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- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)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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- Birney, Ewan, et al.
(author)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Journal article (peer-reviewed)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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8. |
- Wang, Li-San, et al.
(author)
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Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
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In: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
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Journal article (peer-reviewed)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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10. |
- Matilla-Santander, N., et al.
(author)
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COVID-19 and Precarious Employment : Consequences of the Evolving Crisis
- 2021
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In: International Journal of Health Services. - : Sage Publications. - 0020-7314 .- 1541-4469. ; 5:2, s. 226-228
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Journal article (peer-reviewed)abstract
- The world of work is facing an ongoing pandemic and an economic downturn with severe effects worldwide. Workers trapped in precarious employment (PE), both formal and informal, are among those most affected by the COVID-19 pandemic. Here we call attention to at least 5 critical ways that the consequences of the crisis among workers in PE will be felt globally: (a) PE will increase, (b) workers in PE will become more precarious, (c) workers in PE will face unemployment without being officially laid off, (d) workers in PE will be exposed to serious stressors and dramatic life changes that may lead to a rise in diseases of despair, and (e) PE might be a factor in deterring the control of or in generating new COVID-19 outbreaks. We conclude that what we really need is a new social contract, where the work of all workers is recognized and protected with adequate job contracts, employment security, and social protection in a new economy, both during and after the COVID-19 crisis.
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12. |
- Gunn, V., et al.
(author)
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Labour market strategies addressing precarious employment and its impacts : A systematic review
- 2022
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In: European Journal of Public Health. - : Oxford University Press. - 1101-1262 .- 1464-360X. ; 32:Supplement_3, s. iii43-iii44
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Journal article (other academic/artistic)abstract
- BackgroundPrecarious employment (PE), characterized by reduced worker rights, and employment and income insecurity, has complex public health implications including negative impacts on workers’ mental and physical health, occupational health and safety, wellbeing, and inequities in access to health and social protections. There is, however, a knowledge gap regarding effectiveness of interventions. We describe findings from a review of evaluated interventions with potential to address PE.MethodsOur systematic review followed the 2020 PRISMA framework and covered PubMed, Scopus, Web of Science, and sources of grey literature. We included qualitative, quantitative, or mixed-methods studies evaluating initiatives to reduce workers’ PE published from 2000 to 2021 and focused on adult workers.ResultsThe 23 eligible studies from across the world evaluated diverse strategies addressing PE including tax and trade reforms, industrial disputes legislation, business registration, and use of incentives to stimulate permanent contracts. Also included were union strategies to reach precarious workers, the provision of social benefits, and youth apprenticeships. Generally, while most initiatives had the potential to tackle certain PE aspects, they usually acted only on one or two PE dimensions. Additionally, the evaluation components were missing key details, thus, limiting the generalizability of findings, as did the heterogeneity of study designs, initiative purposes, economic and political context, and diverse populations targeted.ConclusionsThe increase in PE prevalence and its complex health implications requires sustainable upstream public health solutions. Multidisciplinary collaborations among public health and occupational health practitioners along with researchers, evaluation specialists, economists, and politicians could facilitate the implementation and evaluation of policies and standards regulating and monitoring PE and its health impacts.Key messages• Precarious employment has complex public health implications.• Sustainable solutions to address precarious employment must be upstream and multidisciplinary.
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14. |
- Thacher, Jesse D., et al.
(author)
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Occupational noise exposure and risk of incident stroke: a pooled study of five Scandinavian cohorts
- 2022
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In: OCCUPATIONAL AND ENVIRONMENTAL MEDICINE. - : BMJ. - 1351-0711 .- 1470-7926. ; 79:9, s. 594-601
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Journal article (peer-reviewed)abstract
- Objectives To investigate the association between occupational noise exposure and stroke incidence in a pooled study of five Scandinavian cohorts (NordSOUND). Methods We pooled and harmonised data from five Scandinavian cohorts resulting in 78 389 participants. We obtained job data from national registries or questionnaires and recoded these to match a job-exposure matrix developed in Sweden, which specified the annual average daily noise exposure in five exposure classes (L-Aeq8h): <70, 70-74, 75-79, 80-84, >= 85 dB(A). We identified residential address history and estimated 1-year average road traffic noise at baseline. Using national patient and mortality registers, we identified 7777 stroke cases with a median follow-up of 20.2 years. Analyses were conducted using Cox proportional hazards models adjusting for individual and area-level potential confounders. Results Exposure to occupational noise at baseline was not associated with overall stroke in the fully adjusted models. For ischaemic stroke, occupational noise was associated with HRs (95% CI) of 1.08 (0.98 to 1.20), 1.09 (0.97 to 1.24) and 1.06 (0.92 to 1.21) in the 75-79, 80-84 and >= 85 dB(A) exposure groups, compared with <70 dB(A), respectively. In subanalyses using time-varying occupational noise exposure, we observed an indication of higher stroke risk among the most exposed (>= 85 dB(A)), particularly when restricting analyses to people exposed to occupational noise within the last year (HR: 1.27; 95% CI: 0.99 to 1.63). Conclusions We found no association between occupational noise and risk of overall stroke after adjustment for confounders. However, the non-significantly increased risk of ischaemic stroke warrants further investigation.
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15. |
- Yi, Chuixiang, et al.
