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  • 1.
    Abdelrahman, Islam
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US. Plastic Surgery Unit, Suez Canal University, Egypt.
    Elmasry, Moustafa
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US. Plastic Surgery Unit, Suez Canal University, Egypt.
    Steinvall, Ingrid
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Turesson, Christina
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för prevention, rehabilitering och nära vård. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Sjöberg, Folke
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Hansson, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Needle Fasciotomy or Collagenase Injection in the Treatment of Dupuytren’s Contracture: A Retrospective Study2020Ingår i: Plastic and Reconstructive Surgery – Global Open, E-ISSN 2169-7574, Vol. 8, nr 1Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Background: Dupuytren’s contracture is common among older people in Sweden. Previous studies comparing the treatment with an injection of collagenase with percutaneous needle fasciotomy found no differences. Methods: We retrospectively compared the degree of improvement in the deficit in extension of the joints in 2 groups of patients who had been treated with collagenase (71 fingers) or needle fasciotomy (109 fingers) before and 1 year after treatment. We compared the improvement of the extension deficit among the metacarpophalangeal (MCP) and proximal interphalangeal joints before and after the intervention; additionally, the level of improvement was classified into 3 levels (mild = 0° to 29°; moderate = 30° to 60°; considerable = 61° and more). Results: The degree of improvement of extension in the MCP joints was 11° greater in the collagenase group (P = 0.001). The number of patients who had an improvement of >60° (considerable) in extension was greater in the collagenase group (P = 0.02). Conclusion: Collagenase was more effective than needle fasciotomy in treating extension deficits of the MCP joints in Dupuytren’s contracture in this retrospective analysis. Further prospective studies are required to confirm the finding.

  • 2.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Ntzouni, Maria
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Wright, Dominic
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    Khan, Kabirul Islam
    Chattogram Vet and Anim Sci Univ, Bangladesh.
    Lopez-Bejar, Manel
    Univ Autonoma Barcelona, Spain.
    Martinez-Serrano, Cristina
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Rodriguez-Martinez, Heriberto
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Chicken seminal fluid lacks CD9-and CD44-bearing extracellular vesicles2020Ingår i: Reproduction in domestic animals, ISSN 0936-6768, E-ISSN 1439-0531Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The avian seminal fluid (SF) is a protein-rich fluid, derived from the testis, the rudimentary epididymis and, finally, from the cloacal gland. The SF interacts with spermatozoa and the inner cell lining of the female genital tract, to modulate sperm functions and female immune responsiveness. Its complex proteome might either be free or linked to extracellular vesicles (EVs) as it is the case in mammals, where EVs depict the tetraspanin CD9; and where those EVs derived from the epididymis (epididymosomes) also present the receptor CD44. In the present study, sperm-free SF from Red Jungle Fowl, White Leghorn and an advanced intercross (AIL, 12th generation) were studied using flow cytometry of the membrane marker tetraspanin CD9, Western blotting of the membrane receptor CD44 and electron microscopy in non-enriched (whole SF) or enriched fractions obtained by precipitation using a commercial kit (Total Exosome Precipitation Solution). Neither CD9- nor CD44 could be detected, and the ultrastructure confirmed the relative absence of EVs, raising the possibility that avian SF interacts differently with the female genitalia as compared to the seminal plasma of mammals.

  • 3.
    Andersson, Asa
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Vilhelmsson, Mattias
    Reg Hosp Vaxjo, Sweden.
    Fomichov Casaballe, Victoria
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för verksamhetsstöd och utveckling, Regionalt Cancercentrum.
    Lindhoff Larsson, Anna
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Björnsson, Bergthor
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Sandström, Per
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Drott, Jenny
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för omvårdnad och reproduktiv hälsa. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Patient involvement in surgical care-Healthcare personnel views and behaviour regarding patient involvement2020Ingår i: Scandinavian Journal of Caring Sciences, ISSN 0283-9318, E-ISSN 1471-6712Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background All professions in surgical care have a responsibility to include patients in their health care. By Swedish law, all care should be done in dialogue with the patient. The essential part of health care is the meeting between patient and healthcare professional. In the interaction, a decision can be made, and needs can be identified to a safer care. Previous studies on patient participation have focussed on patients perspectives in surgical care, but there is a paucity of studies about the personnels perspective of estimated patient involvement in surgical care. Aim The aim of this study was to identify and describe healthcare personnels view and behaviour regarding patient involvement in surgical care. Method A quantitative study with various professions was conducted. A validated questionnaire was used, remaining questions grouped under following areas: patient involvement, acute phase, hospital time, discharge phase and questions on employment and workplace. Results A total of 140 questionnaires were sent out to a surgical clinic in Sweden, and 102 questionnaires were answered. All professionals stated that clear information is an important part of patient involvement in surgical care. Statistically significant differences existed between the professions in the subscale information. Physicians rated their information higher than the Registered Nurses (p = 0.005) and the practical nurses did (p = 0.001). Hindrances to involving patients were lack of time and other priority tasks. Conclusions Professionals in surgical care graded information to be the most important thing for patient involvement. Participation in important decisions, including the possibility to express personal views and ask questions, is important factors for patient involvement. Barriers against patient involvement are lack of time and prioritisation of other work activities.

  • 4.
    Appelgren, Daniel
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten.
    Enocsson, Helena
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten.
    Skogman, Barbro H
    Center for Clinical Research Dalarna-Uppsala University, Region Dalarna and Faculty of Medicine and Health Sciences, Örebro University.
    Nordberg, Marika
    Åland Central Hospital, Department of Infectious Diseases, AX-22 100 Mariehamn, Åland, Finland.
    Perander, Linda
    Åland Central Hospital, Department of Infectious Diseases, AX-22 100 Mariehamn, Åland, Finland.
    Nyman, Dag
    Bimelix AB, AX-22 100 Mariehamn, Åland, Finland.
    Nyberg, Clara
    Åland Central Hospital, Department of Infectious Diseases, AX-22 100 Mariehamn, Åland, Finland.
    Knopf, Jasmin
    Department of Internal Medicine 3-Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), DE-91 054 Erlangen, Germany.
    Muñoz, Luis E
    Department of Internal Medicine 3-Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), DE-91 054 Erlangen, Germany.
    Sjöwall, Christopher
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten.
    Sjöwall, Johanna
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Infektionskliniken i Östergötland.
    Neutrophil Extracellular Traps (NETs) in the Cerebrospinal Fluid Samples from Children and Adults with Central Nervous System Infections.2019Ingår i: Cells, ISSN 2073-4409, Vol. 9, nr 1, artikel-id E43Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Neutrophils operate as part of the innate defence in the skin and may eliminate the Borrelia spirochaete via phagocytosis, oxidative bursts, and hydrolytic enzymes. However, their importance in Lyme neuroborreliosis (LNB) is unclear. Neutrophil extracellular trap (NET) formation, which is associated with the production of reactive oxygen species, involves the extrusion of the neutrophil DNA to form traps that incapacitate bacteria and immobilise viruses. Meanwhile, NET formation has recently been studied in pneumococcal meningitis, the role of NETs in other central nervous system (CNS) infections has previously not been studied. Here, cerebrospinal fluid (CSF) samples from clinically well-characterised children (N = 111) and adults (N = 64) with LNB and other CNS infections were analysed for NETs (DNA/myeloperoxidase complexes) and elastase activity. NETs were detected more frequently in the children than the adults (p = 0.01). NET presence was associated with higher CSF levels of CXCL1 (p < 0.001), CXCL6 (p = 0.007), CXCL8 (p = 0.003), CXCL10 (p < 0.001), MMP-9 (p = 0.002), TNF (p = 0.02), IL-6 (p < 0.001), and IL-17A (p = 0.03). NETs were associated with fever (p = 0.002) and correlated with polynuclear pleocytosis (rs = 0.53, p < 0.0001). We show that neutrophil activation and active NET formation occur in the CSF samples of children and adults with CNS infections, mainly caused by Borrelia and neurotropic viruses. The role of NETs in the early phase of viral/bacterial CNS infections warrants further investigation.

