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1.
  • Hallberg, Ida, et al. (författare)
  • Perfluorononanoic acid (PFNA) alters lipid accumulation in bovine blastocysts after oocyte exposure during in vitro maturation
  • 2019
  • Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 84, s. 1-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Perfluorononanoic acid (PFNA) is one of the perfluoroalkyl acids present in human tissues. In this study, effects on early embryo development after PFNA exposure were investigated using the bovine in vitro production system. Oocytes were exposed to PFNA during maturation in vitro (10 μg mL-1 and 0.1 μg mL-1), and then fertilized and cultured in parallel with control groups. Developmental parameters (cleavage, blastocyst formation) were followed and embryo quality evaluated (stage, grade). Embryos developed after exposure to 0.1 μg mL-1 were stained to distinguish nuclei, active mitochondria and neutral lipids. 10 μg mL-1 of PFNA had a severe negative effect on blastocyst formation (OR: 0.27 p < 0.05), an effect not observed at 0.1 μg mL-1. However, lipid droplet distribution was significantly altered in embryos exposed to 0.1 μg mL-1, suggesting a disturbance of lipid metabolism after exposure to sublethal levels of PFNA during oocyte maturation in vitro.
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2.
  • Gillman, Anna, et al. (författare)
  • Oseltamivir-Resistant Influenza A (H1N1) Virus Strain with an H274Y Mutation in Neuraminidase Persists without Drug Pressure in Infected Mallards
  • 2015
  • Ingår i: Applied and Environmental Microbiology. - : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 81:7, s. 2378-2383
  • Tidskriftsartikel (refereegranskat)abstract
    • Influenza A virus (IAV) has its natural reservoir in wild waterfowl, and emerging human IAVs often contain gene segments from avian viruses. The active drug metabolite of oseltamivir (oseltamivir carboxylate [OC]), stockpiled as Tamiflu for influenza pandemic preparedness, is not removed by conventional sewage treatment and has been detected in river water. There, it may exert evolutionary pressure on avian IAV in waterfowl, resulting in the development of resistant viral variants. A resistant avian IAV can circulate among wild birds only if resistance does not restrict viral fitness and if the resistant virus can persist without continuous drug pressure. In this in vivo mallard (Anas platyrhynchos) study, we tested whether an OC-resistant avian IAV (H1N1) strain with an H274Y mutation in the neuraminidase (NA-H274Y) could retain resistance while drug pressure was gradually removed. Successively infected mallards were exposed to decreasing levels of OC, and fecal samples were analyzed for the neuraminidase sequence and phenotypic resistance. No reversion to wild-type virus was observed during the experiment, which included 17 days of viral transmission among 10 ducks exposed to OC concentrations below resistance induction levels. We conclude that resistance in avian IAV that is induced by exposure of the natural host to OC can persist in the absence of the drug. Thus, there is a risk that human-pathogenic IAVs that evolve from IAVs circulating among wild birds may contain resistance mutations. An oseltamivir-resistant pandemic IAV would pose a substantial public health threat. Therefore, our observations underscore the need for prudent oseltamivir use, upgraded sewage treatment, and surveillance for resistant IAVs in wild birds.
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3.
  • Younis, Shady, et al. (författare)
  • Multiple nuclear-replicating viruses require the stress-induced protein ZC3H11A for efficient growth
  • 2018
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - Washington, United States : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 115:16, s. E3808-E3816
  • Tidskriftsartikel (refereegranskat)abstract
    • The zinc finger CCCH-type containing 11A (ZC3H11A) gene encodes a well-conserved zinc finger protein that may function in mRNA export as it has been shown to associate with the transcription export (TREX) complex in proteomic screens. Here, we report that ZC3H11A is a stress-induced nuclear protein with RNA-binding capacity that localizes to nuclear splicing speckles. During an adenovirus infection, the ZC3H11A protein and splicing factor SRSF2 relocalize to nuclear regions where viral DNA replication and transcription take place. Knockout (KO) of ZC3H11A in HeLa cells demonstrated that several nuclear-replicating viruses are dependent on ZC3H11A for efficient growth (HIV, influenza virus, herpes simplex virus, and adenovirus), whereas cytoplasmic replicating viruses are not (vaccinia virus and Semliki Forest virus). High-throughput sequencing of ZC3H11A-cross-linked RNA showed that ZC3H11A binds to short purine-rich ribonucleotide stretches in cellular and adenoviral transcripts. We show that the RNA-binding property of ZC3H11A is crucial for its function and localization. In ZC3H11A KO cells, the adenovirus fiber mRNA accumulates in the cell nucleus. Our results suggest that ZC3H11A is important for maintaining nuclear export of mRNAs during stress and that several nuclear-replicating viruses take advantage of this mechanism to facilitate their replication.
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4.
  • Kreisel, Katrin, 1991, et al. (författare)
  • DNA polymerase η contributes to genome-wide lagging strand synthesis.
  • 2019
  • Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 47:5, s. 2425-2435
  • Tidskriftsartikel (refereegranskat)abstract
    • DNA polymerase η (pol η) is best known for its ability to bypass UV-induced thymine-thymine (T-T) dimers and other bulky DNA lesions, but pol ηalso has other cellular roles. Here, we present evidence that pol η competes with DNA polymerases α and δfor the synthesis of the lagging strand genome-wide, where it also shows a preference for T-T in the DNA template. Moreover, we found that the C-terminus of pol η,which contains a PCNA-Interacting Protein motif is required for pol ηto function in lagging strand synthesis. Finally, we provide evidence that a pol η dependent signature is also found to be lagging strand specific in patients with skin cancer. Taken together, these findings provide insight into the physiological role of DNA synthesis by pol η and have implications for our understanding of how our genome is replicated to avoid mutagenesis, genome instability and cancer.
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5.
  • Dencker, Lennart, et al. (författare)
  • Position Paper : EUFEPS Network on Veterinary Medicines Initiative: An interdisciplinary forum to support Veterinary Pharmacology and promote the development of new pharmaceuticals for Animal Health
  • 2016
  • Ingår i: European Journal of Pharmaceutical Sciences. - 0928-0987 .- 1879-0720. ; 91, s. I-VII
  • Tidskriftsartikel (refereegranskat)abstract
    • Veterinary medicines account for a substantial portion of the production, sale, and consumption of medicines in Europe, and probably world-wide. This calls our attention to the fact that only healthy farm animals can ensure safe and sufficient livestock products to meet the growing demand for animal protein. Human and veterinary medicine share many common features - expressed and symbolised by the "One Health Concept". This concept forms the logical basis for the maintenance of healthy livestock by the control of zoonoses and foodborne diseases, the prevention of poor sanitary conditions, and the reduction of microbial and parasitic threats, including resistance to antibiotics and anti-parasitic drugs. Achieving these aims will require international cooperation and interdisciplinary action. A new initiative of the European Federation for Pharmaceutical Sciences (EUFEPS) - the Network on Veterinary Medicines - has the potential to manage and overcome these challenges. A number of EUFEPS expertise networks have already been established, and some will be instrumental in supporting the activities of the Network on Veterinary Medicines, e.g., the European Network on PharmacoGenomics Research and Implementation (EPRIN), as well as the Network on Bioavailability and Biopharmaceutics, and the envisioned Network on Systems Pharmacology. Notably, the EUFEPS Networks on Safety Sciences, on Environment and Pharmaceuticals and on NanoMedicine as well as on Regulatory Science, represent promising partners. New technologies are being introduced to veterinary medicine for the treatment of numerous and frequently species-specific conditions. Scientific input from different areas is required to evaluate the potential benefitrisk profiles of these novel products, drug delivery techniques, and medical attention for animals as a whole. Drug treatment of food-producing animals inevitably affects consumer safety and public health, as any administration of medicines to animals may result in the presence of drug residues in edible tissues or products such as milk, eggs, and honey. The many questions surrounding the risks to human health and to the environment posed by exposure to veterinary drug residues cause great concern among health authorities as well as the public. In particular, the shared use of many classes of antimicrobials in both veterinary and human medicine, the emergence and spread of resistant microbes from animals or animal-derived products to humans, and the presence of contaminated manure in the environment are all provoking deep concern throughout the world. The Network on Veterinary Medicines initiative sees itself as broadly positioned. Among its most important goals are contributing to legislative issues in veterinary medicine and to the development of new pharmaceuticals for animal health, including novel drug delivery systems. Efforts to support the academic teaching and training of veterinary professionals and formulators for veterinary drug delivery are also considered imperative objectives of the network. The pursuit of these tasks will depend on interdisciplinary cooperation among experts from pharmaceutical and veterinary sciences, concentrating on issues where scientists from academia, industry and regulatory agencies can collaborate. National and international healthcare bodies, as well as organisations dedicated to the endorsement of teaching and training of scientists in pharmaceutical and veterinary sciences, are also key partners. Major objectives of the network include the following: strengthening academic research to promote the emergence of new concepts, principles and mechanisms of action to develop innovative new veterinary medicinal products, supporting the education and training of future healthcare professionals in veterinary practice, pharmacy and industrial research, including continuing professional development, and supporting Veterinary Universities. Further efforts of the Network will encourage the European Commission to initiate calls for research in the area of veterinary medicines, such as Horizon 2020. Once these calls are in place, the formation of strong consortia to apply for funding (IMI, EU-funding) is projected. The success of the Network depends on the engagement and expertise of cooperating specialists. It will benefit from the experience and means of other EUFEPS networks.
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6.