(author)
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Climate control of terrestrial carbon exchange across biomes and continents
- 2010
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In: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 5:3
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Journal article (peer-reviewed)abstract
- Understanding the relationships between climate and carbon exchange by terrestrial ecosystems is critical to predict future levels of atmospheric carbon dioxide because of the potential accelerating effects of positive climate-carbon cycle feedbacks. However, directly observed relationships between climate and terrestrial CO2 exchange with the atmosphere across biomes and continents are lacking. Here we present data describing the relationships between net ecosystem exchange of carbon (NEE) and climate factors as measured using the eddy covariance method at 125 unique sites in various ecosystems over six continents with a total of 559 site-years. We find that NEE observed at eddy covariance sites is (1) a strong function of mean annual temperature at mid-and high-latitudes, (2) a strong function of dryness at mid-and low-latitudes, and (3) a function of both temperature and dryness around the mid-latitudinal belt (45 degrees N). The sensitivity of NEE to mean annual temperature breaks down at similar to 16 degrees C (a threshold value of mean annual temperature), above which no further increase of CO2 uptake with temperature was observed and dryness influence overrules temperature influence.
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17. |
- Albin, Maria, et al.
(author)
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Asbestos and cancer
- 1995
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In: Medicina del Lavoro. - 0025-7818. ; 86:3, s. 259-262
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Journal article (peer-reviewed)
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18. |
- Albin, Maria, et al.
(author)
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Asbestos and cancer: An overview of current trends in Europe
- 1999
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In: Environmental Health Perspectives. - 1552-9924. ; 107:Suppl. 2, s. 289-298
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Journal article (peer-reviewed)abstract
- This review assesses the contribution of occupational asbestos exposure to the occurrence of mesothelioma and lung cancer in Europe. Available information on national asbestos consumption, proportions of the population exposed, and exposure levels is summarized. Population-based studies from various European regions on occupational asbestos exposure, mesothelioma, and lung cancer are reviewed. Asbestos consumption in 1994 ranged, per capita, between 0. 004 kg in northern Europe and 2.4 kg in the former Soviet Union. Population surveys from northern Europe indicate that 15 to 30% of the male (and a few percent of the female) population has ever had occupational exposure to asbestos, mainly in construction (75% in Finland) or in shipyards. Studies on mesothelioma combining occupational history with biologic exposure indices indicate occupational asbestos exposure in 62 to 85% of the cases. Population attributable risks for lung cancer among males range between 2 and 50% for definite asbestos exposure. After exclusion of the most extreme values because of methodologic aspects, most of the remaining estimates are within the range of 10 to 20%. Estimates of women are lower. Extrapolation of the results to national figures would decrease the estimates. Norwegian estimates indicate that one-third of expected asbestos-related lung cancers might be avoided if former asbestos workers quit smoking. The combination of a current high asbestos consumption per capita, high exposure levels, and high underlying lung cancer rates in Central Europe and the former Soviet Union suggests that the lung cancers will arise from the smoking-asbestos interaction should be a major concern.
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20. |
- Alskär, Linda C., et al.
(author)
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Effect of lipids on absorption of carvedilol in dogs : Is coadministration of lipids as efficient as a lipid-based formulation?
- 2019
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In: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 304, s. 90-100
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Journal article (peer-reviewed)abstract
- Lipid-based formulations (LBFs) is a formulation strategy for enabling oral delivery of poorly water-soluble drugs. However, current use of this strategy is limited to a few percent of the marketed products. Reasons for that are linked to the complexity of LBFs, chemical instability of pre-dissolved drug and a limited understanding of the influence of LBF intestinal digestion on drug absorption. The aim of this study was to explore intestinal drug solubilization from a long-chain LBF, and evaluate whether coadministration of LBF is as efficient as a lipidbased drug formulation containing the pre-dissolved model drug carvedilol. Thus, solubility studies of this weak base were performed in simulated intestinal fluid (SIF) and aspirated dog intestinal fluid (DIF). DIF was collected from duodenal stomas after dosing of water and two levels (1 g and 2 g) of LBF. Similarly, the in vitro SIF solubility studies were conducted prior to, and after addition of, undigested or digested LBF. The DIF fluid was further characterized for lipid digestion products (free fatty acids) and bile salts. Subsequently, carvedilol was orally administered to dogs in a lipid-based drug formulation and coadministered with LBF, and drug plasma exposure was assessed. In addition to these studies, in vitro drug absorption from the different formulation approaches were evaluated in a lipolysis-permeation device, and the obtained data was used to evaluate the in vitro in vivo correlation. The results showed elevated concentrations of free fatty acids and bile salts in the DIF when 2 g of LBF was administered, compared to only water. As expected, the SIF and DIF solubility data revealed that carvedilol solubilization increased by the presence of lipids and lipid digestion products. Moreover, coadministration of LBF and drug demonstrated equal plasma exposure to the lipid-based drug formulation. Furthermore, evaluation of in vitro absorption resulted in the same rank order for the LBFs as in the in vivo dog study. In conclusion, this study demonstrated increased intestinal solubilization from a small amount of LBF, caused by lipid digestion products and bile secretion. The outcomes also support the use of coadministration of LBF as a potential dosing regimen in cases where it is beneficial to have the drug in the solid form, e.g. due to chemical instability in the lipid vehicle. LBFs.
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23. |
- Brijs, J., et al.
