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  • 201. Vagoras, A.
    et al.
    Butylkina, R.
    Juseviciute, V.
    Hallén, A.
    Unemo, Magnus
    Örebro University, Department of Clinical Medicine.
    Domeika, M.
    Diagnosis of non-viral sexually transmitted infections in Lithuania and international recommendations2006In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 11, no 7, p. 161-164Article in journal (Refereed)
    Abstract [en]

    The aim of this study is to evaluate the range, quality and availability of diagnostic services for non-viral sexually transmitted infections (STIs), i.e. C. trachomatis, N. gonorrhoeae, T. vaginalis and T. pallidum, in Lithuania from September 2002 to December 2003. Surveillance data describing the organisation and performance characteristics of non-viral STI diagnostic services in Lithuania were collected using a questionnaire and subsequent site-visits. International evidence-based recommendations for non-viral STI diagnosis were used to evaluate the quality of the STI diagnostics. There were 171 facilities providing non-viral STI diagnostic services for the 3.5 million inhabitants of Lithuania. However, only 6% (n=9) of the respondents (n=153) could provide a confirmatory diagnosis, in accordance with international recommendations, for the full minimum range of relevant non-viral STIs in Lithuania, i.e. C. trachomatis, N. gonorrhoeae, T. pallidum, and T. vaginalis. In addition, accessibility to STI diagnostic services differed significantly among the different counties in Lithuania. Several of the respondents analysed low numbers of samples each year, and overall the sampling size was extremely low, especially for C. trachomatis diagnostics. In Lithuania, optimisation of non-viral STI diagnostics as well as of epidemiological surveillance and management of STIs is crucial. It may be worth considering a decrease in the number of laboratories, with those remaining having the possibility of performing STI diagnostic services that are optimised, in concordance with international recommendations, standardised, and quality assured using systematic internal and external quality controls and systems. In addition, establishment of national inter-laboratory networks and reference centres for non-viral STIs is recommended.

  • 202.
    van den Nieuwboer, M
    et al.
    Athena Inst, Vrije Univ Amsterdam, Amsterdam, Netherlands; Swammerdam Inst Life Sci, Univ Amsterdam, Amsterdam, Netherlands.
    Claassen, E
    Athena Inst, Vrije Univ Amsterdam, Amsterdam, Netherlands; Dept Virosci, Erasmus MC, Rotterdam, Netherlands .
    Morelli, L
    Ist Microbiol, Univ Cattolica SC, Piacenza, Italy.
    Guarner, F
    CIBERehd, Digest Syst Res Unit, Univ Hosp Vall dHebron, Barcelona, Spain.
    Brummer, Robert J
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital.
    Probiotic and synbiotic safety in infants under two years of age2014In: Beneficial Microbes, ISSN 1876-2883, E-ISSN 1876-2891, Vol. 5, no 1, p. 45-60Article in journal (Refereed)
    Abstract [en]

    In this study, we systematically evaluated safety aspects in clinical trials with probiotics and synbiotics in young infants (0-2 years of age). This study is an update of earlier reports and covers the recent literature from 2008-2013. The safety evaluation is performed along the Common Terminology Clinical Adverse Events (CTCAE) version 4.0 scale, hereby also providing guidance for future studies. Safety aspects are represented and related to number of participants per probiotic strain/culture, study duration, dosage, clinical condition and selected afflictions. The results show a deficiency in the precise reporting and classification of adverse events in most studies. Analysis of 57 clinical trials with probiotics and synbiotics in combination with eight follow-up studies indicate that probiotic administration to infants between 0 and 24 months is safe with regard to the evaluated strains in infants with a particular health status or susceptibility. Most adverse events and serious adverse events were considered unrelated to the study product, and there were no major safety concerns. Almost all studies concluded that none of the adverse effects were related to the study product; the study products are generally well tolerated. Finally, inconsistent, imprecise and potentially incomplete reporting as well as the variation in probiotic strains, dosages, administration regimes, study populations and reported outcomes, greatly limit the generalizability of conclusions and argue convincingly for obligatory and standardised behaviour on adverse events (CTCAE) reporting in 'food' studies.