  • Sjölund, Marie (författare)
  • Assigning defined daily doses animal: a European multi-country experience for antimicrobial products authorized for usage in pigs
  • 2015
  • Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 70, s. 294-302
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To establish a consensus defined daily dose animal (DDDA) for each active substance (AS) and administration route for porcine veterinary antimicrobial products authorized in four European countries, thus allowing cross-country quantification and comparison of antimicrobial usage data. METHODS: All veterinary antimicrobial products authorized for porcine use in Belgium, France, Germany and Sweden were listed for each administration route. First, separate DDDAs for each product were defined based on the recommended dosing for the main indication. Second, a consensus DDDA was established by taking the mean of the DDDAs for each product within a certain category of AS plus administration route. RESULTS: One-hundred-and-fifty-nine, 240, 281 and 50 antimicrobial products were licensed in Belgium, France, Germany and Sweden, respectively, in February 2013. Large variations were observed for dosage and treatment duration recommendations between products and between countries for the same ASs. Only 6.8% of feed/water and 29.4% of parenteral AS groups had the same recommended dosage in the four countries. CONCLUSIONS: This study presents a consensus DDDA list for use in the quantification and comparison of antimicrobial consumption. Four major recommendations have been formulated: (i) urgent need for harmonization of authorization and recommended summary of product characteristics (SPC) dosages; (ii) expand the developed preliminary DDDA list to include all authorized veterinary medicinal products in all EU member states and for all (food-producing) animal species; (iii) improved accessibility of country-specific SPC data would be preferable; and (iv) statement of the 'long-acting' duration of a product in the SPC.
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7.
  • Löfgren, Maria, et al. (författare)
  • Time-dependent changes in gene expression induced in vitro by interleukin-1 beta in equine articular cartilage
  • 2018
  • Ingår i: Research in Veterinary Science. - : Elsevier BV. - 0034-5288 .- 1532-2661. ; 118, s. 466-476
  • Tidskriftsartikel (refereegranskat)abstract
    • Osteoarthritis is an inflammatory and degenerative joint disease commonly affecting horses. To identify genes of relevance for cartilage pathology in osteoarthritis we studied the time-course effects of interleukin (IL)-1 beta on equine articular cartilage. Articular cartilage explants from the distal third metacarpal bone were collected postmortem from three horses without evidence of joint disease. The explants were stimulated with IL-1 beta for 27 days and global gene expression was measured by microarray. Gene expression was compared to that of unstimulated explants at days 3, 9, 15, 21 and 27. Release of inflammatory proteins was measured using Proximity Extension Assay. Stimulation with IL-1 beta led to time-dependent changes in gene expression related to inflammation, the extracellular matrix (ECM), and phenotypic alterations. Gene expression and protein release of cytokines, chemokines, and matrix-degrading enzymes increased in the stimulated explants. Collagen type II was down regulated from day 15, whereas other ECM molecules were downregulated earlier. In contrast molecules involved in ECM signaling (perlecan, chondroitin sulfate proteoglycan 4, and syndecan 4) were upregulated. At the late time points, genes related to a chondrogenic phenotype were downregulated, and genes related to a hypertrophic phenotype were upregulated, suggesting a transition towards hypertrophy later in the culturing period. The data suggest that this in vitro model mimics time course events of in vivo inflammation in OA and it may be valuable as an in vitro tool to test treatments and to study disease mechanisms.
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8.
  • Lindahl Rajala, Elisabeth, et al. (författare)
  • Detection and characterization of Brucella spp. in bovine milk in small-scale urban and peri-urban farming in Tajikistan
  • 2017
  • Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 11:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Brucellosis is one of the most common zoonoses globally, and Central Asia remains a Brucella hotspot. The World Health Organization classifies brucellosis as a neglected zoonotic disease that is rarely in the spotlight for research and mainly affects poor, marginalized people. Urban and peri-urban farming is a common practice in many low-income countries, and it increases the incomes of families that are often restrained by limited economic resources. However, there is a concern that the growing number of people and livestock living close together in these areas will increase the transmission of zoonotic pathogens such as Brucella. This study investigates the presence of Brucella DNA in bovine milk in the urban and peri-urban area of Dushanbe, Tajikistan. Brucella DNA was detected in 10.3% of 564 cow milk samples by IS711-based real-time PCR. This finding is concerning because consumption of unpasteurized dairy products is common in the region. Furthermore, Brucella DNA was detected in the milk of all seropositive cows, but 8.3% of the seronegative cows also showed the presence of Brucella DNA. In addition, sequence analysis of the rpoB gene suggests that one cow was infected with B. abortus and another cow was most likely infected with B. melitensis. The discrepancies between the serology and real-time PCR results highlight the need to further investigate whether there is a need for implementing complementary diagnostic strategies to detect false serological negative individuals in Brucella surveillance, control, and eradication programmes. Furthermore, vaccination of cattle with S19 in addition to vaccination of small ruminants with Rev 1 might be needed in order to control Brucella infections in the livestock population but further research focusing on the isolation of Brucella is required to obtain a comprehensive understanding of the Brucella spp. circulating among the livestock in this region.
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9.
  • Lin, Jay, et al. (författare)
  • High prevalence of hepatitis E virus in Swedish moose : A phylogenetic characterization and comparison of the virus from different regions
  • 2015
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Hepatitis E virus (HEV) infects a range of species, including humans, pigs, wild boars and deer. Zoonotic transmission may contribute to the high HEV seroprevalence in the human population of many countries. A novel divergent HEV from moose (Alces alces) in Sweden was recently identified by partial genome sequencing. Since only one strain was found, its classification within the HEV family, prevalence in moose and zoonotic potential was unclear. We therefore investigated samples from 231 moose in seven Swedish counties for HEV, and sequenced a near complete moose HEV genome. Phylogenetic analysis to classify this virus within the family Hepeviridae and to explore potential host specific determinants was performed. Methods and Findings: The HEV prevalence of moose was determined by PCR (marker for active infection) and serological assays (marker of past infection) of sera and 51 fecal samples from 231 Swedish moose. Markers of active and past infection were found in 67 (29%) animals, while 34 (15%) were positive for HEV RNA, 43 (19%) were seropositive for anti-HEV antibodies, and 10 (4%) had both markers. The number of young individuals positive for HEV RNA was larger than for older individuals, and the number of anti-HEV antibody positive individuals increased with age. The high throughput sequenced moose HEV genome was 35-60% identical to existing HEVs. Partial ORF1 sequences from 13 moose strains showed high similarity among them, forming a distinct monophyletic clade with a common ancestor to HEV genotype 1-6 group, which includes members known for zoonotic transmission. Conclusions: This study demonstrates a high frequency of HEV in moose in Sweden, with markers of current and past infection demonstrated in 30% of the animals. Moose is thus an important animal reservoir of HEV. The phylogenetic relationship demonstrated that the moose HEV belonged to the genotype 1-6 group, which includes strains that also infect humans, and therefore may signify a potential for zoonotic transmission of this HEV. © 2015 Lin et al.
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10.
  • Cuevas Romero, Julieta Sandra (författare)
  • Studies of the molecular genetics and epidemiology of porcine rubulavirus infection
  • 2015
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Porcine rubulavirus (PorPV) infection emerged spontaneously in pigs in Mexico in the early 1980s. Since the report of the initial outbreak of the disease, only one full-length genome from a strain isolated in 1984 (PorPV-LPMV/1984) has been sequenced. There is therefore limited information about the genetic variation of this virus. The overall objective of this thesis was to develop molecular techniques to help in the diagnostic field and to investigate in greater detail the full genomes of several isolates, and if possible, gain insights into the persistence, molecular epidemiology and the possible reservoirs of PorPV. In addition, a characterisation of the immune response during acute and persistent infection was included. A real-time RT-PCR was developed for the detection of viral RNA from PorPV in clinical samples using TaqMan technology and primers for the P gene. This assay was highly sensitive (approximately 10 copies per reaction), specific, reproducible and a very useful tool for molecular diagnostics and for enabling studies of various aspects of PorPV throughout this thesis. RT-PCRs based on the NP and P genes were used to study the tissue distribution of the virus. Viral mRNA in the lymph nodes showed that the NP gene was consistently detected in the parotid, submaxilar, cervical and mesenteric nodes and the pancreas. Full-length genomes were sequenced from new isolates obtained from clinical cases of infected swine. The genetic comparison and phylogenetic analysis indicated that three different genetic variants of PorPV had spread in the swine population and that a new generation of circulating virus with a pronounced attenuation has begun to emerge in nature. We also report the isolation of PorPV, or a related virus, from frugivorous, insectivorous, and hematophagous bats. A partial genome sequence analysis showed a 99.97 - 100% amino acid identity to the reference strain isolated from swine. However, larger parts of the genome must be sequenced to ascertain the genetic relationship between these viruses. The study of the immune response during acute and persistent infection revealed enhanced levels of CD8+, CD4+ and CD2+ T-cells in all infected pigs at 10 days PI. CD8+ T-cell subpopulations were significantly higher (p<0.05) at 10 and 250 days PI, and CD4+ T-lymphocytes were also significant at 250 days PI. In summary, this work developed molecular techniques that can be used to study the pathogenesis and molecular epidemiology of PorPV. The knowledge of the presence of different virus variants in nature, associated with a wildlife reservoir of PorPV can provide greater knowledge regarding the molecular genetic changes and useful data to establish new strategies in the control of this virus in Mexico.
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11.
