| 1. |
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| 2. |
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| 3. |
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| 4. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 7. |
- van de Sande-Bruinsma, Nienke, et al.
(författare)
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Antimicrobial drug use and resistance in Europe
- 2008
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Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 14:11, s. 1722-30
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Tidskriftsartikel (refereegranskat)abstract
- Our study confronts the use of antimicrobial agents in ambulatory care with the resistance trends of 2 major pathogens, Streptococcus pneumoniae and Escherichia coli, in 21 European countries in 2000-2005 and explores whether the notion that antimicrobial drug use determines resistance can be supported by surveillance data at national aggregation levels. The data obtained from the European Surveillance of Antimicrobial Consumption and the European Antimicrobial Resistance Surveillance System suggest that variation of consumption coincides with the occurrence of resistance at the country level. Linear regression analysis showed that the association between antimicrobial drug use and resistance was specific and robust for 2 of 3 compound pathogen combinations, stable over time, but not sensitive enough to explain all of the observed variations. Ecologic studies based on routine surveillance data indicate a relation between use and resistance and support interventions designed to reduce antimicrobial drug consumption at a national level in Europe.
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| 8. |
- Dahl-Jensen, D., et al.
(författare)
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Eemian interglacial reconstructed from a Greenland folded ice core
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 493:7433, s. 489-494
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Tidskriftsartikel (refereegranskat)abstract
- Efforts to extract a Greenland ice core with a complete record of the Eemian interglacial (130,000 to 115,000 years ago) have until now been unsuccessful. The response of the Greenland ice sheet to the warmer-than-present climate of the Eemian has thus remained unclear. Here we present the new North Greenland Eemian Ice Drilling ('NEEM') ice core and show only a modest ice-sheet response to the strong warming in the early Eemian. We reconstructed the Eemian record from folded ice using globally homogeneous parameters known from dated Greenland and Antarctic ice-core records. On the basis of water stable isotopes, NEEM surface temperatures after the onset of the Eemian (126,000 years ago) peaked at 8 +/- 4 degrees Celsius above the mean of the past millennium, followed by a gradual cooling that was probably driven by the decreasing summer insolation. Between 128,000 and 122,000 years ago, the thickness of the northwest Greenland ice sheet decreased by 400 +/- 250 metres, reaching surface elevations 122,000 years ago of 130 +/- 300 metres lower than the present. Extensive surface melt occurred at the NEEM site during the Eemian, a phenomenon witnessed when melt layers formed again at NEEM during the exceptional heat of July 2012. With additional warming, surface melt might become more common in the future.
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| 9. |
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| 10. |
- Klionsky, DJ, et al.
(författare)
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Autophagy in major human diseases
- 2021
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Ingår i: The EMBO journal. - : EMBO. - 1460-2075 .- 0261-4189. ; 40:19, s. e108863-
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Tidskriftsartikel (refereegranskat)
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| 11. |
- Roswall, N., et al.
(författare)
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Long-Term Exposure to Transportation Noise and Risk of Incident Stroke: A Pooled Study of Nine Scandinavian Cohorts
- 2021
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 129:10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Transportation noise is increasingly acknowledged as a cardiovascular risk factor, but the evidence base for an association with stroke is sparse. OBJECTIVE: We aimed to investigate the association between transportation noise and stroke incidence in a large Scandinavian population. METHODS: We harmonized and pooled data from nine Scandinavian cohorts (seven Swedish, two Danish), totaling 135,951 participants. We identified residential address history and estimated road, railway, and aircraft noise for all addresses. Information on stroke incidence was acquired through linkage to national patient and mortality registries. We analyzed data using Cox proportional hazards models, including socioeconomic and lifestyle confounders, and air pollution. RESULTS: During follow-up (median = 19.5 y), 11,056 stroke cases were identified. Road traffic noise (Lden) was associated with risk of stroke, with a hazard ratio (HR) of 1.06 [95% confidence interval (CI): 1.03, 1.08] per 10-dB higher 5-y mean time-weighted exposure in analyses adjusted for individual- and area-level socioeconomic covariates. The association was approximately linear and persisted after adjustment for air pollution [particulate matter (PM) with an aerodynamic diameter of <= 2.5 mu m (PM2.5) and NO2]. Stroke was associated with moderate levels of 5-y aircraft noise exposure (40-50 vs. <= 40 dB) (HR = 1.12; 95% CI: 0.99, 1.27), but not with higher exposure (>= 50 dB, HR = 0.94; 95% CI: 0.79, 1.11). Railway noise was not associated with stroke. DISCUSSION: In this pooled study, road traffic noise was associated with a higher risk of stroke. This finding supports road traffic noise as an important cardiovascular risk factor that should be included when estimating the burden of disease due to traffic noise.
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| 12. |
- Travassos, M., et al.
(författare)
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Does Caffeine Consumption Modify Cerebrospinal Fluid Amyloid-beta Levels in Patients with Alzheimer's Disease?
