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  • 1.
    Azharuddin, Mohammad
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences.
    Zhu, Geyunjian H.
    Univ Cambridge, England.
    Das, Debapratim
    Indian Inst Technol Guwahati, India.
    Ozgur, Erdogan
    Hacettepe Univ, Turkey.
    Uzun, Lokman
    Hacettepe Univ, Turkey.
    Turner, Anthony P. F.
    Cranfield Univ, England.
    Patra, Hirak Kumar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Univ Cambridge, England.
    A repertoire of biomedical applications of noble metal nanoparticles2019In: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 55, no 49, p. 6964-6996Article, review/survey (Refereed)
    Abstract [en]

    Noble metals comprise any of several metallic chemical elements that are outstandingly resistant to corrosion and oxidation, even at elevated temperatures. This group is not strictly defined, but the tentative list includes ruthenium, rhodium, palladium, silver, osmium, iridium, platinum and gold, in order of atomic number. The emerging properties of noble metal nanoparticles are attracting huge interest from the translational scientific community and have led to an unprecedented expansion of research and exploration of applications in biotechnology and biomedicine. Noble metal nanomaterials can be synthesised both by top-down and bottom up approaches, as well as via organism-assisted routes, and subsequently modified appropriately for the field of use. Nanoscale analogues of gold, silver, platinum, and palladium in particular, have gained primary importance owing to their excellent intrinsic properties and diversity of applications; they offer unique functional attributes, which are quite unlike the bulk material. Modulation of noble metal nanoparticles in terms of size, shape and surface functionalisation has endowed them with unusual capabilities and manipulation at the chemical level, which can lead to changes in their electrical, chemical, optical, spectral and other intrinsic properties. Such flexibility in multi-functionalisation delivers Ockhams razor to applied biomedical science. In this feature article, we highlight recent advances in the adaptation of noble metal nanomaterials and their biomedical applications in therapeutics, diagnostics and sensing.

    The full text will be freely available from 2020-05-21 00:01
  • 2.
    Bandyopadhyay, Souvik K.
    et al.
    GlaxoSmithKline Asia Pvt. Ltd., Bangalore, India.
    Azharuddin, Mohammad
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences.
    Dasgupta, Anjan K.
    Department of Biochemistry, University of Calcutta, Kolkata, India.
    Ganguli, Bhaswati
    Department of Statistics, University of Calcutta, Kolkata, India.
    SenRoy, Sugata
    Department of Statistics, University of Calcutta, Kolkata, India.
    Patra, Hirak Kumar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Wolfson College, University of Cambridge, Cambridge, United Kingdom; Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom.
    Deb, Suryyani
    Department of Biotechnology, Maulana Abul Kalam Azad University of Technology, Kolkata, India.
    Probing ADP Induced Aggregation Kinetics During Platelet-Nanoparticle Interactions: Functional Dynamics Analysis to Rationalize Safety and Benefits2019In: Frontiers in Bioengineering and Biotechnology, E-ISSN 2296-4185, Vol. 7, p. 163-Article in journal (Refereed)
    Abstract [en]

    Platelets, one of the most sensitive blood cells, can be activated by a range of external and internal stimuli including physical, chemical, physiological, and/or non-physiological agents. Platelets need to respond promptly during injury to maintain blood hemostasis. The time profile of platelet aggregation is very complex, especially in the presence of the agonist adenosine 5′-diphosphate (ADP), and it is difficult to probe such complexity using traditional linear dose response models. In the present study, we explored functional analysis techniques to characterize the pattern of platelet aggregation over time in response to nanoparticle induced perturbations. This has obviated the need to represent the pattern of aggregation by a single summary measure and allowed us to treat the entire aggregation profile over time, as the response. The modeling was performed in a flexible manner, without any imposition of shape restrictions on the curve, allowing smooth platelet aggregation over time. The use of a probabilistic framework not only allowed statistical prediction and inference of the aggregation signatures, but also provided a novel method for the estimation of higher order derivatives of the curve, thereby allowing plausible estimation of the extent and rate of platelet aggregation kinetics over time. In the present study, we focused on the estimated first derivative of the curve, obtained from the platelet optical aggregometric profile over time and used it to discern the underlying kinetics as well as to study the effects of ADP dosage and perturbation with gold nanoparticles. In addition, our method allowed the quantification of the extent of inter-individual signature variations. Our findings indicated several hidden features and showed a mixture of zero and first order kinetics interrupted by a metastable zero order ADP dose dependent process. In addition, we showed that the two first order kinetic constants were ADP dependent. However, we were able to perturb the overall kinetic pattern using gold nanoparticles, which resulted in autocatalytic aggregation with a higher aggregate mass and which facilitated the aggregation rate.

  • 3.
    Boud, David
    et al.
    Deakin University, Geelong, Australia / University of Technology, Sydney, Australia / Middlesex University, London, UK.
    Nyström, Sofia
    Linköping University, Department of Behavioural Sciences and Learning, Education and Adult Learning. Linköping University, Faculty of Educational Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Abrandt Dahlgren, Madeleine
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Gustavsson, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences.
    Kelly, Michelle
    Curtin University, Perth, Australia.
    O’Keeffe, Dara
    Royal College of Surgeons in Ireland, Dublin, Ireland.
    Learning through observation2019In: Interprofessional Simulation in Health Care: Materiality, Embodiment, Interaction / [ed] Madeleine Abrandt Dahlgren, Hans Rystedt, Li Felländer-Tsai & Sofia Nyström, Cham: Springer, 2019, p. 115-137Chapter in book (Refereed)
    Abstract [en]

    This chapter has a particular focus on the observers’ role in simulation-based learning activities. Simulation-based learning is often organised so that participants rotates between active participation in the scenario and participation as observers. The research examples provided show that the conditions for learning are related to the locations where and the ways the observers are situated, and to how the instructions to the observers are formulated. Arguments are put forward that the observers’ role in simulation has unexploited potential for developing skills of noticing.