  • Riihimäki, Miia, et al. (författare)
  • Viral load of equine herpesviruses 2 and 5 in nasal swabs of actively racing Standardbred trotters: Temporal relationship of shedding to clinical findings and poor performance
  • 2015
  • Ingår i: Veterinary Microbiology. - : Elsevier BV. - 0378-1135 .- 1873-2542. ; 179, s. 142-148
  • Tidskriftsartikel (refereegranskat)abstract
    • The equine gamma herpesviruses 2 and 5 (EHV-2 and -5) have frequently been observed in the equine population and until recently presumed low to nonpathogenic. However, recent reports linking presence of equine gamma herpesviruses with clinical signs of mild to severe lung disease, suggest that the role of these viruses in respiratory disease and poor performance syndrome is still unclear. Moreover, baseline data regarding the temporal pattern of shedding of EHV-2 and EHV-5 within stables and within individual actively racing horses have been lacking. In a prospective longitudinal study, we followed elite racing Standardbred trotters at monthly intervals for 13 months, to investigate whether the amount of EHV-2 and EHV-5 shedded in nasal secretions varied over time within and between individual horses. Sixty-six elite horses were investigated by analyzing nasal swabs and serum samples, a health check and evaluation of athletic performance monthly during the study period. Nasal swabs were analyzed with two newly developed qPCR assays for EHV-2 and EHV-5, respectively. Of 663 samples, 197 (30%) were positive for EHV-2 and 492(74%) positive for EHV-5. Furthermore, 176(27%) of the samples were positive for both EHV-2 and EHV-5 simultaneously. There was considerable variation in the amount and frequency of shedding of EHV-2 and EHV-5 within and between individual horses. Viral load varied seasonally, but neither EHV-2 nor EHV-5 viral peaks were associated with clinical respiratory disease and/or poor performance in racing Standardbred trotters. (C) 2015 Elsevier B.V. All rights reserved.
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12.
  • Skiöldebrand, Eva, et al. (författare)
  • Cartilage oligomeric matrix protein neoepitope in the synovial fluid of horses with acute lameness: A new biomarker for the early stages of osteoarthritis
  • 2017
  • Ingår i: Equine Veterinary Journal. - : Wiley. - 0425-1644 .- 2042-3306. ; 49:5, s. 662-667
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundClinical tools to diagnose the early changes of osteoarthritis (OA) that occur in the articular cartilage are lacking. ObjectivesWe sought to identify and quantify a novel cartilage oligomeric matrix protein (COMP) neoepitope in the synovial fluid from the joints of healthy horses and those with different stages of OA. Study designIn vitro quantitative proteomics and assay development with application in synovial fluids samples obtained from biobanks of well-characterised horses. MethodsArticular cartilage explants were incubated with or without interleukin-1 for 25 days. Media were analysed via quantitative proteomics. Synovial fluid was obtained from either normal joints (n = 15) or joints causing lameness (n = 17) or with structural OA lesions (n = 7) and analysed for concentrations of the COMP neoepitope using a custom-developed inhibition enzyme-linked immunosorbent assay (ELISA). Explants were immunostained with polyclonal antibodies against COMP and the COMP neoepitopes. ResultsSemitryptic COMP peptides were identified and quantified in cell culture media from cartilage explants. A rabbit polyclonal antibody was raised against the neoepitope of the N-terminal portion of one COMP fragment (sequence SGPTHEGVC). An inhibition ELISA was developed to quantify the COMP neoepitope in synovial fluid. The mean concentration of the COMP neoepitope significantly increased in the synovial fluid from the joints responsible for acute lameness compared with normal joints and the joints of chronically lame horses and in joints with chronic structural OA. Immunolabelling for the COMP neoepitope revealed a pericellular staining in the interleukin-1-stimulated explants. Main limitationsThe ELISA is based on polyclonal antisera rather than a monoclonal antibody. ConclusionsThe increase in the COMP neoepitope in the synovial fluid from horses with acute lameness suggests that this neoepitope has the potential to be a unique candidate biomarker for the early molecular changes in articular cartilage associated with OA.
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13.
  • Soni, Nikulkumar, 1984, et al. (författare)
  • Eicosapentaenoic and docosahexaenoic acid-enriched high fat diet delays the development of fatty liver in mice
  • 2015
  • Ingår i: Lipids in Health and Disease. - : Springer Science and Business Media LLC. - 1476-511X. ; 14:1, s. 74-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Low hepatic content of n-3 PUFA has been associated with NAFLD in humans. Whether this is associated with reduced dietary intake or increased turnover of these FA is not clear. We have here investigated the effects of dietary fat quality on hepatic lipid storage and transcriptomics over time.AIM:To investigate the effects of quality of fat in a high fat diet (HFD) over time on hepatic lipid storage and liver transcriptomics.METHODS AND RESULTS:Male C57BL/6J mice were fed control, HFD-eicosapentaenoic acid (EPA)/ docosahexaenoic acid (DHA) or HFD-corn oil diet for 8 or 12 weeks. Body weight, body composition, plasma and hepatic triglyceride contents were measured. Hepatic transcriptomes were analysed by microarray followed by gene-set enrichment analyses. At 8 weeks, the HFD-corn oil mice had higher body weight and adipose depot mass than the HFD-EPA/DHA but there were no differences at 12 weeks. Hepatic triglyceride content was lower in HFD-EPA/DHA fed compared with the HFD-corn oil fed mice at both time-points. Enrichment analyses of the hepatic transcriptomes showed that lipid/fatty acid biosynthesis; transport and homeostasis were lower in the HFD-EPA/DHA fed compared with the HFD-corn oil fed mice. Genes encoding proteins associated to cytoplasmic lipid droplets were expressed at higher levels in livers from the HFD-corn oil compared to HFD-EPA/DHA mice.CONCLUSIONS:Dietary EPA and DHA counteracted development of HFD-induced fatty liver. The liver transcriptome data implicate that the quality of dietary fat could modulate Ppar-related gene expression that in turn affects hepatic lipid storage and maintenance of metabolic health.
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14.
  • Ardesjö-Lundgren, Brita, et al. (författare)
  • Comparison of cellular location and expression of Plakophilin-2 in epidermal cells from nonlesional atopic skin and healthy skin in German shepherd dogs
  • 2017
  • Ingår i: Veterinary dermatology (Print). - : Wiley. - 0959-4493 .- 1365-3164. ; 28:4, s. 377-e88
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundCanine atopic dermatitis (CAD) is an inflammatory and pruritic allergic skin disease caused by interactions between genetic and environmental factors. Previously, a genome‐wide significant risk locus on canine chromosome 27 for CAD was identified in German shepherd dogs (GSDs) and Plakophilin‐2 (PKP2) was defined as the top candidate gene. PKP2 constitutes a crucial component of desmosomes and also is important in signalling, metabolic and transcriptional activities.ObjectivesThe main objective was to evaluate the role of PKP2 in CAD by investigating PKP2 expression and desmosome structure in nonlesional skin from CAD‐affected (carrying the top GWAS SNP risk allele) and healthy GSDs. We also aimed at defining the cell types in the skin that express PKP2 and its intracellular location.Animals/MethodsSkin biopsies were collected from nine CAD‐affected and five control GSDs. The biopsies were frozen for immunofluorescence and fixed for electron microscopy immunolabelling and morphology.ResultsWe observed the novel finding of PKP2 expression in dendritic cells and T cells in dog skin. Moreover, we detected that PKP2 was more evenly expressed within keratinocytes compared to its desmosomal binding‐partner plakoglobin. PKP2 protein was located in the nucleus and on keratin filaments attached to desmosomes. No difference in PKP2 abundance between CAD cases and controls was observed.ConclusionPlakophilin‐2 protein in dog skin is expressed in both epithelial and immune cells; based on its subcellular location its functional role is implicated in both nuclear and structural processes.
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15.
  • Björkman, Frida, et al. (författare)
  • Regular moist snuff dipping does not affect endurance exercise performance
  • 2017
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Physiological and medical effects of snuff have previously been obtained either in cross-sectional studies or after snuff administration to non-tobacco users. The effects of snuff cessation after several years of daily use are unknown. 24 participants with >2 years of daily snuff-use were tested before and after >6 weeks snuff cessation (SCG). A control group (CO) of 11 snuff users kept their normal habits. Resting heart rate (HR) and blood pressure (BP) were significantly lower in SCG after snuff cessation, and body mass was increased by 1.4 +/- 1.7 kg. Total cholesterol increased from 4.12 +/- 0.54 (95% CI 3.89-4.35) to 4.46 +/- 0.70 (95% CI 4.16-4.75) mM L-1 in SCG, due to increased LDL, and this change was significantly different from CO. Resting values of HDL, C-reactive protein, and free fatty acids (FFA) remained unchanged in both groups. In SCG group, both HR and BP were reduced during a four-stage incremental cycling test (from 50 to 80% of VO(2)max) and a prolonged cycling test (60 min at 50% of VO(2)max). Oxygen uptake (VO2), respiratory exchange ratio, blood lactate (bLa) and blood glucose (bGlu) concentration, and rate of perceived exertion (RPE) were unchanged. In CO group, all measurements were unchanged. During the prolonged cycling test, FFA was reduced, but with no significant difference between groups. During the maximal treadmill running test peak values of VO2, pulmonary ventilation (VE), time to exhaustion and bLa were unchanged in both groups. In conclusion, endurance exercise performance (VO(2)dmax and maximal endurance time) does not seem to be affected by prolonged snuff use, while effects on cardiovascular risk factors are contradictory. HR and BP during rest and submaximal exercise are reduced after cessation of regular use of snuff. Evidently, the long-time adrenergic stress on circulation is reversible.
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16.
