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  • 1.
    Aalto, K
    et al.
    Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland.
    Korhonen, L
    Department of Neuroscience, Neurobiology, Uppsala University, Box 587, S-75123, Uppsala, Sweden.
    Lahdenne, P
    Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland.
    Pelkonen, P
    Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland.
    Lindholm, D
    Department of Neuroscience, Neurobiology, Uppsala University, Box 587, S-75123, Uppsala, Sweden.
    Nerve growth factor in serum of children with systemic lupus erythematosus is correlated with disease activity2002In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 20, no 3, p. 136-139Article in journal (Refereed)
    Abstract [en]

    Nerve growth factor (NGF) is a neurotrophic factor, which is expressed both in the nervous system and in peripheral organs. NGF is also present in mast cells, and in B- and T-lymphocytes, and may play a role in the immune cell development and differentiation. Various cytokines have been shown to affect NGF expression, and NGF is elevated in inflammation and in some autoimmune diseases. Here we have studied NGF concentrations in serum of pediatric patients with systemic lupus erythematosus (SLE) using a two-site enzyme-linked immunosorbent assay (ELISA). We have further correlated the levels of NGF to the inflammatory state of the disease. The mean value of serum NGF in SLE patients was significantly increased compared with controls (3346 vs 627 pg/ml). There was a correlation between the activity of SLE and the levels of NGF. The results show that NGF is elevated in childhood SLE and that the levels are correlated with disease activity. The present results suggest that NGF may play a role in the pathogenesis of SLE and may have a prognostic value in evaluating the course of the disease and in outlining the medication. (C) 2002 Elsevier Science Ltd. All rights reserved.

  • 2.
    Aaseth, Jan
    et al.
    Innlandet Hosp, Norway; Inland Norway Univ Appl Sci, Norway.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Alehagen, Urban
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Tinkov, Alexey
    Yaroslavl State Univ, Russia; IM Sechenov First Moscow State Med Univ Sechenov, Russia.
    Skalny, Anatoly
    IM Sechenov First Moscow State Med Univ Sechenov, Russia; KG Razumovsky Moscow State Univ Technol & Managem, Russia.
    Larsson, Anders
    Uppsala Univ, Sweden.
    Crisponi, Guido
    Univ Cagliari, Italy.
    Nurchi, Valeria Marina
    Univ Cagliari, Italy.
    The Aging Kidney - As Influenced by Heavy Metal Exposure and Selenium Supplementation2021In: Biomolecules, E-ISSN 2218-273X, Vol. 11, no 8, article id 1078Article, review/survey (Refereed)
    Abstract [en]

    The aging process in the kidneys has been well studied. It is known that the glomerular filtration rate (GFR) declines with age in subjects older than 50-60 years. However, there is still insufficient knowledge regarding the response of the aged kidney to environmental toxicants such as mercury, cadmium, and lead. Here, we present a review on the functional decline and proposed mechanisms in the aging kidney as influenced by metal pollutants. Due to the prevalence of these toxicants in the environment, human exposure is nearly unavoidable. Further, it is well known that acute and chronic exposures to toxic metals may be detrimental to kidneys of normal adults, thus it may be hypothesized that exposure of individuals with reduced GFR will result in additional reductions in renal function. Individuals with compromised renal function, either from aging or from a combination of aging and disease, may be particularly susceptible to environmental toxicants. The available data appear to show an association between exposure to mercury, cadmium and/or lead and an increase in incidence and severity of renal disease in elderly individuals. Furthermore, some physiological thiols, as well as adequate selenium status, appear to exert a protective action. Further studies providing improved insight into the mechanisms by which nephrotoxic metals are handled by aging kidneys, as well as possibilities of therapeutic protection, are of utmost importance.

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  • 3.
    Aaseth, Jan
    et al.
    Innlandet Hospital Trust, Norway; Hedmark University of Appl Science, Norway.
    Alexander, Jan
    Norwegian Institute Public Heatlh, Norway; Norwegian University of Life Science NMBU, Norway.
    Bjorklund, Geir
    Council Nutr and Environm Med, Norway.
    Hestad, Knut
    Innlandet Hospital Trust, Norway; Hedmark University of Appl Science, Norway.
    Dusek, Petr
    Charles University of Prague, Czech Republic; Charles University of Prague, Czech Republic; Gen University Hospital Prague, Czech Republic.
    Roos, Per M.
    Karolinska Institute, Sweden; St Goran Hospital, Sweden.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Treatment strategies in Alzheimers disease: a review with focus on selenium supplementation2016In: Biometals, ISSN 0966-0844, E-ISSN 1572-8773, Vol. 29, no 5, p. 827-839Article in journal (Refereed)
    Abstract [en]

    Alzheimers disease (AD) is a neurodegenerative disorder presenting one of the biggest healthcare challenges in developed countries. No effective treatment exists. In recent years the main focus of AD research has been on the amyloid hypothesis, which postulates that extracellular precipitates of beta amyloid (A beta) derived from amyloid precursor protein (APP) are responsible for the cognitive impairment seen in AD. Treatment strategies have been to reduce A beta production through inhibition of enzymes responsible for its formation, or to promote resolution of existing cerebral A beta plaques. However, these approaches have failed to demonstrate significant cognitive improvements. Intracellular rather than extracellular events may be fundamental in AD pathogenesis. Selenate is a potent inhibitor of tau hyperphosphorylation, a critical step in the formation of neurofibrillary tangles. Some selenium (Se) compounds e.g. selenoprotein P also appear to protect APP against excessive copper and iron deposition. Selenoproteins show anti-inflammatory properties, and protect microtubules in the neuronal cytoskeleton. Optimal function of these selenoenzymes requires higher Se intake than what is common in Europe and also higher intake than traditionally recommended. Supplementary treatment with N-acetylcysteine increases levels of the antioxidative cofactor glutathione and can mediate adjuvant protection. The present review discusses the role of Se in AD treatment and suggests strategies for AD prevention by optimizing selenium intake, in accordance with the metal dysregulation hypothesis. This includes in particular secondary prevention by selenium supplementation to elderly with mild cognitive impairment.

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  • 4.
    Abate, Ebba
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. University of Gondar, Ethiopia.
    Belayneh, Meseret
    University of Addis Ababa, Ethiopia.
    Idh, Jonna
    Vastervik Hospital, Sweden.
    Diro, Ermias
    University of Gondar, Ethiopia.
    Elias, Daniel
    University of Southern Denmark, Denmark.
    Britton, Sven
    Karolinska Hospital, Sweden.
    Aseffa, Abraham
    Armauer Hansen Research Institute, Ethiopia.
    Stendahl, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Kalmar County Hospital, Sweden.
    Asymptomatic Helminth Infection in Active Tuberculosis Is Associated with Increased Regulatory and Th-2 Responses and a Lower Sputum Smear Positivity2015In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 9, no 8, article id e0003994Article in journal (Refereed)
    Abstract [en]

    Background The impact of intestinal helminth infection on the clinical presentation and immune response during active tuberculosis (TB) infection is not well characterized. Our aim was to investigate whether asymptomatic intestinal helminth infection alters the clinical signs and symptoms as well as the cell mediated immune responses in patients with active TB.

    Methodology Consecutive, newly diagnosed TB patients and healthy community controls (CCs) were recruited in North-west Ethiopia. TB-score, body mass index and stool samples were analyzed. Cells from HIV-negative TB patients (HIV-/TB) and from CCs were analyzed for regulatory T-cells (Tregs) and cytokine responses using flow cytometry and ELISPOT, respectively.

    Results A significantly higher ratio of helminth co-infection was observed in TB patients without HIV (Helm+/HIV-/TB) compared to HIV negative CCs, (40% (121/306) versus 28% (85/306), p = 0.003). Helm+/HIV-/TB patients showed significantly increased IL-5 secreting cells compared to Helm-/HIV-/TB (37 SFU (IQR:13-103) versus 2 SFU (1-50); p = 0.02, n = 30). Likewise, levels of absolute Tregs (9.4 (3.2-16.7) cells/mu l versus 2.4 (1.1-4.0) cells/mu l; p = 0.041) and IL-10 secreting cells (65 SFU (7-196) versus 1 SFU (0-31); p = 0.014) were significantly higher in Helm+/HIV-/TB patients compared to Helm-/HIV-/TB patients. In a multivariate analysis, a lower rate of sputum smear positivity for acid fast bacilli, lower body temperature, and eosinophilia were independently associated with helminth infection in TB patients.

    Conclusions Asymptomatic helminth infection is associated with increased regulatory T-cell and Th2-type responses and a lower rate of sputum smear positivity. Further studies are warranted to investigate the clinical and immunological impact of helminth infection in TB patients.

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  • 5.
    Abbas, Zaheer
    et al.
    Beijing Univ Chem Technol, Peoples R China.
    Soomro, Razium Ali
    Beijing Univ Chem Technol, Peoples R China; Beijing Univ Chem Technol, Peoples R China.
    Kalwar, Nazar Hussain
    Shah Abdul Latif Univ Khairpur, Pakistan.
    Tunesi, Mawada
    Beijing Univ Chem Technol, Peoples R China.
    Willander, Magnus
    Linköping University, Department of Science and Technology, Physics, Electronics and Mathematics. Linköping University, Faculty of Science & Engineering.
    Karakus, Selcan
    Istanbul Univ Cerrahpa Avcilar, Turkey.
    Kilislioglu, Ayben
    Istanbul Univ Cerrahpa Avcilar, Turkey.
    In Situ Growth of CuWO4 Nanospheres over Graphene Oxide for Photoelectrochemical (PEC) Immunosensing of Clinical Biomarker2020In: Sensors, E-ISSN 1424-8220, SENSORS, Vol. 20, no 1, article id 148Article in journal (Refereed)
    Abstract [en]

    Procalcitonin (PCT) protein has recently been identified as a clinical marker for bacterial infections based on its better sepsis sensitivity. Thus, an increased level of PCT could be linked with disease diagnosis and therapeutics. In this study, we describe the construction of the photoelectrochemical (PEC) PCT immunosensing platform based on it situ grown photo-active CuWO4 nanospheres over reduced graphene oxide layers (CuWO4@rGO). The in situ growth strategy enabled the formation of small nanospheres (diameter of 200 nm), primarily composed of tiny self-assembled CuWO4 nanoparticles (2-5 nm). The synergic coupling of CuWO4 with rGO layers constructed an excellent photo-active heterojunction for photoelectrochemical (PEC) sensing. The platform was then considered for electrocatalytic (EC) mechanism-based detection of PCT, where inhibition of the photocatalytic oxidation signal of ascorbic acid (AA), subsequent to the antibody-antigen interaction, was recorded as the primary signal response. This inhibition detection approach enabled sensitive detection of PCT in a concentration range of 10 pgmL(-1) to 50 ng.mL(-1) with signal sensitivity achievable up to 0.15 pgmL(-1). The proposed PEC hybrid (CuWO4@rGO) could further be engineered to detect other clinically important species.

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  • 6.
    Abbass, Allan
    et al.
    Dalhousie University, Canada.
    Bernier, Denise
    Dalhousie University, Canada.
    Kisely, Steve
    University of Queensland, Australia.
    Town, Joel
    Dalhousie University, Canada.
    Johansson, Robert
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Dalhousie University, Canada.
    Sustained reduction in health care costs after adjunctive treatment of graded intensive short-term dynamic psychotherapy in patients with psychotic disorders2015In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 228, no 3, p. 538-543Article in journal (Refereed)
    Abstract [en]

    The aim of this pilot study was to evaluate the changes in symptom severity and long-term health care cost after intensive short-term dynamic psychotherapy (ISTDP) individually tailored and administered to patients with psychotic disorders undergoing standard psychiatric care. Eleven therapists with different levels of expertise delivered an average of 13 one-hour sessions of graded ISTDP to 38 patients with psychotic disorders. Costs for health care services were compiled for a one-year period prior to the start of ISTDP (baseline) along with four one-year periods after termination. Two validated self-report scales, the Brief Symptom Inventory and the Inventory of Interpersonal Problems, were administered at intake and termination of ISTDP. Results revealed that health care cost reductions were significant for the one-year post-treatment period relative to baseline year, for both physician costs and hospital costs, and the reductions were sustained for the follow-up period of four post-treatment years. Furthermore, at treatment termination self-reported symptoms and interpersonal problems were significantly reduced. These preliminary findings suggest that this brief adjunctive psychotherapy may be beneficial and reduce costs in selected patients with psychotic disorders, and that gains are sustained in long-term follow-up. Future research directions are discussed. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

  • 7.
    Abbass, Allan
    et al.
    Dalhousie University, Canada.
    Johansson, Robert
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Rasic, Daniel
    Dalhousie University, Canada.
    Town, Joel M.
    Dalhousie University, Canada.
    Johansson, Robert
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Long-term healthcare cost reduction with Intensive Short-term Dynamic Psychotherapy in a tertiary psychiatric service2015In: Journal of Psychiatric Research, ISSN 0022-3956, E-ISSN 1879-1379, Vol. 64, p. 114-120Article in journal (Refereed)
    Abstract [en]

    Objective: To evaluate whether a mixed population of patients treated with Intensive Short-term Dynamic Psychotherapy (ISTDP) would exhibit reduced healthcare costs in long-term follow-up. Methods: A quasi-experimental design was employed in which data on pre- and post-treatment healthcare cost were compared for all ISTDP cases treated in a tertiary care service over a nine year period. Observed cost changes were compared with those of a control group of patients referred but never treated. Physician and hospital costs were compared to treatment cost estimates and normal population cost figures. Results: 1082 patients were included; 890 treated cases for a broad range of somatic and psychiatric disorders and 192 controls. The treatment averaged 7.3 sessions and measures of symptoms and interpersonal problems significantly improved. The average cost reduction per treated case was $12,628 over 3 follow-up years: this compared favorably with the estimated treatment cost of $708 per patient. Significant differences were seen between groups for follow-up hospital costs. Conclusions: ISTDP in this setting appears to facilitate reductions in healthcare costs, supporting the notion that brief dynamic psychotherapy provided in a tertiary setting can be beneficial to health care systems overall. (C) 2015 Elsevier Ltd. All rights reserved.