  • 4.
    Chasapis, Christos T.
    et al.
    Hellas Forth, Greece.
    Makridakis, Manousos
    Acad Athens BRFAA, Greece.
    Damdimopoulos, Anastassios E.
    Karolinska Inst, Sweden.
    Zoidakis, Jerome
    Acad Athens BRFAA, Greece.
    Lygirou, Vasiliki
    Acad Athens BRFAA, Greece.
    Mavroidis, Manolis
    Acad Athens BRFAA, Greece.
    Vlahou, Antonia
    Acad Athens BRFAA, Greece.
    Miranda-Vizuete, Antonio
    Univ Seville, Spain.
    Spyrou, Giannis
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences.
    Vlamis-Gardikas, Alexios
    Univ Patras, Greece.
    Implications of the mitochondrial interactome of mammalian thioredoxin 2 for normal cellular function and disease2019In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 137, p. 59-73Article in journal (Refereed)
    Abstract [en]

    Multiple thioredoxin isoforms exist in all living cells. To explore the possible functions of mammalian mitochondrial thioredoxin 2 (Trx2), an interactome of mouse Trx2 was initially created using (i) a monothiol mouse Trx2 species for capturing protein partners from different organs and (ii) yeast two hybrid screens on human liver and rat brain cDNA libraries. The resulting interactome consisted of 195 proteins (Trx2 included) plus the mitochondrial 16S RNA. 48 of these proteins were classified as mitochondrial (MitoCarta2.0 human inventory). In a second step, the mouse interactome was combined with the current four-membered mitochondrial sub-network of human Trx2 (BioGRID) to give a 53-membered human Trx2 mitochondrial interactome (52 interactor proteins plus the mitochondrial 16S RNA). Although thioredoxins are thiol-employing disulfide oxidoreductases, approximately half of the detected interactions were not due to covalent disulfide bonds. This finding reinstates the extended role of thioredoxins as moderators of protein function by specific non-covalent, protein-protein interactions. Analysis of the mitochondrial interactome suggested that human Trx2 was involved potentially in mitochondrial integrity, formation of iron sulfur clusters, detoxification of aldehydes, mitoribosome assembly and protein synthesis, protein folding, ADP ribosylation, amino acid and lipid metabolism, glycolysis, the TCA cycle and the electron transport chain. The oxidoreductase functions of Trx2 were verified by its detected interactions with mitochondrial peroxiredoxins and methionine sulfoxide reductase. Parkinsons disease, triosephosphate isomerase deficiency, combined oxidative phosphorylation deficiency, and lactate dehydrogenase b deficiency are some of the diseases where the proposed mitochondrial network of Trx2 may be implicated.

  • 5.
    Deb, Suryyani
    et al.
    Maulana Abul Kazam Azad Univ Technol, India.
    Boknäs, Niklas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Sjöström, Clara
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Tharmakulanathan, Anjana
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Lotfi, Kourosh
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Ramström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Orebro Univ, Sweden.
    Varying effects of tyrosine kinase inhibitors on platelet function-A need for individualized CML treatment to minimize the risk for hemostatic and thrombotic complications?2019In: Cancer Medicine, ISSN 2045-7634, E-ISSN 2045-7634Article in journal (Refereed)
    Abstract [en]

    Since their introduction, tyrosine kinase inhibitors (TKIs, eg, imatinib, nilotinib, dasatinib, bosutinib, ponatinib) have revolutionized the treatment of chronic myeloid leukemia (CML). However, long-term treatment with TKIs is associated with serious adverse events including both bleeding and thromboembolism. Experimental studies have shown that TKIs can cause platelet dysfunction. Herein, we present the first side-by-side investigation comparing the effects of currently used TKIs on platelet function and thrombin generation when used in clinically relevant concentrations. A flow cytometry multiparameter protocol was used to study a range of significant platelet activation events (fibrinogen receptor activation, alpha granule, and lysosomal exocytosis, procoagulant membrane exposure, and mitochondrial permeability changes). In addition, thrombin generation was measured in the presence of TKIs to assess the effects on global hemostasis. Results show that dasatinib generally inhibited platelet function, while bosutinib, nilotinib, and ponatinib showed less consistent effects. In addition to these general trends for each TKI, we observed a large degree of interindividual variability in the effects of the different TKIs. Interindividual variation was also observed when blood from CML patients was studied ex vivo with whole blood platelet aggregometry, free oscillation rheometry (FOR), and flow cytometry. Based on the donor responses in the side-by-side TKI study, a TKI sensitivity map was developed. We propose that such a sensitivity map could potentially become a valuable tool to help in decision-making regarding the choice of suitable TKIs for a CML patient with a history of bleeding or atherothrombotic disease.

  • 6.
    Gawria, Ghassaan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Tillmar, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Landberg, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    A comparison of stability of chemical analytes in plasma from the BD Vacutainer (R) Barricor (TM) tube with mechanical separator versus tubes containing gel separator2019In: Journal of clinical laboratory analysis (Print), ISSN 0887-8013, E-ISSN 1098-2825, article id e23060Article in journal (Refereed)
    Abstract [en]

    Background: There is a need of prolonged stability of certain chemical analytes in lithium heparin tubes with separators. A new tube with a mechanical separator has recently been launched (Barricor (TM)), which according to the manufacturer may have these benefits. The aim of this study was to evaluate stability performance of this tube in comparison with plasma gel tubes under clinically realistic circumstances. Methods: Blood was collected in tubes containing lithium heparin with different separators; gel separator (Vacutainer (R) PST (TM), Becton Dickinson and Vacuette (R), Greiner bio-one) and mechanical separator (Vacutainer (R) Barricor (TM), Becton Dickinson). All tubes had an aspiration volume of 3 mL and were centrifuged at similar time and force. Tubes were transported manually or by car. Seven analytes from 122 patients were analyzed after 3 to 80 hours by Cobas c701 (Roche). Results The Barricor (TM) tube showed increased stability of phosphate and potassium and similar stability of aspartate aminotransferase, glucose, homocysteine, lactate dehydrogenase, and magnesium compared with gel tubes. Maximal allowable bias for phosphate was exceeded after 68 hours for Barricor (TM) tubes compared with 29 or 35 hours for gel tubes and for potassium after 40 hours for Barricor (TM) tubes vs 9 or 12 hours for gel tubes. Transportation did not affect stability. Hemolysis index was slightly lower in Barricor tubes than in gel tubes (P = .01). Conclusion Implementing the new Barricor (TM) tube will improve stability of potassium and phosphate in plasma. Blood sampling facilities far from the laboratory may benefit from using these tubes, thus diminishing preanalytical errors.

