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  • 1.
    Aaseth, Jan
    et al.
    Innlandet Hosp, Norway; Inland Norway Univ Appl Sci, Norway.
    Ellefsen, Stian
    Inland Norway Univ Appl Sci, 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.
    Sundfor, Tine M.
    Oslo Univ Hosp, Norway.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Diets and drugs for weight loss and health in obesity: An update2021In: Biomedicine and Pharmacotherapy, ISSN 0753-3322, E-ISSN 1950-6007, Vol. 140, article id 111789Article, review/survey (Refereed)
    Abstract [en]

    Numerous combinations of diets and pharmacological agents, including lifestyle changes, have been launched to treat obesity. There are still ambiguities regarding the efficacies of different approaches despite many clinical trials and the use of animal models to study physiological mechanisms in weight management and obesity comorbidities, Here, we present an update on promising diets and pharmacological aids. Literature published after the year 2005 was searched in PubMed, Medline and Google scholar. Among recommended diets are low-fat (LF) and low-carbohydrate (LC) diets, in addition to the Mediterranean diet and the intermittent fasting approach, all of which presumably being optimized by adequate contents of dietary fibers. A basic point for weight loss is to adopt a diet that creates a permanently negative and acceptable energy balance, and prolonged dietary adherence is a crucial factor. As for pharmacological aids, obese patients with type 2 diabetes or insulin resistance seem to benefit from LC diet combined with a GLP-1 agonist, e.g. semaglutide, which may improve glycemic control, stimulate satiety, and suppress appetite. The lipase inhibitor orlistat is still used to maintain a low-fat approach, which may be favorable e.g. in hypercholesterolemia. The bupropion-naltrexone-combination appears promising for interruption of the vicious cycle of addictive over-eating. Successful weight loss seems to improve almost all biomarkers of obesity comorbidities. Until more support for specific strategies is available, clinicians should recommend an adapted lifestyle, and when necessary, a drug combination tailored to individual needs and comorbidities. Different diets may change hormonal secretion, gut-brain signaling, and influence hunger, satiety and energy expenditure. Further research is needed to clarify mechanisms and how such knowledge can be used in weight management.

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  • 2.
    Aaseth, Jan O.
    et al.
    Innlandet Hosp Trust, Norway; Inland Norway Univ Appl Sci, 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.
    Opstad, Trine Baur
    Oslo Univ Hosp Ullevaal, Norway; Univ Oslo, Norway.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Vitamin K and Calcium Chelation in Vascular Health2023In: Biomedicines, E-ISSN 2227-9059, Vol. 11, no 12, article id 3154Article, review/survey (Refereed)
    Abstract [en]

    The observation that the extent of artery calcification correlates with the degree of atherosclerosis was the background for the alternative treatment of cardiovascular disease with chelator ethylenediamine tetraacetate (EDTA). Recent studies have indicated that such chelation treatment has only marginal impact on the course of vascular disease. In contrast, endogenous calcium chelation with removal of calcium from the cardiovascular system paralleled by improved bone mineralization exerted, i.e., by matrix Gla protein (MGP) and osteocalcin, appears to significantly delay the development of cardiovascular diseases. After post-translational vitamin-K-dependent carboxylation of glutamic acid residues, MGP and other vitamin-K-dependent proteins (VKDPs) can chelate calcium through vicinal carboxyl groups. Dietary vitamin K is mainly provided in the form of phylloquinone from green leafy vegetables and as menaquinones from fermented foods. Here, we provide a review of clinical studies, addressing the role of vitamin K in cardiovascular diseases, and an overview of vitamin K kinetics and biological actions, including vitamin-K-dependent carboxylation and calcium chelation, as compared with the action of the exogenous (therapeutic) chelator EDTA. Consumption of vitamin-K-rich foods and/or use of vitamin K supplements appear to be a better preventive strategy than EDTA chelation for maintaining vascular health.

  • 3.
    Abdelrahman, Islam
    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, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. The Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Elmasry, Moustafa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. The Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Use of the burn intervention score to calculate the charges of the care of burns2019In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 45, no 2, p. 303-309Article in journal (Refereed)
    Abstract [en]

    Background To our knowledge this is the first published estimate of the charges of the care of burns in Sweden. The Linköping Burn Interventional Score has been used to calculate the charges for each burned patient since 1993. The treatment of burns is versatile, and depends on the depth and extension of the burn. This requires a flexible system to detect the actual differences in the care provided. We aimed to describe the model of burn care that we used to calculate the charges incurred during the acute phase until discharge, so it could be reproduced and applied in other burn centres, which would facilitate a future objective comparison of the expenses in burn care. Methods All patients admitted with burns during the period 2010–15 were included. We analysed clinical and economic data from the daily burn scores during the acute phase of the burn until discharge from the burn centre. Results Total median charge/patient was US$ 28 199 (10th–90th centiles 4668-197 781) for 696 patients admitted. Burns caused by hot objects and electricity resulted in the highest charges/TBSA%, while charges/day were similar for the different causes of injury. Flame burns resulted in the highest mean charges/admission, probably because they had the longest duration of stay. Mean charges/patient increased in a linear fashion among the different age groups. Conclusion Our intervention-based estimate of charges has proved to be a valid tool that is sensitive to the procedures that drive the costs of the care of burns such as large TBSA%, intensive care, and operations. The burn score system could be reproduced easily in other burn centres worldwide and facilitate the comparison regardless of the differences in the currency and the economic circumstances.

  • 4.
    Abtahi, Jahan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Tengvall, Pentti
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology. Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Bisphosphonate coating might improve fixation of dental implants in the maxilla: A pilot study2010In: International Journal of Oral and Maxillofacial Surgery, ISSN 0901-5027, E-ISSN 1399-0020, Vol. 39, no 7, p. 673-677Article in journal (Refereed)
    Abstract [en]

    This pilot study evaluates the clinical stability of bisphosphonate-coated dental implants placed using a two-stage surgical procedure in five patients. Each patient received seven regular Branemark implants, one of which was coated with bisphosphonate in a fibrinogen matrix. The coated implant was inserted where the bone was expected to have the least favourable quality. The level of the marginal bone around each implant was measured by intraoral periapical radiographs and implant stability was recorded using resonance frequency measurements. Frequency values (ISQ) were obtained peroperatively before flap closure and after 6 months at abutment connection. At abutment connection the bisphosphonate-coated implants were removed en bloc in two patients for histological examination. An animal experiment had previously confirmed that gamma-sterilization did not reduce bioactivity of the bisphosphonate coating. In each patient, the bisphosphonate-coated implant showed the largest improvement in ISQ level of all implants. Their values at the start tended to be lower, and the absolute value at 6 months did not differ. No complications occurred with the coated implants. Histology showed no abnormalities. Improvement in ISQ values was an expected effect of the bisphosphonate coating, but could be due to the choice of insertion site. This finding warrants a randomized blinded study.

  • 5.
    Aburto Maldonado, Jennifer
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences.
    Eklind, Lisa
    Linköping University, Department of Biomedical and Clinical Sciences.
    Tolksamarbete inom logopediska verksamheter: en enkätstudie ur tolkarnas perspektiv2021Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The need for interpreters in health care has increased as the number of multilingual individuals increases in today´s society. This entails greater demands on healthcare services to maintain a high quality of healthcare for all. Speech therapists often encounter multilingual people and are then in many cases in need of interpreters during assessments or interventions. Currently, there are only a few studies available that describe challenges that may occur in collaborationsbetween interpreters and speech and language therapist, viewed from the interpreters’perspective. The purpose of this study is thus to investigate the role of interpreters and emphasise their perspective on speech and language therapy activities (e.g. assessment and intervention) for multilingual people. Increased knowledge of the interpreters’ perspective may reveal challenges, as well as identify well-functioning working methods that exist. Results of the study may contribute to strengthening the collaboration between interpreters and speech and language therapists.The material for the study consists of questionnaire responses from 209 interpreters from different parts of Sweden. To provide a comprehensive overview of their answers,information about the interpreters was compiled in tables. Free text answers were an accompanying option to many of the fixed questions. The interpreters' free text answers were analysed using thematic analysis. Overall, the results showed that many of the interpreters perceived the collaboration with the speech therapists as positive, but that there are areas for improvement. The most commonly addressed area was that the interpreters felt that the speech therapists did not have sufficient knowledge of how interpreters are required to perform their profession (by oath of conduct). An improved understanding of each other's professions might increase the degree of satisfaction in the collaboration between interpreter and speech and language pathologist. Getting access to the materials that are to be used for assessment or intervention, before the appointment to be interpreted, would provide the interpreter with a fair chance to prepare appropriately. This is something that a majority of the interpreters in the present study pressed would improve their own performance and thus also increase patient safety.

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    Tolksamarbete inom logopediska verksamheter: en enkätstudie ur tolkarnas perspektiv
  • 6.
    Akhtar, Zubair
    et al.
    Univ New South Wales, Australia; Icddr B, Bangladesh; Univ New South Wales, Australia.
    Gotberg, Matthias
    Lund Univ, Sweden.
    Erlinge, David
    Lund Univ, Sweden.
    Christiansen, Evald H.
    Aarhus Univ Hosp, Denmark.
    Oldroyd, Keith G.
    Univ Glasgow, Scotland.
    Motovska, Zuzana
    Charles Univ Prague, Czech Republic; Univ Hosp Kralovske Vinohrady, Czech Republic.
    Erglis, Andrejs
    Univ Latvia, Latvia.
    Hlinomaz, Ota
    St Anne Univ Hosp, Czech Republic; Masaryk Univ, Czech Republic.
    Jakobsen, Lars
    Aarhus Univ Hosp, Denmark.
    Engstrom, Thomas
    Univ Copenhagen, Denmark.
    Jensen, Lisette O.
    Odense Univ Hosp, Denmark.
    Fallesen, Christian O.
    Odense Univ Hosp, Denmark.
    Jensen, Svend E.
    Aalborg Univ Hosp, Denmark; Aalborg Univ, Denmark.
    Angeras, Oskar
    Sahlgrens Univ Hosp, Sweden; Gothenburg Univ, Sweden.
    Calais, Fredrik
    Orebro Univ, Sweden.
    Karegren, Amra
    Vastmanlands Sjukhus Vasteras, Sweden.
    Lauermann, Jorg
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Mokhtari, Arash
    Lund Univ, Sweden.
    Nilsson, Johan
    Umea Univ, Sweden.
    Persson, Jonas
    Karolinska Inst, Sweden.
    Islam, Abu K. M. M.
    Natl Inst Cardiovasc Dis, Bangladesh.
    Rahman, Afzalur
    Natl Inst Cardiovasc Dis, Bangladesh.
    Malik, Fazila
    Natl Heart Fdn Hosp & Res Inst, Bangladesh.
    Choudhury, Sohel
    Natl Heart Fdn Hosp & Res Inst, Bangladesh.
    Collier, Timothy
    London Sch Hyg & Trop Med, England.
    Pocock, Stuart J.
    London Sch Hyg & Trop Med, England.
    Pernow, John
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Macintyre, Chandini R.
    Univ New South Wales, Australia; Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Frobert, Ole
    Orebro Univ, Sweden; Arizona State Univ, AZ USA; Aarhus Univ, Denmark; Aarhus Univ Hosp, Denmark; Aarhus Univ Hosp, Denmark.
    Optimal timing of influenza vaccination among patients with acute myocardial infarction - Findings from the IAMI trial2023In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 41, no 48, p. 7159-7165Article in journal (Refereed)
    Abstract [en]

    Influenza vaccination reduces the risk of adverse cardiovascular events. The IAMI trial randomly assigned 2571 patients with acute myocardial infarction (AMI) to receive influenza vaccine or saline placebo during their index hospital admission. It was conducted at 30 centers in 8 countries from October 1, 2016 to March 1, 2020. In this post-hoc exploratory sub-study, we compare the trial outcomes in patients receiving early season vaccination (n = 1188) and late season vaccination (n = 1344). The primary endpoint was the composite of all-cause death, myocardial infarction (MI), or stent thrombosis at 12 months. The cumulative incidence of the primary and key secondary endpoints by randomized treatment and early or late vaccination was estimated using the Kaplan-Meier method. In the early vaccinated group, the primary composite endpoint occurred in 36 participants (6.0%) assigned to influenza vaccine and 49 (8.4%) assigned to placebo (HR 0.69; 95% CI 0.45 to 1.07), compared to 31 participants (4.7%) assigned to influenza vaccine and 42 (6.2%) assigned to placebo (HR 0.74; 95% CI 0.47 to 1.18) in the late vaccinated group (P = 0.848 for interaction on HR scale at 1 year). We observed similar estimates for the key secondary endpoints of all-cause death and CV death. There was no statistically significant difference in vaccine effectiveness against adverse cardiovascular events by timing of vaccination. The effect of vaccination on all-cause death at one year was more pronounced in the group receiving early vaccination (HR 0.50; 95% CI, 0.29 to 0.86) compared late vaccination group (HR 0.75; 35% CI, 0.40 to 1.40) but there was no statistically significant difference between these groups (Interaction P = 0.335). In conclusion, there is insufficient evidence from the trial to establish whether there is a difference in efficacy between early and late vaccination but regardless of vaccination timing we strongly recommend influenza vaccination in all patients with cardiovascular diseases.

