Safe and Explainable Critical Embedded Systems Based on AI
- 2023
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Ingår i: Proceedings -Design, Automation and Test in Europe, DATE. - : Institute of Electrical and Electronics Engineers Inc.. - 9783981926378
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Konferensbidrag (refereegranskat)abstract
- Deep Learning (DL) techniques are at the heart of most future advanced software functions in Critical Autonomous AI-based Systems (CAIS), where they also represent a major competitive factor. Hence, the economic success of CAIS industries (e.g., automotive, space, railway) depends on their ability to design, implement, qualify, and certify DL-based software products under bounded effort/cost. However, there is a fundamental gap between Functional Safety (FUSA) requirements on CAIS and the nature of DL solutions. This gap stems from the development process of DL libraries and affects high-level safety concepts such as (1) explainability and traceability, (2) suitability for varying safety requirements, (3) FUSA-compliant implementations, and (4) real-time constraints. As a matter of fact, the data-dependent and stochastic nature of DL algorithms clashes with current FUSA practice, which instead builds on deterministic, verifiable, and pass/fail test-based software. The SAFEXPLAIN project tackles these challenges and targets by providing a flexible approach to allow the certification - hence adoption - of DL-based solutions in CAIS building on: (1) DL solutions that provide end-to-end traceability, with specific approaches to explain whether predictions can be trusted and strategies to reach (and prove) correct operation, in accordance to certification standards; (2) alternative and increasingly sophisticated design safety patterns for DL with varying criticality and fault tolerance requirements; (3) DL library implementations that adhere to safety requirements; and (4) computing platform configurations, to regain determinism, and probabilistic timing analyses, to handle the remaining non-determinism.
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| 11. |
- Alafuzoff, Irina, et al.
(författare)
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The need to unify neuropathological assessments of vascular alterations in the ageing brain : Multicentre survey by the BrainNet Europe consortium
- 2012
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Ingår i: Experimental Gerontology. - : Elsevier BV. - 0531-5565 .- 1873-6815. ; 47:11, s. 825-833
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Tidskriftsartikel (refereegranskat)abstract
- Here, we summarise the results after carrying out a large survey regarding the assessment of vascular alterations, both vessel changes and vascular lesions in an inter-laboratory setting. In total, 32 neuropathologists from 22 centres, most being members of BrainNet Europe (BNE), participated by filling out a questionnaire with emphasis on assessment of common vascular alterations seen in the brains of aged subjects. A certain level of harmonisation has been reached among BNE members regarding sectioning of the brain, harvesting of brain tissue for histology and staining used when compared to the survey carried out in 2006 by Pantoni and colleagues. The most significant variability was seen regarding the assessment of severity and of clinical significance of vascular alterations. Two strategies have recently been recommended regarding the assessment of vascular alterations in aged and demented subjects. The National Institute on Aging - Alzheimer's Association (NIA-AA) recommends the assessment of hippocampal sclerosis, vascular brain injury and microvascular lesions in 12 regions. Although this strategy will be easy to follow, the recommendations do not inform how the load of observed alterations should be assessed and when the observed lesions are of significance. Deramecourt and his colleagues recommend an assessment and semiquantitative grading of various pathologies in 4 brain regions. This strategy yielded a total score of 0 to 20 as an estimate of pathology load. It is, however, not clear which score is considered to be of clinical significance. Furthermore, in several BNE trials the semiquantitative assessment has yielded poor agreement rates; an observation that might negatively influence the strategy proposed by Deramecourt and his colleagues. In line with NIA-AA, a dichotomised approach of easily recognisable lesions in a standardised set of brain regions harvested for neuropathological assessment and applying reproducible sampling and staining strategies is recommended by BNE. However, a simple strategy regarding assessment of load of alteration is urgently needed to yield reproducible, and at the same time, comparable results between centres.
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| 12. |
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| 13. |
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| 14. |
- Bergqvist, Filip, et al.
(författare)
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Inhibition of mPGES-1 or COX-2 Results in Different Proteomic and Lipidomic Profiles in A549 Lung Cancer Cells
- 2019
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Pharmacological inhibition of microsomal prostaglandin E synthase (mPGES)-1 for selective reduction in prostaglandin E-2 (PGE(2)) biosynthesis is protective in experimental models of cancer and inflammation. Targeting mPGES-1 is envisioned as a safer alternative to traditional non-steroidal anti-inflammatory drugs (NSAIDs). Herein, we compared the effects of mPGES-1 inhibitor Compound III (CIII) with the cyclooxygenase (COX)-2 inhibitor NS-398 on protein and lipid profiles in interleukin (IL)-1 beta-induced A549 lung cancer cells using mass spectrometry. Inhibition of mPGES-1 decreased PGE(2) production and increased PGF(2 alpha) and thromboxane B-2 (TXB2) formation, while inhibition of COX-2 decreased the production of all three prostanoids. Our proteomics results revealed that CIII downregulated multiple canonical pathways including eIF2, eIF4/P70S6K, and mTOR signaling, compared to NS-398 that activated these pathways. Moreover, pathway analysis predicted that CIII increased cell death of cancer cells (Z = 3.8, p = 5.1E-41) while NS-398 decreased the same function (Z = -5.0, p = 6.5E-35). In our lipidomics analyses, we found alterations in nine phospholipids between the two inhibitors, with a stronger alteration in the lysophospholipid (LPC) profile with NS-398 compared to CIII. Inhibition of mPGES-1 increased the concentration of sphinganine and dihydroceramide (C16:0D hCer), while inhibition of COX-2 caused a general decrease in most ceramides, again suggesting different effects on cell death between the two inhibitors. We showed that CIII decreased proliferation and potentiated the cytotoxic effect of the cytostatic drugs cisplatin, etoposide, and vincristine when investigated in a live cell imaging system. Our results demonstrate differences in protein and lipid profiles after inhibition of mPGES-1 or COX-2 with important implications on the therapeutic potential of mPGES-1 inhibitors as adjuvant treatment in cancer. We encourage further investigations to illuminate the clinical benefit of mPGES-1 inhibitors in cancer.