(author)
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Humane slaughter of African sharptooth catfish (Clarias gariepinus): Effects of various stunning methods on brain function
- 2021
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In: Aquaculture. - : Elsevier BV. - 0044-8486 .- 1873-5622. ; 531
-
Journal article (peer-reviewed)abstract
- © 2020 The Authors Common slaughter procedures for African sharptooth catfish (Clarias gariepinus) include asphyxiation, ice chilling and exsanguination, which may all cause substantial suffering over prolonged periods of time before death. Therefore, comprehensive evaluations of potentially more humane slaughter procedures for this species are urgently needed. Here, we use a non-invasive electroencephalographic (EEG) method to assess the state of sensibility in African sharptooth catfish in response to various stunning methods (e.g. ice chilling, electrical stunning, electrical stunning followed by exsanguination, percussive stunning, and immersion in isoeugenol). Based on the abolition of visually evoked responses (VERs) on the EEG, ice slurry immersion induced insensibility between 2.6 and 7.6 min, during which catfish exhibited aversive behaviours. Once VERs were lost, they remained absent so long as catfish remained immersed in the ice slurry. Electrical stunning (i.e. exposure to ~1.7 A dm−2 at a water conductivity of ~997 μS cm−1) induced insensibility immediately but not irreversibly. Depending on the duration of the stun (i.e. from 1 to 10 s), catfish either regained VERs immediately or within 4.9 min after the completion of the electrical insult. However, when a 10 s electrical stun was immediately followed by exsanguination and immersion in an ice slurry, the duration of insensibility was sufficient to humanely kill catfish. When administered correctly, manual percussive stunning with a fish priest induced insensibility immediately and irreversibly. However, 36% of catfish regained VERs, which is likely explained by the difficulty associated with administering an accurate manual percussive stun of sufficient force on a live and struggling catfish. Catfish appeared to be sedated following immersion in isoeugenol (i.e. catfish were calm and easy to handle), yet VERs remained present at doses exceeding that recommended for euthanasia in salmonids, which indicates that this substance may not be suitable for stunning catfish. However, the potential for using isoeugenol as a pre-stunning sedative for improving handleability and reducing handling stress of this species warrants further investigation. In conclusion, this study clearly demonstrates that when singularly administered, none of the abovementioned stunning methods could reliably induce insensibility immediately and/or irreversibly without welfare implications. Yet, our findings indicate that these shortcomings can be resolved by using a combination of methods. This could include an electrical or percussive stun to immediately induce insensibility that should be immediately followed by exsanguination and immersion in an ice slurry to maintain insensibility until death.
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24. |
- Brijs, J., et al.
(author)
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In vivo aerobic metabolism of the rainbow trout gut and the effects of an acute temperature increase and stress event
- 2018
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In: Journal of Experimental Biology. - : The Company of Biologists. - 0022-0949 .- 1477-9145. ; 221:14
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Journal article (peer-reviewed)abstract
- The fish gut is responsible for numerous potentially energetically costly processes, yet little is known about its metabolism. Here, we provide the first in vivo measurements of aerobic metabolism of the gut in a teleost fish by measuring gut blood flow, as well as arterial and portal venous oxygen content. At 10 degrees C, gut oxygen uptake rate was 4.3 +/- 0.5 ml O-2 h(-1) kg(-1) (similar to 11 % of whole-animal oxygen uptake). Following acute warming to 15 degrees C, gut blood flow increased similar to 3.4-fold and gut oxygen uptake rate increased similar to 3.7-fold (16.0 +/- 3.3 ml O-2 h(-1) kg(-1)), now representing similar to 25% of whole-animal oxygen uptake. Although gut blood flow decreased following an acute stress event at 15 degrees C, gut oxygen uptake remained unchanged as a result of a similar to 2-fold increase in oxygen extraction. The high metabolic thermal sensitivity of the gut could have important implications for the overall aerobic capacity and performance of fish in a warming world and warrants further investigation.
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25. |
- Brijs, J., et al.
(author)
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Prevalence and severity of cardiac abnormalities and arteriosclerosis in farmed rainbow trout (Oncorhynchus mykiss)
- 2020
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In: Aquaculture. - : Elsevier BV. - 0044-8486 .- 1873-5622. ; 526
-
Journal article (peer-reviewed)abstract
- Cardiovascular disease may pose a major threat to the health and welfare of farmed fish. By investigating a range of established cardiovascular disease indicators, we aimed to determine the prevalence, severity and consequences of this affliction in farmed rainbow trout (Oncorhynchus mykiss) from an open cage farm in the Baltic Sea, an open cage farm in a freshwater lake, and a land-based recirculating aquaculture system. We also aimed to identify environmental, anthropogenic and physiological factors contributing towards the development of the disease. The majority of trout possessed enlarged hearts with rounded ventricles (mean height:width ratios of 1.0–1.1 c.f. ~1.3 in wild fish) and a high degree of vessel misalignment (mean angles between the longitudinal ventricular axis and the axis of the bulbus arteriosus of 28–31 °c.f. ~23° in wild fish). The prevalence and severity of coronary arteriosclerosis was also high, as 92–100% of fish from the different aquaculture facilities exhibited coronary lesions. Mean lesion incidence and severity indices were 67–95% and 3.1–3.9, respectively, which resulted in mean coronary arterial blockages of 19–32%. To evaluate the functional significance of these findings, we modelled the effects of arterial blockages on coronary blood flow and experimentally tested the effects of coronary occlusion in a sub-sample of fish. The observed coronary blockages were estimated to reduce coronary blood flow by 34–54% while experimental coronary occlusion adversely affected the electrocardiogram of trout. Across a range of environmental (water current, predation), anthropogenic (boat traffic intensity, hatchery of origin, brand of feed pellets) and physiological factors (condition factor, haematological and plasma indices), the hatchery of origin was the main factor contributing towards the observed variation in the development of cardiovascular disease. Therefore, further research on the effects of selective breeding programs and rearing strategies on the development of cardiovascular disease is needed to improve the welfare and health of farmed fish. © 2020 The Authors
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26. |
- Brijs, J., et al.