  • 5.
    Axelsson, Daniel
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Department of Obstetrics and Gynecology, Ryhov County Hospital, Jönköping, Sweden.
    Brynhildsen, Jan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum.
    Blomberg, Marie
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum.
    Vitamin D deficiency at the time of delivery - Prevalence and risk of postpartum infections.2019Ingår i: PLoS ONE, E-ISSN 1932-6203, Vol. 14, nr 12, artikel-id e0226673Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Postpartum infections are a common cause of morbidity after childbirth. Vitamin D deficiency has been shown to increase the risk for several infections in a non-pregnant population. Vitamin D deficiency has been described as common in pregnant women.

    OBJECTIVE: To investigate whether vitamin D deficiency in pregnant women in labor was associated with an increased risk of overall postpartum infectious morbidity within eight weeks of delivery. A secondary aim was to estimate the prevalence of vitamin D deficiency among pregnant women in Linköping, Sweden at the time of delivery.

    MATERIAL AND METHODS: Serum vitamin D levels in labor were analyzed for 1397 women. Vitamin D deficiency was defined as serum levels <50 nmol/L. All ICD-10 codes given to the women eight weeks postpartum were reviewed and postpartum infections were defined as the presence of an ICD-10 code suggestive of infection. The prevalence of postpartum infections among women with sufficient vitamin D levels was compared with women with vitamin D deficiency. Adjusted Odds Ratios and 95% confidence intervals for postpartum infections were calculated using multivariate logistic regression analysis.

    RESULTS: Fifty eight per cent of the women had serum vitamin D levels <50 nmol/L. The proportion of women with vitamin D deficiency varied, as expected, with season. No association between vitamin D deficiency and postpartum infections was found. For vitamin D 25-50 nmol/L the adjusted Odds Ratio was 0.85 (95% confidence interval 0.56-1.29) and for vitamin D <25 nmol/L the adjusted Odds Ratio was 1.15 (95% confidence interval 0.66-2.03). Women who smoked or who had a cesarean section had an increased risk of postpartum infections.

    CONCLUSIONS: Vitamin D deficiency was more common than previously reported in Swedish pregnant women. No association between vitamin D deficiency and postpartum infections was found. Other well-known risk factors for postpartum infection were identified.

  • 6.
    Balla, Hajnal Zsuzsanna
    et al.
    Orebro Univ, Sweden.
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Ström, Jakob
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Orebro Univ, Sweden.
    Evaluation of commercial, wireless dermal thermometers for surrogate measurements of core temperature2019Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 79, nr 1-2Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Extensive research has been devoted to developing methods for assessing core body temperature, and to determine which method is most accurate. A number of wireless dermal thermometers for home use are presently available, but their relation to core body temperature and suitability for use in clinical research has hitherto not been assessed. The current study aimed to evaluate such thermometers by comparing them to the results of a rectal thermometer. Four wireless dermal thermometers for home use (FeverSmart, iThermonitor, Quest Temp Sitter, and Thermochron iButton) were applied to 15 patients during 24 h, and rectal temperature was measured at four occasions. Pearson correlation revealed moderate correlation for the Feversmart (r = 0.75), iThermonitor (r = 0.79), and Thermochron iButton (r = 0.71) systems. The Quest Temp Sitter system malfunctioned repeatedly, and the correlation (r = 0.29) for this method should therefore be assessed with caution. All dermal thermometers rendered lower average temperatures than Terumo c405 (Feversmart -0.70 +/- 0.65 degrees C; iThermonitor -0.77 +/- 0.53 degrees C, Quest Temp Sitter -1.18 +/- 0.66 degrees C, and Thermochron iButton -0.87 +/- 0.65 degrees C). Sensitivity of the dermal thermometers for detecting core temperatures amp;gt;= 38.0 degrees C was low, ranging from 0.33 to 0.6, but improved to 0.60 to 0.80 after adjusting temperatures by the methods average deviation from rectal temperature. The results from the dermal thermometers tested here showed an insufficient correlation to core temperature to be used for core temperature monitoring in clinical research and practice. Unfortunately, other options for non-invasive temperature measurements are few. The two thermometers with the least unsatisfactory performance profile in our evaluations were the Feversmart and iThermonitor systems.

  • 7.
    Barrett, Elizabeth
    et al.
    Univ Coll Dublin, Ireland; Childrens Univ Hosp, Ireland.
    Jacobs, Brian
    South London and Maudsley Hosp, England; European Union Med Specialists UEMS CAP, Belgium.
    Klasen, Henrikje
    Leiden Univ, Netherlands.
    Herguner, Sabri
    Private Practice, Turkey.
    Agnafors, Sara
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Banjac, Visnja
    Univ Clin Ctr Republ Srpska, Bosnia and Herceg.
    Bezborodovs, Nikita
    Riga Stradins Univ, Latvia.
    Cini, Erica
    East London Fdn Trust, England.
    Hamann, Christoph
    Univ Bern, Switzerland.
    Huscsava, Mercedes M.
    Med Univ Vienna, Austria.
    Kostadinova, Maya
    Univ Hosp Alexandrovska, Bulgaria; DNCC CAMHS, Ireland.
    Kramar, Yuliia
    TMA PSYCHIAT, Ukraine.
    Maravic, Vanja Mandic
    Inst Mental Hlth, Serbia.
    McGrath, Jane
    Cherry Orchard Hosp, Ireland.
    Molteni, Silvia
    Univ Pavia, Italy.
    Moron-Nozaleda, Maria Goretti
    Neurodev Outpatient Clin, Spain; Hosp Infantil Univ Nino Jesus, Spain.
    Mudra, Susanne
    Univ Med Ctr Hamburg Eppendorf, Germany.
    Nikolova, Gordana
    Univ Clin Psychiat, North Macedonia.
    Vorkas, Kallistheni Pantelidou
    Cypriot Soc Child and Adolescent Psychiat, Cyprus.
    Prata, Ana Teresa
    Hosp Dona Estefania, Portugal.
    Revet, Alexis
    Univ Toulouse 3, France.
    Joseph, Judeson Royle
    Univ Hosp North Norway, Norway.
    Serbak, Reelika
    Tallinn Childrens Hosp, Estonia.
    Tomac, Aran
    CAMHS Clare, Ireland.
    Van den Steene, Helena
    Univ Antwerp, Belgium.
    Xylouris, Georgios
    Gen Childrens Hosp Agia Sophia, Greece.
    Zielinska, Anna
    Med Univ Warsaw, Poland.
    Hebebrand, Johannes
    Univ Duisburg Essen, Germany.
    Correction: The child and adolescent psychiatry: study of training in Europe (CAP-STATE) (vol 74, pg 231, 2020)2020Ingår i: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165XArtikel i tidskrift (Refereegranskat)
    Abstract [en]