  • 7.
    Heenkenda, Menikae Kanchena
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Malmström, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Lysiak, Malgorzata
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Mudaisi, Munila
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Bratthall, Charlotte
    Dist Hosp, Sweden.
    Milos, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Strandeus, Michael
    Ryhov Hosp, Sweden.
    Åkesson, Lisa
    Linköping University, Department of Thematic Studies. Linköping University, Faculty of Arts and Sciences.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Uppugunduri, Srinivas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Osman, Abdimajid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Assessment of genetic and non-genetic risk factors for venous thromboembolism in glioblastoma - The predictive significance of B blood group2019In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 183, p. 136-142Article in journal (Refereed)
    Abstract [en]

    Introduction: Venous thromboembolism (VTE) is a common problem among patients with glioblastoma multi-forme (GBM) and with some other cancers. Here, we evaluated genetic and non-genetic potential risk factors for VTE among GBM patients. Materials and methods: A cohort of 139 patients treated with concomitant radiotherapy and temozolomide were included in the study. Next generation sequencing and genotyping approaches were applied to assess genetic risk factors in the haemostatic system. Clinical data including surgery, reoperation as well as blood group and patient information such as age and gender were available from patient records. Logistic regression analysis was performed to asses VTE risk. Results: In the study 47 patients (34%) were diagnosed for VTE during the course of their disease. When genetic and non-genetic potential risk factors were evaluated, only B blood group was found to be significantly associated with VTE incidence (odds ratio [OR] = 6.91; confidence interval [CI] = 2.19-24.14; P = 0.001). In contrast, A and O blood groups did not correlate with VTE risk. Frontal lobe tumor location also seemed to slightly increase VTE risk compared to other brain sites (OR = 3.14; CI = 1.1-10.7) although the significance level was at borderline (P = 0.05). Current study identified B blood group as the component in non-O blood groups that is responsible for increased VTE risk. Conclusion: In conclusion, these results suggest for the first time that B blood group is predictive for VTE incidence among patients with glioblastoma, information that may be potentially valuable when selecting GBM patients who are at risk for VTE for anticoagulant prophylaxis.

    The full text will be freely available from 2020-10-22 14:11
  • 8.
    Hopwood, Nick
    et al.
    University of Technology Sydney, Sydney, Australia / University of StellenboschStellenboschSouth Africa.
    Ahn, Song-ee
    Linköping University, Department of Behavioural Sciences and Learning, Education and Adult Learning. Linköping University, Faculty of Educational Sciences.
    Rimpiläinen, Sanna
    University of StrathclydeGlasgowScotland.
    Dahlberg, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences.
    Nyström, Sofia
    Linköping University, Department of Behavioural Sciences and Learning, Education and Adult Learning. Linköping University, Faculty of Educational Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Johnson, Ericka
    Linköping University, Department of Thematic Studies, The Department of Gender Studies. Linköping University, Faculty of Arts and Sciences.
    Doing interprofessional simulation: Bodily enactments in interprofessional simulation2019In: Interprofessional simulation in health care: Materiality, embodiment, interaction / [ed] Madeleine Abrandt Dahlgren, Hans Rystedt, Li Felländer-Tsai and Sofia Nyström, Cham, Schweiz: Springer, 2019, 1, p. 91-113Chapter in book (Other academic)
    Abstract [en]

    This chapter illustrate how the social and material arrangements for interprofessional simulation produces different conditions for learning. The first section focuses on the emerging medical knowing, affective knowing and communicative knowing in the socio-material arrangements of three locations involved in the simulation, i.e. the simulation room, the observation room and the reflection room, during the course of events in the scenario. The second section focuses on emerging rhythms of collaboration. Different ways of relating to the manikin as a technical, medical and human body, and the relevance of these findings for simulation pedagogy are described.

  • 9.
    Jackmann, Natalja
    et al.
    Univ Childrens Hosp, Sweden.
    Makitie, Outi
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Harila-Saari, Arja
    Univ Childrens Hosp, Sweden.
    Gustafsson, Jan
    Univ Childrens Hosp, Sweden.
    Dernroth, Dzeneta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Frisk, Per
    Univ Childrens Hosp, Sweden.
    Vitamin D status in children with leukemia, its predictors, and association with outcome2020In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, article id e28163Article in journal (Refereed)
    Abstract [en]

    Background Children and adolescents with leukemia are potentially at high risk of vitamin D inadequacy, which may have clinical relevance for skeletal morbidity, infections, and cancer outcome. This study aimed to evaluate vitamin D status at the time of diagnosis to investigate its predictors and association with overall survival in children with leukemia. Procedure We included all 295 children and adolescents diagnosed with leukemia at our institution between 1990 and 2016 who had available serum sample from the time of diagnosis. We analyzed serum 25-hydroxyvitamin D and parathyroid hormone levels and correlated them with clinical data. Results The 25-hydroxyvitamin D level was deficient (amp;lt; 25 nmol/L), insufficient (25-50 nmol/L), sufficient (50-75 nmol/L), and optimal (amp;gt; 75 nmol/L) in 6.4%, 26.8%, 39.7%, and 27.1% of the children, respectively. Older age and a more recent time of sampling (calendar year) predicted lower 25-hydroxyvitamin D level. In preschool children (age amp;lt;= 6 years), lower 25-hydroxyvitamin D level was also associated with acute myeloid leukemia, and a 25-hydroxyvitamin D level amp;lt; 50 nmol/L was associated with inferior overall survival. In school-aged children (age amp;gt; 6 years), the 25-hydroxyvitamin D level showed significant seasonal variation. Conclusion It remains unclear whether vitamin D supplementation in pediatric leukemia patients will improve outcome.