(author)
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Prospects and pitfalls of using heart rate bio-loggers to assess the welfare of rainbow trout (Oncorhynchus mykiss) in aquaculture
- 2019
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In: Aquaculture. - : Elsevier BV. - 0044-8486 .- 1873-5622. ; 509, s. 188-197
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Journal article (peer-reviewed)abstract
- - Investigating real-time stress responses during common aquaculture practices is necessary for improving the welfare of farmed fish. Recently, Star-Oddi DST milli-HRT bio-loggers capable of measuring heart rate (as an indicator for stress) in freely swimming fish have proved to be useful in this regard. However, despite the growing popularity of these devices, they have not yet been stringently evaluated and validated for use in fish. The present study is the first to do so by simultaneously recording heart rate of a commercially important salmonid species (rainbow trout, Oncorhynchus mykiss) using the abovementioned bio-loggers, as well as an established non-invasive wireless heart rate recording technique that has been demonstrated to provide more accurate recordings than those collected using traditional methods requiring a physical connection to recording equipment. The measurement error of the bio-loggers was <1 beat min −1 irrespective of the sampling period when only using measurements graded with the highest quality index (QI 0 ) and it is advised that only QI 0 measurements be used as inclusion of poorer quality measurements (QI 1–3 ) markedly reduce measurement accuracy. Furthermore, sufficiently long recovery periods should be employed prior to collecting data with these devices in salmonids, as anaesthesia and surgical implantation of bio-loggers resulted in transiently elevated resting heart rates for >72 h. Following the successful validation of these bio-loggers, the effects of common aquaculture practices such as netting, grouping and enforced activity on the cardiac performance of freely swimming rainbow trout were investigated. Prior to the subsequent exposure to the abovementioned stressors, mean heart rates of trout were ~42 beats min −1 . Following netting, trout increased heart rates by 57%, which recovered within 3 h. Grouping subsequently induced a more pronounced and prolonged stress response, as heart rates initially increased by 86% and then remained elevated throughout the 8 h recovery period. Consequently, trout were only able to further increase heart rates by 7% following enforced activity. This diminished cardiac response demonstrates a situation where the cumulative allostatic load induced by prior stressors is approaching a level where the animal struggles to perform normal physiological processes in the face of further challenges. These findings are important for the aquaculture industry as exposure to multiple stressors without sufficient recovery times has the potential to result in the collapse of cardiac scope, which combined with unfavourable environmental conditions could lead to increased mortality. © 2019 Elsevier B.V.
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27. |
- Brijs, J., et al.
(author)
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Remote physiological monitoring provides unique insights on the cardiovascular performance and stress responses of freely swimming rainbow trout in aquaculture
- 2019
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
-
Journal article (peer-reviewed)abstract
- Investigating the mechanisms that fish employ to maintain homeostasis in their everyday life requires measurements of physiological and behavioural responses in the field. With multivariate bio-loggers, we continuously measured gastrointestinal blood flow (GBF), heart rate, activity and body temperature in rainbow trout (Oncorhynchus mykiss) swimming freely amongst ~5000 conspecifics in a sea cage. Our findings clearly demonstrate that while both acute aquaculture-related stress and spontaneous activity resulted in transient reductions in GBF (i.e. reductions of up to 65%), recovery from stressful handling practices subsequently involved a substantial and prolonged gastrointestinal hyperemia far beyond the level observed prior to the stressor. The gastrointestinal hyperemia may be necessary to repair the damage to the gastrointestinal tract caused by acute stress. Furthermore, heart rate responses to acute stress or voluntary activity differed depending on the individual’s physiological state. Stressed fish (i.e. mean heart rates >70 beats min−1) exhibited a bradycardic response to acute stress or activity, whereas fish with mean heart rates <60 beats min−1 instead demonstrated strong tachycardic responses. Remote monitoring of physiological and behavioural variables using bio-loggers can provide unique insights into ‘real-life’ responses of animals, which can largely differ from the responses observed in confined laboratory settings. © 2019, The Author(s).
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28. |
- Brijs, Jeroen, et al.
(author)
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The final countdown: Continuous physiological welfare evaluation of farmed fish during common aquaculture practices before and during harvest
- 2018
-
In: Aquaculture. - : Elsevier BV. - 0044-8486 .- 1873-5622. ; 495, s. 903-911
-
Journal article (peer-reviewed)abstract
- Welfare of farmed fish has become of increasing concern for consumers, producers, interest groups and authorities. To improve fish welfare, it is necessary to find indicators that can identify stressful situations early enough so that an intervention can take place before detrimental effects occur. By using heart rate bio-loggers in freely swimming rainbow trout (Oncorhynchus mykiss), combined with plasma cortisol levels and a range of haematological and blood chemistry parameters, we assessed the severity of stress responses induced by a range of common aquaculture practices before and during harvest. Following surgery, transportation and reintroduction with conspecifics in the sea cage, it took similar to 4 days for heart rate to stabilize and for a clear circadian rhythm in heart rate to emerge (i.e. average circadian fluctuation in heart rate of similar to 25 to 27 beats min(-1)). The presence or absence of this circadian rhythm in heart rate could inform researchers in the aquaculture industry whether or not specific farming routines induce unnecessary and prolonged stress. The elevations in heart rate caused by common farming practises such as crowding and transportation (e.g. heart rate increased by similar to 8 and 9 beats min-1 above what would normally be expected for that time of day, respectively) corresponded well with increases in plasma cortisol levels. Stressful farming practises or events (indicated by elevated plasma cortisol levels) such as air exposure during brailing and aquatic hypoxia triggered a hypoxic bradycardia until fish were released back into oxygenated water whereupon heart rate significantly increased to repay the accumulated oxygen debt. Repeated stress induced by multiple farming practises (i.e. combined stressors of crowding, brailing and transportation) clearly had a cumulative and long-lasting effect as heart rate peaked at similar to 25 beats min(-1) above what would normally be expected for that time of day. Heart rate also remained significantly elevated by similar to 9 beats min(-1) the following morning, suggesting that if rainbow trout need to be subjected to multiple stressors during consequtive days, it is recommended that sufficient time for recovery is provided between stressors. This study demonstrates that heart rate monitoring can be useful to assess stress levels of freely swimming fish in sea cages. Moreover, the use of implantable bio-loggers opens up a broad range of possible applications that will allow researchers to investigate the effects of environmental and/or anthropogenic stressors on the welfare of fish under conditions more realistic to the aquaculture industry.