    The original article has been corrected.

  • 8.
    Beeckmans, Dorien
    et al.
    Katholieke Univ Leuven, Belgium.
    Farre, Ricard
    Katholieke Univ Leuven, Belgium.
    Riethorst, Danny
    Katholieke Univ Leuven, Belgium.
    Keita, Åsa
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten.
    Augustijns, Patrick
    Katholieke Univ Leuven, Belgium.
    Söderholm, Johan D
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Vanuytsel, Tim
    Katholieke Univ Leuven, Belgium.
    Vanheel, Hanne
    Katholieke Univ Leuven, Belgium.
    Tack, Jan
    Katholieke Univ Leuven, Belgium.
    Relationship between bile salts, bacterial translocation, and duodenal mucosal integrity in functional dyspepsia2020Ingår i: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, artikel-id e13788Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Functional dyspepsia (FD) is a complex disorder, in which multiple mechanisms underlie symptom generation, including impaired duodenal barrier function. Moreover, an altered duodenal bile salt pool was recently discovered in patients with FD. We aimed to evaluate the relationship between bile salts, bacterial translocation, and duodenal mucosal permeability in FD. Methods Duodenal biopsies from patients with FD and healthy volunteers (HV) were mounted in Ussing chambers to measure mucosal resistance and bacterial passage in the absence and presence of fluorescein-conjugated Escherichia coli and glyco-ursodeoxycholic acid (GUDCA) exposure. In parallel, duodenal fluid aspirates were collected from patients and bile salts were analyzed. Key results The transepithelial electrical resistance of duodenal biopsies from patients was lower compared with HV (21.4 +/- 1.3 omega.cm(2) vs. 24.4 +/- 1.2 omega.cm(2); P = .02; N = 21). The ratio of glyco-cholic and glyco-chenodeoxycholic acid (GCDCA) to tauro- and GUDCA correlated positively with transepithelial electrical resistance in patients. Glyco-ursodeoxycholic acid slightly altered the mucosal resistance, resulting in similar values between patient and healthy biopsies (22.1 +/- 1.0 omega.cm(2) vs. 23.0 +/- 1.0 omega.cm(2); P = .5). Bacterial passage after 120 minutes was lower for patient than for healthy biopsies (0.0 [0.0-681.8] vs. 1684.0 [0.0-4773.0] E coli units; P = .02). Glyco-ursodeoxycholic acid increased bacterial passage in patient biopsies (102.1 [0.0-733.0] vs. 638.9 [280.6-2124.0] E coli units; P = .009). No correlation was found between mucosal resistance and bacterial passage. Conclusions amp; inferences Patients with FD displayed decreased duodenal mucosal resistance associated with bile salts, however, not associated with bacterial passage in vitro. In addition, the hydrophilic bile salt glyco-ursodeoxycholic acid abolished differences in mucosal resistance and bacterial passage between patient and control group.

  • 9.
    Bergkvist, Liza
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten. Van Andel Res Inst, MI USA.
    Du, Zhen
    Univ Cambridge, England; Univ Cambridge, England.
    Elovsson, Greta
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Appelqvist, Hanna
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Itzhaki, Laura S.
    Univ Cambridge, England.
    Kumita, Janet R.
    Univ Cambridge, England.
    Kågedal, Katarina
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Brorsson, Ann-Christin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Mapping pathogenic processes contributing to neurodegeneration in Drosophila models of Alzheimers disease2020Ingår i: FEBS Open Bio, E-ISSN 2211-5463Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Alzheimers disease (AD) is the most common form of dementia, affecting millions of people and currently lacking available disease-modifying treatments. Appropriate disease models are necessary to investigate disease mechanisms and potential treatments. Drosophila melanogaster models of AD include the A beta fly model and the A beta PP-BACE1 fly model. In the A beta fly model, the A beta peptide is fused to a secretion sequence and directly overexpressed. In the A beta PP-BACE1 model, human A beta PP and human BACE1 are expressed in the fly, resulting in in vivo production of A beta peptides and other A beta PP cleavage products. Although these two models have been used for almost two decades, the underlying mechanisms resulting in neurodegeneration are not yet clearly understood. In this study, we have characterized toxic mechanisms in these two AD fly models. We detected neuronal cell death and increased protein carbonylation (indicative of oxidative stress) in both AD fly models. In the A beta fly model, this correlates with high A beta(1-42) levels and down-regulation of the levels of mRNA encoding lysosomal-associated membrane protein 1, lamp1 (a lysosomal marker), while in the A beta PP-BACE1 fly model, neuronal cell death correlates with low A beta(1-42) levels, up-regulation of lamp1 mRNA levels and increased levels of C-terminal fragments. In addition, a significant amount of A beta PP/A beta antibody (4G8)-positive species, located close to the endosomal marker rab5, was detected in the A beta PP-BACE1 model. Taken together, this study highlights the similarities and differences in the toxic mechanisms which result in neuronal death in two different AD fly models. Such information is important to consider when utilizing these models to study AD pathogenesis or screening for potential treatments.

