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  • 1.
    Ahlgren, Kerstin, M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wilbe, Maria
    Sundberg, Katarina
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindblad-Toh, Kerstin
    Andersson, Göran
    Lobell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hansson-Hamlin, Helene
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Type I Interferon signature in Nova Scotia duck tolling retriever dogs with steroid responsive meningitis-arteritisManuscript (preprint) (Other academic)
    Abstract [en]

    Objective: Dogs of the breed Nova Scotia duck tolling retriever (NSDTR) are prone to develop a disease complex in some aspects resembling human systemic lupus erythematosus (SLE). Peripheral blood mononuclear cells (PBMCs) from human SLE patients have an increased mRNA expression type I interferon (IFN) regulated genes. However, it is unknown whether diseased dogs also display the typical type I IFN signature.

    Methods: To test canine sera for their capacity to induce type I IFN response Mardin-Darby canine kidney (MDCK) cells were cultured with sera from healthy dogs (n=25),  immune-mediated rheumatic disease (IMRD) dogs with anti-nuclear antibodies (ANA+) (n=30) or dogs with steroid responsive meningitis-arteritis (SRMA) (n=25). mRNA expression of the genes MX1, IFIT1 and CXCL10 was measured by quantitative Real Time PCR.

    Results: A highly significant (p=0.0009) increase in mRNA expression of the type I IFN responsive gene MX1 was detected in cells stimulated by sera from dogs with SRMA, but not from IMRD ANA+ dogs. Expression of IFIT1 was twice as high in cells stimulated by sera from dogs with SRMA compared to both healthy dogs and ANA+ dogs. The mean expression of CXCL10 was nearly ten times higher in cells stimulated by sera from SRMA dogs than by ANA+ dogs and four times higher compared to cells stimulated by control dogs.

    Conclusion: Presence of type I IFN in sera from diseased NSDTR dogs was found in this study. This implies that this canine model can be used for identification of pathways of importance for autoimmune disorders in humans and for testing of novel therapeutic approaches. Our results can also be a step on the way towards personalized drugs in these dogs.

  • 2. Ahsan, Murshidul
    et al.
    Hasan, Badrul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Algotsson, Magnus
    Sarenbo, Sirkku
    Handling and Welfare of Bovine Livestock at Local Abattoirs in Bangladesh2014In: Journal of Applied Animal Welfare Science, ISSN 1088-8705, E-ISSN 1532-7604, Vol. 17, no 4, p. 340-353Article in journal (Refereed)
    Abstract [en]

    The World Organization for Animal Health (OIE) allows rope casting and the tying of legs for nonhuman animals laughter without stunning. The handling and welfare of bovine livestock (Bosindicus and Bubalus bubalis) were studied in 8 local abattoirs in 5 districts of Bangladesh. A total of 302 animals were evaluated. At the local abattoirs, approximately 1/3 of the cattle and water buffalo were eithere maciated orinjured/sick. The size and vigor of the animals determined the casting method. Small and weak animals were cast on concrete floors by lifting a foreleg followed by pushing, or simply by twisting the head of the animal and then binding the legs with rope. Vigorous animals such as buffalo were castusing ropes and human force. Bleeding was slow and flaying was sometimes initiated before the animals were unconscious. Pulling and tearing of the trachea and pouring of water into the exposed trache a shortly after cutting were also observed in some cases.The over all animal handling was unnecessarily rough and he OIE standards were not implemented. Animals are subjected to considerable mistreatment, and there is an urgent need for the training nde ducation of the staff in a battoirs concerning humanes laughtering practices as well as a need to build moderns laughtering plants in Bangladesh.

  • 3. Alonso, Silvia
    et al.
    Dohoo, Ian
    Lindahl, Johanna
    Verdugo, Cristobal
    Akuku, Isaiah
    Grace, Delia
    Prevalence of tuberculosis, brucellosis and trypanosomiasis in cattle in Tanzania: a systematic review and meta-analysis.2016In: Animal Health Research Reviews, ISSN 1466-2523, E-ISSN 1475-2654, Vol. 17, no 1, p. 16-27Article in journal (Refereed)
    Abstract [en]

    A meta-analysis was performed to derive prevalence estimates for Brucella spp., Mycobacterium spp. and Trypanosoma spp. in cattle in Tanzania using data derived from a systematic review of zoonotic hazards in cattle production systems. Articles published before 2012 reporting prevalence and considered at least moderate in quality were included in the analysis. Results showed high heterogeneity between studies, with wide ranges in the reported prevalence: Brucella (0.3-60.8%), Mycobacterium (0.1-13.2%) and Trypanosoma (0.82-33.3%). Overall meta-analytic mean prevalence estimates were 8.2% (95% CI 6.5-10.2), 1.28% (95% CI 0.35-4.58) and 10.3% (95% CI 6.20-16.70) respectively, for Brucella spp., Mycobacterium spp. and Trypanosoma spp. Time and region were predictors of variability of Brucella spp. prevalence, while diagnostic test was a strong predictor of Mycobacterium spp. prevalence, with higher prevalence estimates given by skin tests compared with post-mortem inspection. None of the studied factors were associated with prevalence of Trypanosoma spp. The small sample sizes, range of study locations, study designs and diagnostics used, contributed to high variability among prevalence estimates. Larger and more robust prevalence studies are needed to adequately support risk assessment and management of animal and public health threats.

  • 4. Alonso, Silvia
    et al.
    Lindahl, Johanna
    Roesel, Kristina
    Traore, Sylvain Gnamien
    Yobouet, Bassa Antoine
    Ndour, Andrée Prisca Ndjoug
    Carron, Maud
    Grace, Delia
    Where literature is scarce: observations and lessons learnt from four systematic reviews of zoonoses in African countries.2016In: Animal Health Research Reviews, ISSN 1466-2523, E-ISSN 1475-2654, Vol. 17, no 1, p. 28-38Article in journal (Refereed)
    Abstract [en]

    The success of a systematic review depends on the availability, accessibility and quality of literature related to the review question. This paper presents the literature found in four systematic reviews conducted for a selection of zoonotic hazards in four livestock value chains in Africa, as well as setting out the challenges in conducting the reviews. The protocol was designed following international standards, and addressed four questions around prevalence, risk factors, control options and impact of various hazards and populations. Searches were conducted in four online databases. Articles were screened for relevance, and quality was assessed before data extraction. Literature on zoonotic hazards was in general scarce and access to full articles was limited. Overall, 25-40% of papers were considered poor quality. The diversity of approaches and designs in the studies compromised the ability to generate summarized estimates. We found that the emphasis of veterinary research has been on livestock problems rather than public health issues, although this seems to be shifting in the last decade; we also found there are limited studies on impact and control. While increasing literature is being published around zoonoses in Africa, this is still inadequate to appropriately inform policy and guide research efforts.

  • 5.
    Alsmark, UCM
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry. Natl Vet Inst, Uppsala, Sweden..
    Nolskog, Peter
    Dept Communicable Dis Control & Prevent Reg Vastr, Gothenburg, Sweden..
    Angervall, Anna Lindqvist
    Dept Communicable Dis Control & Prevent Reg Vastr, Gothenburg, Sweden..
    Toepfer, Michael
    Unilabs AB, Skövde, Sweden..
    Winiecka-Krusnell, Jadwiga
    Publ Hlth Agcy Sweden, Solna, Sweden..
    Bouwmeester, Johanna
    Primary Healthcare Ctr Hjo, Hjo, Sweden..
    Bjelkmar, Par
    Publ Hlth Agcy Sweden, Solna, Sweden..
    Troell, Karin
    Natl Vet Inst, Uppsala, Sweden..
    Lahti, Elina
    Natl Vet Inst, Uppsala, Sweden..
    Beser, Jessica
    Publ Hlth Agcy Sweden, Solna, Sweden..
    Two outbreaks of cryptosporidiosis associated with cattle spring pasture events2018In: Veterinary Parasitology: Regional Studies and Reports, E-ISSN 2405-9390, Vol. 14, p. 71-74Article in journal (Refereed)
    Abstract [en]

    Over a period of less than four weeks, 50 human cases of cryptosporidiosis were reported from a relatively small geographical area in Sweden. All cases were associated with visits to cattle spring pasture events at two farms (referred to as Farm A and B). Epidemiological and microbiological evidence show that contact with calves at the farms was the most likely source of Cryptosporidium infections. Gp60 sequences from human and calf isolates at Farm A were identical to each other, but differed from those at Farm B where, again, human and calf gp60 sequences were identical, proving that the two outbreaks had no common origin. As a direct consequence of these two outbreaks, and guided by knowledge gained from the outbreak investigations, the Swedish Board of Agriculture and all relevant farmer advisory organizations have updated their hygiene instructions for farm visits.

  • 6. Anyango, Gladys
    et al.
    Mutua, Florence
    Kagera, Irene
    Andang‘O, Pauline
    Grace, Delia
    Lindahl, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    A survey of aflatoxin M1 contamination in raw milk produced in urban and peri-urban areas of Kisumu County, Kenya2018In: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Vol. 8, no 1Article in journal (Refereed)
    Abstract [en]

    ABSTRACTBackground: Food safety is of increasing global concern, and a OneHealth issue requiring attention of many disciplines. Aflatoxins are toxins produced by fungi and found in foods and feeds, and exposure causes negative health effects in humans and animals. When lactating animals consume aflatoxin B1, the metabolite (AFM1) is transferred to milk.Methods: A cross-sectional study was designed to determine characteristics of smallholder dairy farming in urban and peri-urban areas of Kisumu and quantify AFM1 in milk. Data was collected from 97 randomly selected dairy farms on farming practices, milk production, and awareness about aflatoxins. Collected milk samples were analyzed using enzyme-linked immunosorbent assay for AFM1.Results: Average milk produced was 13 liters per day per household and mainly used for household consumption and sold to neighbours. Farmers mainly fed cows on forage and concentrates (62.9%). Levels of AFM1 ranged from below the detection limit to 151 ppt, with a mean of 29.67 p...

  • 7.
    Ardesjö-Lundgren, Brita
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Swedish Univ Agr Sci, Dept Anim Breeding & Genet, Box 7023, SE-75007 Uppsala, Sweden.
    Tengvall, Katarina
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Karolinska Inst, Neuroimmunol Unit, Centrum Mol Med, Dept Clin Neurosci, S-17176 Stockholm, Sweden.
    Bergvall, Kerstin
    Swedish Univ Agr Sci, Dept Clin Sci, Box 7054, SE-75007 Uppsala, Sweden.
    Farias, Fabiana H. G.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Wang, Liya
    Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Box 7011, S-75007 Uppsala, Sweden.
    Hedhammar, Åke
    Swedish Univ Agr Sci, Dept Clin Sci, Box 7054, SE-75007 Uppsala, Sweden.
    Lindblad-Toh, Kerstin
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Broad Inst MIT & Harvard, 415 Main St, Cambridge, MA 02142 USA.
    Andersson, Göran
    Swedish Univ Agr Sci, Dept Anim Breeding & Genet, Box 7023, SE-75007 Uppsala, Sweden.
    Comparison of cellular location and expression of Plakophilin-2 in epidermal cells from nonlesional atopic skin and healthy skin in German shepherd dogs2017In: Veterinary dermatology (Print), ISSN 0959-4493, E-ISSN 1365-3164, Vol. 28, no 4, p. 377-e88Article in journal (Refereed)
    Abstract [en]

    Background

    Canine 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.

    Objectives

    The 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/Methods

    Skin 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.

    Results

    We 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.

    Conclusion

    Plakophilin‐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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  • 8.
    Auckburally, Adam
    et al.
    Swedish Univ Agr Sci, Fac Vet Med & Anim Sci, Dept Clin Sci, Uppsala, Sweden..
    Wiklund, Maja K.
    Swedish Univ Agr Sci, Fac Vet Med & Anim Sci, Dept Clin Sci, Uppsala, Sweden..
    Lord, Peter F.
    Swedish Univ Agr Sci, Fac Vet Med & Anim Sci, Dept Clin Sci, Uppsala, Sweden..
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory.
    Nyman, Gorel
    Swedish Univ Agr Sci, Fac Vet Med & Anim Sci, Dept Clin Sci, Uppsala, Sweden..
    Effects of pulsed inhaled nitric oxide delivery on the distribution of pulmonary perfusion in spontaneously breathing and mechanically ventilated anesthetized ponies2022In: American Journal of Veterinary Research, ISSN 0002-9645, E-ISSN 1943-5681, Vol. 83, no 2, p. 171-179Article in journal (Refereed)
    Abstract [en]

    Objective: To measure changes in pulmonary perfusion during pulsed inhaled nitric oxide (PiNO) delivery in anesthetized, spontaneously breathing and mechanically ventilated ponies positioned in dorsal recumbency.

    Animals: 6 adult ponies.

    Procedures: Ponies were anesthetized, positioned in dorsal recumbency in a CT gantry, and allowed to breathe spontaneously. Pulmonary artery, right atrial, and facial artery catheters were placed. Analysis time points were baseline, after 30 minutes of PiNO, and 30 minutes after discontinuation of PiNO. At each time point, iodinated contrast medium was injected, and CT angiography was used to measure pulmonary perfusion. Thermodilution was used to measure cardiac output, and arterial and mixed venous blood samples were collected simultaneously and analyzed. Analyses were repeated while ponies were mechanically ventilated.

    Results: During PiNO delivery, perfusion to aerated lung regions increased, perfusion to atelectatic lung regions decreased, arterial partial pressure of oxygen increased, and venous admixture and the alveolar-arterial difference in partial pressure of oxygen decreased. Changes in regional perfusion during PiNO delivery were more pronounced when ponies were spontaneously breathing than when they were mechanically ventilated.

    Clinical relevance: In anesthetized, dorsally recumbent ponies, PiNO delivery resulted in redistribution of pulmonary perfusion from dependent, atelectatic lung regions to nondependent aerated lung regions, leading to improvements in oxygenation. PiNO may offer a treatment option for impaired oxygenation induced by recumbency.

