| 1. |
- Eriksson, Martin, 1970, et al.
(författare)
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Community-Level Analysis of psbA Gene Sequences and Irgarol Tolerance in Marine Periphyton
- 2009
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Ingår i: Applied and Environmental Microbiology. - Washington, D.C. : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 75:4, s. 897-906
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Tidskriftsartikel (refereegranskat)abstract
- This study analyzes psbA gene sequences, predicted D1 protein sequences, species relative abundance, and pollution-induced community tolerance in marine periphyton communities exposed to the antifouling compound Irgarol 1051. The mechanism of action of Irgarol is the inhibition of photosynthetic electron transport at photosystem II by binding to the D1 protein. The metagenome of the communities was used to produce clone libraries containing fragments of the psbA gene encoding the D1 protein. Community tolerance was quantified with a short-term test for the inhibition of photosynthesis. The communities were established in a continuous flow of natural seawater through microcosms with or without added Irgarol. The selection pressure from Irgarol resulted in an altered species composition and an inducted community tolerance to Irgarol. Moreover, there was a very high diversity in the psbA gene sequences in the periphyton, and the composition of psbA and D1 fragments within the communities was dramatically altered by increased Irgarol exposure. Even though tolerance to this type of compound in land plants often depends on a single amino acid substitution (Ser(264)-> Gly) in the D1 protein, this was not the case for marine periphyton species. Instead, the tolerance mechanism likely involves increased degradation of D1. When we compared sequences from low and high Irgarol exposure, differences in nonconserved amino acids were found only in the so-called PEST region of D1, which is involved in regulating its degradation. Our results suggest that environmental contamination with Irgarol has led to selection for high-turnover D1 proteins in marine periphyton communities at the west coast of Sweden.
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| 2. |
- Selck, H., et al.
(författare)
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Assessing and managing multiple risks in a changing worldThe Roskilde recommendations
- 2017
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Ingår i: Environmental Toxicology and Chemistry. - Hoboken, NJ : Wiley. - 0730-7268 .- 1552-8618. ; 36:1, s. 7-16
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Tidskriftsartikel (refereegranskat)abstract
- Roskilde University (Denmark) hosted a November 2015 workshop, Environmental RiskAssessing and Managing Multiple Risks in a Changing World. This Focus article presents the consensus recommendations of 30 attendees from 9 countries regarding implementation of a common currency (ecosystem services) for holistic environmental risk assessment and management; improvements to risk assessment and management in a complex, human-modified, and changing world; appropriate development of protection goals in a 2-stage process; dealing with societal issues; risk-management information needs; conducting risk assessment of risk management; and development of adaptive and flexible regulatory systems. The authors encourage both cross-disciplinary and interdisciplinary approaches to address their 10 recommendations: 1) adopt ecosystem services as a common currency for risk assessment and management; 2) consider cumulative stressors (chemical and nonchemical) and determine which dominate to best manage and restore ecosystem services; 3) fully integrate risk managers and communities of interest into the risk-assessment process; 4) fully integrate risk assessors and communities of interest into the risk-management process; 5) consider socioeconomics and increased transparency in both risk assessment and risk management; 6) recognize the ethical rights of humans and ecosystems to an adequate level of protection; 7) determine relevant reference conditions and the proper ecological context for assessments in human-modified systems; 8) assess risks and benefits to humans and the ecosystem and consider unintended consequences of management actions; 9) avoid excessive conservatism or possible underprotection resulting from sole reliance on binary, numerical benchmarks; and 10) develop adaptive risk-management and regulatory goals based on ranges of uncertainty. Environ Toxicol Chem 2017;36:7-16. (c) 2016 SETAC
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| 3. |
- Galozy, Alexander, 1991-, et al.