  • Mbotha, D., et al. (författare)
  • Inter-epidemic Rift Valley fever virus seroconversions in an irrigation scheme in Bura, south-east Kenya
  • 2018
  • Ingår i: Transboundary and Emerging Diseases. - : Hindawi Limited. - 1865-1674 .- 1865-1682. ; 65:1, s. e55-e62
  • Tidskriftsartikel (refereegranskat)abstract
    • Rift Valley fever (RVF) is an acute mosquito-borne viral zoonosis whose outbreaks are often associated with prolonged rainfall and flooding, during which large numbers of vectors emerge. Recent studies into the inter-epidemic maintenance of RVF virus (RVFV) suggest that both vertical transmission in vectors and direct transmission between hosts act in combination with predisposing factors for persistence of the virus. A comparative longitudinal survey was carried out in Tana River County, Kenya, in irrigated, riverine and pastoral ecosystems from September 2014-June 2015. The objectives were to investigate the possibility of low-level RVFV transmission in these ecosystems during an inter-epidemic period (IEP), examine variations in RVFV seroprevalence in sheep and goats and determine the risk factors for transmission. Three hundred and sixteen small ruminants were selected and tested for immunoglobulin G antibodies against RVFV nucleoprotein using a competitive ELISA during six visits. Data on potential risk factors were also captured. Inter-epidemic RVFV transmission was evidenced by 15 seroconversions within the irrigated and riverine villages. The number of seroconversions was not significantly different (OR=0.66, CI=0.19-2.17, p=.59) between irrigated and riverine areas. No seroconversions were detected in the pastoral ecosystem. This study highlights the increased risk of inter-epidemic RVFV transmission posed by irrigation, through provision of necessary environmental conditions that enable vectors access to more breeding grounds, resting places and shade, which favour their breeding and survival.
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17.
  • Boulund, Fredrik, 1985, et al. (författare)
  • Computational discovery and functional validation of novel fluoroquinolone resistance genes in public metagenomic data sets
  • 2017
  • Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 18:1, s. Art 682-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Fluoroquinolones are broad-spectrum antibiotics used to prevent and treat a wide range of bacterial infections. Plasmid-mediated qnr genes provide resistance to fluoroquinolones in many bacterial species and are increasingly encountered in clinical settings. Over the last decade, several families of qnr genes have been discovered and characterized, but their true prevalence and diversity still remain unclear. In particular, environmental and host-associated bacterial communities have been hypothesized to maintain a large and unknown collection of qnr genes that could be mobilized into pathogens. Results: In this study we used computational methods to screen genomes and metagenomes for novel qnr genes. In contrast to previous studies, we analyzed an almost 20-fold larger dataset comprising almost 13 terabases of sequence data. In total, 362,843 potential qnr gene fragments were identified, from which 611 putative qnr genes were reconstructed. These gene sequences included all previously described plasmid-mediated qnr gene families. Fifty-two of the 611 identified qnr genes were reconstructed from metagenomes, and 20 of these were previously undescribed. All of the novel qnr genes were assembled from metagenomes associated with aquatic environments. Nine of the novel genes were selected for validation, and six of the tested genes conferred consistently decreased susceptibility to ciprofloxacin when expressed in Escherichia coli. Conclusions: The results presented in this study provide additional evidence for the ubiquitous presence of qnr genes in environmental microbial communities, expand the number of known qnr gene variants and further elucidate the diversity of this class of resistance genes. This study also strengthens the hypothesis that environmental bacterial communities act as sources of previously uncharacterized qnr genes.
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18.
  • Granberg, Fredrik, et al. (författare)
  • Complete Genome Sequence of an African Swine Fever Virus Isolate from Sardinia, Italy
  • 2016
  • Ingår i: Microbiology Resource Announcements. - 2576-098X. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous genetic characterization of African swine fever virus isolates from the Italian island of Sardinia, where the virus has been present since 1978, has largely been limited to a few selected genomic regions. Here, we report the complete genome sequence of the isolate 47/Ss/08 collected during an outbreak in 2008.
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19.
  • Malmberg, Maja, et al. (författare)
  • Genetic characterization of a novel adenovirus detected in captive bottlenose dolphin (Tursiops truncates) suffering from self-limiting gastroenteritis
  • 2016
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Adenoviruses have a wide host range and are common pathogens in vertebrates. In cetaceans, adenoviruses have only rarely been detected and correlated with disease. A novel adenovirus was recently detected in captive bottlenose dolphin (Tursiops truncates) suffering from self-limiting gastroenteritis. The initial analysis of partial pol and hexon gene sequences indicated that this was a hitherto unknown adenovirus with less than 80% sequence identity to previously published sequences. The aim of this study was to further genetically characterize this novel adenovirus using a high-throughput sequencing approach for whole-genome sequencing. Fecal samples from affected bottlenose dolphins were collected as previously described. Samples were homogenized and centrifuged through filters with 0.22 μm pores. To remove non-viral DNA the filtrate was treated with DNase and RNase prior to DNA extraction. Nextera XT sequencing libraries were sequenced at the MiSeq platform. Sequence reads were assembled using the MIRA assembler. The longest contigs were used to identify the most similar reference genome using BLASTn. To generate a draft consensus sequence, matching contigs were aligned against the reference genome using CodonCode Aligner software. The complete genome sequence was verified using PCR and Sanger sequencing. The analysis of phylogenetic relationships was conducted in MEGA 5 [2]. Gene prediction and annotation were used using PROKKA, MAKER and GeneMark.hmm with heuristic models. High-throughput sequencing allowed the recovery of the complete sequence of Bottlenose dolphin Adenovirus-1 (BdAdV-1). The sequence is 34 040bp and has an ITR of about 220bp. A total of 26 coding sequences were identified out of which 3 were assigned as hypothetical and 23 were functionally annotated. The homology analysis indicates that the most similar genome is the Bottlenose dolphin Adenovirus 2 (KR024710) (71% identity), followed by the California sea lion adenovirus 1 (KJ563221), and then Bovine adenovirus type 2 (AF252854). We here describe the complete sequence of a recently identified adenovirus associated with gastroenteritis in dolphins. This virus is clearly different from previously published adenoviruses, demonstrating less than 72% sequence identity. A more in-depth analysis of the obtained sequence data and predicted proteins should allow predictions to be made regarding e.g. tropism. The study also demonstrate the usefulness of high-throughput sequencing to obtain full-length genomes of genetically divergent viruses.
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20.
  • Malmberg, Maja, et al. (författare)
  • Phylogenomic analysis of the complete sequence of a gastroenteritis-associated cetacean adenovirus (bottlenose dolphin adenovirus 1) reveals a high degree of genetic divergence
  • 2017
  • Ingår i: Infection, Genetics and Evolution. - : Elsevier BV. - 1567-1348 .- 1567-7257. ; 53, s. 47-55
  • Tidskriftsartikel (refereegranskat)abstract
    • Adenoviruses are common pathogens in vertebrates, infecting a wide range of hosts, but only having rarely been detected and correlated with disease in cetaceans. This article describes the first complete genomic sequence of a cetacean adenovirus, bottlenose dolphin adenovirus 1 (BdAdV-1), detected in captive bottlenose dolphin population ( Tursiops truncatus) suffering from self-limiting gastroenteritis. The complete genome sequence of BdAdV-1 was recovered from data generated by high-throughput sequencing and validated by Sanger sequencing. The genome is 34,080 bp long and has 220 nucleotides long inverted terminal repeats. A total of 29 coding sequences were identified, 26 of which were functionally annotated. Among the unusual features of this genome is a remarkably long 4380 bp E3 ORF1, that displays no sequence homology with the corresponding E3 regions of other adenoviruses. In addition, the fiber protein only has 26% identity with fiber proteins described in other adenoviruses. Three hypothetical proteins were predicted. The phylogenetic analysis indicates that the closest known relative to BdAdV-1 is an adenovirus detected in bottlenose dolphin (KR024710), with an amino acid sequence identity between 36 and 79% depending on the protein. Based on the phylogenic analysis, the BdAdV-1 appears to have co-evolved with its host.The results indicate that BdAdV-1 belongs to the Mastadenovirus genus of the Adenoviridae family, however, it is clearly different from other adenoviruses, especially in the 3'-end of the viral genome. The high degree of sequence divergence suggests that BdAdV-1 should be considered as a novel species in the Mastadenovirus genus. The study also demonstrates the usefulness of high-throughput sequencing to obtain full-length genomes of genetically divergent viruses. (C) 2017 The Authors. Published by Elsevier B.V.
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21.
  • Rising, Anna, et al. (författare)
  • Systemic AA amyloidosis in the red fox (Vulpes vulpes)
  • 2017
  • Ingår i: Protein Science. - : WILEY. - 0961-8368 .- 1469-896X. ; 26:11, s. 2312-2318
  • Tidskriftsartikel (refereegranskat)abstract
    • Amyloid A (AA) amyloidosis occurs spontaneously in many mammals and birds, but the prevalence varies considerably among different species, and even among subgroups of the same species. The Blue fox and the Gray fox seem to be resistant to the development of AA amyloidosis, while Island foxes have a high prevalence of the disease. Herein, we report on the identification of AA amyloidosis in the Red fox (Vulpes vulpes). Edman degradation and tandem MS analysis of proteolyzed amyloid protein revealed that the amyloid partly was composed of full-length SAA. Its amino acid sequence was determined and found to consist of 111 amino acid residues. Based on inter-species sequence comparisons we found four residue exchanges (Ser31, Lys63, Leu71, Lys72) between the Red and Blue fox SAAs. Lys63 seems unique to the Red fox SAA. We found no obvious explanation to how these exchanges might correlate with the reported differences in SAA amyloidogenicity. Furthermore, in contrast to fibrils from many other mammalian species, the isolated amyloid fibrils from Red fox did not seed AA amyloidosis in a mouse model.
