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  • 1.
    Danielson, U Helena
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Huang, H H
    Seeger, Christian
    Lindblad, Peter
    Analysis of the leakage of gene repression by an artificial TetR-regulated promoter in cyanobacteria2015In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 8, p. 459-Article in journal (Refereed)
  • 2.
    Dey, Sapna
    et al.
    Department of Microbiology, Madhav Science College (MVM), Vikram University, Ujjain, India.
    Rosales-Klintz, Senia
    Department of Public Health Sciences (Global Health/IHCAR), Karolinska Institutet, Stockholm, Sweden.
    Shouche, Shobha
    Department of Microbiology, Madhav Science College (MVM), Vikram University, Ujjain, India.
    Pathak, Jai Prakash Narayan
    Department of Microbiology, Madhav Science College (MVM), Vikram University, Ujjain, India.
    Pathak, Ashish
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Prevalence and risk factors for nasal carriage of Staphylococcus aureus in children attending anganwaries (preschools) in Ujjain, India2013In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 6, p. 265-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Children with nasal carriage of S. aureus play an important role in community spread of S. aureus and methicillin-resistant S. aureus (MRSA). Screening the nasal carriage isolates of S. aureus for antibiotic resistance patterns will provide guidelines for empiric therapy of community-acquired infections. The aim of the present study was to determine the prevalence of S. aureus and MRSA and it's in vitro antibiotic susceptibility pattern among children in anganwaries (preschools) of Ujjain city India. This work is an extension to our previous publication in BMC Pediatrics (http://www.biomedcentral.com/1471-2431/10/100).

    METHODS:

    A prospective study was done among children aged 1 to 6 years of age attending 100 anganwaries chosen purposely for the study to evenly cover the city. From each anganwari 10 children were randomly selected for nasal swabbing. Children having pyoderma were not included. Information on risk factors for nasal colonization was collected using a pre-tested questionnaire. Swabs from anterior nares were plated on 5% sheep blood agar. Antibiotic susceptibility tests were performed using Kirby-Bauer's disc diffusion method according to performance standards of Clinical and Laboratory Standard Institute guidelines.

    RESULTS:

    A total of 1002 children were included in the study. The prevalence of S. aureus nasal carriage was 35% (95% confidence interval CI 32.07 to 37.98) and that of MRSA nasal carriage was 29% (95% CI 24.28 to 33.88). The factors that were independently associated with nasal carriage of S. aureus were: "age-group" i.e. as the age increased beyond the age of 2 years the OR of nasal carriage decreased, "family size of more than 10 members" OR 2.59 (95% CI 1.53-4.37; P < 0.001), and protein energy malnutrition Grade 3 or 4 (OR 1.40, 95% CI 1.04-1.90; P = 0.026). The resistance pattern of S. aureus and MRSA showed resistance not only to single antibiotic class but co-resistance and multi-drug resistance was also common.

    CONCLUSIONS:

    The high rates of nasal carriage of S. aureus and MRSA and presence of resistance to commonly used antibiotics are disturbing. Antibiotic stewardship programmes that promote judicious use of antibiotic along with strategies to prevent community spread of S. aureus are urgently needed.

  • 3.
    Dubois, Louise
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Andersson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Asplund, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Björkelund, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Evaluating real-time immunohistochemistry on multiple tissue samples, multiple targets and multiple antibody labeling methods2013In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 6, p. 542-Article in journal (Refereed)
    Abstract [en]

    Background

    Immunohistochemistry (IHC) is a well-established method for the analysis of protein expression in tissue specimens and constitutes one of the most common methods performed in pathology laboratories worldwide. However, IHC is a multi-layered method based on subjective estimations and differences in staining and interpretation has been observed between facilities, suggesting that the analysis of proteins on tissue would benefit from protocol optimization and standardization. Here we describe how the emerging and operator independent tool of real-time immunohistochemistry (RT-IHC) reveals a time resolved description of antibody interacting with target protein in formalin fixed paraffin embedded tissue. The aim was to understand the technical aspects of RT-IHC, regarding generalization of the concept and to what extent it can be considered a quantitative method.

    Results

    Three different antibodies labeled with fluorescent or radioactive labels were applied on nine different tissue samples from either human or mouse, and the results for all RT-IHC analyses distinctly show that the method is generally applicable. The collected binding curves showed that the majority of the antibody-antigen interactions did not reach equilibrium within 3 hours, suggesting that standardized protocols for immunohistochemistry are sometimes inadequately optimized. The impact of tissue size and thickness as well as the position of the section on the glass petri dish was assessed in order for practical details to be further elucidated for this emerging technique. Size and location was found to affect signal magnitude to a larger extent than thickness, but the signal from all measurements were still sufficient to trace the curvature. The curvature, representing the kinetics of the interaction, was independent of thickness, size and position and may be a promising parameter for the evaluation of e.g. biopsy sections of different sizes.