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| 15. |
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| 16. |
- Capo, Eric, et al.
(författare)
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Lake sedimentary dna research on past terrestrial and aquatic biodiversity: Overview and recommendations
- 2021
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Ingår i: Quaternary. - : MDPI. - 2571-550X. ; 4:1
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Forskningsöversikt (refereegranskat)abstract
- The use of lake sedimentary DNA to track the long-term changes in both terrestrial and aquatic biota is a rapidly advancing field in paleoecological research. Although largely applied nowadays, knowledge gaps remain in this field and there is therefore still research to be conducted to ensure the reliability of the sedimentary DNA signal. Building on the most recent literature and seven original case studies, we synthesize the state-of-the-art analytical procedures for effective sampling, extraction, amplification, quantification and/or generation of DNA inventories from sedimentary ancient DNA (sedaDNA) via high-throughput sequencing technologies. We provide recommendations based on current knowledge and best practises.
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| 17. |
- Diarbakerli, E., et al.
(författare)
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Learning from the past to plan for the future: A scoping review of musculoskeletal clinical research in Sweden 2010-2020
- 2022
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 127:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aims of this study are to 1) determine the scope of musculoskeletal (MSK)-related clinical research in Sweden; 2) collate the amount of first-tier funding received; 3) discuss strategies and infrastructure supporting future MSK clinical trials in Sweden. Methods: A systematic scoping review protocol was applied in PubMed, Scopus, and SweCRIS databases. The articles were examined, and data were extracted in multiple stages by three blinded authors. Results: The search strategy resulted in 3,025 publications from 479 Swedish-affiliated authors. Primary health care was the basis for 14% of the publications, 84% from secondary health care, and 2% from occupational health care with a similar proportional distribution of first-tier research grant financing. Approximately one in six publications were randomized controlled trials (RCTs), while the majority were of observational cohort design. The majority of publications in primary and occupational health care were related to pain disorders (51 and 67%, respectively), especially diagnosis, prognosis, and healthcare organizational-related interventions (34%) and rehabilitation (15%) with similar proportional distribution of first-tier research grant financing. In secondary health care, rheumatic inflammatory disorder-related publications were most prevalent (30%), most frequently concerning diagnosis, prognosis, and healthcare organizational-related interventions (20%), attracting approximately half of all first-tier funding. Publications related to degenerative joint disorders (25%), fractures (16%), and joint, tendon, and muscle injuries (13%) frequently concerned surgical and other orthopedic-related interventions (16, 6, and 8%, respectively). Pain disorder-related publications (10%) as well as bone health and osteoporosis-related publications (4%) most frequently concerned diagnosis, prognosis, and healthcare organizational-related interventions (5 and 3%, respectively). Conclusions: Swedish-affiliated MSK disorder research 2010-2020 was predominantly observational cohort rather than RCT based. There was skewed first-tier funding allocation considering prevalence/incidence and burden of disease. Use of infrastructure supporting register-based RCTs, placebo-controlled RCTs, and hybrid effectiveness-implementation studies on prevention and clinical intervention is important strategies for the future in all healthcare sectors.
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| 18. |
- Englund, E., et al.
(författare)
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Tumours of the central nervous system. Proton magnetic resonance relaxation times T1 and T2 and histopathologic correlates
- 1986
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Ingår i: Acta Radiologica Diagnosis. - : SAGE Publications. - 0567-8056. ; 27:6, s. 653-659
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Tidskriftsartikel (refereegranskat)abstract
- Proton MR relaxation times T1 and T2 were determined in vitro in 136 small specimens of astrocytomas grades I-IV, of oligodendrogliomas, metastases of adenocarcinomas, meningiomas and acoustic neuromas. In addition, 7 samples of peritumoural white matter were analysed. The analysed specimens were studied microscopically in their entirety regarding tumour type and occurrence of necrosis and non-tumour tissue admixture, such as fibrosis and haemorrhage. Most of the gliomas had longer relaxation times than normal white matter and T2 was significantly longer than in the other three tumour groups. The metastases had longer T1 than normal white matter, while T2 varied. The astrocytomas tended to show shorter relaxation times with increasing degree of malignancy, and shortening of T1 and T2 correlating with the proportion of tissue necrosis. Similarly, the metastases with tissue necrosis had shorter T1 and T2 than non-necrotic samples. The meningiomas had T1 values comparable with normal cortex, while the T2 values varied. Tumours containing a large proportion of fibrous tissue had shorter relaxation times than the others. Acoustic neuromas had only slightly longer T1 than normal white matter, while T2 was not prolonged. Both T1 and T2 were significantly shorter than in all other tumours studied. Peritumoural white matter had prolonged relaxation times compared with normal white matter, correlating to increased water content. These in vitro differences regarding relaxation times in various types of tumours of the central nervous system, dependent on various types of tissue alterations, should be of interest for the interpretation of in vivo images.
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| 19. |
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| 20. |
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Frequency of antibiotic-associated diarrhoea in 2462 antibiotic-treated hospitalized patients : a prospective study
- 2001
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 47:1, s. 43-50
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Tidskriftsartikel (refereegranskat)abstract
- The frequency of antibiotic-associated diarrhoea (AAD) and Clostridium difficile-associated diarrhoea (CdAD) was prospectively determined in a population of 2462 patients recruited from five Swedish hospitals, including divisions for infectious diseases, orthopaedics, surgery, geriatrics, nephrology and internal medicine. AAD developed in 4.9% of the treated patients. Faecal samples were obtained from 69% of patients with AAD and 55.4% were positive for C. difficile cytotoxin B. The frequency of AAD varied from 1.8 to 6.9% at the participating centres (P < 0.001). The frequency of AAD also varied considerably between medical disciplines and wards within different hospitals and was highest in the nephrology and geriatric units (6.7 and 7.1%, respectively). There was no difference in frequency of AAD when analysed with respect to gender or age. Medical interventions (laxative treatment, endoscopy and abdominal surgery) or presence of one concomitant disease (diabetes, malignancy, chronic renal disease and inflammatory bowel disease) did not significantly affect the frequency of AAD, whereas patients suffering from two or more of these illnesses had significantly (P = 0.001) higher frequencies of AAD. Patients treated with antibiotics for 3 days had a significantly (P = 0.009) lower frequency of AAD than those treated for longer periods. Treatment with cephalosporins, clindamycin or broad-spectrum penicillins was associated with an increased risk of AAD. With specimens from one centre, 62.5% of tested patients with AAD and 33.8% of asymptomatic patients were positive for cytotoxin B. Although C. difficile cytotoxin B in stool samples was significantly associated with AAD IP = 0.003), the causal relationship with diarrhoea is not always evident.
