| 221. |
- Lewczuk, Piotr, et al.
(författare)
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Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry.
- 2018
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Ingår i: The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry. - : Informa UK Limited. - 1814-1412. ; 19:4, s. 244-328
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Tidskriftsartikel (refereegranskat)abstract
- In the 12 years since the publication of the first Consensus Paper of the WFSBP on biomarkers of neurodegenerative dementias, enormous advancement has taken place in the field, and the Task Force takes now the opportunity to extend and update the original paper. New concepts of Alzheimer's disease (AD) and the conceptual interactions between AD and dementia due to AD were developed, resulting in two sets for diagnostic/research criteria. Procedures for pre-analytical sample handling, biobanking, analyses and post-analytical interpretation of the results were intensively studied and optimised. A global quality control project was introduced to evaluate and monitor the inter-centre variability in measurements with the goal of harmonisation of results. Contexts of use and how to approach candidate biomarkers in biological specimens other than cerebrospinal fluid (CSF), e.g. blood, were precisely defined. Important development was achieved in neuroimaging techniques, including studies comparing amyloid-β positron emission tomography results to fluid-based modalities. Similarly, development in research laboratory technologies, such as ultra-sensitive methods, raises our hopes to further improve analytical and diagnostic accuracy of classic and novel candidate biomarkers. Synergistically, advancement in clinical trials of anti-dementia therapies energises and motivates the efforts to find and optimise the most reliable early diagnostic modalities. Finally, the first studies were published addressing the potential of cost-effectiveness of the biomarkers-based diagnosis of neurodegenerative disorders.
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| 222. |
- Nordin, Joel Z., et al.
(författare)
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Ultrafiltration with size-exclusion liquid chromatography for high yield isolation of extracellular vesicles preserving intact biophysical and functional properties
- 2015
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Ingår i: Nanomedicine. - : Elsevier BV. - 1549-9634 .- 1549-9642. ; 11:4, s. 879-883
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular vesicles (EVs) are natural nanoparticles that mediate intercellular transfer of RNA and proteins and are of great medical interest; serving as novel biomarkers and potential therapeutic agents. However, there is little consensus on the most appropriate method to isolate high-yield and high-purity EVs from various biological fluids. Here, we describe a systematic comparison between two protocols for EV purification: ultrafiltration with subsequent liquid chromatography (UF-LC) and differential ultracentrifugation (UC). A significantly higher EV yield resulted from UF-LC as compared to UC, without affecting vesicle protein composition. Importantly, we provide novel evidence that, in contrast to UC-purified EVs, the biophysical properties of UF-LC-purified EVs are preserved, leading toadifferent in vivo biodistribution, with less accumulation in lungs. Finally, we show that UF-LC is scalable and adaptable for EV isolation from complex media types such as stem cell media, which is of huge significance for future clinical applications involving EVs.
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| 223. |
- Noveir, S. D., et al.
(författare)
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Effect of the ABCA1 agonist CS-6253 on amyloid-β and lipoprotein metabolism in cynomolgus monkeys
- 2022
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Ingår i: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inducing brain ATP-binding cassette 1 (ABCA1) activity in Alzheimer’s disease (AD) mouse models is associated with improvement in AD pathology. The purpose of this study was to investigate the effects of the ABCA1 agonist peptide CS-6253 on amyloid-β peptides (Aβ) and lipoproteins in plasma and cerebrospinal fluid (CSF) of cynomolgus monkeys, a species with amyloid and lipoprotein metabolism similar to humans. Methods: CS-6253 peptide was injected intravenously into cynomolgus monkeys at various doses in three different studies. Plasma and CSF samples were collected at several time points before and after treatment. Levels of cholesterol, triglyceride (TG), lipoprotein particles, apolipoproteins, and Aβ were measured using ELISA, ion-mobility analysis, and asymmetric-flow field-flow fractionation (AF4). The relationship between the change in levels of these biomarkers was analyzed using multiple linear regression models and linear mixed-effects models. Results: Following CS-6253 intravenous injection, within minutes, small plasma high-density lipoprotein (HDL) particles were increased. In two independent experiments, plasma TG, apolipoprotein E (apoE), and Aβ42/40 ratio were transiently increased following CS-6253 intravenous injection. This change was associated with a non-significant decrease in CSF Aβ42. Both plasma total cholesterol and HDL-cholesterol levels were reduced following treatment. AF4 fractionation revealed that CS-6253 treatment displaced apoE from HDL to intermediate-density- and low density-lipoprotein (IDL/LDL)-sized particles in plasma. In contrast to plasma, CS-6253 had no effect on the assessed CSF apolipoproteins or lipids. Conclusions: Treatment with the ABCA1 agonist CS-6253 appears to favor Aβ clearance from the brain.
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| 224. |
- Oliveira, F., et al.