  • 10.
    Kallner, Anders
    et al.
    Karolinska Univ Hosp, Sweden.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    An experimental study of methods for the analysis of variance components in the inference of laboratory information2020In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686Article in journal (Refereed)
    Abstract [en]

    Measurement uncertainty (MU) can be estimated and calculated by different procedures, representing different aspects and intended use. It is appropriate to distinguish between uncertainty determined under repeatability and reproducibility conditions, and to distinguish causes of variation using analysis of variance components. The intra-laboratory MU is frequently determined by repeated measurements of control material(s) of one or several concentrations during a prolonged period of time. We demonstrate, based on experimental results, how such results can be used to identify the repeatability, pure reproducibility and intra-laboratory variance as the sum of the two. Native patient material was used to establish repeatability using the Dahlberg formula for random differences between measurements and an expanded Dahlberg formula if a non-random difference, e.g. bias, was expected. Repeatability and reproducibility have different clinical relevance in intensive care compared to monitoring treatment of chronic diseases, comparison with reference intervals or screening.

  • 11.
    Leijon, Ingemar
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Bladh, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Finnström, Orvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Gäddlin, Per-Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Futurum, Sweden.
    Nelson Follin, Nina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala. Karolinska Univ Hosp, Sweden.
    Hammar, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Sydsjö, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Self-reported mental health and cortisol activity at 27-28 years of age in individuals born with very low birthweight2019In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227Article in journal (Refereed)
    Abstract [en]

    Aim

    To assess mental health outcomes of very low birthweight (VLBW, <1500 g) subjects to adulthood and to examine salivary cortisol and hair cortisol levels and their relation to birth characteristics and mental health.

    Methods

    A Swedish regional cohort of 56 VLBW subjects and 55 full‐term controls were assessed at the ages 27‐28 with adult self‐reported scales and the mean of 2 days diurnal salivary cortisol and hair cortisol. The cohorts had been assessed at 15 years of age with youth self‐reported scales.

    Results

    There were no differences between the groups in youth self‐reported scales and adult self‐reported scores. The 24 participating VLBW girls scored lower on youth self‐reported scales externalising and total problem scores than the control girls. In adulthood, the 21 participating VLBW women had significantly higher morning concentrations of salivary cortisol than control women, P = .014. No significant associations were found between cortisol concentrations and adult self‐reported scales internalising, externalising and total scores.

    Conclusion

    Self‐reported mental health in VLBW subjects was comparable with normal birthweight controls indicating a satisfying transition from adolescence to adulthood. VLBW females had higher morning salivary cortisol concentrations, suggesting a gender difference. We found no correlations between cortisol and mental health.

  • 12.
    Macwan, Ankit
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences.
    Boknäs, Niklas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Ntzouni, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Ramström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Orebro Univ, Sweden.
    Gibbins, Jonathan M.
    Univ Reading, England.
    Faxälv, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Gradient-dependent inhibition of stimulatory signaling from platelet G protein-coupled receptors2019In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 104, no 7Article in journal (Refereed)
    Abstract [en]

    As platelet activation is an irreversible and potentially harmful event, platelet stimulatory signaling must be tightly regulated to ensure the filtering-out of inconsequential fluctuations of agonist concentrations in the vascular milieu. Herein, we show that platelet activation via G protein-coupled receptors is gradient-dependent, i.e., determined not only by agonist concentrations per se but also by how rapidly concentrations change over time. We demonstrate that gradient-dependent inhibition is a common feature of all major platelet stimulatory G protein-coupled receptors, while platelet activation via the non-G protein-coupled receptor glycoprotein VI is strictly concentration-dependent. By systematically characterizing the effects of variations in temporal agonist concentration gradients on different aspects of platelet activation, we demonstrate that gradient-dependent inhibition of protease-activated receptors exhibits different kinetics, with platelet activation occurring at lower agonist gradients for protease-activated receptor 4 than for protease-activated receptor 1, but shares a characteristic bimodal effect distribution, as gradient-dependent inhibition increases over a narrow range of gradients, below which aggregation and granule secretion is effectively shut off. In contrast, the effects of gradient-dependent inhibition on platelet activation via adenosine diphosphate and thromboxane receptors increase incrementally over a large range of gradients. Furthermore, depending on the affected activation pathway, gradient-dependent inhibition results in different degrees of refractoriness to subsequent autologous agonist stimulation. Mechanistically, our study identifies an important role for the cyclic adenosine monophosphate-dependent pathway in gradient-dependent inhibition. Together, our findings suggest that gradient-dependent inhibition may represent a new general mechanism for hemostatic regulation in platelets.