  • 7.
    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.
    Aaseth, Jan
    Innlandet Hosp Trust, Norway.
    Larsson, Anders
    Uppsala Univ, Sweden.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Decreased Concentration of Fibroblast Growth Factor 23 (FGF-23) as a Result of Supplementation with Selenium and Coenzyme Q(10) in an Elderly Swedish Population: A Sub-Analysis2022In: Cells, E-ISSN 2073-4409, Vol. 11, no 3, article id 509Article in journal (Refereed)
    Abstract [en]

    There is a reduced intake of selenium in many countries due to low levels of selenium in the soil. This results in an increased cardiovascular risk. Fibroblast growth factor 23 (FGF-23) is active mainly in the metabolism of vitamin D and phosphorus. However, there are indications that FGF-23 may also provide information both on cardiovascular function and prognosis. The aim of the study was to evaluate the effect of supplementation with selenium and coenzyme Q(10) on the FGF-23 concentration in an elderly population with low concentrations of both selenium and coenzyme Q(10) and in which the supplementation improved cardiac function and mortality. In a randomised double-blind placebo-controlled trial, FGF-23 was measured in 219 individuals at the start and after 48 months. Selenium yeast (200 mu g/day) and coenzyme Q(10) (200 mg/day) (n = 118) or placebo (n = 101) were given as a dietary supplement. The intervention time was 48 months. t-Tests, repeated measures of variance, and ANCOVA analyses were used to evaluate the differences in FGF-23 concentration. Following supplementation with selenium and coenzyme Q(10), a significantly lower level of FGF-23 could be seen (p = 0.01). Applying 10 years of follow-up, those who later died a cardiovascular death had a significantly higher FGF-23 concentration after 48 months compared with those who survived (p = 0.036), and a significantly lower FGF-23 concentration could be seen in those with a normal renal function compared to those with an impaired renal function (p = 0.027). Supplementation with selenium and coenzyme Q(10) to an elderly community-living population low in both substances prevented an increase of FGF-23 and also provided a reduced cardiovascular risk.

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  • 8.
    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.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Aaseth, Jan O.
    Innlandet Hosp Trust, Norway; Inland Norway Univ Appl Sci, Norway.
    Larsson, Anders
    Uppsala Univ, Sweden.
    Svensson, Erland
    Swedish Def Res Agcy, Sweden.
    Opstad, Trine B.
    Oslo Univ Hosp Ulleval, Norway; Univ Oslo, Norway.
    Effects of an Intervention with Selenium and Coenzyme Q(10) on Five Selected Age-Related Biomarkers in Elderly Swedes Low in Selenium: Results That Point to an Anti-Ageing Effect-A Sub-Analysis of a Previous Prospective Double-Blind Placebo-Controlled Randomised Clinical Trial2023In: Cells, E-ISSN 2073-4409, Vol. 12, no 13, article id 1773Article in journal (Refereed)
    Abstract [en]

    Background: Ageing is associated with cardiovascular disease (CVD). As no single biomarker reflects the full ageing process, we aimed to investigate five CVD- and age-related markers and the effects of selenium and coenzyme Q10 intervention to elucidate the mechanisms that may influence the course of ageing. Methods: This is a sub-study of a previous prospective double-blind placebo-controlled randomized clinical trial that included 441 subjects low in selenium (mean age 77, 49% women). The active treatment group (n = 220) received 200 & mu;g/day of selenium and 200 mg/day of coenzyme Q10, combined. Blood samples were collected at inclusion and after 48 months for measurements of the intercellular adhesion molecule (ICAM-1), adiponectin, leptin, stem cell factor (SCF) and osteoprotegerin (OPG), using ELISAs. Repeated measures of variance and ANCOVA evaluations were used to compare the two groups. In order to better understand and reduce the complexity of the relationship between the biomarkers and age, factor analyses and structural equation modelling (SEM) were performed, and a structural model is presented. Results: Correlation analyses of biomarker values at inclusion in relation to age, and relevant markers related to inflammation, endothelial dysfunction and fibrosis, demonstrated the biomarkers association with these pathological processes; however, only ICAM1 and adiponectin were directly correlated with age. SEM analyses showed, however, that the biomarkers ICAM-1, adiponectin, SCF and OPG, but not leptin, all had significant associations with age and formed two independent structural factors, both significantly related to age. While no difference was observed at inclusion, the biomarkers were differently changed in the active treatment and placebo groups (decreasing and increasing levels, respectively) at 48 months (p & LE; 0.02 in all, adjusted), and in the SEM model, they showed an anti-ageing impact. Conclusions: Supplementation with selenium/Q10 influenced the analysed biomarkers in ways indicating an anti-ageing effect, and by applying SEM methodology, the interrelationships between two independent structural factors and age were validated.

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  • 9.
    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.
    Johansson, Peter
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Aaseth, Jan
    Innlandet Hospital Trust, Norway; Hedmark University of Appl Science, Norway.
    Alexander, Jan
    Norwegian Institute Public Heatlh, Norway; Norwegian University of Life Science NMBU, Norway.
    Brismar, Kerstin
    Karolinska University Hospital, Sweden.
    Increase in insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 after supplementation with selenium and coenzyme Q10. A prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens2017In: PLOS ONE, E-ISSN 1932-6203, Vol. 12, no 6, article id e0178614Article in journal (Refereed)
    Abstract [en]

    Background Insulin-like growth factor-1(IGF-1) has a multitude of effects besides cell growth and metabolism. Reports also indicate anti-inflammatory and antioxidative effects. The concentrations of IGF-1 decrease with age and during inflammation. As selenium and coenzyme Q10 are involved in both the antioxidative defense and the inflammatory response, the present study aimed to examine the effects of supplementation with selenium and coenzyme Q10 on concentrations of IGF-1 and its binding protein IGFBP-1 in a population showing reduced cardiovascular mortality following such supplementation. Methods 215 elderly individuals were included and given the intervention for four years. A clinical examination was performed and blood samples were taken at the start and after 48 months. Evaluations of IGF-1, the age adjusted IGF-1 SD score and IGFBP-1 were performed using group mean values, and repeated measures of variance. Findings After supplementation with selenium and coenzyme Q10, applying group mean evaluations, significantly higher IGF-1 and IGF-1 SD scores could be seen in the active treatment group, whereas a decrease in concentration could be seen of the same biomarkers in the placebo group. Applying the repeated measures of variance evaluations, the same significant increase in concentrations of IGF-1 (F = 68; P amp;gt; 0.0001), IGF-1 SD score (F = 29; P amp;lt; 0.0001) and of IGFBP-1 (F = 6.88; P = 0.009) could be seen, indicating the effect of selenium and coenzyme Q10 also on the expression of IGF-1 as one of the mechanistic effects of the intervention. Conclusion Supplementation with selenium and coenzyme Q10 over four years resulted in increased levels of IGF-1 and the postprandial IGFBP-1, and an increase in the age-corrected IGF-1 SD score, compared with placebo. The effects could be part of the mechanistic explanation behind the surprisingly positive clinical effects on cardiovascular morbidity and mortality reported earlier. However, as the effects of IGF-1 are complex, more research on the result of intervention with selenium and coenzyme Q10 is needed.

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  • 10.
    Arlinger, Stig
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Lunner, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Technical Audiology. Linköping University, Faculty of Health Sciences.
    Lyxell, Björn
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Pichora-Fuller, M Kathleen
    University of Toronto.
    The emergence of cognitive hearing science.2009In: Scandinavian journal of psychology, ISSN 1467-9450, Vol. 50, no 5, p. 371-384Article, review/survey (Refereed)
    Abstract [en]

    Cognitive Hearing Science or Auditory Cognitive Science is an emerging field of interdisciplinary research concerning the interactions between hearing and cognition. It follows a trend over the last half century for interdisciplinary fields to develop, beginning with Neuroscience, then Cognitive Science, then Cognitive Neuroscience, and then Cognitive Vision Science. A common theme is that an interdisciplinary approach is necessary to understand complex human behaviors, to develop technologies incorporating knowledge of these behaviors, and to find solutions for individuals with impairments that undermine typical behaviors. Accordingly, researchers in traditional academic disciplines, such as Psychology, Physiology, Linguistics, Philosophy, Anthropology, and Sociology benefit from collaborations with each other, and with researchers in Computer Science and Engineering working on the design of technologies, and with health professionals working with individuals who have impairments. The factors that triggered the emergence of Cognitive Hearing Science include the maturation of the component disciplines of Hearing Science and Cognitive Science, new opportunities to use complex digital signal-processing to design technologies suited to performance in challenging everyday environments, and increasing social imperatives to help people whose communication problems span hearing and cognition. Cognitive Hearing Science is illustrated in research on three general topics: (1) language processing in challenging listening conditions; (2) use of auditory communication technologies or the visual modality to boost performance; (3) changes in performance with development, aging, and rehabilitative training. Future directions for modeling and the translation of research into practice are suggested.

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  • 11.
    Aspenberg, Per
    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 Orthopaedics in Linköping.
    Placeboeffekten är övervärderad: »Återgång till medelvärdet« kan förklara förbättring efter skenbehandling – men misstolkas ofta2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114Article in journal (Refereed)
  • 12.
    Banerjee, Debarshi
    et al.
    Columbia University Medical Center, USA.
    Cieslar-Pobuda, Artur
    University of Oslo, Norway.
    Zhu, Geyunjian Harry
    University of Cambridge, UK.
    Wiechec, Emilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Patra, Hirak
    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, University of Cambridge, UK; Wolfson College, University of Cambridge, UK.
    Adding nanotechnology to the metastasis treatment arsenal2019In: TIPS - Trends in Pharmacological Sciences, ISSN 0165-6147, E-ISSN 1873-3735, Vol. 40, no 6, p. 403-418Article, review/survey (Refereed)
    Abstract [en]

    Metastasis is a major cause of cancer-related mortality, accounting for 90% of cancer deaths. The explosive growth of cancer biology research has revealed new mechanistic network information and pathways that promote metastasis. Consequently, a large number of antitumor agents have been developed and tested for their antimetastatic efficacy. Despite their exciting cytotoxic effects on tumor cells in vitro and antitumor activities in preclinical studies in vivo, only a few have shown potent antimetastatic activities in clinical trials. In this review, we provide a brief overview of current antimetastatic strategies that show clinical efficacy and review nanotechnology-based approaches that are currently being incorporated into these therapies to mitigate challenges associated with treating cancer metastasis.

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  • 13.
    Barathan, Muttiah
    et al.
    Univ Malaya, Malaysia.
    Mohamed, Rosmawati
    Univ Malaya, Malaysia.
    Yong, Yean K.
    Xiamen Univ Malaysia, Malaysia.
    Kannan, Meganathan
    CUTN, India.
    Vadivelu, Jamuna
    Univ Malaya, Malaysia.
    Saeidi, Alireza
    Univ Malaya, Malaysia.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Shankar, Esaki Muthu
    CUTN, India.
    Viral Persistence and Chronicity in Hepatitis C Virus Infection: Role of T-Cell Apoptosis, Senescence and Exhaustion2018In: Cells, E-ISSN 2073-4409, Vol. 7, no 10, article id 165Article, review/survey (Refereed)
    Abstract [en]

    Hepatitis C virus (HCV) represents a challenging global health threat to similar to 200 million infected individuals. Clinical data suggest that only similar to 10-15% of acutely HCV-infected individuals will achieve spontaneous viral clearance despite exuberant virus-specific immune responses, which is largely attributed to difficulties in recognizing the pathognomonic symptoms during the initial stages of exposure to the virus. Given the paucity of a suitable small animal model, it is also equally challenging to study the early phases of viral establishment. Further, the host factors contributing to HCV chronicity in a vast majority of acutely HCV-infected individuals largely remain unexplored. The last few years have witnessed a surge in studies showing that HCV adopts myriad mechanisms to disconcert virus-specific immune responses in the host to establish persistence, which includes, but is not limited to viral escape mutations, viral growth at privileged sites, and antagonism. Here we discuss a few hitherto poorly explained mechanisms employed by HCV that are believed to lead to chronicity in infected individuals. A better understanding of these mechanisms would aid the design of improved therapeutic targets against viral establishment in susceptible individuals.