    Conclusions

    It was found that RT-IHC can be used for the evaluation of a number of different antibodies and tissue types, rendering it a general method. We believe that by following interactions over time during the development of conventional IHC assays, it becomes possible to better understand the different processes applied in conventional IHC, leading to optimized assay protocols with improved sensitivity.

  • 4.
    Hamed, Sarah
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Sociology.
    Klingberg, Sonja
    Cambridge University.
    Mahmud, Amina Jama
    Independant researcher.
    Bradby, Hannah
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Sociology.
    Researching health in diverse neighbourhoods: critical reflection on the use of a community research model in Uppsala, Sweden2018In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 11, no 612, article id s13104-018-3717-7Article in journal (Refereed)
  • 5.
    Holmqvist, Marie
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Photochemistry and Molecular Science, Microbial Chemistry.
    Lindberg, Pia
    Agervald, Åsa
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Photochemistry and Molecular Science, Microbial Chemistry.
    Stensjö, Karin
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Photochemistry and Molecular Science, Microbial Chemistry.
    Lindblad, Peter
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Photochemistry and Molecular Science, Microbial Chemistry.
    Transcript analysis of the extended hyp-operons in the cyanobacteria Nostoc sp. strain PCC 7120 and Nostoc punctiforme ATCC 291332011In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 4, no 186Article in journal (Other academic)
    Abstract [en]

    The ability of cyanobacteria to capture solar energy, via oxygenic photosynthesis, and convert that energy to molecular hydrogen (H2) has made them an interesting group of organisms with potential as future energy producers. There are three types of enzymes directly involved in the cyanobacterial hydrogen metabolism; nitrogenases that produce H2 as a by-product when fixating atmospheric nitrogen, uptake hydrogenases that catalyze the oxidation of H2,thereby preventing energy losses from the cells, and bidirectional hydrogenases that has the capacity to both oxidize and reduce H2. Hydrogenases are complex metalloenzymes, and the insertion of ligands and correct folding of the proteins require assistance of accessory proteins, the Hyp proteins. Cyanobacterial hydrogenases are NiFe-type hydrogenases and consist of a large and a small subunit. Today, the maturation process of the large subunit has been uncovered to a large extent in cyanobacteria, mostly by analogy assumptions from studies done in other bacteria such as Escherichia coli but also from mutational analyses in cyanobacteria, while the maturation process of the small subunit is still unknown. Recently a set of genes, putatively involved in the maturation process of the small subunit, was discovered in Nostoc sp. PCC 7120 and Nostoc punctiforme ATCC 29133. These five ORFs, encoding unknown proteins, are located in between the uptake hydrogenase structural genes and the hyp-genes were shown to be transcribed together with the hyp-genes in Nostoc PCC 7120. The ORFs upstream the hyp-genes can be found in the same genomic arrangement in other filamentous, nitrogen fixing cyanobacterial strains but are interestingly missing in strains incapable of nitrogen fixation. In this study we have further investigated the function of the ORFs upstream the hyp-genes by studying their transcription pattern after nitrogen depletion in the filamentous, nitrogen fixing strains Nostoc PCC 7120 and N. punctiforme. The transcription pattern were compared to the transcription pattern of hupS and hoxY, encoding the uptake and bidirectional hydrogenase small subunits, nifD, encoding a nitrogenase subunit and hypC and hypF, encoding the maturation process accessory proteins HypC and HypF. All the five ORFs upstream the hyp-genes, in both organisms, were upregulated after nitrogen step down in accordance with the transcription pattern for hupS, nifD, hypC and hypF which support the theory that these genes might be involved in the maturation of the small subunit.

  • 6. Huang, Hsin-Ho
    et al.
    Seeger, Christian
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    Danielson, U Helena
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    Lindblad, Peter
    Analysis of the leakage of gene repression by an artificial TetR-regulated promoter in cyanobacteria.2015In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 8, article id 459Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There is a need for strong and tightly regulated promoters to construct more reliable and predictable genetic modules for synthetic biology and metabolic engineering. For this reason we have previously constructed a TetR regulated L promoter library for the cyanobacterium Synechocystis PCC 6803. In addition to the L03 promoter showing wide dynamic range of transcriptional regulation, we observed the L09 promoter as unique in high leaky gene expression under repressed conditions. In the present study, we attempted to identify the cause of L09 promoter leakage. TetR binding to the promoter was studied by theoretical simulations of DNA breathing dynamics and by surface plasmon resonance (SPR) biosensor technology to analyze the kinetics of the DNA-protein interactions.

    RESULTS: DNA breathing dynamics of a promoter was computed with the extended nonlinear Peyrard-Bishop-Dauxois mesoscopic model to yield a DNA opening probability profile at a single nucleotide resolution. The L09 promoter was compared to the L10, L11, and L12 promoters that were point-mutated and different in repressed promoter strength. The difference between DNA opening probability profiles is trivial on the TetR binding site. Furthermore, the kinetic rate constants of TetR binding, as measured by SPR biosensor technology, to the respective promoters are practically identical. This suggests that a trivial difference in probability as low as 1 × 10(-4) cannot lead to detectable variations in the DNA-protein interactions. Higher probability at the downstream region of transcription start site of the L09 promoter compared to the L10, L11, and L12 promoters was observed. Having practically the same kinetics of binding to TetR, the leakage problem of the L09 promoter might be due to enhanced RNA Polymerase (RNAP)-promoter interactions in the downstream region.