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22.
  • Brusini, Irene, et al. (författare)
  • Changes in brain architecture are consistent with altered fear processing in domestic rabbits
  • 2018
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 115:28, s. 7380-7385
  • Tidskriftsartikel (refereegranskat)abstract
    • The most characteristic feature of domestic animals is their change in behavior associated with selection for tameness. Here we show, using high-resolution brain magnetic resonance imaging in wild and domestic rabbits, that domestication reduced amygdala volume and enlarged medial prefrontal cortex volume, supporting that areas driving fear have lost volume while areas modulating negative affect have gained volume during domestication. In contrast to the localized gray matter alterations, white matter anisotropy was reduced in the corona radiata, corpus callosum, and the subcortical white matter. This suggests a compromised white matter structural integrity in projection and association fibers affecting both afferent and efferent neural flow, consistent with reduced neural processing. We propose that compared with their wild ancestors, domestic rabbits are less fearful and have an attenuated flight response because of these changes in brain architecture.
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23.
  • Ågren, Estelle, et al. (författare)
  • Factors affecting costs for on-farm control of salmonella in Swedish dairy herds
  • 2015
  • Ingår i: Acta Veterinaria Scandinavica. - : Springer Science and Business Media LLC. - 0044-605X .- 1751-0147. ; 57
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The Swedish control program for salmonella includes restrictions and on-farm control measures when salmonella is detected in a herd. Required control measures are subsidised by the government. This provides an opportunity to study costs for on-farm salmonella control. The aim of this study was to describe the costs for on-farm salmonella control in Swedish cattle herds and to investigate the effects of herd factors on these costs in dairy herds. Results: During the 15 years studied there had been a total of 124 restriction periods in 118 cattle herds; 89 dairy herds, 28 specialised fattening herds and three suckler herds. The average costs per herd for on-farm salmonella control was 4.60 million SEK with a median of 1.06 million SEK corresponding to approximately 490 000 and 110 000 EUR. The range was 0.01 to 41 million SEK corresponding to 1080 EUR to 4.44 million EUR per farm. The costs cover measures required in herd-specific control plans, generally measures improving herd hygiene. A mixed linear model was used to investigate associations between herd factors and costs for on-farm salmonella control in dairy herds. Herd size and length of the restriction period were both significantly associated with costs for on-farm control of salmonella with larger herds and longer periods of restrictions leading to higher costs. Serotype detected and administrative changes in the Swedish Board of Agriculture aiming at reducing costs were not associated with costs for on-farm salmonella control. Conclusions: On-farm control of salmonella in Swedish cattle herds incurred high costs but the costs also varied largely between herds. Larger herds and longer restriction periods increased the costs for on-farm control of salmonella in Swedish dairy herds. This causes concern for future costs for the Swedish salmonella control program as herd sizes are increasing.
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24.
  • Bergh, Johan, 1983-, et al. (författare)
  • Structural and kinetic analysis of protein-aggregate strains in vivo using binary epitope mapping
  • 2015
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:14, s. 4489-4494
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite considerable progress in uncovering the molecular details of protein aggregation in vitro, the cause and mechanism of protein-aggregation disease remain poorly understood. One reason is that the amount of pathological aggregates in neural tissue is exceedingly low, precluding examination by conventional approaches. We present here a method for determination of the structure and quantity of aggregates in small tissue samples, circumventing the above problem. The method is based on binary epitope mapping using anti-peptide antibodies. We assessed the usefulness and versatility of the method in mice modeling the neurodegenerative disease amyotrophic lateral sclerosis, which accumulate intracellular aggregates of superoxide dismutase-1. Two strains of aggregates were identified with different structural architectures, molecular properties, and growth kinetics. Both were different from superoxide dismutase-1 aggregates generated in vitro under a variety of conditions. The strains, which seem kinetically under fragmentation control, are associated with different disease progressions, complying with and adding detail to the growing evidence that seeding, infectivity, and strain dependence are unifying principles of neurodegenerative disease.
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25.
  • Yakymovych, Ihor, et al. (författare)
  • CIN85 modulates TGF beta signaling by promoting the presentation of TGF beta receptors on the cell surface
  • 2015
  • Ingår i: Journal of Cell Biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 210:2, s. 319-332
  • Tidskriftsartikel (refereegranskat)abstract
    • Members of the transforming growth factor beta (TGF beta) family initiate cellular responses by binding to TGF beta receptor type II (Tf3R11) and type I (TpRI) serine/threonine kinases, whereby Srnad2 and Smad3 are phosphorylated and activated, promoting their association with Smadzi. We report here that T beta RI interacts with the SH3 domains of the adaptor protein CIN85 in response to TGF beta stimulation in a TRAF6-dependent manner. Small interfering RNA mediated knockdown of CIN85 resulted in accumulation of T beta RI in intracellular compartments and diminished TGF beta-stimulated Sniad2 phosphorylation. Overexpression of CIN85 instead increased the amount of T beta RI at the cell surface. This effect was inhibited by a dominant-negative mutant of Rab11, suggesting that CIN85 promoted recycling of TGF beta receptors. CIN85 enhanced TGF beta-stimulated Smad2 phosphorylation, transcriptional responses, and cell migration. CIN85 expression correlated with the degree of malignancy of prostate cancers. Collectively, our results reveal that CIN85 promotes recycling of TGF beta receptors and thereby positively regulates TGF beta signaling.
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26.
  • Malmström, Annika, 1957- (författare)
  • Studies for Better Treatment of Patients with Glioma
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • In Sweden annually over 500 people will be diagnosed with the malignant brain tumor glioma. They are graded from I-IV. The majority are glioblastoma (grade IV) (GBM), these being the most aggressive type. Median survival for those treated with standard of care is expected to be around 15 months. This tumor will mainly affect those 60 years or older.The studies in this thesis focus on treatment of patients with malignant gliomas grade III and IV. The aim of the studies is to improve the care of glioma patients. Papers I and II explored different therapeutic options in randomized trials, to facilitate individualized treatment recommendations. Findings from studies I and II, together with additional trials, demonstrated the importance of analyzing the tumor marker O6-methylguanine DNA methyltransferase (MGMT) methylation status for survival of GBM patients treated with Temozolomide (TMZ). The third paper investigated how the analysis of this marker is implemented internationally.The first study (paper I, Nordic trial) investigated treatment options for patients 60 years or older with GBM. The trial compared standard radiotherapy (SRT) over 6 weeks versus hypofractionated radiotherapy (HRT) over 2 weeks versus single agent TMZ administered in up to six 4 weekly cycles. In all, 342 patients were included in the trial. This study demonstrated that those randomized to TMZ had superior survival as compared to SRT. In addition, quality of life (QoL) data also suggested a better QoL for TMZ treatment than for radiotherapy. The benefit of TMZ treatment seemed to be limited to those with the tumor molecular marker MGMT methylated (inactivated).The second trial (paper II, Neoadjuvant trial) studied whether integrating TMZ treatment with SRT for patients younger than 60 years with GBM (grade IV) and astrocytoma grade III would confer a survival benefit, if administered postoperatively, before the start of SRT (neoadjuvant). TMZ was provided for 2-3 four weekly cycles followed by SRT to patients randomized to neoadjuvant treatment and was compared to postoperative SRT alone. Although this trial could not illustrate any advantage of delaying the start of SRT while administering TMZ for the study cohort in general, for those included as astrocytoma grade III the median survival was found to be superior by 5 years when randomized to neoadjuvant TMZ. This trial also confirmed the importance of MGMT promoter methylation for the efficacy of TMZ.The third study (paper III) investigated international practices for analyzing tumor MGMT promoter methylation status. MGMT analysis can be conducted by various laboratory methods, which in some cases can provide opposing results regarding the MGMT methylation status of the patient´s tumor. This can lead to incorrect treatment recommendations. To establish which methods and cut-offs that are regularly used to determine tumor MGMT status in the clinic, an international survey was provided to those working in the field. We also inquired about opinions regarding an international consensus on how MGMT should be tested. The 152 respondents reported several methodologies and different cut-off levels also for the same method. A majority of respondents warrant international guidelines.In conclusion, the results of the 2 randomized trials contribute to individualized treatment recommendations for patients affected by GBM or astrocytoma grade III. The results of the survey regarding analyses of MGMT clarify the current problematic situation. The request of the respondents regarding international guidelines might contribute to their future development, so that personalized treatment recommendations can be improved.
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27.
  • Appelgren, Lars-Erik (författare)
  • Julgranen – inte bara till lyst
  • 2015
  • Ingår i: Svensk Veterinärtidning. - 0346-2250. ; 67, s. 42-45
  • Tidskriftsartikel (populärvet., debatt m.m.)
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28.
  • Backhans, Annette, et al. (författare)
  • Higher perceived risks of antimicrobial use are related to lower usage among pig farmers in four European countries
  • 2016
  • Ingår i: Veterinary Record. - : Wiley. - 0042-4900 .- 2042-7670. ; 179
  • Tidskriftsartikel (refereegranskat)abstract
    • The prudent use of antimicrobials (AMs) should be widened in pig farming to reduce the risk of AM resistance (AMR) in human and veterinary medicine. It is therefore important to understand pig farmers' motivators and the barriers to AM usage (AMU) on their farms. The authors investigated pig farmers' self-estimated levels of AMU, their perceived benefits and risks and the need for AMs in a cross-sectional survey in Belgium, France, Germany and Sweden. The authors also compared these perceptions between the four countries and related them to pig farmers' actual AMU. The results showed that farmers who used more AMs also estimated their own usage as higher. Farmers perceived many benefits but relatively few risks of AMU in pig farming. Some significant cross-country differences in farmers' perceptions were found, but they were relatively small. After controlling for country differences and farm differences, only perceived risks had a significant association with AMU. The authors therefore conclude that in order to promote prudent AMU, it seems most promising to focus on the structural differences in pig farming and veterinary medicine (e.g. legislation, role of the veterinarian) among countries. In addition, interventions which aim at reducing AMU should increase farmers' awareness of the risks of extensive AMU.