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29. |
- Clulow, Andrew J., et al.
(author)
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Characterization of Solubilizing Nanoaggregates Present in Different Versions of Simulated Intestinal Fluid
- 2017
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In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 121:48, s. 10869-10881
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Journal article (peer-reviewed)abstract
- The absorption of hydrophobic drugs and nutrients from the intestine is principally determined by the amount that can be dissolved by the endogenous fluids present in the gut. Human intestinal fluids (HIFs) comprise a complex mixture of bile salts, phospholipids, steroids and glycerides that vary in composition in the fed and fasted state and between subjects. A number of simulated intestinal fluid (SIF) compositions have been developed to mimic fasted and fed state intestinal conditions and allow the in vitro determination of drug solubility as a proxy for the maximum dissolved concentration it is possible to reach. In particular these solvents are used during the development of lipophilic and poorly water-soluble drugs but questions remain around the differences that may arise from the source and methods of preparation of these fluids. In this work, a range of SIFs were studied using small angle X-ray scattering (SAXS), cryogenic -transmission electron microscopy (cryo-TEM) and molecular dynamics (MD) simulations in order to analyze their structures. In-house prepared SIFs based on sodium taurodeoxycholate (NaTDC) and 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) formed oblate ellipsoidal micelles irrespective of lipid concentration and preparation conditions. In contrast, commercially available SIFs based on sodium taurocholate and lecithin formed prolate ellipsoidal micelles in the fed state and vesicles in the fasted state. These structural variations are the likely reason for the dramatic differences sometimes observed in the solubility enhancements for hydrophobic drugs, nutrients and digestion products when using different SIFs. However, the structural homogeneity of the NaTDC/DOPC micelles makes them ideal candidates for standardizing SIF formulations as the structures of the solubilizing nanoaggregates therein are not sensitive to the preparation method.
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30. |
- Ekblom Bak, Elin, 1981-, et al.
(author)
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Accelerometer derived physical activity patterns in 27.890 middle‐aged adults : The SCAPIS cohort study
- 2022
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In: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 32:5, s. 866-880
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Journal article (peer-reviewed)abstract
- The present study aims to describe accelerometer-assessed physical activity (PA) patterns and fulfillment of PA recommendations in a large sample of middle-aged men and women, and to study differences between subgroups of socio-demographic, socio-economic, and lifestyle-related variables. A total of 27 890 (92.5% of total participants, 52% women, aged 50–64 years) middle-aged men and women with at least four days of valid hip-worn accelerometer data (Actigraph GT3X+, wGT3X+ and wGT3X-BT) from the Swedish CArdioPulmonary bioImage Study, SCAPIS, were included. In total, 54.5% of daily wear time was spent sedentary, 39.1% in low, 5.4% in moderate, and only 0.1% in vigorous PA. Male sex, higher education, low financial strain, born in Sweden, and sedentary/light working situation were related to higher sedentary time, but also higher levels of vigorous PA. High BMI and having multiple chronic diseases associated strongly with higher sedentary time and less time in all three PA intensities. All-year physically active commuters had an overall more active PA pattern. The proportion fulfilling current PA recommendations varied substantially (1.4% to 92.2%) depending on data handling procedures and definition used. Twenty-eight percent was defined as having an “at-risk” behavior, which included both high sedentary time and low vigorous PA. In this large population-based sample, a majority of time was spent sedentary and only a fraction in vigorous PA, with clinically important variations between subgroups. This study provides important reference material and emphasizes the importance of a comprehensive assessment of all aspects of the individual PA pattern in future research and clinical practice.
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31. |
- Fredriksson, Albin, 1984-
(author)
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Robust optimization of radiation therapy accounting for geometric uncertainty
- 2013
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Doctoral thesis (other academic/artistic)abstract
- Geometric errors may compromise the quality of radiation therapy treatments. Optimization methods that account for errors can reduce their effects.The first paper of this thesis introduces minimax optimization to account for systematic range and setup errors in intensity-modulated proton therapy. The minimax method optimizes the worst case outcome of the errors within a given set. It is applied to three patient cases and shown to yield improved target coverage robustness and healthy structure sparing compared to conventional methods using margins, uniform beam doses, and density override. Information about the uncertainties enables the optimization to counterbalance the effects of errors.In the second paper, random setup errors of uncertain distribution---in addition to the systematic range and setup errors---are considered in a framework that enables scaling between expected value and minimax optimization. Experiments on a phantom show that the best and mean case tradeoffs between target coverage and critical structure sparing are similar between the methods of the framework, but that the worst case tradeoff improves with conservativeness.Minimax optimization only considers the worst case errors. When the planning criteria cannot be fulfilled for all errors, this may have an adverse effect on the plan quality. The third paper introduces a method for such cases that modifies the set of considered errors to maximize the probability of satisfying the planning criteria. For two cases treated with intensity-modulated photon and proton therapy, the method increased the number of satisfied criteria substantially. Grasping for a little less sometimes yields better plans.In the fourth paper, the theory for multicriteria optimization is extended to incorporate minimax optimization. Minimax optimization is shown to better exploit spatial information than objective-wise worst case optimization, which has previously been used for robust multicriteria optimization.The fifth and sixth papers introduce methods for improving treatment plans: one for deliverable Pareto surface navigation, which improves upon the Pareto set representations of previous methods; and one that minimizes healthy structure doses while constraining the doses of all structures not to deteriorate compared to a reference plan, thereby improving upon plans that have been reached with too weak planning goals.