    CONCLUSIONS: Both theoretical and experimental analyses of the L09 promoter's leakage problem exclude a mechanism of reduced TetR binding but instead suggest enhanced RNAP binding. These results assist in creating more tightly regulated promoters for realizing synthetic biology and metabolic engineering in biotechnological applications.

  • 7. Jacobsen, Mette
    et al.
    Cirera, Susanna
    Joller, David
    Esteso, Gloria
    Kracht, Steffen S
    Edfors, Inger
    Bendixen, Christian
    Archibald, Alan L
    Vogeli, Peter
    Neuenschwander, Stefan
    Bertschinger, Hans U
    Rampoldi, Antonio
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Fredholm, Merete
    Jørgensen, Claus B
    Characterisation of five candidate genes within the ETEC F4ab/ac candidate region in pigs2011In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 4, p. 225-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Enterotoxigenic Escherichia coli (ETEC) that express the F4ab and F4ac fimbriae is a major contributor to diarrhoea outbreaks in the pig breeding industry, infecting both newborn and weaned piglets. Some pigs are resistant to this infection, and susceptibility is inherited as a simple dominant Mendelian trait. Indentifying the genetics behind this trait will greatly benefit pig welfare as well as the pig breeding industry by providing an opportunity to select against genetically susceptible animals, thereby reducing the number of diarrhoea outbreaks. The trait has recently been mapped by haplotype sharing to a 2.5 Mb region on pig chromosome 13, a region containing 18 annotated genes.

    FINDINGS:

    The coding regions of five candidate genes for susceptibility to ETEC F4ab/ac infection (TFRC, ACK1, MUC20, MUC4 and KIAA0226), all located in the 2.5 Mb region, were investigated for the presence of possible causative mutations. A total of 34 polymorphisms were identified in either coding regions or their flanking introns. The genotyping data for two of those were found to perfectly match the genotypes at the ETEC F4ab/ac locus, a G to C polymorphism in intron 11 of TFRC and a C to T silent polymorphism in exon 22 of KIAA0226. Transcriptional profiles of the five genes were investigated in a porcine tissue panel including various intestinal tissues. All five genes were expressed in intestinal tissues at different levels but none of the genes were found differentially expressed between ETEC F4ab/ac resistant and ETEC F4ab/ac susceptible animals in any of the tested tissues.

    CONCLUSIONS:

    None of the identified polymorphisms are obvious causative mutations for ETEC F4ab/ac susceptibility, as they have no impact on the level of the overall mRNA expression nor predicted to influence the composition of the amino acids composition. However, we cannot exclude that the five tested genes are bona fide candidate genes for susceptibility to ETEC F4ab/ac infection since the identified polymorphism might affect the translational apparatus, alternative splice forms may exist and post translational mechanisms might contribute to disease susceptibility.

  • 8.
    Kaplan-Sturk, Rebecka
    et al.
    Department of Clinical Science and Education, Section of Obstetrics and Gynecology, Karolinska Institute, Soder Hospital, Stockholm, Sweden.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Volgsten, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Wiberg-Itzel, Eva
    Department of Clinical Science and Education, Section of Obstetrics and Gynecology, Karolinska Institute, Soder Hospital, Stockholm, Sweden.
    Outcome of deliveries in healthy but obese women: obesity and delivery outcome2013In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 6, p. 50-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Obesity among fertile women is a global problem. 25% of pregnant Swedish women are overweight at admission to the antenatal clinic and 12% of them are considered as obese. Previous studies have shown an increased risk of delivery complications with an elevated maternal BMI. The aim of this study was to evaluate delivery outcomes in relation to maternal BMI on admission to the antenatal clinic.

    A healthy group of 787 women with full-term pregnancies and spontaneous onset of labor were included in the study. Delivery outcome was assessed in relation to maternal BMI when attending the antenatal clinic.

    RESULTS:

    The results indicated that in deliveries where the maternal BMI was >30 a high frequency of abnormal CTG trace during the last 30 minutes of labor was shown. A blood sample for evaluation of risk of fetal hypoxia was performed in only eight percent of these deliveries. A spontaneous vaginal delivery without intervention was noted in 85.7%, and 12% of neonates were delivered with an adverse fetal outcome compared to 2.8% in the group with a maternal BMI<30 (p<0.001).

    CONCLUSION:

    These results indicate an increased risk at delivery for healthy, but obese women in labor. Furthermore, the delivery management may not always be optimal in these deliveries.