  • 8.
    Abelius, Martina S
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Janefjord, Camilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Matthiesen, Leif
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Helsingborg Hospital, Helsingborg.
    Duchén, Karel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Nilsson, Lennart J
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    The Placental Immune Milieu is Characterized by a Th2- and Anti-Inflammatory Transcription Profile, Regardless of Maternal Allergy, and Associates with Neonatal Immunity2015In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 73, no 5, p. 445-459Article in journal (Refereed)
    Abstract [en]

    PROBLEM: How maternal allergy affects the systemic and local immunological environment during pregnancy and the immune development of the offspring is unclear.

    METHOD OF STUDY: Expression of 40 genes was quantified by PCR arrays in placenta, peripheral blood mononuclear cells (PBMC), and cord blood mononuclear cells (CBMC) from 7 allergic and 12 non-allergic women and their offspring.

    RESULTS: Placental gene expression was dominated by a Th2-/anti-inflammatory profile, irrespectively of maternal allergy, as compared to gene expression in PBMC. p35 expression in placenta correlated with fetal Tbx21 (ρ = -0.88, P < 0.001) and IL-5 expression in PBMC with fetal galectin1 (ρ = 0.91, P < 0.001). Increased expression of Th2-associated CCL22 in CBMC preceded allergy development.

    CONCLUSIONS: Gene expression locally and systemically during pregnancy was partly associated with the offspring's gene expression, possibly indicating that the immunological milieu is important for fetal immune development. Maternal allergy was not associated with an enhanced Th2 immunity in placenta or PBMC, while a marked prenatal Th2 skewing, shown as increased CCL22 mRNA expression, might contribute to postnatal allergy development.

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  • 9.
    Abrahamsson, Annelie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Rzepecka, Anna
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Dabrosin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Equal Pro-inflammatory Profiles of CCLs, CXCLs, and Matrix Metalloproteinases in the Extracellular Microenvironment In Vivo in Human Dense Breast Tissue and Breast Cancer2018In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 8, article id 1994Article in journal (Refereed)
    Abstract [en]

    The inflammatory microenvironment affects breast cancer progression. Proteins that govern the inflammatory response are secreted into the extracellular space, but this compartment still needs to be characterized in human breast tissues in vivo. Dense breast tissue is a major risk factor for breast cancer by yet unknown mechanisms and no non-toxic prevention for these patients exists. Here, we used the minimal invasive technique of microdialysis for sampling of extracellular proteins in live tissues in situ in breast cancers of women before surgery and in healthy women having dense or non-dense breast tissue on mammography. Proteins were profiled using a proximity extension assay. Out of the 32 proteins assessed, 26 exhibited similar profiles in breast cancers and dense breast tissues; CCL-4, -7, -8, -11, -15, -16, -22, -23, and -25, CXCL-5, -8, -9, -16 as well as sIL-6R, IL-18, vascular endothelial growth factor, TGF-a, fibroblast growth factor 19, matrix metalloproteinase (MMP)-1, -2, -3, and urokinase-type plasminogen activator were all increased, whereas CCL-3, CX3CL1, hepatocyte growth factor, and MMP-9 were unaltered in the two tissues. CCL-19 and -24, CXCL-1 and -10, and IL-6 were increased in dense breast tissue only, whereas IL-18BP was increased in breast cancer only. Our results provide novel insights in the inflammatory microenvironment in human breast cancer in situ and define potential novel therapeutic targets. Additionally, we show previously unrecognized similarities of the pro-inflammatory microenvironment in dense breast tissue and breast cancer in vivo suggesting that anti-inflammatory breast cancer prevention trials for women with dense breast tissue may be feasible.

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  • 10.
    Abrahamsson, Thomas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Jakobsson, H.E.
    Karolinska Institute, Stockholm, Sweden.
    Andersson, A.F.
    KTH Royal Institute of Technology, Stockholm, Sweden.
    Björksten, B.
    Karolinska Institute, Stockholm, Sweden; Örebro University, Sweden .
    Engstrand, L.
    Karolinska Institute, Stockholm, Sweden; KTH Royal Institute of Technology, Stockholm, Sweden.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Low gut microbiota diversity in early infancy precedes asthma at school age2014In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 44, no 6, p. 842-850Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Low total diversity of the gut microbiota during the first year of life is associated with allergic diseases in infancy, but little is known how early microbial diversity is related to allergic disease later in school age.

    OBJECTIVE:

    To assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to the prevalence of different allergic diseases in school age, such as asthma, allergic rhinoconjunctivitis (ARC) and eczema.

    METHODS:

    The microbial diversity and composition was analysed with barcoded 16S rDNA 454 pyrosequencing in stool samples at 1 week, 1 month and 12 months of age in 47 infants which were subsequently assessed for allergic disease and skin prick test reactivity at 7 years of age (ClinicalTrials.gov ID NCT01285830).

    RESULTS:

    Children developing asthma (n = 8) had a lower diversity of the total microbiota than non-asthmatic children at 1 week (P = 0.04) and 1 month (P = 0.003) of age, whereas allergic rhinoconjunctivitis (n = 13), eczema (n = 12) and positive skin prick reactivity (n = 14) at 7 years of age did not associate with the gut microbiota diversity. Neither was asthma associated with the microbiota composition later in infancy (at 12 months). Children having IgE-associated eczema in infancy and subsequently developing asthma had lower microbial diversity than those that did not. There were no significant differences, however, in relative abundance of bacterial phyla and genera between children with or without allergic disease.

    CONCLUSION AND CLINICAL RELEVANCE:

    Low total diversity of the gut microbiota during the first month of life was associated with asthma but not ARC in children at 7 years of age. Measures affecting microbial colonization of the infant during the first month of life may impact asthma development in childhood.

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  • 11.
    Abrahamsson, Thomas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Sherman, Philip M.
    University of Toronto, Canada .
    Editorial Material: Multifaceted Effects of Human Milk Oligosaccharides2014In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 209, no 3, p. 323-324Article in journal (Other academic)
    Abstract [en]

    n/a

  • 12.
    Abrahamsson, Thomas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping. University of Toronto, Canada.
    You Wu, Richard
    University of Toronto, Canada.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Gut microbiota and allergy: the importance of the pregnancy period2015In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 77, no 1, p. 214-219Article, review/survey (Refereed)
    Abstract [en]

    Limited microbial exposure is suggested to underlie the increase of allergic diseases in affluent countries, and bacterial diversity seems to be more important than specific bacteria taxa. Prospective studies indicate that the gut microbiota composition during the first months of life influences allergy development, and support the theory that factors influencing the early maturation of the immune system might be important for subsequent allergic disease. However, recent research indicates that microbial exposure during pregnancy may be even more important for the preventative effects against allergic disease. This review gives a background of the epidemiology, immunology, and microbiology literature in this field. It focuses on possible underlying mechanisms such as immune-regulated epigenetic imprinting and bacterial translocation during pregnancy, potentially providing the offspring with a pioneer microbiome. We suggest that a possible reason for the initial exposure of bacterial molecular patterns to the fetus in utero is to prime the immune system and/or the epithelium to respond appropriately to pathogens and commensals after birth.

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  • 13.
    Acevedo, Juan Pablo
    et al.
    Univ Los Andes, Chile; Cells Cells, Chile.
    Angelopoulos, Ioannis
    Univ Los Andes, Chile; Cells Cells, Chile.
    van Noort, Danny
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering. Univ Los Andes, Chile.
    Khoury, Maroun
    Univ Los Andes, Chile; Cells Cells, Chile; Consorcio Regenero, Chile.
    Microtechnology applied to stem cells research and development2018In: Regenerative Medicine, ISSN 1746-0751, E-ISSN 1746-076X, Vol. 13, no 2, p. 233-248Article, review/survey (Refereed)
    Abstract [en]

    Microfabrication and microfluidics contribute to the research of cellular functions of cells and their interaction with their environment. Previously, it has been shown that microfluidics can contribute to the isolation, selection, characterization and migration of cells. This review aims to provide stem cell researchers with a toolkit of microtechnology (mT) instruments for elucidating complex stem cells functions which are challenging to decipher with traditional assays and animal models. These microdevices are able to investigate about the differentiation and niche interaction, stem cells transcriptomics, therapeutic functions and the capture of their secreted microvesicles. In conclusion, microtechnology will allow a more realistic assessment of stem cells properties, driving and accelerating the translation of regenerative medicine approaches to the clinic.

  • 14.
    Ackerley, Rochelle
    et al.
    Aix Marseille Univ, France.
    Croy, Ilona
    Tech Univ Dresden, Germany.
    Olausson, Håkan
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Badre, Gaby
    Gothenburg Univ, Sweden.
    Investigating the Putative Impact of Odors Purported to Have Beneficial Effects on Sleep: Neural and Perceptual Processes2020In: Chemosensory Perception, ISSN 1936-5802, E-ISSN 1936-5810, Vol. 13, no 2, p. 93-105Article in journal (Refereed)
    Abstract [en]

    Introduction Olfaction has an important role in physiological and affective processes, as well as the potential to have profound effects on activities such as sleep and learning. We investigated two commercially manufactured odors ("Deep Sleep" and "Oriental," from This Works) purported to promote sleep, compared with control odor, where we aimed to explore whether neural and behavioral differences existed after odor inhalation. Methods In a neuroimaging study, 30 healthy participants were exposed to the odors via an olfactometer during functional magnetic resonance imaging (fMRI). In a further behavioral study using 12 chronic insomniacs, we investigated whether the commercial odors showed effects on sleep during a double-blind, randomized home evaluation. Results In the neuroimaging, the odors were related to activation of olfactory-relevant areas, such as the orbitofrontal cortex, and we found positive connectivity between the piriform cortex and the hippocampus, amygdala, insula, and middle cingulate cortex. Deep Sleep specifically activated the superior temporal gyrus, whereas Oriental activated the caudate. Further, these commercial odors showed some beneficial impact on sleep. Conclusions The perceptual and neural impacts of the commercial odors showed that olfactory stimulation can potentially aid sleep and modify affective processes in a number of ways. Implications The present work opens up opportunities for further investigations into how different odors may lead to specific behavioral and physiological modifications, such as their impact on sleep and well-being, which may provide non-pharmacological alternative approaches.