- 2015
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 47:4, s. 1069-1078
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Tidskriftsartikel (refereegranskat)abstract
- Caffeine may be protective against Alzheimer's disease (AD) by modulating amyloid-beta (A beta) metabolic pathways. The present work aimed to study a possible association of caffeine consumption with the cerebrospinal fluid (CSF) biomarkers, particularly A beta. The study included 88 patients with AD or mild cognitive impairment. The consumption of caffeine and theobromine was evaluated using a validated food questionnaire. Quantification of caffeine and main active metabolites was performed with liquid chromatography coupled to tandem mass spectrometry. The levels of A beta(1-42), total tau, and phosphorylated tau in the CSF were determined using sandwich ELISA methods and other A beta species, A beta(X-38), A beta(X-40), and A beta(X-42), with the MSD A beta Triplex assay. The concentration of caffeine was 0.79 +/- 1.15 mu g/mL in the CSF and 1.20 +/- 1.88 mu g/mL in the plasma. No correlation was found between caffeine consumption and A beta(42) in the CSF. However, a significant positive correlation was found between the concentrations of theobromine, both in the CSF and in the plasma, with A beta(42) in the CSF. Theobromine in the CSF was positively correlated with the levels of other xanthines in the CSF, but not in the plasma, suggesting that it may be formed by central metabolic pathways. In conclusion, caffeine consumption does not modify the levels of CSF biomarkers, and does not require to be controlled for when measuring CSF biomarkers in a clinical setting. Since theobromine is associated with a favorable A beta profile in the CSF, the possibility that it might have a protective role in AD should be further investigated.
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| 13. |
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| 14. |
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| 15. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
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Ingår i: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
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Forskningsöversikt (refereegranskat)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.
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| 16. |
- Schmidt, Amand F., et al.
(författare)
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PCSK9 genetic variants and risk of type 2 diabetes : a mendelian randomisation study
- 2017
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Ingår i: The Lancet Diabetes and Endocrinology. - : ELSEVIER SCIENCE INC. - 2213-8587 .- 2213-8595. ; 5:2, s. 97-105
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Tidskriftsartikel (refereegranskat)abstract
- Background Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way off sets their substantial benefi ts. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely eff ects of PCSK9 inhibitors on diabetes risk. Methods In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA 1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. Findings Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0.09 mmol/L, 95% CI 0.02 to 0.15), bodyweight (1.03 kg, 0.24 to 1.82), waist-to-hip ratio (0.006, 0.003 to 0.010), and an odds ratio for type diabetes of 1.29 (1.11 to 1.50). Based on the collected data, we did not identify associations with HbA 1c (0.03%, -0.01 to 0.08), fasting insulin (0.00%, -0.06 to 0.07), and BMI (0.11 kg/m(2), -0.09 to 0.30). Interpretation PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefi ts of PCSK9 inhibitor treatment, as was previously done for statins.
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| 17. |
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| 18. |
- Simonsen, Björg O., et al.
(författare)
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Medication knowledge, certainty, and risk of errors in health care: : a cross- sectional study
- 2011
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Ingår i: BMC Health Services Research. - : BioMed Central. - 1472-6963. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Medication errors are often involved in reported adverse events. Drug therapy, prescribed by physicians, is mostly carried out by nurses, who are expected to master all aspects of medication. Research has revealed the need for improved knowledge in drug dose calculation, and medication knowledge as a whole is poorly investigated. The purpose of this survey was to study registered nurses' medication knowledge, certainty and estimated risk of errors, and to explore factors associated with good results. Methods: Nurses from hospitals and primary health care establishments were invited to carry out a multiple-choice test in pharmacology, drug management and drug dose calculations (score range 0-14). Self-estimated certainty in each answer was recorded, graded from 0 = very uncertain to 3 = very certain. Background characteristics and sense of coping were recorded. Risk of error was estimated by combining knowledge and certainty scores. The results are presented as mean (+/- SD). Results: Two-hundred and three registered nurses participated (including 16 males), aged 42.0 (9.3) years with a working experience of 12.4 (9.2) years. Knowledge scores in pharmacology, drug management and drug dose calculations were 10.3 (1.6), 7.5 (1.6), and 11.2 (2.0), respectively, and certainty scores were 1.8 (0.4), 1.9 (0.5), and 2.0 (0.6), respectively. Fifteen percent of the total answers showed a high risk of error, with 25% in drug management. Independent factors associated with high medication knowledge were working in hospitals (p < 0.001), postgraduate specialization (p = 0.01) and completion of courses in drug management (p < 0.01). Conclusions: Medication knowledge was found to be unsatisfactory among practicing nurses, with a significant risk for medication errors. The study revealed a need to improve the nurses' basic knowledge, especially when referring to drug management.
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| 19. |
- Soares, C. G, et al.