(författare)
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Prediction and pattern analysis of medication refill adherence through electronic health records and dispensation data
- 2020
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Ingår i: Journal of Biomedical Informatics: X. - New York, NY : Elsevier. - 2590-177X .- 1532-0464. ; 6-7
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Tidskriftsartikel (refereegranskat)abstract
- Background and purposeLow adherence to medication in chronic disease patients leads to increased morbidity, mortality, and healthcare costs. The widespread adoption of electronic prescription and dispensation records allows a more comprehensive overview of medication utilization. In combination with electronic health records (EHR), such data provides new opportunities for identifying patients at risk of nonadherence and provide more targeted and effective interventions. The purpose of this article is to study the predictability of medication adherence for a cohort of hypertensive patients, focusing on healthcare utilization factors under various predictive scenarios. Furthermore, we discover common proportion of days covered patterns (PDC-patterns) for patients with index prescriptions and simulate medication-taking behaviours that might explain observed patterns.ProceduresWe predict refill adherence focusing on factors of healthcare utilization, such as visits, prescription information and demographics of patient and prescriber. We train models with machine learning algorithms, using four different data splits: stratified random, patient, temporal forward prediction with and without index patients. We extract frequent, two-year long PDC-patterns using K-means clustering and investigate five simple models of medication-taking that can generate such PDC-patterns.FindingsModel performance varies between data splits (AUC test set: 0.77–0.89). Including historical information increases the performance slightly in most cases (approx. 1–2% absolute AUC uplift). Models show low predictive performance (AUC test set: 0.56–0.66) on index-prescriptions and patients with sudden drops in PDC (Recall: 0.58–0.63). We find 21 distinct two-year PDC-patterns, ranging from good adherence to intermittent gaps and early discontinuation in the first or second year. Simulations show that observed PDC-patterns can only be explained by specific medication consumption behaviours.ConclusionsPrediction models developed using EHR exhibit bias towards patients with high healthcare utilization. Even though actual medication-taking is not observable, consumption patterns may not be as arbitrary, provided that medication refilling and consumption is linked. © 2020 The Authors. Published by Elsevier Inc.
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| 4. |
- Urrutia-Cordero, Pablo, et al.
(författare)
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Effects of harmful cyanobacteria on the freshwater pathogenic free-living amoeba Acanthamoeba castellanii
- 2013
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Ingår i: Aquatic Toxicology. - : Elsevier. - 0166-445X .- 1879-1514. ; 130, s. 9-17
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Tidskriftsartikel (refereegranskat)abstract
- Grazing is a major regulating factor in cyanobacterial population dynamics and, subsequently, considerable effort has been spent on investigating the effects of cyanotoxins on major metazoan grazers. However, protozoan grazers such as free-living amoebae can also feed efficiently on cyanobacteria, while simultaneously posing a major threat for public health as parasites of humans and potential reservoirs of opportunistic pathogens. In this study, we conducted several experiments in which the freshwater amoeba Acanthamoeba castellanii was exposed to pure microcystin-LR (MC-LR) and six cyanobacterial strains, three MC-producing strains (MC-LR, MC-RR, MC-YR, MC-WR, [Dha7] MC-RR) and three strains containing other oligopeptides such as anabaenopeptins and cyanopeptolins. Although the exposure to high concentrations of pure MC-LR yielded no effects on amoeba, all MC-producing strains inflicted high mortality rates on amoeba populations, suggesting that toxic effects must be mediated through the ingestion of toxic cells. Interestingly, an anabaenopeptin-producing strain caused the greatest inhibition of amoeba growth, indicating that toxic bioactive compounds other than MCs are of great importance for amoebae grazers. Confocal scanning microscopy revealed different alterations in amoeba cytoskeleton integrity and as such, the observed declines in amoeba densities could have indeed been caused via a cascade of cellular events primarily triggered by oligopeptides with protein-phosphatase inhibition capabilities such as MCs or anabaenopeptins. Moreover, inducible-defense mechanisms such as the egestion of toxic, MC-producing cyanobacterial cells and the increase of resting stages (encystation) in amoebae co-cultivated with all cyanobacterial strains were observed in our experiments. Consequently, cyanobacterial strains showed different susceptibilities to amoeba grazing which were possibly influenced by the potentiality of their toxic secondary metabolites. Hence, this study shows the importance of cyanobacterial toxicity against amoeba grazing and, that cyanobacteria may contain a wide range of chemical compounds capable of negatively affect free-living, herbivorous amoebae. Moreover, this is of high importance for understanding the interactions and population dynamics of such organisms in aquatic ecosystems. (c) 2012 Elsevier B.V. All rights reserved.