  • 9.
    Beasley, Val Richard
    et al.
    University of Illinois at Urbana-Champaign,.
    Adkesson, Adriane Michelle
    University of Illinois at Urbana-Champaign,.
    1. Wildlife and Ecosystem Health2012In: Ecology and Animal Health / [ed] Leif Norrgren and Jeffrey Levengood, Uppsala: Baltic University Press , 2012, 1, p. 13-26Chapter in book (Other (popular science, discussion, etc.))
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    ehsa 2-1
  • 10.
    Beckmann, Katrin M.
    et al.
    Univ Zurich, Vetsuisse Fac Zurich, Dept Small Anim, Sect Neurol, Zurich, Switzerland..
    Wang-Leandro, Adriano
    Univ Zurich, Vetsuisse Fac Zurich, Dept Diagnost & Clin Serv, Clin Diagnost Imaging, Zurich, Switzerland..
    Richter, Henning
    Univ Zurich, Vetsuisse Fac Zurich, Dept Diagnost & Clin Serv, Clin Diagnost Imaging, Zurich, Switzerland.;Univ Hosp Bonn, Clin Neuroradiol, Bonn, Germany..
    Bektas, Rima N.
    Univ Zurich, Vetsuisse Fac, Dept Diagnost & Clin Serv, Sect Anaesthesiol, Zurich, Switzerland..
    Steffen, Frank
    Univ Zurich, Vetsuisse Fac Zurich, Dept Small Anim, Sect Neurol, Zurich, Switzerland..
    Dennler, Matthias
    Univ Zurich, Vetsuisse Fac Zurich, Dept Diagnost & Clin Serv, Clin Diagnost Imaging, Zurich, Switzerland..
    Carrera, Ines
    Willows Vet Ctr & Referral Serv, Highlands Rd, Shirley, England..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, Geneva, Switzerland..
    Increased resting state connectivity in the anterior default mode network of idiopathic epileptic dogs2021In: Scientific Reports, E-ISSN 2045-2322, Vol. 11, no 1, article id 23854Article in journal (Refereed)
    Abstract [en]

    Epilepsy is one of the most common chronic, neurological diseases in humans and dogs and considered to be a network disease. In human epilepsy altered functional connectivity in different large-scale networks have been identified with functional resting state magnetic resonance imaging. Since large-scale resting state networks have been consistently identified in anesthetised dogs' application of this technique became promising in canine epilepsy research. The aim of the present study was to investigate differences in large-scale resting state networks in epileptic dogs compared to healthy controls. Our hypothesis was, that large-scale networks differ between epileptic dogs and healthy control dogs. A group of 17 dogs (Border Collies and Greater Swiss Mountain Dogs) with idiopathic epilepsy was compared to 20 healthy control dogs under a standardized sevoflurane anaesthesia protocol. Group level independent component analysis with dimensionality of 20 components, dual regression and two-sample t test were performed and revealed significantly increased functional connectivity in the anterior default mode network of idiopathic epileptic dogs compared to healthy control dogs (p = 0.00060). This group level differences between epileptic dogs and healthy control dogs identified using a rather simple data driven approach could serve as a starting point for more advanced resting state network analysis in epileptic dogs.

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    FULLTEXT01
  • 11.
    Beckmann, Katrin M.
    et al.
    Univ Zurich, Vetsuisse Fac Zurich, Dept Small Anim, Sect Neurol, Zurich, Switzerland.;Univ Bern, Grad Sch Cellular & Biomed Sci, Bern, Switzerland..
    Wang-Leandro, Adriano
    Univ Zurich, Vetsuisse Fac Zurich, Dept Diagnost & Clin Serv, Clin Diagnost Imaging, Zurich, Switzerland.;Univ Vet Med Hannover, Dept Small Anim Med & Surg, Hannover, Germany..
    Steffen, Frank
    Univ Zurich, Vetsuisse Fac Zurich, Dept Small Anim, Sect Neurol, Zurich, Switzerland..
    Richter, Henning
    Univ Zurich, Vetsuisse Fac Zurich, Dept Diagnost & Clin Serv, Clin Diagnost Imaging, Zurich, Switzerland..
    Dennler, Matthias
    Univ Zurich, Vetsuisse Fac Zurich, Dept Diagnost & Clin Serv, Clin Diagnost Imaging, Zurich, Switzerland..
    Bektas, Rima
    Univ Zurich, Vetsuisse Fac, Dept Clin Diagnost & Serv, Sect Anaesthesiol, Zurich, Switzerland..
    Carrera, Ines
    Vet Oracle Teleradiol, Norfolk, England..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, Geneva, Switzerland..
    Diffusion tensor-based analysis of white matter in dogs with idiopathic epilepsy2023In: Frontiers in Veterinary Science, E-ISSN 2297-1769, Vol. 10, article id 1325521Article in journal (Refereed)
    Abstract [en]

    Introduction: The understanding of epileptic seizure pathogenesis has evolved over time, and it is now generally accepted that not only are cortical and subcortical areas involved but also the connection of these regions in the white matter (WM). Recent human neuroimaging studies confirmed the involvement of the WM in several epilepsy syndromes. Neuroimaging studies investigating WM integrity with diffusion tensor imaging (DTI) in canine idiopathic epilepsy are lacking. This study aimed to test the hypothesis that WM diffusion changes can be found in dogs affected by idiopathic epilepsy.

    Method: Twenty-six dogs with idiopathic epilepsy (15 Border Collies and 11 Greater Swiss Mountain dogs) and 24 healthy controls (11 Beagle dogs, 5 Border Collies, and 8 Greater Swiss Mountain dogs) were prospectively enrolled. Most dogs with idiopathic epilepsy (17/26) were enrolled within 3 months after seizure onset. Diffusion tensor imaging of the brain with 32 diffusion directions (low b value = 0 s/mm2; maximal b value = 800 s/mm2) was performed in a 3 Tesla scanner. Tract-based spatial statistics (TBSS), a voxel-based approach, was used to investigate changes in fractional anisotropy (FA) and mean diffusivity (MD) in the idiopathic epilepsy group compared to the healthy control group. Additionally, FA and MD were investigated in the region of corpus callosum and cingulate white matter in both groups.

    Results: We observed subtle changes in WM DTI between the idiopathic epilepsy group and the healthy control group limited to cingulate WM, with a significantly lower FA in the idiopathic epilepsy group compared to the healthy control group in the region of interest (ROI) approach (p = 0.027). No significant changes were found between the idiopathic epilepsy group and the healthy control group in the TBSS analysis and in the corpus callosum in the ROI approach.

    Conclusion: This study supports the cingulate area as a target structure in canine epilepsy. The subtle changes only might be explained by the short duration of epilepsy, small sample sizes, and the higher variability in canine brain anatomy. Furthermore, all included dogs showed generalized tonic-clonic seizures, possibly affected by generalized epilepsy syndrome, which are also associated with less pronounced DTI changes in humans than focal epilepsy syndromes.

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  • 12.
    Berg, Frida
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Gustafson, Ulla
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    The uncoupling protein 1 gene (UCP1) is disrupted in the pig lineage: A genetic explanation for poor thermoregulation in piglets2006In: PLoS Genetics, ISSN 1553-7390, Vol. 2, no 8, p. 1178-1181Article in journal (Refereed)
    Abstract [en]

    Piglets appear to lack brown adipose tissue, a specific type of fat that is essential for nonshivering thermogenesis in mammals, and they rely on shivering as the main mechanism for thermoregulation. Here we provide a genetic explanation for the poor thermoregulation in pigs as we demonstrate that the gene for uncoupling protein 1 (UCP1) was disrupted in the pig lineage. UCP1 is exclusively expressed in brown adipose tissue and plays a crucial role for thermogenesis by uncoupling oxidative phosphorylation. We used long-range PCR and genome walking to determine the complete genome sequence of pig UCP1. An alignment with human UCP1 revealed that exons 3 to 5 were eliminated by a deletion in the pig sequence. The presence of this deletion was confirmed in all tested domestic pigs, as well as in European wild boars, Bornean bearded pigs, wart hogs, and red river hogs. Three additional disrupting mutations were detected in the remaining exons. Furthermore, the rate of nonsynonymous substitutions was clearly elevated in the pig sequence compared with the corresponding sequences in humans, cattle, and mice, and we used this increased rate to estimate that UCP1 was disrupted about 20 million years ago.

  • 13.
    Berglund, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Separation of Water and Fat Signal in Magnetic Resonance Imaging: Advances in Methods Based on Chemical Shift2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Magnetic resonance imaging (MRI) is one of the most important diagnostic tools of modern healthcare. The signal in medical MRI predominantly originates from water and fat molecules. Separation of the two components into water-only and fat-only images can improve diagnosis, and is the premier non-invasive method for measuring the amount and distribution of fatty tissue.

    Fat-water imaging (FWI) enables fast fat/water separation by model-based estimation from chemical shift encoded data, such as multi-echo acquisitions. Qualitative FWI is sufficient for visual separation of the components, while quantitative FWI also offers reliable estimates of the fat percentage in each pixel. The major problems of current FWI methods are long acquisition times, long reconstruction times, and reconstruction errors that degrade image quality.

    In this thesis, existing FWI methods were reviewed, and novel fully automatic methods were developed and evaluated, with a focus on fast 3D image reconstruction. All MRI data was acquired on standard clinical scanners.

    A triple-echo qualitative FWI method was developed for the specific application of 3D whole-body imaging. The method was compared with two reference methods, and demonstrated superior image quality when evaluated in 39 volunteers.

    The problem of qualitative FWI by dual-echo data with unconstrained echo times was solved, allowing faster and more flexible image acquisition than conventional FWI. Feasibility of the method was demonstrated in three volunteers and the noise performance was evaluated.

    Further, a quantitative multi-echo FWI method was developed. The signal separation was based on discrete whole-image optimization. Fast 3D image reconstruction with few reconstruction errors was demonstrated by abdominal imaging of ten volunteers.

    Lastly, a method was proposed for quantitative mapping of average fatty acid chain length and degree of saturation. The method was validated by imaging different oils, using gas-liquid chromatography (GLC) as the reference. The degree of saturation agreed well with GLC, and feasibility of the method was demonstrated in the thigh of a volunteer.

    The developed methods have applications in clinical settings, and are already being used in several research projects, including studies of obesity, dietary intervention, and the metabolic syndrome.

    List of papers
    1. Three-point Dixon method enables whole-body water and fat imaging of obese subjects
    Open this publication in new window or tab >>Three-point Dixon method enables whole-body water and fat imaging of obese subjects
    2010 (English)In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 63, no 6, p. 1659-1668Article in journal (Refereed) Published
    Abstract [en]

    Dixon imaging techniques derive chemical shift-separated water and fat images, enabling the quantification of fat content and forming an alternative to fat suppression. Whole-body Dixon imaging is of interest in studies of obesity and the metabolic syndrome, and possibly in oncology. A three-point Dixon method is proposed where two solutions are found analytically in each voxel. The true solution is identified by a multiseed three-dimensional region-growing scheme with a dynamic path, allowing confident regions to be solved before unconfident regions, such as background noise. 2 pi-Phase unwrapping is not required. Whole-body datasets (256 x 184 x 252 voxels) were collected from 39 subjects (body mass index 19.8-45.4 kg/m(2)), in a mean scan time of 5 min 15 sec. Water and fat images were reconstructed offline, using the proposed method and two reference methods. The resulting images were subjectively graded on a four-grade scale by two radiologists, blinded to the method used. The proposed method was found superior to the reference methods. It exclusively received the two highest grades, implying that only mild reconstruction failures were found. The computation time for a whole-body dataset was 1 min 51.5 sec +/- 3.0 sec. It was concluded that whole-body water and fat imaging is feasible even for obese subjects, using the proposed method.

    Keywords
    three-point Dixon, whole-body MRI, water and fat separation, chemical shift imaging, fat suppression
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-129498 (URN)10.1002/mrm.22385 (DOI)000278164400026 ()20512869 (PubMedID)
    Available from: 2010-08-17 Created: 2010-08-17 Last updated: 2017-12-12Bibliographically approved
    2. Two-point dixon method with flexible echo times
    Open this publication in new window or tab >>Two-point dixon method with flexible echo times
    2011 (English)In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 65, no 4, p. 994-1004Article in journal (Refereed) Published
    Abstract [en]

    The two-point Dixon method is a proton chemical shift imaging technique that produces separated water-only and fat-only images from a dual-echo acquisition. It is shown how this can be achieved without the usual constraints on the echo times. A signal model considering spectral broadening of the fat peak is proposed for improved water/fat separation. Phase errors, mostly due to static field inhomogeneity, must be removed prior to least-squares estimation of water and fat. To resolve ambiguity of the phase errors, a corresponding global optimization problem is formulated and solved using a message-passing algorithm. It is shown that the noise in the water and fat estimates matches the Cramér-Rao bounds, and feasibility is demonstrated for in vivo abdominal breath-hold imaging. The water-only images were found to offer superior fat suppression compared with conventional spectrally fat suppressed images.

    Keywords
    chemical shift imaging, fat suppression, two-point Dixon, water and fat separation
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-150936 (URN)10.1002/mrm.22679 (DOI)000288612000011 ()21413063 (PubMedID)
    Available from: 2011-04-08 Created: 2011-04-08 Last updated: 2017-12-11Bibliographically approved
    3. Three-dimensional water/fat separation and T2* estimation based on whole-image optimization: application in breathhold liver imaging at 1.5 T
    Open this publication in new window or tab >>Three-dimensional water/fat separation and T2* estimation based on whole-image optimization: application in breathhold liver imaging at 1.5 T
    2012 (English)In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 67, no 6, p. 1684-1693Article in journal (Refereed) Published
    Abstract [en]

    The chemical shift of water and fat resonances in proton MRI allows separation of water and fat signal from chemical shift encoded data. This work describes an automatic method that produces separate water and fat images as well as quantitative maps of fat signal fraction and T2* from complex multi-echo gradient recalled datasets. Accurate water and fat separation is challenging due to signal ambiguity at the voxel level. Whole-image optimization can resolve this ambiguity, but might be computationally demanding, especially for three-dimensional (3D) data. In this work, periodicity of the model fit residual as a function of the off-resonance was utilized to modify a previously proposed formulation of the problem. This gives a smaller solution space and allows rapid optimization. Feasibility and accurate separation of water and fat signal was demonstrated in breathhold 3D liver imaging of ten volunteer subjects, with both acquisition and reconstruction times below 20 seconds.

