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  • 1.
    Ahlbeck Bergendahl, Ida
    et al.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Salvanes, Anne Gro V.
    Braithwaite, Victoria A.
    Determining the effects of duration and recency of exposure to environmental enrichment2016In: Applied Animal Behaviour Science, ISSN 0168-1591, E-ISSN 1872-9045, Vol. 176, 163-169 p.Article in journal (Refereed)
    Abstract [en]

    Experience can help animals adapt their behaviour to fit the environment or conditions that they find themselves in. Understanding how and when experience affects behaviour is important for the animals we rear in captivity. This is particularly true when we rear animals with the intent of releasing them into the wild as part of population rehabilitation and conservation efforts. We investigated how exposure to a changing, more complex environment promotes behavioural development in juvenile trout. Four groups of fish were compared; (i) fish that were maintained without enrichment, (ii) fish that were exposed to an early period of enrichment, but were then returned to a plain environment, (iii) fish that were maintained in plain conditions, but were then exposed to enrichment towards the end of the rearing phase, (iv) a group that were kept in enriched conditions throughout the 12 week rearing period. We then assessed fish anxiety levels, their spatial learning ability, and the capacity of the fish to find their way through a barrier where different routes were presented across 4 different trials. Fish that experienced enriched conditions for the longest duration had superior spatial learning abilities, and they were better at finding the correct route to get past the barrier than fish from the remaining three treatments. Positive effects on behaviour were, however, also found in the fish that only experienced enrichment in the last part of the rearing period, compared to the control, or fish exposed to early enrichment. No effect of enrichment was found on levels of anxiety in any of the groups.

  • 2.
    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.

  • 3. 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, 340-353 p.Article 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.

  • 4.
    Akanda, Nesar
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Voltage-dependent anion channels (VDAC) in the plasma membrane induce apoptosis2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Apoptosis, or programmed cell death, is essential for proper development and functioning of the body systems. During development, apoptosis plays a central role to sculpt the embryo, and in adults, to maintain tissue homeostasis by eliminating redundant, damaged or effete cells. Therefore, a tight regulation of this process is essential. Cell shrinkage associated efflux of K+ and Cl through plasma membrane ion channels is an early event of apoptosis. However, little is known about these fluxes. The aim of this thesis was to investigate ion channels in the plasma membrane of neurons undergoing apoptosis. We studied differentiated (the mouse hippocampal cell line HT22, the human neuroblastoma cell line SK-N-MC, and rat primary hippocampal neurons) and undifferentiated (rat primary cortical neural stem cells cNSCs) cells with the patch-clamp technique. All cell types displayed a low electrical activity under control conditions. However, during apoptosis in differentiated neurons, we found an activation of a voltage-dependent anion channel. The conductance of the channel is 400 pS, the voltage dependence of the opening is bell shaped with respect to membrane voltage with a maximum open probability at 0 mV, and the Cl to cation selectivity is >5:1. These biophysical properties remind about the voltage-dependent anion channel normally found in the outer mitochondrial membrane (VDACmt). Hence, we call our apoptosis-inducing plasma membrane channel VDACpl. The molecular identity of the channel was corroborated with the specific labelling of different anti-VDAC antibodies. Block of this channel either with antibodies or with sucrose prevented apoptosis, suggesting a critical role for VDACpl in the apoptotic process. VDACpl is a NADH (-ferricyanide) reductase in control cells. We found that the enzymatic activity is altered while the VDACpl channel is activated during apoptosis. Surprisingly, in cNSCs we did not find any activation of VDACpl, no VDACpl-specific labelling, no enzymatic activity, and no prevention of apoptosis with VDACpl-blocking strategies. Instead, we found an activation of a voltage-independent 37 pS ion channel, and that the Cl channel blocker DIDS prevented apoptosis in cNSCs. Our finding that activation of VDACpl is critical for apoptosis in differentiated neurons hopefully can lead to new strategies in the treatment of several diseases related to apoptosis.

  • 5. Aleksandrova, Krasimira
    et al.
    Jenab, Mazda
    Boeing, Heiner
    Jansen, Eugene
    Bueno-de-Mesquita, H Bas
    Rinaldi, Sabina
    Riboli, Elio
    Overvad, Kim
    Dahm, Christina C
    Olsen, Anja
    Tjønneland, Anne
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Françoise
    Morois, Sophie
    Palli, Domenico
    Krogh, Vittorio
    Tumino, Rosario
    Vineis, Paolo
    Panico, Salvatore
    Kaaks, Rudolf
    Rohrmann, Sabine
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    van Duijnhoven, Fränzel JB
    Leufkens, Anke M
    Peeters, Petra H
    Rodríguez, Laudina
    Bonet, Catalina
    Sánchez, María-José
    Dorronsoro, Miren
    Navarro, Carmen
    Barricarte, Aurelio
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Khaw, Kay-Tee
    Wareham, Nicholas
    Allen, Naomi E
    Spencer, Elizabeth
    Romaguera, Dora
    Norat, Teresa
    Pischon, Tobias
    Circulating C-reactive protein concentrations and risks of colon and rectal cancer: a nested case-control study within the European Prospective Investigation into Cancer and Nutrition2010In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 172, no 4, 407-418 p.Article in journal (Refereed)
    Abstract [en]

    The authors investigated associations between serum C-reactive protein (CRP) concentrations and colon and rectal cancer risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (1992-2003) among 1,096 incident cases and 1,096 controls selected using risk-set sampling and matched on study center, age, sex, time of blood collection, fasting status, menopausal status, menstrual cycle phase, and hormone replacement therapy. In conditional logistic regression with adjustment for education, smoking, nutritional factors, body mass index, and waist circumference, CRP showed a significant nonlinear association with colon cancer risk but not rectal cancer risk. Multivariable-adjusted relative risks for CRP concentrations of > or = 3.0 mg/L versus <1.0 mg/L were 1.36 (95% confidence interval (CI): 1.00, 1.85; P-trend = 0.01) for colon cancer and 1.02 (95% CI: 0.67, 1.57; P-trend = 0.65) for rectal cancer. Colon cancer risk was significantly increased in men (relative risk = 1.74, 95% CI: 1.11, 2.73; P-trend = 0.01) but not in women (relative risk = 1.06, 95% CI: 0.67, 1.68; P-trend = 0.13). Additional adjustment for C-peptide, glycated hemoglobin, and high density lipoprotein cholesterol did not attenuate these results. These data provide evidence that elevated CRP concentrations are related to a higher risk of colon cancer but not rectal cancer, predominantly among men and independently of obesity, insulin resistance, and dyslipidemia.

  • 6.
    Andersson, Anna
    Linköping University, Faculty of Health Sciences, Engelska: Faculty of Health Sciences, Medical Programme.
    Adjuvant and Down-Staging Treatment with Imatinib in Gastrointestinal Stromal Tumours2008Independent thesis Advanced level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: GISTs are gastrointestinal mesenchymal tumours that express the type III receptor tyrosine kinase KIT. The KIT proto-oncogene encodes the receptor KIT. Most GISTs have gain-of-function mutations in the KIT or PDGFRA gene. The tyrosine kinase is therefore continuously activated leading to ligand-independent dimerization. Imatinib mesylate (Glivec®) is considered to be the first-line palliative treatment. The activated form of the KIT receptor tyrosine kinase is inhibited by imatinib. The aim of the study was to compare the survival of patients treated with either adjuvant or down-staging imatinib with historic controls treated with radical surgery (R0) only.