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| 21. |
- Garza, Raquel, et al.
(författare)
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LINE-1 retrotransposons drive human neuronal transcriptome complexity and functional diversification
- 2023
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Ingår i: Science Advances. - 2375-2548. ; 9:44
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Tidskriftsartikel (refereegranskat)abstract
- The genetic mechanisms underlying the expansion in size and complexity of the human brain remain poorly understood. Long interspersed nuclear element-1 (L1) retrotransposons are a source of divergent genetic information in hominoid genomes, but their importance in physiological functions and their contribution to human brain evolution are largely unknown. Using multiomics profiling, we here demonstrate that L1 promoters are dynamically active in the developing and the adult human brain. L1s generate hundreds of developmentally regulated and cell type-specific transcripts, many that are co-opted as chimeric transcripts or regulatory RNAs. One L1-derived long noncoding RNA, LINC01876, is a human-specific transcript expressed exclusively during brain development. CRISPR interference silencing of LINC01876 results in reduced size of cerebral organoids and premature differentiation of neural progenitors, implicating L1s in human-specific developmental processes. In summary, our results demonstrate that L1-derived transcripts provide a previously undescribed layer of primate- and human-specific transcriptome complexity that contributes to the functional diversification of the human brain.
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| 22. |
- Granholm, Ann-Charlotte E, et al.
(författare)
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Neuropathological findings in Down syndrome, Alzheimer's disease and control patients with and without SARS-COV-2 : preliminary findings
- 2024
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Ingår i: Acta Neuropathologica. - 1432-0533. ; 147, s. 1-21
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Tidskriftsartikel (refereegranskat)abstract
- The SARS-CoV-2 virus that led to COVID-19 is associated with significant and long-lasting neurologic symptoms in many patients, with an increased mortality risk for people with Alzheimer's disease (AD) and/or Down syndrome (DS). However, few studies have evaluated the neuropathological and inflammatory sequelae in postmortem brain tissue obtained from AD and people with DS with severe SARS-CoV-2 infections. We examined tau, beta-amyloid (Aβ), inflammatory markers and SARS-CoV-2 nucleoprotein in DS, AD, and healthy non-demented controls with COVID-19 and compared with non-infected brain tissue from each disease group (total n = 24). A nested ANOVA was used to determine regional effects of the COVID-19 infection on arborization of astrocytes (Sholl analysis) and percent-stained area of Iba-1 and TMEM 119. SARS-CoV-2 antibodies labeled neurons and glial cells in the frontal cortex of all subjects with COVID-19, and in the hippocampus of two of the three DS COVID-19 cases. SARS-CoV-2-related alterations were observed in peri-vascular astrocytes and microglial cells in the gray matter of the frontal cortex, hippocampus, and para-hippocampal gyrus. Bright field microscopy revealed scattered intracellular and diffuse extracellular Aβ deposits in the hippocampus of controls with confirmed SARS-CoV-2 infections. Overall, the present preliminary findings suggest that SARS-CoV-2 infections induce abnormal inflammatory responses in Down syndrome.
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| 23. |
- Györffy-Wagner, Z., et al.
(författare)
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Proton magnetic resonance relaxation times T1 and T2 related to postmortem interval : An Investigation on Porcine Brain Tissue
- 1986
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Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 0567-8056. ; 27:1, s. 115-118
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Forskningsöversikt (refereegranskat)abstract
- In order to establish the validity of in vitro determination of the proton magnetic resonance (MR) relaxation times T1 and T2 in brain tissue at increasing time delay after death or operative excision, 81 brain tissue samples from 23 pigs were analyzed repeatedly. These samples, representing cortex, caudate nucleus and white matter, were studied microscopically after MR measurements. The T1 values exhibited no time dependence and the T2 values decreased slightly during the interval 2 to 90 hours after death. The samples were stored at +8°C between the measurements. These results indicate that reliable in vitro measurements can be obtained in autopsy or surgical brain tissue specimens within 90 hours after death or excision, if handled properly.
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| 24. |
- Hunsicker, Mary E., et al.
(författare)
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Functional responses and scaling in predator-prey interactions of marine fishes : contemporary issues and emerging concepts
- 2011
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Ingår i: Ecology Letters. - : Wiley-Blackwell. - 1461-023X .- 1461-0248. ; 14:12, s. 1288-1299
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Forskningsöversikt (refereegranskat)abstract
- Predatorprey interactions are a primary structuring force vital to the resilience of marine communities and sustainability of the worlds oceans. Human influences on marine ecosystems mediate changes in species interactions. This generality is evinced by the cascading effects of overharvesting top predators on the structure and function of marine ecosystems. It follows that ecological forecasting, ecosystem management, and marine spatial planning require a better understanding of food web relationships. Characterising and scaling predatorprey interactions for use in tactical and strategic tools (i.e. multi-species management and ecosystem models) are paramount in this effort. Here, we explore what issues are involved and must be considered to advance the use of predatorprey theory in the context of marine fisheries science. We address pertinent contemporary ecological issues including (1) the approaches and complexities of evaluating predator responses in marine systems; (2) the scaling up of predatorprey interactions to the population, community, and ecosystem level; (3) the role of predatorprey theory in contemporary fisheries and ecosystem modelling approaches; and (4) directions for the future. Our intent is to point out needed research directions that will improve our understanding of predatorprey interactions in the context of the sustainable marine fisheries and ecosystem management.