  • 9. Myrnäs, Anna
    et al.
    Castegren, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Fatal hemolytic uremic syndrome associated with day care surgery and anaesthesia: a case report2013In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 6, no 1, p. 242-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Thrombotic angiopathies, i.e. haemolytic uremic syndrome and thrombotic thrombocytopenic purpura, are thought to occur in patients with a combination of risk factors (e.g., an infection with shiga-toxin-producing Escherichia coli (E. coli) or low activity of the metalloproteinase Adamts-13) and a pathophysiological trigger (e.g., anti-endothelial antibodies, cytokines or activation of chemokine receptor 4). To our knowledge, this is the first report describing an association between haemolytic uremic syndrome and routine surgery and anaesthesia.

    CASE PRESENTATION:

    We present a case in which a 67-year-old Caucasian female developed fatal haemolytic uremic syndrome in the immediate postoperative period of uncomplicated day care surgery. The patient had suffered gastrointestinal symptoms followed by confusion approximately two weeks before surgery, but had been without any symptoms in the week before surgery. Haemolytic uremic syndrome with cerebral symptoms ranging from initial anxiety to subsequent seizures and coma developed within a few hours after the end of surgery. In addition, acute kidney failure and severe thrombocytopenia occurred about the same time. During intensive care, the patient was found to be positive for enterohaemorrhagic E. coli (EHEC) in faeces.

    CONCLUSION:

    Anaesthesiologists should be notified that haemolytic uremic syndrome is an uncommon differential diagnosis in patients with postoperative seizures and coma. Patients with a recent enterohemmoragic E.Coli infection should be followed postoperatively for signs of haemolytic uremic syndrome.

  • 10. Nelson, Ronald M
    et al.
    Shen, Xia
    Carlborg, Örjan
    SLU.
    qtl.outbred: Interfacing outbred line cross data with the R/qtl mapping software.2011In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 4Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: qtl.outbred is an extendible interface in the statistical environment, R, for combining quantitative trait loci (QTL) mapping tools. It is built as an umbrella package that enables outbred genotype probabilities to be calculated and/or imported into the software package R/qtl.

    FINDINGS: Using qtl.outbred, the genotype probabilities from outbred line cross data can be calculated by interfacing with a new and efficient algorithm developed for analyzing arbitrarily large datasets (included in the package) or imported from other sources such as the web-based tool, GridQTL.

    CONCLUSION: qtl.outbred will improve the speed for calculating probabilities and the ability to analyse large future datasets. This package enables the user to analyse outbred line cross data accurately, but with similar effort than inbred line cross data.

  • 11. Nelson, Ronald
    et al.
    Shen, Xia
    Carlborg, Örjan
    SLU.
    qtl.outbred: interfacing outbred line cross data with the R/qtl mapping software2011In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 4, no 154Article in journal (Refereed)
  • 12.
    Nerpin, Elisabet
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Jobs, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Ingelsson, Erik
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Inflammation, oxidative stress, glomerular filtration rate, and albuminuria in elderly men: a cross-sectional study2012In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 5, no 1, p. 537-Article in journal (Refereed)
    Abstract [en]

     BACKGROUND: The role of inflammation and oxidative stress in mild renal impairment in the elderly is not well studied. Accordingly, we aimed at investigating the associations between estimated glomerular filtration rate (eGFR), albumin/creatinine ratio (ACR), and markers of different inflammatory pathways and oxidative stress in a community based cohort of elderly men.

    FINDINGS: Cystatin C-based GFR, ACR, and biomarkers of cytokine-mediated inflammation (interleukin-6, high-sensitivity C-reactive protein[CRP], serum amyloid A[SAA]), cyclooxygenase-mediated inflammation (urinary prostaglandin F2alpha [PGF2alpha]), and oxidative stress (urinary F2 isoprostanes) were assessed in the Uppsala Longitudinal Study of Adult Men(n = 647, mean age 77 years).

    RESULTS: In linear regression models adjusting for age, BMI, smoking, blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides, and treatment with statins, ACE-inhibitors, ASA, and anti-inflammatory agents, eGFR was inversely associated with CRP, interleukin-6, and SAA (beta-coefficient -0.13 to -0.19, p < 0.001 for all), and positively associated with urinary F2-isoprostanes (beta-coefficient 0.09, p = 0.02). In line with this, ACR was positively associated with CRP, interleukin-6, and SAA (beta- coefficient 0.09-0.12, p < 0.02 for all), and negatively associated with urinary F2-isoprostanes (beta-coefficient -0.12, p = 0.002). The associations were similar but with lower regression coefficients in a sub-sample with normal eGFR (>60 ml/min/1.73 m2, n = 514), with the exception that F2-isoprostane and SAA were no longer associated with eGFR.

    CONCLUSION: Our data indicate that cytokine-mediated inflammation is involved in the early stages of impaired kidney function in the elderly, but that cyclooxygenase-mediated inflammation does not play a role at this stage. The unexpected association between higher eGFR/lower albuminuria and increased F2-isoprostanes in urine merits further studies.