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  • 14.
    Berglund, Caroline
    et al.
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Ekströmer, Karin
    Department of Radiology, Mälarsjukhuset Eskilstuna Hospital, Sweden.
    Abtahi, Jahan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Primary Chronic Osteomyelitis of the Jaws in Children: An Update on Pathophysiology, Radiological Findings, Treatment Strategies, and Prospective Analysis of Two Cases2015In: Case Reports in Dentistry, ISSN 2090-6447, E-ISSN 2090-6455, Vol. 2015, no 152717Article in journal (Refereed)
    Abstract [en]

    Objective. Primary chronic osteomyelitis (PCO) of the jaws in children is associated with pain, trismus, and swelling. In children, temporomandibular joint involvement is rare and few studies have been published due to the relatively low incidence. This paper presents two cases of mandibular PCO in children with the involvement of the collum mandibulae. In addition, a review of the literature regarding demographic data, histological, radiological, and laboratory findings, and treatment strategies of PCO was also performed. Material and Methods. Prospective analyses of two PCO cases. A PubMed search was used and the articles were sorted according to their corresponding key area of focus. Results. Review of the literature revealed twenty-four cases of PCO with two cases of mandibular condyle involvement. The mean age was 18 years; the male to female ratio was 1 : 3. Most of the patients were treated with anti-inflammatory drugs in combination with decortication. Clinical recurrence was seen in 7 cases. Conclusion. A combination of anti-inflammatory drugs and surgical intervention appears to be the first choice of treatment. However, surgical removal of necrotic tissue adjacent to collum mandibulae has its limitations in children. Further investigations are of utmost importance in order to increase our knowledge and understanding of this disease.

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  • 15.
    Bergquist, Annika
    et al.
    Karolinska Univ Hosp, Sweden; European Reference Network Hepatol Dis, Sweden.
    Weismüller, Tobias J.
    Univ Bonn, Germany.
    Levy, Cynthia
    Univ Miami, FL USA; Univ Miami, FL USA.
    Rupp, Christian
    Heidelberg Univ Hosp, Germany.
    Joshi, Deepak
    Kings Coll Hosp London, England.
    Nayagam, Jeremy Shanika
    Kings Coll Hosp London, England; Pomeranian Med Univ, Poland.
    Montano-Loza, Aldo J.
    Univ Alberta, Canada.
    Lytvyak, Ellina
    Univ Alberta, Canada.
    Wunsch, Ewa
    Med Univ Warsaw, Poland.
    Milkiewicz, Piotr
    Med Univ Warsaw, Poland.
    Zenouzi, Roman
    Univ Med Ctr Hamburg Eppendorf, Germany.
    Schramm, Christoph
    Univ Med Ctr Hamburg Eppendorf, Germany.
    Cazzagon, Nora
    Univ Padua, Italy; Univ Padua, Italy.
    Floreani, Annarosa
    Univ Padua, Italy.
    Liby, Ingalill Friis
    Sahlgrens Univ Hosp, Sweden.
    Wiestler, Miriam
    Hannover Med Sch, Germany; European Reference Network Hepatol Dis, Germany.
    Wedemeyer, Heiner
    Hannover Med Sch, Germany; European Reference Network Hepatol Dis, Germany.
    Zhou, Taotao
    Univ Bonn, Germany.
    Strassburg, Christian P.
    Univ Bonn, Germany.
    Rigopoulou, Eirini
    Gen Univ Hosp Larissa, Greece.
    Dalekos, George
    Gen Univ Hosp Larissa, Greece.
    Narasimman, Manasa
    Univ Miami, FL USA.
    Verhelst, Xavier
    Ghent Univ Hosp, Belgium; Univ Ghent, Belgium.
    Degroote, Helena
    Univ Ghent, Belgium; European Reference Network Hepatol Dis, Belgium.
    Vesterhus, Mette
    Oslo Univ Hosp, Norway; Univ Bergen, Norway; Haraldsplass Deaconess Hosp, Norway.
    Kremer, Andreas E.
    Friedrich Alexander Univ Erlangen Nurnberg, Germany; Univ Hosp Erlangen, Germany; Univ Hosp Zurich, Switzerland.
    Buendgens, Bennet
    Univ Duisburg, Germany.
    Rorsman, Fredrik
    Univ Hosp, Sweden.
    Nilsson, Emma
    Lund Univ, Sweden; Skåne Univ Hosp, Sweden.
    Jorgensen, Kristin Kaasen
    Akershus Univ Hosp, Norway.
    von Seth, Erik
    Karolinska Univ Hosp, Sweden; European Reference Network Hepatol Dis, Stockholm, Sweden.
    Cornillet Jeannin, Martin
    Karolinska Univ Hosp, Sweden.
    Nyhlin, Nils
    Örebro Univ, Sweden.
    Martin, Harry
    Univ Coll Hosp NHS Fdn Trust, England.
    Kechagias, Stergios
    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.
    Wiencke, Kristine
    Oslo Univ Hosp, Norway.
    Werner, Marten
    Umeå Univ, Sweden.
    Beretta-Piccoli, Benedetta Terziroli
    Univ Svizzera Italiana, Switzerland.
    Marzioni, Marco
    Univ Politecn Marche, Italy.
    Isoniemi, Helena
    Helsinki Univ Hosp, Finland.
    Arola, Johanna
    Univ Helsinki, Finland.
    Wefer, Agnes
    Karolinska Univ Hosp, Sweden.
    Soderling, Jonas
    Karolinska Inst, Sweden.
    Farkkila, Martti
    Univ Helsinki, Finland; Helsinki Univ Hosp, Finland.
    Lenzen, Henrike
    Hannover Med Sch, Germany; European Reference Network Hepatol Dis, Hannover, Germany; Univ Duisburg, Univ Hosp Essen, Germany.
    The International PSC Study Group,
    Impact on follow-up strategies in patients with primary sclerosing cholangitis2023In: Liver international (Print), ISSN 1478-3223, E-ISSN 1478-3231, Vol. 43, no 1, p. 127-138Article in journal (Refereed)
    Abstract [en]

    Background & Aims: Evidence for the benefit of scheduled imaging for early detection of hepatobiliary malignancies in primary sclerosing cholangitis (PSC) is limited. We aimed to compare different follow-up strategies in PSC with the hypothesis that regular imaging improves survival.

    Methods: We collected retrospective data from 2975 PSC patients from 27 centres. Patients were followed from the start of scheduled imaging or in case of clinical follow-up from 1 January 2000, until death or last clinical follow-up alive. The primary endpoint was all-cause mortality.

    Results: A broad variety of different follow-up strategies were reported. All except one centre used regular imaging, ultrasound (US) and/or magnetic resonance imaging (MRI). Two centres used scheduled endoscopic retrograde cholangiopancreatography (ERCP) in addition to imaging for surveillance purposes. The overall HR (CI95%) for death, adjusted for sex, age and start year of follow-up, was 0.61 (0.47-0.80) for scheduled imaging with and without ERCP; 0.64 (0.48-0.86) for US/MRI and 0.53 (0.37-0.75) for follow-up strategies including scheduled ERCP. The lower risk of death remained for scheduled imaging with and without ERCP after adjustment for cholangiocarcinoma (CCA) or high-grade dysplasia as a time-dependent covariate, HR 0.57 (0.44-0.75). Hepatobiliary malignancy was diagnosed in 175 (5.9%) of the patients at 7.9 years of follow-up. Asymptomatic patients (25%) with CCA had better survival if scheduled imaging had been performed.

    Conclusions: Follow-up strategies vary considerably across centres. Scheduled imaging was associated with improved survival. Multiple factors may contribute to this result including early tumour detection and increased endoscopic treatment of asymptomatic benign biliary strictures.

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  • 16.
    Bergström, Ida
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Lundberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Jönsson, Simon
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Sarndahl, Eva
    Örebro University, Sweden.
    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.
    Jonasson, Lena
    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.
    Annexin A1 in blood mononuclear cells from patients with coronary artery disease: Its association with inflammatory status and glucocorticoid sensitivity2017In: PLOS ONE, E-ISSN 1932-6203, Vol. 12, no 3, article id e0174177Article in journal (Refereed)
    Abstract [en]

    Annexin A1 (AnxA1) is a key player in resolution of inflammation and a mediator of glucocorticoid actions. In atherosclerotic tissue, increased expression of AnxA1 has been associated with protective plaque-stabilizing effects. Here, we investigated the expression of AnxA1 in peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD). Blood was collected from 57 patients with stable CAD (SCAD) and 41 healthy controls. We also included a minor group (n = 10) with acute coronary syndrome (ACS). AnxA1 mRNA was measured in PBMCs. Expression of AnxA1 protein (total and surface-bound) and glucocorticoid receptors (GR) were detected in PBMC subsets by flow cytometry. Also, salivary cortisol, interleukin(IL)-6 and IL-10 in plasma, and LPS-induced cytokine secretion from PBMCs, with or without dexamethasone, were assessed. AnxA1 mRNA was found to be slightly increased in PBMCs from SCAD patients compared with controls. However, protein expression of AnxA1 or GRs in PBMC subsets did not differ between SCAD patients and controls, despite SCAD patients showing a more proinflammatory cytokine profile ex vivo. Only surface expression of AnxA1 on monocytes correlated with dexamethasone-mediated suppression of cytokines. In ACS patients, a marked activation of AnxA1 was seen involving both gene expression and translocation of protein to cell surface probably reflecting a rapid glucocorticoid action modulating the acute inflammatory response in ACS. To conclude, surface expression of AnxA1 on monocytes may reflect the degree of glucocorticoid sensitivity. Speculatively, "normal" surface expression of AnxA1 indicates that anti-inflammatory capacity is impaired in SCAD patients.

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  • 17.
    Biskou, Olga
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Meira de Faria, Felipe
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Walter, Susanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Tinnerfelt Winberg, Martin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Haapaniemi, Staffan
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology.
    Myrelid, Pär
    Linköping University, Department of Biomedical and Clinical Sciences, 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 Surgery in Linköping.
    Söderholm, Johan D
    Linköping University, Department of Biomedical and Clinical Sciences, 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 Surgery in Linköping.
    Keita, Åsa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Increased Numbers of Enteric Glial Cells in the Peyers Patches and Enhanced Intestinal Permeability by Glial Cell Mediators in Patients with Ileal Crohns Disease2022In: Cells, E-ISSN 2073-4409, Vol. 11, no 3, article id 335Article in journal (Refereed)
    Abstract [en]

    Enteric glial cells (EGC) are known to regulate gastrointestinal functions; however, their role in Crohns disease (CD) is elusive. Microscopic erosions over the ileal Peyers patches are early signs of CD. The aim of this work was to assess the localization of EGC in the follicle and interfollicular region of the Peyers patches and in the lamina propria and study the effects of EGC mediators on barrier function in CD patients and non-inflammatory bowel disease (non-IBD) controls. EGC markers, glial fibrillary acidic protein (GFAP), and S100 calcium-binding protein β (S100β) were quantified by immunofluorescence and Western blotting. Both markers showed significantly more EGC in the Peyers patches and lamina propria of CD patients compared to the non-IBD controls. In CD patients there were significantly more EGC in Peyers patches compared to lamina propria, while the opposite pattern was seen in controls. Barrier function studies using Ussing chambers showed increased paracellular permeability by EGC mediators in CD patients, whereas permeability decreased by the mediators in controls. We show the accumulation of EGC in Peyers patches of CD patients. Moreover, EGC mediators induced barrier dysfunction in CD patients. Thus, EGC might have harmful impacts on ongoing inflammation and contribute to the pathophysiology of the disease.

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  • 18.
    Borendal Wodlin, Ninnie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Kjölhede, Preben
    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 Gynaecology and Obstetrics in Linköping.
    Snabbspår har fördelar vid elektiv gynekologisk kirurgi.2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 25-26, p. 2-7Article in journal (Refereed)
    Abstract [en]

    Fast-track is a multimodal strategy aimed at achieving an improved and accelerated postoperative recovery. The strategy combines unimodal evidence-based interventions concerning preoperative preparation, peroperative principles and postoperative care. There is substantial evidence for the benefits of following fast-track concepts in general elective surgery to enhance postoperative recovery. The main findings of this review are that there are benefits likewise within elective gynecological surgery, but studies of quality of life, patient satisfaction and health economics are needed. Studies of fast-track within non-elective surgery and gynaecological oncology surgery are lacking. Widespread information and education is needed to improve the rate of implementation of fast-track. Comprehensive involvement of the entire staff dealing with the patient in the perioperative period is crucial to ensure implementation and development of surgical care aiming for enhanced postoperative recovery.

  • 19.
    Borg, Mathias
    Linköping University, Department of Physics, Chemistry and Biology.
    Study of the insulin-like peptide 3 in human platelets2009Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The insulin-like 3 peptide is autocrine/paracrine insulin-related hormone with a size of approximately 6kDa [1]. It mediates through a leucine richG-coupled receptor named LGR8. INSL3 is mainly expressed in human Leydig cells and is directly responsible for migration of the testis during the pre-natal period in maledevelopment. [2]

    INSL3 mRNA has recently been verified in human platelets whereas no mRNA has been detected for LGR8 (by Sanofi-Aventis GmbH in Frankfurt,Germany), indicating that INSL3 might be released through paracrine functions at sites of platelet adhesion and aggregation upon a vascular injury.Furthermore, has activated platelets been shown to translate essential proteins upon activation, in a term called “signal-dependent protein synthesis”.The B-Cell lymphoma-3 protein (BCL-3) is an example of such a protein [3], and there is a possibility that INSL3 might be also.