    Keywords
    water and fat separation, chemical shift imaging, quantitative MRI, liver fat, T2* mapping, QPBO
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-158097 (URN)10.1002/mrm.23185 (DOI)000304086000020 ()22189760 (PubMedID)
    Available from: 2011-08-31 Created: 2011-08-31 Last updated: 2017-12-08Bibliographically approved
    4. Model-based mapping of fat unsaturation and chain length by chemical shift imaging: phantom validation and in vivo feasibility
    Open this publication in new window or tab >>Model-based mapping of fat unsaturation and chain length by chemical shift imaging: phantom validation and in vivo feasibility
    2012 (English)In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 68, no 6, p. 1815-1827Article in journal (Refereed) Published
    Abstract [en]

    Knowledge about the triglyceride (fat) 1H spectrum enables quantitative determination of several triglyceride characteristics. This work describes a model-based chemical shift imaging method that separates water and fat signal and provides maps of three triglyceride quantities: fatty acid carbon chain length (CL), number of double bond pairs (ndb), and number of methylene-interrupted double bonds (nmidb). The method was validated by imaging a phantom containing ten different oils using 1.5 T and 3.0 T clinical scanners, with gas-liquid chromatography (GLC) as reference. Repeated acquisitions demonstrated high reproducibility of the method. Statistical tests of correlation and linear regression were performed to examine the accuracy of the method. Significant correlation was found at both field strengths for all three quantities, and high correlation (r2 > 0.96) was found for measuring ndb and nmidb. Feasibility of the method for in vivo imaging of the thigh was demonstrated at both field strengths. The estimates of ndb and nmidb in subcutaneous adipose tisse were in agreement with literature values, while CL appears overestimated. The method has potential use in large-scale cross-sectional and longitudinal studies of triglyceride composition, and its relation to diet and various diseases.

    Keywords
    water/fat separation, chemical shift imaging, quantitative MRI, fat unsaturation, triglyceride mapping, fatty acid composition
    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Identifiers
    urn:nbn:se:uu:diva-158098 (URN)10.1002/mrm.24196 (DOI)000311398600015 ()22334300 (PubMedID)
    Available from: 2011-08-31 Created: 2011-08-31 Last updated: 2017-12-08Bibliographically approved
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  • 14.
    Bergman, Daniel
    et al.
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, 750 07, Uppsala, Sweden.
    Bäckström, Camilla
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, 750 07, Uppsala, Sweden.
    Hansson-Hamlin, Helene
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, 750 07, Uppsala, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Ström Holst, Bodil
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, 750 07, Uppsala, Sweden.
    Pre-existing canine anti-IgG antibodies: implications for immunotherapy, immunogenicity testing and immunoassay analysis2020In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 12696Article in journal (Refereed)
    Abstract [en]

    One of the most enigmatic features of humoral immunity is the prevalent presence of circulating autoantibodies against IgG. These autoantibodies consist of several subsets, including rheumatoid factors, anti-Fab/anti-F(ab')2-autoantibodies, and anti-idiotypic antibodies. Anti-IgG autoantibodies can impair the safety and efficacy of therapeutic antibodies and interfere with immunogenicity tests in clinical trials. They can also cross-react with allospecific IgG, presenting as heterophilic antibodies that interfere with diagnostic immunoassays. Owing to these factors, recent years have seen a resurgent interest in anti-IgG autoantibodies, but their underlying clinical significance, as well as biological roles and origins, remain opaque. Increased knowledge about canine anti-IgG autoantibodies could facilitate the development of canine immunotherapies and help in understanding and counteracting immunoassay interference. This study investigated the clinical significance and interconnection of heterophilic antibodies, anti-Fab, and anti-F(ab')2-autoantibodies in dogs. We performed a 2-year prospective follow-up of dogs with heterophilic antibodies and analyzed serum for anti-Fab and anti-F(ab')2-autoantibodies. Canine heterophilic antibodies can persist for at least 2 years in serum. A widespread occurrence of anti-Fab and anti-F(ab')2-autoantibodies was found, with reactivity to cryptic epitopes in the IgG hinge region and sporadic cross-reactivity with mouse IgG. Canine anti-Fab and anti-F(ab')2-autoantibodies are thus potential sources of clinical immunogenicity and immunoassay interference.

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  • 15.
    Bergman, Daniel
    et al.
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hansson-Hamlin, Helene
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Ström Holst, Bodil
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Investigation of interference from canine anti-mouse antibodies in hormone immunoassays2019In: Veterinary clinical pathology, ISSN 0275-6382, E-ISSN 1939-165X, Vol. 48, no S1, p. 59-69Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Canine anti-mouse antibodies are a potential source of immunoassay interference, but erroneous immunoassay results are not always easily identifiable. Anti-Müllerian hormone (AMH) is a marker for the presence of gonads in dogs, but elevated AMH concentrations in neutered dogs could also be caused by antibody interference. For other assays, a discrepant result obtained after antibody precipitation might indicate antibody interference.

    OBJECTIVES: We aimed to evaluate if canine anti-mouse antibodies are a source of erroneous results in the AMH assay and if antibody precipitation with polyethylene glycol (PEG) is a useful tool for detecting antibody interference in a variety of immunoassays used in the veterinary clinical laboratory.

    METHODS: Twenty-nine positive and 25 negative samples for anti-mouse antibodies were analyzed for AMH, canine total thyroxine (TT4), canine thyroid-stimulating hormone (TSH) and progesterone before and after treatment with PEG. Results that differed by more than four SDs from the intra-assay coefficients of variation were considered discrepant. Elevated AMH concentrations in neutered dogs with anti-mouse antibodies and no visible gonads present were considered evidence of interference.

    RESULTS: Evidence of antibody interference was found in two samples analyzed for AMH. The presence of anti-mouse antibodies did not lead to a higher proportion of discrepant results after PEG treatment for any of the immunoassays. The overall incidence of discrepant results for healthy controls was very high (73%).

    CONCLUSIONS: Canine anti-mouse antibodies are a source of erroneous AMH results. Antibody precipitation with PEG is not a useful tool for detecting interference caused by such antibodies.

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  • 16.
    Bergman, Daniel
    et al.
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hansson-Hamlin, Helene
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden..
    Svensson, Anna
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden..
    Holst, Bodil Ström
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden..
    Prevalence of interfering antibodies in dogs and cats evaluated using a species-independent assay.2018In: Veterinary clinical pathology, ISSN 0275-6382, E-ISSN 1939-165X, Vol. 47, no 2, p. 205-212Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Interfering antibodies in human serum and plasma are known to react with mammalian antibodies in immunoassays and cause false-positive test results. Although this phenomenon was recently shown in companion animals, knowledge regarding immunoassay interference in veterinary medicine is very limited.

    OBJECTIVES: The aims of this study were to set up a species-independent immunoassay procedure to detect interference in serum samples, to screen for interference in a cross-section of canine and feline patient samples from an animal hospital, and to determine if the detected interference could be neutralized using an immunoassay based on nonmammalian reagents.

    METHODS: A 2-site sandwich-type interference assay was set up using commercially available mouse reagents. A total of 369 serum samples from 320 dogs and 263 samples from 218 cats were analyzed using the interference assay. Multiple samples were submitted from 36 dogs and 39 cats. Nineteen samples identified as interference-positive were analyzed in an assay using chicken antibodies.

    RESULTS: Interference was detected in samples from 28 dogs (9%) and 10 cats (5%) screened with the interference assay. Except for 1 cat, consistent results were obtained for all 75 dogs and cats that submitted more than 1 sample. The interference was eliminated when analyzed in the chicken-based assay (P < .001).

    CONCLUSIONS: Substances with reactivity toward mouse IgG can be detected in serum samples from dog and cat patients using a 2-site interference assay. The detected substances are most likely interfering antibodies, possibly originating from immunization with other mammalian species.

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  • 17.
    Bergman, Daniel
    et al.
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, 750 07, Sweden. .
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hansson-Hamlin, Helene
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, 750 07, Sweden. .
    Åhlén, Emma
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, 750 07, Sweden. .
    Holst, Bodil Ström
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, 750 07, Sweden. .
    Characterization of canine anti-mouse antibodies highlights that multiple strategies are needed to combat immunoassay interference2019In: Scientific Reports, E-ISSN 2045-2322, Vol. 9, no 1, article id 14521Article in journal (Refereed)
    Abstract [en]

    Immunoassays are widely used for detection and quantification of analytes in biological samples, but are vulnerable to analytical errors caused by interfering sample substances. Of particular interest are endogenous anti-animal antibodies that may bind to the immunoassay antibodies and cause erroneous test results. This phenomenon is a hazard to patient safety in both human and veterinary medicine. Here, we demonstrate that anti-mouse antibodies in dogs bind selectively to different regions of the murine IgG molecule, cross-react with IgG from different species, and consist of all major antibody classes present in canine serum (IgA, IgG and IgM). The antibody characteristics varied among individuals and their prevalence differed between two dog breeds. The selective binding to different IgG regions suggests that the antibodies might not originate from immunization through exposure to mice or other species. These findings show that canine anti-mouse antibodies are highly heterogeneous in nature and therefore require a combination of strategies to be counteracted.

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  • 18.
    Betsholtz, Christer
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer and Vascular Biology.
    Keller, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer and Vascular Biology.
    PDGF, Pericytes and the Pathogenesis of Idiopathic Basal Ganglia Calcification (IBGC)2014In: Brain Pathology, ISSN 1015-6305, E-ISSN 1750-3639, Vol. 24, no 4, p. 387-395Article in journal (Refereed)
    Abstract [en]

    Platelet-derived growth factors (PDGFs) are important mitogens for various types of mesenchymal cells, and as such, they exert critical functions during organogenesis in mammalian embryonic and early postnatal development. Increased or ectopic PDGF activity may also cause or contribute to diseases such as cancer and tissue fibrosis. Until recently, no loss-of-function (LOF) mutations in PDGF or PDGF receptor genes were reported as causally linked to a human disease. This changed in 2013 when reports appeared on presumed LOF mutations in the genes encoding PDGF-B and its receptor PDGF receptor-beta (PDGF-R) in familial idiopathic basal ganglia calcification (IBGC), a brain disease characterized by anatomically localized calcifications in or near the blood microvessels. Here, we review PDGF-B and PDGF-R biology with special reference to their functions in brain-blood vessel development, pericyte recruitment and the regulation of the blood-brain barrier. We also discuss various scenarios for IBGC pathogenesis suggested by observations in patients and genetically engineered animal models of the disease.

  • 19. Bett, B
    et al.
    Kiunga, P
    Gachohi, J
    Sindato, C
    Mbotha, D
    Robinson, T
    Lindahl, J
    Grace, D
    Effects of climate change on the occurrence and distribution of livestock diseases.2017In: Preventive Veterinary Medicine, ISSN 0167-5877, E-ISSN 1873-1716, Vol. 137, no Pt B, p. 119-129, article id S0167-5877(16)30631-6Article in journal (Refereed)
    Abstract [en]

    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.

  • 20.
    Bett, B
    et al.
    Int Livestock Res Inst, Nairobi, Kenya.
    Lindahl, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Int Livestock Res Inst, Nairobi, Kenya; Swedish Univ Agr Sci, Uppsala, Sweden.
    Sang, R
    Kenya Govt Med Res Ctr, Nairobi, Kenya.
    Wainaina, M
    Int Livestock Res Inst, Nairobi, Kenya.
    Kairu-Wanyoike, S
    Minist Agr Livestock & Fisheries, Dept Vet Serv, Nairobi, Kenya.
    Bukachi, S
    Univ Nairobi, Inst Anthropol Gender & African Studies, Nairobi, Kenya.
    Njeru, I
    Kenyatta Natl Hosp, Minist Hlth, Div Dis Surveillance & Response, Nairobi, Kenya.
    Karanja, J
    Kenyatta Natl Hosp, Minist Hlth, Div Dis Surveillance & Response, Nairobi, Kenya.
    Ontiri, E
    Int Livestock Res Inst, Nairobi, Kenya.
    Kariuki Njenga, M
    Washington State Univ, Paui Men Sch Global Anim Hlth, Pullman, WA 99164 USA.
    Wright, D
    Univ Oxford, Jenner Inst, Oxford, England.
    Warimwe, G M
    KEMRI Wellcome Trust Res Programme, Kilifi, Kenya; Univ Oxford, Ctr Trop Med & Global Hlth, Oxford, England.
    Grace, D
    Int Livestock Res Inst, Nairobi, Kenya.
    Association between Rift Valley fever virus seroprevalences in livestock and humans and their respective intra-cluster correlation coefficients, Tana River County, Kenya2019In: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 147, article id e67Article in journal (Refereed)
    Abstract [en]

    We implemented a cross-sectional study in Tana River County, Kenya, a Rift Valley fever (RVF)-endemic area, to quantify the strength of association between RVF virus (RVFv) seroprevalences in livestock and humans, and their respective intra-cluster correlation coefficients (ICCs). The study involved 1932 livestock from 152 households and 552 humans from 170 households. Serum samples were collected and screened for anti-RVFv immunoglobulin G (IgG) antibodies using inhibition IgG enzyme-linked immunosorbent assay (ELISA). Data collected were analysed using generalised linear mixed effects models, with herd/household and village being fitted as random variables. The overall RVFv seroprevalences in livestock and humans were 25.41% (95% confidence interval (CI) 23.49-27.42%) and 21.20% (17.86-24.85%), respectively. The presence of at least one seropositive animal in a household was associated with an increased odds of exposure in people of 2.23 (95% CI 1.03-4.84). The ICCs associated with RVF virus seroprevalence in livestock were 0.30 (95% CI 0.19-0.44) and 0.22 (95% CI 0.12-0.38) within and between herds, respectively. These findings suggest that there is a greater variability of RVF virus exposure between than within herds. We discuss ways of using these ICC estimates in observational surveys for RVF in endemic areas and postulate that the design of the sentinel herd surveillance should consider patterns of RVF clustering to enhance its effectiveness as an early warning system for RVF epidemics.