(författare)
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Data driven diagnostic classification in Alzheimer's disease based on different reference regions for normalization of PiB-PET images and correlation with CSF concentrations of A beta species
- 2018
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Ingår i: Neuroimage-Clinical. - : Elsevier BV. - 2213-1582. ; 20, s. 603-610
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Tidskriftsartikel (refereegranskat)abstract
- Positron emission tomography (PET) neuroimaging with the Pittsburgh Compound_B (PiB) is widely used to assess amyloid plaque burden. Standard quantification approaches normalize PiB-PET by mean cerebellar gray matter uptake. Previous studies suggested similar pons and white-matter uptake in Alzheimer's disease (AD) and healthy controls (HC), but lack exhaustive comparison of normalization across the three regions, with data-driven diagnostic classification. We aimed to compare the impact of distinct reference regions in normalization, measured by data-driven statistical analysis, and correlation with cerebrospinal fluid (CSF) amyloid beta (A beta) species concentrations. 243 individuals with clinical diagnosis of AD, HC, mild cognitive impairment (MCI) and other dementias, from the Biomarkers for Alzheimer's/Parkinson's Disease (BIOMARKAPD) initiative were included. PiB-PET images and CSF concentrations of A beta(38), A beta(40) and A beta(42) were submitted to classification using support vector machines. Voxel-wise group differences and correlations between normalized PiB-PET images and CSF A beta concentrations were calculated. Normalization by cerebellar gray matter and pons yielded identical classification accuracy of AD (accuracy-96%, sensitivity-96%, specificity-95%), and significantly higher than A beta concentrations (best accuracy 91%). Normalization by the white-matter showed decreased extent of statistically significant multivoxel patterns and was the only method not outperforming CSF biomarkers, suggesting statistical inferiority. A beta(38) and A beta(40) correlated negatively with PiB-PET images normalized by the white-matter, corroborating previous observations of correlations with non-AD-specific subcortical changes in white-matter. In general, when using the pons as reference region, higher voxel-wise group differences and stronger correlation with A beta(42), the A beta(42)/A beta(40) or A beta(42)/A beta(38) ratios were found compared to normalization based on cerebellar gray matter.
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| 225. |
- Pauly, C., et al.
(författare)
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The pp→ppπππ reaction channels in the threshold region
- 2007
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 649:2-3, s. 122-127
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Tidskriftsartikel (refereegranskat)abstract
- The cross section for direct neutral and charged three pion production in pp interactions was measured at excess energies in the range 160–216 MeV. That comprises the first measurement of the pp→ppπ0π0π0 reaction and the direct comparison with the pp→ppπ+π−π0 process. The experiment was performed above the η meson production threshold and the cross section could be directly normalized to the cross section of the pp→ppη reaction, with the η decaying into 3 pions. Since the same final states are selected, the measurement has a low systematical error. The measured cross section ratio σ(pp→ppπ+π−π0)/σ(pp→ppπ0π0π0) is compared to predictions of dominance of different isobars in the intermediate state.
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| 226. |
- Pettersson, Henrik, et al.
(författare)
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eta PRODUCTION IN PROTON-PROTON COLLISIONS AT 72 MeV EXCESS ENERGY
- 2009
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Ingår i: International Journal of Modern Physics A. - 0217-751X .- 1793-656X. ; 24:2-3, s. 446-449
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Tidskriftsartikel (refereegranskat)abstract
- The production of eta mesons at an excess energy of 72 MeV has been studied in the reaction pp -> pp(eta)gamma gamma. It is shown that a simple model with Pp. final states included reproduces observed differential distributions better than the same model restricted to Ss, Sd and Ds final states. The strong influence of the Pp states could be taken as an indication of rho dominance within an one boson exchange model for the excitation of N*(1535).
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| 227. |
- Simonson, Oscar E., et al.
(författare)
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In Vivo Effects of Mesenchymal Stromal Cells in Two Patients With Severe Acute Respiratory Distress Syndrome
- 2015
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Ingår i: Stem Cells Translational Medicine. - : Oxford University Press (OUP). - 2157-6564 .- 2157-6580. ; 4:10, s. 1199-1213
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Tidskriftsartikel (refereegranskat)abstract
- Mesenchymal stromal cells (MSCs) have been investigated as a treatment for various inflammatory diseases because of their immunomodulatory and reparative properties. However, many basic questions concerning their mechanisms of action after systemic infusion remain unanswered. We performed a detailed analysis of the immunomodulatory properties and proteomic profile of MSCs systemically administered to two patients with severe refractory acute respiratory distress syndrome (ARDS) on a compassionate use basis and attempted to correlate these with in vivo anti-inflammatory actions. Both patients received 2 x 10(6) cells per kilogram, and each subsequently improved with resolution of respiratory, hemodynamic, and multiorgan failure. In parallel, a decrease was seen in multiple pulmonary and systemic markers of inflammation, including epithelial apoptosis, alveolar-capillary fluid leakage, and proinflammatory cytokines, microRNAs, and chemokines. In vitro studies of the MSCs demonstrated a broad anti-inflammatory capacity, including suppression of T-cell responses and induction of regulatory phenotypes in T cells, monocytes, and neutrophils. Some of these in vitro potency assessments correlated with, and were relevant to, the observed in vivo actions. These experiences highlight both the mechanistic information that can be gained from clinical experience and the value of correlating in vitro potency assessments with clinical effects. The findings also suggest, but do not prove, a beneficial effect of lung protective strategies using adoptively transferred MSCs in ARDS. Appropriate randomized clinical trials are required to further assess any potential clinical efficacy and investigate the effects on in vivo inflammation. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:1199-1213
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| 228. |
- Skorodko, T., et al.