  • 13.
    Ramji, Rathi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Arnetz, Judy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Nilsson, Maria
    Department of Public Health and Clinical Medicine, Epidemiology and Global Health, Umeå University, Umeå, Sweden.
    Jamil, Hikmet
    Department of Family Medicine, College of Human Medicine, Michigan State University, 788 Service Road, East Lansing, MI, USA.
    Norstrom, Fredrik
    pidemiology and Global Health, Umeå University, Umeå, Sweden.
    Maziak, Wasim
    Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL, USA.
    Wiklund, Yvonne
    Västerbotten County Council, Umeå, Sweden.
    Arnetz, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Determinants of waterpipe use amongst adolescents in Northern Sweden: a survey of use pattern, risk perception, and environmental factors2015In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 8, article id 441Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Determinants of waterpipe use in adolescents are believed to differ from those for other tobacco products, but there is a lack of studies of possible social, cultural, or psychological aspects of waterpipe use in this population. This study applied a socioecological model to explore waterpipe use, and its relationship to other tobacco use in Swedish adolescents.

    METHODS: A total of 106 adolescents who attended an urban high-school in northern Sweden responded to an anonymous questionnaire. Prevalence rates for waterpipe use were examined in relation to socio-demographics, peer pressure, sensation seeking behavior, harm perception, environmental factors, and depression.

    RESULTS: Thirty-three percent reported ever having smoked waterpipe (ever use), with 30 % having done so during the last 30 days (current use). Among waterpipe ever users, 60 % had ever smoked cigarettes in comparison to 32 % of non-waterpipe smokers (95 % confidence interval 1.4-7.9). The odds of having ever smoked waterpipe were three times higher among male high school seniors as well as students with lower grades. Waterpipe ever users had three times higher odds of having higher levels of sensation-seeking (95 % confidence interval 1.2-9.5) and scored high on the depression scales (95 % confidence interval 1.6-6.8) than non-users. The odds of waterpipe ever use were four times higher for those who perceived waterpipe products to have pleasant smell compared to cigarettes (95 % confidence interval 1.7-9.8). Waterpipe ever users were twice as likely to have seen waterpipe use on television compared to non-users (95 % confidence interval 1.1-5.7). The odds of having friends who smoked regularly was eight times higher for waterpipe ever users than non-users (95 % confidence interval 2.1-31.2).

    CONCLUSION: The current study reports a high use of waterpipe in a select group of students in northern Sweden. The study adds the importance of looking at socioecological determinants of use, including peer pressure and exposure to media marketing, as well as mental health among users.

  • 14. Rincon, Gonzalo
    et al.
    Tengvall, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Belanger, Janelle M
    Lagoutte, Laetitia
    Medrano, Juan F
    André, Catherine
    Thomas, Anne
    Lawley, Cynthia Taylor
    Hansen, Mark St
    Lindblad-Toh, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Oberbauer, Anita M
    Comparison of buccal and blood-derived canine DNA, either native or whole genome amplified, for array-based genome-wide association studies2011In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 4, p. 226-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The availability of array-based genotyping platforms for single nucleotide polymorphisms (SNPs) for the canine genome has expanded the opportunities to undertake genome-wide association (GWA) studies to identify the genetic basis for Mendelian and complex traits. Whole blood as the source of high quality DNA is undisputed but often proves impractical for collection of the large numbers of samples necessary to discover the loci underlying complex traits. Further, many countries prohibit the collection of blood from dogs unless medically necessary thereby restricting access to critical control samples from healthy dogs. Alternate sources of DNA, typically from buccal cytobrush extractions, while convenient, have been suggested to have low yield and perform poorly in GWA. Yet buccal cytobrushes provide a cost-effective means of collecting DNA, are readily accepted by dog owners, and represent a large resource base in many canine genetics laboratories. To increase the DNA quantities, whole genome amplification (WGA) can be performed. Thus, the present study assessed the utility of buccal-derived DNA as well as whole genome amplification in comparison to blood samples for use on the most recent iteration of the canine HD SNP array (Illumina).

    FINDINGS:

    In both buccal and blood samples, whether whole genome amplified or not, 97% of the samples had SNP call rates in excess of 80% indicating that the vast majority of the SNPs would be suitable to perform association studies regardless of the DNA source. Similarly, there were no significant differences in marker intensity measurements between buccal and blood samples for copy number variations (CNV) analysis.

    CONCLUSIONS:

    All DNA samples assayed, buccal or blood, native or whole genome amplified, are appropriate for use in array-based genome-wide association studies. The concordance between subsets of dogs for which both buccal and blood samples, or those samples whole genome amplified, was shown to average >99%. Thus, the two DNA sources were comparable in the generation of SNP genotypes and intensity values to estimate structural variation indicating the utility for the use of buccal cytobrush samples and the reliability of whole genome amplification for genome-wide association and CNV studies.