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| 5. |
- Warrén Stomberg, Margareta, et al.
(författare)
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Symptoms and signs in interpreting Gamma-hydroxybutyrate (GHB) intoxication - an explorative study
- 2014
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Ingår i: Scandinavian Journal of Trauma Resuscitation & Emergency Medicine. - London : Springer Science and Business Media LLC. - 1757-7241. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background: Acute poisoning with gamma-hydroxybutyrate (GHB) has been a serious medical and social problem in different parts of the world including Sweden. GHB is a drug of abuse which acts primarily as central nervous system (CNS) depressants. GHB has serious toxicity, although many young users do not recognise GHB as a dangerous drug. The aim of this pilot study was to explore how symptoms with risk of failure in vital functions would be valued among professionals that encounter GHB intoxication in the emergency phase. Methods: A web-based survey focusing on the assessment of vital clinical signs for possible GHB intoxication using a numeric scale was carried out during April and May 2011. The participants, n 105, are all professionals who encounter GHB intoxicated in the emergency phase, but have different levels of training in GHB intoxication, mainly Registered Nurses (RNs) in southwest Sweden, employed in pre-hospital or emergency departments at somatic and most psychiatric health care facilities, as well as police officers who in their work come into contact with drug users. Responses in the survey were scored according to risk of GHB intoxication with serious failure of vital functions. The score value was then referred to a so-called evidence based priority (EBP) scale and analysed using descriptive statistics and Fisher's exact test. Results: Cardiac arrest, coma, hypoxia, general convulsions, slow respiratory and heart rate and pale skin are symptoms with the highest risk of serious failure in vital physical functions and were predominantly recognised as such. Conclusion: Despite the professionals' different levels of training in GHB intoxication, all of them were relatively well aware of and in accordance regarding the most risky symptoms. The interpretation score for the less risky symptoms and signs of GHB intoxication varied depending on their degree of training. The results should be viewed cautiously, as the size of the professional groups and their general knowledge of critical symptoms of GHB poisoning varied.
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| 6. |
- Mogard, Elisabeth, et al.
(författare)
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A combination of two or more unhealthy lifestyle factors is associated with impaired physical and mental health in patients with spondyloarthritis : a cross-sectional study
- 2022
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Ingår i: BMC Rheumatology. - London : BioMed Central (BMC). - 2520-1026. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is increasing knowledge of how individual lifestyle factors affect patients with spondyloarthritis, while studies exploring the combination of unhealthy lifestyle factors are lacking. Thus, our aim was to study the frequency of two or more unhealthy lifestyle factors and their associations with physical and mental health in patients with spondyloarthritis (SpA).Methods: A population-based postal survey involving questions on lifestyle factors was completed by 1793 patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA), and undifferentiated spondyloarthritis (USpA). Self-reported physical activity, body mass index, and tobacco use were respectively dichotomized as “healthy” or “unhealthy”, summarized for each patient and stratified into four groups (0–3; 0 = no unhealthy lifestyle factors). Group comparisons were performed with Chi-squared tests, and associations with physical and mental health outcomes were performed with analysis of covariance and logistic regression analysis.Results: Out of 1426 patients (52% women) with complete information for all studied lifestyle factors, 43% reported ≥ two unhealthy lifestyle factors—more frequently patients with PsA (48%) than AS (39%) or USpA (38%)—and with no difference between women and men (p = 0.399). Two or more unhealthy lifestyle factors were associated with worse health-related quality of life, disease activity, physical function, pain, fatigue, anxiety, and depression, adjusted for age and SpA-subgroup. If an unhealthy level of physical activity was one of the two unhealthy lifestyle factors, patients reported worse health outcomes.Conclusion: Reporting two or more unhealthy lifestyle factors were associated with worse physical and mental health in patients with SpA. This highlights the need to screen for a combination of unhealthy lifestyle factors and offer individualized coordinated interventions, and tailored coaching to support behavioral change, in order to promote sustainable health. © 2022, The Author(s).