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| 25. |
- Ilinca, A., et al.
(författare)
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MAP3K6 Mutations in a Neurovascular Disease Causing Stroke, Cognitive Impairment, and Tremor
- 2021
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Ingår i: Neurology-Genetics. - : Ovid Technologies (Wolters Kluwer Health). - 2376-7839. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective To describe a possible novel genetic mechanism for cerebral small vessel disease (cSVD) and stroke. Methods We studied a Swedish kindred with ischemic stroke and intracerebral hemorrhage, tremor, dysautonomia, and mild cognitive decline. Members were examined clinically, radiologically, and by histopathology. Genetic workup included whole-exome sequencing (WES) and whole-genome sequencing (WGS) and intrafamilial cosegregation analyses. Results Fifteen family members were examined clinically. Twelve affected individuals had white matter hyperintensities and 1 or more of (1) stroke episodes, (2) clinically silent lacunar ischemic lesions, and (3) cognitive dysfunction. All affected individuals had tremor and/or atactic gait disturbance. Mild symmetric basal ganglia calcifications were seen in 3 affected members. Postmortem examination of 1 affected member showed pathologic alterations in both small and large arteries the brain. Skin biopsies of 3 affected members showed extracellular amorphous deposits within the subepidermal zone, which may represent degenerated arterioles. WES or WGS did not reveal any potentially disease-causing variants in known genes for cSVDs or idiopathic basal ganglia calcification, but identified 1 heterozygous variant, NM_004672.4 MAP3K6 c.322G>A p.(Asp108Asn), that cosegregated with the disease in this large family. MAP3K6 has known functions in angiogenesis and affects vascular endothelial growth factor expression, which may be implicated in cerebrovascular disease. Conclusions Our data strongly suggest the MAP3K6 variant to be causative for this novel disease phenotype, but the absence of functional data and the present lack of additional families with this disease and MAP3K6 mutations still limit the formal evidence for the variant's pathogenicity.
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| 26. |
- Larsson, E. M., et al.
(författare)
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Regional differences in the proton magnetic resonance relaxation times T1 and T2 within the normal human brain
- 1986
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Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 0567-8056. ; 27:2, s. 231-234
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Forskningsöversikt (refereegranskat)abstract
- The proton magnetic resonance (MR) relaxation times T1 and T2 were determined in autopsy specimens from 13 different regions of normal human brains. One hundred and seventy-four tissue samples from 25 brains were examined in a pulsed MR analyzer of 0.25 T and were then also studied histologically. There were regional differences in T1 and T2 within the cerebral gray matter but not within the white matter. These regional differences might reflect the different composition and cytoarchitectonic structure of the cortical regions and should be taken into consideration in the interpretation of cortical lesions on MR images.
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| 27. |
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| 28. |
- Matthews, Bethany E., et al.
(författare)
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Micro- and Nanoscale Surface Analysis of Late Iron Age Glass from Broborg, a Vitrified Swedish Hillfort
- 2023
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Ingår i: Microscopy and Microanalysis. - : Oxford University Press. - 1431-9276 .- 1435-8115. ; 29:1, s. 50-68
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Tidskriftsartikel (refereegranskat)abstract
- Archaeological glasses with prolonged exposure to biogeochemical processes in the environment can be used to understand glass alteration, which is important for the safe disposal of vitrified nuclear waste. Samples of mafic and felsic glasses with different chemistries, formed from melting amphibolitic and granitoid rocks, were obtained from Broborg, a Swedish Iron Age hillfort. Glasses were excavated from the top of the hillfort wall and from the wall interior. A detailed microscopic, spectroscopic, and diffraction study of surficial textures and chemistries were conducted on these glasses. Felsic glass chemistry was uniform, with a smooth surface showing limited chemical alteration (<150 nm), irrespective of the position in the wall. Mafic glass was heterogeneous, with pyroxene, spinel, feldspar, and quartz crystals in the glassy matrix. Mafic glass surfaces in contact with topsoil were rougher than those within the wall and had carbon-rich material consistent with microbial colonization. Limited evidence for chemical or physical alteration of mafic glass was found; the thin melt film that coated all exposed surfaces remained intact, despite exposure to hydraulically unsaturated conditions, topsoil, and associated microbiome for over 1,500 years. This supports the assumption that aluminosilicate nuclear waste glasses will have a high chemical durability in near-surface disposal facilities.
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| 29. |
- Olsson, E., et al.
(författare)
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Ultra-high field magnetic resonance imaging parameter mapping in the posterior horn of ex vivo human menisci
- 2019
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 27:3, s. 476-483
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the relationship between meniscus magnetic resonance (MR) relaxation parameters and meniscus degradation through quantitative imaging of ex vivo posterior horns of menisci from subjects with and without knee osteoarthritis (OA). Design: We sampled medial and lateral menisci from ten medial compartment knee OA patients (mean age 63 years) undergoing total knee replacement and from ten deceased donors (references, mean age 51 years). MR relaxation parameters T2*, T2 and T1 of the posterior horn were measured at a 9.4 T scanner. Comparisons were made between OA patients and references (with adjustment for age) as well as between medial and lateral menisci from the same knees. Results: Mean values (standard deviation) of mean T2* were 13 (3.8), 6.9 (2.3), 7.2 (1.9) and 7.2 (1.7) ms for the medial and lateral patient menisci and the medial and lateral reference menisci, respectively. Corresponding values were 17 (3.7), 9.0 (2.2), 12 (4) and 9.0 (1.3) ms for T2 and 1810 (150), 1630 (30), 1580 (90) and 1560 (50) ms for T1. All three relaxation times were significantly longer in medial OA menisci compared to the other groups. Among medial reference menisci, relaxation times (mainly T1) tended to increase with age. Conclusions: MR relaxation times T2*, T2 and T1 in the posterior horn are longer in the medial menisci of patients with end-stage medial compartment knee OA compared to the corresponding lateral menisci and to reference menisci. The meniscus seems to undergo intrasubstance alterations related to both OA and ageing.