    In this thesis we wanted to detect the relaxin- like peptide 3 hormone (INSL3). (Its function, location and the timeframe of its release, when/if it issecreated in stimulated platelets).The source of platelet-derived INSL3 can be found with Western blotting and Enzyme immunoassay.

    Detection of the insulin-like 3 peptide in human platelets turned out to be a difficult challenge due to the small amount of INSL3 secretion uponplatelet activation; hence the total amount of INSL3 produced might be below detection limit.

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  • 20.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Themistocleous, Andreas
    Univ Oxford, England.
    Stensson, Niclas
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Rice, Andrew S. C.
    Imperial Coll London, England.
    Tesfaye, Solomon
    Sheffield Teaching Hosp NHS Fdn Trust, England.
    Bennett, David L.
    Univ Oxford, England; John Radcliffe Hosp, England.
    Gerdle, Björn
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ghafouri, Bijar
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Serum levels of endocannabinoids and related lipids in painful vs painless diabetic neuropathy: results from the Pain in Neuropathy Study2024In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 165, no 1, p. 225-232Article in journal (Refereed)
    Abstract [en]

    N-arachidonoylethanolamine (also known as anandamide) and 2-arachidonoylglycerol are activators of the cannabinoid receptors. The endocannabinoid system also includes structurally and functionally related lipid mediators that do not target cannabinoid receptors, such as oleoylethanolamide, palmitoylethanolamide, and stearoylethanolamide. These bioactive lipids are involved in various physiological processes, including regulation of pain. The primary aim of the study was to analyze associations between serum levels of these lipids and pain in participants in the Pain in Neuropathy Study, an observational, cross-sectional, multicentre, research project in which diabetic patients with painless or painful neuropathy underwent deep phenotyping. Our hypothesis was that painful neuropathy would be associated with higher levels of the 5 lipids compared with painless neuropathy. Secondary aims were to analyze other patient-reported outcome measures and clinical data in relationship to lipid levels. The lipid mediators were analyzed in serum samples using liquid chromatography tandem mass spectrometry (LC-MS/MS). Serum levels of anandamide were significantly higher in the painful group, but the effect size was small (Cohen d = 0.31). Using cluster analysis of lipid data, patients were dichotomized into a "high-level" endocannabinoid group and a "low-level" group. In the high-level group, 61% of patients had painful neuropathy, compared with 45% in the low-level group (P = 0.039). This work is of a correlative nature only, and the relevance of these findings to the search for analgesics targeting the endocannabinoid system needs to be determined in future studies.

  • 21.
    Bäckström, Denise
    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, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Change in child mortality patterns after injuries in Sweden: a nationwide 14-year study.2017In: European Journal of Trauma and Emergency Surgery, ISSN 1863-9933, E-ISSN 1863-9941, Vol. 43, no 3, p. 343-349Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Sweden has one of the world's lowest child injury mortality rates, but injuries are still the leading cause of death among children. Child injury mortality in the country has been declining, but this decline seems to decrease recently. Our objective was therefore to further examine changes in the mortality of children's death from injury over time and to assess the contribution of various effects on mortality. The underlying hypothesis for this investigation is that the incidence of lethal injuries in children, still is decreasing and that this may be sex specific.

    PATIENTS AND METHODS: We studied all deaths from injury in Sweden under-18-year-olds during the 14 years 1999-2012. We identified those aged under 18 whose underlying cause of death was recorded as International Classification of Diseases, 10th Revision (ICD-10) diagnosis from V01 to X39 in the Swedish cause of death, where all dead citizens are registered.

    RESULTS: From the 1 January 1999 to 31 December 2012, 1213 children under the age of 18 died of injuries in Sweden. The incidence declined during this period (r = -0.606, p = 0.02) to 3.3 deaths/100,000 children-years (95 % CI 2.6-4.2). Death from unintentional injury was more common than that after intentional injury (p < 0.0001). There was a reduction in the incidence of unintentional injuries during the study period (r = -0.757, p = 0.03). The most common causes of death were injury to the brain (n = 337, 41 %), followed by drowning (n = 109, 13 %). The number of deaths after intentional injury increased (r = 0.585, p = 0.03) and at the end of the period was 1.5 deaths/100,000 children-years. The most common causes of death after intentional injuries were asphyxia (n = 177, 45 %), followed by injury to the brain (n = 76, 19 %).

    DISCUSSION: Mortality patterns in injured children in Sweden have changed from being dominated by unintentional injuries to a more equal distribution between unintentional and intentional injuries as well as between sexes and the overall rate has declined further. These findings are important as they might contribute to the preventive work that is being done to further reduce mortality in injured children.

  • 22.
    Casado Bedmar, Maite
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Keita, Åsa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Potential neuro-immune therapeutic targets in irritable bowel syndrome2020In: Therapeutic Advances in Gastroenterology, ISSN 1756-283X, E-ISSN 1756-2848, Vol. 13, article id 1756284820910630Article, review/survey (Refereed)
    Abstract [en]

    Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder characterized by recurring abdominal pain and disturbed bowel habits. The aetiology of IBS is unknown but there is evidence that genetic, environmental and immunological factors together contribute to the development of the disease. Current treatment of IBS includes lifestyle and dietary interventions, laxatives or antimotility drugs, probiotics, antispasmodics and antidepressant medication. The gut-brain axis comprises the central nervous system, the hypothalamic pituitary axis, the autonomic nervous system and the enteric nervous system. Within the intestinal mucosa there are close connections between immune cells and nerve fibres of the enteric nervous system, and signalling between, for example, mast cells and nerves has shown to be of great importance during GI disorders such as IBS. Communication between the gut and the brain is most importantly routed via the vagus nerve, where signals are transmitted by neuropeptides. It is evident that IBS is a disease of a gut-brain axis dysregulation, involving altered signalling between immune cells and neurotransmitters. In this review, we analyse the most novel and distinct neuro-immune interactions within the IBS mucosa in association with already existing and potential therapeutic targets.

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  • 23.
    Cirillo, Marco Domenico
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Mirdell, Robin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Pham, Tuan
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Time-Independent Prediction of Burn Depth using Deep Convolutional Neural Networks2019In: Journal of Burn Care & Research, ISSN 1559-047X, E-ISSN 1559-0488, Vol. 40, no 6, p. 857-863Article in journal (Refereed)
    Abstract [en]

    We present in this paper the application of deep convolutional neural networks, which are a state-of-the-art artificial intelligence (AI) approach in machine learning, for automated time-independent prediction of burn depth. Colour images of four types of burn depth injured in first few days, including normal skin and background, acquired by a TiVi camera were trained and tested with four pre-trained deep convolutional neural networks: VGG-16, GoogleNet, ResNet-50, and ResNet-101. In the end, the best 10-fold cross-validation results obtained from ResNet- 101 with an average, minimum, and maximum accuracy are 81.66%, 72.06% and 88.06%, respectively; and the average accuracy, sensitivity and specificity for the four different types of burn depth are 90.54%, 74.35% and 94.25%, respectively. The accuracy was compared to the clinical diagnosis obtained after the wound had healed. Hence, application of AI is very promising for prediction of burn depth and therefore can be a useful tool to help in guiding clinical decision and initial treatment of burn wounds.

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  • 24.
    Deb, Suryyani
    et al.
    Maulana Abul Kalam Azad Univ Technol, India.
    Azharuddin, Mohammad
    Cambridge Display Technol Ltd, England.
    Ramstrom, Sofia
    Orebro Univ, Sweden.
    Ghosh, Kanjaksha
    KEM Hosp Campus, India.
    Singha, Santiswarup
    Natl Inst Immunol, India.
    Romu, Thobias
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Patra, Hirak Kumar
    UCL, England.
    Self-Reporting Theranostic: Nano Tool for Arterial Thrombosis2023In: Bioengineering, E-ISSN 2306-5354, Vol. 10, no 9, article id 1020Article in journal (Refereed)
    Abstract [en]

    Arterial thrombosis (AT) originates through platelet-mediated thrombus formation in the blood vessel and can lead to heart attack, stroke, and peripheral vascular diseases. Restricting the thrombus growth and its simultaneous monitoring by visualisation is an unmet clinical need for a better AT prognosis. As a proof-of-concept, we have engineered a nanoparticle-based theranostic (combined therapy and monitoring) platform that has the potential to monitor and restrain the growth of a thrombus concurrently. The theranostic nanotool is fabricated using biocompatible super-paramagnetic iron oxide nanoparticles (SPIONs) as a core module tethered with the anti-platelet agent Abciximab (ReoPro) on its surface. Our in vitro feasibility results indicate that ReoPro-conjugated SPIONS (Tx@ReoPro) can effectively prevent thrombus growth by inhibiting fibrinogen receptors (GPIIbIIIa) on the platelet surface, and simultaneously, it can also be visible through non-invasive magnetic resonance imaging (MRI) for potential reporting of the real-time thrombus status.

  • 25.
    Drevinge, Christina
    et al.
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Karlsson, Lars O.
    Univ Gothenburg, Sweden.
    Ståhlman, Marcus
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Larsson, Thomas
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Sundelin, Jeanna Perman
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Grip, Lars
    Univ Gothenburg, Sweden.
    Andersson, Linda
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Borén, Jan
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Levin, Malin C.
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Cholesteryl Esters Accumulate in the Heart in a Porcine Model of Ischemia and Reperfusion2013In: PLOS ONE, E-ISSN 1932-6203, Vol. 8, no 4, article id e61942Article in journal (Refereed)
    Abstract [en]

    Myocardial ischemia is associated with intracellular accumulation of lipids and increased depots of myocardial lipids are linked to decreased heart function. Despite investigations in cell culture and animal models, there is little data available on where in the heart the lipids accumulate after myocardial ischemia and which lipid species that accumulate. The aim of this study was to investigate derangements of lipid metabolism that are associated with myocardial ischemia in a porcine model of ischemia and reperfusion. The large pig heart enables the separation of the infarct area with irreversible injury from the area at risk with reversible injury and the unaffected control area. The surviving myocardium bordering the infarct is exposed to mild ischemia and is stressed, but remains viable. We found that cholesteryl esters accumulated in the infarct area as well as in the bordering myocardium. In addition, we found that expression of the low density lipoprotein receptor (LDLr) and the low density lipoprotein receptor-related protein 1 (LRP1) was up-regulated, suggesting that choleteryl ester uptake is mediated via these receptors. Furthermore, we found increased ceramide accumulation, inflammation and endoplasmatic reticulum (ER) stress in the infarcted area of the pig heart. In addition, we found increased levels of inflammation and ER stress in the myocardium bordering the infarct area. Our results indicate that lipid accumulation in the heart is one of the metabolic derangements remaining after ischemia, even in the myocardium bordering the infarct area. Normalizing lipid levels in the myocardium after ischemia would likely improve myocardial function and should therefore be considered as a target for treatment.

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  • 26.
    Edvardsson, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Finspång, Primary Health Care in Finspång.
    Sund-Levander, Märtha
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine. Linköping University, Faculty of Health Sciences.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Grodzinsky, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. Rättsmedicinalverket, Linköping, Sweden.
    Clinical use of conventional reference intervals in the frail elderly2015In: Journal of Evaluation In Clinical Practice, ISSN 1356-1294, E-ISSN 1365-2753, Vol. 21, no 2, p. 229-235Article in journal (Refereed)
    Abstract [en]

    Rationale, aims and objectives

    Reference intervals provided by the laboratory are commonly established by measuring samples from apparently healthy subjects in the ages 18–65 years, excluding elderly individuals with chronic diseases and medication. The aim of our study was to establish whether current reference intervals for immune parameters and chemical biomarkers are valid for older individuals including those with chronic diseases, so-called frail elderly.

    Methods

    Data from our cohort of 138 non-infected nursing home residents (NHR), mean age 86.8 years, range 80–98, were compared with raw data, as basis for the development of reference intervals, obtained from reference populations, like blood donors (IgA, IgG, IgM, C3 and C4) and from the Nordic Reference Interval Project (NORIP) (alanine aminotransferase, albumin, aspartate aminotransferase, creatinine, gamma-glutamyl transferase, lactate dehydrogenase, phosphate, sodium and urea). Immune parameters were measured by nephelometry and in NORIP the measurements were performed by means of different routine methods, in more than 100 laboratories.

    Results

    Only nine individuals (7%) of NHR were found to be free from chronic disease. C3, C4 (P < 0.001) and IgG levels (P < 0.05) were higher, while IgM levels (P < 0.001) were lower in NHR compared with reference blood donors. Levels of alanine aminotransferase, phosphate (P < 0.001), albumin (P < 0.05) and sodium (P < 0.01) were lower while creatinine and urea levels were higher (P < 0.001) in NHR compared with NORIP subjects.

