| 1. |
- Jansen, Willemijn J, et al.
(författare)
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Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
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Tidskriftsartikel (refereegranskat)abstract
- One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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| 2. |
- Lindgaard, S. C., et al.
(författare)
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Hepatic arterial therapy with oxaliplatin and systemic capecitabine for patients with liver metastases from breast cancer
- 2019
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Ingår i: Breast. - : Elsevier BV. - 0960-9776. ; 43, s. 113-119
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Hepatic arterial treatment (HAT) for liver metastases in patients with metastatic breast cancer (MBC) has only been investigated in few studies. Materials and methods: Two phase II trials were initiated simultaneously to evaluate capecitabine in combination with oxaliplatin in patients with MBC and liver metastases. These two trials are reported together. Continuous capecitabine (1300 mg/m2) was combined with oxaliplatin (85 mg/m2) alternating between systemic treatment and HAT followed by degradable starch microspheres with EmboCept® S every second week. Four patients participated in a pharmacokinetic analysis of oxaliplatin. Each patient had samples taken when receiving oxaliplatin systemically and as HAT with and without EmboCept® S. Results: Totally, 52 patients received HAT: 14 with liver metastases only and 38 patients with additional limited metastatic disease. The patients had previously received a median of 2 (range 0–6) chemotherapeutic regimens for MBC. The response rate was 42.3% (95% confidence interval (CI) 28.7–56.8%) with 7.7% complete and 34.6% partial responses. Median progression free survival was 10.8 months (95% CI 6.9–14.7 months) and median overall survival 27.6 months (95% CI 20.4–34.8 months). The toxicity was moderate with hand-foot syndrome (15.4%), neuropathy (9.6%), fatigue (9.6%), and abdominal pain (9.6%) being the most common grade 3 adverse events. There was no clear difference between systemic blood concentrations of oxaliplatin when given systemic or as HAT. Conclusion: HAT oxaliplatin in combination with capecitabine is safe and efficient in patients with MBC. The results are promising with high response rates and a long median progression free and overall survival.
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| 3. |
- Andersson, Hanna, et al.
(författare)
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Natur på skolgården för lärande, hälsa och hållbarhet
- 2024. - 2024
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Rapport (populärvet., debatt m.m.)abstract
- Gröna och artrika utemiljöer främjar barns och ungas välbefinnande och kunskap, bådegenom hälsofördelar kopplade till biologisk mångfald och genom att skapa förutsättningarför lek och lärande om natur och miljöfrågor. Skolgården skulle kunna bidra till allt detta,men är idag i hög grad en outnyttjad plats för biologisk mångfald och klimatanpassningav städer. I denna policy brief presenteras huvudsakliga motiv och möjliga åtgärder för attutveckla gröna miljöer och biologisk mångfald på skolgårdar och förskolegårdar.
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| 4. |
- Ekblad, Alf, 1957-, et al.
(författare)
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The production and turnover of extramatrical mycelium of ectomycorrhizal fungi in forest soils : role in carbon cycling
- 2013
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Ingår i: Plant and Soil. - : Springer Science and Business Media LLC. - 0032-079X .- 1573-5036. ; 366:1-2, s. 1-27
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Forskningsöversikt (refereegranskat)abstract
- There is growing evidence of the importance of extramatrical mycelium (EMM) of mycorrhizal fungi in carbon (C) cycling in ecosystems. However, our understanding has until recently been mainly based on laboratory experiments, and knowledge of such basic parameters as variations in mycelial production, standing biomass and turnover as well as the regulatory mechanisms behind such variations in forest soils is limited. Presently, the production of EMM by ectomycorrhizal (EM) fungi has been estimated at similar to 140 different forest sites to be up to several hundreds of kg per ha per year, but the published data are biased towards Picea abies in Scandinavia. Little is known about the standing biomass and turnover of EMM in other systems, and its influence on the C stored or lost from soils. Here, focussing on ectomycorrhizas, we discuss the factors that regulate the production and turnover of EMM and its role in soil C dynamics, identifying important gaps in this knowledge. C availability seems to be the key factor determining EMM production and possibly its standing biomass in forests but direct effects of mineral nutrient availability on the EMM can be important. There is great uncertainty about the rate of turnover of EMM. There is increasing evidence that residues of EM fungi play a major role in the formation of stable N and C in SOM, which highlights the need to include mycorrhizal effects in models of global soil C stores.
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| 5. |
- Ladd, Brenton, et al.