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| 30. |
- Rostgaard, Nina, et al.
(författare)
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TMEM106B and ApoE polymorphisms in CHMP2B-mediated frontotemporal dementia (FTD-3)
- 2017
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 59, s. 1-221
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Tidskriftsartikel (refereegranskat)abstract
- Single-nucleotide polymorphisms in the TMEM106B gene have been identified as a risk factor in frontotemporal dementia (FTD). The major allele of SNP rs3173615 is a risk factor in sporadic FTD, whereas the minor allele seems protective in GRN- and C9orf72-mediated FTD. The role of apolipoprotein E (ApoE) in FTD is uncertain, though an established risk factor in Alzheimer's disease. In a unique Danish family, inherited FTD is caused by a mutation in the CHMP2B gene located on chromosome 3 (FTD-3). In this family, both risk factors TMEM106B and ApoE were analyzed and correlated to age at onset (AAO) and progression in terms of age at institutionalization (AAI) and age at death (AAD). Although TMEM106B and CHMP2B share cellular function in that both localize to endolysosomes, TMEM106B genotypes appeared to have no influence on the clinical disease course. ApoE ε4 was found to be a protective factor with later AAO and AAI, whereas ε2 seemed to aggravate the disease with earlier AAO and AAD. These results indicate ApoE ε2 as a risk factor in FTD-3 and suggest a protective role of ε4.
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| 31. |
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| 32. |
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| 33. |
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| 34. |
- Skulason, Skuli, et al.
(författare)
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A way forward with eco evo devo : an extended theory of resource polymorphism with postglacial fishes as model systems
- 2019
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Ingår i: Biological Reviews. - : John Wiley & Sons. - 1464-7931 .- 1469-185X. ; 94:5, s. 1786-1808
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Forskningsöversikt (refereegranskat)abstract
- A major goal of evolutionary science is to understand how biological diversity is generated and altered. Despite considerable advances, we still have limited insight into how phenotypic variation arises and is sorted by natural selection. Here we argue that an integrated view, which merges ecology, evolution and developmental biology (eco evo devo) on an equal footing, is needed to understand the multifaceted role of the environment in simultaneously determining the development of the phenotype and the nature of the selective environment, and how organisms in turn affect the environment through eco evo and eco devo feedbacks. To illustrate the usefulness of an integrated eco evo devo perspective, we connect it with the theory of resource polymorphism (i.e. the phenotypic and genetic diversification that occurs in response to variation in available resources). In so doing, we highlight fishes from recently glaciated freshwater systems as exceptionally well‐suited model systems for testing predictions of an eco evo devo framework in studies of diversification. Studies on these fishes show that intraspecific diversity can evolve rapidly, and that this process is jointly facilitated by (i) the availability of diverse environments promoting divergent natural selection; (ii) dynamic developmental processes sensitive to environmental and genetic signals; and (iii) eco evo and eco devo feedbacks influencing the selective and developmental environments of the phenotype. We highlight empirical examples and present a conceptual model for the generation of resource polymorphism – emphasizing eco evo devo, and identify current gaps in knowledge.
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| 35. |
- Abbott, Allan, 1978-, et al.
(författare)
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Understanding the role of diabetes in the osteoarthritis disease and treatment process: a study protocol for the Swedish Osteoarthritis and Diabetes (SOAD) cohort
- 2019
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 9:12
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Osteoarthritis (OA) is the most common form of arthritis and a leading cause of disability worldwide. Metabolic comorbidities such as type II diabetes occur with a higher rate in people with OA than in the general population. Several factors including obesity, hyperglycaemia toxicity and physical inactivity have been suggested as potential links between diabetes and OA, and have been shown to negatively impact patients' health and quality of life. However, little is known on the role of diabetes in determining the outcome of non-surgical and surgical management of OA, and at the same time, how different OA interventions may affect diabetes control. Thus, the overall aim of this project is to explore (1) the impact of diabetes on the outcome of non-surgical and surgical OA treatments and (2) the impact of non-surgical and surgical OA treatments on diabetes control. Methods and analysis The study cohort is based on prospectively ascertained register data on a national level in Sweden. Data from OA patients who received a first-line non-surgical intervention and are registered in the National Quality Register for Better Management of Patients with Osteoarthritis will be merged with data from the Swedish Knee and Hip Arthroplasty Registers and the National Diabetes Register. Additional variables regarding patients' use of prescribed drugs, comorbidities, socioeconomic status and cause of death will be obtained through other national health and population data registers. The linkage will be performed on an individual level using unique personal identity numbers. Ethics and dissemination This study received ethical approval (2019-02570) from the Swedish Ethical Review Authority. Results from this cohort will be submitted to peer-reviewed scientific journals and reported at the leading national and international meetings in the field.
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| 36. |
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| 37. |
- af Geijersstam, E, et al.
(författare)
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Mercury uptake and kinetics after ingestion of dental amalgam
- 2001
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Ingår i: Journal of dental research. - : SAGE Publications. - 0022-0345 .- 1544-0591. ; 80:9, s. 1793-1796
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to investigate the G-I uptake of mercury (Hg) after intake of a single dose of amalgam-Hg, followed by pharmacokinetic analysis of the data. Eleven volunteers without amalgam fillings ingested 1.00 g amalgam powder. Hg in plasma vs. time was analyzed with a two-compartment model by means of mixed-effects modeling. A fraction of the absorption rate of Hg to the central compartment was inversely proportional to the plasma ferritin levels. The population mean half-life of the terminal phase of Hg in plasma was 37 days, with a considerable standard deviation in the population. The absorbed fraction of the administered dose was estimated to be about 0.04%. It is concluded that the G-I uptake of Hg is of quantitative importance during dental treatment.