    Methods: A historic control group was chosen from a population-based series from western Sweden (population 1.6 million) that matched the adjuvant (n=23) and down-staging (n=7) groups respectively. Mutation analysis was performed in all cases with bidirectional direct sequencing. The recurrence-free survival was calculated.

    Results: There was only one recurrence (4 %) in the adjuvant group, and no recurrences in the down-staging study group, compared to 32/48 patients (67 %) in the control group. Tumour size decreased in diameter from 20 cm to 11 cm with down-staging treatment.

    Conclusion: Adjuvant imatinib improves recurrence-free survival in R0 resected patients. Down-staging treatment with imatinib is recommended for patients with large tumours or metastases. The importance of mutation analysis was established.

  • 7.
    Andersson, David
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Boyacioglu, Anders
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Bilateral deficit vid excentrisk och koncentrisk muskelaktion: En jämförande studie mellan den summerade unilaterala och bilaterala kraftutvecklingen hos roddare visavi sprinters2006Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpStudent thesis
    Abstract [en]

    Aim

    The main aim of the study was to investigate the difference in bilateral deficit between rowers and sprinters during maximal eccentric/concentric muscle actions.

    • Are there any significant differences in bilateral deficit between rowers and sprinters?

    • Do the amount of years in practice effect the bilateral deficit?

    Method

    Fourteen male subject participants divided in 2 equal sized groups (7 individuals in each group; rowers and sprinters) performed maximal unilateral/bilateral eccentric and concentric muscle actions in a leg press machine at a velocity of 0.2m/s. The range of motion in the knee joint was 70° – 140°. Dependent t-tests have been performed within each group pre and post test. P was set to 0,05 to prevent type I faults (false positive) a Bonferroni test was made for two comparisons and set to 0,0253.

    Results

    Average bilateral deficit for rowers were: 11% concentric and 33% eccentric. Number of years in practice and bilateral deficit: practiced >8years concentric 7% and eccentric 24%. Practiced <8 years concentric 21% and eccentric 55%.

    Average bilateral deficit for sprinters were: 5% concentric and 24% eccentric. Number of years in practice and bilateral deficit: practiced >8years concentric 4% and eccentric 26%. Practiced <8years concentric 16% and eccentric 11%.

    Conclusions

    The main explanation for the larger differences in bilateral deficit for rowers in eccentric muscle action compared to sprinters may be related for the fact that the rowers have an almost non - eccentric phase during rowing. When comparing the amount of years in practice and bilateral deficit we saw that it decreased with the number of practiced years for booth rowers and sprinters. The reason to this pattern is probably on a neural base.

  • 8.
    Andersson, Gunnel
    Örebro University, School of Health and Medical Sciences.
    Urinary incontinence: prevalence, treatment seeking behaviour, experiences, and perceptions among persons with and without urinary leakage2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The overall aim of this thesis is to describe urinary incontinence (UI) from a population perspective and to describe experiences and perceptions of UI from an individual perspective. This includes assessing the prevalence of urinary incontinence as well as describing treatment seeking and experiences of living with UI. A secondary aim was to describe the perception of UI among cultures other than the Swedish mainstream, exemplified in this case by Syrian women living in Sweden. Both quantitative and qualitative methods were used, including questionnaires and interviews.

    Studies I and II were quantitative studies based on a population-based study. Together with a postal survey on general health and living conditions “Life & Health”, a questionnaire on urinary incontinence was sent out to 15 360 randomly-selected residents aged 18-79 in Orebro County, Sweden. In Study I, UI was found to affect 19%. The majority of the respondents experienced minor problems, and only 18% of those reporting UI wanted treatment. However, there was also a group who reported severe problems, but despite this 42% of them did not want treatment. Study II investigated why people with UI refrain from seeking care and treatment. It was found that the desire for treatment was regulated by the frequency of UI, being restricted from participating in various activities, the degree of inconvenience, and the type of UI.

    Studies III and IV were both qualitative interview studies, describing older women’s experiences of living with UI (Study III) and Syrian women’s perceptions of UI (Study IV). There were similarities between the results of these two studies; the women described UI as a normal and expected problem, and they knew that the district nurse could prescribe incontinence protections and that treatments existed. In both studies, the women expressed difficulties in making contact with the health care service, while the women who did not speak Swedish (Study IV) also had difficulties due to different communication problems.

    In conclusion, it is important that health care resources are optimized to identify and meet the needs of those who experience major problems with UI, and that there is awareness of the communication difficulties that can be present in meeting with people who speak other languages. However it is also important not to medicalize those who experience minor problems and who have the desire to manage on their own.

  • 9.
    Anderzén-Carlsson, Agneta
    Örebro University, Department of Clinical Medicine.
    Children with cancer: focusing on their fear and on how their fear is handled2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Various fears in children with cancer have previously been identified as a result of studying e.g. symptom experiences, distress and uncertainty within this population. Studies of the meaning the children give to their fear, as well as the handling of their fear seem to be sparse, however. Also, fear has not been an exclusive focus in previous studies. Professionals in clinical practice have pointed to the need for such research, which has prompted the present research work. The overall aim of this thesis was therefore twofold; firstly, the aim was to elucidate fear in children and adolescents with cancer in order to gain an understanding from the perspective of adolescents and parents. Secondly, it was to elucidate parents’ and professionals’ handling of the fear. This in order to gain a deeper understanding of what performances and manners the children and adolescents can face when being fearful. A qualitative descriptive design was adopted in the five included studies. The methods used in the data analysis were phenomenological hermeneutical method (studies I–III) and qualitative content analysis (studies IV–V).

    In study I six adolescent girls, aged 14–16 years, with experiences of various cancer diagnoses, but now declared fit, were interviewed. The results reveal that they experience their fear as embodied, which in the comprehensive understanding of the results was interpreted as a threat to their personal self, their whole existence. Their fear was seen as a holistic intertwined experience, including fear related to the physical body and to the social self. Also, existential fear was described. Their described experience was interpreted as suffering.

    Studies II and III share the same data. Fifteen parents of children at various ages with various cancer diagnoses were interviewed in focus groups about their experience of their child’s fear. In study II the result reveals how the parents experienced and understood their child’s fear. The fear was described as a multidimensional phenomenon, which was not always easy to identify. It was contrasted to feelings of unease and to absence of fear. In the comprehensive understanding the fear was interpreted as a suffering, as that was regarded to be what was the common meaning in the narratives. The suffering was interpreted as an ethical demand to the parents to take action. In study III the parents described their actions, i.e. they described how they dealt with the fear. Their actions were described as acting in the best interests of the child, which included striving to make the child feel secure and experience wellbeing, up to a certain point. However, after this point the parents used their parental authority to maintain the child’s physical health rather than trying to prevent or relieve the child’s fear. In the comprehensive understanding the parents’ handling of their child’s fear was interpreted as revealing mercy and as being synonymous with meeting the ethical demand put on them.

    In study IV ten experienced nurses and physicians were individually interviewed about how they handled fear in children with cancer. The result reveals that the existential issues were dealt with within the relationship with the child, on a sliding scale between closeness and distance, and that the fear related to medical procedures occurred on a continuum between support and lack of support. The various actions involved, and the manner in which these actions were performed, was described.

    In the observational study (study V) eleven parents and their children as well as eleven health professionals participated. They were observed at children’s routine visits at the outpatient clinic. The aim was to study the interactions related to fear. The result reveals that when children were fearful they expressed this both verbally and non-verbally. The parents’ and professionals’ actions and interactions in these situations were found to be characterized by recognition of the fear or lack of attention to the fear.