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  • 15.
    Adolfsson, Emma
    et al.
    Orebro Univ Hosp, Sweden; Orebro Univ, Sweden.
    Qvick, Alvida
    Orebro Univ Hosp, Sweden; Orebro Univ, Sweden.
    Green, Henrik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Kling, Daniel
    Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Gunnarsson, Cecilia
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics. Region Östergötland, Regionledningskontoret, Övr Regionledningskontoret.
    Jonasson, Jon
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics. Orebro Univ Hosp, Sweden.
    Green, Anna
    Orebro Univ Hosp, Sweden; Orebro Univ, Sweden.
    Technical in-depth comparison of two massive parallel DNA-sequencing methods for formalin-fixed paraffin-embedded tissue from victims of sudden cardiac death2021In: Forensic Science International: Genetics, ISSN 1872-4973, E-ISSN 1878-0326, Vol. 53, article id 102522Article in journal (Refereed)
    Abstract [en]

    Sudden cardiac death (SCD) is a tragic and traumatic event. SCD is often associated with hereditary genetic disease and in such cases, sequencing of stored formalin fixed paraffin embedded (FFPE) tissue is often crucial in trying to find a causal genetic variant. This study was designed to compare two massive parallel sequencing assays for differences in sensitivity and precision regarding variants related to SCD in FFPE material. From eight cases of SCD where DNA from blood had been sequenced using HaloPlex, corresponding FFPE samples were collected six years later. DNA from FFPE samples were amplified using HaloPlex HS, sequenced on MiSeq, representing the first method, as well as amplified using modified Twist and sequenced on NextSeq, representing the second method. Molecular barcodes were included to distinguish artefacts from true variants. In both approaches, read coverage, uniformity and variant detection were compared using genomic DNA isolated from blood and corresponding FFPE tissue, respectively. In terms of coverage uniformity, Twist performed better than HaloPlex HS for FFPE samples. Despite higher overall coverage, amplicon-based HaloPlex technologies, both for blood and FFPE tissue, suffered from design and/or performance issues resulting in genes lacking complete coverage. Although Twist had considerably lower overall mean coverage, high uniformity resulted in equal or higher fraction of genes covered at &gt;= 20X. By comparing variants found in the matched samples in a pre-defined cardiodiagnostic gene panel, HaloPlex HS for FFPE material resulted in high sensitivity, 98.0% (range 96.6-100%), and high precision, 99.9% (range 99.5-100%) for moderately fragmented samples, but suffered from reduced sensitivity (range 74.2-91.1%) in more severely fragmented samples due to lack of coverage. Twist had high sensitivity, 97.8% (range 96.8-98.7%) and high precision, 99.9% (range 99.3-100%) in all analyzed samples, including the severely fragmented samples.

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  • 16.
    Adolfsson, Per I
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Bloth, Björn
    Department of Clinical Neuroscience, Laboratory of Translational Neuropharmacology, Center of Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Futurum Academy for Health and Care, Jönköping County Council, Sweden.
    Svensson, Samuel P S
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Zinc Induces a Bell-shaped Proliferative Dose-response Effect in Cultured Smooth Muscle Cells From Benign Prostatic Hyperplasia.2015In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 85, no 3, p. 704.e15-704.e19Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the effects of zinc (Zn(2+)) concentrations on cultured benign prostatic hyperplasia (BPH) smooth muscle cell (SMC) proliferation.

    METHODS: The effects of Zn(2+) were studied in primary cultures of human BPH SMC, stimulated with either 10-μM lysophosphatidic acid (LPA) or LPA in combination with 100-nM testosterone. Deoxyribonucleic acid replication and protein synthesis using [(3)H]-thymidine and [(35)S]-methionine incorporation were measured. Furthermore, studies were performed to evaluate if Zn(2+) could potentiate the inhibitory effect of phosphodiesterase-5 blockers, on BPH SMC proliferation.

    RESULTS: Zn(2+) generated a bell-shaped concentration response, both regarding deoxyribonucleic acid replication and protein synthesis in cultured BPH SMC. Below a threshold value (approximately 200 μM), a significant mitogenic effect was seen, whereas higher concentrations inhibited SMC proliferation after stimulation with LPA. This effect was even more pronounced after stimulation of LPA in combination with testosterone. Moreover, phosphodiesterase-5 inhibitors, that is, sildenafil blocked LPA-stimulated BPH SMC proliferation. This antiproliferative effect, was significantly potentiated by coincubation with Zn(2+) in an additative manner.

    CONCLUSION: The bell-shaped concentration response of Zn(2+) on cultured BPH SMC proliferation suggests that changes in prostate Zn(2+) concentrations, during aging, diet, or inflammatory conditions, may be of importance in the pathogenesis of BPH.

  • 17.
    Adori, Csaba
    et al.
    Karolinska Inst, Sweden.
    Daraio, Teresa
    Karolinska Inst, Sweden.
    Kuiper, Raoul
    Karolinska Inst, Sweden.
    Barde, Swapnali
    Karolinska Inst, Sweden.
    Horvathova, Lubica
    Slovak Acad Sci, Slovakia.
    Yoshitake, Takashi
    Karolinska Inst, Sweden.
    Ihnatko, Robert
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Georg August Univ Gottingen, Germany.
    Valladolid-Acebes, Ismael
    Karolinska Inst, Sweden.
    Vercruysse, Pauline
    Karolinska Inst, Sweden.
    Wellendorf, Ashley M.
    Cincinnati Childrens Hosp Med Ctr, OH 45229 USA.
    Gramignoli, Roberto
    Karolinska Inst, Sweden.
    Bozoky, Bela
    Karolinska Univ Hosp, Sweden.
    Kehr, Jan
    Karolinska Inst, Sweden.
    Theodorsson, Elvar
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Cancelas, Jose A.
    Cincinnati Childrens Hosp Med Ctr, OH 45229 USA; Univ Cincinnati, OH 45267 USA.
    Mravec, Boris
    Slovak Acad Sci, Slovakia; Comenius Univ, Slovakia.
    Jorns, Carl
    Karolinska Univ Hosp Huddinge, Sweden.
    Ellis, Ewa
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Mulder, Jan
    Karolinska Inst, Sweden.
    Uhlen, Mathias
    Karolinska Inst, Sweden; Royal Inst Technol, Sweden.
    Bark, Christina
    Karolinska Inst, Sweden.
    Hökfelt, Tomas
    Karolinska Inst, Sweden.
    Disorganization and degeneration of liver sympathetic innervations in nonalcoholic fatty liver disease revealed by 3D imaging2021In: Science Advances, E-ISSN 2375-2548, Vol. 7, no 30, article id eabg5733Article in journal (Refereed)
    Abstract [en]

    Hepatic nerves have a complex role in synchronizing liver metabolism. Here, we used three-dimensional (3D) immunoimaging to explore the integrity of the hepatic nervous system in experimental and human nonalcoholic fatty liver disease (NAFLD). We demonstrate parallel signs of mild degeneration and axonal sprouting of sympathetic innervations in early stages of experimental NAFLD and a collapse of sympathetic arborization in steatohepatitis. Human fatty livers display a similar pattern of sympathetic nerve degeneration, correlating with the severity of NAFLD pathology. We show that chronic sympathetic hyperexcitation is a key factor in the axonal degeneration, here genetically phenocopied in mice deficient of the Rac-1 activator Vav3. In experimental steatohepatitis, 3D imaging reveals a severe portal vein contraction, spatially correlated with the extension of the remaining nerves around the portal vein, enlightening a potential intrahepatic neuronal mechanism of portal hypertension. These fundamental alterations in liver innervation and vasculature uncover previously unidentified neuronal components in NAFLD pathomechanisms.

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  • 18.
    Adua, Eric
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Oteng Danso, Frank
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Mensah Boa-Amponsem, Oswald
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Adusei-Mensah, Frank
    University of Cape Coast, Ghana.
    Effect of Neutrophils on Nitric Oxide Production from Stimulated Macrophages2015In: Iranian Journal of Immunology, ISSN 1735-1383, E-ISSN 1735-367X, Vol. 12, no 2, p. 94-103Article in journal (Refereed)
    Abstract [en]

    Background: During the initial phase of an infection, there is an upregulation of inducible nitric oxide synthase in the macrophages for the production of nitric oxide. This is followed by the recruitment of polymorphonuclear leukocytes (neutrophils) which release arginase. Arginase competes with inducible nitric oxide synthase for a common substrate L-arginine. Objective: To investigate whether the entry of neutrophils and release of arginase can interfere with nitric oxide production from stimulated mouse macrophages. Methods: Neutrophils were isolated from human blood and stimulated with cytodex-3 beads. Cultured macrophages were stimulated with lipopolysaccharide and interferon gamma with or without N (G)-nitro-L-arginine methyl ester or N (omega)-hydroxy-nor-L-arginine. Measurement of NO2-/NO3- and urea were done using the spectrophotometer. Results: A significantly higher level of nitric oxide production from stimulated macrophages was observed compared to control. There was a decrease in nitric oxide production when stimulated macrophages were treated with the supernatant from activated neutrophils (pless than0.05). Conclusion: Arginase from neutrophils can modulate nitric oxide production from activated macrophages which may affect the course of infection by intracellular bacteria.

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  • 19.
    Agalave, Nilesh M
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Max
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Abdelmoaty, Sally
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Su, Jie
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Baharpoor, Azar
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Lundbäck, Peter
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Palmblad, Karin
    Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.
    Andersson, Ulf
    Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.
    Harris, Helena
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Svensson, Camilla I
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Spinal HMGB1 induces TLR4-mediated long-lasting hypersensitivity and glial activation and regulates pain-like behavior in experimental arthritis.2014In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 155, no 9, p. 1802-1813Article in journal (Refereed)
    Abstract [en]

    Extracellular high mobility group box-1 protein (HMGB1) plays important roles in the pathogenesis of nerve injury- and cancer-induced pain. However, the involvement of spinal HMGB1 in arthritis-induced pain has not been examined previously and is the focus of this study. Immunohistochemistry showed that HMGB1 is expressed in neurons and glial cells in the spinal cord. Subsequent to induction of collagen antibody-induced arthritis (CAIA), Hmgb1 mRNA and extranuclear protein levels were significantly increased in the lumbar spinal cord. Intrathecal (i.t.) injection of a neutralizing anti-HMGB1 monoclonal antibody or recombinant HMGB1 box A peptide (Abox), which each prevent extracellular HMGB1 activities, reversed CAIA-induced mechanical hypersensitivity. This occurred during ongoing joint inflammation as well as during the postinflammatory phase, indicating that spinal HMGB1 has an important function in nociception persisting beyond episodes of joint inflammation. Importantly, only HMGB1 in its partially oxidized isoform (disulfide HMGB1), which activates toll-like receptor 4 (TLR4), but not in its fully reduced or fully oxidized isoforms, evoked mechanical hypersensitivity upon i.t. injection. Interestingly, although both male and female mice developed mechanical hypersensitivity in response to i.t. HMGB1, female mice recovered faster. Furthermore, the pro-nociceptive effect of i.t. injection of HMGB1 persisted in Tlr2- and Rage-, but was absent in Tlr4-deficient mice. The same pattern was observed for HMGB1-induced spinal microglia and astrocyte activation and cytokine induction. These results demonstrate that spinal HMGB1 contributes to nociceptive signal transmission via activation of TLR4 and point to disulfide HMGB1 inhibition as a potential therapeutic strategy in treatment of chronic inflammatory pain.

  • 20.
    Agholme, Lotta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Getting rid of intracellular Aβ- loss of cellular degradation leads to transfer between connected neurons2014In: Current pharmaceutical design, ISSN 1381-6128, E-ISSN 1873-4286, Vol. 20, no 15, p. 2458-2468Article in journal (Refereed)
    Abstract [en]

    The sporadic, late onset form of Alzheimers disease (AD) shares pathological hallmarks with the familial form; however, no clear reason for increased beta-amyloid (A beta) generation has been found in the former. It has long been speculated that the late onset form of AD is caused by reduced degradation and/or clearance of A beta. Indeed, both intracellular degradation systems, the proteasomal and lysosomal systems, have been shown to be defective in AD. Reduced proteasome activity increases levels of intracellular and secreted A beta. Furthermore, accumulation of improperly degraded A beta in the lysosomes causes lysosomal disruption and cell death. We recently showed that oligomeric A beta can be transmitted from one neuron to another, which causes neurotoxicity. In both the donating and receiving cells, A beta accumulates in the endo-lysosomal compartment. It is possible that ineffective degradation of A beta causes its transfer to neighboring neurons, thereby spreading AD pathology. This review summarizes the data underlying the idea of reduced A beta clearance and subsequent A beta spread in AD, and also suggests new therapeutic methods, which are aimed at targeting the degradation systems and synaptic transfer. By enhancing degradation of intracellular accumulated A beta, it can be possible to remove it and avoid A beta-induced neurodegeneration without disturbing the endogenously important pool of secreted A beta. Additionally, drugs targeted to inhibit the spread of intracellular toxic A beta aggregates may also be useful in stopping the progression of pathology, without affecting the level of A beta that normally occurs in the brain.

  • 21.
    Agnvall, Beatrix
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Bélteky, Johan
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Brain size is reduced by selectionfor tameness in Red Junglefowl–correlated effects in vital organs2017In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, article id 3306Article in journal (Refereed)
    Abstract [en]

    During domestication animals have undergone changes in size of brain and other vital organs. We hypothesize that this could be a correlated effect to increased tameness. Red Junglefowl (ancestors of domestic chickens) were selected for divergent levels of fear of humans for five generations. The parental (P0) and the fifth selected generation (S5) were culled when 48–54 weeks old and the brains were weighed before being divided into telencephalon, cerebellum, mid brain and optic lobes. Each single brain part as well as the liver, spleen, heart and testicles were also weighed. Brains of S5 birds with high fear scores (S5 high) were heavier both in absolute terms and when corrected for body weight. The relative weight of telencephalon (% of brain weight) was significantly higher in S5 high and relative weight of cerebellum was lower. Heart, liver, testes and spleen were all relatively heavier (% of body weight) in S5 high. Hence, selection for tameness has changed the size of the brain and other vital organs in this population and may have driven the domesticated phenotype as a correlated response.