(författare)
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Damage Assessment After Accidental Events : Report of Committee V.1
- 2009. - 1
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Ingår i: Proceedings of the 17<sup>th</sup> International Ship and Offshore Structures Congress. - Seoul, Korea : Seoul National University. ; , s. 1-72
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This paper contains the report of the Committee, which is a new one that was created todeal with the methods to assess damage and residual strength after accidental events.The name of the committee, being a short one may give a wrong impression about itsscope as it mentions damage assessment while the mandate refers that there should beconcern for the extent of damage and local and global residual strength of shipstructures, after accidental events. Therefore the contents of the report deal also withmethods to determine local and global residual strength, including the specification ofthe appropriate loads.It starts by providing a description of the type of damages that can be found in thevarious accidental events. Representative scenarios are described and the typicaldamages that results from the specific accidents are indicated. Next section describeshow in real situations the damaged state is perceived. Thus, inspection methods aredescribed as well as the available approaches to derive information about the status ofthe structure from indirect measurements.Loads on the structure are treated afterwards, including the loads that are generatedduring the accidental situation itself and also after the accident when the ship is indamaged state, often listed and with non symmetric sections. The loads are used todetermine ship strength using the assessment methods described in section 5, whichdeals with various types of components.If the ship is considered not having enough strength for temporary voyage to repairyard local repairs are necessary. Otherwise she will travel to a repair shipyard and berepaired there. The various types of problems raised in repair are dealt with in thefollowing section.Finally last section deals with salvage and recovery strategies which are necessary inthe cases of very large damage in ships.
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| 20. |
- Steentoft, A., et al.
(författare)
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Fatal poisoning in drug addicts in the Nordic countries
- 2001
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Ingår i: Forensic Science International. - 0379-0738 .- 1872-6283. ; 123:1, s. 63-69
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Tidskriftsartikel (refereegranskat)abstract
- The study includes medicolegally examined fatal poisonings among drug addicts in 1997 in the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden, and the results are compared to a similar investigation from 1991. A common definition of "drug addict" was applied by the participating countries. The highest death rate by poisoning in drug addicts was observed in Denmark, where it was 6.54 per 105 inhabitants, followed by Norway with 6.35, Sweden with 2.21, Finland with 1.63 and Iceland with 1.20 per 105 inhabitants. All countries showed a higher death rate in 1997 than in 1991. For all countries the distribution of deaths according to geographical regions showed a decreasing number of drug deaths in the metropolitan area and an increasing number in other cities. Heroin/morphine dominated as the cause of death and was responsible for about 90% of the cases in Norway. In Sweden and Denmark, however, heroin/morphine caused only about 70% of the fatal poisonings. About 30% of the fatal poisonings in Denmark and Sweden were caused by other group I drugs, in Denmark mainly methadone and in Sweden mainly propoxyphene. Apart from two cases in Sweden methadone deaths were not seen in the other Nordic countries. In Finland heroin/morphine deaths have increased from about 10% in 1991 to about 40% in 1997. Forty-four percent of the fatal poisonings in Finland were caused by other group I drugs, mainly codeine and propoxyphene. The two fatal poisonings in Iceland were caused by carbon monoxide. Only few deaths in this investigation were caused by amphetamine and cocaine. A widespread use of alcohol, cannabis and benzodiazepines, especially diazepam, was seen in all the countries. © 2001 Elsevier Science Ireland Ltd. All rights reserved.
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| 21. |
- Travassos, Maria, et al.
(författare)
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Does Caffeine Consumption Modify Cerebrospinal Fluid Amyloid-β Levels in Patients with Alzheimer's Disease?
- 2015
-
Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 47:4, s. 1069-78
-
Tidskriftsartikel (refereegranskat)abstract
- Caffeine may be protective against Alzheimer's disease (AD) by modulating amyloid-β (Aβ) metabolic pathways. The present work aimed to study a possible association of caffeine consumption with the cerebrospinal fluid (CSF) biomarkers, particularly Aβ. The study included 88 patients with AD or mild cognitive impairment. The consumption of caffeine and theobromine was evaluated using a validated food questionnaire. Quantification of caffeine and main active metabolites was performed with liquid chromatography coupled to tandem mass spectrometry. The levels of A(1-42), total tau, and phosphorylated tau in the CSF were determined using sandwich ELISA methods and other Aβ species, Aβ(X-38), Aβ(X-40), and Aβ(X-42), with the MSD Aβ Triplex assay. The concentration of caffeine was 0.79±1.15 μg/mL in the CSF and 1.20±1.88 μg/mL in the plasma. No correlation was found between caffeine consumption and Aβ42 in the CSF. However, a significant positive correlation was found between the concentrations of theobromine, both in the CSF and in the plasma, with Aβ42 in the CSF. Theobromine in the CSF was positively correlated with the levels of other xanthines in the CSF, but not in the plasma, suggesting that it may be formed by central metabolic pathways. In conclusion, caffeine consumption does not modify the levels of CSF biomarkers, and does not require to be controlled for when measuring CSF biomarkers in a clinical setting. Since theobromine is associated with a favorable Aβ profile in the CSF, the possibility that it might have a protective role in AD should be further investigated.
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| 22. |
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| 23. |
- Aman, Y, et al.
(författare)
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Autophagy in healthy aging and disease
- 2021
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Ingår i: Nature aging. - : Springer Science and Business Media LLC. - 2662-8465. ; 1:8, s. 634-650
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Tidskriftsartikel (refereegranskat)
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| 24. |
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| 25. |
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| 26. |
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| 27. |
- Davies, SJ, et al.
