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| 2. |
- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 4. |
- Berglund, Björn, et al.
(författare)
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Occurrence and removal efficiency of parasitic protozoa in Swedish wastewater treatment plants
- 2017
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 598, s. 821-827
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Tidskriftsartikel (refereegranskat)abstract
- Giardia intestinalis, Cryptosporidium spp., Entamoeba histolytica and Dientamoeba fragilis are parasitic protozoa and causative agents of gastroenteritis in humans. G. intestinalis and Cryptosporidium spp. in particular are the most common protozoa associated with waterborne outbreaks in high-income countries. Surveillance of protozoan prevalence in wastewater and evaluation of wastewater treatment removal efficiencies of protozoan pathogens is therefore imperative for assessment of human health risk. In this study, influent and effluent wastewater samples from three wastewater treatment plants in Sweden were collected over nearly one year and assessed for prevalence of parasitic protozoa. Quantitative real-time PCR using primers specific for the selected protozoa Cryptosporidium spp., G. intestinalis, E. histolytica, Entamoeba dispar and D. fragilis was used for protozoan DNA detection and assessment of wastewater treatment removal efficiencies. Occurrence of G. intestinalis, E. dispar and D. fragilis DNA was assessed in both influent (44, 30 and 39 out of 51 samples respectively) and effluent wastewater (14, 9 and 33 out of 51 samples respectively) in all three wastewater treatment plants. Mean removal efficiencies of G. intestinalis, E. dispar and D. fragilis DNA quantities, based on all three wastewater treatment plants studied varied between 67 and 87%, 37–75% and 20–34% respectively. Neither E. histolytica nor Cryptosporidium spp. were detected in any samples. Overall, higher quantities of protozoan DNA were observed from February to June 2012. The high prevalence of protozoa in influent wastewater indicates the need for continued monitoring of these pathogens in wastewater-associated aquatic environments to minimise the potential risk for human infection.
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| 5. |
- Chudinova, E., et al.
(författare)
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Determination of the properties and loading efficiency of encapsulated BSA-FITC and dexamethasone for drug delivery systems
- 2019
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Ingår i: IOP Conference Series. - : Institute of Physics Publishing (IOPP).
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Konferensbidrag (refereegranskat)abstract
- In this work porous microparticles of calcium carbonate were synthesized with bovine serum albumin - fluorescein isothiocyanate conjugate (BSA-FITC) and dexamethasone, and then used for encapsulation in polymer microcapsules by means of layer-by-layer assembly (LbL). The properties of the obtained microcapsules were characterized by scanning electron microscopy, dynamic light scattering, infrared-, ultraviolet- and visible spectroscopy. According to the performed DLS measurements, an average hydrodynamic diameter ranged from 4 to 8 m and zeta-potential for all types of capsules was determined as -18 and -21 mV. BSA-FITC was encapsulated using this approach yielded a loading efficiency of 49 % protein. This value calculated for dexamethasone was of 38%. The microcapsules filled with an encapsulated drug may find applications in the field of biotechnology, biochemistry, and medicine.
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| 6. |
- Chudinova, E., et al.
(författare)
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Functionalization of additive-manufactured Ti6Al4V scaffolds with poly(allylamine hydrochloride)/poly(styrene sulfonate) bilayer microcapsule system containing dexamethasone
- 2021
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Ingår i: Materials Chemistry and Physics. - : Elsevier BV. - 0254-0584 .- 1879-3312. ; 273
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Tidskriftsartikel (refereegranskat)abstract
- Porous titanium alloy Ti6Al4V scaffolds manufactured via electron beam melting (EBM®) reveal broad prospects for applications in bone tissue engineering. However, local inflammation and even implant failure may occur while placing an implant into the body. Thus, the application of drug carriers to the surface of a metallic implant can provide treatment at the inflammation site. In this study, we propose to use polyelectrolyte (PE) microcapsules formed by layer-by-layer (LbL) synthesis loaded with both porous calcium carbonate (CaCO3) microparticles and the anti-inflammatory drug dexamethasone (DEX) to functionalize implant surfaces and achieve controlled drug release. Scanning electron microscopy indicated that the CaCO3 microparticles coated with PE bilayers loaded with DEX had a spherical shape with a diameter of 2.3 ± 0.2 μm and that the entire scaffold surface was evenly coated with the microcapsules. UV spectroscopy showed that LbL synthesis allows the manufacturing of microcapsules with 40% DEX. According to high performance liquid chromatography (HPLC) analysis, 80% of the drug was released within 24 h from the capsules consisting of three bilayers of polystyrene sulfonate (PSS) and poly(allylamine)hydrochloride (PAH). The prepared scaffolds functionalized with CaCO3 microparticles loaded with DEX and coated with PE bilayers showed hydrophilic surface properties with a water contact angle below 5°. Mouse embryonic fibroblast cells were seeded on Ti6Al4V scaffolds with and without LbL surface modification. The surface modification with LbL PE microcapsules with CaCO3 core affected cell morphology in vitro. The results confirmed that DEX had no toxic effect and did not prevent cell adhesion and spreading, thus no cytotoxic effect was observed, which will be further studied in vivo.
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| 10. |
- Palin, K, et al.