  • 10.
    Bergström, Maria
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för prevention, rehabilitering och nära vård. Linköpings universitet, Medicinska fakulteten.
    Sverker, Annette
    Linköpings universitet, Institutionen för kultur och samhälle, Avdelningen för socialt arbete. Linköpings universitet, Filosofiska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Rörelse och Hälsa.
    Larsson Ranada, Åsa
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för prevention, rehabilitering och nära vård. Linköpings universitet, Medicinska fakulteten.
    Valtersson, Eva
    Linköpings universitet, Institutionen för hälsa, medicin och vård. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Rörelse och Hälsa.
    Thyberg, Ingrid
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Ostlund, Gunnel
    Malardalen Univ, Sweden.
    Björk, Mathilda
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för prevention, rehabilitering och nära vård. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Significant others influence on participation in everyday life - the perspectives of persons with early diagnosed rheumatoid arthritis2020Ingår i: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, Vol. 42, nr 3, s. 385-393Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To describe the meaning of significant others in relation to participation in everyday life of persons with early diagnosed rheumatoid arthritis (RA). Materials and methods: Fifty-nine persons participated in this interview study. Inclusion criteria were three years experience of diagnosis and being of working age. Semi-structured interviews were conducted using critical incident technique (CIT), and the material was analysed using content analysis. Results: Four categories were revealed: (1) My early RA causes activity adaptations for us all, referring to the person and significant others modifying activities. (2) Making the significant others balance between shortfalls and participation, where the participants distinguished between needing help and feeling involved in activities. (3) Physical interactions with significant others, referring to both the problematic and manageable impact RA could have on body contact. (4) Emotions in relation to activities with others, where participants described feelings of failing others, and anxiety about future activities. Conclusions: For persons with early diagnosed RA, significant others can be both hindering and facilitating for participation in everyday life. As a clinical implication, it is valuable to identify how significant others can be involved in the rehabilitation process, to enhance participation in everyday life early in the disease process.

  • 11.
    Bird, Philippa K
    et al.
    Department of Health Sciences, University of York, York, North Yorkshire, UK // Leeds Teaching Hospitals NHS Trust, Leeds, UK.
    Pickett, Kate E
    Department of Health Sciences, University of York, York, North Yorkshire, UK.
    Graham, Hilary
    Department of Health Sciences, University of York, York, North Yorkshire, UK.
    Faresjö, Tomas
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för prevention, rehabilitering och nära vård. Linköpings universitet, Medicinska fakulteten.
    Jaddoe, Vincent W V
    Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands // Department of Pediatrics, Erasmus Medical Center, Rotterdam, The Netherlands.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Raat, Hein
    Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands.
    Seguin, Louise
    Department of Social and Preventive Medicine, Universite de Montreal, Montreal, Québec, Canada.
    Wijtzes, Anne I
    Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands.
    McGrath, Jennifer J
    Department of Psychology, Concordia University, Montreal, Québec, Canada.
    Income inequality and social gradients in children's height: a comparison of cohort studies from five high-income countries.2019Ingår i: BMJ paediatrics open, ISSN 2399-9772, Vol. 3, nr 1, artikel-id e000568Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Health and well-being are better, on average, in countries that are more equal, but less is known about how this benefit is distributed across society. Height is a widely used, objective indicator of child health and predictor of lifelong well-being. We compared the level and slope of social gradients in children's height in high-income countries with different levels of income inequality, in order to investigate whether children growing up in all socioeconomic circumstances are healthier in more equal countries.

    Methods: We conducted a coordinated analysis of data from five cohort studies from countries selected to represent different levels of income inequality (the USA, UK, Australia, the Netherlands and Sweden). We used standardised methods to compare social gradients in children's height at age 4-6 years, by parent education status and household income. We used linear regression models and predicted height for children with the same age, sex and socioeconomic circumstances in each cohort.

    Results: The total analytic sample was 37 063 children aged 4-6 years. Gradients by parent education and household income varied between cohorts and outcomes. After adjusting for differences in age and sex, children in more equal countries (Sweden, the Netherlands) were taller at all levels of parent education and household income than children in less equal countries (USA, UK and Australia), with the greatest between-country differences among children with less educated parents and lowest household incomes.

    Conclusions: The study provides preliminary evidence that children across society do better in more equal countries, with greatest benefit among children from the most disadvantaged socioeconomic groups.

  • 12.
    Bolckmans, Roel
    et al.
    Oxford Univ Hosp Natl Hlth Serv Fdn Trust, England.
    Kalman, Thordis Disa
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Singh, Sandeep
    Oxford Univ Hosp Natl Hlth Serv Fdn Trust, England.
    Ratnatunga, Keshara C.
    Oxford Univ Hosp Natl Hlth Serv Fdn Trust, England.
    Myrelid, Pär
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Travis, Simon
    Oxford Univ Hosp Natl Hlth Serv Fdn Trust, England.
    George, Bruce D.
    Oxford Univ Hosp Natl Hlth Serv Fdn Trust, England.
    Does Smoking Cessation Reduce Surgical Recurrence After Primary Ileocolic Resection for Crohns Disease?2020Ingår i: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 63, nr 2, s. 200-206Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Tobacco smoking is a known risk factor for recurrence of Crohns disease after surgical resection. OBJECTIVE: This study assessed the effect of smoking cessation on long-term surgical recurrence after primary ileocolic resection for Crohns disease. DESIGN: A retrospective review of a prospectively maintained database was conducted. SETTINGS: Patient demographic data and medical and surgical details were combined from 2 specialist centers. After ethical approval, patients were contacted in case of missing data regarding smoking habit. PATIENTS: All patients undergoing ileocolic resection between 2000 and 2012 for histologically confirmed Crohns disease were included. Those with previous intestinal resection, strictureplasty for Crohns disease, leak after ileocolic resection, or who were never reversed were excluded. MAIN OUTCOME MEASURES: The primary end point was surgical recurrence measured by Kaplan-Meier survival analysis and secondary medical therapy at time of follow-up. RESULTS: Over a 12-year period, 290 patients underwent ileocolic resection. Full smoking data were available for 242 (83%) of 290 patients. There were 169 nonsmokers (70%; group 1), 42 active smokers at the time of ileocolic resection who continued smoking up to last follow-up (17%; group 2), and 31 (13%) who quit smoking after ileocolic resection (group 3). The median time of smoking exposure after ileocolic resection for group 3 was 3 years (interquartile range, 0-6 y), and median follow-up time for the whole group was 112 months (9 mo; interquartile range, 84-148 mo). Kaplan-Meier survival analysis showed a significantly higher surgical recurrence rate for group 2 compared with group 3 (16/42 (38%) vs 3/31 (10%); p = 0.02; risk ratio = 3.9 (95% CI, 1-12)). In addition, significantly more patients in group 2 without surgical recurrence received immunomodulatory maintenance therapy compared with group 3 (12/26 (46%) vs 4/28 (14%); p = 0.01; risk ratio = 3.2 (95% CI, 1-9)). LIMITATIONS: The study was limited by its retrospective design and small number of patients. CONCLUSIONS: Smoking cessation after primary ileocolic resection for Crohns disease may significantly reduce long-term risk of surgical recurrence and is associated with less use of maintenance therapy. See Video Abstract at http://links.lww.com/DCR/B86.