  • 13.
    Patra, Hirak Kumar
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Department of Chemical Engineering and Biotechnology, Cambridge University, Cambridge, UK; Wolfson College, University of Cambridge, Cambridge, UK.
    Azharuddin, Mohammad
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences.
    Islam, Mohammad Mirazul
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Massachusetts Eye and Ear and Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, USA.
    Papapavlou, Georgia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Deb, Suryyani
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Department of Biochemistry, University of Calcutta, Calcutta, India; Department of Biotechnology, Maulana Abul Kalam Azad University of Technology (MAKAUT), West Bengal, India.
    Osterrieth, Johannes
    Department of Chemical Engineering and Biotechnology, Cambridge University, Philippa Fawcett Drive, Cambridge, UK.
    Zhu, Geyunjian Harry
    Department of Chemical Engineering and Biotechnology, Cambridge University, Philippa Fawcett Drive, Cambridge, UK.
    Romu, Thobias
    Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dhara, Ashis K.
    Centre for Image Analysis, Uppsala University, Uppsala, Sweden; Department of Electrical Engineering, National Institute of Technology Durgapur, West Bengal, India.
    Jafari, Mohammad Javad
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Gadheri, Amineh
    Department of Oncology‐Pathology, Karolinska Institute, Stockholm, Sweden.
    Hinkula, Jorma
    Linköping University, Department of Clinical and Experimental Medicine, Division of Hematopoiesis and Developmental Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Rajan, Madhavan S.
    Department of Ophthalmology, Cambridge University Hospitals NHS Trust and Vision and Eye Research Institute (VERI), Anglia Ruskin University, Cambridge, UK.
    Slater, Nigel K. H.
    Department of Chemical Engineering and Biotechnology, Cambridge University, Philippa Fawcett Drive, Cambridge, UK.
    Rational Nanotoolbox with Theranostic Potential for Medicated Pro-Regenerative Corneal Implants2019In: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, article id 1903760Article in journal (Refereed)
    Abstract [en]

    Cornea diseases are a leading cause of blindness and the disease burden is exacerbated by the increasing shortage around the world for cadaveric donor corneas. Despite the advances in the field of regenerative medicine, successful transplantation of laboratory‐made artificial corneas is not fully realized in clinical practice. The causes of failure of such artificial corneal implants are multifactorial and include latent infections from viruses and other microbes, enzyme overexpression, implant degradation, extrusion or delayed epithelial regeneration. Therefore, there is an urgent unmet need for developing customized corneal implants to suit the host environment and counter the effects of inflammation or infection, which are able to track early signs of implant failure in situ. This work reports a nanotoolbox comprising tools for protection from infection, promotion of regeneration, and noninvasive monitoring of the in situ corneal environment. These nanosystems can be incorporated within pro‐regenerative biosynthetic implants, transforming them into theranostic devices, which are able to respond to biological changes following implantation.

    The full text will be freely available from 2020-07-15 00:01
  • 14.
    Rajan, Meenu Rohini
    et al.
    Univ Gothenburg, Sweden.
    Sotak, Matus
    Univ Gothenburg, Sweden.
    Barrenas, Fredrik
    Univ Gothenburg, Sweden; Uppsala Univ, Sweden.
    Shen, Tong
    Univ Calif Davis, CA 95616 USA.
    Borkowski, Kamil
    Univ Calif Davis, CA 95616 USA.
    Ashton, Nicholas J.
    Univ Gothenburg, Sweden; Kings Coll London, England; NIHR Biomed Res Ctr Mental Hlth, England; Biomed Res Unit Dementia South London, England; Maudsley NHS Fdn, England.
    Biorserud, Christina
    Univ Gothenburg, Sweden.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Ramström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Orebro Univ, Sweden.
    Scholl, Michael
    Univ Gothenburg, Sweden; UCL, England.
    Lindahl, Per
    Univ Gothenburg, Sweden.
    Fiehn, Oliver
    Univ Calif Davis, CA 95616 USA.
    Newman, John W.
    Univ Calif Davis, CA 95616 USA; ARS, CA USA.
    Perkins, Rosie
    Univ Gothenburg, Sweden.
    Wallenius, Ville
    Univ Gothenburg, Sweden.
    Lange, Stephan
    Univ Gothenburg, Sweden; Univ Calif San Diego, CA 92103 USA.
    Borgeson, Emma
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Comparative analysis of obesity-related cardiometabolic and renal biomarkers in human plasma and serum2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 15385Article in journal (Refereed)
    Abstract [en]

    The search for biomarkers associated with obesity-related diseases is ongoing, but it is not clear whether plasma and serum can be used interchangeably in this process. Here we used high-throughput screening to analyze 358 proteins and 76 lipids, selected because of their relevance to obesity-associated diseases, in plasma and serum from age- and sex-matched lean and obese humans. Most of the proteins/lipids had similar concentrations in plasma and serum, but a subset showed significant differences. Notably, a key marker of cardiovascular disease PAI-1 showed a difference in concentration between the obese and lean groups only in plasma. Furthermore, some biomarkers showed poor correlations between plasma and serum, including PCSK9, an important regulator of cholesterol homeostasis. Collectively, our results show that the choice of biofluid may impact study outcome when screening for obesity-related biomarkers and we identify several markers where this will be the case.

  • 15.
    Ramström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Orebro Univ, Sweden.
    Arachidonic acid causes lysis of blood cells and ADP-dependent platelet activation responses in platelet function tests2019In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 30, no 8, p. 1001-1007Article in journal (Refereed)
    Abstract [en]

    The use of arachidonic acid (AA) to stimulate platelets is considered as a specific approach to study aspirin treatment efficacy. However, very high concentrations of AA are used, and it has been previously reported that AA can induce cell lysis in other settings. Several clinical studies have reported decreased responses to AA in whole blood tests in the presence of clopidogrel. Our aim was to investigate whether unspecific effects contribute to AA-induced aggregation and platelet activation in light transmission aggregometry (LTA) in platelet-rich plasma (PRP), and in assays using whole blood, multiple electrode aggregometry (MEA, Multiplate?), and flow cytometry. We report that cell lysis, especially of red blood cells, does occur at concentrations of AA used in the clinical tests and that ADP is very important for the AA-induced platelet activation responses. In flow cytometry, very limited platelet activation was detected before reaching AA concentrations in the millimolar range, where cell lysis also occurred, making it problematic to develop a reliable flow cytometry assay using AA as reagent. We conclude that cell lysis and ADP release contribute to AA-induced platelet responses, most markedly in whole blood assays. This finding could potentially explain some differences between studies comparing methods using whole blood and PRP and also how clopidogrel treatment could influence AA-induced aggregation results in previously published studies. Our findings highlight some issues with AA as reagent for platelet activation, which also have an impact on how platelet activation assays using AA should be interpreted.

