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- Munk, P., et al.
(författare)
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Genomic analysis of sewage from 101 countries reveals global landscape of antimicrobial resistance
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance (AMR) is a major threat to global health. Understanding the emergence, evolution, and transmission of individual antibiotic resistance genes (ARGs) is essential to develop sustainable strategies combatting this threat. Here, we use metagenomic sequencing to analyse ARGs in 757 sewage samples from 243 cities in 101 countries, collected from 2016 to 2019. We find regional patterns in resistomes, and these differ between subsets corresponding to drug classes and are partly driven by taxonomic variation. The genetic environments of 49 common ARGs are highly diverse, with most common ARGs carried by multiple distinct genomic contexts globally and sometimes on plasmids. Analysis of flanking sequence revealed ARG-specific patterns of dispersal limitation and global transmission. Our data furthermore suggest certain geographies are more prone to transmission events and should receive additional attention.
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| 4. |
- Dyer, A. H., et al.
(författare)
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Cognitive Outcomes of Long-term Benzodiazepine and Related Drug (BDZR) Use in People Living With Mild to Moderate Alzheimer's Disease: Results From NILVAD
- 2020
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Ingår i: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610. ; 21:2, s. 194-200
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Benzodiazepines and related drugs (BDZRs) have been associated with an increased risk of Alzheimer's disease (AD) in later life. Despite this, it remains unclear whether ongoing BDZR use may further accelerate cognitive decline in those diagnosed with mild to moderate AD. Design: This study was embedded within NILVAD, a randomized controlled trial of nilvadipine in mild to moderate AD. Cognition was measured at baseline and 18 months using the Alzheimer Disease Assessment Scale, Cognitive Subsection (ADAS-Cog). We assessed predictors of long-term BDZR use and analyzed the effect of ongoing BDZR use on ADAS-Cog scores at 18 months. Additionally, the impact of BDZR use on adverse events, incident delirium, and falls over 18-month follow-up was assessed adjusting for relevant covariates. Setting and Participants: 448 participants with mild to moderate AD recruited from 23 academic centers in 9 European countries. Results: Overall, 14% (62/448) were prescribed an ongoing BDZR for the study duration. Increasing total number of (non-BDZR) medications was associated with a greater likelihood of BDZR prescription (odds ratio 1.16, 95% confidence interval 1.05-1.29). At 18 months, BDZR use was not associated with greater cognitive decline on the ADAS-Cog controlling for baseline ADAS-Cog scores, age, gender, study arm, and other clinical covariates (beta = 1.62, -1.34 to 4.56). However, ongoing BDZR use was associated with a greater likelihood of adverse events [incidence rate ratio (IRR) 1.19, 1.05-1.34], incident delirium (IRR 2.31, 1.45-3.68), and falls (IRR 1.66, 1.02-2.65) over 18 months that persisted after robust adjustment for covariates. Conclusions and Implications: This study found no effect of ongoing BDZR use on ADAS-Cog scores in those with mild to moderate AD over 18 months. However, ongoing use of these medications was associated with an increased risk of adverse events, delirium, and falls. Thus, BDZR use should be avoided where possible and deprescribing interventions should be encouraged in older adults with AD. (C) 2019 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
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| 5. |
- Custodio, C. L., et al.
(författare)
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Effect of a chemical treatment series on the structure and mechanical properties of abaca fiber (Musa textilis)
- 2020
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Ingår i: Materials Science Forum. - : Trans Tech Publications, Ltd.. ; , s. 64-69
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Konferensbidrag (refereegranskat)abstract
- This study investigates the relationships between the composition, cell wall microstructure, and mechanical properties of the abaca fiber. Raw abaca fibers have undergone a series of sequential chemical treatments (acetone/methanol, boiling water, EDTA, HCl, NaClO2, and NaOH) to selectively remove certain non-cellulosic components (NCCs) in the fiber, such as waxes, water-soluble fragments, pectin, and lignin in a step-by-step manner. Changes in composition, morphology, and mechanical properties were observed using FTIR spectroscopy and ion chromatography, digital microscope and SEM, and tensile tests, respectively. The raw fiber was composed of 23% NCCs, 18% hemicellulose, and 58% cellulose, and exhibited a 17.4 GPa Young’s modulus and a 444 MPa tensile strength. Furthermore, the raw abaca fibers demonstrated a linear tensile graph without yielding, and a planar fracture surface without fiber pull-outs, thus suggesting a highly elastic but brittle nature. At the end of the alkali treatment, the fibrillated fiber was 83% cellulose, yet the stiffness and strength dropped to 7.3 GPa and 55 MPa, respectively, as more components were removed, and microfibril relaxation and realignment have occurred. Load-bearing cellulose and hemicellulose accounted for 42% and 36% of the stiffness, respectively, due to –OH groups capable of hydrogen bonding. 63% of the strength was due to thenative NCC matrices, which contribute a significant role within the cell wall’s load-transfer activities.
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| 6. |
- Huber, S., et al.