  • 13.
    Bratengeier, Cornelia
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Liszka, Aneta
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Hoffman, Johan
    KTH Royal Inst Technol, Sweden.
    Bakker, Astrid D.
    Univ Amsterdam, Netherlands; Vrije Univ Amsterdam, Netherlands.
    Fahlgren, Anna
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    High shear stress amplitude in combination with prolonged stimulus duration determine induction of osteoclast formation by hematopoietic progenitor cellsIngår i: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To date, it is unclear how fluid dynamics stimulate mechanosensory cells to induce an osteoprotective or osteodestructive response. We investigated how murine hematopoietic progenitor cells respond to 2 minutes of dynamic fluid flow stimulation with a precisely controlled sequence of fluid shear stresses. The response was quantified by measuring extracellular adenosine triphosphate (ATP), immunocytochemistry of Piezo1, and sarcoplasmic/endoplasmic Ca2+ reticulum ATPase 2 (SERCA2), and by the ability of soluble factors produced by mechanically stimulated cells to modulate osteoclast differentiation. We rejected our initial hypothesis that peak wall shear stress rate determines the response of hematopoietic progenitor cells to dynamic fluid shear stress, as it had only a minor correlation with the abovementioned parameters. Low stimulus amplitudes corresponded to activation of Piezo1, SERCA2, low concentrations of extracellular ATP, and inhibition of osteoclastogenesis and resorption area, while high amplitudes generally corresponded to osteodestructive responses. At a given amplitude (3 Pa) and waveform (square), the duration of individual stimuli (duty cycle) showed a strong correlation with the release of ATP and osteoclast number and resorption area. Collectively, our data suggest that hematopoietic progenitor cells respond in a viscoelastic manner to loading, since a combination of high shear stress amplitude and prolonged duty cycle is needed to trigger an osteodestructive response. Plain Language Summary In case of painful joints or missing teeth, the current intervention is to replace them with an implant to keep a high-quality lifestyle. When exercising or chewing, the cells in the bone around the implant experience mechanical loading. This loading generally supports bone formation to strengthen the bone and prevent breaking, but can also stimulate bone loss when the mechanical loading becomes too high around orthopedic and dental implants. We still do not fully understand how cells in the bone can distinguish between mechanical loading that strengthens or weakens the bone. We cultured cells derived from the bone marrow in the laboratory to test whether the bone loss response depends on (i) how fast a mechanical load is applied (rate), (ii) how intense the mechanical load is (amplitude), or (iii) how long each individual loading stimulus is applied (duration). We mimicked mechanical loading as it occurs in the body, by applying very precisely controlled flow of fluid over the cells. We found that a mechanosensitive receptor Piezo1 was activated by a low amplitude stimulus, which usually strengthens the bone. The potential inhibitor of Piezo1, namely SERCA2, was only activated by a low amplitude stimulus. This happened regardless of the rate of application. At a constant high amplitude, a longer duration of the stimulus enhanced the bone-weakening response. Based on these results we deduce that a high loading amplitude tends to be bone weakening, and the longer this high amplitude persists, the worse it is for the bone.

  • 14.
    Carlhäll, Sara
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Kallen, Karin
    Lund Univ, Sweden.
    Blomberg, Marie
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    The effect of maternal body mass index on duration of induced labor2020Ingår i: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction Obese primiparous women with induction of labor are at high risk for a cesarean section. There are contradictory results regarding time in induced labor in relation to maternal body mass index (BMI). It is important to characterize the course of induced labor to prevent unnecessary cesarean section. We aimed to evaluate whether the duration of labor was associated with maternal BMI in primiparous women with induction of labor. Material and methods A national retrospective cohort study, including 15 259 primiparae with a single term pregnancy, admitted for induction of labor from January 2014 to August 2017. Data were obtained from the Swedish Pregnancy Registry. Cox regression analyses were used to illustrate the association between BMI and active labor and between BMI and time from admission until start of active labor. Results Duration of active labor was shorter in underweight women and prolonged in women with BMI amp;gt;= 40 kg/m(2) compared with women in other BMI classes, illustrated by Cox regression graphs (P amp;lt; .001). The median durations of active labor in underweight women were 6.1 and 7.4 hours in women with BMI amp;gt;= 40 kg/m(2). The time from admission until start of active labor increased with maternal BMI, illustrated by Cox regression graphs (P amp;lt; .001) and the median duration increased from 12.9 hours in underweight women to 22.6 hours in women with BMI amp;gt;= 40 kg/m(2). The cesarean section rate in active labor increased significantly with BMI (P amp;lt; .001) from 7.4% in underweight women to 22.0% in women with BMI amp;gt;= 40 kg/m(2). Obese and normal weight women had similar rates of spontaneous vaginal delivery (69.9% in the total study population). Conclusions The duration of active labor was associated with maternal BMI for underweight women and women with BMI amp;gt;= 40 kg/m(2). Although women with BMI amp;gt;= 40 kg/m(2) who reached the active phase of labor had the same chance for a spontaneous vaginal delivery as normal weight women, the duration of active labor and the cesarean section rate were increased. The time from admission until start of active labor increased successively with maternal BMI.

  • 15.
    Carlsson, Annelie
    et al.
    Lund Univ, Sweden.
    Shepherd, Maggie
    Univ Exeter, England.
    Ellard, Sian
    Univ Exeter, England; Royal Devon and Exeter NHS Fdn Trust, England.
    Weedon, Michael
    Univ Exeter, England.
    Lernmark, Ake
    Lund Univ, Sweden.
    Forsander, Gun
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Colclough, Kevin
    Royal Devon and Exeter NHS Fdn Trust, England.
    Brahimi, Qefsere
    Lund Univ, Sweden.
    Valtonen-Andre, Camilla
    Univ and Reg Labs Reg, Sweden.
    Ivarsson, Sten A.
    Lund Univ, Sweden.
    Elding Larsson, Helena
    Lund Univ, Sweden.
    Samuelsson, Ulf
    Region Östergötland, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Norrköping.
    Ortqvist, Eva
    Karolinska Inst, Sweden.
    Groop, Leif
    Univ Helsinki, Finland.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Marcus, Claude
    Karolinska Inst, Sweden.
    Hattersley, Andrew T.
    Univ Exeter, England.
    Absence of Islet Autoantibodies and Modestly Raised Glucose Values at Diabetes Diagnosis Should Lead to Testing for MODY: Lessons From a 5-Year Pediatric Swedish National Cohort Study2020Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 43, nr 1, s. 82-89Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE Identifying maturity-onset diabetes of the young (MODY) in pediatric populations close to diabetes diagnosis is difficult. Misdiagnosis and unnecessary insulin treatment are common. We aimed to identify the discriminatory clinical features at diabetes diagnosis of patients with glucokinase (GCK), hepatocyte nuclear factor-1A (HNF1A), and HNF4A MODY in the pediatric population.

    RESEARCH DESIGN AND METHODS Swedish patients (n = 3,933) aged 1–18 years, diagnosed with diabetes May 2005 to December 2010, were recruited from the national consecutive prospective cohort Better Diabetes Diagnosis. Clinical data, islet autoantibodies (GAD insulinoma antigen-2, zinc transporter 8, and insulin autoantibodies), HLA type, and C-peptide were collected at diagnosis. MODY was identified by sequencing GCKHNF1A, and HNF4A, through either routine clinical or research testing.