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  • 22.
    Agreus, Lars
    et al.
    Institutionen för neurobiologi, vårdvetenskap och samhälle, Karolinska institutet, Stockholm, Sverige; Öregrunds vårdcentral, Sverige.
    Borgquist, Lars
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Tsoposidis, Alexandros
    Avdelningen för kirurgi, institutionen för kliniska vetenskaper, Göteborgs universitet, Sverige; Sahlgrenska universitetssjukhuset/Östra, Göteborg, Sverige.
    Wallenius, Ville
    Avdelningen för kirurgi, institutionen för kliniska vetenskaper, Göteborgs universitet, Sverige; Sahlgrenska universitetssjukhuset/Östra, Göteborg, Sverige.
    Kostic, Srdjan
    Avdelningen för kirurgi, institutionen för kliniska vetenskaper, Göteborgs universitet, Sverige; Sahlgrenska universitetssjukhuset/Östra, Göteborg, Sverige.
    Lundell, Lars
    Avdelningen för kirurgi, CLINTEC, Karolinska institutet, Stockholm, Sverige.
    Lindberg, Greger
    Institutionen för medicin Huddinge, Karolinska institutet, Sverige; PF mag- och tarmsjukdomar, Karolinska universitetssjukhuset, Stockholm, Sverige.
    Stor överförskrivning och ökat bruk av protonpumpshämmare: Utbildning och information är en nyckel till att vägleda läkare och allmänhet till rätt användning [Significant over- and misuse of PPIs]2021In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 118Article in journal (Refereed)
    Abstract [en]

    PPIs (Proton-pump inhibitors) offers the best treatment for acid related diseases. The predominant indications for PPI prescription are:

    • GERD
    • eradication of H. pylori-infection in combination with antibiotics
    • H. pylori-negative peptic ulcer 
    • healing of and prophylaxis against NSAID/COXIB--induced gastroduodenal lesions 
    • acid hypersecretory states such as Zollinger-Ellisons syndrome.

    The market for PPIs continues to expand in most countries. A significant over- and misuse of PPIs prevails in hospital care as well as in general practice. The predominant reasons for and mechanisms behind the over- and misuse of PPIs are well recognised. The most important consequences of this overprescription of PPIs are increasing medical costs and risk for long-term adverse side effects. Continued education and dedicated information are key factors to guide physicians, medical personnel and patients to adopt to generally accepted principles for and balanced use of PPIs.

  • 23.
    Aguila, Monica
    et al.
    UCL Inst Ophthalmol, England.
    Bellingham, James
    UCL Inst Ophthalmol, England.
    Athanasiou, Dimitra
    UCL Inst Ophthalmol, England.
    Bevilacqua, Dalila
    UCL Inst Ophthalmol, England.
    Duran, Yanai
    UCL Inst Ophthalmol, England.
    Maswood, Ryea
    UCL Inst Ophthalmol, England.
    Parfitt, David A.
    UCL Inst Ophthalmol, England.
    Iwawaki, Takao
    Kanazawa Med Univ, Japan.
    Spyrou, Ioannis
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences.
    Smith, Alexander J.
    UCL Inst Ophthalmol, England.
    Ali, Robin R.
    UCL Inst Ophthalmol, England.
    Cheetham, Michael E.
    UCL Inst Ophthalmol, England.
    AAV-mediated ERdj5 overexpression protects against P23H rhodopsin toxicity2020In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 29, no 8, p. 1310-1318Article in journal (Refereed)
    Abstract [en]

    Rhodopsin misfolding caused by the P23H mutation is a major cause of autosomal dominant retinitis pigmentosa (adRP). To date, there are no effective treatments for adRP. The BiP co-chaperone and reductase ERdj5 (DNAJC10) is part of the endoplasmic reticulum (ER) quality control machinery, and previous studies have shown that overexpression of ERdj5 in vitro enhanced the degradation of P23H rhodopsin, whereas knockdown of ERdj5 increased P23H rhodopsin ER retention and aggregation. Here, we investigated the role of ERdj5 in photoreceptor homeostasis in vivo by using an Erdj5 knockout mouse crossed with the P23H knock-in mouse and by adeno-associated viral (AAV) vector-mediated gene augmentation of ERdj5 in P23H-3 rats. Electroretinogram (ERG) and optical coherence tomography of Erdj5(-/-) and P23H(+/-):Erdj5(-/-) mice showed no effect of ERdj5 ablation on retinal function or photoreceptor survival. Rhodopsin levels and localization were similar to those of control animals at a range of time points. By contrast, when AAV2/8-ERdj5-HA was subretinally injected into P23H-3 rats, analysis of the full-field ERG suggested that overexpression of ERdj5 reduced visual function loss 10 weeks post-injection (PI). This correlated with a significant preservation of photoreceptor cells at 4 and 10 weeks PI. Assessment of the outer nuclear layer (ONL) morphology showed preserved ONL thickness and reduced rhodopsin retention in the ONL in the injected superior retina. Overall, these data suggest that manipulation of the ER quality control and ER-associated degradation factors to promote mutant protein degradation could be beneficial for the treatment of adRP caused by mutant rhodopsin.

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  • 24.
    Aguilar-Calvo, Patricia
    et al.
    Univ Calif San Diego, CA 92093 USA; Univ Calif San Diego, CA 92093 USA.
    Bett, Cyrus
    Univ Calif San Diego, CA 92093 USA; Univ Calif San Diego, CA 92093 USA.
    Sevillano, Alejandro M.
    Univ Calif San Diego, CA 92093 USA; Univ Calif San Diego, CA 92093 USA.
    Kurt, Timothy D.
    Univ Calif San Diego, CA 92093 USA; Univ Calif San Diego, CA 92093 USA.
    Lawrence, Jessica
    Univ Calif San Diego, CA 92093 USA; Univ Calif San Diego, CA 92093 USA.
    Soldau, Katrin
    Univ Calif San Diego, CA 92093 USA; Univ Calif San Diego, CA 92093 USA.
    Hammarström, Per
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Sigurdson, Christina J.
    Univ Calif San Diego, CA 92093 USA; Univ Calif San Diego, CA 92093 USA; Univ Calif Davis, CA USA.
    Generation of novel neuroinvasive prions following intravenous challenge2018In: Brain Pathology, ISSN 1015-6305, E-ISSN 1750-3639, Vol. 28, no 6, p. 999-1011Article in journal (Refereed)
    Abstract [en]

    Prions typically spread into the central nervous system (CNS), likely via peripheral nerves. Yet prion conformers differ in their capacity to penetrate the CNS; certain fibrillar prions replicate persistently in lymphoid tissues with no CNS entry, leading to chronic silent carriers. Subclinical carriers of variant Creutzfeldt-Jakob (vCJD) prions in the United Kingdom have been estimated at 1:2000, and vCJD prions have been transmitted through blood transfusion, however, the circulating prion conformers that neuroinvade remain unclear. Here we investigate how prion conformation impacts brain entry of transfused prions by challenging mice intravenously to subfibrillar and fibrillar strains. We show that most strains infiltrated the brain and caused terminal disease, however, the fibrillar prions showed reduced CNS entry in a strain-dependent manner. Strikingly, the highly fibrillar mCWD prion strain replicated in the spleen and emerged in the brain as a novel strain, indicating that a new neuroinvasive prion had been generated from a previously non-neuroinvasive strain. The new strain showed altered plaque morphology, brain regions targeted and biochemical properties and these properties were maintained upon intracerebral passage. Intracerebral passage of prion-infected spleen re-created the new strain. Splenic prions resembled the new strain biochemically and intracerebral passage of prion-infected spleen re-created the new strain, collectively suggesting splenic prion replication as a potential source. Taken together, these results indicate that intravenous exposure to prion-contaminated blood or blood products may generate novel neuroinvasive prion conformers and disease phenotypes, potentially arising from prion replication in non-neural tissues or from conformer selection.

  • 25.
    Ahlberg, Emelie
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Al-Kaabawi, Ahmed
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Thune, Rebecka
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Simpson, Melanie Rae
    Norwegian Univ Sci & Technol NTNU, Norway.
    Pedersen, Sindre Andre
    Norwegian Univ Sci & Technol NTNU, Norway.
    Cione, Erika
    Univ Calabria, Italy.
    Jenmalm, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Tingö, Lina
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Orebro Univ, Sweden; Orebro Univ, Sweden.
    Breast milk microRNAs: Potential players in oral tolerance development2023In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 14, article id 1154211Article, review/survey (Refereed)
    Abstract [en]

    Breast milk is an essential source of nutrition and hydration for the infant. In addition, this highly complex biological fluid contains numerous immunologically active factors such as microorganisms, immunoglobulins, cytokines and microRNAs (miRNAs). Here, we set out to predict the function of the top 10 expressed miRNAs in human breast milk, focusing on their relevance in oral tolerance development and allergy prevention in the infant. The top expressed miRNAs in human breast milk were identified on basis of previous peer-reviewed studies gathered from a recent systematic review and an updated literature search. The miRNAs with the highest expression levels in each study were used to identify the 10 most common miRNAs or miRNA families across studies and these were selected for subsequent target prediction. The predictions were performed using TargetScan in combination with the Database for Annotation, Visualization and Integrated Discovery. The ten top expressed miRNAs were: let-7-5p family, miR-148a-3p, miR-30-5p family, miR-200a-3p + miR-141-3p, miR-22-3p, miR-181-5p family, miR-146b-5p, miR-378a-3p, miR-29-3p family, miR-200b/c-3p and miR-429-3p. The target prediction identified 3,588 potential target genes and 127 Kyoto Encyclopedia of Genes and Genomes pathways; several connected to the immune system, including TGF-b and T cell receptor signaling and T-helper cell differentiation. This review highlights the role of breast milk miRNAs and their potential contribution to infant immune maturation. Indeed, breast milk miRNAs seem to be involved in several pathways that influence oral tolerance development.

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  • 26.
    Ahlberg, Emelie
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Tingö, Lina
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Orebro Univ, Sweden.
    Evaluation of five column-based isolation kits and their ability to extract miRNA from human milk2021In: Journal of Cellular and Molecular Medicine (Print), ISSN 1582-1838, E-ISSN 1582-4934, Vol. 25, no 16, p. 7973-7979Article in journal (Refereed)
    Abstract [en]

    MicroRNA can be found in various body fluids, including breast milk. MicroRNA may be transferred from mother to infant via breast milk and potentially regulate the development of the infants immune system on a post-transcriptional level. This study aimed to determine the microRNA extraction efficiency of five RNA extraction kits from human skim milk samples. Their efficiency was determined by comparing microRNA concentrations, total RNA yield and purity. Furthermore, hsa-miR-148a-3p expression and the recovery of an exogenous control, cel-miR-39-3p, were quantified using qPCR. Each kit extracted different amounts of microRNA and total RNA, with one kit tending to isolate the highest amount of both RNA species. Based on these results, the extraction kit ReliaPrep (TM) miRNA Cell and Tissue Miniprep System from Promega was found to be the most appropriate kit for microRNA extraction from human skim milk. Moreover, further research is needed to establish a standardized protocol for microRNA extraction from breast milk.

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  • 27.
    Ahlenius, Sven
    et al.
    Göteborgs universitet.
    Heimann, Mikael
    Göteborgs universitet.
    Larsson, Knut
    Göteborgs universitet.
    Prolongation of the ejaculation latency in the male rat by thioridazine and chlorimipramine.1979In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 65, no 2, p. 137-140Article in journal (Refereed)
    Abstract [en]

    Thioridazine (3 mg/kg) and chlorimipramine (1.5–6.0 mg/kg) prolonged the ejaculation latency and increased the number of mounts but did not change the number of intromissions preceding ejaculation. Blockade of peripheral and central noradrenaline receptors by phentolamine and phenoxybenzamine respectively resulted in a suppression of all aspects of the sexual behavior with increasing doses. dl-5-HTP (25–100 mg/kg) in combination with an inhibitor of peripheral 5-HTP decarboxylase (benserazide, 25 mg/kg) produced, like chlorimipramine and thioridazine, a prolongation of ejaculation latency and an increase in the number of mounts preceding ejaculation. Selective inhibition of 5-HT reuptake however, by zimelidine (0–20 mg/kg) or alaproclate (0–20 mg/kg) did not affect the mating behavior. At higher doses of these drugs some animals failed to initiate sexual activities. There was an increase in the postejaculatory interval but no change in the ejaculatory latency.It is concluded that the prolonged ejaculation latencies observed following treatment with thioridazine or chlorimipramine is not due to a blockade of central or peripheral adrenergic -receptors.