    The findings can contribute to a broadened knowledge on fear in children and adolescents with cancer. Awareness and understanding of the meaning adolescents give to their fear, and furthermore, of the parents’ experience and understanding of their child’s fear can provide tools for interacting with these groups. The findings on how fear is dealt with by the ones children have claimed as important sources for support, can give insights into what the child may face when being fearful. These insights can form the basis for individual, as well as collegial, reflections on what is done when children face fear, how fear is handled on an everyday basis and why it is handled in this way. Such reflections could lead to an ethical awareness of handling fear in children with cancer.

  • 10.
    Apró, William
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Tannerstedt, Jörgen
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Nutrition och muskeluppbyggnad2007Student thesis
    Abstract [sv]

    Senare års studier har gett oss en klarare bild av hur muskeluppbyggnaden stimuleras och regleras av styrketräning och nutrition. Mycket forskning kvarstår dock innan fullständiga rekommendationer kan ges. Vad som dock är klart är att de allmänna rekommendationerna som idag uppgår till 0.8 g protein • kg-1 kroppsvikt • dag-1 i de flesta länder (Lemon, 2000) inte räcker till för fysiskt aktiva individer. Atletens ökade proteinbehov kan dock enkelt tillgodoses via ökat matintag varvid supplementering ur den aspekten inte är nödvändig.

    Vidare vet man att tillgängligheten och tillförseln av aminosyror runt träningen är avgörande för maximal stimulering av proteinsyntesen. Muskeln behöver tillgång till essentiella aminosyror när träningen påbörjas för maximal stimulering av proteinsyntesen. Huruvida aminosyrorna behöver tas i form av en dryck i kosttillskottsform eller kan intas i form av vanlig mat för att tillräckligt fort kunna förse muskeln med EAA är inte utrett.

  • 11.
    Arama, Charles
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. University of Sciences Techniques and Technologies of Bamako, Mali.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    The path of malaria vaccine development: challenges and perspectives2014In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 275, no 5, 456-466 p.Article, review/survey (Refereed)
    Abstract [en]

    Malaria is a life-threatening disease caused by parasites of the Plasmodium genus. In many parts of the world, the parasites have developed resistance to a number of antimalarial agents. Key interventions to control malaria include prompt and effective treatment with artemisinin-based combination therapies, use of insecticidal nets by individuals at risk and active research into malaria vaccines. Protection against malaria through vaccination was demonstrated more than 30years ago when individuals were vaccinated via repeated bites by Plasmodium falciparum-infected and irradiated but still metabolically active mosquitoes. However, vaccination with high doses of irradiated sporozoites injected into humans has long been considered impractical. Yet, following recent success using whole-organism vaccines, the approach has received renewed interest; it was recently reported that repeated injections of irradiated sporozoites increased protection in 80 vaccinated individuals. Other approaches include subunit malaria vaccines, such as the current leading candidate RTS,S (consisting of fusion between a portion of the P.falciparum-derived circumsporozoite protein and the hepatitis B surface antigen), which has been demonstrated to induce reasonably good protection. Although results have been encouraging, the level of protection is generally considered to be too low to achieve eradication of malaria. There is great interest in developing new and better formulations and stable delivery systems to improve immunogenicity. In this review, we will discuss recent strategies to develop efficient malaria vaccines.

  • 12.
    Arneson, Sofia
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Att motverka dehydrering hos äldre i teori och praktik2015Independent thesis Basic level (degree of Bachelor), 180 HE creditsStudent thesis
    Abstract [en]

    Objective: To identify similarities and differences in methods and aids used to prevent dehydraton in the elderly as identified from the scientific literature and from interviews with caretakers.

    Method: Literature studies was performed through the University Library search service ”OneSearch” and further from references in key papers. Three interviews were conducted on nursing assistants in two retirement homes and home care services, to offer some insight into the practical activities.

    Results : The following factors were identified as important in both literature and interviews: (1) knowledge of the elderly through documentation, (2) adapted approach when serving drinks after the elderly person's preferences and condition, (3) a homely environment with social interactions, (4) assessments of fluid intake, fluid balance and risk factors through attention, fluid registration and with the help of several other professional groups, and given the history of the elderly, (5) reminders for dementia and a accessibility of large amount of easily absorbed beverages consumed gradually during diarrhea and vomiting, (6) easy-to-use and specially designed drinking aids. For the following factors differences were obeserved between literature survey and interviews: (1) education for caregivers; limited to the investigated sites, (2) technical aids and swallowing therapy (dietary modifications, adapted head positions, swallowing training) in dysphagia; diet modification is used at the investigated sites (3) the importance of cup and jug colours; blue cups used in practice, no support in literature.

    Conclusions: Differences were found in terms of education and the use of swallowing therapy, assistive technology and infusions. Education, more frequent fluid registration and a complete swallowing therapy are improvement opportunites, some of them requires extra resources and/or clear guidelines. Acceptance of technical aids is not self-evident. Investigation of the effect of cup color and design that can encourage the elderly to drink could potentially be a way forward. The results of the interviews are not generalizable because they only aimed to give an insight into the practical activities. Most of the strategies that have been identified are "soft" in nature. It is difficult to get a clear picture of the efficiency of different methods. Methods that have been evaluated with good results in dysphagia and therefore offer potential to improve liquid intake, are swallowing therapy and stimulation of swallowing musculature.

  • 13.
    Arvidsson, D.
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Dept Clin Nutr, SE-40530 Gothenburg, Sweden.
    Slinde, Frode
    University of Skövde, School of Life Sciences.
    Larsson, S.
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med Respirat Med & Allergology, Gothenburg, Sweden.
    Hulthén, L.
    Univ Gothenburg, Sahlgrenska Acad, Dept Clin Nutr, SE-40530 Gothenburg, Sweden.
    Energy cost of physical activities in children: Validation of SenseWear Armband2007In: Medicine & Science in Sports & Exercise, ISSN 0195-9131, E-ISSN 1530-0315, Vol. 39, no 11, 2076-2084 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To examine the validity of SenseWear Pro2 Armband in assessing energy cost of physical activities in children, and to contribute with values of energy costs in an overview of physical activities in children. METHODS: Energy cost was assessed by SenseWear Pro2 Armband in 20 healthy children, 11-13 yr, while lying down resting, sitting playing games on mobile phone, stepping up and down on a step board, bicycling on a stationary bike, jumping on a trampoline, playing basketball, and walking/running on a treadmill at the speeds 2, 3, 4, 5, 6, 7, 8, and 10 km x h(-1). During these activities, energy cost was also assessed from VO2 and VCO2 measured by Oxycon Mobile portable metabolic system, which was used as criterion method. RESULTS: The difference in energy cost between SenseWear Pro2 Armband and Oxycon Mobile was -0.7 (0.5) (P < 0.001) for resting, -2.0 (0.9) (P < 0.001) for playing games on mobile phone, -6.6 (2.3) (P < 0.001) for stepping on the step board, -12.0 (3.7) (P < 0.001) for bicycling, -2.7 (11.9) (P = 0.34) for jumping on the trampoline, and -14.8 (6.4) kJ x min(-1) (P < 0.001) for playing basketball. The difference in energy cost between SenseWear Pro2 Armband and Oxycon Mobile for increasing treadmill speed was 1.3 (3.1) (P = 0.048), 0.1 (2.9) (P = 0.82), -1.2 (2.6) (P = 0.049), -1.6 (3.2) (P = 0.044), -3.1 (3.7) (P = 0.0013), -4.9 (3.7) (P < 0.001), -5.3 (3.7) (P < 0.001), and -11.1 (3.5) kJ x min(-1) (P < 0.001). CONCLUSIONS: SenseWear Pro2 Armband underestimated energy cost of most activities in this study, an underestimation that increased with increased physical activity intensity. A table of energy costs (MET values) of physical activities in children measured by indirect calorimetry is presented as an initiation of the creation of a compendium of physical activities in children