(författare)
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Icodextrin improves the fluid status of peritoneal dialysis patients: Results of a double-blind randomized controlled trial
- 2003
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673. ; 14:9, s. 2338-2344
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Tidskriftsartikel (refereegranskat)abstract
- Worsening fluid balance results in reduced technique and patient survival in peritoneal dialysis. Under these conditions, the glucose polymer icodextrin is known to enhance ultrafiltration in the long dwell. A multicenter, randomized, double-blind, controlled trial was undertaken to compare icodextrin versus 2.27% glucose to establish whether icodextrin improves fluid status. Fifty patients with urine output <750 ml/d, high solute transport, and either treated hypertension or untreated BP >140/90 mmHg, or a requirement for the equivalent of all 2.27% glucose exchanges, were randomized 1: 1 and evaluated at 1, 3, and 6 mo. Members of the icodextrin group lost weight, whereas the control group gained weight. Similar differences in total body water were observed, largely explained by reduced extracellular fluid volume in those receiving icodextrin, who also achieved better ultrafiltration and total sodium losses at 3 mo (P < 0.05) and had better maintenance of urine volume at 6 mo (P = 0.039). In patients fulfilling the study's inclusion criteria, the use of icodextrin, when compared with 2.27% glucose, in the long exchange improves fluid removal and status in peritoneal dialysis. This effect is apparent within I mo of commencement and was sustained for 6 mo without harmful effects on residual renal function.
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| 28. |
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| 29. |
- Giovannucci, Tatiana A., et al.
(författare)
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Identification of a novel compound that simultaneously impairs the ubiquitin-proteasome system and autophagy
- 2022
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Ingår i: Autophagy. - : Taylor & Francis. - 1554-8627 .- 1554-8635. ; 18:7, s. 1486-1502
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Tidskriftsartikel (refereegranskat)abstract
- The ubiquitin-proteasome system (UPS) and macroautophagy/autophagy are the main proteolytic systems in eukaryotic cells for preserving protein homeostasis, i.e., proteostasis. By facilitating the timely destruction of aberrant proteins, these complementary pathways keep the intracellular environment free of inherently toxic protein aggregates. Chemical interference with the UPS or autophagy has emerged as a viable strategy for therapeutically targeting malignant cells which, owing to their hyperactive state, heavily rely on the sanitizing activity of these proteolytic systems. Here, we report on the discovery of CBK79, a novel compound that impairs both protein degradation by the UPS and autophagy. While CBK79 was identified in a high-content screen for drug-like molecules that inhibit the UPS, subsequent analysis revealed that this compound also compromises autophagic degradation of long-lived proteins. We show that CBK79 induces non-canonical lipidation of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 beta) that requires ATG16L1 but is independent of the ULK1 (unc-51 like autophagy activating kinase 1) and class III phosphatidylinositol 3-kinase (PtdIns3K) complexes. Thermal preconditioning of cells prevented CBK79-induced UPS impairment but failed to restore autophagy, indicating that activation of stress responses does not allow cells to bypass the inhibitory effect of CBK79 on autophagy. The identification of a small molecule that simultaneously impairs the two main proteolytic systems for protein quality control provides a starting point for the development of a novel class of proteostasis-targeting drugs.
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| 30. |
- Gleerup, H. S., et al.
(författare)
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Saliva Neurofilament Light Chain Is Not a Diagnostic Biomarker for Neurodegeneration in a Mixed Memory Clinic Population
- 2021
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Neurodegeneration and axonal injury result in an increasing release of neurofilament light chain (NfL) into bodily fluids, including cerebrospinal fluid (CSF) and blood. Numerous studies have shown that NfL levels in CSF and blood are increased in neurodegenerative disorders and monitor neurodegeneration. Saliva is an easily accessible biofluid that could be utilized as a biofluid measurement of Alzheimer's disease (AD) biomarkers. In this study, for the first time, salivary NfL was measured and compared to plasma NfL in a consecutive cohort of patients referred to cognitive assessments. In two mixed memory clinic cohorts, saliva samples were taken from 152 patients, AD (n = 49), mild cognitive impairment (MCI) (n = 47), non-AD (n = 56), and also 17 healthy controls. In addition, 135 also had a matching plasma sample. All saliva and plasma samples were analyzed for NfL, and the association between saliva and plasma NfL and CSF levels of total tau (t-tau), phosphorylated tau (p-tau), and beta amyloid 1-42 (A beta 42) were investigated. In total, 162/169 had quantifiable levels of salivary NfL by single molecule array (Simoa). No statistically significant differences were found in salivary NfL concentration across the diagnostic groups, but as expected, significant increases were found for plasma NfL in dementia cases (P < 0.0001). There was no association between saliva and plasma NfL levels. Furthermore, saliva NfL did not correlate with CSF A beta 42, p-tau, or tau concentrations. In conclusion, NfL is detectable in saliva but does not reflect neurodegeneration in the brain.
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| 31. |
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| 32. |
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| 33. |
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| 34. |
- Hansen, Nicolai S.B., et al.