(författare)
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ISOSPIN DECOMPOSITION OF pp -> NN pi pi CROSS SECTIONS : DO WE SEE A SIGN OF Delta(1600) EXCITATION IN THE nn pi(+)pi(+) CHANNEL?
- 2009
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Ingår i: International Journal of Modern Physics A. - 0217-751X .- 1793-656X. ; 24:2-3, s. 450-453
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Tidskriftsartikel (refereegranskat)abstract
- The two-pion production in pp-collisions has been investigated in exclusive measurements from threshold up to T-p = 1.36 GeV. Total and differential cross sections have been obtained for the channels pn pi(+) pi(0), pp pi(+) pi(-), pp pi(0)pi(0) and also nn pi(+)pi(+). For intermediate incident energies T-p > 1 GeV, i.e. in the region, which is beyond the Roper excitation but at the onset of Delta Delta excitation the total pp pi(0)pi(0) cross section falls behind theoretical predictions by as much as an order of magnitude near 1.2 GeV, whereas the nn pi(+)pi(+) cross section is a factor of five larger than predicted. A model-unconstrained isospin decompostion of the cross section points to a significant contribution of an isospin 3/2 resonance other than the Delta(1232). As a possible candidate the Delta(1600) is discussed.
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| 229. |
- Skorodko, T, et al.
(författare)
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Two-pion production in proton-proton collisions : experimental total cross sections and their isospin decomposition
- 2009
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 679:1, s. 30-35
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Tidskriftsartikel (refereegranskat)abstract
- The two-pion production in pp-collisions has been investigated at CELSIUS in exclusive measurements from threshold up to T-P = 1.36 GeV. Total and differential Cross sections have been obtained for the channels pn pi(+)pi(0), pp pi(+)pi(-), pp pi(0)pi(0) and also nn pi(+)pi(+). For intermediate incident energies T-P > 1GeV, i.e. in the region which is beyond the Roper excitation but at the onset of Delta Delta excitation, the total pp pi(0)pi(0) cross section falls behind theoretical predictions by as much as all order of magnitude near 1.2 GeV, whereas the nn pi(+)pi(+) cross section is a factor of five larger than predicted. An isospin decomposition of the total cross sections exhibits a s-channel-like energy dependence in the region of the Roper excitation as well as a significant contribution of an isospin 3/2 resonance other than the Delta(1232). As possible candidates the Delta(1600) and the Delta(1700) are discussed. (C) 2009 Elsevier B.V. All rights reserved.
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| 230. |
- Cummings, J., et al.
(författare)
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Cognitive Effects of the BET Protein Inhibitor Apabetalone: A Prespecified Montreal Cognitive Assessment Analysis Nested in the BETonMACE Randomized Controlled Trial
- 2021
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 83:4, s. 1703-1715
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epigenetic changes may contribute importantly to cognitive decline in late life including Alzheimer's disease (AD) and vascular dementia (VaD). Bromodomain and extra-terminal (BET) proteins are epigenetic "readers" that may distort normal gene expression and contribute to chronic disorders. Objective: To assess the effects of apabetalone, a small molecule BET protein inhibitor, on cognitive performance of patients 70 years or older participating in a randomized trial of patients at high risk for major cardiovascular events (MACE). Methods: The Montreal Cognitive Assessment (MoCA) was performed on all patients 70 years or older at the time of randomization. 464 participants were randomized to apabetalone or placebo in the cognition sub-study. In a prespecified analysis, participants were assigned to one of three groups: MoCA score >= 26 (normal performance), MoCA score 25-22 (mild cognitive impairment), and MoCA score <= 21 (dementia). Exposure to apabetalone was equivalent in the treatment groups in each MoCA-defined group. Results: Apabetalone was associated with an increased total MoCA score in participants with baseline MoCA score of <= 21 (p = 0.02). There was no significant difference in change from baseline in the treatment groups with higher MoCA scores. In the cognition study, more patients randomized to apabetalone discontinued study drug for adverse effects (11.3% versus 7.9%). Conclusion: In this randomized controlled study, apabetalone was associated with improved cognition as measured by MoCA scores in those with baseline scores of 21 or less. BET protein inhibitors warrant further investigation for late life cognitive disorders.
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