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  • 21. Bett, Bernard
    et al.
    Grace, Delia
    Lee, Hu Suk
    Lindahl, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. International Livestock Research Institute, Nairobi, Kenya; Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Nguyen-Viet, Hung
    Phuc, Pham-Duc
    Quyen, Nguyen Huu
    Tu, Tran Anh
    Phu, Tran Dac
    Tan, Dang Quang
    Nam, Vu Sinh
    Spatiotemporal analysis of historical records (2001-2012) on dengue fever in Vietnam and development of a statistical model for forecasting risk2019In: PLOS ONE, E-ISSN 1932-6203, Vol. 14, no 11, article id e0224353Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Dengue fever is the most widespread infectious disease of humans transmitted by Aedes mosquitoes. It is the leading cause of hospitalization and death in children in the Southeast Asia and western Pacific regions. We analyzed surveillance records from health centers in Vietnam collected between 2001-2012 to determine seasonal trends, develop risk maps and an incidence forecasting model.

    METHODS: The data were analyzed using a hierarchical spatial Bayesian model that approximates its posterior parameter distributions using the integrated Laplace approximation algorithm (INLA). Meteorological, altitude and land cover (LC) data were used as predictors. The data were grouped by province (n = 63) and month (n = 144) and divided into training (2001-2009) and validation (2010-2012) sets. Thirteen meteorological variables, 7 land cover data and altitude were considered as predictors. Only significant predictors were kept in the final multivariable model. Eleven dummy variables representing month were also fitted to account for seasonal effects. Spatial and temporal effects were accounted for using Besag-York-Mollie (BYM) and autoregressive (1) models. Their levels of significance were analyzed using deviance information criterion (DIC). The model was validated based on the Theil's coefficient which compared predicted and observed incidence estimated using the validation data. Dengue incidence predictions for 2010-2012 were also used to generate risk maps.

    RESULTS: The mean monthly dengue incidence during the period was 6.94 cases (SD 14.49) per 100,000 people. Analyses on the temporal trends of the disease showed regular seasonal epidemics that were interrupted every 3 years (specifically in July 2004, July 2007 and September 2010) by major fluctuations in incidence. Monthly mean minimum temperature, rainfall, area under urban settlement/build-up areas and altitude were significant in the final model. Minimum temperature and rainfall had non-linear effects and lagging them by two months provided a better fitting model compared to using unlagged variables. Forecasts for the validation period closely mirrored the observed data and accurately captured the troughs and peaks of dengue incidence trajectories. A favorable Theil's coefficient of inequality of 0.22 was generated.

    CONCLUSIONS: The study identified temperature, rainfall, altitude and area under urban settlement as being significant predictors of dengue incidence. The statistical model fitted the data well based on Theil's coefficient of inequality, and risk maps generated from its predictions identified most of the high-risk provinces throughout the country.

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  • 22. Bett, Bernard
    et al.
    Lindahl, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. International Livestock Research Institute, Nairobi, Kenya; Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Delia, Grace
    Climate Change and Infectious Livestock Diseases: The Case of Rift Valley Fever and Tick-Borne Diseases2019In: The Climate-Smart Agriculture Papers: Investigating the Business of a Productive, Resilient and Low Emission Future / [ed] Todd S. Rosenstock, Andreea Nowak & Evan Girvetz, Cham: Springer, 2019, p. 29-37Chapter in book (Refereed)
    Abstract [en]

    Climate change influences the occurrence and transmission of a wide range of livestock diseases through multiple pathways. Diseases caused by pathogens that spent part of their life cycle outside the host (e.g. in vectors or the environment) are more sensitive in this regard, compared to those caused by obligate pathogens. In this chapter, we use two well-studied vector-borne diseases—Rift Valley fever (RVF) and tick-borne diseases (TBDs)—as case studies to describe direct pathways through which climate change influences infectious disease-risk in East and southern Africa. The first case study demonstrates that changes in the distribution and frequency of above-normal precipitation increases the frequency of RVF epidemics. The second case study suggests that an increase in temperature would cause shifts in the spatial distribution of TBDs, with cooler and wetter areas expected to experience heightened risk with climate change. These diseases already cause severe losses in agricultural productivity, food security and socio-economic development wherever they occur, and an increase in their incidence or geographical coverage would intensify these losses. We further illustrate some of the control measures that can be used to manage these diseases and recommend that more research should be done to better understand the impacts of climate change on livestock diseases as well as on the effectiveness of the available intervention measures.

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  • 23.
    Bignert, Anders
    et al.
    Swedish Museum of Natural History, Stockholm, Sweden.
    Bäcklin, Britt-Marie
    Swedish Museum of Natural History, Stockholm, Sweden.
    Helander, Björn
    Swedish Museum of Natural History, Stockholm, Sweden.
    Roos, Anna
    Swedish Museum of Natural History, Stockholm, Sweden.
    9. Contaminants and Health of Aquatic Wildlife2012In: Ecology and Animal Health / [ed] Leif Norrgren and Jeffrey Levengood, Uppsala: Baltic University Press , 2012, 1, p. 73-85Chapter in book (Other (popular science, discussion, etc.))
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    ehsa 2-9
  • 24.
    Björkman, Ingeborg
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research.
    Röing, Marta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research.
    Sternberg Lewerin, Susanna
    Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Stålsby Lundborg, Cecilia
    Karolinska Inst, Dept Global Publ Hlth Hlth Syst & Policy HSP Impr, Stockholm, Sweden.
    Eriksen, Jaran
    Karolinska Inst, Dept Global Publ Hlth Hlth Syst & Policy HSP Impr, Stockholm, Sweden; Karolinska Inst, Sodersjukhuset, Venhalsan, Dept Clin Sci & Educ,Unit Infect Dis, Stockholm, Sweden.
    Animal Production With Restrictive Use of Antibiotics to Contain Antimicrobial Resistance in Sweden: A Qualitative Study2021In: Frontiers in Veterinary Science, E-ISSN 2297-1769, Vol. 7, article id 619030Article in journal (Refereed)
    Abstract [en]

    Antibacterial resistance (ABR), is a growing global threat to human and animal health. Efforts to contain ABR are urgently needed. This qualitative interview study explored perceptions of work to contain ABR among stakeholders in food animal production in Sweden, with focus on broiler production. Semi-structured interviews were carried out with a strategic sample of 13 stakeholders in different parts of production, from professionals at policy level, veterinary authorities, to poultry farmers and poultry veterinarians. Conventional inductive content analysis was used for data analysis. A latent theme, "Working in unison," emerged, based on the consistency expressed by the informants when they discussed ABR, use of antibiotics, and animal health management. This theme was built on four domains representing the content of the interviews: Knowledge and engagement; Cooperation; Animal health concept; and Development in balance with economic prerequisites. According to the informants, ABR has not been an isolated issue in Sweden but has been included in a tradition of animal health and welfare, and actions have been driven by the industry or by government regulations. Veterinarians described how they worked closely with farmers. Farmers felt involved in the development of animal health management methods. The One Health concept was well-known among stakeholders at national level but not at farm level. Close cooperation between stakeholders seems to facilitate development of animal production with low use of antibiotics.

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  • 25.
    Björnström, Agnes
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Blomström, Anne-Lie
    Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, Box 7028, S-75007 Uppsala, Sweden..
    Singh, Manish Chandra
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Hesson, Jenny C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sindbis virus neutralising antibodies detected in Swedish horses2021In: One Health, ISSN 2352-7714, Vol. 12, article id 100242Article in journal (Refereed)
    Abstract [en]

    A number of viruses transmitted by mosquitoes are well known to cause disease in both humans and horses, ranging from mild fevers to mortal neurological disease. A recently discovered connection between the alphavirus Sindbis virus (SINV) and neurological disease in horses in South Africa initiated this serological study in northern Europe, where the same genotype of SINV (SINV-I) is also highly endemic. We tested 171 serum samples, originally obtained from horses for other reasons from April to October 2019, for presence of SINV neutralising antibodies using a plaque reduction neutralisation test (PRNT). The serum from six horses reduced the plaque count more than 80%, and two out of these reduced the plaque count more than 90%. These horses were sampled in six different regions of Sweden, and included individuals sampled from April to August. This study shows that horses in Sweden have become infected with SINV and developed neutralising antibodies. Potential connections between infection and development of disease are important questions for future studies.

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  • 26.
    Brantberg, Ida
    et al.
    School of Veterinary Science, The University of Liverpool, Leahurst Campus, Chester High Road, Neston CH64 7TE, Wirral, UK;Djursjukhuset Malmö, IVC Evidensia, Cypressvägen 11, SE-213 63 Malmö, Sweden.
    Grooten, Wilhelmus J. A.
    Division of Physiotherapy, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Alfred Nobels Allé 23, SE-141 83 Huddinge, Sweden;Women’s Health and Allied Health Professionals’ Theme, Department of Occupational Therapy and Physiotherapy, Karolinska University Hospital, Solna N1:00, SE-171 76 Stockholm, Sweden.
    Essner, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Djurkliniken Gefle, IVC Evidensia, Norra Gatan 1, SE-803 21 Gävle, Sweden;Uppsala University Hospital, SE-751 85 Uppsala, Sweden.
    The Effect of Therapeutic Exercise on Body Weight Distribution, Balance, and Stifle Function in Dogs following Stifle Injury2023In: Animals, E-ISSN 2076-2615, Vol. 14, no 1, article id 92Article in journal (Refereed)
    Abstract [en]

    Stifle injury is common in the companion dog population, affecting weight bearing, neuromuscular control, and balance. Therapeutic exercises after stifle injury seem to be effective, but high-quality research evaluating the effects is lacking. This randomized controlled trial evaluated the effects of a 12-week progressive therapeutic home exercise protocol on three-legged standing, targeting balance and postural- and neuromuscular control and disability in dogs with stifle injury. Thirty-three dogs with stifle injury were randomly allocated to intervention (n = 18) and control groups (n = 15), both receiving a standard rehabilitation protocol. Additionally, the intervention group received a progressive therapeutic exercise protocol. The outcome measures were static body weight distribution between hindlimbs, balance control, the canine brief pain inventory, and the Finnish canine stifle index. Both groups improved after the intervention period, but the group using the progressive therapeutic exercise protocol improved to a greater extent regarding static body weight distribution between the hindlimbs (I: median = 2.5%, IQR = 1.0–4.5; C: median = 5.5%, IQR = 3.0–8.8), pain-related functional disability (I: median = 0.0, IQR = 0.0–0.2; C: median = 0.9, IQR = 0.1–1.8), and stifle function (I: median = 25.0, IQR = 9.4–40.6; C: median = 75.0, IQR = 31.3–87.5), with intermediate to strong effects. These clinically relevant results indicate that this home exercise program can improve hindlimb function and restore neuromuscular control.

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  • 27.
    Brebu, M.
    et al.
    Petru Poni Inst Macromol Chem, Iasi, Romania..
    Beleno, K.
    Petru Poni Inst Macromol Chem, Iasi, Romania.;Univ Pamplona, Pamplona, Colombia..
    Ionescu, Radu
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Solid State Physics.
    Turcu, D.
    Spiru Haret Univ, Fac Vet Med, Bucharest, Romania..
    Dinu, H.
    Pasteur Inst, Bucharest, Romania..
    Caciandone, H.
    CSV Targusor, Constanta, Romania..
    Enache, A. A.
    Apel Laser, Mogosoaia, Ilfov, Romania..
    Volatolomic analysis applied to farm animals. II.: Volatile compounds emitted from the faeces of cattle2020In: REVISTA ROMANA DE MEDICINA VETERINARA, ISSN 1220-3173, Vol. 30, no 1, p. 34-38Article in journal (Refereed)
    Abstract [en]

    Volatolomics opens new possibilities for the study of the biological systems. The volatility distribution of highly- and semi-volatile organic compounds released from the faeces of cattle was studied. Samples were collected from farm animals in three regions of Romania, namely Ramnicu Valcea, Bistri.a Nasaud and Constanta. Special procedures for sample collection, storage, transportation and analysis were developed. Organic compounds were found in a broad boiling point range, from n-C-6 (36 degrees C) up to n-C-17 (302 degrees C), but the highest concentration of about 80 % was found in the range of n-C-9-n-C-12 (151-216 degrees C), with a peak at n-C-10 (151-174 degrees C). Only slight variations were observed among the samples collected from different geographical regions.

  • 28.
    Brebu, M.
    et al.
    Petru Poni Inst Macromol Chem, Iasi, Jud Iasi, Romania..
    Mogollon, Lisset
    Univ Pamplona, Pamplona, Colombia..
    Ionescu, Radu
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Solid State Physics.
    Turcu, D.
    Spiru Haret Univ, Fac Vet Med, Bucharest, Romania..
    Grigorescu, P.
    Spiru Haret Univ, Fac Vet Med, Bucharest, Romania..
    Iordache, A.
    CSV Tetoiu, Jud Valcea, Romania..
    Enache, A. A.
    Apel Laser, Mogosoaia, Jud Ilfov, Romania..
    Volatolomic analysis applied to farm animals. III.: Volatile compounds emitted through skin of cattle2020In: REVISTA ROMANA DE MEDICINA VETERINARA, ISSN 1220-3173, Vol. 30, no 2, p. 29-32Article in journal (Refereed)
    Abstract [en]

    Volatolomics opens new possibilities for the study of biological systems. Volatility distribution of highly-and semi-volatile organic compounds emitted through the skin of cattle was studied. Samples were collected from farm animals in three regions of Romania, namely Ramnicu Valcea, Bistrita Nasaud and Constanta. Special procedures for sample collection, storage, transportation and analysis were developed. About 62 -68 % of organic compounds emitted through skin had the volatility in the boiling point range of n-C(10 )ormal paraffin (151-174 degrees C) and another 16-18 % was in the range of n-C-11- n-C-12 (174-216 degrees C). Only slight variations were observed among samples collected from different geographical regions.