    RESULTS The minimal prevalence of MODY was 1.2%. Discriminatory factors for MODY at diagnosis included four islet autoantibody negativity (100% vs. 11% not-known MODY; P = 2 × 10−44), HbA1c (7.0% vs. 10.7% [53 vs. 93 mmol/mol]; P = 1 × 10−20), plasma glucose (11.7 vs. 26.7 mmol/L; P = 3 × 10−19), parental diabetes (63% vs. 12%; P = 1 × 10−15), and diabetic ketoacidosis (0% vs. 15%; P = 0.001). Testing 303 autoantibody-negative patients identified 46 patients with MODY (detection rate 15%). Limiting testing to the 73 islet autoantibody-negative patients with HbA1c <7.5% (58 mmol/mol) at diagnosis identified 36 out of 46 (78%) patients with MODY (detection rate 49%). On follow-up, the 46 patients with MODY had excellent glycemic control, with an HbA1c of 6.4% (47 mmol/mol), with 42 out of 46 (91%) patients not on insulin treatment.

    CONCLUSIONS At diagnosis of pediatric diabetes, absence of all islet autoantibodies and modest hyperglycemia (HbA1c <7.5% [58 mmol/mol]) should result in testing for GCK, HNF1A, and HNF4A MODY. Testing all 12% patients negative for four islet autoantibodies is an effective strategy for not missing MODY but will result in a lower detection rate. Identifying MODY results in excellent long-term glycemic control without insulin.

  • 16.
    Derolf, Asa
    et al.
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Juliusson, Gunnar
    Skane Univ Hosp, Sweden.
    Benson, Lina
    Epidemiol and Reg Oncol Ctr Stockholm, Sweden.
    Floisand, Yngvar
    Oslo Univ Hosp, Norway.
    Lazarevic, Vladimir
    Skane Univ Hosp, Sweden.
    Antunovic, Petar
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US.
    Mollgard, Lars
    Sahlgrens Univ Hosp, Sweden.
    Lehmann, Soren
    Uppsala Univ, Sweden.
    Uggla, Bertil
    Orebro Univ Hosp, Sweden.
    Wahlin, Anders
    Umea Univ, Sweden.
    Hoglund, Martin
    Uppsala Univ, Sweden.
    Deneberg, Stefan
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Letter: Decreasing early mortality in acute myeloid leukaemia in Sweden 1997-2014: improving performance status is a major contributing factor in BRITISH JOURNAL OF HAEMATOLOGY, vol 188, issue 1, pp 187-1912020Ingår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 188, nr 1, s. 187-191Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    n/a

  • 17.
    Engström, Karolina
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Vanky, Farkas
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten.
    Rehnberg, Malin
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Trinks, Cecilia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Jonasson, Jon
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Green, Anna
    Orebro Univ, Sweden.
    Gunnarsson, Cecilia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Novel SMAD3 p.Arg386Thr genetic variant co-segregating with thoracic aortic aneurysm and dissection2020Ingår i: Molecular Genetics & Genomic Medicine, ISSN 2324-9269, artikel-id e1089Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Pathogenic variants in the SMAD3 gene affecting the TGF-beta/SMAD3 signaling pathway with aortic vessel involvement cause Loeys-Dietz syndrome 3, also known as aneurysms-osteoarthritis syndrome. Methods Description of clinical history of a family in Sweden using clinical data, DNA sequencing, bioinformatics, and pedigree analysis. Results We report a novel SMAD3 variant, initially classified as a genetic variant of uncertain clinical significance (VUS), and later found to be co-segregating with aortic dissection in the family. The index patient presented with a dissecting aneurysm of the aorta including the ascending, descending, and abdominal parts. Genotype analysis revealed a heterozygous missense SMAD3 variant: NM_005902.3(SMAD3): c.11576G amp;gt; C (p.Arg386Thr). The same variant was also identified in a 30 years old formalin-fixed paraffin-embedded block of tissue from a second cousin, who died at 26 years of age from a dissecting aneurysm of the aorta. Conclusion A "variant of uncertain significance" according to the ACMG guidelines has always a scope for reappraisal. Genetic counselling to relatives, and the offering of surveillance service is important to families with aortic aneurysm disease. The report also highlight the potential use of FFPE analysis from deceased relatives to help in the interpretation of variants.

  • 18.
    Enocsson, Helena
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten.
    Wirestam, Lina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Dahle, Charlotte
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin. Linköpings universitet, Medicinska fakulteten.
    Padyukov, Leonid
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Jonsen, Andreas
    Lund Univ, Sweden.
    Urowitz, Murray B.
    Toronto Western Hosp, Canada; Univ Toronto, Canada.
    Gladmane, Dafna D.
    Toronto Western Hosp, Canada; Univ Toronto, Canada.
    Romero-Diaz, Juanita
    Inst Nacl Ciencias Med and Nutr Salvador Zubiran, Mexico.
    Bae, Sang-Cheol
    Hanyang Univ, South Korea.
    Fortin, Paul R.
    Univ Laval, Canada.
    Sanchez-Guerrero, Jorge
    Toronto Western Hosp, Canada; Univ Toronto, Canada.
    Clarke, Ann E.
    Univ Calgary, Canada.
    Bernatsky, Sasha
    McGill Univ, Canada.
    Gordon, Caroline
    Univ Birmingham, England.
    Hanly, John G.
    Queen Elizabeth 2 Hlth Sci Ctr, Canada; Queen Elizabeth 2 Hlth Sci Ctr, Canada; Dalhousie Univ, Canada.
    Wallace, Daniel J.
    Univ Calif Los Angeles, CA USA.
    Isenberg, David A.
    UCL, England.
    Rahman, Anisur
    UCL, England.
    Merrill, Joan T.
    Oklahoma Med Res Fdn, OK 73104 USA.
    Ginzler, Ellen
    Suny Downstate Med Ctr, NY 11203 USA.
    Alarcon, Graciela S.
    Univ Alabama Birmingham, AL 35294 USA.
    Chatham, W. Winn
    Univ Alabama Birmingham, AL 35294 USA.
    Petri, Michelle
    Johns Hopkins Univ, MD USA.
    Khamashta, Munther
    Kings Coll London, England.
    Aranow, Cynthia
    Feinstein Inst Med Res, NY USA.
    Mackay, Meggan
    Feinstein Inst Med Res, NY USA.
    Dooley, Mary Anne
    Univ N Carolina, NC 27515 USA.
    Manzi, Susan
    Allegheny Hlth Network, PA USA.
    Ramsey-Goldman, Rosalind
    Northwestern Univ, IL 60611 USA; Feinberg Sch Med, IL USA.
    Nived, Ola
    Lund Univ, Sweden.
    Steinsson, Kristjan
    Landspitali Univ Hosp, Iceland.
    Zoma, Asad A.
    Hairmyres Hosp, Scotland.
    Ruiz-Irastorza, Guillermo
    Univ Basque Country, Spain.
    Lim, S. Sam
    Emory Univ, GA USA.
    Kalunian, Kenneth C.
    UCSD Sch Med, CA USA.
    Inanc, Murat
    Istanbul Univ, Turkey.
    van Vollenhoven, Ronald F.
    Univ Amsterdam, Netherlands; Free Univ VU Amsterdam, Netherlands; Amsterdam Rheumatol and Immunol Ctr, Netherlands.
    Ramos-Casals, Manuel
    Hosp Clin Barcelona, Spain.
    Kamen, Diane L.
    Med Univ South Carolina, SC 29425 USA.
    Jacobsen, Soren
    Copenhagen Univ Hosp, Denmark.
    Peschken, Christine A.
    Univ Manitoba, Canada.
    Askanase, Anca
    Columbia Univ, NY USA.
    Stoll, Thomas
    Kantousspital, Switzerland.
    Bruce, Ian N.
    Univ Manchester, England; Manchester Univ Hosp NHS Fdn Trust, England.
    Wetterö, Jonas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten.
    Sjöwall, Christopher
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Soluble urokinase plasminogen activator receptor (suPAR) levels predict damage accrual in patients with recent-onset systemic lupus erythematosus2020Ingår i: Journal of Autoimmunity, ISSN 0896-8411, E-ISSN 1095-9157, Vol. 106, artikel-id 102340Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective

    The soluble urokinase plasminogen activator receptor (suPAR) has potential as a prognosis and severity biomarker in several inflammatory and infectious diseases. In a previous cross-sectional study, suPAR levels were shown to reflect damage accrual in cases of systemic lupus erythematosus (SLE). Herein, we evaluated suPAR as a predictor of future organ damage in recent-onset SLE.

    Methods

    Included were 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who met the 1997 American College of Rheumatology classification criteria with 5-years of follow-up data available. Baseline sera from patients and age- and sex-matched controls were assayed for suPAR. Organ damage was assessed annually using the SLICC/ACR damage index (SDI).

    Results

    The levels of suPAR were higher in patients who accrued damage, particularly those with SDI≥2 at 5 years (N = 32, 46.8% increase, p = 0.004), as compared to patients without damage. Logistic regression analysis revealed a significant impact of suPAR on SDI outcome (SDI≥2; OR = 1.14; 95% CI 1.03–1.26), also after adjustment for confounding factors. In an optimized logistic regression to predict damage, suPAR persisted as a predictor, together with baseline disease activity (SLEDAI-2K), age, and non-Caucasian ethnicity (model AUC = 0.77). Dissecting SDI into organ systems revealed higher suPAR levels in patients who developed musculoskeletal damage (SDI≥1; p = 0.007).

    Conclusion

    Prognostic biomarkers identify patients who are at risk of acquiring early damage and therefore need careful observation and targeted treatment strategies. Overall, suPAR constitutes an interesting biomarker for patient stratification and for identifying SLE patients who are at risk of acquiring organ damage during the first 5 years of disease.

  • 19.
    Eriksson, Per
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Segelmark, Mårten
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Njurmedicinska kliniken US.
    Systemisk vaskulit2018Ingår i: Internmedicin / [ed] Ulf Dahlström, Stergios Kechagias, Leif Stenke, Stockholm: Liber, 2018, 6, Vol. Sidorna 939-949, s. 939-949Kapitel i bok, del av antologi (Övrigt vetenskapligt)
  • 20.
    Escudero-Hernández, Celia
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för molekylär medicin och virologi. Linköpings universitet, Medicinska fakulteten.
    Bernardo, David
    Univ Valladolid, Spain.
    Arranz, Eduardo
    Univ Valladolid, Spain.
    Antonio Garrote, Jose
    Univ Valladolid, Spain; Hosp Univ Rio Hortega, Spain.
    Is celiac disease really associated with inflammatory bowel disease?2020Ingår i: Revista española de enfermedades digestivas, ISSN 1130-0108, E-ISSN 2340-4167, Vol. 112, nr 1, s. 4-6Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    n/a

  • 21.
    Eskilsson, Anna
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Inflammatory Signaling Across the Blood-Brain Barrier and the Generation of Fever2020Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Fever is a cardinal sign of inflammation and is evolutionary conserved. Fever is known to be beneficial during acute inflammation, but over time and if very high it can be detrimental. The signaling pathways by which fever is initiated by the brain and the peripheral mechanisms through which the temperature increase is generated were studied from several point of views. Fever is known to be dependent on prostaglandin E2 (PGE2) binding to its receptors in the median preoptic nucleus of the hypothalamus, which signals to the brainstem and through sympathetic nerves to heat conserving and heat producing effector organs. This thesis focuses on identifying the cells that produce the PGE2 critical for the fever response; showing where in the brain the critical PGE2 production takes place; demonstrating how peripheral inflammation activates these cells to produce PGE2; and finally, identifying the effector mechanisms behind the temperature elevation in fever. By using a newly developed specific antibody we showed that the enzyme responsible for the terminal step in the production of PGE2, microsomal prostaglandin E-synthase 1 (mPGES-1), is expressed in endothelial cells of brain blood vessels in mice where it is co-expressed with the enzyme cyclooxygenase-2 (Cox-2), which is known to be induced in these cells and to be rate limiting for the PGE2 production. The mPGES-1 enzyme was also expressed in several other cell types and structures which however did not express Cox-2, such as capillary-associated pericytes, astroglial cells, leptomeninges, and the choroid plexus. The role of the mPGES-1 in these other cells/structures remains unknown. Next, by using mice with selective deletion of Cox-2 in brain endothelial cells, we showed that local PGE2 production in deep brain areas, such as the hypothalamus, is critical for the febrile response to peripheral inflammation. In contrast, PGE2 production in other brain areas and the overall PGE2 level in the brain were not critical for the febrile response. Partly restoring the PGE2 synthesizing capacity in the anterior hypothalamus of mice lacking such capacity with a lentiviral vector resulted in a temperature elevation in response to an intraperitoneal injection of bacterial wall lipopolysaccharide (LPS). The data show that the febrile response is dependent on the local release of PGE2 onto its target neurons, possibly by a paracrine mechanism. Deletion of the receptor for the pyrogenic cytokine IL-6 on brain endothelial cells, but not on neurons or peripheral nerves, strongly attenuated the febrile response to LPS and reduced the induction of the Cox-2 expression in the hypothalamus. Furthermore, mice deficient of the IL- 6Rα gene in the brain endothelial cells showed a reduced SOCS3 mRNA induction, whereas IκB mRNA-levels were unaffected, suggesting that the IL-6 signaling occurs via STAT3 activation and not signaling through the transcription factor NF-κB. This idea was confirmed by the observation of attenuated fever in mice deficient of STAT3 in brain endothelial cells. These data show that IL-6, when endogenously released during systemic inflammation, is pyrogenic by binding to IL-6R on brain endothelial cells to induce prostaglandin synthesis in these cells. Finally, we demonstrate that mice with genetic deletion of uncoupling protein-1 (UCP-1), hence lacking functional brown adipose tissue, had a normal fever response to LPS, and that LPS caused no activation of brown adipose tissue in wild type mice. However, blocking peripheral cutaneous vasoconstriction resulted in a blunted fever response to LPS, suggesting that heat conservation, possibly together with shivering or non-shivering thermogenesis in the musculature, is responsible for the generation of immune-induced fever, whereas brown adipose tissue thermogenesis is not involved.  