  • 15.
    Schell, Carl Otto
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Castegren, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Lugazia, Edwin
    Blixt, Jonas
    Mulungu, Moses
    Konrad, David
    Baker, Tim
    Severely deranged vital signs as triggers for acute treatment modifications on an intensive care unit in a low-income country2015In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 8, article id 313Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Critical care saves lives of the young with reversible disease. Little is known about critical care services in low-income countries. In a setting with a shortage of doctors the actions of the nurse bedside are likely to have a major impact on the outcome of critically ill patients with rapidly changing physiology. Identification of severely deranged vital signs and subsequent treatment modifications are the basis of modern routines in critical care, for example goal directed therapy and rapid response teams. This study assesses how often severely deranged vital signs trigger an acute treatment modification on an Intensive Care Unit (ICU) in Tanzania.

    METHODS: A medical records based, observational study. Vital signs (conscious level, respiratory rate, oxygen saturation, heart rate and systolic blood pressure) were collected as repeated point prevalences three times per day in a 1-month period for all adult patients on the ICU. Severely deranged vital signs were identified and treatment modifications within 1 h were noted.

    RESULTS: Of 615 vital signs studied, 126 (18%) were severely deranged. An acute treatment modification was in total indicated in 53 situations and was carried out three times (6%) (2/32 for hypotension, 0/8 for tachypnoea, 1/6 for tachycardia, 0/4 for unconsciousness and 0/3 for hypoxia).

    CONCLUSIONS: This study suggests that severely deranged vital signs are common and infrequently lead to acute treatment modifications on an ICU in a low-income country. There may be potential to improve outcome if nurses are guided to administer acute treatment modifications by using a vital sign directed approach. A prospective study of a vital sign directed therapy protocol is underway.

  • 16.
    Sobol, Maria
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics.
    Dahl, Niklas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics.
    Klar, Joakim
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics.
    FATP4 missense and nonsense mutations cause similar features in Ichthyosis Prematurity Syndrome2011In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 4, p. 90-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Ichthyosis Prematurity Syndrome (IPS) is an autosomal recessive disorder characterized by premature birth, non-scaly ichthyosis and atopic manifestations. The disease was recently shown to be caused by mutations in the gene encoding the fatty acid transport protein 4 (FATP4) and a specific reduction in the incorporation of very long chain fatty acids (VLCFA) into cellular lipids.

    FINDINGS:

    We screened probands from five families segregating IPS for mutations in the FATP4 gene. Four probands were compound heterozygous for four different mutations of which three are novel. Four patients were heterozygous and one patient homozygous for the previously reported non-sense mutation p.C168X (c.504c > a). All patients had clinical characteristics of IPS and a similar clinical course.

    CONCLUSIONS:

    Missense mutations and non-sense mutations in FATP4 are associated with similar clinical features suggesting that missense mutations have a severe impact on FATP4 function. The results broaden the mutational spectrum in FATP4 associated with IPS for molecular diagnosis of and further functional analysis of FATP4.

  • 17. Srithunyarat, Thanikul
    et al.
    Hagman, Ragnvi
    Höglund, Odd V
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Olsson, Ulf
    Hanson, Jeanette
    Nonthakotr, Chalermkwan
    Lagerstedt, Anne-Sofie
    Pettersson, Ann
    Catestatin, vasostatin, cortisol, and pain assessments in dogs suffering from traumatic bone fractures.2017In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 10, no 1, article id 129Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Traumatic bone fractures cause moderate to severe pain, which needs to be minimized for optimal recovery and animal welfare, illustrating the need for reliable objective pain biomarkers for use in a clinical setting. The objectives of this study were to investigate catestatin (CST) and vasostatin (VS) concentrations as two new potential biomarkers, and cortisol concentrations, scores of the short form of the Glasgow composite measure pain scale (CMPS-SF), and visual analog scale (VAS) in dogs suffering from traumatic bone fractures before and after morphine administration in comparison with healthy dogs.

    METHODS: Fourteen dogs with hind limb or pelvic fractures and thirty healthy dogs were included. Dogs with fractures were divided into four groups according to analgesia received before participation. Physical examination, CMPS-SF, pain and stress behavior VAS scores were recorded in all dogs. Saliva and blood were collected once in healthy dogs and in dogs with fractures before and 35-70 min after morphine administration. Blood samples were analyzed for CST, VS, and cortisol. Saliva volumes, however, were insufficient for analysis.

    RESULTS: Catestatin and cortisol concentrations, and CMPS-SF, and VAS scores differed significantly between dogs with fractures prior to morphine administration and healthy dogs. After morphine administration, dogs with fractures had significantly decreased CMPS-SF and VAS scores and, compared to healthy dogs, CST concentrations, CMPS-SF, and VAS scores still differed significantly. However, CST concentrations remained largely within the normal range. Absolute delta values for CST significantly correlated with delta values for CMPS-SF. Catestatin and cortisol did not differ significantly before and after morphine administration. Vasostatin concentrations did not differ significantly between groups.