(författare)
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Development and mechanistic investigation of the dehydrogenation of alcohols with an iron(iii) salen catalyst
- 2023
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Ingår i: Organic and biomolecular chemistry. - : Royal Society of Chemistry (RSC). - 1477-0520 .- 1477-0539. ; 21:23, s. 4794-4800
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Tidskriftsartikel (refereegranskat)abstract
- The iron(iii) salen complex (R,R)-N,N′-bis(salicylidene)-1,2-cyclohexanediamineiron(iii) chloride has been developed as a catalyst for the acceptorless dehydrogenation of alcohols. The complex catalyzes the direct synthesis of imines in good yields from different primary alcohols and amines with the liberation of hydrogen gas. The mechanism has been investigated experimentally with labelled substrates and theoretically with density functional theory calculations. In contrast to the corresponding manganese(iii) salen-catalyzed dehydrogenation, it has not been possible to identify a homogeneous catalytic pathway with the iron complex. Instead, poisoning experiments with trimethylphosphine and mercury indicated that the catalytically active species are heterogeneous small iron particles.
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| 35. |
- Herukka, Sanna-Kaisa, et al.
(författare)
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Recommendations for cerebrospinal fluid Alzheimer's disease biomarkers in the diagnostic evaluation of mild cognitive impairment.
- 2017
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 13:3, s. 285-295
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Tidskriftsartikel (refereegranskat)abstract
- This article presents recommendations, based on the Grading of Recommendations, Assessment, Development, and Evaluation method, for the clinical application of cerebrospinal fluid (CSF) amyloid-β1-42, tau, and phosphorylated tau in the diagnostic evaluation of patients with mild cognitive impairment (MCI). The recommendations were developed by a multidisciplinary working group and based on the available evidence and consensus from focused group discussions for 1) prediction of clinical progression to Alzheimer's disease (AD) dementia, 2) cost-effectiveness, 3) interpretation of results, and 4) patient counseling. The working group recommended using CSF AD biomarkers in the diagnostic workup of MCI patients, after prebiomarker counseling, as an add-on to clinical evaluation to predict functional decline or conversion to AD dementia and to guide disease management. Because of insufficient evidence, it was uncertain whether CSF AD biomarkers outperform imaging biomarkers. Furthermore, the working group provided recommendations for interpretation of ambiguous CSF biomarker results and for pre- and post-biomarker counseling.
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| 36. |
- Holm, A. M., et al.
(författare)
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Lung transplantation for bronchiolitis obliterans syndrome after allo-SCT
- 2013
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 48:5, s. 703-707
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Tidskriftsartikel (refereegranskat)abstract
- Chronic GVHD (cGVHD) associated bronchiolitis obliterans syndrome (BOS) is a serious complication after allo-SCT, and lung transplantation (LTx) may be the ultimate treatment option. To evaluate this treatment, data on all patients with LTx after allo-SCT ever performed in Sweden, Norway, Denmark and Finland were recorded and compared with survival data from the Scandiatransplant registry. In total, LTx after allo-SCT had been performed in 13 patients. Allo-SCT was done because of AML (n = 6), CML (n = 3), ALL (n = 2), immunodeficiency (n = 1) and aplastic anemia (n = 1). All developed clinical cGVHD, with median interval from allo-SCT to LTx of 8.2 (0.7-16) years. Median age at LTx was 34 (16-55) years, and the median postoperative observation time was 4.2 (0.1-15) years. Two patients died, one due to septicemia, the other of relapsing leukemia, after 2 and 14 months, respectively. Four developed BOS, one of these was retransplanted. The survival did not significantly differ from the survival in matched LTx controls, being 90% 1 year and 75% 5 years after LTx compared with 85% and 68% in the controls. We therefore suggest that LTx may be considered in carefully selected patients with BOS due to cGVHD after allo-SCT.
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| 37. |
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| 38. |
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| 39. |
- Jensen, C. S., et al.
(författare)
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Effect of physical exercise on markers of neuronal dysfunction in cerebrospinal fluid in patients with Alzheimer's disease
- 2017
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Ingår i: Alzheimer's and Dementia: Translational Research and Clinical Interventions. - : Wiley. - 2352-8737. ; 3:2, s. 284-290
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Physical exercise has gained increasing focus as a potential mean to maintain cognitive function in patients with Alzheimer's disease (AD). Alongside the markers of specific AD pathology (amyloid β and tau), other pathologies such as neuronal damage and synaptic loss have been proposed as markers of the disease. Here, we study the effect of physical exercise on biomarkers of neuronal and synaptic integrity. Methods Cerebrospinal fluid (CSF) from 51 AD subjects who participated in the randomized controlled trial Preserving Cognition, Quality of Life, Physical Health and Functional Ability in Alzheimer's Disease: The Effect of Physical Exercise (ADEX) was analyzed for the concentration of neurofilament light (NFL), neurogranin (Ng), visinin-like protein-1 (VILIP-1), and chitinase-3–like protein 1 (YKL-40). Participants were subjected to either 16weeks of moderate- to high-intensity exercise (n=25) or treatment as usual (control group, n=26), and CSF was collected before and after intervention. Results No significant differences in CSF concentrations of VILIP-1, YKL-40, NFL, and Ng were observed when comparing mean change from baseline between the exercise and control groups. Similarly, when classifying subjects based on their exercise levels, no significant changes were observed for the biomarkers in the control group compared with the high-exercise group (attending 80% of the exercise sessions with an intensity of 70% of maximum heart rate or above). Discussion These results are not supportive of a modulatory effect of physical exercise on the selected biomarkers of neuronal and synaptic integrity in patients with AD. © 2017 The Authors
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| 40. |
- Jensen, C. S., et al.