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29.
  • Duse, Anna, et al. (författare)
  • Risk factors for quinolone-resistant Escherichia coli in feces from preweaned dairy calves and postpartum dairy cows
  • 2015
  • Ingår i: Journal of Dairy Science. - : American Dairy Science Association. - 0022-0302 .- 1525-3198. ; 98, s. 6387-6398
  • Tidskriftsartikel (refereegranskat)abstract
    • Quinolone resistance may emerge in gut bacteria (e.g., in Escherichia coli) of animals. Such bacteria could cause infections in the animal itself or be transmitted to humans via the food chain. Quinolone resistance is also observed in fecal E. coli of healthy dairy cattle, but the prevalence varies between farms, not solely as a result of varying degree of fluoroquinolone exposure. The objective of this study was to identify risk factors for the fecal shedding of quinolone-resistant E. coli (QREC) from dairy calves and postpartum cows. Rectal swabs from 15 preweaned calves and 5 postpartum cows per farm were collected on 23 Swedish dairy farms to determine the prevalence of QREC. Risk factors for the shedding of QREC were investigated using multivariable statistical models. Quinolone-resistant E. coli were found on all but one farm. Factors associated with QREC shedding by calves were being younger than 18 d, being fed milk from cows treated with antimicrobials, recent use of fluoroquinolones in the herd, carriage of QREC by postpartum cows, and using the calving area never or rarely as a sick pen compared with often. Factors associated with QREC shedding by cows were calving in group pens or freestalls compared with single pens or tiestalls, purchasing cattle, sharing animal transports with other farmers, and poor farm hygiene. Proper biosecurity and improved hygiene, as well as minimizing fluoroquinolone exposure and waste milk feeding, may be important factors to reduce the burden of QREC on dairy farms.
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30.
  • Wårdell, Karin, et al. (författare)
  • Deep Brain Stimulation of the Pallidum Internum for Gilles de la Tourette Syndrome : A Patient-Specific Model-Based Simulation Study of the Electric Field
  • 2015
  • Ingår i: Neuromodulation. - : John Wiley & Sons. - 1094-7159 .- 1525-1403. ; :2, s. 90-96
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesThe aim of this study was to investigate the deep brain stimulation (DBS) electric field distribution in proton-density MRI scans visualizing the globus pallidus internus (GPi) of patients with Gilles de la Tourette syndrome (GTS), along with its relation to the anatomy.MethodsPatient-specific brain tissue models (n = 7) with bilateral DBS electrodes in the GPi were set up using the finite element method in five patients who had undergone stereotactic proton-density MRI-guided surgery and showed variable improvement with DBS. Simulations (n = 27) of the electric field were performed and the results visualized on the respective preoperative stereotactic MRI scans. The mean electric field volumes (n = 81) within the 0.1, 0.15, and 0.2 V/mm isosurfaces were calculated and compared with the anatomy.ResultsVisualization of the simulated electric field confirmed that the anteromedial limbic GPi was the main stimulated target for four of the patients and the posteromedial sensorimotor GPi for one. Larger volumes extended asymmetrically, with parts of fields stretching into the lamina between GPi and globus pallidus externus and into the internal capsule. There was a high correlation (r = 0.994, n = 54) between volumes and brain sides, but with a systematic shift toward the right side, especially for the larger volumes. Simulations with homogeneous tissue models showed no differences.ConclusionsPatient-specific DBS electric field simulations in the GPi as visualized on proton-density MR scans can be implemented in patients with GTS. Visualization of electric fields together with stereotactic thin-slice MRI can provide further support when predicting anatomical structures possibly influenced by DBS in this complex disorder.
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31.
  • Åström, Mattias, et al. (författare)
  • Relationship between Neural Activation and Electric Field Distribution during Deep Brain Stimulation
  • 2015
  • Ingår i: IEEE Transactions on Biomedical Engineering. - : IEEE. - 0018-9294 .- 1558-2531. ; 62:2, s. 664-72
  • Tidskriftsartikel (refereegranskat)abstract
    • Models and simulations are commonly used to study deep brain stimulation (DBS). Simulated stimulation fields are often defined and visualized by electric field isolevels or volumes of tissue activated (VTA). The aim of the present study was to evaluate the relationship between stimulation field strength as defined by the electric potential V, the electric field E, and the divergence of the electric field ∇(2) V, and neural activation. Axon cable models were developed and coupled to finite-element DBS models in three-dimensional (3-D). Field thresholds ( VT , ET, and ∇(2) VT ) were derived at the location of activation for various stimulation amplitudes (1 to 5 V), pulse widths (30 to 120 μs), and axon diameters (2.0 to 7.5 μm). Results showed that thresholds for VT and ∇(2) VT were highly dependent on the stimulation amplitude while ET were approximately independent of the amplitude for large axons. The activation field strength thresholds presented in this study may be used in future studies to approximate the VTA during model-based investigations of DBS without the need of computational axon models.
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32.
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33.
  • Chenais, Erika, et al. (författare)
  • Quantitative assessment of social and economic impact of African swine fever outbreaks in northern Uganda
  • 2017
  • Ingår i: Preventive Veterinary Medicine. - : Elsevier BV. - 0167-5877 .- 1873-1716. ; 144, s. 134-148
  • Tidskriftsartikel (refereegranskat)abstract
    • African swine fever (ASF) is one of the most important pig diseases, causing high case fatality rate and trade restrictions upon reported outbreaks. In Uganda, a low-income country with the largest pig population in East Africa, ASF is endemic.Animal disease impact is multidimensional and include social and economic impact along the value chain. In low-income settings, this impact keep people poor and push those that have managed to escape poverty back again. If the diseases can be controlled, their negative consequences can be mitigated. However, to successfully argue for investment in disease control, its cost-benefits need to be demonstrated. One part in the cost-benefit equations is disease impact quantification. The objective of this study was therefore to investigate the socio-economic impact of ASF outbreaks at household level in northern Uganda.In a longitudinal study, structured interviews with two hundred, randomly selected, pig-keeping households were undertaken three times with a six month interval. Questions related to family and pig herd demographics, pig trade and pig business.Associations between ASF outbreaks and economic and social impact variables were evaluated using linear regression models. The study showed that pigs were kept in extreme low-input-low-output farming systems involving only small monetary investments. Yearly incidence of ASF on household level was 19%. Increasing herd size was positively associated with higher economic output. The interaction between ASF outbreaks and the herd size showed that ASF outbreaks were negatively associated with economic output at the second interview occasion and with one out of two economic impact variables at the third interview occasion. No significant associations between the social impact variables included in the study and ASF outbreaks could be established. Trade and consumption of sick and dead pigs were coping strategies used to minimize losses of capital and animal protein.The results indicate that causality of social and economic impact of ASF outbreaks in smallholder systems is complex. Pigs are mostly kept as passive investments rather than active working capital, complicating economic analyses and further disqualifying disease control arguments based only on standard economic models. (C) 2017 The Authors. Published by Elsevier B.V.
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34.
  • Höglund, Johan (författare)
  • Prevalence of anthelmintic resistance on Lithuanian sheep farms assessed by in vitro methods
  • 2015
  • Ingår i: Acta Veterinaria Scandinavica. - : Springer Science and Business Media LLC. - 0044-605X .- 1751-0147. ; 57
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: This study examines the prevalence of drug resistance in gastrointestinal nematodes to macrocyclic lactones (ML) and benzimidazoles (BZ) in Lithuanian sheep using sensitive and precise in vitro methods. The survey was conducted from August 2013 to November 2014. Thirty-three farms with sheep previously treated with BZ and ivermectin (IVM) were included in the study. On 12 farms where only BZ were used, egg hatch discrimination dose testing (EHDDT) was conducted to detect anthelmintic resistance (AR) to BZ. On eight farms where only ML were used, micro agar larval development testing (MALDT) was conducted to detect AR to ivermectin (IVM). On the remaining 13 farms, where both classes of drugs were used, EHDDT and MALDT were both applied to detect multidrug resistance to BZ and IVM.Results: BZ-resistant gastrointestinal nematodes were found on all 25 farms with a previous history of BZ use. High levels of resistance (>40 % of hatching) were recorded on 36 % of these farms, and low levels (<20 % of hatching) on 40 % of farms. IVM-resistant populations were found on 13 out of 21 sheep farms using this drug. Of these 13 farms with AR to IVM, low levels of resistance (<30 % development) were recorded on 84.6 % of farms and high levels (>30 % development) on 15.4 % of farms. No resistance to IVM was recorded on 38.1 % of farms. Multi-drug resistance was detected on five farms out of 13 (38.5 %) using both classes of drugs.Conclusions: The present study demonstrates the existence of AR to BZ and ML on Lithuanian sheep farms thus confirming results in a previous in vivo study. Cases of multi-drug resistance were recorded in the present study and require further consideration. An appropriate strategy for anthelmintic treatment, measures to prevent gastrointestinal nematode infection and a better understanding of the management practices associated with resistance may slow down further development of AR.