(författare)
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Novel approach to large-scale monitoring of submerged aquatic vegetation: A nationwide example from Sweden
- 2022
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Ingår i: Integrated Environmental Assessment and Management. - : Wiley. - 1551-3777 .- 1551-3793. ; 18:4, s. 909-20
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Tidskriftsartikel (refereegranskat)abstract
- According to the EU Habitats directive, the Water Framework Directive, and the Marine Strategy Framework Directive, member states are required to map, monitor, and evaluate changes in quality and areal distribution of different marine habitats and biotopes to protect the marine environment more effectively. Submerged aquatic vegetation (SAV) is a key indicator of the ecological status of coastal ecosystems and is therefore widely used in reporting related to these directives. Environmental monitoring of the areal distribution of SAV is lacking in Sweden due to the challenges of large-scale monitoring using traditional small-scale methods. To address this gap, in 2020, we embarked on a project to combine Copernicus Sentinel-2 satellite imagery, novel machine learning (ML) techniques, and advanced data processing in a cloud-based web application that enables users to create up-to-date SAV classifications. At the same time, the approach was used to derive the first high-resolution SAV map for the entire coastline of Sweden, where an area of 1550 km(2) was mapped as SAV. Quantitative evaluation of the accuracy of the classification using independent field data from three different regions along the Swedish coast demonstrated relative high accuracy within shallower areas, particularly where water transparency was high (average total accuracy per region 0.60-0.77). However, the classification missed large proportions of vegetation growing in deeper water (on average 31%-50%) and performed poorly in areas with fragmented or mixed vegetation and poor water quality, challenges that should be addressed in the development of the mapping methods towards integration into monitoring frameworks such as the EU directives. In this article, we present the results of the first satellite-derived SAV classification for the entire Swedish coast and show the implementation of a cloud-based SAV mapping application (prototype) developed within the frame of the project. Integr Environ Assess Manag 2021;00:1-12. (c) 2021 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).
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| 7. |
- Rosentau, A., et al.
(författare)
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A Holocene relative sea-level database for the Baltic Sea
- 2021
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 266
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Tidskriftsartikel (refereegranskat)abstract
- We present a compilation and analysis of 1099 Holocene relative shore-level (RSL) indicators located around the Baltic Sea including 867 relative sea-level data points and 232 data points from the Ancylus Lake and the following transitional phase. The spatial distribution covers the Baltic Sea and near-coastal areas fairly well, but some gaps remain mainly in Sweden. RSL data follow the standardized HOLSEA format and, thus, are ready for spatially comprehensive applications in, e.g., glacial isostatic adjustment (GIA) modelling. We apply a SQL database system to store the nationally provided data sets in their individual form and to map the different input into the HOLSEA format as the information content of the individual data sets from the Baltic Sea area differs. About 80% of the RSL data is related to the last marine stage in Baltic Sea history after 8.5 ka BP (thousand years before present). These samples are grouped according to their dominant RSL tendencies into three clusters: regions with negative, positive and complex (transitional) RSL tendencies. Overall, regions with isostatic uplift driven negative tendencies dominate and show regression in the Baltic Sea basin during the last marine stage. Shifts from positive to negative tendencies in RSL data from transitional regions show a mid-Holocene highstand around 7.5-6.5 ka BP which is consistent with the end of the final melting of the Laurentide Ice Sheet. Comparisons of RSL data with GIA predictions including global ICE-5G and ICE-6G_C ice histories show good fit with RSL data from the regions with negative tendencies, whereas in the transitional areas in the eastern Baltic, predictions for the mid-Holocene clearly overestimate the RSL and fail to recover the midHolocene RSL highstand derived from the proxy reconstructions. These results motivate improvements of ice-sheet and Earth-structure models and show the potential and benefits of the new compilation for future studies. (C) 2021 The Authors. Published by Elsevier Ltd.
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| 10. |
- Das, I, et al.
(författare)
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AXL and CAV-1 play a role for MTH1 inhibitor TH1579 sensitivity in cutaneous malignant melanoma
- 2020
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Ingår i: Cell death and differentiation. - : Springer Science and Business Media LLC. - 1476-5403 .- 1350-9047. ; 27:7, s. 2081-2098
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Tidskriftsartikel (refereegranskat)abstract
- Cutaneous malignant melanoma (CMM) is the deadliest form of skin cancer and clinically challenging due to its propensity to develop therapy resistance. Reactive oxygen species (ROS) can induce DNA damage and play a significant role in CMM. MTH1 protein protects from ROS damage and is often overexpressed in different cancer types including CMM. Herein, we report that MTH1 inhibitor TH1579 induced ROS levels, increased DNA damage responses, caused mitotic arrest and suppressed CMM proliferation leading to cell death both in vitro and in an in vivo xenograft CMM zebrafish disease model. TH1579 was more potent in abrogating cell proliferation and inducing cell death in a heterogeneous co-culture setting when compared with CMM standard treatments, vemurafenib or trametinib, showing its broad anticancer activity. Silencing MTH1 alone exhibited similar cytotoxic effects with concomitant induction of mitotic arrest and ROS induction culminating in cell death in most CMM cell lines tested, further emphasizing the importance of MTH1 in CMM cells. Furthermore, overexpression of receptor tyrosine kinase AXL, previously demonstrated to contribute to BRAF inhibitor resistance, sensitized BRAF mutant and BRAF/NRAS wildtype CMM cells to TH1579. AXL overexpression culminated in increased ROS levels in CMM cells. Moreover, silencing of a protein that has shown opposing effects on cell proliferation, CAV-1, decreased sensitivity to TH1579 in a BRAF inhibitor resistant cell line. AXL-MTH1 and CAV-1-MTH1 mRNA expressions were correlated as seen in CMM clinical samples. Finally, TH1579 in combination with BRAF inhibitor exhibited a more potent cell killing effect in BRAF mutant cells both in vitro and in vivo. In summary, we show that TH1579-mediated efficacy is independent of BRAF/NRAS mutational status but dependent on the expression of AXL and CAV-1.
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