  • 203. Verberkmoes, Nathan C.
    et al.
    Russell, Alison L.
    Shah, Manesh
    Godzik, Adam
    Rosenquist, Magnus
    Halfvarson, Jonas
    Lefsrud, Mark G.
    Apajalahti, Juha
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Hettich, Robert L.
    Jansson, Janet K.
    Shotgun metaproteomics of the human distal gut microbiota2009In: ISME Journal, ISSN 1751-7370, Vol. 3, no 2, p. 179-189Article in journal (Refereed)
    Abstract [en]

    The human gut contains a dense, complex and diverse microbial community, comprising the gut microbiome. Metagenomics has recently revealed the composition of genes in the gut microbiome, but provides no direct information about which genes are expressed or functioning. Therefore, our goal was to develop a novel approach to directly identify microbial proteins in fecal samples to gain information about the genes expressed and about key microbial functions in the human gut. We used a non-targeted, shotgun mass spectrometry-based whole community proteomics, or metaproteomics, approach for the first deep proteome measurements of thousands of proteins in human fecal samples, thus demonstrating this approach on the most complex sample type to date. The resulting metaproteomes had a skewed distribution relative to the metagenome, with more proteins for translation, energy production and carbohydrate metabolism when compared to what was earlier predicted from metagenomics. Human proteins, including antimicrobial peptides, were also identified, providing a non-targeted glimpse of the host response to the microbiota. Several unknown proteins represented previously undescribed microbial pathways or host immune responses, revealing a novel complex interplay between the human host and its associated microbes.

  • 204.
    Vincent, Leah R.
    et al.
    Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda MD, United States; NIAID, Bethesda MD, United States.
    Kerr, Samuel R.
    Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill NC, United States; Yale University, New Haven CT, United States.
    Tan, Yang
    Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill NC, United States.
    Tomberg, Joshua
    Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill NC, United States.
    Raterman, Erica L.
    Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda MD, United States.
    Hotopp, Julie C. Dunning
    Department of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD, United States.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. World Health Organization Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, Swedish Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Nicholas, Robert A.
    Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill NC, United States; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill NC, United States.
    Jerse, Ann E.
    Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda MD, United States.
    In Vivo-Selected Compensatory Mutations Restore the Fitness Cost of Mosaic penA Alleles That Confer Ceftriaxone Resistance in Neisseria gonorrhoeae2018In: mBio, ISSN 2161-2129, E-ISSN 2150-7511, Vol. 9, no 2, article id e01905-17Article in journal (Refereed)
    Abstract [en]

    Resistance to ceftriaxone in Neisseria gonorrhoeae is mainly conferred by mosaic penA alleles that encode penicillin-binding protein 2 (PBP2) variants with markedly lower rates of acylation by ceftriaxone. To assess the impact of these mosaic penA alleles on gonococcal fitness, we introduced the mosaic penA alleles from two ceftriaxone-resistant (Cro(r)) clinical isolates (H041 and F89) into a Cro(s) strain (FA19) by allelic exchange and showed that the resultant Cro(r) mutants were significantly outcompeted by the Cro(s) parent strain in vitro and in a murine infection model. Four Cro(r) compensatory mutants of FA19 penA41 were isolated independently from mice that outcompeted the parent strain both in vitro and in vivo. One of these compensatory mutants (LV41C) displayed a unique growth profile, with rapid log growth followed by a sharp plateau/gradual decline at stationary phase. Genome sequencing of LV41C revealed a mutation (G348D) in the acnB gene encoding the bifunctional aconitate hydratase 2/2 methylisocitrate dehydratase. Introduction of the acnB G348D allele into FA19 penA41 conferred both a growth profile that phenocopied that of LV41C and a fitness advantage, although not as strongly as that exhibited by the original compensatory mutant, suggesting the existence of additional compensatory mutations. The mutant aconitase appears to be a functional knockout with lower activity and expression than wild-type aconitase. Transcriptome sequencing (RNA-seq) analysis of FA19 penA41 acnB(G348D) revealed a large set of upregulated genes involved in carbon and energy metabolism. We conclude that compensatory mutations can be selected in Cro(r) gonococcal strains that increase metabolism to ameliorate their fitness deficit.