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| 38. |
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| 39. |
- Ahmad Kiadaliri, Aliasghar, et al.
(författare)
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Fall-related mortality in southern Sweden : a multiple cause of death analysis, 1998-2014
- 2019
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Ingår i: Injury Prevention. - : BMJ. - 1353-8047 .- 1475-5785. ; 25:2, s. 129-135
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate temporal trend in fall mortality among adults (aged ≥20 years) in southern Sweden using multiple cause of death data.METHODS: We examined all death certificates (DCs, n=2 01 488) in adults recorded in the Skåne region during 1998-2014. We identified all fall deaths using International Statistical Classification of Diseases (ICD)-10 codes (W00-W19) and calculated the mortality rates by age and sex. Temporal trends were evaluated using joinpoint regression and associated causes were identified by age-adjusted and sex-adjusted observed/expected ratios.RESULTS: Falls were mentioned on 1.0% and selected as underlying cause in 0.7% of all DCs, with the highest frequency among those aged ≥70 years. The majority (75.6%) of fall deaths were coded as unspecified fall (ICD-10 code: W19) followed by falling on or from stairs/steps (7.7%, ICD-10 code: W10) and other falls on the same level (6.3%, ICD-10 code: W18). The mean age at fall deaths increased from 77.5 years in 1998-2002 to 82.9 years in 2010-2014 while for other deaths it increased from 78.5 to 79.8 years over the same period. The overall mean age-standardised rate of fall mortality was 8.3 and 4.0 per 1 00 000 person-years in men and women, respectively, and increased by 1.7% per year in men and 0.8% per year in women during 1998-2014. Head injury and diseases of the circulatory system were recorded as contributing cause on 48.7% of fall deaths.CONCLUSIONS: There is an increasing trend of deaths due to falls in southern Sweden. Further investigations are required to explain this observation particularly among elderly men.
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| 40. |
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| 41. |
- Allard, Per, et al.
(författare)
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Reduced number of caudate nucleus dopamine uptake sites in vascular dementia.
- 1999
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Ingår i: Dementia and Geriatric Cognitive Disorders. - 1420-8008 .- 1421-9824. ; 10:2, s. 77-80
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Tidskriftsartikel (refereegranskat)abstract
- The dopamine (DA) uptake sites in the caudate nucleus were studied in patients with vascular dementia (VAD) and in a control group using the presynaptic DA uptake site marker [3H][2beta-carbomethoxy-3beta-(4-fluorophenyl) tropane] as radioligand. There was a significant decrease in the number of DA uptake sites in the VAD group, while the binding affinity was unchanged. The present results indicate that in the patients investigated, the cerebrovascular disease process involves dopaminergic neuron terminals in the caudate nucleus. Our findings are discussed in relation to the reductions in number of DA uptake sites that have previously been revealed in Alzheimer's and Parkinson's diseases.
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| 42. |
- B. Wrammerfors, E. Tobias, et al.
(författare)
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Exploratory neutron tomography of articular cartilage
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Ingår i: Osteoarthritis and Cartilage. - 1063-4584.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the feasibility of using neutron tomography to gain new knowledge of human articular cartilage degeneration in osteoarthritis (OA). Different sample preparation techniques were evaluated to identify maximum intra-tissue contrast. Design: Human articular cartilage samples from 14 deceased donors (18–75 years, 9 males, 5 females) and 4 patients undergoing total knee replacement due to known OA (all female, 61–75 years) were prepared using different techniques: control in saline, treated with heavy water saline, fixed and treated in heavy water saline, and fixed and dehydrated with ethanol. Neutron tomographic imaging (isotropic voxel sizes from 7.5 to 13.5 µm) was performed at two large scale facilities. The 3D images were evaluated for gradients in hydrogen attenuation as well as compared to images from absorption X-ray tomography, magnetic resonance imaging, and histology. Results: Cartilage was distinguishable from background and other tissues in neutron tomographs. Intra-tissue contrast was highest in heavy water-treated samples, which showed a clear gradient from the cartilage surface to the bone interface. Increased neutron flux or exposure time improved image quality but did not affect the ability to detect gradients. Samples from older donors showed high variation in gradient profile, especially from donors with known OA. Conclusions: Neutron tomography is a viable technique for specialized studies of cartilage, particularly for quantifying properties relating to the hydrogen density of the tissue matrix or water movement in the tissue.
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| 43. |
- Baldo, B., et al.
(författare)
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SIRT1 is increased in affected brain regions and hypothalamic metabolic pathways are altered in Huntington disease
- 2019
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Ingår i: Neuropathology and Applied Neurobiology. - : Wiley. - 0305-1846 .- 1365-2990. ; 45:4, s. 361-379
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Metabolic dysfunction is involved in modulating the disease process in Huntington disease (HD) but the underlying mechanisms are not known. The aim of this study was to investigate if the metabolic regulators sirtuins are affected in HD. Methods: Quantitative real-time polymerase chain reactions were used to assess levels of SIRT1-3 and downstream targets in post mortem brain tissue from HD patients and control cases as well as after selective hypothalamic expression of mutant huntingtin (HTT) using recombinant adeno-associated viral vectors in mice. Results: We show that mRNA levels of the metabolic regulator SIRT1 are increased in the striatum and the cerebral cortex but not in the less affected cerebellum in post mortem HD brains. Levels of SIRT2 are only increased in the striatum and SIRT3 is not affected in HD. Interestingly, mRNA levels of SIRT1 are selectively increased in the lateral hypothalamic area (LHA) and ventromedial hypothalamus (VMH) in HD. Further analyses of the LHA and VMH confirmed pathological changes in these regions including effects on SIRT1 downstream targets and reduced mRNA levels of orexin (hypocretin), prodynorphin and melanin-concentrating hormone (MCH) in the LHA and of brain-derived neurotrophic factor (BDNF) in the VMH. Analyses after selective hypothalamic expression of mutant HTT suggest that effects on BDNF, orexin, dynorphin and MCH are early and direct, whereas changes in SIRT1 require more widespread expression of mutant HTT. Conclusions: We show that SIRT1 expression is increased in HD-affected brain regions and that metabolic pathways are altered in the HD hypothalamus.