  • 16.
    Singh, Sukhi
    et al.
    Univ Gothenburg, Sweden.
    Damen, Tor
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Nygren, Andreas
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Hakimi, Caroline Shams
    Univ Gothenburg, Sweden.
    Ramström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Orebro Univ, Sweden.
    Dellborgl, Mikael
    Univ Gothenburg, Sweden.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Hesse, Camilla
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Jeppsson, Anders
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Adrenaline Improves Platelet Reactivity in Ticagrelor-Treated Healthy Volunteers2019In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 119, no 5, p. 735-743Article in journal (Refereed)
    Abstract [en]

    Background Administration of agents that enhance platelet reactivity may reduce the perioperative bleeding risk in patients treated with the adenosine diphosphate (ADP)-receptor antagonist ticagrelor. Adrenaline potentiates ADP-induced aggregation and activation in blood samples from ticagrelor-treated patients, but it has not previously been evaluated in vivo. Methods Ten healthy male subjects were included in an interventional study. A loading dose of ticagrelor (180 mg) was administered, followed 2 hours later by a gradually increased intravenous adrenaline infusion (0.01, 0.05, 0.10 and 0.15 mu g/kg/min; 15 minutes at each step). Blood pressure, heart rate, platelet aggregation (impedance aggregometry), platelet activation (flow cytometry), clot formation (rotational thromboelastometry) and adrenaline plasma concentration were determined before and after ticagrelor administration and at the end of each adrenaline step. Results Infusion of adrenaline increased ADP-induced aggregation at all doses above 0.01 mu g/kg/min. The aggregation increased from median 17 (25-75th percentiles: 14-31) to 25 (21-34) aggregation units (p = 0.012) at 0.10 mu g/kg/min. Adrenaline infusion also increased ADP-induced fibrinogen receptor activation (from 29 [22-35] to 46 [38-57%]) and P-selectin expression (from 3.7 [3.0-4.3] to 7.7 [4.7-8.6%]), both p=0.012. Adrenaline infusion reduced clot formation time (97 [89-110] to 83 [76-90] seconds, p = 0.008) and increased maximum clot firmness (59 [57-60] to 62 [61-64] mm, p = 0.007). Conclusion Infusion of adrenaline at clinically relevant doses improves in vivo platelet reactivity and clot formation in ticagrelor-treated subjects. Adrenaline could thus potentially be used to prevent perioperative bleeding complications in ticagrelor-treated patients. Studies in patients are necessary to determine the clinical importance of our observations.

  • 17.
    Singh, Sukhi
    et al.
    Univ Gothenburg, Sweden.
    Damen, Tor
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Nygren, Andreas
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Hakimi, Caroline Shams
    Univ Gothenburg, Sweden.
    Ramström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Orebro Univ, Sweden.
    Dellborgl, Mikael
    Univ Gothenburg, Sweden.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Hesse, Camilla
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Jeppsson, Anders
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Adrenaline Improves Platelet Reactivity in Ticagrelor-Treated Healthy Volunteers2019In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 119, no 5, p. 735-743Article in journal (Refereed)
    Abstract [en]

    Background Administration of agents that enhance platelet reactivity may reduce the perioperative bleeding risk in patients treated with the adenosine diphosphate (ADP)-receptor antagonist ticagrelor. Adrenaline potentiates ADP-induced aggregation and activation in blood samples from ticagrelor-treated patients, but it has not previously been evaluated in vivo. Methods Ten healthy male subjects were included in an interventional study. A loading dose of ticagrelor (180 mg) was administered, followed 2 hours later by a gradually increased intravenous adrenaline infusion (0.01, 0.05, 0.10 and 0.15 mu g/kg/min; 15 minutes at each step). Blood pressure, heart rate, platelet aggregation (impedance aggregometry), platelet activation (flow cytometry), clot formation (rotational thromboelastometry) and adrenaline plasma concentration were determined before and after ticagrelor administration and at the end of each adrenaline step. Results Infusion of adrenaline increased ADP-induced aggregation at all doses above 0.01 mu g/kg/min. The aggregation increased from median 17 (25-75th percentiles: 14-31) to 25 (21-34) aggregation units (p = 0.012) at 0.10 mu g/kg/min. Adrenaline infusion also increased ADP-induced fibrinogen receptor activation (from 29 [22-35] to 46 [38-57%]) and P-selectin expression (from 3.7 [3.0-4.3] to 7.7 [4.7-8.6%]), both p=0.012. Adrenaline infusion reduced clot formation time (97 [89-110] to 83 [76-90] seconds, p = 0.008) and increased maximum clot firmness (59 [57-60] to 62 [61-64] mm, p = 0.007). Conclusion Infusion of adrenaline at clinically relevant doses improves in vivo platelet reactivity and clot formation in ticagrelor-treated subjects. Adrenaline could thus potentially be used to prevent perioperative bleeding complications in ticagrelor-treated patients. Studies in patients are necessary to determine the clinical importance of our observations.