  • 14.
    Atikuzzaman, Mohammad
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Seminal Influence on the Oviduct: Mating and/or semen components induce gene expression changes in the pre-ovulatory functional sperm reservoir in poultry and pigs2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Internal fertilization occurs in birds and eutherian mammals. Foetal development, however, is either extra- respectively intra-corpore (egg vs uterus). In these animal classes, the female genital tract stores ejaculated spermatozoa into a restricted oviductal segment; the functional pre-ovulatory sperm reservoir, where they survive until ovulation/s occur. Paradoxically, this immunologically foreign sperm suspension in seminal fluid/plasma, often microbiologically contaminated, ought to be promptly eliminated by the female local immune defence which, instead, tolerates its presence. The female immune tolerance is presumably signalled via a biochemical interplay of spermatozoa, as well as the peptides and proteins of the extracellular seminal fluid, with female epithelial and immune cells. Such interplay can result in gene expression shifts in the sperm reservoir in relation to variations in fertility. To further aid our understanding of the underlying mechanisms, this thesis studied the proteome of the seminal fluid (using 2D SDS-PAGE and mass spectrometry) including cytokine content (using Luminex and/or ELISA) of healthy, sexually mature and fertile boars and cocks. As well, gene expression changes (using cDNA microarray) in the oviductal sperm reservoirs of sexually-mature females, mated or artificially infused with homologous sperm-free seminal fluid/plasma were studied. Pigs were of commercial, fertility-selected modern breeds (Landrace), while chicken belonged to the ancestor Red Junglefowl (RJF, low egg laying-capacity), a selected egg-layer White Leghorn (WL) and of their Advanced Intercross Line (AIL). Ejaculates were manually collected as single sample in cocks or as the sperm-rich fraction [SRF] and the post- SRF fraction in boars to harvest seminal fluid/plasma for proteome/cytokine and infusion-studies. Oviducts were retrieved for gene-expression analyses via microarray immediately post-mortem (chicken) or at surgery (pig), 24 h after mating or genital infusion. In pigs, the protein-rich seminal plasma showed the highest amounts of cytokines [interferon-γ, interferon gamma-induced protein 10 (IP-10/CXCL10), macrophage derived chemokine (MDC/CCL22), growth-regulated oncogene (GRO/CXCL1), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemo-attractant protein-1 (MCP-1/ CCL2), interleukin (IL)-6, IL-8/CXCL8, IL-10, IL-15, IL-17 and transforming growth factor (TGF)-β1-3) in the larger, protein-rich and sperm-poor post-SRF, indicating its main immune signalling influence. Chicken showed also a plethora of seminal fluid proteins with serum albumin and ovotransferrin being conserved through selection/evolution. However, they showed fewer cytokines than pigs, as the anti-inflammatory/immune-modulatory TGF-β2 or the pro-inflammatory CXCL10. The RJF contained fewer immune system process proteins and lacked TGF-β2 compared to WL and AIL, suggesting selection for increased fertility could be associated with higher expression of immune-regulating peptides/proteins. The oviductal sperm reservoir reacted in vivo to semen exposure. In chicken, mating significantly changed the expression of immune-modulatory and pH-regulatory genes in AIL. Moreover, modern fertile pigs (Landrace) and chicken (WL), albeit being taxonomically distant, shared gene functions for preservation of viable sperm in the oviduct. Mating or SP/SF-infusion were able to change the expression of comparable genes involved in pH-regulation (SLC16A2, SLC4A9, SLC13A1, SLC35F1, ATP8B3, ATP13A3) or immune-modulation (IFIT5, IFI16, MMP27, ADAMTS3, MMP3, MMP12). The results of the thesis demonstrate that both mating and components of the sperm-free seminal fluid/plasma elicit gene expression changes in the pre-ovulatory female sperm reservoir of chickens and pigs, some conserved over domestication and fertility-selection.

  • 15.
    Avall Lundqvist, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Nordström, L
    Sjövall, K
    Eneroth, P
    Evaluation of seven different tumour markers for the establishment of tumour marker panels in gynecologic malignancies.1989In: European journal of gynaecological oncology, ISSN 0392-2936, Vol. 10, no 6, 395-405 p.Article in journal (Refereed)
    Abstract [en]

    Seven tumour markers, i.e. squamous cell carcinoma antigen (SCC), cancer antigen 125 (CA 125), tissue polypeptide antigen (TPA), neopterin, C-reactive protein (CRP), carcinoembryonic antigen (CEA) and deoxythymidine kinase (TK) were analysed in sera from 104 women with benign and 61 women with malignant gynecologic diseases, in order to create tumour marker panels for various gynecologic malignancies, for monitoring and prediction of disease development. The incidence of elevated tumour marker levels, in cervical carcinoma was 78% when SCC, CA 125 and CEA were used. In ovarian carcinoma one of the markers CA 125, TPA and CEA was elevated in 91% and for endometrial carcinoma the best combination of markers was SCC, CA 125 and CEA (57%). No individual marker was superior to the above combinations. However, in patients with a fatal outcome of their malignant gynecologic disease (mean survival time from serum sampling was 16 months), the incidence of death was highest among those who had TPA elevated (91%) followed by neopterin (86%) and CRP (76%). Although intercurrent diseases affected tumour marker levels the markers picked up a majority of patients with a poor prognosis. This demonstrates the importance of interpreting tumour marker results against a background of detailed clinical information.

  • 16.
    Bailey, Leslie
    Umeå University, Faculty of Medicine, Molecular Biology (Faculty of Medicine).
    Infection biology of Chlamydia pneumoniae2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    There are two main human pathogens in the family of Chlamydiaceae. Different serovars of Chlamydia trachomatis cause sexually-transmitted disease and eye infections whereas C. pneumoniae (TWAR) is a common cause of community-acquired respiratory infection. Chlamydia species are obligate, intracellular bacteria sharing a unique developmental cycle that occurs within a protected vacuole termed an inclusion. These microorganisms can be distinguished by two different forms: the infectious, metabolically inert elementary body (EB) and the reproducing non-infectious form, termed the reticulate body (RB). The cycle is terminated when re-differentiation of RBs back to infectious EBs occurs. Chlamydia possesses a type III secretion system (T3SS) essential for delivery of effector proteins into the host for host-cell interactions. This virulence system has been systematically characterized in several mammalian pathogens. Due to lack of a tractable genetic system for Chlamydia species, we have employed chemical genetics as a strategy to investigate molecular aspects of the T3SS. We have identified that the T3S-inhibitors INP0010 and INP0400 block the developmental cycle and interfere with secretion of T3S effector proteins in C. pneumoniae and C. trachomatis, without any cytotoxic effect. We have further shown that INP0010 decreases initiation of transcription in C. pneumoniae during the early mid-developmental cycle as demonstrated by a novel calculation, useful for measurement of transcription initiation in any intracellular pathogen. The mechanism regulating the signal(s) for primary as well as terminal differentiation of RBs has not been defined in Chlamydia. We show using T3S-inhibitors that INP0010 targets the T3SS and thereby arrests RB proliferation as well as RB to EB re-differentiation of C. pneumoniae as where INP0400 targets the T3SS and provokes a bacterial dissociation from the inclusion membrane presumed to mimic the natural occurrence of terminal differentiation. The effect of INP0010 on iron-responsive genes indicates a role for T3S in iron acquisition. Accordingly, our results suggest the possibility that C. pneumoniae acquires iron via the intracellular trafficking pathway of endocytosed transferrin. Moreover, we have for the first time presented data showing generalized bone loss from C. pneumoniae infection in mice. The infection was associated with increased levels of the bone resorptive cytokines IL-6 and IL-1beta. In addition, an increased sub-population of T-cells expressed RANKL during infection. Additionally, C. pneumoniae established an infection in a human osteoblast cell line in vitro with a similar cytokine profile as seen in vivo, supporting a causal linkage. Collectively, these data may indicate a previously unknown pathological role of C. pneumoniae in generalized bone loss.