(författare)
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Exercise as a potential modulator of inflammation in patients with Alzheimer's disease measured in cerebrospinal fluid and plasma
- 2019
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Ingår i: Experimental Gerontology. - : Elsevier BV. - 0531-5565. ; 121, s. 91-98
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neuroinflammation is recognized as part of the pathological progression of Alzheimer's disease (AD), but the molecular mechanisms are still not entirely clear. Systemically, physical exercise has shown to have a positive modulating effect on markers of inflammation. It is not known if this general effect also takes place in the central nervous system in AD. The aim of this study was to investigate the effect of 16 weeks of moderate to high-intensity physical exercise on selected biomarkers of inflammation both systemically and in the CNS, in patients with AD. Methods: Plasma and cerebrospinal fluid (CSF) from 198 patients with Alzheimer's disease participating in the Preserving Cognition, Quality of Life, Physical Health and Functional Ability in Alzheimer's Disease: The Effect of Physical Exercise (ADEX) study were analyzed for concentrations of 8‑isoprostane, soluble trigger receptor expressed on myeloid cells 2 (sTREM2), and the MSD v-plex proinflammation panel 1 human containing interferon gamma (IFNγ), Interleukin-10 (IL10), IL12p70, IL13, IL1β, IL2, IL4, IL6, IL8, and tumor necrosis factor alpha (TNFα), before and after a 16-week intervention with physical exercise, and we studied whether changes were modulated by the patients' APOE genotype. Results: Most inflammatory markers remained unchanged after exercise. We found an increasing effect of 16 weeks of physical exercise on sTREM2 measured in CSF. Further, IL6 in plasma increased in the exercise group after physical exercise (mean relative change 41.03, SD 76.7), compared to controls (−0.97, SD 49.4). In a sub-analysis according to APOE genotype, we found that in ε4 carriers, exercise had a stabilizing effect on IFNγ concentration with a mean relative change of 7.84 (SD 42.6), as compared to controls (114.7 (SD 188.3), p = 0.038. Conclusion: Our findings indicate an effect of physical exercise on markers of neuroinflammation in CSF measured by an increase in sTREM2 in patients with AD. Further, there may be a small inflammatory systemic effect related to physical exercise in patients with AD. © 2019 The Authors
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| 41. |
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| 42. |
- Järnum, Hanna, et al.
(författare)
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Longitudinal MRI study of cortical thickness, perfusion, and metabolite levels in major depressive disorder
- 2011
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Ingår i: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 124:6, s. 435-446
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine whether patients with major depressive disorder (MDD) display morphologic, functional, and metabolic brain abnormalities in limbic-cortical regions at a baseline magnetic resonance (MR) scan and whether these changes are normalized in MDD patients in remission at a follow-up scan. Method: A longitudinal 3.0-Tesla (T) magnetic resonance imaging (MRI) study was carried out with cortical thickness measurements with a surface-based approach, perfusion measurements with three-dimensional (3D) pseudo-continuous arterial spin labeling (pCASL), and spectroscopy (1H-MRS) measurements in the anterior cingulate cortex (ACC) with water as an internal reference adjusted for cerebrospinal fluid content. We examined 23 MDD patients and 26 healthy controls. MDD patients underwent a baseline MRI at inclusion and were invited to a follow-up scan when they were in remission or after a 6-month follow-up period. Results: Major findings were a significantly thinner posterior cingulate cortex in non-remitters than in remitters, a significant decrease in perfusion in the frontal lobes and the ACC in non-remitters compared with healthy controls at baseline and significantly reduced N-acetylaspartate, myo-inositol, and glutamate levels in MDD patients compared with healthy controls at baseline. Conclusion: Using novel MRI techniques, we have found abnormalities in cerebral regions related to cortical-limbic pathways in MDD patients.
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| 43. |
- Järnum, Hanna, et al.
(författare)
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Perfusion MRI of brain tumours : a comparative study of pseudo-continuous arterial spin labelling and dynamic susceptibility contrast imaging
- 2010
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Ingår i: Neuroradiology. - : Springer Science and Business Media LLC. - 0028-3940 .- 1432-1920. ; 52:4, s. 307-317
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The purpose of this study was to compare the non-invasive 3D pseudo-continuous arterial spin labelling (PC ASL) technique with the clinically established dynamic susceptibility contrast perfusion magnetic resonance imaging (DSC-MRI) for evaluation of brain tumours. METHODS: A prospective study of 28 patients with contrast-enhancing brain tumours was performed at 3 T using DSC-MRI and PC ASL with whole-brain coverage. The visual qualitative evaluation of signal enhancement in tumour was scored from 0 to 3 (0 = no signal enhancement compared with white matter, 3 = pronounced signal enhancement with equal or higher signal intensity than in grey matter/basal ganglia). The extent of susceptibility artefacts in the tumour was scored from 0 to 2 (0 = no susceptibility artefacts and 2 = extensive susceptibility artefacts (maximum diameter > 2 cm)). A quantitative analysis was performed with normalised tumour blood flow values (ASL nTBF, DSC nTBF): mean value for region of interest (ROI) in an area with maximum signal enhancement/the mean value for ROIs in cerebellum. RESULTS: There was no difference in total visual score for signal enhancement between PC ASL and DSC relative cerebral blood flow (p = 0.12). ASL had a lower susceptibility-artefact score than DSC-MRI (p = 0.03). There was good correlation between DSC nTBF and ASL nTBF values with a correlation coefficient of 0.82. CONCLUSION: PC ASL is an alternative to DSC-MRI for the evaluation of perfusion in brain tumours. The method has fewer susceptibility artefacts than DSC-MRI and can be used in patients with renal failure because no contrast injection is needed.