    Conclusion

    Comparing laboratory results from elderly people with conventional reference intervals can be misleading or even dangerous, as normal conditions may appear pathological, or vice versa and thus lead to unnecessary or even harmful treatment.

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  • 27.
    Elmasry, Moustafa
    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, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Plastic Surgery Unit, Surgery Department, Suez Canal University, Egypt.
    Mirdell, Robin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Tesselaar, Erik
    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 Diagnostics, Medical radiation physics. Linköping University, Department of Medical and Health Sciences.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Laser speckle contrast imaging in children with scalds: Its influence on timing of intervention, duration of healing and care, and costs2019In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 45, no 4, p. 798-804Article in journal (Refereed)
    Abstract [sv]

    Background

    Scalds are the most common type of burn injury in children, and the initial evaluation of burn depth is a problem. Early identification of deep dermal areas that need excision and grafting would save unnecessary visits and stays in hospital. Laser speckle contrast imaging (LSCI) shows promise for the evaluation of this type of burn. The aim of this study was to find out whether perfusion measured with LSCI has an influence on the decision for operation, duration of healing and care period, and costs, in children with scalds.

    Methods

    We studied a group of children with scalds whose wounds were evaluated with LSCI on day 3–4 after injury during the period 2012–2015. Regression (adjustment for percentage total body surface area burned (TBSA%), age, and sex) was used to analyse the significance of associations between degree of perfusion and clinical outcome.

    Results

    We studied 33 children with a mean TBSA% of 6.0 (95% CI 4.4–7.7)%. Lower perfusion values were associated with operation (area under the receiver-operating characteristic curve 0.86, 95% CI 0.73–1.00). The perfusion cut-off with 100% specificity for not undergoing an operation was ≥191 PU units (66.7% sensitivity and 72.7% accurately classified). Multivariable analyses showed that perfusion was independently associated with duration of healing and care period.

    Conclusion

    Lower perfusion values, as measured with LSCI, are associated with longer healing time and longer care period. By earlier identification of burns that will be operated, perfusion measurements may further decrease the duration of care of burns in children with scalds.

  • 28.
    Eriksson, Ida
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Ward, Liam J.
    Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, S-58785 Linkoping, Sweden.
    Vainikka, Linda
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Sultana, Nargis
    Region Östergötland, Center for Diagnostics, Laboratoriemedicin sjukhus.
    Leandersson, Per
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Occupational and Environmental Medicine Center.
    Flodin, Ulf
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Occupational and Environmental Medicine Center.
    Li, Wei
    Linköping University, Department of Biomedical and Clinical Sciences, 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.
    Yuan, Ximing
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Occupational and Environmental Medicine Center.
    Imidacloprid Induces Lysosomal Dysfunction and Cell Death in Human Astrocytes and Fibroblasts-Environmental Implication of a Clinical Case Report2023In: Cells, E-ISSN 2073-4409, Vol. 12, no 24, article id 2772Article in journal (Refereed)
    Abstract [en]

    Imidacloprid (IMI), a neonicotinoid insecticide, has potential cytotoxic and genotoxic effects on human and experimental models, respectively. While being an emerging environmental contaminant, occupational exposure and related cellular mechanisms are unknown. Herein, we were motivated by a specific patient case where occupational exposure to an IMI-containing plant protection product was associated with the diagnosis of Bell's palsy. The aim was to investigate the toxic effects and cellular mechanisms of IMI exposure on glial cells (D384 human astrocytes) and on human fibroblasts (AG01518). IMI-treated astrocytes showed a reduction in cell number and dose-dependent cytotoxicity at 24 h. Lower doses of IMI induced reactive oxygen species (ROS) and lysosomal membrane permeabilisation (LMP), causing apoptosis and autophagic dysfunction, while high doses caused significant necrotic cell death. Using normal fibroblasts, we found that IMI-induced autophagic dysfunction and lysosomal damage, activated lysophagy, and resulted in a compensatory increase in lysosomes. In conclusion, the observed IMI-induced effects on human glial cells and fibroblasts provide a possible link between IMI cytotoxicity and neurological complications observed clinically in the patient exposed to this neonicotinoid insecticide.

  • 29.
    Eriksson, Per
    et al.
    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.
    Andersson, Carina
    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.
    Cassel, Petra
    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.
    Nyström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    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.
    Letter: Increase in Th17-associated CCL20 and decrease in Th2-associated CCL22 plasma chemokines in active ANCA-associated vasculitis2015In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 44, no 1, p. 80-83Article in journal (Other academic)
    Abstract [en]

    n/a

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  • 30.
    Ewerman, Lea
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Endocrinology.
    Landberg, Eva
    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, Department of Clinical Chemistry.
    Hellberg, Sandra
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Hovland, Mina
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Sundin, Anna
    Linköping University, Department of Biomedical and Clinical Sciences. 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.
    Ekman, Bertil
    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, Medicine Center, Department of Endocrinology.
    Ernerudh, Jan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Wahlberg, Jeanette
    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, Medicine Center, Department of Endocrinology.
    Immunomodulating Effects Depend on Prolactin Levels in Patients with Hyperprolactinemia2020In: Hormone and Metabolic Research, ISSN 0018-5043, E-ISSN 1439-4286, Vol. 52, no 4, p. 228-235Article in journal (Refereed)
    Abstract [en]

    Prolactin is known to have immune modulatory effects acting through the prolactin receptor, which is present on a variety of immune cells. Certain chemokines contribute to form the type of T helper (Th) preponderance in the immune response. The objective of this work was to assess if hyperprolactinemia not related to pregnancy is associated with changes in circulating levels of chemokines and other immunological markers. In this cross sectional study, 35 patients with hyperprolactinemia (5 men), and 102 healthy blood donors (19 men) were included. Serum levels of Th1- Th2- and Th17-associated chemokines, C-reactive protein, immunoglobulins, and the B cell attracting chemokine CXCL13 were assessed. The hyperprolactinemic group had significantly higher levels of Th2 associated CCL22 (p=0.022), Th17 associated CXCL1 (p=0.001), B cell attracting CXCL13 (p=0.003), and C-reactive protein (p&lt;0.001) compared to controls, and these proteins were also positively correlated with prolactin levels. While differences in CCL22, CXCL1, CXCL13, and C-reactive protein were present in patients with low or moderate hyperprolactinemia, no differences were observed at high (&gt;3600 mU/l) prolactin levels. To evaluate a possible dose-associated response to prolactin, an in vitro model was used, showing prolactin-induced increase in T-helper cell activation at moderate levels, while activation decreased at higher levels. Hyperprolactinemia seems to have several immunomodulatory effects and was associated with increased levels of chemokines associated with Th2 and Th17 responses and B cell attraction. However, patients with greatly increased prolactin had normal levels of chemokines, and in vitro, high levels of prolactin decreased T-helper cell activation.

  • 31.
    Fjälldal, S.
    et al.
    Skåne Univ Hosp, Sweden.
    Follin, C.
    Skane Univ Hosp, Sweden.
    Gabery, S.
    Lund Univ, Sweden.
    Sundgren, P. C.
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Bjorkman-Burtscher, I. M.
    Skane Univ Hosp, Sweden; Lund Univ, Sweden; Lund Univ, Sweden.
    Latt, J.
    Skane Univ Hosp, Sweden.
    Mannfolk, P.
    Skane Univ Hosp, Sweden.
    Nordstrom, C. H.
    Skane Univ Hosp, Sweden.
    Rylander, L.
    Lund Univ, Sweden.
    Ekman, Bertil
    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 Endocrinology.
    Cheong, R.
    Lund Univ, Sweden.
    Palsson, A.
    Skane Univ Hosp, Sweden.
    Petersen, A.
    Lund Univ, Sweden.
    Erfurth, E. M.
    Skane Univ Hosp, Sweden.
    Detailed assessment of hypothalamic damage in craniopharyngioma patients with obesity2019In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 43, no 3, p. 533-544Article in journal (Refereed)
    Abstract [en]

    Background/objectives Hypothalamic obesity (HO) occurs in 50% of patients with the pituitary tumor craniopharyngioma (CP). Attempts have been made to predict the risk of HO based on hypothalamic (HT) damage on magnetic resonance imaging (MRI), but none have included volumetry. We performed qualitative and quantitative volumetric analyses of HT damage. The results were explored in relation to feeding related peptides and body fat. Subjects/methods A cross-sectional study of childhood onset CPs involving 3 Tesla MRI, was performed at median 22 years after first operation; 41 CPs, median age 35 (range: 17-56), of whom 23 had HT damage, were compared to 32 controls. After exclusions, 35 patients and 31 controls remained in the MRI study. Main outcome measures were the relation of metabolic parameters to HT volume and qualitative analyses of HT damage. Results Metabolic parameters scored persistently very high in vascular risk particularly among HT damaged patients. Patients had smaller HT volumes compared to controls 769 (35-1168) mm(3) vs. 879 (775-1086) mm(3); P amp;lt; 0.001. HT volume correlated negatively with fat mass and leptin among CP patients (r(s) = -0.67; P amp;lt; .001; r(s) = -0.53; P = 0.001), and explained 39% of the variation in fat mass. For every 100 mm(3) increase in HT volume fat mass decreased by 2.7 kg (95% CI: 1.5-3.9; P amp;lt; 0.001). Qualitative assessments revealed HT damage in three out of six patients with normal volumetry, but HT damage according to operation records. Conclusions A decrease in HT volume was associated with an increase in fat mass and leptin. We present a method with a high inter-rater reliability (0.94) that can be applied by nonradiologists for the assessment of HT damage. The method may be valuable in the risk assessment of diseases involving the HT.

  • 32.
    Gao, Feng
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Yuan, Y.
    Nanjing University, 210093 China.
    Wang, K. F.
    Nanjing University, 210093 China.
    Chen, X. Y.
    Nanjing University, 210093 China.
    Chen, F.
    Nanjing University, 210093 China.
    Liu, J. -M.
    Nanjing University, 210093 China.
    Preparation and photoabsorption characterization of BiFeO3 nanowires2006In: Applied Physics Letters, ISSN 0003-6951, E-ISSN 1077-3118, Vol. 89, no 10, p. 102506-Article in journal (Refereed)
    Abstract [en]

    Perovskite-type polycrystalline BiFeO3 (BFO) nanowires (similar to 50 nm in diameter and similar to 5 mu m in length) were synthesized using the anodized alumina template technique. An energy band gap of similar to 2.5 eV was determined from the UV-visible diffuse reflectance spectrum, and its photocatalytic ability to produce O-2 was revealed under UV irradiation. Weak ferromagnetism at room temperature and superparamagnetism at low temperature were observed for the BFO nanowires, different from the antiferromagnetic order in bulk BFO, reflecting the significant size effects on the magnetic ordering of BFO. (c) 2006 American Institute of Physics.

  • 33.
    Ghannan, Zahra
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences.
    Rustum, Sami
    Linköping University, Department of Biomedical and Clinical Sciences.
    Theory of Mind i en narrativ aktivitet: Hur påverkar digitala media och bokläsning barns ToM-förmåga?2022Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Currently, the use of digital media has increased significantly and has become dominant in manyareas in our society. The use of mobile touch screen devices has increased gradually in youngchildren and preschool children, and the age at which children are first exposed to these deviceshas decreased. Unlike earlier eras, children today are exposed to a substantial quantity of stimulifrom digital media during their developmental years. The short- and long-term effects of thistype of exposure are still not fully explored. Theory of Mind is an essential part of thedevelopmental process in children. In this study, we examined children's ToM in a narrative context, where we analyzed their statements and behavioural patterns that show ToM abilities both linguistically and interactively. Multimodal interaction analysis was the basis for the analyses in this study, where 45 children were recorded when they told a story called "Frog, where are you?". The results were reported qualitatively to answer the question of how children show ToM ability in a narrative context, and quantitatively to answer the question of whether there is acorrelation between ToM ability and children’s digital media use. The quantitative result showed no significant relation between digital media usage or book reading and children’s ToM ability.The qualitative result shows that children integrate several different areas of knowledge to present their ToM both linguistically and interactively, during the narrative activity.