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| 44. |
- Berg, B., et al.
(författare)
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Development of osteoarthritis in patients with degenerative meniscal tears treated with exercise therapy or surgery : a randomized controlled trial
- 2020
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 28:7, s. 897-906
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate progression of individual radiographic features 5 years following exercise therapy or arthroscopic partial meniscectomy as treatment for degenerative meniscal tear. Design: Randomized controlled trial including 140 adults, aged 35–60 years, with a magnetic resonance image verified degenerative meniscal tear, and 96% without definite radiographic knee osteoarthritis. Participants were randomized to either 12-weeks of supervised exercise therapy or arthroscopic partial meniscectomy. The primary outcome was between-group difference in progression of tibiofemoral joint space narrowing and marginal osteophytes at 5 years, assessed semi-quantitatively by the OARSI atlas. Secondary outcomes included incidence of radiographic knee osteoarthritis and symptomatic knee osteoarthritis, medial tibiofemoral fixed joint space width (quantitatively assessed), and patient-reported outcome measures. Statistical analyses were performed using a full analysis set. Per protocol and as treated analysis were also performed. Results: The risk ratios (95% CI) for progression of semi-quantitatively assessed joint space narrowing and medial and lateral osteophytes for the surgery group were 0.89 (0.55–1.44), 1.15 (0.79–1.68) and 0.77 (0.42–1.42), respectively, compared to the exercise therapy group. In secondary outcomes (full-set analysis) no statistically significant between-group differences were found. Conclusion: The study was inconclusive with respect to potential differences in progression of individual radiographic features after surgical and non-surgical treatment for degenerative meniscal tear. Further, we found no strong evidence in support of differences in development of incident radiographic knee osteoarthritis or patient-reported outcomes between exercise therapy and arthroscopic partial meniscectomy.
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| 45. |
- Bergkvist, Dan, et al.
(författare)
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Sick leave before and after arthroscopic partial meniscectomy due to traumatic meniscal tear
- 2020
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Ingår i: Osteoarthritis and Cartilage Open. - : Elsevier BV. - 2665-9131. ; 2:2
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Tidskriftsartikel (refereegranskat)abstract
- Summary Objective There is limited knowledge on sick leave associated with arthroscopic partial meniscectomy (APM) due to traumatic meniscal tear and its potential gender differences. Thus, our aim was to determine gender-specific sick leave before and after APM. Method In Skåne region, Sweden, we identified patients, aged 18–59 years diagnosed with traumatic meniscal tear without ligament injury, who had APM during 2004–2012. For each patient, we randomly sampled four age- and sex-matched reference subjects from the general population. We retrieved social insurance register data of all-cause sick leave exceeding two weeks. We analyzed the proportions and duration of sick leave with respect to days of sick leave, age, and gender. Results The cohort comprised 604 patients (29% women), mean (SD) age 40 (11) years, and 2254 reference subjects. Thirty-nine percent of women and 27% of men had a sick leave period longer than 14 days after APM. Still, we found that a new period of sick leave longer than 14 days, initiated on the day of APM (and not before), was relatively uncommon and equally distributed (15%) between women and men. Conclusion About one-third of the patients have more than 2 weeks of sick leave after APM for a traumatic meniscal tear and women are overrepresented in this category. Prolonged sick leave initiated on the day of APM was relatively uncommon. Other factors than surgery seem to explain the prolonged sick leave.
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| 46. |
- Brantsaeter, A. L., et al.
(författare)
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Maternal intake of seafood and supplementary long chain n-3 poly-unsaturated fatty acids and preterm delivery
- 2017
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Ingår i: Bmc Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Preterm delivery increases the risk of neonatal morbidity and mortality. Studies suggest that maternal diet may affect the prevalence of preterm delivery. The aim of this study was to assess whether maternal intakes of seafood and marine long chain n-3 polyunsaturated fatty acids (LCn-3PUFA) from supplements were associated with preterm delivery. Methods: The study population included 67,007 women from the Norwegian Mother and Child Cohort Study. Maternal food and supplement intakes were assessed by a validated self-reported food frequency questionnaire in mid-pregnancy. Information about gestational duration was obtained from the Medical Birth Registry of Norway. We used Cox regression to estimate hazard ratios (HR) with 95% confidence intervals (CI) for associations between total seafood, lean fish, fatty fish, and LCn-3PUFA intakes and preterm delivery. Preterm was defined as any onset of delivery before gestational week 37, and as spontaneous or iatrogenic deliveries and as preterm delivery at early, moderate, and late preterm gestations. Results: Lean fish constituted 56%, fatty fish 34% and shellfish 10% of seafood intake. Any intake of seafood above no/rare intake (> 5 g/d) was associated with lower prevalence of preterm delivery. Adjusted HRs were 0.76 (CI: 0.66, 0.88) for 1-2 servings/week (20-40 g/d), 0.72 (CI: 0.62, 0.83) for 2-3 servings/week (40-60 g/d), and 0.72 (CI: 0.61, 0. 85) for >= 3 servings/week (>60 g/d), p-trend <0.001. The association was seen for lean fish (p-trend: 0.005) but not for fatty fish (p-trend: 0.411). The intake of supplementary LCn-3PUFA was associated only with lower prevalence of early preterm delivery (before 32 gestational weeks), while increasing intake of LCn-3PUFA from food was associated with lower prevalence of overall preterm delivery (p-trend: 0.002). Any seafood intake above no/rare was associated with lower prevalence of both spontaneous and iatrogenic preterm delivery, and with lower prevalence of late preterm delivery. Conclusions: Any intake of seafood above no/rare consumption was associated with lower prevalence of preterm delivery. The association was stronger for lean than for fatty fish. Intake of supplementary LCn-3PUFA was associated only with early preterm delivery. The findings corroborate the current advice to include fish and seafood as part of a balanced diet during pregnancy.