  • 29. Breed, Andrew C.
    et al.
    Breed, Martin F.
    Australian Centre for Evolutionary Biology and Biodiversity (ACEBB), and School of Earth and Environmental Sciences, University of Adelaide.
    Meers, Joanne
    Field, Hume E.
    Evidence of endemic Hendra virus infection in flying-foxes (Pteropus conspicillatus): implications for disease risk management2011In: PLOS ONE, E-ISSN 1932-6203, Vol. 6, p. e28816-Article in journal (Refereed)
    Abstract [en]

    This study investigated the seroepidemiology of Hendra virus in a spectacled flying-fox (Pteropus conspicillatus) population in northern Australia, near the location of an equine and associated human Hendra virus infection in late 2004. The pattern of infection in the population was investigated using a serial cross-sectional serological study over a 25-month period, with blood sampled from 521 individuals over six sampling sessions. Antibody titres to the virus were determined by virus neutralisation test. In contrast to the expected episodic infection pattern, we observed that seroprevalence gradually increased over the two years suggesting infection was endemic in the population over the study period. Our results suggested age, pregnancy and lactation were significant risk factors for a detectable neutralizing antibody response. Antibody titres were significantly higher in females than males, with the highest titres occurring in pregnant animals. Temporal variation in antibody titres suggests that herd immunity to the virus may wax and wane on a seasonal basis. These findings support an endemic infection pattern of henipaviruses in bat populations suggesting their infection dynamics may differ significantly from the acute, self limiting episodic pattern observed with related viruses (e.g. measles virus, phocine distemper virus, rinderpest virus) hence requiring a much smaller critical host population size to sustain the virus. These findings help inform predictive modelling of henipavirus infection in bat populations, and indicate that the life cycle of the reservoir species should be taken into account when developing risk management strategies for henipaviruses.

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  • 30.
    Bremer, Hanna D.
    et al.
    Swedish Univ Agr Sci SLU, Dept Clin Sci, Box 7054, SE-75007 Uppsala, Sweden..
    Lattwein, Erik
    Euroimmun AG, Lubeck, Germany..
    Renneker, Stefanie
    Euroimmun AG, Lubeck, Germany..
    Lilliehook, Inger
    Swedish Univ Agr Sci, Univ Anim Hosp, Clin Pathol Lab, Uppsala, Sweden..
    Rönnelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Hansson-Hamlin, Helene
    Swedish Univ Agr Sci SLU, Dept Clin Sci, Box 7054, SE-75007 Uppsala, Sweden..
    Identification of specific antinuclear antibodies in dogs using a line immunoassay and enzyme-linked immunosorbent assay2015In: Veterinary Immunology and Immunopathology, ISSN 0165-2427, E-ISSN 1873-2534, Vol. 168, no 3-4, p. 233-241Article in journal (Refereed)
    Abstract [en]

    Circulating antinuclear antibodies (ANA) are commonly present in the systemic autoimmune disease Systemic Lupus Erythematosus (SLE) and in other systemic rheumatic diseases, in humans as well as in dogs. The indirect immunofluorescence (IIF)-ANA test is the standard method for detecting ANA. Further testing for specific ANA with immunoblot techniques or ELISAs is routinely performed in humans to aid in the diagnosis and monitoring of disease. Several specific ANA identified in humans have been identified also in suspected canine SLE but, in contrast to humans, investigation of autoantibodies in canine SLE is mainly restricted to the IIF-ANA test. Our aim was to identify both known and novel specific ANA in dogs and to investigate if different IIF-ANA patterns are associated with different specific ANA in dogs. Sera from 240 dogs with suspicion of autoimmune disease (210 IIF-ANA positive (ANA(pos)) and 30 IIF-ANA negative (ANA(neg))) as well as sera from 27 healthy controls were included. The samples were analysed with a line immunoassay, LIA (Euroline ANA Profile 5, Euroimmun, Lubeck, Germany) and four different ELISAs (Euroimmun). The ANA(pos) dogs were divided in two groups depending on the type of IIF-ANA pattern. Of the 210 ANA(pos) samples 68 were classified as ANA homogenous (ANA(H)) and 141 as ANA speckled (ANA(S)), one sample was not possible to classify. Dogs in the ANA(H) group had, compared to the other groups, most frequently high levels of anti-double stranded deoxyribonucleic acid (dsDNA) and anti-nucleosome ANA. Anti-dsDNA antibodies were confirmed in some dogs with the Crithidia luciliae indirect immunofluorescence test (CLIFT).The frequency of ANA(H) dogs with values above those observed in the healthy group was significantly higher compared to ANA(S) dogs for anti-dsDNA, anti-nucleosome, and anti-histone reactivity. Dogs in the ANA(S) group had, compared to the other groups, most frequently high levels of anti-ribonucleoproteins (RNP) and/or anti-Smith (Sm) antibodies. Reactivity against Sjogren's syndrome related antigens (SS)-A (including the Ro-60 and Ro-52 subcomponents), SS-B, histidyl tRNA synthetase (Jo-1), topoisomerase I antigen (Scl-70), polymyositis-scleroderma antigen (PM-Scl) and proliferating cell nuclear antigen (PCNA) was also noted in individual dogs. In conclusion, by using a commercial LIA and different ELISAs originally developed for detection of human ANA, we identified several specific ANA in serum samples from dogs sampled for IIF-ANA testing. Further, we found that the types of IIF-ANA pattern were associated with reactivity against some particular nuclear antigens.

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  • 31. Bröjer, Caroline
    et al.
    Järhult, Josef D.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Muradrasoli, Shaman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Virology.
    Söderström, Hanna
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Gavier-Widén, Dolores
    Pathobiology and virus shedding of low-pathogenic avian influenza virus (A/H1N1) infection in mallards exposed to oseltamivir2013In: Journal of Wildlife Diseases, ISSN 0090-3558, E-ISSN 1943-3700, Vol. 49, no 1, p. 103-113Article in journal (Refereed)
    Abstract [en]

    Low-pathogenic avian influenza (LPAI) viruses in wild birds are important as they can constitute the basis for the development of high-pathogenic avian influenza (HPAI) viruses or form part of human-adapted strains with pandemic potential. However, the LPAI infection as such is not very well characterized in the natural reservoir, dabbling ducks, and results are in part contradictory. The effects on the infection by artificial versus natural infection, exposure to antiviral drugs or development of resistance have not been studied. Therefore, we used q-PCR, histopathology and immunohistochemistry (IHC) to study mallards infected with an influenza A/H1N1 virus isolated from a wild mallard in Sweden. The mallards were either inoculated intra-esophageally or infected by virus shed by other ducks in the experiment. The birds were subjected to low levels of the active metabolite of oseltamivir (Tamiflu®) and the resistance mutation H274Y developed during the course of the experiment.

    All mallards but one had a strictly intestinal localization of the LPAI infection. The exception was a bird euthanized one day post artificial inoculation whose infection was located solely in the lung, possibly due to intra-tracheal deposition of virus. The intestinal infection was characterized by degenerating cells in the lamina propria, infiltrating heterophils and lymphocytes as well as positivity of IHC and q-PCR on samples from feces and intestinal contents. Histopathological changes, IHC positivity and viral shedding all indicate that the infection peaked early, around two days post infection. Furthermore, the infection had a longitudinal progression in the intestine with more activity in the proximal parts early in the infection and vice versa as observed both by IHC and by q-PCR. There was no obvious difference in the course of the infection in artificial versus natural infection, when the level of OC was increased from 80 ng/L to 80 µg/L or when the resistance mutation H274Y developed.

  • 32.
    Börjesson, Andreas
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Investigations of Strategies to Counteract Proinflammatory Cytokines in Experimental Type 1 Diabetes2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Type 1 diabetes (T1D) is a chronic autoimmune disease targeted against the pancreatic β-cells. Proinflammatory cytokines are considered to play a major role in the destruction of the insulin-producing β-cells. This thesis studied strategies to counteract proinflammatory cytokines in experimental T1D. Both animal models for T1D as well as β-cell preparations exposed in vitro to putative noxious conditions were examined.

    In the first study we observed that cytokine treatment of mouse pancreatic islets lacking inducible nitric oxide synthase (iNOS) induced a prolongation of the early stimulatory phase of glucose stimulated insulin secretion. Various experiments led to the conclusion that this prolonged stimulatory effect may involve the DAG/PLD/PKC pathway.

    Next, we transplanted mouse islets deficient in iNOS to spontaneously diabetic NOD mice. We observed a normalization of hyperglycemia but not a delayed allograft rejection compared to transplanted wild type islets. Thus, absence of iNOS in the graft was not sufficient to prolong allograft survival.

    In paper III we found that sustained glucose stimulation of rat pancreatic islets was coupled to a decreased conversion of proinsulin to insulin. Islet treatment with IL-1β was also coupled to a decreased proinsulin conversion. Islet proconvertase activity may be a target in islet damage.

    In paper IV prolactin (PRL) was administered to mice in the multiple low dose streptozotocin model and we observed that PRL enhanced a Th2 response. This may contribute to the protective action by PRL in this model of autoimmune T1D.

    Finally, by examining β-cells overexpressing Suppressor of cytokine signalling 3 (SOCS-3) it was found that this could inhibit IL-1β induced signalling through the NF-κB and MAPK pathways. SOCS-3 overexpression also inhibited apoptosis induced by cytokines in primary β-cells. Lastly, we demonstrated that SOCS-3 transgenic islets were protected in an allogeneic transplantation model.

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    5. Suppressor of cytokine signalling-3 expression inhibits cytokine-mediated destruction of primary mouse and rat pancreatic islets and delays allograft rejection
    Open this publication in new window or tab >>Suppressor of cytokine signalling-3 expression inhibits cytokine-mediated destruction of primary mouse and rat pancreatic islets and delays allograft rejection
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    2008 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 51, no 10, p. 1873-1882Article in journal (Refereed) Published
    Abstract [en]

    Aims/hypothesis The pro-inflammatory cytokines IL-1 and IFN gamma are critical molecules in immune-mediated beta cell destruction leading to type 1 diabetes mellitus. Suppressor of cytokine signalling (SOCS)-3 inhibits the cytokine-mediated destruction of insulinoma-1 cells. Here we investigate the effect of SOCS3 in primary rodent beta cells and diabetic animal models. Methods Using mice with beta cell-specific Socs3 expression and a Socs3-encoding adenovirus construct, we characterised the protective effect of SOCS3 in mouse and rat islets subjected to cytokine stimulation. In transplantation studies of NOD mice and alloxan-treated mice the survival of Socs3 transgenic islets was investigated. Results Socs3 transgenic islets showed significant resistance to cytokine-induced apoptosis and impaired insulin release. Neither glucose-stimulated insulin release, insulin content or glucose oxidation were affected by SOCS3. Rat islet cultures transduced with Socs3-adenovirus displayed reduced cytokine-induced nitric oxide and apoptosis associated with inhibition of the IL-1-induced nuclear factor-kappa B and mitogen-activated protein kinase (MAPK) pathways. Transplanted Socs3 transgenic islets were not protected in diabetic NOD mice, but showed a prolonged graft survival when transplanted into diabetic allogenic BALB/c mice. Conclusions/interpretation SOCS3 inhibits IL-1-induced signalling through the nuclear factor-kappa B and MAPK pathways and apoptosis induced by cytokines in primary beta cells. Moreover, Socs3 transgenic islets are protected in an allogenic transplantation model. SOCS3 may represent a target for pharmacological or genetic engineering in islet transplantation for treatment of type 1 diabetes mellitus.

    Keywords
    apoptosis, autoimmunity, diabetes, IFN gamma, IL-1, inflammation; signalling, SOCS, suppressor of cytokine signalling
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-97610 (URN)10.1007/s00125-008-1090-0 (DOI)000258958400017 ()
    Available from: 2008-10-10 Created: 2008-10-10 Last updated: 2017-12-14Bibliographically approved
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  • 33.
    Cancar, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Serbia’s way to accession with the European Union and the European Medicines Agency: a comparison of regulatory activity in the field of pharmaceuticals in Serbia and Sweden2014Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Introduction:  On 24 January, 2014 Serbia was approved opening negotiations on accession into the European Union (EU). The European Commission is responsible for launching assistance programmes to support preparatory procedures for the candidate countries; one of those programmes is the Instrument for pre-accession Assistance (IPA) programme. The aim of the IPA programme is to build contacts and relationships between the European Medicines Agency (EMA) and Serbia’s Medicines and Medical Devices Agency (ALIMS), for future collaboration in the EMA activities and its relationship with the Member States of EU.

    Aim: The aim is to describe regulatory activities of ALIMS on human medicines, since the country is not yet a Member State of the EU and to put this into relation with Sweden, a Member State of the EU, which may promote new activities to be introduced in ALIMS’s regulatory work.

    Method: This is a descriptive comparative literature report of institutions working with pharmaceutical regulatory activities.

    Findings: The Serbian Law on Medicines and Medical Devices, established in 2010 suggests that the activities of ALIMS are generally in accordance with the EU standards and guidelines. Since Serbia is not yet a member of the EU, the pharmaceutical regulatory system for granting centralized authorization or marketing authorization based on mutual recognition is not yet possible. However, the Law of Medicines and Medical Devices states that exceptions can be made and ALIMS can issue authorization of centrally authorized medicines if it has reasons related to protection of public health.

    Conclusions: ALIMS has a well developed regulatory authority thanks to international collaboration and a desire to become an EU Member State. 

  • 34.
    Carlsson, Hans-Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Royo, Felix
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Faheem, Shaik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Tufvesson, Måns
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Hau, Jann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Separation of pair housed roosters is associated with transient increased fecal corticosterone excretion2009In: Research in Veterinary Science, ISSN 0034-5288, E-ISSN 1532-2661, Vol. 86, no 1, p. 183-187Article in journal (Refereed)
    Abstract [en]

    Immunoreactive corticosterone and corticosterone metabolites (ICCM) were quantified in excreta of permanently single housed (n=10) and permanently pair housed (n=20) roosters. The pair housed roosters were separated and single housed, and ICCM were quantified in the droppings before and during 15 days after separation. There was no statistically significant difference in ICCM excretion in the droppings between the permanently single or pair housed roosters. After separation, however, the previously pair housed roosters showed a significantly transient elevated excretion of ICCM in droppings the second day after separation indicating that the separation and relocation is associated with an activation of the hypothalamic-pituitary-adrenal axis. The excretion of ICCM in droppings was not correlated to the concentration of ICCM in droppings. It is thus important that excretion of ICCM be expressed as amount excreted per time unit since the total excretion is dependant on both concentration of ICCM and amount of droppings produced.