    CONCLUSIONS: Catestatin and cortisol concentrations, CMPS-SF, and VAS scores differed significantly in the dogs with traumatic bone fractures compared to the healthy dogs. Morphine treatment partially relieved pain and stress according to the subjective but not according to the objective assessments performed. However, because of the large degree of overlap with normal values, our results suggest that plasma CST concentrations have a limited potential as a clinically useful biomarker for pain-induced stress.

  • 18. Srithunyarat, Thanikul
    et al.
    Höglund, Odd V
    Hagman, Ragnvi
    Olsson, Ulf
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Lagerstedt, Anne-Sofie
    Pettersson, Ann
    Catestatin, vasostatin, cortisol, temperature, heart rate, respiratory rate, scores of the short form of the Glasgow composite measure pain scale and visual analog scale for stress and pain behavior in dogs before and after ovariohysterectomy.2016In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 9, article id 381Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The stress reaction induced by surgery and associated pain may be detrimental for patient recovery and should be minimized. The neuropeptide chromogranin A (CGA) has shown promise as a sensitive biomarker for stress in humans. Little is known about CGA and its derived peptides, catestatin (CST) and vasostatin (VS), in dogs undergoing surgery. The objectives of this study were to investigate and compare concentrations of CGA epitopes CST and VS, cortisol, body temperature, heart rate, respiratory rate, scores of the short form of the Glasgow composite measure pain scale (CMPS-SF) and visual analog scales (VAS) for stress and pain behavior in dogs before and after ovariohysterectomy.

    METHODS: Thirty healthy privately owned female dogs admitted for elective ovariohysterectomy were included. Physical examination, CMPS-SF, pain behavior VAS, and stress behavior VAS were recorded and saliva and blood samples were collected before surgery, 3 h after extubation, and once at recall 7-15 days after surgery. Dogs were premedicated with morphine and received carprofen as analgesia for 7 days during the postoperative period.

    RESULTS: At 3 h after extubation, CMPS-SF and pain behavior VAS scores had increased (p < 0.0001) and stress behavior VAS scores, temperature, respiratory rate (p < 0.0001), plasma CST concentrations (p = 0.002) had decreased significantly compared to before surgery. No significant differences were observed in the subjective and physiological parameters between before surgery and at recall, but plasma CST (p = 0.04) and serum cortisol (p = 0.009) were significantly lower at recall. Plasma VS, saliva CST, and heart rate did not differ significantly at any observed time.

    CONCLUSION: Study parameters for evaluating surgery-induced stress and pain changed in dogs subjected to ovariohysterectomy. To further evaluate CST and VS usefulness as pain biomarkers, studies on dogs in acute painful situations are warranted.

  • 19.
    Strand, Tanja M.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Population and Conservation Biology.
    Höglund, Jacob
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Population and Conservation Biology.
    Genotyping of black grouse MHC class II B using Reference Strand-Mediated Conformational Analysis (RSCA)2011In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 4, no 183Article in journal (Refereed)
    Abstract [en]

    Background

    The Major Histocompatibility Complex (MHC) is a cluster of genes involved in the vertebrate immune system and includes loci with an extraordinary number of alleles. Due to the complex evolution of MHC genes, alleles from different loci within the same MHC class can be very similar and therefore difficult to assign to separate loci. Consequently, single locus amplification of MHC genes is hard to carry out in species with recently duplicated genes in the same MHC class, and multiple MHC loci have to be genotyped simultaneously. Since amplified alleles have the same length, accurate genotyping is difficult. Reference Strand-Mediated Conformational Analysis (RSCA), which is increasingly used in studies of natural populations with multiple MHC genes, is a genotyping method capable to provide high resolution and accuracy in such cases.

    Findings

    We adapted the RSCA method to genotype multiple MHC class II B (BLB) genes in black grouse (Tetrao tetrix), a non-model galliform bird species, using a 96-Capillary Array Electrophoresis, the MegaBACE™ 1000 DNA Analysing System (GE Healthcare). In this study we used fluorescently labelled reference strands from both black grouse and hazel grouse and observed good agreement between RSCA and cloning/sequencing since 71 alleles were observed by cloning/sequencing and 76 alleles by RSCA among the 24 individuals included in the comparison. At the individual level however, there was a trend towards more alleles scored with RSCA (1-6 per individual) than cloning/sequencing (1-4 per individual). In 63% of the pair-wise comparison, the identical allele was scored in RSCA as in cloning/sequencing. Nine out of 24 individuals had the same number of alleles in RSCA as in cloning/sequencing. Our RSCA protocol allows a faster RSCA genotyping than presented in many other RSCA studies.

    Conclusions

    In this study, we have developed the RSCA typing method further to work on a 96-Capillary Array Electrophoresis (MegaBACE™ 1000). Our RSCA protocol can be applied to fast and reliable screening of MHC class II B diversity of black grouse populations. This will facilitate future large-scale population studies of black grouse and other galliformes species with multiple inseparable MHC loci.