  • 28.
    Ahlner, Alexandra
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Biotechnology. Linköping University, The Institute of Technology.
    Carlsson, Mats
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Biotechnology. Linköping University, The Institute of Technology.
    Jonsson, Bengt-Harald
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Biotechnology. Linköping University, The Institute of Technology.
    Lundström, Patrik
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Biotechnology. Linköping University, The Institute of Technology.
    PINT: a software for integration of peak volumes and extraction of relaxation rates2013In: Journal of Biomolecular NMR, ISSN 0925-2738, E-ISSN 1573-5001, Vol. 56, no 3, p. 191-202Article in journal (Refereed)
    Abstract [en]

    We present the software Peak INTegration (PINT), designed to perform integration of peaks in NMR spectra. The program is very simple to run, yet powerful enough to handle complicated spectra. Peaks are integrated by fitting predefined line shapes to experimental data and the fitting can be customized to deal with, for instance, heavily overlapped peaks. The results can be inspected visually, which facilitates systematic optimization of the line shape fitting. Finally, integrated peak volumes can be used to extract parameters such as relaxation rates and information about low populated states. The utility of PINT is demonstrated by applications to the 59 residue SH3 domain of the yeast protein Abp1p and the 289 residue kinase domain of murine EphB2.

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  • 29.
    Ahlstrand, I.
    et al.
    School of Health Sciences, Jönköping University, Jönköping, Sweden.
    Thyberg, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. School of Health Sciences, Jönköping University, Jönköping, Sweden; School of Occupational Therapy and Social Work, CHIRI, Curtin University, Perth, WA, Australia.
    Dahlström, Örjan
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    Björk, Mathilda
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Rehabilitation Center. School of Health Sciences, Jönköping University, Jönköping, Sweden.
    Pain and activity limitations in women and men with contemporary treated early RA compared to 10 years ago: the Swedish TIRA project2015In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 44, no 4, p. 259-264Article in journal (Refereed)
    Abstract [en]

    Objectives: To study differences regarding pain and activity limitations during the 3 years following diagnosis in women and men with contemporary treated early RA compared with their counterparts who were diagnosed 10 years earlier. Method: This study was based on patients recruited to the Early Intervention in RA (TIRA) project. In the first cohort (TIRA-1) 320 patients were included in time for diagnosis during 1996-1998 and 463 patients were included in the second cohort (TIRA-2) during 2006-2009. Disease activity, pain intensity (Visual Analogue Scale, VAS), bodily pain (BP) in the 36-item Short Form Health Survey (SF-36), activity limitations (Health Assessment Questionnaire, HAQ), and medication were reported at inclusion and at follow-up after 1, 2, and 3 years. Results: Disease activity, pain, and activity limitations were pronounced at inclusion across both genders and in both cohorts, with some improvement observed during the first year after diagnosis. Disease activity did not differ between cohorts at inclusion but was significantly lower at the follow-ups in the TIRA-2 cohort, in which the patients were prescribed traditional disease-modifying anti-rheumatic drugs (DMARDs) and biological agents more frequently. In TIRA-2, patients reported significantly lower pain and activity limitations at all follow-ups, with men reporting lower pain than women. Women reported significantly higher activity limitations at all time points in TIRA-2. Conclusions: Pain and activity limitations were still pronounced in the contemporary treated early RA cohort compared with their counterparts diagnosed 10 years earlier and both of these factors need to be addressed in clinical settings.

  • 30.
    Ahlstrand, Inger
    et al.
    Jonköping University, Sweden.
    Björk, Mathilda
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Rehabilitation Center. Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Jonköping University, Sweden.
    Thyberg, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Jonköping University, Sweden; Curtin University, Australia.
    Pain and difficulties performing valued life activities in women and men with rheumatoid arthritis2015In: Clinical Rheumatology, ISSN 0770-3198, E-ISSN 1434-9949, Vol. 34, no 8, p. 1353-1362Article in journal (Refereed)
    Abstract [en]

    This study aimed to examine the difficulties with performing valued life activities in relation to pain intensity in women and men with rheumatoid arthritis (RA). In total, 737 persons with RA (73 % women) from three rheumatology units in Sweden responded to a questionnaire measuring performance of 33 valued life activities and self-rated pain. The relationships between performance of valued life activities (VLAs) and pain (measured by visual analogue scale (VAS)) were analysed based on gender. Multiple linear regression analyses were conducted with the total VLA score as dependent variable. Women reported more pain and difficulties in performing valued life activities than men. Across genders, 85 % reported at least one valued life activity affected by RA. Significantly more women than men encountered difficulties in performing some activities such as cooking, gardening and meeting new people. Women reported higher pain intensity (35 mm) than men (31 mm). Almost all 33 difficulty ratings for valued life activities were higher among persons with high pain (greater than 40 mm) than persons with lower pain. Difficulty ratings for valued life activities correlated positively with pain in persons with lower pain, but not among those with high pain. The results highlight the importance of addressing pain, especially among women with RA, as they reported pain to impact on their valued life activities. Interestingly, this was evident also in women with lower levels of pain.

  • 31.
    Ahlstrom, Christina A.
    et al.
    US Geol Survey, AK 99508 USA.
    Bonnedahl, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Kalmar Cty Hosp, Sweden.
    Woksepp, Hanna
    Kalmar Cty Hosp, Sweden.
    Hernandez, Jorge
    Uppsala Univ, Sweden.
    Olsen, Bjorn
    Uppsala Univ, Sweden.
    Ramey, Andrew M.
    US Geol Survey, AK 99508 USA.
    Acquisition and dissemination of cephalosporin-resistant E.coli in migratory birds sampled at an Alaska landfill as inferred through genomic analysis2018In: Scientific Reports, E-ISSN 2045-2322, Vol. 8, article id 7361Article in journal (Refereed)
    Abstract [en]

    Antimicrobial resistance (AMR) in bacterial pathogens threatens global health, though the spread of AMR bacteria and AMR genes between humans, animals, and the environment is still largely unknown. Here, we investigated the role of wild birds in the epidemiology of AMR Escherichia coli. Using next-generation sequencing, we characterized cephalosporin-resistant E. coli cultured from sympatric gulls and bald eagles inhabiting a landfill habitat in Alaska to identify genetic determinants conferring AMR, explore potential transmission pathways of AMR bacteria and genes at this site, and investigate how their genetic diversity compares to isolates reported in other taxa. We found genetically diverse E. coli isolates with sequence types previously associated with human infections and resistance genes of clinical importance, including blaCTX-M and blaCMY. Identical resistance profiles were observed in genetically unrelated E. coli isolates from both gulls and bald eagles. Conversely, isolates with indistinguishable core-genomes were found to have different resistance profiles. Our findings support complex epidemiological interactions including bacterial strain sharing between gulls and bald eagles and horizontal gene transfer among E. coli harboured by birds. Results suggest that landfills may serve as a source for AMR acquisition and/or maintenance, including bacterial sequence types and AMR genes relevant to human health.

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  • 32.
    Ahlstrom, Christina A.
    et al.
    US Geol Survey, AK 99508 USA.
    Frick, Anna
    State Alaska Dept Hlth & Social Serv, AK USA.
    Pongratz, Catherine
    State Alaska Dept Hlth & Social Serv, AK USA.
    Spink, Kimberly
    State Alaska Dept Hlth & Social Serv, AK USA.
    Xavier, Catherine
    State Alaska Dept Hlth & Social Serv, AK USA.
    Bonnedahl, Jonas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Kalmar Cty Council, Sweden.
    Ramey, Andrew M.
    US Geol Survey, AK 99508 USA.
    Genomic comparison of carbapenem-resistant Enterobacteriaceae from humans and gulls in Alaska2021In: Journal of Global Antimicrobial Resistance, ISSN 2213-7165, E-ISSN 2213-7173, Vol. 25, p. 23-25Article in journal (Refereed)
    Abstract [en]

    Objectives: Wildlife may harbour clinically important antimicrobial-resistant bacteria, but the role of wildlife in the epidemiology of antimicrobial-resistant bacterial infections in humans is largely unknown. In this study, we aimed to assess dissemination of the bla(KPC) carbapenemase gene among humans and gulls in Alaska. Methods: We performed whole-genome sequencing to determine the genetic context of bla(KPC) in bacterial isolates from all four human carbapenemase-producing Enterobacteriaceae (CPE) infections reported in Alaska between 2013-2018 and to compare the sequences with seven previously reported CPE isolates from gull faeces within the same region and time period. Results: Genomic analysis of CPE isolates suggested independent acquisition events among humans with no evidence for direct transmission of bla(KPC) between people and gulls. However, some isolates shared conserved genetic elements surrounding bla(KPC), suggesting possible exchange between species. Conclusion: Our results highlight the genomic plasticity associated with bla(KPC) and demonstrate that sampling of wildlife may be useful for identifying clinically relevant antimicrobial resistance not observed through local passive surveillance in humans. Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.

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  • 33.
    Ahlstrom, Christina A.
    et al.
    US Geol Survey, AK USA; US Geol Survey, AK 99508 USA.
    Scott, Laura C.
    US Geol Survey, AK USA.
    Woksepp, Hanna
    Reg Kalmar Cty, Sweden; Linnaeus Univ, Sweden.
    Bonnedahl, Jonas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Reg Kalmar Cty, Sweden.
    Ramey, Andrew M.
    US Geol Survey, AK USA.
    Environmental antimicrobial resistance gene detection from wild bird habitats using two methods: A commercially available culture-independent qPCR assay and culture of indicator bacteria followed by whole-genome sequencing2023In: Journal of Global Antimicrobial Resistance, ISSN 2213-7165, E-ISSN 2213-7173, Vol. 33, p. 186-193Article in journal (Refereed)
    Abstract [en]

    Objectives: A variety of methods have been developed to detect antimicrobial resistance (AMR) in differ-ent environments to better understand the evolution and dissemination of this public health threat. Com-parisons of results generated using different AMR detection methods, such as quantitative PCR (qPCR) and whole-genome sequencing (WGS), are often imperfect, and few studies have analysed samples in parallel to evaluate differences. In this study, we compared bacterial culture and WGS to a culture-independent commercially available qPCR assay to evaluate the concordance between methods and the utility of each in answering research questions regarding the presence and epidemiology of AMR in wild bird habitats.Methods: We first assessed AMR gene detection using qPCR in 45 bacterial isolates from which we had existing WGS data. We then analysed 52 wild bird faecal samples and 9 spatiotemporally collected water samples using culture-independent qPCR and WGS of phenotypically resistant indicator bacterial isolates.Results: Overall concordance was strong between qPCR and WGS of bacterial isolates, although concor-dance differed among antibiotic classes. Analysis of wild bird faecal and water samples revealed that more samples were determined to be positive for AMR via qPCR than via culture and WGS of bacterial isolates, although qPCR did not detect AMR genes in two samples from which phenotypically resistant isolates were found.Conclusions: Both qPCR and culture followed by sequencing may be effective approaches for characteris-ing AMR genes harboured by wild birds, although data streams produced using these different tools may have advantages and disadvantages that should be considered given the application and sample matrix.Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

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  • 34.
    Ahlström, Stina
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Sweden.
    Ahlner, Johan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
    Jönsson, Anna K
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, S-58758 Linkoping, Sweden.
    Green, Henrik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, S-58758 Linkoping, Sweden.
    The Importance of BHB Testing on the Post-Mortem Diagnosis of Ketoacidosis2022In: Biomolecules, E-ISSN 2218-273X, Vol. 12, no 1, article id 9Article in journal (Refereed)
    Abstract [en]

    Although beta-hydroxybutyrate (BHB) analysis has proved its importance in forensic pathology, its effects on cause-of-death diagnostics are unaddressed. Therefore, this study aims at evaluating the effects of BHB analysis on the number of deaths by DKA (diabetes ketoacidosis), AKA (alcoholic ketoacidosis), HHS (hyperosmolar hyperglycaemic state), hypothermia, diabetes, alcoholism, and acidosis NOS (not otherwise specified). All 2900 deaths from 2013 through 2019 in which BHB was analysed at the National Board of Forensic Medicine, and 1069 DKA, AKA, HHS, hypothermia, diabetes, alcoholism, and acidosis cases without BHB analysis were included. The prevalence of BHB-positive cases for each cause of death, and trends and proportions of different BHB concentrations, were investigated. The number of BHB analyses/year increased from 13 to 1417. AKA increased from three to 66 and acidosis from one to 20. The deaths from alcoholism, DKA, and hypothermia remained stable. It is unclear why death from alcoholism remained stable while AKA increased. The increase in unspecific acidosis deaths raises the question why a more specific diagnosis had not been used. In conclusion, BHB analysis is instrumental in detecting AKA and acidosis. The scientific basis for the diagnosis of DKA and hypothermia improved, but the number of cases did not change.