(författare)
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Contribution of allelic imbalance to colorectal cancer
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 3664-
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Tidskriftsartikel (refereegranskat)abstract
- Point mutations in cancer have been extensively studied but chromosomal gains and losses have been more challenging to interpret due to their unspecific nature. Here we examine high-resolution allelic imbalance (AI) landscape in 1699 colorectal cancers, 256 of which have been whole-genome sequenced (WGSed). The imbalances pinpoint 38 genes as plausible AI targets based on previous knowledge. Unbiased CRISPR-Cas9 knockout and activation screens identified in total 79 genes within AI peaks regulating cell growth. Genetic and functional data implicate loss of TP53 as a sufficient driver of AI. The WGS highlights an influence of copy number aberrations on the rate of detected somatic point mutations. Importantly, the data reveal several associations between AI target genes, suggesting a role for a network of lineage-determining transcription factors in colorectal tumorigenesis. Overall, the results unravel the contribution of AI in colorectal cancer and provide a plausible explanation why so few genes are commonly affected by point mutations in cancers.
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| 11. |
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| 12. |
- Smelov, V, et al.
(författare)
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Beta and gamma human papillomaviruses in anal and genital sites among men: prevalence and determinants
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 8241-
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Tidskriftsartikel (refereegranskat)abstract
- Data regarding the anogenital distribution of and type-specific concordance for cutaneous β- and γ-HPV types in men who have sex with women is limited and geographically narrow. Knowledge of determinants of anogenital detection of cutaneous HPV types in different regions is needed for better understanding of the natural history and transmission dynamics of HPV, and its potential role in the development of anogenital diseases. Genital and anal canal samples obtained from 554 Russian men were screened for 43 β-HPVs and 29 γ-HPVs, using a multiplex PCR combined with Luminex technology. Both β- and γ-HPVs were more prevalent in the anal (22.8% and 14.1%) samples than in the genital (16.8% and 12.3%) samples. Low overall and type-specific concordance for β-HPVs (3.5% and 1.1%) and γ-HPVs (1.3% and 0.6%) were observed between genital and anal samples. HIV-positive men had higher anal β- (crude OR = 12.2, 95% CI: 5.3–28.1) and γ-HPV (crude OR = 7.2, 95% CI: 3.3–15.4) prevalence than HIV-negative men. Due to the lack of genital samples from the HIV-positive men, no comparison was possible for HIV status in genital samples. The lack of type-specific positive concordance between genital and anal sites for cutaneous β- and γ-HPV types in heterosexual men posits the needs for further studies on transmission routes to discriminate between contamination and true HPV infection. HIV-positive status may favor the anal acquisition or modify the natural history of cutaneous HPV types.
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| 16. |
- Sokolova, Ekaterina, 1986, et al.
(författare)
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Microbial risk assessment of drinking water based on hydrodynamic modelling of pathogen concentrations in source water
- 2015
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 526, s. 177-186
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Tidskriftsartikel (refereegranskat)abstract
- Norovirus contamination of drinking water sources is an important cause of waterborne disease outbreaks. Knowledge on pathogen concentrations in source water is needed to assess the ability of a drinking water treatment plant (DWTP) to provide safe drinking water. However, pathogen enumeration in source water samples is often not sufficient to describe the source water quality. In this study, the norovirus concentrations were characterised at the contamination source, i.e. in sewage discharges. Then, the transport of norovirus within the water source (the river Gota alv in Sweden) under different loading conditions was simulated using a hydrodynamic model. Based on the estimated concentrations in source water, the required reduction of norovirus at the DWTP was calculated using quantitative microbial risk assessment (QMRA). The required reduction was compared with the estimated treatment performance at the DWTP. The average estimated concentration in source water varied between 4.8 x 10(2) and 7.5 x 10(3) genome equivalents L-1; and the average required reduction by treatment was between 7.6 and 8.8 Log(10). The treatment performance at the DWTP was estimated to be adequate to deal with all tested loading conditions, but was heavily dependent on chlorine disinfection, with the risk of poor reduction by conventional treatment and slow sand filtration. To our knowledge, this is the first article to employ discharge-based QMRA, combined with hydrodynamic modelling, in the context of drinking water. (C) 2015 Elsevier B.V. All rights reserved.
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| 18. |
- Vuorinen, Katariina E.M., et al.
(författare)
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Growth rings show limited evidence for ungulates' potential to suppress shrubs across the Arctic
- 2022
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Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9318 .- 1748-9326. ; 17:3
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Tidskriftsartikel (refereegranskat)abstract
- Global warming has pronounced effects on tundra vegetation, and rising mean temperatures increase plant growth potential across the Arctic biome. Herbivores may counteract the warming impacts by reducing plant growth, but the strength of this effect may depend on prevailing regional climatic conditions. To study how ungulates interact with temperature to influence growth of tundra shrubs across the Arctic tundra biome, we assembled dendroecological data from 20 sites, comprising 1153 individual shrubs and 223 63 annual growth rings. Evidence for ungulates suppressing shrub radial growth was only observed at intermediate summer temperatures (6.5 °C-9 °C), and even at these temperatures the effect was not strong. Multiple factors, including forage preferences and landscape use by the ungulates, and favourable climatic conditions enabling effective compensatory growth of shrubs, may weaken the effects of ungulates on shrubs, possibly explaining the weakness of observed ungulate effects. Earlier local studies have shown that ungulates may counteract the impacts of warming on tundra shrub growth, but we demonstrate that ungulates' potential to suppress shrub radial growth is not always evident, and may be limited to certain climatic conditions.
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