  • 17.
    Barranco, Isabel
    et al.
    University of Murcia, Spain.
    Roca, Jordi
    University of Murcia, Spain.
    Tvarijonaviciute, Asta
    University of Murcia, Spain.
    Rubér, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Vicente Carrillo, Alejandro
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Atikuzzaman, Mohammad
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Ceron, Jose J.
    University of Murcia, Spain.
    Martinez, Emilio A.
    University of Murcia, Spain.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Measurement of Activity and Concentration of Paraoxonase 1 (PON-1) in Seminal Plasma and Identification of PON-2 in the Sperm of Boar Ejaculates2015In: Molecular Reproduction and Development, ISSN 1040-452X, E-ISSN 1098-2795, Vol. 82, no 1, 58-65 p.Article in journal (Refereed)
    Abstract [en]

    This study revealed and characterised the presence of the antioxidant enzymes paraoxonase (PON) type 1 (PON-1, extracellular) and type 2 (PON-2, intracellular) in boar semen. To evaluate PON-1, an entire ejaculate from each of ten boars was collected and the seminal plasma was harvested after double centrifugation (1,500g for 10min). Seminal plasma was analysed for concentration as well as enzymatic activity of PON-1 and total cholesterol levels. Seminal-plasma PON-1 concentration ranged from 0.961 to 1.670ng/ml while its enzymatic activity ranged from 0.056 to 0.400 IU/ml, which represent individual variance. Seminal-plasma PON-1 concentration and enzymatic activity were negatively correlated (r=-0.763; Pless than0.01). The activity of seminal-plasma PON-1 negatively correlated with ejaculate volume (r=-0.726, Pless than0.05), but positively correlated with sperm concentration (r=0.654, Pless than0.05). Total seminal-plasma cholesterol concentration positively correlated with PON-1 activity (r=0.773; Pless than0.01), but negatively correlated with PON-1 concentration (r=-0.709; Pless than0.05). The presence of intracellular PON-2 was determined via immunocytochemistry in spermatozoa derived from artificial insemination. PON-2 localised to the post-acrosomal area of the sperm head and principal piece of the tail in membrane-intact spermatozoa. In summary, PON is present in boar semen, with PON-1 at low levels in seminal plasma and PON-2 within the spermatozoa. Further studies are needed to characterise the relationship between antioxidant PONs with sperm and other seminal-plasma parameters. Mol. Reprod. Dev. 82: 58-65, 2015. (c) 2014 Wiley Periodicals, Inc.

  • 18.
    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, 13-26 p.Chapter in book (Other (popular science, discussion, etc.))
  • 19.
    Beck-Friis, Johan
    et al.
    Sveriges veterinärförbund.
    Danielsson-Tham, Marie-Louise (intervjuobjekt)
    Örebro University, School of Hospitality, Culinary Arts & Meal Science, Örebro University, Grythyttan, Sweden.
    Salmonella: en smitta att ta på allvar2004In: Svensk veterinärtidning, ISSN 0346-2250, Vol. 56, no 10, 33-34 p.Article in journal (Refereed)
  • 20. Benetou, Vassiliki
    et al.
    Orfanos, Philippos
    Benetos, Ioannis S
    Pala, Valeria
    Evangelista, Alberto
    Frasca, Graziella
    Giurdanella, Maria Concetta
    Peeters, Petra HM
    van der Schouw, Yvonne T
    Rohrmann, Sabine
    Linseisen, Jakob
    Boeing, Heiner
    Weikert, Cornelia
    Pettersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bueno-de-Mesquita, H Bas
    Altzibar, Jone
    Boffetta, Paolo
    Trichopoulou, Antonia
    Anthropometry, physical activity and hip fractures in the elderly2011In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 42, no 2, 188-193 p.Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Hip fractures constitute a major and growing public health problem amongst the elderly worldwide. We examined the association of anthropometry and physical activity with hip fracture incidence in a cohort of elderly Europeans, participants in the European Prospective Investigation into Cancer and nutrition (EPIC) study.

    MATERIALS AND METHODS: The study population consisted of 27982 volunteers (10553 men and 17429 women) aged 60 years and above from five European countries. Information on anthropometry, physical activity, medical history and other characteristics was collected at baseline. During a median follow-up of 8 years, 261 incident hip fractures (203 women and 58 men) were recorded. Data were analysed through Cox proportional hazard regression with adjustment for potential confounders.

    RESULTS: A higher body mass index (BMI) was associated with lower hip fracture risk (hazard ratio (HR) per increasing sex-specific-quintile: 0.85, 95% confidence interval (95% CI): 0.77-0.94). Body height was associated with increased hip fracture risk (HR per 5cm: 1.13, 95% CI: 1.01-1.25). Waist-to-hip ratio was not related to hip fracture risk. Increasing levels of leisure-time physical activity were related to lower risk (HR per increasing tertile: 0.84, 95% CI: 0.70-0.99, p for trend: 0.039).

    CONCLUSIONS: In a prospective cohort study of elderly Europeans, we found evidence that high body stature increased and high BMI decreased the incidence of hip fractures. After adjustment for BMI, waist-to-hip ratio was not associated with hip fracture risk. Leisure-time physical activity appears to play a beneficial role in the prevention of hip fractures.

  • 21.
    Beniamin, Armanos
    University of Skövde, School of Life Sciences.
    Establishment of an Expression and Purification System for Plasmodium falciparum Multi Drug Resistance (pfmdr) Transporter2007Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Malaria is a life threatening parasite disease caused and transmitted by infected female anopheles mosquito. However, the parasite, Plasmodium falciparum, has become resistant to most anti malarial drugs, such as chloroquine, which contributes to fever and anaemia because of its ability to digest the haemoglobin in the red blood cells. The aims of this project were to establish whether “Bac to Bac” Baculoviral Expression System is suitable for expression of pfmdr 1 gene and for purification of the pgh 1 protein. The pfmdr 1 gene encodes an ABC transporter protein, pgh 1, fixed in the cell membrane of the Plasmodium falciparuum gut, which assist in elimination of drug compounds. Furthermore, “Bac to Bac” Baculoviral Expression System uses vectors with histidine tags to clone the pfmdr 1 gene and subsequently transform these into DH10Bac cells to produce the recombinant bacmid DNA. Since pfmdr 1 gene is an AT-rich sequence, PCR was optimized, by lowering the annealing and extension temperature to 47Co and 66Co respectively. The results show that “Bac to Bac” Baculoviral Expression System can be used to express the pfmdr 1 gene, though further experiments has to be performed.