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32. |
- Gräns, Albin, 1979, et al.
(author)
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A fully implantable multi-channel biotelemetry system for measurement of blood flow and temperature: A first evaluation in the green sturgeon
- 2009
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In: Hydrobiologia.. - : Springer Science and Business Media LLC. - 0018-8158 .- 1573-5117. ; 619:1, s. 11-25
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Journal article (peer-reviewed)abstract
- The objective of this study was to evaluate a novel fully implantable radio-based blood flow biotelemetry system which allows simultaneously measurement of blood flow on two channels and temperature on one channel, in fish. These are the first recordings of blood flow from free-swimming fish, showing that the system is capable of recording blood flow in the ventral aorta (cardiac output) and celiacomesenteric artery (gastrointestinal blood flow) in green sturgeon Acipenser medirostris exposed to a series of different stimuli for up to 7 days after implantation. The results showed stable base line recordings and blood flow was used to calculated heart rate (f H) and stroke volume (V s). It was possible to reproduce the same type of responses as has previously been reported during exposure to hypoxia, temperature, stress and feeding. The mass of our implant was less than 2% of the body mass which is well within the recommended sizes for surgically implanted telemetry transmitters and it fitted easily within the abdominal cavity of the sturgeon. A fully implantable system minimizes the risk of infection/expulsion and maximizes the likelihood that the studied fish will behave naturally and be treated normally by surrounding fish. The use of biotelemetry in basic comparative physiology and applied animal ecology could help scientists to collect information that has previously been challenging to obtain and to open the possibility for new types of physiological and ecophysiological studies.
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37. |
- Hjelmstedt, P., et al.
(author)
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Assessing the effectiveness of percussive and electrical stunning in rainbow trout: Does an epileptic-like seizure imply brain failure?
- 2022
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In: Aquaculture. - : Elsevier BV. - 0044-8486 .- 1873-5622. ; 552
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Journal article (peer-reviewed)abstract
- Both percussive and electrical stunning have been highlighted as methods that can be used to quickly render fish unconscious before being killed. However, accurately assessing unconsciousness in animals following stunning remains challenging, and thus methods for reliable interpretation and validation of different stunning methods are urgently needed. Here, we used a non-invasive technique to continuously record electroencephalograms (EEG) of rainbow trout (Oncorhynchus mykiss) enabling us to compare the effects of both percussive stunning, using a captive bolt gun, and various combinations of electrical stun parameters delivered in water. The EEG signals were assessed for the absence or presence of an epileptic-like seizure and for visually evoked responses (VERs). No epileptic-like seizures or VERs were observed after captive bolt stunning. We found that it is possible to reliably induce an epileptic-like seizure and an immediate, but short lasting, loss of VERs following a 1 s exposure to an electrical field strength of at least 2.8 VRMS cm−1 and current density of 0.22 ARMS dm−2 in water of conductivity of ~1000 μS cm−1 using a 50 Hz AC current. However, to avoid recovery of VERs shortly after the stun, it was necessary to increase the duration of the stun application (≥30 s), the electrical field strength (10.2 VRMS cm−1) and the current density (0.84 ARMS dm−2 respectively). We found no clear relationship between presence and absence of ventilation and VERs following electrical stunning in rainbow trout, highlighting that loss of ventilation may not be a good indicator of brain failure in rainbow trout. Our results clearly show that the presence of an epileptic-like seizure following an electrical stun does not guarantee a prolonged period where the fish is unresponsive to visual stimulation (i.e. absence of VERs). It was further found that VERs can return before the end of the seizure. As both presence of a seizure and absence of VERs have been used independently as indicators of unconsciousness in fish, we emphasize the necessity to carefully consider and evaluate the reliability of neurophysiological indicators of unconsciousness when validating methods to stun fish. © 2022
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38. |
- Hjelmstedt, P., et al.
(author)
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Continuous physiological welfare evaluation of European whitefish (Coregonus lavaretus) during common aquaculture practices leading up to slaughter
- 2021
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In: Aquaculture. - : Elsevier BV. - 0044-8486 .- 1873-5622. ; 534
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Journal article (peer-reviewed)abstract
- European whitefish (Coregonus lavaretus) is an aquaculture species with the potential for expanded cultivation in the fresh and brackish waters of Northern Europe. Yet, relatively little species-specific information is available regarding the stress responses and associated welfare implications for this species in captivity. We addressed this knowledge gap by using a combination of implantable heart rate bio-loggers and a range of traditional stress indicators (e.g. haematological parameters and plasma concentrations of cortisol, glucose and ions) to comprehensively evaluate the physiological responses of freely swimming whitefish in captivity, as well as when subjected to aquaculture practices and stressors that commonly occur prior to and during slaughter. Whitefish appeared to recover rapidly from surgery, as resting heart rate decreased within 36 h to stabilize at similar to 25 beats min(-1) for the next 18 days when fish were left relatively undisturbed (i.e. personnel were only present when feeding fish). In contrast with previous studies on farmed rainbow trout and Atlantic salmon, whitefish did not exhibit a clear circadian heart rate rhythm, which may be related to species-specific differences in diurnal locomotor activity. Whitefish also appear to have a well-developed capacity for thermal acclimation of heart rate, as daily resting heart rate did not change during the undisturbed period despite an increase in body temperature from similar to 6.8 to 11.2 degrees C. Following acute stressors such as crowding and transportation, the physiological response of whitefish typically involved transient elevations in heart rate, plasma cortisol and glucose, and red blood cell swelling, while plasma [K+] decreased. In contrast, the heart rate of whitefish plummeted following the combination of brailing (i.e. to haul in fish with a brail/net) and CO2 exposure prior to slaughter, while plasma cortisol, glucose and [Ca2+] significantly increased. An unforeseen finding concerns the substantial and long-lasting physiological stress response observed in whitefish when held in close proximity (i.e. within similar to 10 m) to a rainbow trout net pen, as the mean heart rate of whitefish increased from similar to 32 to 43 beats min(-1) (i.e. an increase of similar to 34%). This may represent an innate physiological response to the threat of predation, which consequently increases the allostatic load and energetic expenditure of whitefish when farmed alongside salmonids. To conclude, this study highlights the importance of performing long-term, species-specific evaluations of freely swimming fish in real aquaculture settings, and provides a platform for further research aiming to determine the welfare implications of simultaneously farming predatory and prey species in close proximity.