    IMPORTANCE: The emergence of ceftriaxone-resistant (Cro(r)) Neisseria gonorrhoeae has led to the looming threat of untreatable gonorrhea. Whether Cro resistance is likely to spread can be predicted from studies that compare the relative fitnesses of susceptible and resistant strains that differ only in the penA gene that confers Cro resistance. We showed that mosaic penA alleles found in Cro(r) clinical isolates are outcompeted by the Cro(s) parent strain in vitro and in vivo but that compensatory mutations that allow ceftriaxone resistance to be maintained by increasing bacterial fitness are selected during mouse infection. One compensatory mutant that was studied in more detail had a mutation in acnB, which encodes the aconitase that functions in the tricarboxylic acid (TCA) cycle. This study illustrates that compensatory mutations can be selected during infection, which we hypothesize may allow the spread of Cro resistance in nature. This study also provides novel insights into gonococcal metabolism and physiology.

  • 205.
    Waak, Elisabet
    et al.
    Arla Foods Innovation, Stockholm, Sweden.
    Tham, Wilhelm
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Danielsson-Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Prevalence and fingerprinting of Listeria monocytogenes strains isolated from raw whole milk in farm bulk tanks and in dairy plant receiving tanks2002In: Applied and Environmental Microbiology, ISSN 0099-2240, E-ISSN 1098-5336, Vol. 68, no 7, p. 3366-3370Article in journal (Refereed)
    Abstract [en]

    The incidence of Listeria species in raw whole milk from farm bulk tanks and from raw milk in storage at a Swedish dairy plant was studied. Listeria monocytogenes was found in 1.0% and Listeria innocua was found in 2.3% of the 294 farm bulk tank (farm tank) milk specimens. One farm tank specimen contained 60 CFU of L. monocytogenes ml-1. L. monocytogenes was detected in 19.6% and L. innocua was detected in 8.5% of the milk specimens from the silo receiving tanks at the dairy (dairy silos). More dairy silo specimens were positive for both Listeria species during winter than during summer. Restriction enzyme analysis and pulsed-field gel electrophoresis were applied to 65 isolates of L. monocytogenes, resulting in 16 different clonal types. Two clonal types were shared by the farm tank milk and the dairy silo milk. All except one clonal type belonged to serovar 1/2a. In the dairy silo milk five clonal types were found more frequently and for a longer period than the others. No Listeria species were found in any other samples from the plant.

  • 206.
    Wadström, Torkel
    et al.
    Institutionen för Bakteriologi och Epizootologi, Veterinärmedicinska Fakulteten, SLU, Uppsala.
    Möllby, Roland
    Institutionen för Bakteriologi och Epizootologi, Veterinärmedicinska Fakulteten, SLU, Uppsala.
    Danielsson Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Tre livsmedelsburna utbrott av enterotoxinbildande Escherichia coli och Klebsiella pneumonia1978In: XXXV Läkaresällskapets Riksstämma anordnad av Svenska Läkaresällskapet på Stockholmsmässan, Älvsjö, Stockholm, 29 november–2 december, 1978: sammanfattningar, Stockholm: Svenska läkaresällskapet , 1978, Vol. 87, p. 35-35Conference paper (Refereed)
  • 207.
    Wentzel, Ann-Kristin
    et al.
    Forskning och framsteg.
    Danielsson-Tham (intervjuobjekt), Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Törs vi äta julskinkan?1989Other (Other (popular science, discussion, etc.))
  • 208.
    Wiklund, E.
    et al.
    Swedish University of Agricultural Sciences, Dept. of Food Science, Uppsala, Sweden .
    Rehbinder, C.
    National Veterinary Institute, Dept. of Pathology, Uppsala, Sweden.
    Malmfors, G.
    Swedish University of Agricultural Sciences, Dept. of Food Science, Uppsala, Sweden .
    Hansson, I.
    National Veterinary Institute, Dept. of Bacteriology, Uppsala, Sweden.
    Danielsson Tham, Marie-Louise
    Swedish University of Agricultural Sciences, Dept. of Food Hygiene, Uppsala, Sweden.
    Ultimate pH values and bacteriological condition of meat and stress metabolites in blood of transported reindeer bulls2001In: Rangifer, ISSN 0333-256X, E-ISSN 1890-6729, Vol. 21, no 1, p. 3-12Article in journal (Refereed)
    Abstract [en]