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| 44. |
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| 45. |
- Knorr, U., et al.
(författare)
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Biomarkers in cerebrospinal fluid of patients with bipolar disorder versus healthy individuals: A systematic review
- 2018
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Ingår i: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X. ; 28:7, s. 783-794
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Tidskriftsartikel (refereegranskat)abstract
- Background: The pathophysiological processes of bipolar disorder (BD) may be detectable by the use of cerebrospinal fluid (CSF) biomarkers. Aim: We aimed for the first time to review studies of CSF biomarkers in patients with BD compared to healthy control individuals (HC). We investigated the effect of diagnosis, age, gender, clinical state, medication, technical characteristics of tests, fasting state and, cognitive function if applicable. Method: We did a systematic review according to the PRISMA Statement based on comprehensive database searches for studies on cerebrospinal biomarkers in patients with bipolar disorder versus HC. Risk of bias was systematically assessed. Results: The search strategy identified 410 studies of which thirty-four fulfilled the inclusion criteria. A total of 117 unique biomarkers were investigated, out of which 11 were evaluated in more than one study. Forty biomarkers showed statistically significant differences between BD and HC in single studies. Only the findings of elevated homovanillic acid and 5-hydroxyindoleacetic acid were replicated across studies. Most studies had a cross sectional design and were influenced by risk of bias mainly due to small sample size, lack of data on mood state at the time of the CSF puncture and not considering potential confounders including age, gender, diagnoses, BMI, life style factors such as smoking, and psychotropic medication. Conclusion: Specific monoamine CSF biomarkers may be related to the pathophysiology of BD. Future studies must aim at increasing the level of evidence by validating the positive findings in prospective studies with stringent methodology. (C) 2018 Elsevier B.V. and ECNP. All rights reserved.
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| 46. |
- Manniche, C., et al.
(författare)
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Cerebrospinal Fluid Biomarkers to Differentiate Idiopathic Normal Pressure Hydrocephalus from Subcortical Ischemic Vascular Disease
- 2020
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 75:3, s. 937-947
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Tidskriftsartikel (refereegranskat)abstract
- Background: Idiopathic normal pressure hydrocephalus (iNPH) remains a challenge to differentiate from subcortical ischemic vascular disease (SIVD). Despite major research efforts, the cerebrospinal fluid (CSF) biomarker profiles of the two diseases are still not known in detail. Objective: To determine if novel CSF biomarkers, neurofilament light (NFL) reflecting axonal damage, the synaptic protein neurogranin (NG), and the astroglial marker chitinase-3-like protein 1 (YKL-40), and the core Alzheimer's disease (AD) biomarkers, amyloid-beta 42 (A beta(42)), total tau (t-tau), phosphorylated tau (p-tau), can differentiate iNPH from SIVD. Patients with AD and healthy controls (HC) were included for comparison purposes. Methods: Patients with iNPH (n = 28), SIVD (n = 30), AD (n = 57), and HC (n = 33) were retrospectively included from the Danish Dementia Biobank. All patients with iNPH had effect of shunt surgery with a follow-up period of 4 to 69 months. CSF biomarkers were measured using immunoassays. Results: Lower levels of NFL, NG, A beta(42), and t-tau were found in patients with iNPH versus SIVD, while YKL-40 and p-tau were similar in the two diseases. NFL and A beta(42) were the most reliable biomarkers to differentiate iNPH from SIVD with an area under the curve (AUC) on 0.82 and 0.80, respectively. Combining NFL with A beta(42), t-tau, and p-tau resulted in an AUC of 0.90, which was equivalent to the diagnostic accuracy of all six biomarkers combined. Conclusion: An addition of NFL to the CSF panel of A beta(42), t-tau, and p-tau may improve the differentiation of iNPH from SIVD.
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| 47. |
- Messias, M. J, et al.