  • 22.
    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, 1178-1181 p.Article 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.

  • 23.
    Berg, Monica
    Karlstad University, Faculty of Arts and Education.
    God hälsa som mål: En textanalys av olika rekommendationer2007Independent thesis Basic level (professional degree), 10 points / 15 hpStudent thesis
    Abstract [sv]

    Syftet med denna uppsats är undersöka om det finns skillnader och likheter i rekommendationer inom tre olika fält där kostsammansättning och fysisk aktivitet behandlas.

    Frågor som besvaras är vilka skillnader och likheter i rekommendationer angående intag av protein, kolhydrater och fett och motion som ges. För att få svar på dessa frågor har en textanalys som baseras på Holliday’s tredimensionella modell för diskursanalys använts. Resultatet visar att de främsta skillnaderna i rekommendationer rör hur man ska fördela det totala energiintaget mellan de energigivande näringsämnena. Likheter som visar sig är att andelen snabba kolhydrater i kosten bör minskas samt att daglig motion påverkar vår hälsa positivt.

  • 24. Berggren, D. Moreno
    et al.
    Folkvaljon, Y.
    Engvall, M.
    Sundberg, J.
    Lehman, S.
    Lambe, M.
    Antunovic, P.
    Garelius, H.
    Hellstrom-Lindberg, E.
    Jadersten, M.
    Lorenz, Fryderyk
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Nilsson, L.
    Ejerblad, E.
    VALIDATION OF PROGNOSTIC SCORING SYSTEMS FOR MYELODYSPLASTIC SYNDROMES IN THE SWEDISH MDS-REGISTER2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, 243-243 p.Article in journal (Other academic)
  • 25. Bergh, Anna
    et al.
    Nordlöf, H
    Essén-Gustavsson, B
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Evaluation of neuromuscular electrical stimulation on fibre characteristics and oxidative capacity in equine skeletal muscles2010In: Equine Veterinary Journal, ISSN 0425-1644, Vol. 42, no Suppl 38, 671-675 p.Article in journal (Refereed)
    Abstract [en]

    Reasons for performing study: Neuromuscular electrical stimulation (NMES) is used to increase or maintain muscle strength during rehabilitation. Human studies investigating different protocols show that some treatments induce changes in muscle characteristics. Despite the frequent use of NMES in horses, no studies have been published describing its efficacy.

    Objectives: To investigate the effects of a NMES protocol on equine fibre types and areas, glycogen concentrations and enzyme activities.

    Methods: NMES was administrated to m. gluteus medius and m. longissimus dorsi, on one side of 6 healthy Standardbred horses. The contralateral side of each muscle served as a nonstimulated control. The horses were stimulated at 50 Hz a day, with 21-39 mA, for 45-60 min, 5 days a week for 4 weeks. Needle biopsies were obtained from the muscles on both sides before and after the experimental period. Muscle samples were analysed for fibre type proportions and area using histochemical methods and for glycogen and enzyme activities (citrate synthase, 3-OH-acyl CoA dehydrogenase, hexokinase and lactate dehydrogenase) using biochemical methods. Muscle contractions at the location and depth of the muscle biopsy were confirmed by diagnostic ultrasound. Nonparametric tests (Mann-Whitney, Wilcoxon sign-rank) were used for statistical analysis. Results: No significant differences were observed in the percentage of types I, IIA or IIX fibres, fibre areas, glycogen levels or enzyme activities either when comparing stimulated and nonstimulated muscles before and after the NMES treatment, or when comparing the left and right muscle samples.

    Conclusions: The NMES treatment was well tolerated by the horses, but the present protocol did not induce significant muscle adaptations. Further studies are needed to describe the effect of more intense and/or prolonged NMES treatment protocols on muscles of healthy horses, and to describe if stimulation protocols induce positive changes in atrophied muscles.

  • 26.
    Bergh, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Zetterström, Per
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Andersen, Peter M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Graffmo, Karin Sixtensdotter
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Jonsson, P. Andreas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Lang, Lisa
    Stockholm, Sweden.
    Danielsson, Jens
    Stockholm, Sweden.
    Oliveberg, Mikael
    Stockholm, Sweden.
    Marklund, Stefan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Structural and kinetic analysis of protein-aggregate strains in vivo using binary epitope mapping2015In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, no 14, 4489-4494 p.Article in journal (Refereed)
    Abstract [en]

    Despite considerable progress in uncovering the molecular details of protein aggregation in vitro, the cause and mechanism of protein-aggregation disease remain poorly understood. One reason is that the amount of pathological aggregates in neural tissue is exceedingly low, precluding examination by conventional approaches. We present here a method for determination of the structure and quantity of aggregates in small tissue samples, circumventing the above problem. The method is based on binary epitope mapping using anti-peptide antibodies. We assessed the usefulness and versatility of the method in mice modeling the neurodegenerative disease amyotrophic lateral sclerosis, which accumulate intracellular aggregates of superoxide dismutase-1. Two strains of aggregates were identified with different structural architectures, molecular properties, and growth kinetics. Both were different from superoxide dismutase-1 aggregates generated in vitro under a variety of conditions. The strains, which seem kinetically under fragmentation control, are associated with different disease progressions, complying with and adding detail to the growing evidence that seeding, infectivity, and strain dependence are unifying principles of neurodegenerative disease.

  • 27.
    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.

  • 28.
    Bergman, Ingrid-Maria
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Edman, Kjell
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Rosengren, K. Johan
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Edfors, Inger
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    European wild boars and domestic pigs display different polymorphic patterns in the Toll-like receptor (TLR)1, TLR2, TLR6, and TLR10 genes.2010In: International Symposium on Animal Genomics for Animal Health Paris, France, 31 May – 2 June 2010: The AGAH 2010 Abstract Book, 2010, 35- p.Conference paper (Other academic)
    Abstract [en]

    The Toll-like receptors (TLR) are vitally important pattern recognition receptors linking innate and adaptive immunity. Several single nucleotide polymorphisms (SNP) in human TLR genes have been associated with disease. There are few studies on associations between polymorphisms in TLR genes and disease in pigs, but the TLR2/TLR6 heterodimer is activated by Mycoplasma hyopneumoniae, and the expression of TLR2, TLR4, and TLR9 is modulated in the presence of different Salmonella serovars. Porcine TLR1, TLR6, and TLR10 are located in a cluster on the p arm of chromosome 8, while TLR2 resides on the q arm. Previously, we identified quantitative trait loci (QTL) for immune-related traits on pig chromosome 8, close to the KIT gene and the microsatellite S0225, respectively. In order to explore polymorphism in some TLR genes in European wild boars and domestic pigs, TLR1, TLR2, and TLR6 were sequenced in 25 wild boars, representing three populations, and in 15 domestic pigs of Hampshire, Landrace, and Large White origin. Similarly, TLR10 was sequenced in 15 wild boars and 15 domestic pigs. In TLR1 and TLR2, more SNP were present in the domestic pigs than in the wild boars. In TLR6, SNP numbers were similar in both animal groups, but the level of heterozygosity was higher in the domestic pigs than in the wild boars. In TLR10, again, more SNP were present in the domestic pigs, and a higher number of nonsynonymous SNP were detected in TLR10 compared to the other genes. This may suggest redundancy for TLR10 in pigs. 