    Twenty-three reindeer bulls, aged 2-3 years, fed during two winter months at the Vuolda reindeer research station in Arjeplog, Sweden, were used in the study. The first group of eight reindeer was moved from their feeding corral to a selection corral, captured by lasso and stunned with a captive bolt outside the selection corral. The second group of seven reindeer was moved to the selection corral, captured by lasso and restrained, after which they were loaded onto a lorry- and transported for 1 hour and then slaughtered. The third group of eight reindeer was moved to the selection corral and herded directly onto the lorry, without any manual handling. They were transported for 5 h and then slaughtered. In both transport groups, four reindeer were fitted with pre-programmed automatic blood sampling equipment (ABSE). ABSE sampled blood at predetermined times via a jugular vein catheter. Ultimate pH-values in three muscles (Mm. longissimus, triceps brachii and biceps femoris) were significantly lower in the group carefully handled and transported for 5 h compared with the other two groups. The physiological mechanisms behind these results are discussed. Samples from M. semimembranosus were collected at slaughter and after 2, 6 and 10 days of refrigerated storage (+4 °C). The samples were analysed for total counts of aerobic bacteria (pour-plated in Tryptone Glucose Extract Agar, Difco, incubated at 20 °C and 30 °C, respectively for 72 h), coliform bacteria 37 °C (pour-plated in Violet Red Bile Agar, Oxoid, incubated at 37 °C for 24 h), Enterococci (surface-plated onto Slantez and Bartley Agar, Oxoid, incubated at 44 °C for 48 h) and Bacillus cereus (surface-plated onto Blood Agar Plates (Blood Agar Base, Difco, supplemented with 5% defibrinated horse blood) 30 °C for 24 h). All samples fell in the range 'fit for consumption'. At slaughter, there was no difference in ASAT activity, urea and Cortisol concentrations between the two transported groups. However, the plasma ASAT activity and urea concentrations at slaughter were significantly lower in the non-transported group. In both transport groups, the plasma Cortisol concentrations increased during loading onto and unloading from the lorry. Abomasal lesions were observed in all treatment groups. It was concluded that reindeer showed an acute stress response to manual handling and transport.

  • 209. Åkerlund, Thomas
    et al.
    Persson, Ingela
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences.
    Norén, Torbjörn
    Svenungsson, Bo
    Wullt, Marlene
    Burman, Lars G.
    Increased sporulation rate of epidemic Clostridium difficile Type 027/NAP12008In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 46, no 4, p. 1530-1533Article in journal (Refereed)
    Abstract [en]

    Clostridium difficile PCR ribotype 027 comprised 0.2% of a collection of Swedish isolates in 1997-2001 (3 of 1,325 isolates). These isolates had lower moxifloxacin MICs than the epidemic type 027 isolates, but they had the same tcdC sequence and toxin yield. Type 027 produced 3- to 13-fold more toxin than did major Swedish types. One epidemic strain (027/NAP1a) sporulated more than did other type 027 isolates, a feature that should contribute to its survival and spread. 

  • 210.
    Önnberg, Anna
    et al.
    Departments of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    Departments of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Zimmermann, Johanna
    Departments of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences. Departments of Laboratory Medicine, Clinical Microbiology and Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Molecular and phenotypic characterization of Escherichia coli and Klebsiella pneumoniae producing extended-spectrum β-lactamases with focus on CTX-M in a low-endemic area in Sweden2011In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 119, no 4-5, p. 287-295Article in journal (Refereed)
    Abstract [en]

    During the last decade increasing prevalence of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae has been detected worldwide, mainly due to dissemination of Escherichia coli and Klebsiella pneumoniae producing CTX-M-type ESBLs. CTX-M-15 is the most widespread CTX-M type, and the predominant type in various countries. Dissemination of ESBL-producing organisms is caused not only by horizontal transfer of plasmids, but also by clonal spread of ESBL-producing strains. In this study, the molecular epidemiology of class A ESBL (ESBL(A))-producing E. coli and K. pneumoniae isolated in Örebro County, Sweden, was investigated. Out of 200 ESBL(A) -producing E. coli and K. pneumoniae isolates, collected over a 10-year period, 87% were producing CTX-M, belonging to subgroup CTX-M-1 (64%), CTX-M-9 (34%), or CTX-M-2 (2%). The remaining isolates were producing variants of SHV and TEM. Sequencing of the bla(CTX-M) genes revealed 10 different CTX-M types, with a dominance of CTX-M-15 (E. coli 54%, K. pneumoniae 50%) followed by CTX-M-14 (E. coli 28%, K. pneumoniae 27%). Phenotypic characterization of the CTX-M-producing isolates was performed using the PhenePlate system. Although a few minor clusters of CTX-M-15 and CTX-M-14 producers were identified, the majority of the isolates did not appear to be clonally related.

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