  • 35.
    Chea, Rortana
    et al.
    Natl Anim Hlth & Prod Res Inst, Gen Directorate Anim Hlth & Prod, Phnom Penh, Cambodia.;Int Livestock Res Inst, Nairobi, Kenya.;Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, Uppsala, Sweden..
    Nguyen-Viet, Hung
    Int Livestock Res Inst, Nairobi, Kenya..
    Tum, Sothyra
    Natl Anim Hlth & Prod Res Inst, Gen Directorate Anim Hlth & Prod, Phnom Penh, Cambodia..
    Unger, Fred
    Int Livestock Res Inst, Nairobi, Kenya..
    Lindahl, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, SWEDESD - Sustainability Learning and Research Centre. Int Livestock Res Inst, Nairobi, Kenya.;Swedish Univ Agr Sci, Dept Clin Sci, Uppsala, Sweden.;Uppsala Univ, Dept Med Biochem & Microbiol, Uppsala, Sweden..
    Grace, Delia
    Int Livestock Res Inst, Nairobi, Kenya.;Univ Greenwich, Nat Resources Inst, Greenwich, Kent, England..
    Ty, Chhay
    Livestock Dev Community Livelihood Org, Phnom Penh, Cambodia..
    Koam, Sok
    Natl Anim Hlth & Prod Res Inst, Gen Directorate Anim Hlth & Prod, Phnom Penh, Cambodia..
    Sina, Vor
    Livestock Dev Community Livelihood Org, Phnom Penh, Cambodia..
    Sokchea, Huy
    Livestock Dev Community Livelihood Org, Phnom Penh, Cambodia..
    Pov, Son
    Livestock Dev Community Livelihood Org, Phnom Penh, Cambodia..
    Heng, Theng
    Natl Anim Hlth & Prod Res Inst, Gen Directorate Anim Hlth & Prod, Phnom Penh, Cambodia..
    Phirum, Or
    Natl Anim Hlth & Prod Res Inst, Gen Directorate Anim Hlth & Prod, Phnom Penh, Cambodia..
    Dang-Xuan, Sinh
    Int Livestock Res Inst, Nairobi, Kenya.;Hanoi Univ Publ Hlth, Ctr Publ Hlth & Ecosyst Res, Hanoi, Vietnam..
    Experimental cross-contamination of chicken salad with Salmonella enterica serovars Typhimurium and London during food preparation in Cambodian households2022In: PLOS ONE, E-ISSN 1932-6203, Vol. 17, no 8, article id e0270425Article in journal (Refereed)
    Abstract [en]

    Non-typhoidal Salmonellae are common foodborne pathogens that can cause gastroenteritis and other illnesses in people. This is the first study to assess the transfer of Salmonella enterica from raw chicken carcasses to ready-to-eat chicken salad in Cambodia. Twelve focus group discussions in four Cambodian provinces collected information on typical household ways of preparing salad. The results informed four laboratory experiments that mimicked household practices, using chicken carcasses inoculated with Salmonella. We developed four scenarios encompassing the range of practices, varying by order of washing (chicken or vegetables first) and change of chopping utensils (same utensils or different). Even though raw carcasses were washed twice, Salmonella was isolated from 32 out of 36 chicken samples (88.9%, 95% CI: 73.0-96.4) and two out of 18 vegetable samples (11.1%, 95% CI: 1.9-36.1). Salmonella was detected on cutting boards (66.7%), knives (50.0%) and hands (22.2%) after one wash; cross-contamination was significantly higher on cutting boards than on knives or hands (p-value < 0.05). The ready-to-eat chicken salad was contaminated in scenario 1 (wash vegetables first, use same utensils), 2 (wash vegetables first, use different utensils) and 3 (wash chicken first, use same utensils) but not 4 (wash chicken first, use different utensils) (77.8%, 11.1%, 22.2% and 0%, respectively). There was significantly higher Salmonella cross-contamination in scenario 1 (wash vegetables first, use same utensils) than in the other three scenarios. These results show how different hygiene practices influence the risk of pathogens contaminating chicken salad. This information could decrease the risk of foodborne disease in Cambodia and provides inputs to a quantitative risk assessment model.

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  • 36.
    Chee-Sanford, Joanne C.
    et al.
    U.S. Department of Agriculture , Agricultural Research Service, Urbana, IL, USA.
    Krapac, Ivan J.
    Illinois State Geological Survey, Champaign, IL, USA.
    Yannarell, Anthony C.
    University of Illinois at Urbana-Champaign.
    Mackie, Roderick I.
    University of Illinois at Urbana-Champaign.
    29. Environmental Impacts of Antibiotic Use in the Animal Production Industry2012In: Ecology and Animal Health / [ed] Leif Norrgren and Jeffrey Levengood, Uppsala: Baltic University Press , 2012, 2, p. 228-239Chapter in book (Other (popular science, discussion, etc.))
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    ehsa 2-29
  • 37.
    Chenais, Erika
    et al.
    Natl Vet Inst, Uppsala, Sweden..
    Wennström, Patrick
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Peace and Conflict Research.
    Kartskhia, Natia
    Natl Food Agcy, Tbilisi, Georgia..
    Fischer, Klara
    Swedish Univ Agr Sci, Uppsala, Sweden..
    Risatti, Guillermo
    Univ Connecticut, Storrs, CT USA..
    Chaligava, Tengiz
    Natl Food Agcy, Tbilisi, Georgia..
    Enukidze, Tea
    State Lab Agr, Tbilisi, Georgia..
    Ståhl, Karl
    Natl Vet Inst, Uppsala, Sweden..
    Vepkhvadze, Nino G.
    State Lab Agr, Tbilisi, Georgia..
    Perceptions of pastoralist problems: A participatory study on animal management, disease spectrum and animal health priorities of small ruminant pastoralists in Georgia2021In: Preventive Veterinary Medicine, ISSN 0167-5877, E-ISSN 1873-1716, Vol. 193, article id 105412Article in journal (Refereed)
    Abstract [en]

    Small ruminants support the livelihoods of millions of poor pastoralist and sedentary households around the world. While pastoralists are generally not amongst the poorest in terms of assets, they are frequently marginalised in terms of their access to political power, health and education. This study was undertaken among pastoralist households keeping small ruminants in four regions of the country of Georgia. Small ruminants are an important cultural, social and economic asset in Georgia and are mainly managed in a transhumant pastoralist system. Georgia suffered its first, and so far only outbreak of peste des petits ruminants (PPR) in 2016. This qualitative interview study was designed to acquire contextual understanding of local small ruminant husbandry and the livelihood situations of the participating pastoralists, and to detect historical, unreported PPR outbreaks. Focus group discussions comprising participatory epidemiology tools and other forms of interviews were used to explore small ruminant management, disease spectrum and management, and animal health priorities. The participants had experienced a wide variety of animal health constraints, with intestinal worms, braxy, piroplasmosis, pasture-related problems, predators and lameness emerging as priorities. No historic, unreported PPR outbreak was detected in this study, and PPR was not a priority for participants. Instead, the day-to-day reality of animal health for the pastoralists was characterised by co-infections of mainly endemic pathogens, and problems related to other challenges such as access to land, feed and genetic resources. The rationale behind the participants' prioritisation of animal health problems was supported by the need to pay extra attention to animals in order to avoid risk factors, keep animals healthy and minimise the negative impact of diseases or management problems; the various epidemiological and clinical parameters of the prioritised diseases; the economic impact of the specific problems and the zoonotic potential of diseases and predation. Even within regions, and within seemingly socially and culturally homogenous groups, there were important local differences in the problems faced by pastoralists that affect their livestock management. This study underlines the importance of a contextualised understanding of the local disease panorama and complexities in the livelihood situations of rural people when designing actions to improve animal health in general or, more specifically, passive surveillance as well as prevention or control measures. Finally, it is concluded that to achieve such an understanding, there is a need for participatory, scoping-style studies that specifically acknowledge diversity and power relations.

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  • 38.
    Cooray, Ruby
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Waller, Karin Persson
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Haptoglobin comprises about 10% of granule protein extracted from bovine granulocytes isolated from healthy cattle2007In: Veterinary Immunology and Immunopathology, ISSN 0165-2427, E-ISSN 1873-2534, Vol. 119, no 3-4, p. 310-315Article in journal (Refereed)
    Abstract [en]

    Haptoglobin (Hp) is a plasma protein with haemoglobin binding capacity important in maintaining the iron homeostasis and in disease processes influenced by iron metabolism. In cattle Hp is one of the major acute phase proteins, and increases rapidly during infectious disease. At acute clinical mastitis in dairy cows the Hp concentration increases markedly both in blood and milk. Hepatocytes are considered to be the main origin of Hp, but expression of Hp mRNA has also been found in the mammary gland and leukocytes in healthy cattle. In the present study we show that bovine granulocytes, isolated from peripheral blood of healthy cattle, contain abundant amounts of Hp within the granules. As shown by two-dimensional gel electrophoresis (2-DE) in combination with matrix assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-ToF-MS) bovine granulocyte Hp consists of two sets of peptides ca. 20 kDa (a-chains) and ca. 40 kDa ((3-chains) with multiple iso-forms.

  • 39.
    Cristea, Alexander
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Effects of Ageing and Physical Activity on Regulation of Muscle Contraction2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aims of this study were to investigate the mechanisms underlying (1) the ageing-related motor handicap at the whole muscle, cellular, contractile protein and myonuclear levels; and (2) ageing-related differences in muscle adaptability.

    In vivo muscles function was studied in the knee extensors. Decreases were observed in isokinetic and isometric torque outputs in old age in the sedentary men and women and elite master sprinters. A 20-week long specific sprint and resistance training successfully improved the maximal isometric force and rate of force development in a subgroup of master sprinters.

    In vitro measurements were performed in muscle biopsies from the vastus lateralis muscle. Immunocytochemical and contractile measurements in single membrane permeabilized muscle fibres demonstrated ageing- and gender-related changes at the myofibrillar level. In sedentary subjects, data showed a preferential decrease in the size of muscle fibres expressing type IIa MyHC in men, lower force generating capacity in muscle fibres expressing the type I MyHC isoform in both men and women and lower maximum velocity of unloaded shortening (V0) in fibres expressing types I and IIa MyHC isoforms in both men and women. The master sprinters also experienced the typical ageing-related reduction in the size of fast-twitch fibres, a shift toward a slower MyHC isoform profile and a lower V0 of type I MyHC fibres, which played a role in the decline in explosive force production capacity. The fast-twitch fibre area increased after the resistance training period. A model combining single muscle fibre confocal microscopy with a novel algorithm for 3D imaging of myonuclei in single muscle fibre segments was introduced to study the spatial organisation of myonuclei and the size of individual myonuclear domains (MNDs). Significant changes in the MND size variability and myonuclear organization were observed in old age, irrespective gender and fibre type. Those changes may influence the local quantity of specific proteins per muscle fibre volume by decreased and/or local cooperativity of myonuclei in a gender and muscle fibre specific manner.

    In conclusion, the ageing-related impairments in in vivo muscle function were related to significant changes in morphology, contractile protein expression and regulation at the muscle fibre level. It is suggested that the altered myonuclear organisation observed in old age impacts on muscle fibre protein synthesis and degradation with consequences for the ageing-related changes in skeletal muscle structure and function. However, the improved muscle function in response to a 20-week intense physical training regime in highly motivated physically active old subjects demonstrates that all ageing-related in muscle function are not immutable.

    List of papers
    1. Effects of ageing and gender on contractile properties in human skeletal muscle and single fibres
    Open this publication in new window or tab >>Effects of ageing and gender on contractile properties in human skeletal muscle and single fibres
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    2007 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 190, no 3, p. 229-241Article in journal (Refereed) Published
    Abstract [en]

    Aim: The objective of this study is to improve our understanding of the mechanisms underlying the ageing- and gender-related muscle weakness.

    Methods: Ageing- and gender-related differences in regulation of muscle contraction have been studied in knee-extensor muscles at the whole muscle and single muscle fibre levels in young and old sedentary men and women. In vivo knee-extensor muscle function was measured at slow (30° s−1) and faster (180 ° s−1) speeds of movement. Maximum velocity of unloaded shortening (V0) and maximum force normalized to cross-sectional area (CSA) [specific tension (ST)] were measured in single 'skinned' skeletal muscle fibre segments.

    Results: Significant ageing- and gender-related differences were observed in muscle torque. A 33–55% ageing-related decline (P < 0.001) in maximum torque was observed irrespective of gender. At the single muscle fibre level, the ageing-related decline in knee-extensor muscle function was accompanied by a 20–28% decline in ST in muscle fibres expressing the type I MyHC isoform in both men and women, and a 29% decline in type IIa muscle fibre CSA, but the decreased fast-twitch fibre size was restricted to the men. Furthermore, in both men and women, V0 decreased in muscle cells expressing the type I and IIa MyHC isoforms.

    Conclusion: The present results provide evidence of specific ageing- and gender-related differences in regulation of muscle contraction at the cellular level. It is suggested that these cellular changes have a significant impact on muscle function and the ageing-related motor handicap.