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| 7. |
- Poljakovic, Mirjana, et al.
(författare)
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Signalling pathways regulating inducible nitric oxide synthase expression in human kidney epithelial cells
- 2003
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Ingår i: European Journal of Pharmacology. - 0014-2999 .- 1879-0712. ; 469:1-3, s. 21-28
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to elucidate the signalling pathways involved in the cytokine-activated inducible nitric oxide synthase (iNOS) response in a human kidney epithelial cell line, A498. Unstimulated cells did not express iNOS. Exposure of A498 cells to a cytokine mixture consisting of interferon gamma, interleukin-1 beta and tumor necrosis factor-alpha (TNF-alpha) increased nitrite production, iNOS mRNA and protein expression. Pharmacological inhibition of tyrosine kinases, including janus kinase (JAK2), and protein kinase C (PKC) inhibited cytokine-mediated nitrite production and iNOS protein expression. The involvement of mitogen-activated protein kinases (MAPKs) was investigated. Inhibition of p38 MAPK, but not of an upstream activator of extracellular signal-regulated kinase (ERK), caused a decrease in iNOS expression and nitrite production in response to cytokines. Electrophoretic mobility shift assay of nuclear extract from cytokine-stimulated cells demonstrated a pronounced binding to a nuclear factor kappa B (NF-kappa B) sequence present in the human iNOS promoter. Furthermore, the NF-kappa B inhibitor pyrrolidinedithiocarbamate (PDTC) decreased cytokine-activated iNOS protein expression and nitrite production. The present study has demonstrated that cytokine-stimulated iNOS expression in human kidney epithelial cells involves activation of tyrosine kinases, including JAK2, PKC, p38 MAPK and NF-kappa B.
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| 8. |
- Andersson, Patrik, et al.
(författare)
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Toxicity with LXR agonists – Problem solving activities for mechanistic understanding
- 2012
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Ingår i: Toxicology Letters. - Shannon : Elsevier. - 0378-4274 .- 1879-3169. ; 211:Suppl. (S), s. S39-S39
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Tidskriftsartikel (refereegranskat)abstract
- Several lines of evidence points toward the potential positive effects of LXR (Liver X Receptor) modulators for effective and safe therapy of cardiovascular diseases (CVDs). LXR is a dimeric nuclear hormone receptor that exists as a combination of RXR and one of two subtypes LXR alpha or beta, which act as cholesterol sensors. LXR alpha is highly expressed in the liver, intestine and adipose tissue while LXR beta is ubiquitously expressed. Activation of LXR up-regulates several genes involved in reverse cholesterol transport (RCT), including ABC transporters. This results in increased efflux of cholesterol from macrophages in atherosclerotic vascular lesions to the circulation and further on to other tissues to ultimately be excreted into the faeces. These effects together with systemic and local anti-inflammatory properties of LXR modulation are likely to contribute to decreased atherosclerosis. The positive effects of LXR activation on RCT and cholesterol balance must be obtained without negative lipid effects, since LXR also activates lipogenic genes. Other types of toxicity and approaches to better understand the mechanism(s) behind these will be presented. Copyright © 2012 Published by Elsevier Ireland Ltd.
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| 9. |
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