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    Theory of Mind i en narrativ aktivitet: Hur påverkar digitala media och bokläsning barns Tom-förmåga?
  • 34.
    Grahn Kronhed, Ann-charlotte
    Region Östergötland, Local Health Care Services in West Östergötland, Department of Rehabilitation in Motala. Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Would the first fragility fracture be tha last one: a physiotherapeutic perspective2017In: Physical Medicine and Rehabilitation Research, ISSN 2398-3353, Vol. 2, no 3, p. 1-2Article in journal (Other academic)
  • 35.
    Grams, M
    et al.
    John Hopkins University, USA.
    Sang, Yingying
    John Hopkins University, USA.
    Ballew, Shoshana
    John Hopkins University, USA.
    Szabó, Zoltán
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Matsushita, Kunihiro
    John Hopkins University, USA.
    Kalantar-Zadeh, Kamyar
    UC Irvine, USA.
    Coresh, Josef
    John Hopkins University, USA.
    Kovesdy, Csaba
    Memphis VA, USA.
    Incidence of and risk factors for acute kidney injury after major surgery2014Conference paper (Refereed)
  • 36.
    Grundström, Hanna
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Norrköping.
    Alehagen, Siw
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Berterö, Carina
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Kjölhede, Preben
    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.
    Impact of Pelvic Pain and Endometriosis on Patient-Reported Outcomes and Experiences of Benign Hysterectomy: A Study from the Swedish National Register for Gynecological Surgery2018In: Journal of Women's Health, ISSN 1540-9996, E-ISSN 1931-843X, Vol. 27, no 5, p. 691-698Article in journal (Refereed)
    Abstract [en]

    Background: The study objective was to analyze and compare patient-reported experience measures (PREMs) and patient-reported outcome measures (PROMs) after hysterectomy in women with and without a preoperative complaint of pelvic pain associated with and without a confirmed diagnosis of endometriosis. Methods: Retrospective nationwide register study. Data on 28,776 hysterectomies performed on benign indication between 2004 and 2016 were retrieved from the Swedish National Register for Gynecological Surgery. Multivariable logistic regression models were used to compare the PREMs and PROMs items. The results are presented as adjusted odds ratios (aORs) and 95% confidence intervals (CI). Results: Regardless of the occurrence of pelvic pain preoperatively and a diagnosis of endometriosis, 1 year after surgery, the women were satisfied or very satisfied (amp;gt;90%) with the hysterectomy, and their medical condition was improved or much improved (amp;gt;95%). The women with a preoperative complaint of pelvic pain and endometriosis more often reported excessively short hospital stays (aOR 1.45, 95% CI 1.17-1.79), more severe complications after discharge (aOR 2.02, 95% CI 1.59-2.66) at the 8-week follow-up and at the 1-year follow-up (aOR 2.31, 95% CI 1.57-3.39), and more dissatisfaction with the operation (aOR 1.83, 95% CI 1.35-2.48) than preoperative pelvic pain-free women without endometriosis at the 1-year follow-up. Conclusions: The majority of the women were satisfied after their hysterectomy. The women with pelvic pain and endometriosis were at a higher risk of being dissatisfied. Pelvic pain per se seemed to be the main factor affecting the rating in the PREMs and PROMs, and the endometriosis was a significant contributing factor.

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  • 37.
    Hagstrom, Hannes
    et al.
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Ndegwa, Nelson
    Karolinska Inst, Sweden; Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Jalmeus, Molly
    Karolinska Inst, Sweden.
    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.
    Posserud, Iris
    Univ Gothenburg, Sweden.
    Rorsman, Fredrik
    Uppsala Univ Hosp, Sweden.
    Nyhlin, Nils
    Orebro Univ, Sweden.
    Klintman, Daniel
    Skane Univ Hosp, Sweden.
    Werner, Marten
    Umea Univ, Sweden.
    Marschall, Hanns-Ulrich
    Univ Gothenburg, Sweden.
    Askling, Johan
    Karolinska Inst, Sweden.
    Stal, Per
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Morbidity, risk of cancer and mortality in 3645 HFE mutations carriers2021In: Liver international (Print), ISSN 1478-3223, E-ISSN 1478-3231, Vol. 41, no 3, p. 545-553Article in journal (Refereed)
    Abstract [en]

    Background & Aims Mutations in the HFE gene can lead to hereditary haemochromatosis (HH) and have been suggested to increase the risk of extra-hepatic diseases, especially breast and colorectal cancer. Here we investigated long-term outcomes of Swedish patients with HFE mutations. Methods We identified 3645 patients with a homozygous p.C282Y (62%) or a compound heterozygous p.C282Y/p.H63D (38%) mutation from eight centres in Sweden between 1997 and 2017. These were matched 1:10 by age, sex and county of residence to reference individuals from the general population. We ascertained incident outcomes until the end of 2017 by linkage to national registers. Studied outcomes were HH, cirrhosis, hepatocellular carcinoma (HCC), breast cancer (in women), colorectal cancer, type 1 and 2 diabetes, hypothyroidism, Parkinsons disease and mortality. Cox proportional hazards regression was used to estimate hazard ratios for these outcomes. Results Median age at diagnosis was 52 years, 44% were females. During a mean follow-up of 7.9 years, we found an increased risk for HCC, HH, cirrhosis, type 2 diabetes, osteoarthritis and death. Excess mortality was only seen in men. No increased risk was seen for colorectal or breast cancer. Liver-related outcomes were rare, with a cumulative incidence of HFE mutation carriers in a university hospital setting had an increased risk for mortality in men, along with increased risks of cirrhosis, HCC, diabetes type 2, and osteoarthritis. In general, the absolute risk for adverse outcomes was low and no increased risk for colon or breast cancer was observed.

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  • 38.
    Hahn, Robert G.
    et al.
    Sodertalje Hosp, Sweden; Karolinska Inst Danderyds Hosp KIDS, Sweden.
    Hasselgren, Emma
    Karolinska Univ Hosp, Sweden.
    Bjorne, Hakan
    Karolinska Univ Hosp, Sweden.
    Zdolsek, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Zdolsek, Joachim
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping (ANOPIVA).
    Biomarkers of endothelial injury in plasma are dependent on kidney function2019In: Clinical hemorheology and microcirculation, ISSN 1386-0291, E-ISSN 1875-8622, Vol. 72, no 2, p. 161-168Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Injury (shedding) of the endothelial glycocalyx layer, which alters local blood flow and microvascular permeability, is assessed by measuring components of this layer in circulating blood. The influence of renal function on their concentrations is unknown. METHODS: Plasma and urine concentrations of three shedding products (syndecan-1, hyaluronic acid, and heparan sulfate) and creatinine were measured over 5 hours in 15 healthy volunteers and 15 postoperative patients; this guaranteed a spread of kidney functions. Renal clearances were calculated. RESULTS: Low renal clearances of syndecan-1 (mean 3.5 mL/min) and hyaluronic acid (0.8 mL/min) correlated inversely with the 6-fold variability in the plasma concentrations of these substances (r = -0 . 45 and-0.49). Low creatinine clearance correlated inversely (r = -0.60) and plasma creatinine directly (r = 0.52) with the two-fold variability in heparan sulfate, which was the only shedding substance that also correlated with C-reactive protein (r= 0.51) and, therefore, showed higher concentrations after surgery. CONCLUSIONS: The present explorative study suggests that a 6-fold variability in the plasma concentrations of three commonly measured endothelial shedding products can be understood by the kidneys ability to excrete them. This finding has implications when interpreting results of studies where shedding is assessed.

  • 39.
    Hahn, Robert G.
    et al.
    Sodertalje Hosp, Sweden; Karolinska Inst, Sweden.
    Zdolsek, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping (ANOPIVA).
    Hasselgren, Emma
    Karolinska Univ Hosp, Sweden.
    Zdolsek, Joachim
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping (ANOPIVA).
    Bjoerne, Hakan
    Karolinska Univ Hosp, Sweden.
    Fluid volume kinetics of 20% albumin2019In: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 85, no 6, p. 1303-1311Article in journal (Refereed)
    Abstract [en]

    Aims A population kinetic model was developed for the body fluid shifts occurring when 20% albumin is given by intravenous infusion. The aim was to study whether its efficacy to expand the plasma volume is impaired after major surgery. Methods An intravenous infusion of 3 mL/kg 20% albumin over 30 minutes was given to 15 volunteers and to 15 patients on the 1(st) day after major open abdominal surgery. Blood samples and urine were collected during 5 hours. Mixed-effect modelling software was used to develop a fluid volume kinetic model, using blood haemoglobin and urine excretion the estimate body fluid shifts, to which individual-specific covariates were added in sequence. Results The rise in plasma albumin expanded the plasma volume in excess of the infused volume by relocating noncirculating fluid (rate constant k(21)), but it also increased losses of fluid from the kinetic system (k(b)). The balance between k(21) and k(b) maintained the rise in plasma albumin and plasma volume at a virtual steady-state for almost 2 hours. The rate constant for urinary excretion (k(10)) was slightly reduced by the preceding surgery, by a marked rise in plasma albumin, and by a high preinfusion urinary concentration of creatinine. The arterial pressure, body weight, and plasma concentrations of C-reactive protein and shedding products of the endothelial glycocalyx layer (syndecan-1, heparan sulfate, and hyaluronic acid) did not serve as statistically significant covariates. Conclusions There were no clinically relevant differences in the kinetics of 20% albumin between postoperative patients and volunteers.

  • 40.
    Henriksson, Pontus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Eriksson, B
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Forsum, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Löf, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Gestational weight gain according to Institute of Medicine recommendations in relation to infant size and body composition.2015In: Pediatric Obesity, ISSN 2047-6302, E-ISSN 2047-6310, Vol. 10, no 5, p. 388-394Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Intrauterine life may be a critical period for programming childhood obesity; however, there is insufficient knowledge concerning how gestational weight gain (GWG) affects infant fat mass (FM) and fat-free mass (FFM).

    OBJECTIVES: The aim of this study was to investigate relationships between GWG according to Institute of Medicine (IOM) recommendations and infant size, FM and FFM. We also investigated if the associations were different for normal-weight and overweight/obese women.

    METHODS: This study included 312 healthy Swedish mother-infant pairs. Infant body composition at 1 week of age was assessed using air-displacement plethysmography. Maternal GWG was defined as below, within or above the 2009 IOM recommendations. Multiple regression analyses were used.

    RESULTS: Compared with women whose weight gain was within IOM recommendations, women with weight gain below the recommendations had infants that were shorter (-0.7 cm, P = 0.008) when adjusting for confounders. Normal-weight women exceeding IOM recommendations had infants with higher FM (+58 g, P = 0.008) compared with normal-weight women who gained within the recommendations. No corresponding association was observed for overweight/obese women.

    CONCLUSIONS: Inadequate GWG was associated with shorter infants, while excessive GWG was associated with greater infant FM for women who were of normal weight before pregnancy.

  • 41. Order onlineBuy this publication >>
    Hilborn, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    The role of the androgen receptor and hydroxysteroid 17β dehydrogenase in breast cancer: Impact on tamoxifen treatment2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The healthy breast is a tissue composed of centrally located milk producing glands connected to the nipple by ducts, surrounded by fat tissue and connective tissue. The growth of the breast is primarily mediated by the estrogens, while the androgens mediate tissue homeostasis and protect against growth signals. In breast cancer, the cells of the glands or ducts undergo malignant transformation, and start proliferating in an uncontrollable fashion. Breast cancer is the most common malignancy in women, and it is estimated that 10% of all women will be diagnosed with breast cancer during their life-time. The primary classification of breast cancer is based mainly on the expression of the estrogen receptor, and 70-80% of breast cancers are estrogen receptor positive, and are classified as luminal. The remaining breast cancers are classified into HER2 positive or triple negative breast cancer. Out of all breast cancers, ~80% are androgen receptor positive. This varies in different subtypes, however, with the highest expression in luminal and lowest expression in triple negative breast cancers. The role of androgen receptor varies depending on subtype. It is considered tissue-protective in luminal breast cancer, while it’s role in HER2 positive and triple negative breast cancers is less defined, but is generally considered to be associated with worse outcome. The primary treatment for breast cancer is surgery, followed by chemotherapy and/or radiotherapy to reduce the risk of recurrence. Treatment is also subtype specific, and luminal breast cancers in premenopausalwomen are treated using the estrogen receptor blocker (antagonist) tamoxifen, which blocks estrogen signaling. In postmenopausal women, luminal breast  cancers are treated using tamoxifen or aromatase inhibitors, which prevent the formation of estrogen. The knowledge of which patient will respond and who will develop treatment resistance is of great importance, and the development of markers which can be analyzed prior to treatment in order to reduce the risk of unwanted side effects or complications is the focus of a large body of research. One of the primary goals of this thesis was to establish biomarkers for prognosis and tamoxifen treatment in breast cancer, and paper I, paper II and paper III address this aim.