  • 29.
    Berndtson, E.
    et al.
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Emanuelson, U.
    Swedish Association for Livestock Breeding and Production, Eskilstuna, Sweden .
    Engvall, A.
    Department of Epizootiology, National Veterinary Institute, Uppsala, Sweden .
    Danielsson-Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    A 1-year epidemiological study of campylobacters in 18 Swedish chicken farms1996In: Preventive Veterinary Medicine, ISSN 0167-5877, E-ISSN 1873-1716, Vol. 26, no 3-4, 167-185 p.Article in journal (Refereed)
    Abstract [en]

    Broiler chickens are often intestinal carriers of Campylobacter. During processing, Campylobacter may be spread over the carcass. Thus, undercooked chicken meat, or other foods contaminated by raw chicken can act as a source of infection to humans. This study was conducted to identify risk factors for chicken flocks being colonized with Campylobacter. Eighteen chicken farms with altogether 62 chicken compartments were studied for 1 year with visits during each growing period and sampling of chicken caecal contents at slaughter. Four to six subsequent flocks were raised in each compartment during the study. A detailed questionnaire was used to record farm parameters such as building materials, feed and water equipment, hygiene and management routines. Campylobacter prevalence varied between farms, between growing periods within the farms and also during the year, with lowest prevalence during the spring. Campylobacters were isolated from 27% out of 287 flocks. Only two farms were negative at all samplings. Often the flock following a positive flock in a compartment was negative, indicating that normal cleaning and disinfecting routines are sufficient for eliminating the bacteria from the house. Usually only one serotype was found in each positive flock. Campylobacter occurrence increased with the age of the chickens at slaughter, and also with flock size.

    Univariable chi-square tests were done of the association between possible risk factors and Campylobacter prevalence. Factors associated with higher Campylobacter prevalence in flocks were lack of or diffuse hygiene barriers, increasing flock size, increasing age at slaughter, short vs. long empty periods, wet litter beds, other poultry nearby or staff handling other poultry, flocks divided before slaughter, staff loading to slaughter at several farms and occurrence of mice. Under Swedish conditions, water does not seem to be a source of infection for chickens. Origin and handling of day-old chickens, feed additives, houses and litter were not associated with higher Campylobacter prevalence.

  • 30.
    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, 387-395 p.Article 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.

  • 31.
    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, 73-85 p.Chapter in book (Other (popular science, discussion, etc.))
  • 32.
    Borssén, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Nordlund, J
    Haider, Z
    Landfors, M
    Larsson, P
    Forestier, E
    Heyman, M
    Hultdin, M
    Lönnerholm, G
    Syvänen, AC
    Degerman, S
    DNA methylation holds prognostic information in relapsed precursor B-cell acute lymphoblastic leukemiaManuscript (preprint) (Other academic)
  • 33. 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, ISSN 1932-6203, Vol. 6, e28816- p.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.

  • 34.
    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, 233-241 p.Article 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.

  • 35. Bröjer, Caroline
    et al.
    Järhult, Josef D
    Muradrasoli, Shaman
    Söderström, Hanna
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Olsen, Björn
    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, 103-113 p.Article 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 highly pathogenic avian influenza viruses or form part of human-adapted strains with pandemic potential. However, the pathogenesis of LPAI viruses is not well characterized in dabbling ducks, one of the natural reservoirs of LPAI viruses. Between 21 September 2009 and 21 December 2009, we used real-time reverse transcriptase polymerase chain reaction (q-PCR), histopathology, and immunohistochemistry (IHC) to study Mallards (Anas platyrhynchos) infected with an influenza A/H1N1 virus isolated from a wild Mallard in Sweden. The ducks were either inoculated intraesophageally ("artificial infection") or infected by virus shed by other ducks in the experiment ("contact infection"). The ducks were subjected to three low concentrations (80 ng/L, 1 μg/L, and 80 μg/L) of the active metabolite of oseltamivir (Tamiflu(®)), oseltamivir carboxylate (OC), which resulted in the development of the viral resistance mutation H274Y at 1 and 80 μg/L. The LPAI virus infection was localized to the intestinal tract and cloacal bursa except in one Mallard. The exception was a duck euthanized 1 day postinoculation, whose infection was located solely in the lung, possibly due to intratracheal deposition of virus. The intestinal infection was characterized by occasional degenerating cells in the lamina propria and presence of viral antigen as detected by IHC, as well as positive q-PCR performed on samples from feces and intestinal contents. Histopathologic changes, IHC positivity, and viral shedding all indicated that the infection peaked early, around 2 days postinfection. Furthermore, more viral antigen and viral RNA were detected with IHC and q-PCR in the proximal parts early in the infection. There was no obvious difference in the course of the infection in artificial versus contact infection, when the level of OC was increased from 80 ng/L to 1 μg/L (based on IHC and q-PCR), when the level of OC was increased to 80 μg/L, or when the resistance mutation H274Y developed (based on q-PCR).

  • 36. 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, 103-113 p.Article 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.

  • 37.
    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.

  • 38.
    Böttiger, Anna
    Örebro University, School of Health and Medical Sciences.
    Genetic variation in the folate receptor-alpha and methylenetetrahydrofolate reductase genes as determinants of plasma homocysteine concentrations2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Elevated total plasma homocysteine (tHcy) is a risk factor for cardiovascular disease and neurocognitive disease such as dementia. The B vitamins folate and B12 are the main de terminants of tHcy. tHcy concentration can also be affected by mutations in genes coding for receptors, enzymes and transporters important in the metabolism of Hcy. This thesis focuses on mutations in the genes for folate receptor-alpha and methylenetetrahydrofolate reductase (MTHFR) and the effect they have on tHcy concentrations.

    Six novel mutations in the gene for folate receptor-alpha were described in Paper I. Taken together they exist in a population with a prevalence of approximately 1% and thus are not unusual. There may be an association of –69dupA and –18C>T to tHcy but for the 25-bp deletion, –856C>T, –921T>C and –1043G>A there is probably no association to tHcy. Mutation screening was continued and four additional mutations, 1314G>A, 1816delC, 1841G>A and 1928C>T, were described in Paper II. The prevalences for the heterozygotes were between 0.5% and 13% in an elderly population. There was no significant difference in prevalence between the elderly subjects and patients with dementia. The 1816(–)-allele and the 1841A-allele were in complete linkage and the haplotype 1816(–)-1841A may possibly have a tHcy raising effect. The 1314G>A and 1928C>T mutations had no association to tHcy.

    The genotype prevalences and haplotype frequencies of the MTHFR 677C>T, 1298A>C and 1793G>A polymorphisms were determined in a population sample of Swedish children and adolescents (Paper III). The MTHFR 677T-allele was associated with increased tHcy concentrations in both children and adolescents. A small elevating effect of the 1298C-allele and a small lowering effect of the 1793A-allele could be shown. In an epidemiological sample of adults from the Canary Islands, Spain, data for serum folate and vitamin B12 were used for a broader study of the nutrigenetic impact on tHcy (Paper IV). The 677T-allele had a significant tHcy increasing effect in men but not in women. The 1298C-allele had a minor elevating effect on tHcy in men with the 677CT genotype. It was not possible to document any effect of the 1793A-allele on tHcy due to its low prevalence. A slightly superior explanatory power for the genetic impact was obtained using the MTHFR haplotypes in the analysis compared to the MTHFR 677C>T genotype-based approach in both the Swedish children and adolescents and in the Spanish adults. Therefore MTHFR haplotypes should be considered when analysing the impact of the MTHFR 677C>T, 1298A>C and 1793G>A polymorphisms on tHcy.