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39. |
- Hjelmstedt, P., et al.
(author)
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Effects of prophylactic antibiotic-treatment on post-surgical recovery following intraperitoneal bio-logger implantation in rainbow trout
- 2020
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- Bio-logging devices can provide unique insights on the life of freely moving animals. However, implanting these devices often requires invasive surgery that causes stress and physiological side-effects. While certain medications in connection to surgeries have therapeutic capacity, others may have aversive effects. Here, we hypothesized that the commonly prescribed prophylactic treatment with enrofloxacin would increase the physiological recovery rate and reduce the presence of systemic inflammation following the intraperitoneal implantation of a heart rate bio-logger in rainbow trout (Oncorhynchus mykiss). To assess post-surgical recovery, heart rate was recorded for 21 days in trout with or without enrofloxacin treatment. Contrary to our hypothesis, treated trout exhibited a prolonged recovery time and elevated resting heart rates during the first week of post-surgical recovery compared to untreated trout. In addition, an upregulated mRNA expression of TNFα in treated trout indicate a possible inflammatory response 21 days post-surgery. Interestingly, the experience level of the surgeon was observed to have a long-lasting impact on heart rate. In conclusion, our study showed no favorable effects of enrofloxacin treatment. Our findings highlight the importance of adequate post-surgical recovery times and surgical training with regards to improving the welfare of experimental animals and reliability of research outcomes. © 2020, The Author(s).
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40. |
- Hossain, Md Shakhawath, et al.
(author)
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Explicit-pH Coarse-Grained Molecular Dynamics Simulations Enable Insights into Restructuring of Intestinal Colloidal Aggregates with Permeation Enhancers
- 2022
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In: Processes. - : MDPI. - 2227-9717. ; 10:1, s. 29-
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Journal article (peer-reviewed)abstract
- Permeation enhancers (PEs) can increase the bioavailability of drugs. The mechanisms of action of these PEs are complex, but, typically, when used for oral administration, they can transiently induce the alteration of trans- and paracellular pathways, including increased solubilization and membrane fluidity, or the opening of the tight junctions. To elucidate these mechanistic details, it is important to understand the aggregation behavior of not only the PEs themselves but also other molecules already present in the intestine. Aggregation processes depend critically on, among other factors, the charge state of ionizable chemical groups, which is affected by the pH of the system. In this study, we used explicit-pH coarse-grained molecular dynamics simulations to investigate the aggregation behavior and pH dependence of two commonly used PEs—caprate and SNAC—together with other components of fasted- and fed-state simulated intestinal fluids. We also present and validate a coarse-grained molecular topology for the bile salt taurocholate suitable for the Martini3 force-field. Our results indicate an increase in the number of free molecules as a function of the system pH and for each combination of FaSSIF/FeSSIF and PEs. In addition, there are differences between caprate and SNAC, which are rationalized based on their different molecular structures and critical micelle concentrations.
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41. |
- Johansson, L, et al.
(author)
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Immunohistochemical study of 158 lung carcinomas
- 1992
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In: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - 1600-0463. ; 100:10, s. 914-921
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Journal article (peer-reviewed)abstract
- Lung carcinomas were studied immunohistochemically and the results were related to type of tissue sample (bronchoscopic biopsies, surgical specimens, autopsies). All cytokeratins (CAM 5.2, PKK-1, AE1/AE3) reacted with virtually all adenocarcinomas, most squamous, and 65% of the large cell carcinomas, while CAM 5.2 was most efficient with the small cell carcinomas. CEA stained 33% and 60% of the small and large cell carcinomas, respectively, most adenocarcinomas, and 84% of the squamous cell carcinomas, among which staining decreased with dedifferentiation and was often focal. EMA reacted with 90%, and NSE with 20% of all histological types. There was no staining for NF. All antibodies, except EMA, were more efficient with surgical specimens. Our study implies that the cytokeratins we used work better with surgical material, but are generally comparable to monospecific cytokeratin antibodies. Also, EMA is a reliable marker for epithelial differentiation with all types of tissue samples. Moreover, CEA negativity in several poorly differentiated lung carcinomas might have implications in the differential diagnosis against pleural mesothelioma.
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44. |
- Lu, S. S., et al.
(author)
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Are urinary PAHs biomarkers of controlled exposure to diesel exhaust?
- 2014
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In: Biomarkers. - : Informa UK Limited. - 1354-750X .- 1366-5804. ; 19:4, s. 332-339
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Journal article (peer-reviewed)abstract
- Urinary polycyclic aromatic hydrocarbons (PAHs) were evaluated as possible biomarkers of exposure to diesel exhaust (DE) in two controlled-chamber studies. We report levels of 14 PAHs from 28 subjects in urine that were collected before, immediately after and the morning after exposure. Using linear mixed-effects models, we tested for effects of DE exposure and several covariates (time, age, gender and urinary creatinine) on urinary PAH levels. DE exposures did not significantly alter urinary PAH levels. We conclude that urinary PAHs are not promising biomarkers of short-term exposures to DE in the range of 106-276 mu g/m(3).