    Steroid hormones, including estrogens and androgens, are normally synthesized from cholesterol in the adrenal gland, as well as in gender specific tissues such as ovaries in women or the testis or prostate in men. This synthesis takes place as a number of enzymatic conversions, mediated by several different enzymes, and the expression of these enzymes determines the final product of this conversion. In the adrenal gland, testis and prostate, androgens are the end-product, while the ovaries synthesize estrogens. These hormones are transported through the circulation, and upon reaching their target tissues, they mediate their effect. The impact of the steroids on their destination tissue is dependent on their relative concentration and exposure time, which in turn is dependent on the amount in the circulation, but also on the presence of local steroid converting enzymes, which are present in most tissues. The enzymes of the hydroxysteroid 17β dehydrogenase family are present in most tissues, primarily the oxidative member hydroxysteroid 17β dehydrogenase type 2, which facilitate the conversion of estrogens and androgens to the less active forms, thus protecting the tissues from their effect. In breast cancer, the reductive form, hydroxysteroid 17β dehydrogenase type 1 is often up-regulated, and mediates increased activation of estrogens, resulting in increased estrogen signaling, which results in increased proliferation and growth. The second goal of this thesis was to further study the role of hydroxysteroid 17β dehydrogenase enzymes in breast cancer, and paper I and paper IV address different  aspects of their role in breast cancer.

    Following reduction of the expression of hydroxysteroid 17β dehydrogenase type 14, an oxidative member of the family, in breast cancer, the expression of C-X-C ligand 10 was found to be altered. In paper I, in order to determine the role of C-X-C ligand 10 and C-X-C receptor 3 in breast cancer, their expression was quantified using immunohistochemistry in breast cancer patients randomized to tamoxifen or no endocrine treatment irrespectively of estrogen receptor status. The expression of C-XC ligand 10 and C-X-C receptor 3 was found to be associated with increased tamoxifen treatment benefit in the estrogen receptor positive group of patients, indicating that they could be useful markers for determining which patient would respond well to this treatment. Further, C-X-C receptor 3 expression was associated with worse outcome in patients who did not receive tamoxifen, and could be a potential target for inhibitors in order to improve patient outcome. The role of the androgen receptor in breast cancer was evaluated. In paper II the expression was quantified using immunohistochemistry in the same cohort as in paper I. We show that in patients with estrogen receptor negative tumors, the androgen receptor is associated with worse outcome. In patients with high tumoral androgen receptor expression, tamoxifen signaling results in significant improvement in outcome, despite lack of the estrogen receptor. The opposite was observed in patients without tumoral androgen receptor expression, and tamoxifen treatment was associated with adverse outcome. Similar findings were made in the triple negative cases. In the luminal cases, the androgen receptor does not provide further information pertaining to outcome. In paper III we evaluated the role of mutations in the androgen receptor in the cohort of estrogen receptor-negative and androgen receptorpositive cases from paper II. The role of mutations in the androgen receptor appear to have a modest role in regard to patient outcome, but rs17302090 appear associated with tamoxifen treatment benefit. The modulation of the members of the hydroxysteroid 17β dehydrogenase in breast cancer is associated with changes in the local steroid balance, and has been associated with worse outcome and changes in the response to tamoxifen. Further, the inhibition of hydroxysteroid 17β dehydrogenase type 1 has been proposed as an alternate treatment for breast cancer, but no inhibitors are currently used in the clinic. In paper IV, we evaluated several different mechanisms by which the expression of hydroxysteroid 17β dehydrogenase type 1 and type 2 are modulated in breast cancer. We show that the most potent estrogen estradiol, in an estrogen receptor dependent fashion, can result in decreased hydroxysteroid 17β dehydrogenase type 1 expression, and a short term reduction in type 2 expression or long term increased type 2 expression. We also show that the most potent androgen, dihydrotestosterone, can increase hydroxysteroid 17β dehydrogenase type 2 expression, but has limited impact on hydroxysteroid 17β dehydrogenase type 1. Further, we show that a number of genes involved in breast cancer, and microRNA are involved in modulating the expression of the hydroxysteroid 17β dehydrogenase type 1 and type 2 in breast cancer. These findings could potentially be used as an alternative to inhibitors, and help modulate the steroidal balance in target tissue.

    List of papers
    1. C-X-C ligand 10 and C-X-C receptor 3 status can predict tamoxifen treatment response in breast cancer patients
    Open this publication in new window or tab >>C-X-C ligand 10 and C-X-C receptor 3 status can predict tamoxifen treatment response in breast cancer patients
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    2014 (English)In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 145, no 1, p. 73-82Article in journal (Refereed) Published
    Abstract [en]

    To investigate the expression levels of CXCL10 and CXCR3 in tumors from breast cancer patients randomized to adjuvant tamoxifen treatment or no endocrine treatment, in order to further study the connection to prognosis and prediction of tamoxifen treatment outcome. Immunohistochemistry on tissue microarrays from 912 breast cancer patients randomized to tamoxifen or no endocrine treatment. CXCR3 status was found to be a prognostic tool in predicting distant recurrence, as well as reduced breast cancer-specific survival. In patients with estrogen receptor (ER)-positive tumors, tumors with strong CXCL10 levels had improved effect of tamoxifen treatment in terms of local recurrence-free survival [risk ratio (RR) 0.46 (95 % CI 0.25-0.85, P = 0.01)] compared with patients with tumors expressing weak CXCL10 expression. Further, patients with ER-positive tumors with strong CXCR3 expression had an improved effect of tamoxifen in terms of breast cancer-specific survival [RR 0.34 (95 % CI 0.19-0.62, P less than 0.001)] compared with the group with weak CXCR3 levels [RR 1.33 (95 % CI 0.38-4.79, P = 0.65)]. We show here for the first time that CXCL10 and CXCR3 expression are both predictors of favorable outcome in patients treated with tamoxifen.

    Place, publisher, year, edition, pages
    Springer Verlag (Germany), 2014
    Keywords
    CXCL10; CXCR3; Endocrine treatment; Prognosis; Tamoxifen
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-106833 (URN)10.1007/s10549-014-2933-7 (DOI)000334519400007 ()
    Available from: 2014-05-28 Created: 2014-05-23 Last updated: 2017-12-05Bibliographically approved
    2. Androgen receptor expression predicts beneficial tamoxifen response in oestrogen receptor-alpha-negative breast cancer
    Open this publication in new window or tab >>Androgen receptor expression predicts beneficial tamoxifen response in oestrogen receptor-alpha-negative breast cancer
    Show others...
    2016 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 114, no 3, p. 248-255Article in journal (Refereed) Published
    Abstract [en]

    Background: Although the androgen receptor (AR) is frequently expressed in breast cancer, its relevance in the disease is not fully understood. In addition, the relevance of AR in determining tamoxifen treatment efficiency requires evaluation. Purpose: To investigate the tamoxifen predictive relevance of the AR protein expression in breast cancer. Methods Patients were randomised to tamoxifen 40 mg daily for 2 or 5 years or to no endocrine treatment. Mean follow-up was 15 years. Hazard ratios were calculated with recurrence-free survival as end point. Results: In patients with oestrogen receptor (ER)-negative tumours, expression of AR predicted decreased recurrence rate with tamoxifen (hazard ratio (HR) = 0.34; 95% confidence interval (CI) = 0.14-0.81; P = 0.015), whereas the opposite was seen in the AR- group (HR = 2.92; 95% CI = 1.16-7.31; P = 0.022). Interaction test was significant P &lt; 0.001. Patients with triple-negative and AR+ tumours benefitted from tamoxifen treatment (HR = 0.12; 95% CI = 0.014-0.95 P = 0.044), whereas patients with AR- tumours had worse outcome when treated with tamoxifen (HR = 3.98; 95% CI = 1.32-12.03; P = 0.014). Interaction test was significant P = 0.003. Patients with ER+ tumours showed benefit from tamoxifen treatment regardless of AR expression. Conclusions: AR can predict tamoxifen treatment benefit in patients with ER- tumours and triple-negative breast cancer.

    Place, publisher, year, edition, pages
    NATURE PUBLISHING GROUP, 2016
    Keywords
    Androgen receptor; breast cancer; tamoxifen; oestrogen receptor; triple-negative breast cancer
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:liu:diva-125675 (URN)10.1038/bjc.2015.464 (DOI)000369223600003 ()26742006 (PubMedID)
    Note

    Funding Agencies|Swedish research council [A0346701]; Swedish cancer foundation [13 0435]

    Available from: 2016-03-02 Created: 2016-02-29 Last updated: 2017-05-03
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  • 42.
    Hildebrand, Eric
    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 Gynaecology and Obstetrics in Linköping.
    Abrandt Dahlgren, Madeleine
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Sved, Catarina
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Gottvall, Tomas
    Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Blomberg, Marie
    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 Gynaecology and Obstetrics in Linköping.
    Janerot Sjöberg, Birgitta
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Impact of a standardized training program on midwive’s ability to assess fetal heart anatomy by ultrasound2014In: BMC Medical Imaging, ISSN 1471-2342, E-ISSN 1471-2342, Vol. 14, no 20Article in journal (Refereed)
    Abstract [en]

    Background: Studies of prenatal detection of congenital heart disease (CDH) in the UK, Italy, and Norway indicate that it should be possible to improve the prenatal detection rate of CDH in Sweden. These studies have shown that training programs, visualization of the outflow tracts and color-Doppler all can help to speed up and improve the detection rate and accuracy. We aimed to introduce a more accurate standardized fetal cardiac ultrasound screening protocol in Sweden.

    Methods: A novel pedagogical model for training midwives in standardized cardiac imaging was developed, a model using a think-aloud analysis during a pre- and post-course test and a subsequent group reflection. The self-estimated difficulties and knowledge gaps of four midwives were identified. A two-day course with mixed lectures, demonstrations and handson sessions was followed by a feedback session one month later consisting of an interview and check-up. The long-term effects were tested two years later.

    Results: At the post-course test the self-assessed uncertainty was lower than at the pre-course test. The qualitative evaluation showed that the color Doppler images were difficult to interpret, but the training seems to have enhanced the familiarity with the new technique. The ability to perform the method remained at the new level at follow-up both three months and two years later.

    Conclusions: Our results indicate that by implementing new imaging modalities and providing hands-on training, uncertainty can be reduced and time decreased, but they also show that continuous on-site training with clinical and technical back-up is important.

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  • 43.
    Hildebrand, Eric
    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 Gynaecology and Obstetrics in Linköping.
    Källén, Bengt
    Tornblad Institute, University of Lund, Sweden.
    Josefsson, Ann
    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 Gynaecology and Obstetrics in Linköping.
    Gottvall, Tomas
    Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Blomberg, Marie
    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 Gynaecology and Obstetrics in Linköping.
    Maternal obesity and risk of Down syndrome in the offspring2014In: Prenatal Diagnosis, ISSN 0197-3851, E-ISSN 1097-0223, Vol. 34, no 4, p. 310-315Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The objective of this article is to determine if maternal obesity is associated with an increased risk of Down syndrome in the offspring and whether the risk estimates for trisomy 21 based on combined screening is affected by maternal body mass index (BMI).

    METHODS: Study group I consisted of a nationwide cohort of 168 604 women giving birth; outcome was infants born with Down syndrome. Adjustment was made for maternal age. Study group II consisted of 10 224 women undergoing 1st trimester combined screening. Outcome was risk assessment for Down syndrome. All women were divided into six BMI groups, and outcomes were evaluated over the BMI strata with BMI 18.5 to 24.9 as reference and correcting for maternal age.

    RESULTS: Obese women had an increased risk for giving birth to an infant with Down syndrome compared with normal-weight women, BMI 30 to 34.9 odds ratio (OR) 1.31 [95% confidence interval (CI) 1.10-1.55], BMI 35 to 39.9 OR 1.12 (95% CI 0.82-1.53), BMI ≥ 40 OR 1.56 (95% CI 1.00-2.43). The observed and the expected numbers of women with a risk of Down syndrome >1/300 based on 1st trimester combined screen and maternal age were similar in each BMI group.

    CONCLUSION: Maternal obesity seems to increase the risk for Down syndrome births. The risk estimate for Down syndrome with 1st trimester combined screening is unaffected by BMI. © 2013 John Wiley & Sons, Ltd.

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  • 44.
    Johansson, Martina
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Activity and Health.
    Vavruch, Camilla
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ekholmen.
    Östgren, Carl Johan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ekholmen. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Nyström, Fredrik H
    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, Primary Care Center, Primary Health Care Center Cityhälsan Centrum.
    Circulating TNFrII levels predict incidence of ischemic heart disease and total mortality, independently of intima media thickness and pulse wave velocity in male with type 2 diabetes2021In: Heart and Vessels, ISSN 0910-8327, E-ISSN 1615-2573, Vol. 36, no 10, p. 1591-1596Article in journal (Refereed)
    Abstract [en]

    New and clinically useful markers of cardiovascular risk are of great importance in patients with type 2 diabetes since cardiovascular disease is a major cause of death in these patients. We analyzed inflammatory markers and other risk factors for heart disease in 761 patients who participated in the CARDIPP-study, Cardiovascular Risk factors in Patients with Diabetes-a Prospective study in Primary care. All participants had type 2 diabetes and were 55-66 years old at recruitment during the years 2005-2008. Patients were followed for incidence of stroke, myocardial infarction, or death from cardiovascular disease until the end of the year 2018 using the national Swedish Cause of Death and Hospitalization Registries. Besides traditional risk-markers for vascular disease, we also measured carotid-femoral pulse-wave velocity and intima-media thickness of carotid arteries. During a median period of 13 years, 165 men and 65 women died or were hospitalized for ischemic heart disease and stroke. TNFrII showed statistically significance as a risk factor for stroke, ischemic heart disease, and total mortality in male patients with diabetes type 2, independently of age, diabetes duration, BMI, Hba1c, systolic blood pressure, triglycerides, IMT and PWV (p = 0.002, HR 2.70, CI 1.42:5.13, p = 0.002). Circulating TNFrII levels failed to present a similar correlation in women (p = 0.48, CI 0.48:4.84). TNFrII stayed significant in males when HDL/LDL-ratio, CRP and smoking were added to the statistical analysis. Our data support the use of serum TNFrII in male type 2 diabetes patients to add independent prognostic information in terms of mortality and heart disease independently of other strong and well-established risk markers including cholesterol, inflammatory cytokines, PWV and IMT. Trial registration: ClinicalTrials.gov NCT01049737.