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35.
  • Höglund, Johan (författare)
  • Seasonal patterns of gastrointestinal nematode infection in goats on two Lithuanian farms
  • 2015
  • Ingår i: Acta Veterinaria Scandinavica. - : Springer Science and Business Media LLC. - 0044-605X .- 1751-0147. ; 57
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: This study investigated seasonal changes in naturally acquired gastrointestinal nematode (GIN) infections on two Lithuanian goat farms with different parasite control practices.Findings: On both farms, nematode faecal egg counts (FEC) and larval cultures were obtained from 15 adult and 10 young goats at bi-weekly intervals from April 2012 to April 2013. Goats on farm A were dewormed with ivermectin (0.3 mg/kg body weight) in October/November 2012, whereas the animals on farm B were left untreated. Thirteen young goats were slaughtered in August/November 2012 and April 2013 and worm burdens in the gastrointestinal tract were enumerated. In goats from both farms, Teladorsagia, Trichostrongylus, Oesophagostomum, Chabertia and Haemonchus were the dominant GIN genera. Herbage contamination with infective third-stage larvae (L-3) peaked in July/August and resulted in high FEC in September/October. Parasitological examination at slaughter showed that Teladorsagia spp. and Haemonchus contortus survived the winter, both in the abomasal mucosa as adults and as early fourth-stage larvae (EL4). Deworming on farm A significantly reduced FEC, especially of H. contortus, at the start of the grazing period compared with the untreated farm B (P < 0.05).Conclusions: Goats were heavily infected with several GIN throughout the year. Strategic anthelmintic treatment during housing significantly reduced nematode egg output, in particular by H. contortus, at the start of the grazing season.
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36.
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37.
  • Persson-Sjödin, Emma, et al. (författare)
  • Effect of meloxicam treatment on movement asymmetry in riding horses in training
  • 2019
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Quantitative gait analysis has revealed that a large proportion of horses in training, perceived as free from lameness by their owners, show movement asymmetries of equal magnitude to horses with mild clinical lameness. Whether these movement asymmetries are related to orthopaedic pain and/or pathology has yet to be further investigated. Therefore, the objective of this study was to determine whether movement asymmetries in riding horses in training are affected by anti-inflammatory treatment with meloxicam. In a crossover design, horses were treated with meloxicam or placebo for four days respectively, with a 14-16 day washout period between treatments. Objective movement analysis utilising body mounted accelerometers was performed on a hard and a soft surface before and on day four of each treatment. A trial mean was calculated for the differences between the two vertical displacement minima and maxima of head (HDmin, HDmax) and pelvis (PDmin, PDmax) per stride. Horses (n = 66) with trial mean asymmetries greater than 6 mm for HDmin or HDmax, or more than 3 mm for PDmin or PDmax, at baseline were included. The difference before and after each treatment in the measured movement asymmetry was assessed with linear mixed models. Treatment with meloxicam did not significantly affect the movement asymmetry in any of the models applied (all p>0.30). These results raise new questions: are the movement asymmetries in riding horses in training simply expressions of biological variation or are they related to pain/dysfunction that is non-responsive to meloxicam treatment?
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38.
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39.
  • Bett, B, et al. (författare)
  • Effects of climate change on the occurrence and distribution of livestock diseases.
  • 2017
  • Ingår i: Preventive Veterinary Medicine. - : Elsevier BV. - 0167-5877 .- 1873-1716. ; 137:Pt B, s. 119-129
  • Tidskriftsartikel (refereegranskat)abstract
    • The planet's mean air and ocean temperatures have been rising over the last century because of increasing greenhouse gas (GHG) emissions. These changes have substantial effects on the epidemiology of infectious diseases. We describe direct and indirect processes linking climate change and infectious diseases in livestock with reference to specific case studies. Some of the studies are used to show a positive association between temperature and expansion of the geographical ranges of arthropod vectors (e.g. Culicoides imicola, which transmits bluetongue virus) while others are used to illustrate an opposite trend (e.g. tsetse flies that transmit a range of trypanosome parasites in sub-Saharan Africa). We further describe a positive association between extreme events: droughts and El Niño/southern oscillation (ENSO) weather patterns and Rift Valley fever outbreaks in East Africa and some adaptation practices used to mitigate the impacts of climate change that may increase risk of exposure to infectious pathogens. We conclude by outlining mitigation and adaptation measures that can be used specifically in the livestock sector to minimize the impacts of climate change-associated livestock diseases.
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40.
  • Boqvist, Sofia, et al. (författare)
  • Prevalence of and factors associated with Brucella sero-positivity in cattle in urban and peri-urban Gulu and Soroti towns of Uganda
  • 2015
  • Ingår i: Journal of Veterinary Medical Science. - : Japanese Society of Veterinary Science. - 0916-7250 .- 1347-7439. ; 77, s. 557-564
  • Tidskriftsartikel (refereegranskat)abstract
    • Brucellosis is a key zoonosis of major public health, animal welfare and economic significance, and is endemic in livestock in Uganda. A cross-sectional epidemiological study was carried out to estimate the sero-prevalence of brucellosis and identify factors associated with sero-positivity in cattle in urban and pen-urban Gulu and Soroti towns of Northern and Eastern Uganda, respectively. A total of 1007 sera and data on biologically plausible risk factors from 166 herds and their spatial locations, were collected from cattle reared in urban and pen-urban Gulu and Soroti towns of Uganda. The sera were analyzed using indirect ELISA and sero-positive reactors confirmed by competitive ELISA. Multivariable models were used to investigate for risk factors. The overall animal-level and herd-level sero-prevalence was 7.5% (76/1007, 95% Confidence Interval (CI): 6.15-9.4%) and 27.1% (45/166, 95% CI: 20.9-34.3%), respectively. Herd-level sero-prevalence was significantly (P<0.001) higher in Soroti than Gulu. In Gulu town, sero-positivity increased with an increase in herd size (P=0.03) and age (P=0.002), and was higher in cattle brought in from western Uganda (P<0.0001). In Soroti town, introduction of new cattle into a herd was significantly (P=0.027) associated with herd sero-positivity. There was a geographically differential risk (clustering) of Brucella sero- positivity in herds in Soroti, while sero-positivity was homogeneously distributed in Gulu. The data highlight brucellosis occurrence and major risk factors for its transmission in cattle in urban and pen-urban areas.
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41.
  • Ekstrand, Carl, et al. (författare)
  • Cetirizine per os : exposure and antihistamine effect in the dog
  • 2018
  • Ingår i: Acta Veterinaria Scandinavica. - : BMC. - 0044-605X .- 1751-0147. ; 60
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundCetirizine is an antihistamine used in dogs, but plasma concentrations in relation to effect after oral administration are not well studied. This study investigated cetirizine exposure and the plasma cetirizine concentration-antihistamine response relation in the dog following oral administration of cetirizine.ResultsEight Beagle dogs were included in a cross-over study consisting of two treatments. In treatment one, cetirizine 2-4mg/kg was administered per os once daily for 3days. The other treatment served as a control. Wheal diameter induced by intra-dermal histamine injections served as response-biomarker. Cetirizine plasma concentration was quantified by UHPLC-MS/MS. Median (range) cetirizine plasma terminal half-life was 10h (7.9-16.5). Cetirizine significantly inhibited wheal formation compared with the premedication baseline. Maximum inhibition of wheal formation after treatment with cetirizine per os was 100% compared with premedication wheal diameter. The median (range) IC50-value for reduction in wheal area was 0.33 mu g/mL (0.07-0.45). The median (range) value for the sigmoidicity factor was 1.8 (0.8-3.5). A behavioral study was also conducted and revealed no adverse effects, such as sedation.ConclusionThe results indicate that a once-daily dosing regimen of 2-4mg/kg cetirizine per os clearly provides a sufficient antihistamine effect. Based on this experimental protocol, cetirizine may be an option to treat histamine-mediated inflammation in the dog based on this experimental protocol but additional clinical studies are required.
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42.
  • Enström, Sofie, et al. (författare)
  • Brucella seroprevalence in cattle near a wildlife reserve in Kenya.
  • 2017
  • Ingår i: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Brucellosis is caused by bacteria from the genus Brucella which infect human and domestic animals as well as wildlife. The Maasai Mara National Reserve has vast populations of wild ruminants such as buffaloes and wildebeest which could contribute to the risk of brucellosis in livestock, and the surrounding pastoralist communities grazing cattle in and around the reserve may be exposed to a higher risk of zoonotic diseases like brucellosis due to the close contact with livestock. In this study, cattle from three villages at varying distance from the reserve, were screened for antibodies against Brucella abortus.RESULTS: In total, 12.44% of 225 sampled animals were seropositive, with more females (15%) infected than males (5%). Seroprevalence was higher in livestock closer to Maasai Mara with the cattle in the village Mara Rianta having an odds ratio of 7.03 compared to Endoinyo Narasha further away (95% CI 1.4-11.1, p = 0.003), suggesting that a closer contact with wildlife may increase the circulation of infectious diseases between livestock and wildlife. Symptoms consistent with brucellosis were reported to occur in both humans and animals, and we thus conclude that brucellosis may be an important problem, both for the health and the economy.
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43.
  • Frössling, Jenny, et al. (författare)
  • Detection of Treponema phagedenis-like antibodies in serum and bulk milk from cows with and without digital dermatitis.