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  • 35.
    Aho, Nikolas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Proczkowska-Björklund, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Svedin, Carl Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Victimization, polyvictimization , and health in Swedish adolescents2016In: Adolescent Health, Medicine and Therapeutics, ISSN 1179-318X, Vol. 7, p. 89-99Article in journal (Refereed)
    Abstract [en]

    The main objective of this article was to study the relationship between the different areas of victimization (eg, sexual victimization) and psychological symptoms, taking into account the full range of victimization domains. The final aim was to contribute further evidence regarding the bias that studies that focus on just one area of victimization may be introduced into our psychological knowledge. The sample included 5,960 second-year high school students in Sweden with a mean age of 17.3 years (range =16–20 years, standard deviation =0.652), of which 49.6% were females and 50.4% males. The Juvenile Victimization Questionnaire and the Trauma Symptom Checklist for Children were used to assess victimization and psychological problems separately. The results show that a majority of adolescents have been victimized, females reported more total events and more sexual victimization and childhood maltreatment, and males were more often victims of conventional crime. The majority of victimization domains as well as the sheer number of events (polyvictimization [PV]) proved to be harmful to adolescent health, affecting females more than males. PV explained part of the health effect and had an impact on its own and in relation to each domain. This suggests the possibility that PV to a large degree explains trauma symptoms. In order to understand the psychological effects of trauma, clinicians and researchers should take into account the whole range of possible types of victimization.

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  • 36. Order onlineBuy this publication >>
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics. Linköping University, The Institute of Technology.
    Polypeptide-Based Nanoscale Materials2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Self-assembly has emerged as a promising technique for fabrication of novel hybrid materials and nanostructures. The work presented in this thesis has been focused on developing nanoscale materials based on synthetic de novo designed polypeptides. The polypeptides have been utilized for the assembly of gold nanoparticles, fibrous nanostructures, and for sensing applications.

    The 42-residue polypeptides are designed to fold into helix-loop-helix motifs and dimerize to form four-helix bundles. Folding is primarily driven by the formation of a hydrophobic core made up by the hydrophobic faces of the amphiphilic helices. The peptides have either a negative or positive net charge at neutral pH, depending on the relative abundance of Glu and Lys. Charge repulsion thus prevents homodimerization at pH 7 while promoting hetero-dimerization through the formation of stabilising salt bridges. A Cys incorporated in position 22, located in the loop region, allowed for directed, thiol-dependent, immobilization on planar gold surfaces and gold nanoparticles. The negatively charged (Glu-rich) peptide formed homodimers and folded in solution at pH < 6 or in the presence of certain metal ions, such as Zn2+. The folding properties of this peptide were retained when immobilized directly on gold, which enabled reversible assembly of gold nanoparticles resulting in aggregates with well-defined interparticle separations. Particle aggregation was found to induce folding of the immobilized peptides but folding could also be utilized to induce aggregation of the particles by exploiting the highly specific interactions involved in both homodimerization and hetero-association. The possibility to control the assembly of polypeptide-functionalized gold nanoparticles was utilized in a colorimetric protein assay. Analyte binding to immobilized ligands prevented the formation of dense particle aggregates when subjecting the particles to conditions normally causing extensive aggregation. Analyte binding could hence easily be distinguished by the naked eye. Moreover, the peptides were utilized to assemble gold nanoparticles on planar gold and silica substrates.

    Fibrous nanostructures were realized by linking monomers through a disulphide-bridge. The disulphide-linked peptides were found to spontaneously assemble into long and extremely thin peptide fibres as a result of a propagating association mediated by folding into four-helix bundles.

    List of papers
    1. Alpha-helix-inducing dimerization of synthetic polypeptide scaffolds on gold
    Open this publication in new window or tab >>Alpha-helix-inducing dimerization of synthetic polypeptide scaffolds on gold
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    2005 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 21, no 6, p. 2480-2487Article in journal (Refereed) Published
    Abstract [en]

    Designed, synthetic polypeptides that assemble into four-helix bundles upon dimerization in solution were studied with respect to folding on planar gold surfaces. A model system with controllable dimerization properties was employed, consisting of negatively and positively charged peptides. Circular dichroism spectroscopy and surface plasmon resonance based measurements showed that at neutral pH, the peptides were able to form heterodimers in solution, but unfavorable electrostatic interactions prevented the formation of homodimers. The dimerization propensity was found to be both pH- and buffer-dependent. A series of infrared absorption−reflection spectroscopy experiments of the polypeptides attached to planar gold surfaces revealed that if the negatively charged peptide was immobilized from a loading solution where it was folded, its structure was retained on the surface provided it had a cysteine residue available for anchoring to gold. If it was immobilized as random coil, it remained unstructured on the surface but was able to fold through heterodimerization if subsequently exposed to a positively charged polypeptide. When the positively charged peptide was immobilized as random coil, heterodimerization could not be induced, probably because of high-affinity interactions between the charged primary amine groups and the gold surface. These observations are intended to pave the way for future engineering of functional surfaces based on polypeptide scaffolds where folding is known to be crucial for function.

    Place, publisher, year, edition, pages
    ACS Publications, 2005
    National Category
    Other Basic Medicine
    Identifiers
    urn:nbn:se:liu:diva-15115 (URN)10.1021/la048029u (DOI)
    Available from: 2008-10-16 Created: 2008-10-16 Last updated: 2018-01-12Bibliographically approved
    2. Aggregation-Induced Folding of a de novo Designed Polypeptide Immobilized on Gold Nanoparticles
    Open this publication in new window or tab >>Aggregation-Induced Folding of a de novo Designed Polypeptide Immobilized on Gold Nanoparticles
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    2006 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 128, no 7, p. 2194 -2195Article in journal (Refereed) Published
    Abstract [en]

    This communication reports the first steps in the construction of a novel, nanoparticle-based hybrid material for biomimetic and biosensor applications. Gold nanoparticles were modified with synthetic polypeptides to enable control of the particle aggregation state in a switchable manner, and particle aggregation was, in turn, found to induce folding of the immobilized peptides.

    Place, publisher, year, edition, pages
    ACS Publications, 2006
    Keywords
    Not aviable
    National Category
    Other Basic Medicine
    Identifiers
    urn:nbn:se:liu:diva-14041 (URN)10.1021/ja057056j (DOI)
    Available from: 2006-09-28 Created: 2006-09-28 Last updated: 2018-01-13Bibliographically approved
    3. Folding Induced Assembly of Polypeptide Decorated Gold Nanoparticles
    Open this publication in new window or tab >>Folding Induced Assembly of Polypeptide Decorated Gold Nanoparticles
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    2008 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 130, no 17, p. 5780-5788Article in journal (Refereed) Published
    Abstract [en]

    Reversible assembly of gold nanoparticles controlled by the homodimerization and folding of an immobilized de novo designed synthetic polypeptide is described. In solution at neutral pH, the polypeptide folds into a helix–loop–helix four-helix bundle in the presence of zinc ions. When immobilized on gold nanoparticles, the addition of zinc ions induces dimerization and folding between peptide monomers located on separate particles, resulting in rapid particle aggregation. The particles can be completely redispersed by removal of the zinc ions from the peptide upon addition of EDTA. Calcium ions, which do not induce folding in solution, have no effect on the stability of the peptide decorated particles. The contribution from folding on particle assembly was further determined utilizing a reference peptide with the same primary sequence but containing both D and L amino acids. Particles functionalized with the reference peptide do not aggregate, as the peptides are unable to fold. The two peptides, linked to the nanoparticle surface via a cysteine residue located in the loop region, form submonolayers on planar gold with comparable properties regarding surface density, orientation, and ability to interact with zinc ions. These results demonstrate that nanoparticle assembly can be induced, controlled, and to some extent tuned, by exploiting specific molecular interactions involved in polypeptide folding.

    Place, publisher, year, edition, pages
    ACS Publications, 2008
    National Category
    Other Basic Medicine
    Identifiers
    urn:nbn:se:liu:diva-15116 (URN)10.1021/ja711330f (DOI)
    Available from: 2008-10-16 Created: 2008-10-16 Last updated: 2018-01-12Bibliographically approved
    4. Controlled Assembly of Gold Nanoparticles using De Novo Designed Polypeptide Scaffolds
    Open this publication in new window or tab >>Controlled Assembly of Gold Nanoparticles using De Novo Designed Polypeptide Scaffolds
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    2008 (English)In: Proceedings SPIE, Vol. 6885, Photonic Biosensing and Microoptics, 2008, p. 688506-1-688506-8Conference paper, Published paper (Refereed)
    Abstract [en]

    Heterodimerization between designed helix-loop-helix polypeptides was utilized in order to assemble gold nanoparticles on planar substrates. The peptides were designed to fold into four-helix bundles upon dimerization. A Cys-residue in the loop region was used to immobilize one of the complementary peptides on a maleimide containing SAM on planar gold substrates whereas the second peptide was immobilized directly on gold nanoparticles. Introducing the peptide decorated particles over a peptide functionalized surface resulted in particle assembly. Further, citrate stabilized particles were assembled on amino-silane modified glass and silicon substrates. By subsequently introducing peptides and gold nanoparticles, particle-peptide hybrid multi layers could be formed.

    Keywords
    Heterodimerization, polypeptides, gold nanoparticles, four-helix bundle, helix-loop-helix, self-assembly
    National Category
    Other Basic Medicine
    Identifiers
    urn:nbn:se:liu:diva-15118 (URN)10.1117/12.775806 (DOI)
    Available from: 2008-10-16 Created: 2008-10-16 Last updated: 2018-01-12Bibliographically approved
    5. Self-Assembly of Fibers and Nanorings from Disulfide-Linked Helix–Loop–Helix Polypeptides
    Open this publication in new window or tab >>Self-Assembly of Fibers and Nanorings from Disulfide-Linked Helix–Loop–Helix Polypeptides
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    2008 (English)In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 47, no 30, p. 5554-5556Article in journal (Refereed) Published
    Place, publisher, year, edition, pages
    Wiley InterScience, 2008
    Keywords
    fibers, helical structures, nanostructures, polypeptides, self-assembly
    National Category
    Other Basic Medicine
    Identifiers
    urn:nbn:se:liu:diva-15120 (URN)10.1002/anie.200801155 (DOI)
    Available from: 2008-10-16 Created: 2008-10-16 Last updated: 2018-01-12Bibliographically approved
    6. Assembly of Polypeptide-Functionalized Gold Nanoparticles through a Heteroassociation- and Folding-Dependent Bridging
    Open this publication in new window or tab >>Assembly of Polypeptide-Functionalized Gold Nanoparticles through a Heteroassociation- and Folding-Dependent Bridging
    2008 (English)In: Nano letters (Print), ISSN 1530-6984, E-ISSN 1530-6992, Vol. 8, no 8, p. 2473-2478Article in journal (Refereed) Published
    Abstract [en]

    Gold nanoparticles were functionalized with a synthetic polypeptide, de novo-designed to associate with a charge complementary linker polypeptide in a folding-dependent manner. A heterotrimeric complex that folds into two disulphide-linked four-helix bundles is formed when the linker polypeptide associates with two of the immobilized peptides. The heterotrimer forms in between separate particles and induces a rapid and extensive aggregation with a well-defined interparticle spacing. The aggregated particles are redispersed when the disulphide bridge in the linker polypeptide is reduced.