(författare)
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Carbon isotopic signatures of soil organic matter correlate with leaf area index across woody biomes
- 2014
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Ingår i: Journal of Ecology. - : Wiley. - 0022-0477 .- 1365-2745. ; 102:6, s. 1606-1611
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Tidskriftsartikel (refereegranskat)abstract
- Leaf area index (LAI), a measure of canopy density, is a key variable for modelling and understanding primary productivity, and also water use and energy exchange in forest ecosystems. However, LAI varies considerably with phenology and disturbance patterns, so alternative approaches to quantifying stand-level processes should be considered. The carbon isotope composition of soil organic matter (C-13(SOM)) provides a time-integrated, productivity-weighted measure of physiological and stand-level processes, reflecting biomass deposition from seasonal to decadal time scales.Our primary aim was to explore how well LAI correlates with C-13(SOM) across biomes.Using a global data set spanning large environmental gradients in tropical, temperate and boreal forest and woodland, we assess the strength of the correlation between LAI and C-13(SOM); we also assess climatic variables derived from the WorldClim database.We found that LAI was strongly correlated with C-13(SOM), but was also correlated with Mean Temperature of the Wettest Quarter, Mean Precipitation of Warmest Quarter and Annual Solar Radiation across and within biomes.Synthesis. Our results demonstrate that C-13(SOM) values can provide spatially explicit estimates of leaf area index (LAI) and could therefore serve as a surrogate for productivity and water use. While C-13(SOM) has traditionally been used to reconstruct the relative abundance of C-3 versus C-4 species, the results of this study demonstrate that within stable C-3- or C-4-dominated biomes, C-13(SOM) can provide additional insights. The fact that LAI is strongly correlated to C-13(SOM) may allow for a more nuanced interpretation of ecosystem properties of palaeoecosystems based on palaeosol C-13 values.
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| 6. |
- Liang, Min, et al.
(författare)
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Combined lack of estrogen receptors alpha and beta affects vascular iNOS protein expression.
- 2003
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Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 1432-0878 .- 0302-766X. ; 313:1, s. 63-70
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Tidskriftsartikel (refereegranskat)abstract
- Endothelial and vascular smooth muscle cells express both estrogen receptor (ER) agr and beta. Recent findings indicate that vascular ERbeta and ERagr may substitute for one another. Here, we investigate vascular morphology, contractility and protein expression in intact aorta from adult (4 months old) female mice lacking both ERagr and ERbeta (DERKO). The body weights were 17% higher (P<0.01) in DERKO than in wild-type mice. Vascular morphology, investigated in paraffin sections from aorta stained with hematoxylin-eosin or van Gieson, was identical in DERKO and wild-type mice. Endothelial cells were clearly visible in aorta of both DERKO and wild-type animals. Morphometric analysis of media thickness and wall to lumen ratio using a computerized image analyzing system demonstrated no differences between the two groups of mice. The vascular expression of endothelial nitric oxide synthase (eNOS, NOS III) and inducible nitric oxide synthase (iNOS, NOS II) was investigated using Western blotting. Aorta from both DERKO and wild-type mice expressed iNOS protein, but the iNOS expression was 3 times lower (P<0.05) in DERKO compared to wild-type mice. No difference in eNOS protein level between the two groups of animals was observed. Force responses to noradrenaline, determined either in the absence or in the presence of the nitric oxide synthase inhibitor l-NAME and the cyclo-oxygenase inhibitor indomethacin, were unaffected by the lack of functional ERagr/ERbeta. In summary, combined lack of functional ERagr and ERbeta lowers the vascular expression of iNOS but has no effects on morphology, eNOS expression, and noradrenaline sensitivity in the intact aorta.
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| 7. |
- Mccourt, Andy, et al.
(författare)
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Characterization of Gastric Mucosa Biopsies Reveals Alterations in Huntington's Disease.
- 2015
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Ingår i: PLoS Currents. - : Public Library of Science (PLoS). - 2157-3999. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Weight loss is an important complication of Huntington's disease (HD), however the mechanism for weight loss in HD is not entirely understood. Mutant huntingtin is expressed in the gastrointestinal (GI) tract and, in HD mice, mutant huntingtin inclusions are found within the enteric nervous system along the GI tract. A reduction of neuropeptides, decreased mucosal thickness and villus length, as well as gut motility impairment, have also been shown in HD mice. We therefore set out to study gastric mucosa of patients with HD, looking for abnormalities of mucosal cells using immunohistochemistry. In order to investigate possible histological differences related to gastric acid production, we evaluated the cell density of acid producing parietal cells, as well as gastrin producing cells (the endocrine cell controlling parietal cell function). In addition, we looked at chief cells and somatostatin-containing cells. In gastric mucosa from HD subjects, compared to control subject biopsies, a reduced expression of gastrin (a marker of G cells) was found. This is in line with previous HD mouse studies showing reduction of GI tract neuropeptides.
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| 8. |
- Ravi, Naveen, et al.