  • 2018
  • Ingår i: Journal of Veterinary Diagnostic Investigation. - : SAGE Publications. - 1040-6387 .- 1943-4936. ; 30, s. 86-92
  • Tidskriftsartikel (refereegranskat)abstract
    • Digital dermatitis (DD) in dairy cows is a widespread disease linked to infection with Treponema. The traditional diagnostic method is clinical inspection, which is subjective and laborious. We explored the performance of 4 different immunogenic proteins from Treponema phagedenis in a new antibody ELISA for analysis of serum or milk. Analysis of samples from 390 cows in 25 herds showed that the ELISA could distinguish the majority of cows with DD from healthy cows. By changing the cutoff and applying parallel or serial testing, high sensitivity or specificity could be achieved. The investigation indicated that aggregated test results can be useful in the assessment of a herd's DD status. In addition, analysis of bulk tank milk samples showed good agreement with results from individual cows. The test system could be useful in research on the epidemiology and immunology of DD.
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44.
  • Huber, Nikolaus, et al. (författare)
  • Quantifying capture stress in free ranging European roe deer (Capreolus capreolus)
  • 2017
  • Ingår i: BMC Veterinary Research. - : Springer Science and Business Media LLC. - 1746-6148. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundTo understand and reduce the concomitant effects of trapping and handling procedures in wildlife species, it is essential to measure their physiological impact. Here, we examined individual variation in stress levels in non-anesthetized European roe deer (Capreolus capreolus), which were captured in box traps and physically restrained for tagging, biometrics and bio-sampling. In winter 2013, we collected venous blood samples from 28 individuals during 28 capture events and evaluated standard measurements for stress (heart rate, body temperature, neutrophil to lymphocyte ratio, lactate and total cortisol). Additionally, we assessed stress using the immunological tool, Leukocyte Coping Capacity (LCC), a real-time proxy for stress measuring oxygen radical production by leukocytes. Finally, the behavioral response to handling was recorded using a scoring system.ResultsLCC and therefore stress levels were negatively influenced by the time animals spent in the box trap with human presence at the capture site prior to handling. In contrast, none of the classical stress measures, including total cortisol, nor the behavioral assessment, were correlated with the stressor tested (time of human presence prior to handling) and thus did not provide a clear depiction regarding the extent of the animals short-term stress response.ConclusionsOverall our study verifies the LCC as a strong method to quantify short-term stress reactions in wildlife. Moreover, our results clearly show that human presence at the trapping site prior to handling should be kept to an absolute minimum in order to reduce stress levels.
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45.
  • Kagera, Irene, et al. (författare)
  • Status of aflatoxin contamination in cow milk produced in smallholder dairy farms in urban and peri-urban areas of Nairobi County : a case study of Kasarani sub county, Kenya.
  • 2019
  • Ingår i: Infection Ecology & Epidemiology. - : Informa UK Limited. - 2000-8686. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Milk consumption in Kenya supersedes other countries in East Africa. However, milk contamination with aflatoxin M1 (AFM1) is common, but the magnitude of this exposure and the health risks are poorly understood and need to be monitored routinely. This study aimed at assessing the awareness, knowledge and practices of urban and peri-urban farmers about aflatoxins and determining the levels of aflatoxin contamination in on-farm milk in a selected area within Nairobi County. Materials and methods: A cross-sectional study was undertaken to assess aflatoxin contamination levels of milk in Kasarani sub-county. A total of 84 milk samples were collected from small-holder dairy farms and analyzed for AFM1 using Enzyme-Linked Immunosorbent Assay (ELISA). Results and Discussion: Ninety nine percent of the samples (83/84) analysed were contaminated with AFM1. The mean aflatoxin level was 84 ng/kg with 64% of the samples exceeding the EU legal limit of 50 ng/kg. Whereas 80% of the farmers were aware of aflatoxin, there was no correlation between farmers' knowledge and gender with AFM1 prevalence. Conclusion: This study concludes that AFM1 is a frequent contaminant in milk and there is need to enhance farmers awareness on mitigation.
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46.
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47.
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48.
  • Osbjer, Kristina, et al. (författare)
  • Household practices related to disease transmission between animals and humans in rural Cambodia
  • 2015
  • Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Zoonotic diseases are disproportionately affecting poor societies in low-income countries and pose a growing threat to public health and global food security. Rural Cambodian households may face an increased likelihood of exposure to zoonotic diseases as people there live in close association with livestock. The objectives of the study was to identify practices known to influence zoonosis transmission in rural Cambodian households and relate the practices to agro-ecological region, socio-economic position, demographics, livestock management and zoonosis awareness.Methods: The study was conducted in three different agro-ecological regions of Cambodia; 10 villages each in the central lowlands, north-west wetlands and on the south coast, where information was obtained in questionnaires administered to 300 households, and 30 village heads and animal health workers.Results: Descriptive analysis revealed a gender difference in responsibility for livestock and that the main purpose of raising livestock was for sale. Few respondents (6%) perceived a likelihood of disease transmission in their village between livestock, humans and wildlife, despite household practices related to zoonosis transmission being common. More than one-forth of households practised behaviours such as culling sick animals for consumption, eating animals found dead and allowing animals to enter sleeping and food preparation areas. Associations between household practices and possible explanatory factors were analysed with multivariable models using generalised estimation equations to account for clustering of practices within villages. Factors found to influence household practices were agro-ecological region, socio-economic position, number of people in the household, livestock species reared and awareness of zoonoses.Conclusions: Cambodia has experienced numerous fatal human cases of zoonotic influenza and extensive influenza information campaigns have been run, yet only a few of the households surveyed here reported the threat of zoonosis to be a concern in their village. Zoonosis awareness was positively related to hand washing behaviour, but other practices associated with an increased or decreased likelihood of exposure to zoonotic pathogens were unaffected by awareness. The findings indicate a knowledge-to-action gap among rural farmers and highlight the necessity for reconstructed interventions in zoonotic disease control.
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49.
  • Stanezai, S., et al. (författare)
  • Higher intensity of Low Molecular Weight Protein Tyrosine Phosphatase/ ACP-1 in survivors of patients diagnosed with Diffuse Large B Cell Lymphoma (DLBCL) compared to non-survivors
  • 2016
  • Ingår i: Austin Biology. - : Austin Publishing. ; 1:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Adult Diffuse Large B Cell Lymphoma (DLBCL) is a heterogeneous form of hematopoietic cancer and difficult to treat. In order to find a better diagnostic indication for the disease, we analyzed Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP) that in humans is encoded by the ACP1 gene. LMWPTP is an enzyme shown to counteract Protein Tyrosine Kinases (PTK) and was suggested to be a negative growth factor regulator. However, the 18 kDa PTP can also have a positive effect on cell growth and proliferation, indicating a controversial role in the tumorigenic process. LMWPTP exists in different isoforms which are electrophoretically, kinetically and immunologically distinct. We have studied two subgroups of DLBCL consisting of a Germinal Center B cell like (GCB) and a non-Germinal Center B cell like (non-GCB) group. The two subgroups have been defined by gene-expressing profiling and are associated with differential outcome. The expression levels of LMWPTP protein was compared and showed significant differences between the GCB and non- GCB subgroups (p=0.012). Interestingly, when the samples were divided into survivors and non-survivors, and thereafter analyzed for LMWPTP expression, the samples from patients with a higher survival rate showed increased staining intensity, whereas the samples from patients with lower intensity of LMWPTP did not survive the disease (p=0.001). In conclusion, we have shown that DLBCL patients with worse outcome express LMWPTP with a lower intensity, suggesting a tumor suppressor role for this form of the enzyme.
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50.
  • Söder, Josefin (författare)
  • Metabolic variations in canine overweight : aspects of lipid metabolism in spontaneously overweight Labrador Retriever dogs
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The prevalence of overweight in dogs is increasing. Canine overweight is associated with reduced quality of life, shorter life expectancy and metabolic variations such as insulin resistance and postprandial hyperlipidaemia. Previous metabolic research on overweight dogs has been performed mainly in fasting condition and studies on spontaneously overweight dogs using dynamic metabolic tests are scarce. This thesis therefore evaluated metabolic variations in spontaneously overweight dogs using a feed-challenge test. Lean and overweight healthy Labrador Retriever dogs underwent a feed-challenge test. Blood and urine samples collected at fasting and after food intake were analysed with serum biochemistry, ELISA and metabolomics techniques. Multivariate and mixed model repeated measurements analyses were used to evaluate responses between body condition groups and/or between time points in the feed-challenge test. Postprandial serum triglycerides were higher in prominently overweight dogs compared with lean, while no differences between groups were found at fasting. Only one fasted plasma phosphatidylcholine showed higher concentration in prominently overweight compared with lean dogs. Postprandial urine metabolomes, but not fasting metabolomes, distinguished between lean and overweight groups of dogs. Prominently overweight dogs had higher fasting urine cortisol/creatinine ratio than lean dogs, and overweight dogs showed signs of amino acid catabolism in postprandial urine. The acetylcarnitine response in overweight dogs indicated low fatty acid oxidation at fasting and metabolic inflexibility to food intake. Overweight dogs also showed lower carnitine and taurine status than lean dogs, potentially representing an interrelated insufficiency that could theoretically slow down lipid metabolism. In conclusion, spontaneously overweight Labrador Retriever dogs displayed variations in metabolic parameters compared with lean dogs. Use of a feed-challenge test allowed detection of subtle metabolic variations not noticeable in fasted condition, emphasising the importance of using dynamic tests in metabolic research on canine overweight. Six parameters, all directly or indirectly associated with lipid metabolism, differed between overweight and lean dogs. In this thesis, the complexity of lipid metabolism in canine overweight was revealed by identifying previously known and new metabolic variations in spontaneously overweight Labrador Retriever dogs.
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