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| 47. |
- Brun, A, et al.
(författare)
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Brain changes in dementia of Alzheimer's type relevant to new imaging diagnostic methods
- 1986
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Ingår i: Progress in Neuro-Psychopharmacology and Biological Psychiatry. - : Elsevier BV. - 0278-5846. ; 10:3-5, s. 297-308
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the article is to correlate grey and white matter changes and their topography to the results of modern methods for brain imaging such as CT, rCBF, PET, SPECT and NMR in Alzheimer's type of dementia. The findings are based on the study of a large material investigated thoroughly patho-anatomically. The findings are correlated with psychiatric and neurophysiologic follow-up studies. The degenerative grey matter process shows a regionally varying accent according to a pattern which is consistent and typical for the disease. This corresponds to metabolic changes on rCBF, PET and SPECT and thereby becomes of diagnostic value. This pattern is largely symmetric. Metabolic asymmetries have however been reported on PET scans. In this context individual variations of the topographic degenerative brain pattern and normal anatomical brain asymmetries are of interest. The white matter however also frequently shows changes, in particular loss of myelin and axons and a mild gliosis, slight in 1/3 of the cases and severe in an additional 1/3. These changes cause a decrease of density in the centrum semiovale correlating to lipid depletion. They may also influence the ventricular shape and size, of interest in CT or NMR studies. Also here variations in ventricular shape, normal and such due to pathological processes unrelated to the Alzheimer disease, may cause confusion, regarding degree of atrophy and even type of brain process. Such factors should be considered in the interpretation of non-invasive brain studies.
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| 48. |
- Brun, A, et al.
(författare)
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Regional pattern of degeneration in Alzheimer's disease : neuronal loss and histopathological grading
- 1981
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Ingår i: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 5:5, s. 64-549
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Tidskriftsartikel (refereegranskat)abstract
- The various structural components of the cortical degeneration of Alzheimer's disease were defined and graded. The severity of the degenerative process was thus mapped in different cortical areas where neuronal numbers and cortical width were also measured and compared with controls. Contrary to the general opinion that the degenerative process is rather uniformly diffuse, though accentuated in the medial temporal and frontal cortex, we found a consistent and more elaborate pattern with clearcut regional differences. Thus the degeneration involved, besides basal medial temporal limbic areas, the posterior cingulate gyrus and superior parietal lobule particularly, with somewhat less marked changes in the inferior parietal lobule and inferior temporal gyri. The sensorimotor, calcarine and anterior cingulate areas of the cortex were notably spared until very late stages. This regionally variable severity of the degeneration was also paralleled by a regionally varying reduction in neuronal numbers and cortical width, and agrees with our previously published results of a regional pattern which closely correlates with clinical parameters, including symptom pattern and regional cerebral blood flow alterations.
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| 49. |
- Brunnström, Hans, et al.
(författare)
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Differential degeneration of the locus coeruleus in dementia subtypes.
- 2011
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Ingår i: Clinical Neuropathology. - 0722-5091. ; 30:3, s. 104-110
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Neuronal loss in the locus coeruleus (LC) is common in Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). The aims of the present study were to investigate LC degeneration in different dementia disorders including vascular dementia (VaD) and frontotemporal lobar degeneration (FTLD), to compare LC degeneration with severity of pathology in AD and DLB/PDD, to further evaluate the usefulness of a previously presented scoring system and to examine the predictive value of macroscopic assessment of the LC. Methods: A horizontal mid-level section of the pons was examined in 200 neuropathologically examined cases with clinical dementia. A previous macroscopic assessment of the LC was performed in 149 of the cases. Results: Cases with DLB/ PDD and AD presented with the highest microscopic LC degeneration scores, with significant differences compared to combined AD + VaD, in turn with a higher score than VaD, FTLD and other dementia disorders. Interrater agreement (weighted kappa;) for LC degeneration scoring was 0.83 - 0.91. DLB/ PDD, AD and AD + VaD were the diagnoses for 85% of the cases with macroscopic LC depigmentation. Conclusion: LC degeneration, which may be macroscopically noted, often indicates synuclein and/or Alzheimer pathology among demented. When clinical information is scarce or inconsistent, a macroscopic assessment of the LC may facilitate focusing of the subsequent neuropathological investigation. Also, the semiquantitative scoring system is a reliable tool for histological assessment of LC degeneration.
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| 50. |
- Burguillos Garcia, Miguel, et al.
(författare)
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Apoptosis-inducing factor mediates dopaminergic cell death in response to lps-induced inflammatory stimulus Evidence in Parkinson's disease patients.
- 2011
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961 .- 1095-953X. ; 41, s. 177-188
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Tidskriftsartikel (refereegranskat)abstract
- We show that intranigral lipopolysaccharide (LPS) injection, which provokes specific degeneration of DA neurons, induced caspase-3 activation in the rat ventral mesencephalon, which was mostly associated with glial cells. In contrast, nigral DA neurons exhibited AIF nuclear translocation in response to LPS. A significant decrease of the Bcl-2/Bax ratio in nigral tissue after LPS injection was observed. We next developed an in vitro co-culture system with the microglial BV2 and the DA neuronal MN9D murine cell lines. The silencing of caspase-3 or AIF by small interfering RNAs exclusively in the DA MN9D cells demonstrated the key role of AIF in the LPS-induced death of DA cells. In vivo chemical inhibition of caspases and poly(ADP-ribose)polymerase-1, an upstream regulator of AIF release and calpain, proved the central role of the AIF-dependent pathway in LPS-induced nigral DA cell death. We also observed nuclear translocation of AIF in the ventral mesencephalon of Parkinson's disease subjects.
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