(författare)
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Identification of targetable lesions in anaplastic thyroid cancer by genome profiling
- 2019
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Anaplastic thyroid cancer (ATC) is a rare and extremely malignant tumor with no available cure. The genetic landscape of this malignancy has not yet been fully explored. In this study, we performed whole exome sequencing and the RNA-sequencing of fourteen cases of ATC to delineate copy number changes, fusion gene events, and somatic mutations. A high frequency of genomic amplifications was seen, including 29% of cases having amplification of CCNE1 and 9% of CDK6; these events may be targetable by cyclin dependent kinase (CDK) inhibition. Furthermore, 9% harbored amplification of TWIST1, which is also a potentially targetable lesion. A total of 21 fusion genes in five cases were seen, none of which were recurrent. Frequent mutations included TP53 (55%), the TERT promoter (36%), and ATM (27%). Analyses of mutational signatures showed an involvement of processes that are associated with normal aging, defective DNA mismatch repair, activation induced cytidine deaminase (AID)/apolipoprotein B editing complex (APOBEC) activity, failure of DNA double-strand break repair, and tobacco exposure. Taken together, our results shed new light on the tumorigenesis of ATC and show that a relatively large proportion (36%) of ATCs harbor genetic events that make them candidates for novel therapeutic approaches. When considering that ATC today has a mortality rate of close to 100%, this is highly relevant from a clinical perspective.
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| 9. |
- Sand, Elin, et al.
(författare)
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Buserelin treatment to rats causes enteric neurodegeneration with moderate effects on CRF-immunoreactive neurons and Enterobacteriaceae in colon, and in acetylcholine-mediated permeability in ileum
- 2015
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Ingår i: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The gonadotropin-releasing hormone (GnRH) analog buserelin causes enteric neuronal loss. Acute stress or injection of corticotropin-releasing factor (CRF) affects motility, secretion, and barrier function of the gastrointestinal tract. The aim of the study was to characterize the CRF immunoreactivity in enteric neurons after buserelin treatment, and to evaluate possible effects of enteric neuropathy on gut microbiota, intestinal permeability, and stress response behavior. Results: Sixty rats were given buserelin (20 μg) or saline subcutaneously for 5 days, repeated four times with 3 weeks in-between. At the study end, enteric neuronal density, enteric expression of CRF, gut microbial composition, and plasma levels of adrenocorticotropic hormone (ACTH) and CRF were analyzed. Intestinal permeability was examined in Ussing chambers and the reaction to stressful events was measured by behavior tests. Buserelin treatment reduced the number of neurons along the entire gastrointestinal tract, with increased relative numbers of CRF-immunoreactive submucosal and myenteric neurons in colon (p < 0.05 and p < 0.01, respectively). The overall microbial diversity and relative abundance did not differ between groups, but Enterobacteriaceae was decreased in colon in buserelin-treated rats (p = 0.020). Basal intestinal permeability did not differ between groups, whereas carbachol stimulation increased ileum permeability in controls (p < 0.05), but not in buserelin-treated rats. Buserelin did not affect stress behavior. Conclusions: Although buserelin treatment leads to enteric neuronal loss along the gastrointestinal tract with an increased percentage of CRF-immunoreactive neurons in colon, the physiology is well preserved, with modest effects on colon microbiota and absence of carbachol-induced permeability in ileum as the only observed changes. © 2015 Sand et al.
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| 10. |
- Wallander, Håkan, et al.
(författare)
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Evaluation of methods to estimate production, biomass and turnover of ectomycorrhizal mycelium in forests soils : a review
- 2013
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Ingår i: Soil Biology and Biochemistry. - : Elsevier BV. - 0038-0717 .- 1879-3428. ; 57, s. 1034-1047
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Forskningsöversikt (refereegranskat)abstract
- Mycorrhizal fungi constitute a considerable sink for carbon in most ecosystems. This carbon is used for building extensive mycelial networks in the soil as well as for metabolic activity related to nutrient uptake. A number of methods have been developed recently to quantify production, standing biomass and turnover of extramatrical mycorrhizal mycelia (EMM) in the field. These methods include minirhizotrons, in-growth mesh bags and cores, and indirect measurements of EMM based on classification of ectomycorrhizal fungi into exploration types. Here we review the state of the art of this methodology and discuss how it can be developed and applied most effectively in the field, Furthermore, we also discuss different ways to quantify fungal biomass based on biomarkers such as chitin, ergosterol and PLFAs, as well as molecular methods, such as qPCR. The evidence thus far indicates that mycorrhizal fungi are key components of microbial biomass in many ecosystems. We highlight the need to extend the application of current methods to focus on a greater range of habitats and mycorrhizal types enabling incorporation of mycorrhizal fungal biomass and turnover into biogeochemical cycling models.
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