(författare)
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The Greenland Sea tracer experiment 1996–2002: Horizontal mixing and transport of Greenland Sea Intermediate Water
- 2008
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Ingår i: Progress In Oceanography. - : Elsevier BV. - 0079-6611. ; 78:1, s. 85-105
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Tidskriftsartikel (refereegranskat)abstract
- In summer 1996, a tracer release experiment using sulphur hexafluoride (SF6) was launched in the intermediate-depth waters of the central Greenland Sea (GS), to study the mixing and ventilation processes in the region and its role in the northern limb of the Atlantic overturning circulation. Here we describe the hydrographic context of the experiment, the methods adopted and the results from the monitoring of the horizontal tracer spread for the 1996–2002 period documented by 10 shipboard surveys. The tracer marked “Greenland Sea Arctic Intermediate Water” (GSAIW). This was redistributed in the gyre by variable winter convection penetrating only to mid-depths, reaching at most 1800 m depth during the strongest event observed in 2002. For the first 18 months, the tracer remained mainly in the Greenland Sea. Vigorous horizontal mixing within the Greenland Sea gyre and a tight circulation of the gyre interacting slowly with the other basins under strong topographic influences were identified. We use the tracer distributions to derive the horizontal shear at the scale of the Greenland Sea gyre, and rates of horizontal mixing at 10 and 300 km scales. Mixing rates at small scale are high, several times those observed at comparable depths at lower latitudes. Horizontal stirring at the sub-gyre scale is mediated by numerous and vigorous eddies. Evidence obtained during the tracer release suggests that these play an important role in mixing water masses to form the intermediate waters of the central Greenland Sea. By year two, the tracer had entered the surrounding current systems at intermediate depths and small concentrations were in proximity to the overflows into the North Atlantic. After 3 years, the tracer had spread over the Nordic Seas basins. Finally by year six, an intensive large survey provided an overall synoptic documentation of the spreading of the tagged GSAIW in the Nordic Seas. A circulation scheme of the tagged water originating from the centre of the GS is deduced from the horizontal spread of the tracer. We present this circulation and evaluate the transport budgets of the tracer between the GS and the surroundings basins. The overall residence time for the tagged GSAIW in the Greenland Sea was about 2.5 years. We infer an export of intermediate water of GSAIW from the GS of 1 to 1.85 Sv (1 Sv = 106 m3 s−1) for the period from September 1998 to June 2002 based on the evolution of the amount of tracer leaving the GS gyre. There is strong exchange between the Greenland Sea and Arctic Ocean via Fram Strait, but the contribution of the Greenland Sea to the Denmark Strait and Iceland Scotland overflows is modest, probably not exceeding 6% during the period under study.
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| 48. |
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| 49. |
- Roos, P., et al.
(författare)
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Inflammatory markers of CHMP2B-mediated frontotemporal dementia
- 2018
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Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728. ; 324, s. 136-142
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Tidskriftsartikel (refereegranskat)abstract
- Histopathological studies and animal models have suggested an inflammatory component in the patho-mechanism of the CHMP2B associated frontotemporal dementia (FTD-3). In this cross-sectional study, serum and cerebrospinal fluid were analyzed for inflammatory markers in CHMP2B mutation carriers. Serum levels of CCL4 were increased throughout life. Serum levels of IL-15, CXCL10, CCL22 and TNF-alpha were significantly associated with cognitive decline, suggesting a peripheral inflammatory response to neurodegeneration. CSF levels of sTREM2 appeared to increase more rapidly with age in CHMP2B mutation carriers. The identification of a peripheral inflammatory response to disease progression supports the involvement of an inflammatory component in FTD-3.
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| 50. |
- Rostgaard, N., et al.
(författare)
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Differential proteomic profile of lumbar and ventricular cerebrospinal fluid
- 2023
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Ingår i: Fluids and Barriers of the Cns. - : Springer Science and Business Media LLC. - 2045-8118. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPathological cerebral conditions may manifest in altered composition of the cerebrospinal fluid (CSF). Although diagnostic CSF analysis seeks to establish pathological disturbances in the brain proper, CSF is generally sampled from the lumbar compartment for reasons of technical ease and ethical considerations. We here aimed to compare the molecular composition of CSF obtained from the ventricular versus the lumbar CSF compartments to establish a relevance for employing lumbar CSF as a proxy for the CSF bathing the brain tissue.MethodsCSF was collected from 46 patients with idiopathic normal pressure hydrocephalus (iNPH) patients during their diagnostic workup (lumbar samples) and in connection with their subsequent CSF diversion shunt surgery (ventricular samples). The mass-spectrometry-based proteomic profile was determined in these samples and in addition, selected biomarkers were quantified with ELISA (S100B, neurofilament light (NfL), amyloid-beta (A beta(40), A beta(42)), and total tau (T-tau) and phosphorylated tau (P-tau) forms). The latter analysis was extended to include paired porcine samples obtained from the lumbar compartment and the cerebromedullary cistern closely related to the ventricles.ResultsIn total 1231 proteins were detected in the human CSF. Of these, 216 distributed equally in the two CSF compartments, whereas 22 were preferentially (or solely) present in the ventricular CSF and four in the lumbar CSF. The selected biomarkers of neurodegeneration and Alzheimer's disease displayed differential distribution, some with higher (S100B, T-tau, and P-tau) and some with lower (NfL, A beta(40), A beta(42)) levels in the ventricular compartment. In the porcine samples, all biomarkers were most abundant in the lumbar CSF.ConclusionsThe overall proteomic profile differs between the ventricular and the lumbar CSF compartments, and so does the distribution of clinically employed biomarkers. However, for a range of CSF proteins and biomarkers, one can reliably employ lumbar CSF as a proxy for ventricular CSF if or a lumbar/cranial index for the particular molecule has been established. It is therefore important to verify the compartmental preference of the proteins or biomarkers of interest prior to extrapolating from lumbar CSF to that of the ventricular fluid bordering the brain.
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