    Notwithstanding the large geographical distance between our study populations the haplotype composition is quite similar. The MTHFR 677T-allele is slightly more prevalent in Spain compared to Sweden but it has only an effect on tHcy in the Spanish men. Age, gender and factors linked to the ethnicity of the studied subjects, seem to be able to override the nutrigenetic impact of tHcy-raising genotypes or haplotypes in particular settings, such as in the Spanish women in our study. Gene-nutrient interactions on plasma tHcy levels thus may or may not exist in a certain population. The transferability of nutrigenetic findings may therefore be limited, and must be re-evaluated for each particular setting of age-gender-ethnicity.

  • 39.
    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. 

  • 40.
    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, Vol. 86, no 1, 183-187 p.Article 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.

  • 41.
    Cederquist, Kristina
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Palmqvist, Richard
    Emanuelsson, Monica
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Grönberg, Henrik
    Retained immunohistochemical staining in a large Swedish HNPCC family with a pathogenic MLH1 missense mutationManuscript (preprint) (Other academic)
  • 42.
    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, 228-239 p.Chapter in book (Other (popular science, discussion, etc.))
  • 43. Cif, Laura
    et al.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Unit of Functional Neurosurgery, University College London-Institute of Neurology, Queen Square, London, UK.
    Seventy Years of Pallidotomy for Movement Disorders2017In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 32, no 7, 972-982 p.Article in journal (Other academic)
    Abstract [en]

    The year 2017 marks the 70th anniversary of the birth of human stereotactic neurosurgery. The first procedure was a pallidotomy for Huntington's disease. However, it was for Parkinson's disease that pallidotomy was soon adopted worldwide. Pallidotomy was abandoned in the late 1950s in favor of thalamotomy because of the latter's more striking effect on tremor. The advent of levodopa put a halt to all surgery for PD. In the mid-1980s, Laitinen reintroduced the posteroventral pallidotomy of Leksell, and this procedure spread worldwide thanks to its efficacy on most parkinsonian symptoms including levodopa-induced dyskinesias and thanks to basic scientific work confirming the role of the globus pallidus internus in the pathophysiology of PD. With the advent of deep brain stimulation of the subthalamic nucleus, pallidotomy was again abandoned, and even DBS of the GPi has been overshadowed by STN DBS. The GPi reemerged in the late 1990s as a major stereotactic target for DBS in dystonia and, recently, in Tourette syndrome. Lately, lesioning of the GPI is being proposed to treat refractory status dystonicus or to treat DBS withdrawal syndrome in PD patients. Hence, the pallidum as a stereotactic target for either lesioning or DBS has been the phoenix of functional stereotactic neurosurgery, constantly abandoned and then rising again from its ashes. This review is a tribute to the pallidum on its 70th anniversary as a surgical target for movement disorders, analyzing its ebbs and flows and highlighting its merits, its versatility, and its resilience.

  • 44.
    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, 310-315 p.Article 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.

  • 45.
    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.

  • 46.
    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, 3022-3033 p.Article 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.

  • 47.
    Dahlin, Anna M
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Henriksson, Maria L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Jacobsson, Maria
    Eklöf, Vincy
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Rutegård, Jörgen
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Öberg, Åke
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    The role of the CpG island methylator phenotype in colorectal cancer prognosis depends on microsatellite instability screening status2010In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 16, no 6, 1845-1855 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The aim of this study was to relate the CpG island methylator phenotype (CIMP; characterized by extensive promoter hypermethylation) to cancer-specific survival in colorectal cancer, taking into consideration relevant clinicopathologic factors, such as microsatellite instability (MSI) screening status and the BRAF V600E mutation.

    EXPERIMENTAL DESIGN: Archival tumor samples from 190 patients from the Northern Sweden Health and Disease Study (NSHDS) and 414 patients from the Colorectal Cancer in Umeå Study (CRUMS), including 574 with cancer-specific survival data, were analyzed for an eight-gene CIMP panel using quantitative real-time PCR (MethyLight). MSI screening status was assessed by immunohistochemistry.

    RESULTS: CIMP-low patients had a shorter cancer-specific survival compared with CIMP-negative patients (multivariate hazard ratio in NSHDS, 2.01; 95% confidence interval, 1.20-3.37; multivariate hazard ratio in CRUMS, 1.48; 95% confidence interval, 1.00-2.22). This result was similar in subgroups based on MSI screening status and was statistically significant in microsatellite stable (MSS) tumors in NSHDS. For CIMP-high patients, a shorter cancer-specific survival compared with CIMP-negative patients was observed in the MSS subgroup. Statistical significance was lost after adjusting for the BRAF mutation, but the main findings were generally unaffected.

    CONCLUSIONS: In this study, we found a poor prognosis in CIMP-low patients regardless of MSI screening status, and in CIMP-high patients with MSS. Although not consistently statistically significant, these results were consistent in two separate patient groups and emphasize the potential importance of CIMP and MSI status in colorectal cancer research.

  • 48.
    Dahlström, Örjan
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, The Swedish Institute for Disability Research. Linköping University, Faculty of Arts and Sciences.
    Zetterqvist, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Lundh, Lars-Gunnar
    Department of Psychology, Lund University, Lund, Sweden..
    Svedin, Carl Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Functions of Nonsuicidal Self-Injury: Exploratory and Confirmatory Factor Analyses in a Large Community Sample of Adolescents2015In: Psychological Assessment, ISSN 1040-3590, E-ISSN 1939-134X, Vol. 27, no 1, 302-313 p.Article in journal (Refereed)
    Abstract [en]

    Given that nonsuicidal self-injury (NSSI) is prevalent in adolescents, structured assessment is an essential tool to guide treatment interventions. The Functional Assessment of Self-Mutilation (FASM) is a self-report scale that assesses frequency, methods, and functions of NSSI. FASM was administered to 3,097 Swedish adolescents in a community sample. With the aim of examining the underlying factor structure of the functions of FASM in this sample, the adolescents with NSSI who completed all function items (n = 836) were randomly divided into 2 subsamples for cross-validation purposes. An exploratory factor analysis (EFA) was followed by a confirmatory factor analysis (CFA) using the mean and variance adjusted weighted least squares (WLSMV) estimator in the Mplus statistical modeling program. The results of the EFA suggested a 3-factor model (social influence, automatic functions, and nonconformist peer identification), which was supported by a good fit in the CFA. Factors differentiated between social/interpersonal and automatic/intrapersonal functions. Based on learning theory and the specific concepts of negative and positive reinforcement, the nonconformist peer identification factor was then split into 2 factors (peer identification and avoiding demands). The resulting 4-factor model showed an excellent fit. Dividing social functions into separate factors (social influence, peer identification, and avoiding demands) can be helpful in clinical practice, where the assessment of NSSI functions is an important tool with direct implications for treatment.

  • 49.
    Danielsson-Tham, Marie-Louise
    Örebro University, School of Hospitality, Culinary Arts & Meal Science, Örebro University, Grythyttan, Sweden.
    Den veterinäre livsmedelshygienikern: från patolog till risk- och faroanaytiker2004In: Svensk veterinärtidning, ISSN 0346-2250, Vol. 56, no 10, 19-23 p.Article in journal (Other academic)
  • 50.
    Danielsson-Tham, Marie-Louise
    Örebro University, School of Hospitality, Culinary Arts & Meal Science, Örebro University, Grythyttan, Sweden.
    Hurdan veterinär vill det svenska samhället ha?2004In: Svensk veterinärtidning, ISSN 0346-2250, Vol. 56, no 1, 39-41 p.Article in journal (Other (popular science, discussion, etc.))
1234567 1 - 50 of 358
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