    Keywords
    maximum velocity of unloaded shortening, muscle mass, skinned fibres, slack test, specific tension, torque-velocity
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-97417 (URN)10.1111/j.1748-1716.2007.01699.x (DOI)000247318600006 ()
    Available from: 2008-08-29 Created: 2008-08-29 Last updated: 2017-12-14Bibliographically approved
    2. Aging, muscle fiber type, and contractile function in sprint-trained athletes
    Open this publication in new window or tab >>Aging, muscle fiber type, and contractile function in sprint-trained athletes
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    2006 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 101, no 3, p. 906-917Article in journal (Refereed) Published
    Abstract [en]

    Biopsy samples were taken from the vastus lateralis of 18- to 84-yr-old male sprinters (n = 91). Fiber-type distribution, cross-sectional area, and myosin heavy chain (MHC) isoform content were identified using ATPase histochemistry and SDS-PAGE. Specific tension and maximum shortening velocity (V-o) were determined in 144 single skinned fibers from younger (18-33 yr, n = 8) and older (53-77 yr, n = 9) runners. Force-time characteristics of the knee extensors were determined by using isometric contraction. The cross-sectional area of type I fibers was unchanged with age, whereas that of type II fibers was reduced (P < 0.001). With age there was an increased MHC I (P < 0.01) and reduced MHC IIx isoform content (P < 0.05) but no differences in MHC IIa. Specific tension of type I and IIa MHC fibers did not differ between younger and older subjects. V-o of fibers expressing type I MHC was lower (P < 0.05) in older than in younger subjects, but there was no difference in V-o of type IIa MHC fibers. An aging-related decline of maximal isometric force (P < 0.001) and normalized rate of force development (P < 0.05) of knee extensors was observed. Normalized rate of force development was positively associated with MHC II (P < 0.05). The sprint-trained athletes experienced the typical aging-related reduction in the size of fast fibers, a shift toward a slower MHC isoform profile, and a lower V-o of type I MHC fibers, which played a role in the decline in explosive force production. However, the muscle characteristics were preserved at a high level in the oldest runners, underlining the favorable impact of sprint exercise on aging muscle.

    Keywords
    exercise, myosin heavy chain, single-fiber contractile properties, muscle strength
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-97418 (URN)10.1152/japplphysiol.00299.2006 (DOI)000240124100031 ()16690791 (PubMedID)
    Available from: 2008-08-29 Created: 2008-08-29 Last updated: 2017-12-14Bibliographically approved
    3. Effects of combined strength and sprint training on regulation of muscle contraction at the whole-muscle and single fibre levels in elite master sprinters
    Open this publication in new window or tab >>Effects of combined strength and sprint training on regulation of muscle contraction at the whole-muscle and single fibre levels in elite master sprinters
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    2008 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 193, no 3, p. 275-289Article in journal (Refereed) Published
    Abstract [en]

    AIM: This study aims at examining the effects of progressive strength and sprint training on regulation of muscle contraction at the whole-muscle and single-fibre levels in older sprint-trained athletes. METHODS: Eleven men (52-78 years) were randomized to a training (EX, n = 7) or control (CTRL, n = 4) group. EX participated in a 20-week programme that combined sprint training with heavy and explosive strength exercises, while CTRL maintained their usual run-based training schedules. RESULTS: EX improved maximal isometric and dynamic leg strength, explosive jump performance and force production in running. Specific tension and maximum shortening velocity of single fibres from the vastus lateralis were not altered in EX or CTRL. Fibre type and myosin heavy chain isoform distributions remained unchanged in the two groups. There was a general increase in fibre areas in EX, but this was significant only in IIa fibres. The 10% increase in squat jump in EX was accompanied by a 9% increase in the integrated EMG (iEMG) of the leg extensors but the 21-40% increases in isometric and dynamic strength were not paralleled by changes in iEMG. CONCLUSION: Adding strength training stimulus to the training programme improved maximal, explosive and sport-specific force production in elite master sprinters. These improvements were primarily related to hypertrophic muscular adaptations.

    Keywords
    ageing, fibre types, hypertrophy, master athletes, neural activity, skinned fibres
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-97419 (URN)10.1111/j.1748-1716.2008.01843.x (DOI)000256442100010 ()18284658 (PubMedID)
    Available from: 2008-08-29 Created: 2008-08-29 Last updated: 2022-01-28Bibliographically approved
    4. Effects of ageing and gender on the spatial organisation of nuclei in single human skeletal muscle cells
    Open this publication in new window or tab >>Effects of ageing and gender on the spatial organisation of nuclei in single human skeletal muscle cells
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    2009 (English)In: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 19, no 8, p. 605-606Article in journal (Refereed) Published
    National Category
    Medical Image Processing
    Research subject
    Computerized Image Processing
    Identifiers
    urn:nbn:se:uu:diva-97420 (URN)10.1016/j.nmd.2009.06.196 (DOI)
    Available from: 2008-08-29 Created: 2008-08-29 Last updated: 2018-12-18
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  • 40.
    Dahlberg, Josef
    et al.
    Swedish Univ Agr Sci, Dept Anim Nutr & Management, Uppsala, Sweden.;Swedish Univ Agr Sci, Dept Clin Sci, Uppsala, Sweden..
    Johnzon, Carl-Fredrik
    Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden..
    Sun, Li
    Swedish Univ Agr Sci, Dept Mol Sci, Uppsala, Sweden..
    Pejler, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden..
    Östensson, Karin
    Swedish Univ Agr Sci, Dept Clin Sci, Uppsala, Sweden..
    Dicksved, Johan
    Swedish Univ Agr Sci, Dept Anim Nutr & Management, Uppsala, Sweden..
    Absence of changes in the milk microbiota during Escherichia coli endotoxin induced experimental bovine mastitis2023In: Veterinary research (Print), ISSN 0928-4249, E-ISSN 1297-9716, Vol. 54, article id 46Article in journal (Refereed)
    Abstract [en]

    Changes in the milk microbiota during the course of mastitis are due to the nature of a sporadic occurring disease difficult to study. In this study we experimentally induced mastitis by infusion of Escherichia coli endotoxins in one udder quarter each of nine healthy lactating dairy cows and assessed the bacteriological dynamics and the milk microbiota at four time points before and eight time points after infusion. As control, saline was infused in one udder quarter each of additionally nine healthy cows that followed the same sampling protocol. The milk microbiota was assessed by sequencing of the 16 S rRNA gene and a range of positive and negative controls were included for methodological evaluation. Two different data filtration models were used to identify and cure data from contaminating taxa. Endotoxin infused quarters responded with transient clinical signs of inflammation and increased SCC while no response was observed in the control cows. In the milk microbiota data no response to inflammation was identified. The data analysis of the milk microbiota was largely hampered by laboratory and reagent contamination. Application of the filtration models caused a marked reduction in data but did not reveal any associations with the inflammatory reaction. Our results indicate that the microbiota in milk from healthy cows is unaffected by inflammation.

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  • 41.
    Dahlgren, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Roos, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Johansson, Pernilla
    AstraZeneca R&D, SE-43150 Gothenburg, Sweden..
    Lundqvist, Anders
    AstraZeneca R&D, SE-43150 Gothenburg, Sweden..
    Tannergren, Christer
    AstraZeneca R&D, SE-43150 Gothenburg, Sweden..
    Abraharnsson, Bertil
    AstraZeneca R&D, SE-43150 Gothenburg, Sweden..
    Sjögren, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Lennernäs, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Regional Intestinal Permeability in Dogs: Biopharmaceutical Aspects for Development of Oral Modified-Release Dosage Forms2016In: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392, Vol. 13, no 9, p. 3022-3033Article in journal (Refereed)
    Abstract [en]

    The development of oral modified-release (MR) dosage forms requires an active pharmaceutical ingredient (API) with a sufficiently high absorption rate in both the small and large intestine. Dogs are commonly used in preclinical evaluation of regional intestinal absorption and in the development of novel MR dosage forms. This study determined regional intestinal effective permeability (P-eff) in dogs with the aim to improve regional Peff prediction in humans. Four model drugs, atenolol, enalaprilat, metoprolol, and ketoprofen, were intravenously and regionally dosed twice as a solution into the proximal small intestine (P-SI) and large intestine (LI) of three dogs with intestinal stomas. Based on plasma data from two separate study occasions for each dog, regional Peff values were calculated using a validated intestinal deconvolution method. The determined mean P-eff values were 0.62, 0.14, 1.06, and 3.66 X 10(-4) cm/s in the P-SI, and 0.13, 0.02, 1.03, and 2.20 X 10(-4) cm/s in the LI, for atenolol, enalaprilat, metoprolol, and ketoprofen, respectively. The determined P-SI Peff values in dog were highly correlated (R-2 = 0.98) to the historically directly determined human jejunal P-eff after a single-pass perfusion. The determined dog P-SI P-eff values were also successfully implemented in GI-Sim to predict the risk for overestimation of LI absorption of low permeability drugs. We conclude that the dog intestinal stoma model is a useful preclinical tool for determination of regional intestinal permeability. Still, further studies are recommended to evaluate additional APIs, sources of variability, and formulation types, for more accurate determination of the dog model in the drug development process.

  • 42. Deka, Ram Pratim
    et al.
    Magnusson, Ulf
    Grace, Delia
    Lindahl, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Bovine brucellosis: prevalence, risk factors, economic cost and control options with particular reference to India- a review2018In: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Vol. 8, no 1Article in journal (Refereed)
    Abstract [en]

    ABSTRACTBackground: Brucellosis is an economically important zoonotic disease with worldwide distribution, with low-income countries being more affected. The disease is endemic in India, a country that house the world’s largest cattle and buffalo population and produce the most milk in the world.Results: Prevalence of the disease in the country is reported as low as 1% to as high as 60% by different researchers but many of the published studies that reported higher prevalence were conducted in non-randomised samples. Based on this review, overall prevalence in the country is likely 12% or less. About 20 different risk factors are reported that contribute/predispose to occurrence of bovine brucellosis. The risk factors could be classified in four groups: host factors, farmer’s factors, managemental factors, and agro-ecological factors. Various studies reported high economic burden of the diseases in dairy animals but there is dearth of comprehensive and rigorous economic studies.Conclusions: In the absence...

  • 43. Deka, Ram Pratim
    et al.
    Magnusson, Ulf
    Grace, Delia
    Randolph, Thomas F.
    Shome, Rajeswari
    Lindahl, Johanna F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Swedish University of Agricultural Sciences; International Livestock Research Institute (ILRI), Nairobi 00100, Kenya.
    Estimates of the Economic Cost Caused by Five Major Reproductive Problems in Dairy Animals in Assam and Bihar, India2021In: Animals, E-ISSN 2076-2615, Vol. 11, no 11, article id 3116Article in journal (Refereed)
    Abstract [en]

    Reproductive problems in dairy animals reduce fertility, prevent conception, create problems in the delivery of healthy calves, lead to postpartum complications, increase inter-calving periods, reduce milk yield, and lower overall lifetime productivity. This study aimed at understanding the incidence of reproductive problems and the cost caused by these. The study covered 954 dairy animals in Bihar and 1348 dairy animals in Assam that were selected using a multi-stage random sampling method. The costs were calculated as the sum of income losses and expenditures incurred. The major cost incurred resulted from extended calving intervals (46.1% of the total cost), followed by loss through salvage selling (38.1%), expenditure for treatment of repeat breeders (5.9%), loss of milk production (5.3%) and expenditure for extra inseminations (2.0%). About one fifth of the selected reproductive problems were left untreated. The estimated cost of reproductive problems was Indian Rupees (INR) 2424.9 (USD 36.1) per dairy animal per year (of the total dairy animal population) which represented approximately 4.1% of the mean value loss of dairy animals (INR 58,966/USD 877) per year. Reproductive problems were significantly (p < 0.001) higher among improved (exotic breed or cross-bred) dairy animals than indigenous (native breed or nondescript indigenous) dairy animals. The study suggests that with the increase of improved dairy animal population, the loss may further increase. The study concludes that any economic estimation of reproduction problems based on aetiology without confirmatory diagnoses could be highly misleading because of the complex nature of the problems.

    Simple Summary

    Large ruminant dairy animals (i.e., cattle and buffalo) suffer from several reproductive problems (such as abortion) that reduce ther ability to produce milk and offspring, resulting in huge economic costs to farmers; however, there are few studies in India that estimate such costs. Therefore, an attempt was made to assess the economic cost of five major reproductive problems in two of the poorest Indian states—Assam and Bihar. We estimated the cost by interviewing 534 randomly selected dairy farming households in both the states. Based on this, we found that 32.9% of dairy animals (milking, not-milking and heifer) in Assam and 43.1% dairy animals in Bihar suffered from one or more reproductive problems. The most common reproductive problem was failing to conceive after breeding (23.2% of surveyed dairy animals) followed by retained placenta (6.1%), abortion (4.9%), purulent vaginal discharge (2.9%) and stillbirths (1.0%). It was estimated that the selected reproductive problems caused an annual economic cost of Indian Rupees (INR), 3963.1 million (USD 59.0 million) in Assam, and INR 30,500.0 million (USD 453.9 million) in Bihar. The study concludes that adequate awareness, capacity building, adoption of good reproductive health management practices, proper farm record keeping and improved access to quality veterinary services are essential to address reproductive problems and reduce the cost caused by these reproductive problems.

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  • 44.
    Deka, Ram Pratim
    et al.
    Swedish Univ Agr Sci SLU, Dept Clin Sci, S-75007 Uppsala, Sweden; Int Livestock Res Inst ILRI, Dept Anim & Human Hlth, Nairobi 00100, Kenya.
    Shome, Rajeswari
    Natl Inst Vet Epidemiol & Dis Informat NIVEDI, Bangalore 560064, Karnataka, India.
    Dohoo, Ian
    Univ Prince Edward Isl, Epidemiol, Charlottetown, PE C1A 4P3, Canada.
    Magnusson, Ulf
    Swedish Univ Agr Sci SLU, Dept Clin Sci, S-75007 Uppsala, Sweden.
    Randolph, Delia Grace
    Int Livestock Res Inst ILRI, Dept Anim & Human Hlth, Nairobi 00100, Kenya; Univ Greenwich, Nat Resources Inst, Food Safety Syst, Chatham ME4 4TB, Kent, England.
    Lindahl, Johanna F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Swedish Univ Agr Sci SLU, Dept Clin Sci, S-75007 Uppsala, Sweden; Int Livestock Res Inst ILRI, Dept Anim & Human Hlth, Nairobi 00100, Kenya.
    Seroprevalence and Risk Factors of Brucella Infection in Dairy Animals in Urban and Rural Areas of Bihar and Assam, India2021In: Microorganisms, E-ISSN 2076-2607, Vol. 9, no 4, article id 783Article in journal (Refereed)
    Abstract [en]

    This study assessed seropositivity of Brucella infection in dairy animals and risk factors associated with it. The cross-sectional study used multi-stage, random sampling in the states of Bihar and Assam in India. In total, 740 dairy animals belonging to 534 households of 52 villages were covered under this study. Serological testing was conducted by indirect enzyme-linked immunosorbent assay (iELISA). Animal-level Brucella seropositivity was found to be 15.9% in Assam and 0.3% in Bihar. Seropositivity in urban areas (18.7%) of Assam was found to be higher than in rural areas (12.4%). Bihar was excluded from the risk factor analysis, as only one Brucella seropositive sample was detected in the state. A total of 30 variables were studied for assessing risk factors, of which 15 were selected for multivariable regression analyses following a systematic process. Finally, only three risk factors were identified as statistically significant. It was found that animals belonging to districts having smaller-sized herds were less likely (p < 0.001) to be Brucella seropositive than animals belonging to districts having larger-sized herds. Furthermore, the chance of being Brucella seropositive increased (p = 0.007) with the increase in age of dairy animals, but decreased (p = 0.072) with the adoption of artificial insemination (AI) for breeding. We speculated that the identified risk factors in Assam likely explained the reason behind lower Brucella seropositivity in Bihar, and therefore any future brucellosis control program should focus on addressing these risk factors.