  • 45.
    Kallner, Anders
    et al.
    Karolinska Univ Hosp, Sweden.
    Petersmann, Astrid
    Univ Med, Germany.
    Nauck, Matthias
    Univ Med, Germany.
    Theodorsson, Elvar
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Response to Dr. Sadlers comments2020In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 80, no 6, p. 448-449Article in journal (Other academic)
    Abstract [en]

    n/a

  • 46.
    Karlsson, Matilda
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Lindgren, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Jarnhed-Andersson, Ingmarie
    Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Tarpila, Erkki
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Dressing the split-thickness skin graft donor site: a randomized clinical trial2014In: Advances in Skin & Wound Care, ISSN 1527-7941, E-ISSN 1538-8654, Vol. 27, no 1, p. 20-25Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The primary objective of this study was to compareAquacel (ConvaTec, Skillman, New Jersey), Allevyn (Smith &Nephew, St Petersburg, Florida), and Mediskin I (Mo¨ lnlycke, HealthCare AB, Gothenburg, Sweden) in the treatment of split-thicknessskin graft donor sites.

    DESIGN: This study was performed as a prospective randomized,3-arm, clinical study.

    SETTING: A clinical study performed at a hand and plastic surgerydepartment with burn unit.

    PARTICIPANTS: The study included 67 adults with a total of73 donor sites, which were on the thigh, not reharvested, andranged between 30- and 400-cm2 area.

    INTERVENTIONS: Subjects were randomly assigned to treatmentwith Aquacel, Allevyn, or Mediskin I.

    MAIN OUTCOME MEASURES: The donor site was assessed onpostoperative days 3, 14, and 21 for healing, infection, pain,impact on everyday life, ease of use, and cost.

    MAIN RESULTS: The obtained results demonstrate significantlyfaster re-epithelialization for patients treated with Aquacel orMediskin I compared with Allevyn. Regarding infections, therewere no significant differences between the groups. Patientswearing Aquacel experienced significantly less pain changing thedressing and less impact on everyday life than the patientswearing Allevyn. Aquacel was shown to be significantly easier forthe caregiver to use than Allevyn and Mediskin I. There is asignificant difference in cost of treatment between the dressings,whereas Mediskin I is the most expensive.

    CONCLUSION: The authors’ results support the use of Aquacel in thetreatment of split-thickness skin graft donor sites. Aquacel has alow cost per unit, is user friendly, gives short healing time, andminimizes patient discomfort.

     

  • 47.
    Kassymova, Gulnara
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health.
    Sydsjö, Gunilla
    Linköping University, Department of Biomedical and Clinical Sciences, 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.
    Borendal Wodlin, Ninnie
    Linköping University, Department of Biomedical and Clinical Sciences, 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.
    Nilsson, Lena
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, ANOPIVA US. Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology.
    Kjölhede, Preben
    Linköping University, Department of Biomedical and Clinical Sciences, 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.
    The Effect of Follow-Up Contact on Recovery After Benign Hysterectomy: A Randomized, Single-Blinded, Four-Arm, Controlled Multicenter Trial2021In: Journal of Women's Health, ISSN 1540-9996, E-ISSN 1931-843X, Vol. 30, no 6, p. 872-881Article in journal (Refereed)
    Abstract [en]

    Background: The objective of this trial was to analyze the effect of follow-up programs using standard follow-up protocol and structured coaching on recovery after hysterectomy in an enhanced recovery after surgery setting. Materials and Methods: A randomized, four-armed, single-blinded, controlled multicenter trial comprising 487 women was conducted at five hospitals in the southeast region of Sweden. The women were allocated (1:1:1:1) to Group A: no planned follow-up contact; Group B: a single, planned, structured, broadly kept, follow-up telephone contact with the research nurse the day after discharge; Group C: planned, structured, broadly kept follow-up telephone contact with the research nurse the day after discharge and then once weekly for 6 weeks; and Group D: as Group C, but with planned, structured, coaching telephone contact. Recovery was assessed by the health-related quality of life (HRQoL) questionnaires EuroQoL-5 Dimension with three levels (EQ-5D-3L) and Short-Form-Health Survey with 36 items (SF-36) and duration of sick leave. Results: Neither the recovery of HRQoL as measured by the EQ-5D-3L and the SF-36 nor the duration of sick leave (mean 26.8-28.1 days) differed significantly between the four intervention groups. Irrespective of mode of follow-up contact used, the women had recovered to their baseline EQ-5D-3L health index 4 weeks after surgery. The occurrence of unplanned telephone contact was significantly lower (by nearly 30%) in the women who had structured coaching. Conclusion: Follow-up contact, including coaching, did not seem to expedite the postoperative recovery in HRQoL or reduce the sick leave after hysterectomy, but the coaching seemed to reduce unplanned telephone contact with the health care services. ClinicalTrial.gov (NCT01526668).

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  • 48.
    Kim, Woojin Scott
    et al.
    Neuroscience Research Australia, Barker Street, Randwick 2031, NSW, Australia; School of Medical Sciences, University of New South Wales, Sydney 2052, NSW, Australia.
    Kågedal, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Halliday, Glenda M
    Neuroscience Research Australia, Barker Street, Randwick 2031, NSW, Australia; School of Medical Sciences, University of New South Wales, Sydney 2052, NSW, Australia.
    Alpha-synuclein biology in Lewy body diseases.2014In: Alzheimer's research & therapy, ISSN 1758-9193, Vol. 6, no 5, article id 73Article in journal (Refereed)
    Abstract [en]

    α-Synuclein is an abundantly expressed neuronal protein that is at the center of focus in understanding a group of neurodegenerative disorders called α-synucleinopathies, which are characterized by the presence of aggregated α-synuclein intracellularly. Primary α-synucleinopathies include Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy, with α-synuclein also found secondarily in a number of other diseases, including Alzheimer's disease. Understanding how α-synuclein aggregates form in these different disorders is important for the understanding of its pathogenesis in Lewy body diseases. PD is the most prevalent of the α-synucleinopathies and much of the initial research on α-synuclein Lewy body pathology was based on PD but is also relevant to Lewy bodies in other diseases (dementia with Lewy bodies and Alzheimer's disease). Polymorphism and mutation studies of SNCA, the gene that encodes α-synuclein, provide much evidence for a causal link between α-synuclein and PD. Among the primary α-synucleinopathies, multiple system atrophy is unique in that α-synuclein deposition occurs in oligodendrocytes rather than neurons. It is unclear whether α-synuclein originates from oligodendrocytes or whether it is transmitted somehow from neurons. α-Synuclein exists as a natively unfolded monomer in the cytosol, but in the presence of lipid membranes it is thought to undergo a conformational change to a folded α-helical secondary structure that is prone to forming dimers and oligomers. Posttranslational modification of α-synuclein, such as phosphorylation, ubiquitination and nitration, has been widely implicated in α-synuclein aggregation process and neurotoxicity. Recent studies using animal and cell models, as well as autopsy studies of patients with neuron transplants, provided compelling evidence for prion-like propagation of α-synuclein. This observation has implications for therapeutic strategies, and much recent effort is focused on developing antibodies that target extracellular α-synuclein.

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  • 49.
    Knopf, Jasmin
    et al.
    Friedrich Alexander Univ Erlangen Nurnberg FAU, Germany; Univ Klinikum Erlangen, Germany; Friedrich Alexander Univ Erlangen Nurnberg FAU, Germany.
    Sjöwall, Johanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Frodlund, Martina
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Rheumatology.
    Hinkula, Jorma
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Herrmann, Martin
    Friedrich Alexander Univ Erlangen Nurnberg FAU, Germany; Univ Klinikum Erlangen, Germany; Friedrich Alexander Univ Erlangen Nurnberg FAU, Germany.
    Sjöwall, Christopher
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Rheumatology.
    NET Formation in Systemic Lupus Erythematosus: Changes during the COVID-19 Pandemic2022In: Cells, E-ISSN 2073-4409, Vol. 11, no 17, article id 2619Article in journal (Refereed)
    Abstract [en]

    The severity of the coronavirus disease in 2019 (COVID-19) is strongly linked to a dysregulated immune response. This fuels the fear of severe disease in patients with autoimmune disorders continuously using immunosuppressive/immunomodulating medications. One complication of COVID-19 is thromboembolism caused by intravascular aggregates of neutrophil extracellular traps (NETs) occluding the affected vessels. Like COVID-19, systemic lupus erythematosus (SLE) is characterized by, amongst others, an increased risk of thromboembolism. An imbalance between NET formation and clearance is suggested to play a prominent role in exacerbating autoimmunity and disease severity. Serologic evidence of exposure to SARS-CoV-2 has a minor impact on the SLE course in a Swedish cohort reportedly. Herein, we assessed NET formation in patients from this cohort by neutrophil elastase (NE) activity and the presence of cell-free DNA, MPO-DNA, and NE-DNA complexes and correlated the findings to the clinical parameters. The presence of NE-DNA complexes and NE activity differed significantly in pre-pandemic versus pandemic serum samples. The latter correlated significantly with the hemoglobin concentration, blood cell counts, and complement protein 3 and 4 levels in the pre-pandemic but only with the leukocyte count and neutrophil levels in the pandemic serum samples. Taken together, our data suggest a change, especially in the NE activity independent of exposure to SARS-CoV-2.

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  • 50.
    Kowald, Saskia
    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.
    Huge, Ylva
    Linköping University, Department of Biomedical and Clinical Sciences, 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 Urology in Östergötland.
    Tandiono, Decky
    BioReper AB, SE-58213 Linkoping, Sweden.
    Ali, Zaheer
    BioReper AB, SE-58213 Linkoping, Sweden.
    Vazquez-Rodriguez, Gabriela
    BioReper AB, SE-58213 Linkoping, Sweden.
    Erkstam, Anna
    BioReper AB, SE-58213 Linkoping, Sweden.
    Fahlgren, Anna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. BioReper AB, SE-58213 Linkoping, Sweden.
    Sherif, Amir
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Umea Univ, Sweden.
    Cao, Yihai
    Karolinska Inst, Sweden.
    Jensen, Lasse
    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, Department of Clinical Pharmacology. BioReper AB, SE-58213 Linkoping, Sweden.
    Novel Zebrafish Patient-Derived Tumor Xenograft Methodology for Evaluating Efficacy of Immune-Stimulating BCG Therapy in Urinary Bladder Cancer2023In: Cells, E-ISSN 2073-4409, Vol. 12, no 3, article id 508Article in journal (Refereed)
    Abstract [en]

    Background: Bacillus Calmette-Guerin (BCG) immunotherapy is the standard-of-care adjuvant therapy for non-muscle-invasive bladder cancer in patients at considerable risk of disease recurrence. Although its exact mechanism of action is unknown, BCG significantly reduces this risk in responding patients but is mainly associated with toxic side-effects in those facing treatment resistance. Methods that allow the identification of BCG responders are, therefore, urgently needed. Methods: Fluorescently labelled UM-UC-3 cells and dissociated patient tumor samples were used to establish zebrafish tumor xenograft (ZTX) models. Changes in the relative primary tumor size and cell dissemination to the tail were evaluated via fluorescence microscopy at three days post-implantation. The data were compared to the treatment outcomes of the corresponding patients. Toxicity was evaluated based on gross morphological evaluation of the treated zebrafish larvae. Results: BCG-induced toxicity was avoided by removing the water-soluble fraction of the BCG formulation prior to use. BCG treatment via co-injection with the tumor cells resulted in significant and dose-dependent primary tumor size regression. Heat-inactivation of BCG decreased this effect, while intravenous BCG injections were ineffective. ZTX models were successfully established for six of six patients based on TUR-B biopsies. In two of these models, significant tumor regression was observed, which, in both cases, corresponded to the treatment response in the patients. Conclusions: The observed BCG-related anti-tumor effect indicates that ZTX models might predict the BCG response and thereby improve treatment planning. More experiments and clinical studies are needed, however, to elucidate the BCG mechanism and estimate the predictive value.

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