  • 20.
    Stridsberg, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Pettersson, Ann
    Hagman, Ragnvi
    Westin, Christoffer
    Höglund, Odd
    Chromogranins can be measured in samples from cats and dogs2014In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 7, article id 336Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Methods for objective evaluation of stress in animals are important, but clinically difficult. An alternative method to study the sympathetic activity may be to investigate Chromogranin A (CGA), Chromogranin B (CGB) and Secretogranin II (SG2). The aim of this study was to investigate the cross-reactivity of CGA, CGB and SG2 between man, cat and dog and to explore possibilities to measure these proteins in samples from cats and dogs.

    RESULTS: Adrenal gland extracts from feline and canine species were measured by region-specific radioimmunoassays in different dilution steps to explore possible inter species cross reactivity. High cross reactivity was found for cats in the CGA17-38, CGA324-337, CGA361-372, CGB and SG2 assays. High cross reactivity was found for dogs in the CGA17-38, CGA361-372, CGB and SN assays. The method measuring the intact CGA was not useful for measurements in cats and dogs.

    CONCLUSIONS: Region-specific assays measuring defined parts of CGA, CGB and SG2 can be used for measurements in samples from cats and dogs. These results are promising and will allow for further studies of these proteins as possible clinical biomarkers in cats and dogs.

  • 21.
    Söndergaard, Hans Peter
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Sweden.
    Kushnir, Mark M
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Aronsson, Bernice
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Sweden.
    Sandstedt, Per
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Sweden.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Patterns of endogenous steroids in apathetic refugee children are compatible with long-term stress2012In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 5, no 186Article in journal (Refereed)
    Abstract [en]

    BACKGROUND

    During the last few years, a number of children of asylum applicants in Sweden developed an apathetic or unconscious state. The syndrome was perceived as new, and various explanations were advanced such as; factitious disorder, intoxication, or stress. Considering a potential association between traumatic stress and regulation of steroids biosynthesis, this study explored whether changes in concentrations of endogenous steroids were associated with the above syndrome.

    METHODS

    Eleven children were recruited in the study. Concentrations of steroids in blood samples were determined using high sensitivity liquid chromatography tandem mass spectrometry methods. Symptoms were assessed with a clinical rating scale developed for the study. Steroid concentrations were measured at the entry into study and after recovery; and concentrations were evaluated for the association with the symptoms in apathetic children.

    RESULTS

     Cortisol and cortisone concentrations at baseline were negatively associated with duration of the symptoms from entry into the study to clinical recovery. Concentrations of pregnanes (pregnenolone, 17-OH-pregnenolone, and dehydroepiandrosterone) and 17-OH-progesterone were increased in the symptomatic state and decreased after the recovery.

    CONCLUSIONS

     Pattern of low cortisol concentrations found in apathetic children is consistent with long-term stress. An increase of upstream steroid metabolites such as pregnanes and 17-OH-progesterone was found to be associated with the symptomatic state.

  • 22.
    Willighagen, Egon
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Jeliazkova, Nina
    Ideaconsult Ltd.
    Hardy, Barry
    Douglas Connect.
    Grafström, Roland
    Karolinska Institutet.
    Spjuth, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Computational toxicology using the OpenTox application programming interface and Bioclipse2011In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 4, no 1, p. 487-Article in journal (Refereed)
    Abstract [en]

    Background: Toxicity is a complex phenomenon involving the potential adverse effect on a range of biological functions. Predicting toxicity involves using a combination of experimental data (endpoints) and computational methods to generate a set of predictive models. Such models rely strongly on being able to integrate information from many sources. The required integration of biological and chemical information sources requires, however, a common language to express our knowledge ontologically, and interoperating services to build reliable predictive toxicology applications.

    Findings: This article describes progress in extending the integrative bio- and cheminformatics platform Bioclipse to interoperate with OpenTox, a semantic web framework which supports open data exchange and toxicology model building. The Bioclipse workbench environment enables functionality from OpenTox web services and easy access to OpenTox resources for evaluating toxicity properties of query molecules. Relevant cases and interfaces based on ten neurotoxins are described to demonstrate the capabilities provided to the user. The integration takes advantage of semantic web technologies, thereby providing an open and simplifying communication standard. Additionally, the use of ontologies ensures proper interoperation and reliable integration of toxicity information from both experimental and computational sources.

    Conclusions: A novel computational toxicity assessment platform was generated from integration of two open science platforms related to toxicology: Bioclipse, that combines a rich scriptable and graphical workbench environment for integration of diverse sets of information sources, and OpenTox, a platform for interoperable toxicology data and computational services. The combination provides improved reliability and operability for handling large data sets by the use of the Open Standards from the OpenTox Application Programming Interface. This enables simultaneous access to a variety of distributed predictive toxicology databases, and algorithm and model resources, taking advantage of the Bioclipse workbench handling the technical layers.

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