  • 18.
    Sundman, Ann-Sofie
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    van Poucke, Enya
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Svensson Holm, Ann-Charlotte
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Olsen Faresjö, Åshild
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Roth, Lina
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Long-term stress levels are synchronized in dogs and their owners2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 7391Article in journal (Refereed)
    Abstract [en]

    This study reveals, for the first time, an interspecific synchronization in long-term stress levels. Previously, acute stress, has been shown to be highly contagious both among humans and between individuals of other species. Here, long-term stress synchronization in dogs and their owners was investigated. We studied 58 dog-human dyads and analyzed their hair cortisol concentrations (HCC) at two separate occasions, reflecting levels during previous summer and winter months. The personality traits of both dogs and their owners were determined through owner-completed Dog Personality Questionnaire (DPQ) and human Big Five Inventory (BFI) surveys. In addition, the dogs activity levels were continuously monitored with a remote cloud-based activity collar for one week. Shetland sheepdogs (N = 33) and border collies (N = 25), balanced for sex, participated, and both pet dogs and actively competing dogs (agility and obedience) were included to represent different lifestyles. The results showed significant interspecies correlations in long-term stress where human HCC from both summer and winter samplings correlated strongly with dog HCC (summer: N = 57, chi(2) = 23.697, P amp;lt; 0.001, beta = 0.235; winter: N = 55, chi(2) = 13.796, P amp;lt; 0.001, beta = 0.027). Interestingly, the dogs activity levels did not affect HCC, nor did the amount of training sessions per week, showing that the HCC levels were not related to general physical activity. Additionally, there was a seasonal effect in HCC. However, although dogs personalities had little effects on their HCC, the human personality traits neuroticism, conscientiousness, and openness significantly affected dog HCC. Hence, we suggest that dogs, to a great extent, mirror the stress level of their owners.

  • 19.
    Svedlund, A.
    et al.
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Hallbook, T.
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Magnusson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Dahlgren, J.
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Swolin-Eide, D.
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Prospective study of growth and bone mass in Swedish children treated with the modified Atkins diet2019In: European journal of paediatric neurology, ISSN 1090-3798, E-ISSN 1532-2130, Vol. 23, no 4, p. 629-638Article in journal (Refereed)
    Abstract [en]

    Purpose: The modified Atkins diet (MAD) is a less restrictive treatment option than the ketogenic diet (KD) for intractable epilepsy and some metabolic conditions. Prolonged KD treatment may decrease bone mineralization and affect linear growth; however, long-term studies of MAD treatment are lacking. This study was designed to assess growth, body composition, and bone mass in children on MAD treatment for 24 months. Methods: Thirty-eight patients, mean age (SD) 6.1 years (4.8 years), 21 girls, with intractable epilepsy (n = 22), glucose transporter type 1 deficiency syndrome (n = 7), or pyruvate dehydrogenase complex deficiency (n = 9) were included. Body weight, height, body mass index (BMI), bone mass, and laboratory tests (calcium, phosphorus, magnesium, alkaline phosphatase, cholesterol, 25-hydroxyvitamin D, insulin-like growth factor-I and insulin-like growth factor binding protein 3) were assessed at baseline and after 24 months of MAD treatment. Results: Approximately 50% of the patients responded with more than 50% seizure reduction. Weight and height standard deviation score (SDS) were stable over 24 months, whereas median (minimum maximum) BMI SDS increased from 0.2 (-3.3 to 4.5) to 0.7 (-0.9 to 2.6), p amp;lt; 0.005. No effects were observed for bone mass (total body, lumbar spine and hip) or fat mass. Conclusions: The MAD was efficient in reducing seizures, and no negative effect was observed on longitudinal growth or bone mass after MAD treatment for 24 months. (C) 2019 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.

  • 20.
    Sydsjö, Gunilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Törnblom, Pia
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Gäddlin, Per-Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Finnström, Orvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Leijon, Ingemar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Nelson Follin, Nina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus. Karolinska Univ Hosp, Sweden.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Hammar, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Women born with very low birth weight have similar menstrual cycle pattern, pregnancy rates and hormone profiles compared with women born at term2019In: BMC Women's Health, ISSN 1472-6874, E-ISSN 1472-6874, Vol. 19, no 1, article id 56Article in journal (Refereed)
    Abstract [en]

    Background

    Individuals born very preterm or with very low birth weight (VLBW) have a reduced likelihood to reproduce according to population-based register studies. Extremely low-birth weight born adults had a lower reproduction rate for both men and women in a follow-up study.

    Aim

    To investigate if being born with VLBW is associated with differences in the reproductive health, i.e. age of menarche, menstrual cycle pattern, pregnancy rates and hormone profile compared with women born at term.

    Methods

    A prospective long-term follow-up of a cohort of live-born VLBW children and their controls studied repeatedly since birth and now assessed at 26–28 years of age. Of the totally 80 girls enrolled from birth 49 women (24 VLBW women and 25 controls) participated in the current follow-up. The women’s anthropometric data and serum hormone levels were analysed.

    Results

    The reproductive hormone levels, including Anti-Mullerian Hormone, did not differ significantly between VLBW women and their controls. Both groups reported menstrual cycle irregularities and pregnancies to the same extent but the VLBW women reported 1.5 years later age of menarche. The VLBW subjects had a catch-up growth within 18 months of birth but remained on average 5 cm shorter in adult height. There were no significant differences in BMI, sagittal abdominal diameter, blood pressure or in their answers regarding life style between the VLBW women and the controls.

    Conclusion

    No differences in the reproductive hormone levels were found between VLBW women and their controls. Although age at menarche was somewhat higher in the VLBW group menstrual cycles and pregnancy rates were similar in the VLBW and control groups. Further follow-up studies are required to elucidate the health outcomes of being born VLBW.

  • 21.
    Tufvesson Stiller, Helena
    et al.
    Region Östergötland, Center for Business support and Development, Regional Cancer Center. Dermatology, Department of Public Health and Clincal Medicine, Umeå University, Sweden.
    Mikiver, R.
    Region Östergötland, Center for Business support and Development, Regional Cancer Center.
    Uppugunduri, Srinivas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Lindholm, C.
    Region Östergötland, Center for Business support and Development, Regional Cancer Center.
    Mansson Brahme, Eva
    Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
    Schmitt-Egenolf, Marcus
    Department of Public Health and Clinical Medicine, Umeå University, Sweden.
    Health-related quality of life in patients with melanoma - characterization of a Swedish cohort2019In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133Article in journal (Other academic)
    Abstract [en]

    Abstract not available.