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45. |
- Ludvigsson, Johnny, et al.
(author)
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Combined Etanercept, GAD-alum and vitamin D treatment: an open pilot trial to preserve beta cell function in recent onset type 1 diabetes
- 2021
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In: Diabetes-Metabolism Research and Reviews. - : Wiley. - 1520-7552 .- 1520-7560.
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Journal article (peer-reviewed)abstract
- Aim We aimed to study the feasibility and tolerability of a combination therapy consisting of glutamic acid decarboxylase (GAD-alum), Etanercept and vitamin D in children and adolescents with newly diagnosed with type 1 diabetes (T1D), and evaluate preservation of beta cell function. Material and Methods Etanercept Diamyd Combination Regimen is an open-labelled multi-centre study pilot trial which enrolled 20 GAD antibodies positive T1D patients (7 girls and 13 boys), aged (mean +/- SD): 12.4 +/- 2.3 (8.3-16.1) years, with a diabetes duration of 81.4 +/- 22.1 days. Baseline fasting C-peptide was 0.24 +/- 0.1 (0.10-0.35) nmol/l. The patients received Day 1-450 Vitamin D (Calciferol) 2000 U/d per os, Etanercept sc Day 1-90 0.8 mg/kg once a week and GAD-alum sc injections (20 mu g, Diamyd (TM)) Day 30 and 60. They were followed for 30 months. Results No treatment related serious adverse events were observed. After 6 months 90-min stimulated C-peptide had improved in 8/20 patients and C-peptide area under the curve (AUC) after Mixed Meal Tolerance Test in 5 patients, but declined thereafter, while HbA1c and insulin requirement remained close to baseline. Administration of Etanercept did not reduce tumour necrosis factor (TNF) spontaneous secretion from peripheral blood mononuclear cells, but rather GAD65-induced TNF-alpha increased. Spontaneous interleukin-17a secretion increased after the administration of Etanercept, and GAD65-induced cytokines and chemokines were also enhanced following 1 month of Etanercept administration. Conclusions Combination therapy with parallel treatment with GAD-alum, Etanercept and vitamin D in children and adolescents with type 1 diabetes was feasible and tolerable but had no beneficial effects on the autoimmune process or beta cell function.
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46. |
- Martin, Myriam, et al.
(author)
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Plasma C4d Correlates With C4d Deposition in Kidneys and With Treatment Response in Lupus Nephritis Patients
- 2020
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In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 11
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Journal article (peer-reviewed)abstract
- Objective: To examine whether C4d plasma levels correlate with treatment response and C4d kidney deposition in systemic lupus erythematosus (SLE) with lupus nephritis (LN). Methods: C4d plasma levels were analyzed by a unique assay specifically detecting C4d arising from complement activation and C4 plasma levels were quantified with competitive ELISA. SLE patients with LN (71) and active SLE patients without LN (22) plus 145 controls were included. For 52 LN patients samples were available both at baseline and after immunosuppressive treatment. C4d kidney deposition was detected using immunohistochemistry in two matching kidney biopsies of 12 LN patients. Results: In comparison to population-based controls, plasma C4d levels were significantly increased in SLE patients (0.33 mg/L versus 0.94 mg/ml, p < 0.0001) with significantly higher levels in LN patients (1.02 mg/L) than in non-renal SLE patients (0.57 mg/L, p = 0.004). The C4d/C4 ratio was also significantly higher in LN (11.2) than in non-renal SLE patients (2.5, p = 0.0002). According to ROC curve analysis, C4d was found to be an accurate marker to discriminate LN from non-renal SLE patients (p = 0.004). The C4d/C4 ratio displayed even higher specificity, sensitivity and overall accuracy as marker for LN than C4d and C4 alone. At baseline, C4d levels correlated significantly with urine-albumin to creatinine ratio (rs = 0.43, p = 0.011) and with renal activity index (rs = 0.37, p = 0.002). Immunohistochemical staining showed glomerular deposits of C4d in kidney biopsies, which strikingly correlated with plasma C4d levels (rs = 0.7, p = 0.0002). Plasma C4d declined significantly after treatment in patients that experienced favorable clinical and histopathological response (p < 0.0001), while levels remained mainly unchanged in non-responders. Conclusion: Plasma C4d discriminates LN from active non-renal SLE, correlates with C4d kidney deposits and appears valuable in monitoring responsiveness to various treatments. The C4d/C4 ratio might be superior to C4d alone.
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49. |
- Roswall, N., et al.
(author)
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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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In: Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 129:10
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Journal article (peer-reviewed)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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50. |
- Stock, Kristin, et al.
(author)
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Capturing tumor complexity in vitro: Comparative analysis of 2D and 3D tumor models for drug discovery
- 2016
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6:1
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Journal article (peer-reviewed)abstract
- Two-dimensional (2D) cell cultures growing on plastic do not recapitulate the three dimensional (3D) architecture and complexity of human tumors. More representative models are required for drug discovery and validation. Here, 2D culture and 3D mono- and stromal co-culture models of increasing complexity have been established and cross-comparisons made using three standard cell carcinoma lines: MCF7, LNCaP, NCI-H1437. Fluorescence-based growth curves, 3D image analysis, immunohistochemistry and treatment responses showed that end points differed according to cell type, stromal co-culture and culture format. The adaptable methodologies described here should guide the choice of appropriate simple and complex in vitro models.
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