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  • 45.
    Deksne, Gunita
    et al.
    Inst Food safety Anim Hlth & Environm BIOR, Lejupes Str 3, Riga LV-1076, Latvia.;Univ Latvia, Fac Biol, Jelgavas Str 1, Riga LV-1004, Latvia..
    Mateusa, Maira
    Inst Food safety Anim Hlth & Environm BIOR, Lejupes Str 3, Riga LV-1076, Latvia.;Univ Life Sci & Technol, Fac Vet Med, K Helmana Str 8, Jelgava LV-3004, Latvia..
    Cvetkova, Svetlana
    Inst Food safety Anim Hlth & Environm BIOR, Lejupes Str 3, Riga LV-1076, Latvia..
    Derbakova, Alina
    Univ Life Sci & Technol, Fac Vet Med, K Helmana Str 8, Jelgava LV-3004, Latvia..
    Keida, Dace
    Faculty of Veterinary Medicine, University of Life sciences and Technologies, K. Helmaņa Str. 8, Jelgava LV-3004, Latvia.
    Troell, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Natl Vet Inst, SE-75189 Uppsala, Sweden.
    Schares, Gereon
    Friedrich Loeffler Inst, Fed Res Inst Anim Hlth, Sudufer 10, D-17493 Greifswald, Germany..
    Prevalence, risk factor and diversity of Cryptosporidium in cattle in Latvia2022In: Veterinary Parasitology: Regional Studies and Reports, E-ISSN 2405-9390, Vol. 28, article id 100677Article in journal (Refereed)
    Abstract [en]

    The epidemiology of Cryptosporidium spp. in Latvia was investigated by testing fecal samples from 926 animals aged from one day to 24 years for the presence of Cryptosporidium spp. oocysts. The samples were collected from 87 cattle farms and from four slaughterhouses, and analyzed by conventional and fluorescent microscopy, fol-lowed by Cryptosporidium species and C. parvum subtype differentiation. Moreover, using a questionnaire, we surveyed factors that could be relevant as risk factors of Cryptosporidium spp. infection on the farms. Crypto-sporidium spp. were shed by 33.8% of the investigated cattle and at least one shedding animal was found on 77.8% of the farms. In the present study, all four Cryptosporidium species reported to commonly infect cattle and two additional Cryptosporidium species (C. scrofarum and C. ubiquitum) were identified. In addition, mix in-fections of C. parvum/C. bovis, C. bovis/C. ryanae, C. parvum/C. ryanae, C. parvum/C. andersoni and C. bovis/ C. andersoni were observed. C. parvum and C. bovis was mostly prevalent in young animals (0-3 months old) and in addition, diarrhea associated with C. parvum infection was observed only in very young animals. Cryptosporidium andersoni and C. ryanae in age group 0-3 months was observed in low prevalence, while a higher proportion of animals with diarrhea associated with C. andersoni infection was observed in very young animals and with C. ryanae in animals age group 4-24 months. Eight previously described C. parvum subtypes were observed. The majority of the subtypes were in the IIa subtype family, while one subtype was identified from the IId subtype family. The most common subtype was IIaA15G2R1, which was found in 34.2% of the C. parvum successfully subtyped samples. The probability of Cryptosporidium spp. associated diarrhea in cattle decreased significantly with the age of the animals and a prolonged period during which calves were fed with milk.

  • 46.
    Dencker, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Hellmann, K.
    Klifovet AG, Geyerspergerstr 27, D-80689 Munich, Germany..
    Mochel, J.
    Leiden Acad Ctr Drug Res, Dept Pharmacol, NL-2300 Leiden, Netherlands..
    Senel, S.
    Hacettepe Univ, Fac Pharm, Dept Pharmaceut Technol, TR-06100 Ankara, Turkey..
    Tyden, E.
    Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, Div Parasitol, Box 7036, S-75007 Uppsala, Sweden..
    Vendrig, J. C.
    Univ Utrecht, Fac Vet Med, Inst Risk Assessment Sci Vet Pharmacol Pharmacoth, Yalelaan 104,Postbus 80152, NL-3584 CM Utrecht, Netherlands..
    Linden, H.
    EUFEPS, Veddesta Business Ctr, SE-17572 Jarfalla, Stockholm, Sweden..
    Schmerold, I.
    Univ Vet Med Vienna, A-1020 Vienna, Austria.;Obere Donaustr 21-3-4, A-1020 Vienna, Austria..
    Position Paper: EUFEPS Network on Veterinary Medicines Initiative: An interdisciplinary forum to support Veterinary Pharmacology and promote the development of new pharmaceuticals for Animal Health2016In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 91, p. I-VIIArticle in journal (Refereed)
    Abstract [en]

    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.

  • 47.
    Dey, Tushar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Department of Biosciences, International Livestock Research Institute, Nairobi 00100, Kenya;Zoonosis Science Center, Department of Medical Biochemistry and Microbiology, Uppsala University, 75123 Uppsala, Sweden;ICAR-National Institute of Veterinary Epidemiology and Disease Informatics, Bengaluru 560064, India.
    Sharma, Garima
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Lundkvist, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Grace, Delia
    Department of Biosciences, International Livestock Research Institute, Nairobi, Kenya .
    Pal Singh, Vijay
    Food Safety and Standards Authority of India, New Delhi, India .
    Shome, Rajeswari
    National Institute of Veterinary Epidemiology and Disease Informatics, Bengaluru, India .
    H. M, Yathish
    Department of Animal Genetics and Breeding, Veterinary College, KVAFSU, Hebbal, Bengaluru, India.
    Ahmed Hazarika, Razibuddin
    Department of Veterinary Public Health and Epidemiology, Assam Agricultural University, Guwahati, India .
    Shome, Bibek
    National Institute of Veterinary Epidemiology and Disease Informatics, Bengaluru, India .
    Ghatak, Sandeep
    Division of Animal and Fisheries Sciences, ICAR Research Complex for North-Eastern Hill Region, Meghalaya, India .
    Sawalgi, Veeresh
    National Institute of Veterinary Epidemiology and Disease Informatics, Bengaluru, India .
    Lindahl, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Department of Biosciences, International Livestock Research Institute, Nairobi, Kenya .
    Antibiotic Residues and Antimicrobial Resistant bacteria in the Poultry Value Chain of Two Indian StatesManuscript (preprint) (Other academic)
    Abstract [en]

    The poultry industry's rapid expansion has made it a significant global meat source, especially in India, which ranks as the eighth largest broiler meat producer. However, severe concerns have arisen over the increasing antibiotic resistance in low and middle-income countries, including India. This study systematically investigated the prevalence of Non-Typhoidal Salmonella (NTS) and Escherichia coli (E. coli) strains, along with their antimicrobial resistance (AMR) profiles, in poultry samples from Assam and Karnataka states in India. We found high prevalence of NTS (26%) and E. coli (53%) in various poultry samples, with substantial regional variations. Assam and Karnataka contribute differently to the overall NTS prevalence, with Karnataka bearing the highest burden (39% versus 14%). The presence of NTS and E. coli in treated water intended for watering poultry raises concerns about the effectiveness of water disinfection methods. Serovar analysis highlights the dominance of Typhimurium, Kentucky, Infantis and other serovars, some exhibiting multidrug resistance (MDR), including resistance to fluoroquinolones. The emergence of antibiotic-resistant strains, including carbapenem-resistant E. coli, presents a potential decline in treatment options. The study highlights the presence of MDR among NTS and stresses the importance of monitoring resistance profiles to devise effective antimicrobial strategies. The study underscores the necessity of collaborative efforts to combat AMR and ensure food safety, health, and wellbeing on a global scale.

  • 48. Drögemüller, Cord
    et al.
    Becker, Doreen
    Kessler, Barbara
    Kemter, Elisabeth
    Tetens, Jens
    Jurina, Konrad
    Jäderlund, Karin Hultin
    Flagstad, Annette
    Perloski, Michele
    Lindblad-Toh, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Matiasek, Kaspar
    A deletion in the N-myc downstream regulated gene 1 (NDRG1) gene in Greyhounds with polyneuropathy2010In: PloS one, ISSN 1932-6203, Vol. 5, no 6, p. e11258-Article in journal (Refereed)
    Abstract [en]

    The polyneuropathy of juvenile Greyhound show dogs shows clinical similarities to the genetically heterogeneous Charcot-Marie-Tooth (CMT) disease in humans. The pedigrees containing affected dogs suggest monogenic autosomal recessive inheritance and all affected dogs trace back to a single male. Here, we studied the neuropathology of this disease and identified a candidate causative mutation. Peripheral nerve biopsies from affected dogs were examined using semi-thin histology, nerve fibre teasing and electron microscopy. A severe chronic progressive mixed polyneuropathy was observed. Seven affected and 17 related control dogs were genotyped on the 50k canine SNP chip. This allowed us to localize the causative mutation to a 19.5 Mb interval on chromosome 13 by homozygosity mapping. The NDRG1 gene is located within this interval and NDRG1 mutations have been shown to cause hereditary motor and sensory neuropathy-Lom in humans (CMT4D). Therefore, we considered NDRG1 a positional and functional candidate gene and performed mutation analysis in affected and control Greyhounds. A 10 bp deletion in canine NDRG1 exon 15 (c.1080_1089delTCGCCTGGAC) was perfectly associated with the polyneuropathy phenotype of Greyhound show dogs. The deletion causes a frame shift (p.Arg361SerfsX60) which alters several amino acids before a stop codon is encountered. A reduced level of NDRG1 transcript could be detected by RT-PCR. Western blot analysis demonstrated an absence of NDRG1 protein in peripheral nerve biopsy of an affected Greyhound. We thus have identified a candidate causative mutation for polyneuropathy in Greyhounds and identified the first genetically characterized canine CMT model which offers an opportunity to gain further insights into the pathobiology and therapy of human NDRG1 associated CMT disease. Selection against this mutation can now be used to eliminate polyneuropathy from Greyhound show dogs.

  • 49.
    Edner, Ann
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery.
    Lindström Nilsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Low risk of transmission of pathogenic bacteria between children and the assistance dog during animal-assisted if strict rules are followed2021In: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 115, p. 5-9Article in journal (Refereed)
    Abstract [en]

    This study explored the bacterial transmission between patients and dogs during dog assisted therapy (DAT). Twenty children (55% girls) with a median age of 7 years (range 3-17 years) were included. Two dogs assisted and the conditions were more restricted hygienically with dog 2. Samples from child and dog were collected and cultured before and after each DAT visit. The results showed that dog 1 transmitted bacteria repeatedly to the children. No bacteria were transmitted with dog 2. In conclusion, exchange of bacteria can occur between dog and child during DAT, but it can be reduced by simple infection control measures. (c) 2021 Published by Elsevier Ltd on behalf of The Healthcare Infection Society.

  • 50. Edner, Anna H.
    et al.
    Essén-Gustavsson, Birgitta
    Nyman, Görel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Metabolism during anaesthesia and recovery in colic and healthy horses: a microdialysis study2009In: Acta Veterinaria Scandinavica, ISSN 0044-605X, E-ISSN 1751-0147, Vol. 51, no 1, p. 10-Article in journal (Refereed)
    Abstract [en]

    Background: Muscle metabolism in horses has been studied mainly by analysis of substances in blood or plasma and muscle biopsy specimens. By using microdialysis, real-time monitoring of the metabolic events in local tissue with a minimum of trauma is possible. There is limited information about muscle metabolism in the early recovery period after anaesthesia in horses and especially in the colic horse. The aims were to evaluate the microdialysis technique as a complement to plasma analysis and to study the concentration changes in lactate, pyruvate, glucose, glycerol, and urea during anaesthesia and in the recovery period in colic horses undergoing abdominal surgery and in healthy horses not subjected to surgery. Methods: Ten healthy university-owned horses given anaesthesia alone and ten client-owned colic horses subjected to emergency abdominal surgery were anaesthetised for a mean (range) of 230 min (193-273) and 208 min (145-300) respectively. Venous blood samples were taken before anaesthesia. Venous blood sampling and microdialysis in the gluteal muscle were performed during anaesthesia and until 24 h after anaesthesia. Temporal changes and differences between groups were analysed with an ANOVA for repeated measures followed by Tukey Post Hoc test or Planned Comparisons. Results: Lactate, glucose and urea, in both dialysate and plasma, were higher in the colic horses than in the healthy horses for several hours after recovery to standing. In the colic horses, lactate, glucose, and urea in dialysate, and lactate in plasma increased during the attempts to stand. The lactate-to-pyruvate ratio was initially high in sampled colic horses but decreased over time. In the colic horses, dialysate glycerol concentrations varied considerably whereas in the healthy horses, dialysate glycerol was elevated during anaesthesia but decreased after standing. In both groups, lactate concentration was higher in dialysate than in plasma. The correspondence between dialysate and plasma concentrations of glucose, urea and glycerol varied. Conclusion: Microdialysis proved to be suitable in the clinical setting for monitoring of the metabolic events during anaesthesia and recovery. It was possible with this technique to show greater muscle metabolic alterations in the colic horses compared to the healthy horses in response to regaining the standing position.

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