  • 22.
    Uhlin, Fredrik
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology. Tallinn Univ Technol, Estonia.
    Fernström, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    Knapen, Marjo H. J.
    Maastricht Univ, Netherlands.
    Vermeer, Cees
    Maastricht Univ, Netherlands.
    Magnusson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Long-term follow-up of biomarkers of vascular calcification after switch from traditional hemodialysis to online hemodiafiltration2019In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 79, no 3, p. 174-181Article in journal (Refereed)
    Abstract [en]

    Rapid progression of vascular calcification (VC) in hemodialysis (HD) patients is caused by several factors including inflammation and an imbalance between active inducers and inhibitors of VC. Growing evidence shows that online hemodiafiltration (ol-HDF), a combination of diffusive and convective solute transport, has positive effects on the uremic environment that affects patients on dialysis. However, we recently reported that serum 25-hydroxyvitamin D (25(OH)D) decreased after a switch from HD to ol-HDF. As a consequence of this finding, the present study was undertaken to investigate if inducers and inhibitors of VC (i.e. the inactive matrix Gla protein fractions dp-ucMGP and t-ucMGP, fetuin-A, Gla-rich protein (GRP), osteopontin (OPN), bone-specific alkaline phosphatase (BALP), and osteoprotegerin (OPG)) also are affected by ol-HDF. This non-comparative prospective study comprised 35 prevalent patients who were investigated 6, 12, and 24 months after their switch from HD to ol-HDF. Most patients had increased levels of the calcification inhibitors OPN and OPG; and of the inactive calcification inhibitor dp-ucMGP during the study period irrespective of the dialysis modality. BALP and t-ucMGP were mostly within the reference interval, but fetuin-A was mostly below the reference interval during the study period. OPN was significantly associated with BALP and parathyroid hormone, r = 0.62 and r = 0.65 (p amp;lt; .001), respectively. In conclusion, in contrast to decreased 25(OH)D levels, no differences were found for any of the measured biomarkers of VC following the switch from HD to ol-HDF. Further studies are needed to elucidate how these biomarkers can contribute to calcification risk assessment.

  • 23.
    Wei, Yong
    et al.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering. Univ Hlth Network, Canada; Struct Genom Consortium, Canada.
    Resetca, Diana
    Univ Hlth Network, Canada; Univ Toronto, Canada.
    Li, Zhe
    Yokohama City Univ, Japan.
    Johansson-Åkhe, Isak
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Ahlner, Alexandra
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Helander, Sara
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences.
    Wallenhammar, Amélie
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Morad, Vivian
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Raught, Brian
    Univ Hlth Network, Canada; Univ Toronto, Canada.
    Wallner, Björn
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Kokubo, Tetsuro
    Yokohama City Univ, Japan.
    Tong, Yufeng
    Struct Genom Consortium, Canada; Univ Windsor, Canada.
    Penn, Linda Z.
    Univ Hlth Network, Canada; Univ Toronto, Canada.
    Sunnerhagen, Maria
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Multiple direct interactions of TBP with the MYC oncoprotein2019In: Nature Structural & Molecular Biology, ISSN 1545-9993, E-ISSN 1545-9985, Vol. 26, no 11, p. 1035-+Article in journal (Refereed)
    Abstract [en]

    Transcription factor c-MYC is a potent oncoprotein; however, the mechanism of transcriptional regulation via MYC-protein interactions remains poorly understood. The TATA-binding protein (TBP) is an essential component of the transcription initiation complex TFIID and is required for gene expression. We identify two discrete regions mediating MYC-TBP interactions using structural, biochemical and cellular approaches. A 2.4 -angstrom resolution crystal structure reveals that human MYC amino acids 98-111 interact with TBP in the presence of the amino-terminal domain 1 of TBP-associated factor 1 (TAF1(TAND1)). Using biochemical approaches, we have shown that MYC amino acids 115-124 also interact with TBP independently of TAF1(TAND1). Modeling reveals that this region of MYC resembles a TBP anchor motif found in factors that regulate TBP promoter loading. Site-specific MYC mutants that abrogate MYC-TBP interaction compromise MYC activity. We propose that MYC-TBP interactions propagate transcription by modulating the energetic landscape of transcription initiation complex assembly.

  • 24.
    Zimdahl Kahlin, Anna
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Helander, Sara
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences.
    Skoglund, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Mårtensson, Lars-Göran
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Lindqvist Appell, Malin
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Comprehensive study of thiopurine methyltransferase genotype, phenotype, and genotype-phenotype discrepancies in Sweden2019In: Biochemical Pharmacology, ISSN 0006-2952, E-ISSN 1356-1839, Vol. 164, p. 263-272Article in journal (Refereed)
    Abstract [en]

    Thiopurines are widely used in the treatment of leukemia and inflammatory bowel diseases. Thiopurine metabolism varies among individuals because of differences in the polymorphic enzyme thiopurine methyltransferase (TPMT, EC 2.1.1.67), and to avoid severe adverse reactions caused by incorrect dosing it is recommended that the patients TPMT status be determined before the start of thiopurine treatment. This study describes the concordance between genotyping for common TPMT alleles and phenotyping in a Swedish cohort of 12,663 patients sampled before or during thiopurine treatment. The concordance between TPMT genotype and enzyme activity was 94.5%. Compared to the genotype, the first measurement of TPMT enzyme activity was lower than expected for 4.6% of the patients. Sequencing of all coding regions of the TPMT gene in genotype/phenotype discrepant individuals led to the identification of rare and novel TPMT alleles. Fifteen individuals (0.1%) with rare or novel genotypes were identified, and three TPMT alleles (TPMT*42, *43, and *44) are characterized here for the first time. These 15 patients would not have been detected as carrying a deviating TPMT genotype if only genotyping of the most common TPMT variants had been performed. This study highlights the benefit of combining TPMT genotype and phenotype determination in routine testing. More accurate dose recommendations can be made, which might decrease the number of adverse reactions and treatment failures during thiopurine treatment.

    The full text will be freely available from 2020-04-18 07:47
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