    Place, publisher, year, edition, pages
    ACS Publications, 2008
    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:liu:diva-15121 (URN)10.1021/nl8014796 (DOI)
    Note
    The original title of this article was "Assembly of Decorated Gold Nanoparticles through a Hetero-Association and Folding-Dependent Bridging".Available from: 2008-10-16 Created: 2008-10-16 Last updated: 2017-12-07
    7. Colorimetric Protein Sensing by Controlled Assembly of Gold Nanoparticles Functionalized with Synthetic Receptors
    Open this publication in new window or tab >>Colorimetric Protein Sensing by Controlled Assembly of Gold Nanoparticles Functionalized with Synthetic Receptors
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    2009 (English)In: Small, ISSN 1613-6810, Vol. 5, no 21, p. 2445-2452Article in journal (Refereed) Published
    Abstract [en]

    A strategy for colorimetric sensing of proteins, based on the induced assembly of polypeptide-functionalized gold nanoparticles, is described. Recognition was accomplished using a polypeptide sensor scaffold designed to specifically bind the model analyte, human carbonic anhydrase II (HCAII). The extent of particle aggregation, induced by the Zn2+-triggered dimerization and folding of a second polypeptide also present on the surface of the gold nanoparticle, gave a readily detectable colorimetric shift that was dependent on the concentration of the target protein. In the absence of HCAII, particle aggregation resulted in a major redshift of the plasmon peak whereas analyte binding prevented formation of dense aggregates, significantly reducing the magnitude of the redshift. The limit of detection of HCAII was estimated to be around 15 nM. The versatility of the technique was demonstrated using a second model system based on the recognition of a peptide sequence from the tobacco mosaic virus coat protein (TMVP by a recombinant antibody fragment. This strategy is proposed as a generic platform for robust and specific protein analysis that can be further developed for monitoring a wide range of target proteins.

    Keywords
    Not available.
    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:liu:diva-15122 (URN)10.1002/smll.200900530 (DOI)
    Available from: 2008-10-16 Created: 2008-10-16 Last updated: 2019-01-22Bibliographically approved
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  • 37.
    Aili, Daniel
    et al.
    Linköping University, The Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Enander, Karin
    Linköping University, The Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Rydberg, Johan
    Linköping University, The Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Nesterenko, Irina
    Linköping University, The Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Björefors, Fredrik
    Linköping University, The Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Baltzer, Lars
    Division of Organic Chemistry, Department of Biochemistry and Organic Chemistry, BMC, Box 599, Uppsala University, SE-751 24 Uppsala, Sweden..
    Liedberg, Bo
    Linköping University, The Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Controlled Assembly of Gold Nanoparticles using De Novo Designed Polypeptide Scaffolds2008In: Proceedings SPIE, Vol. 6885, Photonic Biosensing and Microoptics, 2008, p. 688506-1-688506-8Conference paper (Refereed)
    Abstract [en]

    Heterodimerization between designed helix-loop-helix polypeptides was utilized in order to assemble gold nanoparticles on planar substrates. The peptides were designed to fold into four-helix bundles upon dimerization. A Cys-residue in the loop region was used to immobilize one of the complementary peptides on a maleimide containing SAM on planar gold substrates whereas the second peptide was immobilized directly on gold nanoparticles. Introducing the peptide decorated particles over a peptide functionalized surface resulted in particle assembly. Further, citrate stabilized particles were assembled on amino-silane modified glass and silicon substrates. By subsequently introducing peptides and gold nanoparticles, particle-peptide hybrid multi layers could be formed.

  • 38.
    Aili, Daniel
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Enander, Karin
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Rydberg, Johan
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Nesterenko, Irina
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Björefors, Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Baltzer, Lars
    Department of Biochemistry and Organic Chemistry, BMC, Box 599, Uppsala UniVersity, SE-751 24 Uppsala, Sweden.
    Liedberg, Bo
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Folding Induced Assembly of Polypeptide Decorated Gold Nanoparticles2008In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 130, no 17, p. 5780-5788Article in journal (Refereed)
    Abstract [en]

    Reversible assembly of gold nanoparticles controlled by the homodimerization and folding of an immobilized de novo designed synthetic polypeptide is described. In solution at neutral pH, the polypeptide folds into a helix–loop–helix four-helix bundle in the presence of zinc ions. When immobilized on gold nanoparticles, the addition of zinc ions induces dimerization and folding between peptide monomers located on separate particles, resulting in rapid particle aggregation. The particles can be completely redispersed by removal of the zinc ions from the peptide upon addition of EDTA. Calcium ions, which do not induce folding in solution, have no effect on the stability of the peptide decorated particles. The contribution from folding on particle assembly was further determined utilizing a reference peptide with the same primary sequence but containing both D and L amino acids. Particles functionalized with the reference peptide do not aggregate, as the peptides are unable to fold. The two peptides, linked to the nanoparticle surface via a cysteine residue located in the loop region, form submonolayers on planar gold with comparable properties regarding surface density, orientation, and ability to interact with zinc ions. These results demonstrate that nanoparticle assembly can be induced, controlled, and to some extent tuned, by exploiting specific molecular interactions involved in polypeptide folding.

  • 39.
    Aili, Daniel
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Tai, Feng-I
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Enander, Karin
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Baltzer, Lars
    Department of Biochemistry andOrganic Chemistry Uppsala University, BMC, Box 576, 75123 Uppsala, Sweden.
    Liedberg, Bo
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Self-Assembly of Fibers and Nanorings from Disulfide-Linked Helix–Loop–Helix Polypeptides2008In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 47, no 30, p. 5554-5556Article in journal (Refereed)
  • 40.
    Aili, Daniel
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Enander, Karin
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Rydberg, Johan
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Lundström, Ingemar
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics . Linköping University, The Institute of Technology.
    Baltzer, Lars
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Liedberg, Bo
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Aggregation-Induced Folding of a de novo Designed Polypeptide Immobilized on Gold Nanoparticles2006In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 128, no 7, p. 2194 -2195Article in journal (Refereed)
    Abstract [en]

    This communication reports the first steps in the construction of a novel, nanoparticle-based hybrid material for biomimetic and biosensor applications. Gold nanoparticles were modified with synthetic polypeptides to enable control of the particle aggregation state in a switchable manner, and particle aggregation was, in turn, found to induce folding of the immobilized peptides.

  • 41.
    Aira, Naomi
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Andersson, Anna-Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Singh, Susmita K.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Mckay, Derek M.
    University of Calgary, Canada.
    Blomgran, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Species dependent impact of helminth-derived antigens on human macrophages infected with Mycobacterium tuberculosis: Direct effect on the innate anti-mycobacterial response2017In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 11, no 3, article id e0005390Article in journal (Refereed)
    Abstract [en]

    Background In countries with a high prevalence of tuberculosis there is high coincident of helminth infections that might worsen disease outcome. While Mycobacterium tuberculosis (Mtb) gives rise to a pro-inflammatory Th1 response, a Th2 response is typical of helminth infections. A strong Th2 response has been associated with decreased protection against tuberculosis. Principal findings We investigated the direct effect of helminth-derived antigens on human macrophages, hypothesizing that helminths would render macrophages less capable of controlling Mtb. Measuring cytokine output, macrophage surface markers with flow cytometry, and assessing bacterial replication and phagosomal maturation revealed that antigens from different species of helminth directly affect macrophage responses to Mtb. Antigens from the tapeworm Hymenolepis diminuta and the nematode Trichuris muris caused an anti-inflammatory response with M2-type polarization, reduced macrophage phagosome maturation and ability to activate T cells, along with increased Mtb burden, especially in T. muris exposed cells which also induced the highest IL-10 production upon co-infection. However, antigens from the trematode Schistosoma mansoni had the opposite effect causing a decrease in IL-10 production, M1-type polarization and increased control of Mtb. Conclusion We conclude that, independent of any adaptive immune response, infection with helminth parasites, in a species-specific manner can influence the outcome of tuberculosis by either enhancing or diminishing the bactericidal function of macrophages.

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  • 42.
    Ajileye, Adebisi
    et al.
    Birmingham Heartlands Hospital, England.
    Alvarez, Nataly
    Corp Invest Biol, Colombia; University of Pontificia Bolivariana, Colombia.
    Merker, Matthias
    Research Centre Borstel, Germany; German Centre Infect Research, Germany.
    Walker, Timothy M.
    University of Oxford, England.
    Akter, Suriya
    Institute Trop Med, Belgium.
    Brown, Kerstin
    Birmingham Heartlands Hospital, England.
    Moradigaravand, Danesh
    Wellcome Trust Sanger Institute, England.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Kalmar County Hospital, Sweden.
    Andres, Soenke
    Research Centre Borstel, Germany.
    Schleusener, Viola
    Research Centre Borstel, Germany.
    Omar, Shaheed V.
    Centre TB, South Africa.
    Coll, Francesc
    London School Hyg and Trop Med, England.
    Huang, Hairong
    Capital Medical University, Peoples R China.
    Diel, Roland
    University Hospital, Germany.
    Ismail, Nazir
    Centre TB, South Africa.
    Parkhill, Julian
    Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
    de Jong, Bouke C.
    Institute Trop Med, Belgium.
    Peto, Tim E. A.
    University of Oxford, England.
    Crook, Derrick W.
    University of Oxford, England; Public Health England Microbiol Serv, England.
    Niemann, Stefan
    Research Centre Borstel, Germany; German Centre Infect Research, Germany.
    Robledo, Jaime
    Corp Invest Biol, Colombia; University of Pontificia Bolivariana, Colombia.
    Grace Smith, E.
    Birmingham Heartlands Hospital, England.
    Peacock, Sharon J.
    Wellcome Trust Sanger Institute, England; London School Hyg and Trop Med, England; University of Cambridge, England.
    Koeser, Claudio U.
    University of Cambridge, England.
    Some Synonymous and Nonsynonymous gyrA Mutations in Mycobacterium tuberculosis Lead to Systematic False-Positive Fluoroquinolone Resistance Results with the Hain GenoType MTBDRsl Assays2017In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 61, no 4, article id e02169-16Article in journal (Refereed)
    Abstract [en]

    In this study, using the Hain GenoType MTBDRsl assays (versions 1 and 2), we found that some nonsynonymous and synonymous mutations in gyrA in Mycobacterium tuberculosis result in systematic false-resistance results to fluoroquinolones by preventing the binding of wild-type probes. Moreover, such mutations can prevent the binding of mutant probes designed for the identification of specific resistance mutations. Although these mutations are likely rare globally, they occur in approximately 7% of multidrug-resistant tuberculosis strains in some settings.

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  • 43.
    Albrecht, Matthew A.
    et al.
    Curtin University, Australia .
    Stuart, Geoffrey W.
    La Trobe University, Australia .
    Falkmer, Marita
    Curtin University, Australia, Jonköping University, Sweden .
    Ordqvist, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Leung, Denise
    Curtin University, Australia .
    Foster, Jonathan K.
    Curtin University, Australia Health Department WA, Australia .
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Brief Report: Visual Acuity in Children with Autism Spectrum Disorders2014In: Journal of autism and developmental disorders, ISSN 0162-3257, E-ISSN 1573-3432, Vol. 44, no 9, p. 2369-2374Article in journal (Refereed)
    Abstract [en]

    Recently, there has been heightened interest in suggestions of enhanced visual acuity in autism spectrum disorders (ASD) which was sparked by evidence that was later accepted to be methodologically flawed. However, a recent study that claimed children with ASD have enhanced visual acuity (Brosnan et al. in J Autism Dev Disord 42:2491-2497, 2012) repeated a critical methodological flaw by using an inappropriate viewing distance for a computerised acuity test, placing the findings in doubt. We examined visual acuity in 31 children with ASD and 33 controls using the 2 m 2000 Series Revised Early Treatment Diabetic Retinopathy Study chart placed at twice the conventional distance to better evaluate possible enhanced acuity. Children with ASD did not demonstrate superior acuity. The current findings strengthen the argument that reports of enhanced acuity in ASD are due to methodological flaws and challenges the reported association between visual acuity and systemising type behaviours.

  • 44.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Aaseth, Jan
    Innlandet Hosp Trust, Norway; Inland Norway Univ Appl Sci, Norway.
    Larsson, Anders
    Uppsala Univ, Sweden.
    Decrease in inflammatory biomarker concentration by intervention with selenium and coenzyme Q10: a subanalysis of osteopontin, osteoprotergerin, TNFr1, TNFr2 and TWEAK2019In: Journal of Inflammation, E-ISSN 1476-9255, Vol. 16, article id 5Article in journal (Refereed)
    Abstract [en]

    Background: Inflammation is central to the pathogenesis of many diseases. Supplementation with selenium and coenzyme Q10 has been shown to reduce cardiovascular mortality, and increase cardiac function in elderly persons with a low intake of selenium. There are indications that one of the mechanisms of this positive effect is a decrease in inflammation. Methods: Osteopontin, osteoprotegerin, sTNF receptor 1, sTNF receptor 2 and the tumor necrosis factor-like weak inducer of apoptosis called TWEAK, were determined in plasma after 6 months and 42months in 219 community-living elderly persons, of whom 119 received supplements of selenium (200g/day) and coenzyme Q10 (200mg/day), and 101 received a placebo. Repeated measures of variance were used to evaluate the levels, and the results were validated through ANCOVA analyses with adjustments for important covariates. Results: Significantly lower concentrations of four of the five biomarkers for inflammation were observed as a result of the intervention with the supplements. Only TWEAK did not show significant differences. Conclusion: In this sub-analysis of the intervention with selenium and coenzyme Q10 or placebo in an elderly community-living population, biomarkers for inflammation were evaluated. A significantly lower concentration in four of the five biomarkers tested could be demonstrated as a result of the supplementation, indicating a robust effect on the inflammatory system. The decrease in inflammation could be one of the mechanisms behind the positive clinical results on reduced cardiovascular morbidity and mortality reported earlier as a result of the intervention. The study is small and should be regarded as hypothesis-generating, but nonetheless adds important data about mechanisms presently known to increase the risk of clinical effects such as reduced cardiovascular mortality, increased cardiac function and better health-related quality of life scoring, as previously demonstrated in the active treatment group.

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  • 45.
    Alehagen, Urban
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Opstad, Trine B.
    Oslo Univ Hosp Ulleval, Norway; Univ Oslo, Norway.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Larsson, Anders
    Uppsala Univ, Sweden.
    Aaseth, Jan
    Innlandet Hosp Trust, Norway; Inland Norway Univ Appl Sci, Norway.
    Impact of Selenium on Biomarkers and Clinical Aspects Related to Ageing. A Review2021In: Biomolecules, E-ISSN 2218-273X, Vol. 11, no 10, article id 1478Article, review/survey (Refereed)
    Abstract [en]

    Selenium (Se) is an essential dietary trace element that plays an important role in the prevention of inflammation, cardiovascular diseases, infections, and cancer. Selenoproteins contain selenocysteine in the active center and include, i.a., the enzymes thioredoxin reductases (TXNRD1-3), glutathione peroxidases (GPX1-4 and GPX6) and methionine sulfoxide reductase, involved in immune functions, metabolic homeostasis, and antioxidant defense. Ageing is an inevitable process, which, i.a., involves an imbalance between antioxidative defense and reactive oxygen species (ROS), changes in protein and mitochondrial renewal, telomere attrition, cellular senescence, epigenetic alterations, and stem cell exhaustion. These conditions are associated with mild to moderate inflammation, which always accompanies the process of ageing and age-related diseases. In older individuals, Se, by being a component in protective enzymes, operates by decreasing ROS-mediated inflammation, removing misfolded proteins, decreasing DNA damage, and promoting telomere length. Se-dependent GPX1-4 and TXNRD1-3 directly suppress oxidative stress. Selenoprotein H in the cell nucleus protects DNA, and selenoproteins residing in the endoplasmic reticulum (ER) assist in the removal of misfolded proteins and protection against ER stress. In this review, we highlight the role of adequate Se status for human ageing and prevention of age-related diseases, and further its proposed role in preservation of telomere length in middle-aged and elderly individuals.

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  • 46.
    Alexander, Helen K.
    et al.
    Cancer Care Manitoba, Manitoba Institute of Cell Biology, University of Manitoba.
    Booy, Evan P.
    Cancer Care Manitoba, Manitoba Institute of Cell Biology, University of Manitoba; Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Canada .
    Xiao, Wenyan
    Cancer Care Manitoba, Manitoba Institute of Cell Biology, University of Manitoba.
    Ezzati, Peyman
    Cancer Care Manitoba, Manitoba Institute of Cell Biology, University of Manitoba.
    Baust, Heinrich
    Department of Radiooncology, University of Erlangen, Erlangen, Germany .
    Los, Marek Jan
    Manitoba Institute of Cell Biology, Cancer Care Manitoba; Manitoba Institute of Child Health; Department of Biochemistry and Medical Genetics; Department of Human Anatomy and Cell Science, University Manitoba, Winnipeg, Canada, .
    Selected technologies to control genes and their products for experimental and clinical purposes2007In: Archivum Immunologiae et Therapiae Experimentalis, ISSN 0004-069X, E-ISSN 1661-4917, Vol. 55, no 3, p. 139-149Article in journal (Refereed)
    Abstract [en]

    "On-demand" regulation of gene expression is a powerful tool to elucidate the functions of proteins and biologically-active RNAs. We describe here three different approaches to the regulation of expression or activity of genes or proteins. Promoter-based regulation of gene expression was among the most rapidly developing techniques in the 1980s and 1990s. Here we provide basic information and also some characteristics of the metallothionein-promoter-based system, the tet-off system, Muristerone-A-regulated expression through the ecdysone response element, RheoSwitch (R), coumermycin/novobiocin-regulated gene expression, chemical dimerizer-based promoter activation systems, the "Dual Drug Control" system, "constitutive androstane receptor"-based regulation of gene expression, and RU486/mifepristone-driven regulation of promoter activity. A large part of the review concentrates on the principles and usage of various RNA interference techniques (RNAi: siRNA, shRNA, and miRNA-based methods). Finally, the last part of the review deals with historically the oldest, but still widely used, methods of temperature-dependent regulation of enzymatic activity or protein stability (temperature-sensitive mutants). Due to space limitations we do not describe in detail but just mention the tet-regulated systems and also fusion-protein-based regulation of protein activity, such as estrogen-receptor fusion proteins. The information provided below is aimed to assist researchers in choosing the most appropriate method for the planned development of experimental systems with regulated expression or activity of studied proteins.

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  • 47.
    Aleynick, Mark
    et al.
    Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, USA.
    Svensson-Arvelund, Judit
    Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, USA.
    Flowers, Christopher R.
    Winship Cancer Institute of Emory University, Emory University School of Medicine, Atlanta, Georgia, USA.
    Marabelle, Aurélien
    Cancer Immunotherapy Program, Gustave Roussy, Villejuif, France.
    Brody, Joshua D.
    1Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York.;4Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, New York..
    Pathogen Molecular Pattern Receptor Agonists: Treating Cancer by Mimicking Infection2019In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 25, no 21, p. 6283-6294Article in journal (Refereed)
    Abstract [en]

    mmunotherapies such as checkpoint blockade have achieved durable benefits for patients with advanced stage cancer and have changed treatment paradigms. However, these therapies rely on a patient's own a priori primed tumor-specific T cells, limiting their efficacy to a subset of patients. Because checkpoint blockade is most effective in patients with inflamed or "hot" tumors, a priority in the field is learning how to "turn cold tumors hot." Inflammation is generally initiated by innate immune cells, which receive signals through pattern recognition receptors (PRR)–a diverse family of receptors that sense conserved molecular patterns on pathogens, alarming the immune system of an invading microbe. Their immunostimulatory properties can reprogram the immune suppressive tumor microenvironment and activate antigen-presenting cells to present tumors antigens, driving de novo tumor-specific T-cell responses. These features, among others, make PRR-targeting therapies an attractive strategy in immuno-oncology. Here, we discuss mechanisms of PRR activation, highlighting ongoing clinical trials and recent preclinical advances focused on therapeutically targeting PRRs to treat cancer. 

  • 48.
    Aleynick, Mark
    et al.
    Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
    Svensson-Arvelund, Judit
    Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
    Pantsulaia, Gvantsa
    Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
    Kim, Kristy
    Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
    Rose, Samuel A.
    Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, USA.
    Upadhyay, Ranjan
    Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
    Yellin, Michael
    Celldex Therapeutics Inc, Hampton, New Jersey, USA.
    Marsh, Henry
    Celldex Therapeutics Inc, Hampton, New Jersey, USA.
    Oreper, Daniel
    Genentech Inc, South San Francisco, California, USA.
    Jhunjhunwala, Suchit
    Genentech Inc, South San Francisco, California, USA.
    Moussion, Christine Carine
    Genentech Inc, South San Francisco, California, USA.
    Merad, Miriam
    Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, USA.
    Brown, Brian D.
    Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, USA.
    Brody, Joshua D.
    Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
    Pattern recognition receptor agonists in pathogen vaccines mediate antitumor T-cell cross-priming2023In: Journal for ImmunoTherapy of Cancer, E-ISSN 2051-1426, Vol. 11, no 7, article id e007198Article in journal (Refereed)
    Abstract [en]

    Background Cancer immunotherapies are generallyeffective in patients whose tumors contain a prioriprimed T-cells reactive to tumor antigens (TA). Oneapproach to prime TA-reactive T-cells is to administerimmunostimulatory molecules, cells, or pathogens directlyto the tumor site, that is, in situ vaccination (ISV). Werecently described an ISV using Flt3L to expand and recruitdendritic cells (DC), radiotherapy to load DC with TA, andpattern recognition receptor agonists (PRRa) to activateTA-loaded DC. While ISV trials using synthetic PRRa haveyielded systemic tumor regressions, the optimal method toactivate DCs is unknown.Methods To discover optimal DC activators and increaseaccess to clinical grade reagents, we assessed whetherviral or bacterial components found in common pathogenvaccines are an effective source of natural PRRa(naPRRa). Using deep profiling (155-metric) of naPRRaimmunomodulatory effects and gene editing of specificPRR, we defined specific signatures and molecularmechanisms by which naPRRa potentiate T-cell priming.Results We observed that vaccine naPRRa can be evenmore potent in activating Flt3L-expanded murine andhuman DCs than synthetic PRRa, promoting cross-primingof TA-reactive T-cells. We developed a mechanisticallydiverse naPRRa combination (BCG, PedvaxHIB, Rabies)and noted more potent T-cell cross-priming than withany single naPRRa. The naPRRa triplet—as part of Flt3Lprimed ISV—induced greater intratumoral CD8 T-cellinfiltration, T-cells reactive to a newly defined tumorousneoantigen, durable tumor regressions.Conclusions This work provides rationale for thetranslation of pathogen vaccines as FDA-approved clinicalgrade DC activators which could be exploited as immunestimulants for early phase trials.

  • 49.
    Alfredsson, Joakim
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Duke University, NC 27710 USA.
    Alexander, Karen P.
    Duke University, NC 27710 USA.
    Multiple Chronic Conditions in Older Adults with Acute Coronary Syndromes2016In: Clinics in Geriatric Medicine, ISSN 0749-0690, E-ISSN 1879-8853, Vol. 32, no 2, p. 291-+Article in journal (Refereed)
    Abstract [en]

    Older adults presenting with acute coronary syndromes (ACSs) often have multiple chronic conditions (MCCs). In addition to traditional cardiovascular (CV) risk factors (ie, hypertension, hyperlipidemia, and diabetes), common CV comorbidities include heart failure, stroke, and atrial fibrillation, whereas prevalent non-CV comorbidities include chronic kidney disease, anemia, depression, and chronic obstructive pulmonary disease. The presence of MCCs affects the presentation (eg, increased frequency of type 2 myocardial infarctions [MIs]), clinical course, and prognosis of ACS in older adults. In general, higher comorbidity burden increases mortality following MI, reduces utilization of ACS treatments, and increases the importance of developing individualized treatment plans.

  • 50.
    Alfredsson, Joakim
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Region Östergötland, Heart Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Omar, Kime
    Vastmanland Cty Hosp, Sweden.
    Csog, Jozsef
    Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Venetsanos, Dimitrios
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Janzon, Magnus
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Cardiology in Linköping.
    Ekstedt, Mattias
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Bleeding complications with clopidogrel or ticagrelor in ST-elevation myocardial infarction patients: A real life cohort study of two treatment strategies2020In: IJC Heart & Vasculature, E-ISSN 2352-9067, Vol. 27, article id 100495Article in journal (Refereed)
    Abstract [en]

    Introduction

    Dual antiplatelet therapy (DAPT), including potent P2Y12 inhibition after ST-elevation myocardial infarction (STEMI) is recommended in clinical guidelines. However, bleeding complications are common, and associated with worse outcomes. The aim of this study was to assess incidence of bleeding events with a clopidogrel-based compared to a ticagrelor-based DAPT strategy, in a real world population. Secondary aims were to assess ischemic complications and mortality.

    Methods and Results

    We identified 330 consecutive STEMI patients with a clopidogrel-based and 330 with a ticagrelor-based DAPT strategy. Patientś medical records were searched for bleeding and ischemic complications, over 6 months follow-up.

    The two groups were well balanced in baseline characteristics, age (69 years inboth groups), sex (31% vs 32% females), history of diabetes (19% vs 21%), hypertension (43% in both) and MI (17% vs 15%). There was no difference in CRUSADE bleeding score (28 vs 29). After discharge, there were more than twice as many bleeding events with a ticagrelor-based compared with a clopidogrel-based strategy (13.3% vs. 6.5%, p = 0.005). Bleeding events included significantly more severe bleeding complications (TIMI major/minor [5.8 vs 1.0, p = 0.001]) during the ticagrelor-based period. There was no significant difference in the composite of death, MI or stroke (7.8% vs 7.1%, p = 0.76).

    Conclusions

    In this observational study, a ticagrelor-based DAPT strategy was associated with significantly more bleeding complications, without any significant change in death, MI or stroke. Larger studies are needed to determine whether bleeding complications off-sets benefits with a more potent DAPT strategy in older and more comorbid real-life patients.

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