    Delarbeten
    1. Distribution of microsomal prostaglandin E synthase-1 in the mouse brain
    Öppna denna publikation i ny flik eller fönster >>Distribution of microsomal prostaglandin E synthase-1 in the mouse brain
    2014 (Engelska)Ingår i: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 522, nr 14, s. 3229-3244Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Previous studies in rats have demonstrated that microsomal prostaglandin E synthase-1 (mPGES-1) is induced in brain vascular cells that also express inducible cyclooxygenase-2, suggesting that such cells are the source of the increased PGE2 levels that are seen in the brain following peripheral immune stimulation, and that are associated with sickness responses such as fever, anorexia, and stress hormone release. However, while most of what is known about the functional role of mPGES-1 for these centrally evoked symptoms is based on studies on genetically modified mice, the cellular localization of mPGES-1 in the mouse brain has not been thoroughly determined. Here, using a newly developed antibody that specifically recognizes mouse mPGES-1 and dual-labeling for cell-specific markers, we report that mPGES-1 is constitutively expressed in the mouse brain, being present not only in brain endothelial cells, but also in several other cell types and structures, such as capillary-associated pericytes, astroglial cells, leptomeninges, and the choroid plexus. Regional differences were seen with particularly prominent labeling in autonomic relay structures such as the area postrema, the subfornical organ, the paraventricular hypothalamic nucleus, the arcuate nucleus, and the preoptic area. Following immune stimulation, mPGES-1 in brain endothelial cells, but not in other mPGES-1-positive cells, was coexpressed with cyclooxygenase-2, whereas there was no coexpression between mPGES-1 and cyclooxygenase-1. These data imply a widespread synthesis of PGE2 or other mPGES-1-dependent products in the mouse brain that may be related to inflammation-induced sickness symptom as well as other functions, such as blood flow regulation.

    Ort, förlag, år, upplaga, sidor
    John Wiley & Sons, 2014
    Nyckelord
    Astroglial cells; Cyclooxygenase; Endothelial cells; Immune challenge; Pericytes; Prostaglandin synthesis
    Nationell ämneskategori
    Klinisk medicin
    Identifikatorer
    urn:nbn:se:liu:diva-109962 (URN)10.1002/cne.23593 (DOI)000339967300006 ()24668417 (PubMedID)2-s2.0-84904553311 (Scopus ID)
    Tillgänglig från: 2014-09-12 Skapad: 2014-08-29 Senast uppdaterad: 2020-01-08
    2. Immune-Induced Fever Is Dependent on Local But Not Generalized Prostaglandin E-2 Synthesis in the Brain
    Öppna denna publikation i ny flik eller fönster >>Immune-Induced Fever Is Dependent on Local But Not Generalized Prostaglandin E-2 Synthesis in the Brain
    Visa övriga...
    2017 (Engelska)Ingår i: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 37, nr 19, s. 5035-5044Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Fever occurs upon binding of prostaglandin E-2 (PGE(2)) to EP3 receptors in the median preoptic nucleus of the hypothalamus, but the origin of the pyrogenic PGE(2) has not been clearly determined. Here, using mice of both sexes, we examined the role of local versus generalized PGE(2) production in the brain for the febrile response. In wild-type mice and in mice with genetic deletion of the prostaglandin synthesizing enzyme cyclooxygenase-2 in the brain endothelium, generated with an inducible CreER(T2) under the Slco1c1 promoter, PGE(2) levels in the CSF were only weakly related to the magnitude of the febrile response, whereas the PGE(2) synthesizing capacity in the hypothalamus, as reflected in the levels of cyclooxygenase-2 mRNA, showed strong correlation with the immune-induced fever. Histological analysis showed that the deletion of cyclooxygenase-2 in brain endothelial cells occurred preferentially in small-and medium-sized vessels deep in the brain parenchyma, such as in the hypothalamus, whereas larger vessels, and particularly those close to the neocortical surface and in the meninges, were left unaffected, hence leaving PGE(2) synthesis largely intact in major parts of the brain while significantly reducing it in the region critical for the febrile response. Furthermore, injection of a virus vector expressing microsomal prostaglandin E synthase-1 (mPGES-1) into the median preoptic nucleus of fever-refractive mPGES-1 knock-out mice, resulted in a temperature elevation in response to LPS. We conclude that the febrile response is dependent on local release of PGE(2) onto its target neurons and not on the overall PGE(2) production in the brain.

    Ort, förlag, år, upplaga, sidor
    SOC NEUROSCIENCE, 2017
    Nyckelord
    cyclooxygenase-2; endothelial cells; fever; median preoptic nucleus; microsomal prostaglandin E synthase-1; prostaglandin E2
    Nationell ämneskategori
    Neurovetenskaper
    Identifikatorer
    urn:nbn:se:liu:diva-138257 (URN)10.1523/JNEUROSCI.3846-16.2017 (DOI)000401118600015 ()28438967 (PubMedID)
    Anmärkning

    Funding Agencies|Swedish Medical Research Council; Swedish Cancer Foundation; European Research Council; Knut and Alice Wallenberg Foundation; Swedish Brain foundation; County Council of Ostergotland

    Tillgänglig från: 2017-06-13 Skapad: 2017-06-13 Senast uppdaterad: 2020-01-08
    3. Immune-Induced Fever Is Mediated by IL-6 Receptors on Brain Endothelial Cells Coupled to STAT3-Dependent Induction of Brain Endothelial Prostaglandin Synthesis
    Öppna denna publikation i ny flik eller fönster >>Immune-Induced Fever Is Mediated by IL-6 Receptors on Brain Endothelial Cells Coupled to STAT3-Dependent Induction of Brain Endothelial Prostaglandin Synthesis
    Visa övriga...
    2014 (Engelska)Ingår i: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 34, nr 48, s. 15957-15961Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The cytokine IL-6, which is released upon peripheral immune challenge, is critical for the febrile response, but the mechanism by which IL-6 is pyrogenic has remained obscure. Herewegenerated mice with deletion of themembranebound IL-6 receptor alpha (IL-6R alpha) onneural cells, on peripheral nerves, on fine sensory afferent fibers, and on brain endothelial cells, respectively, and examined its role for the febrile response to peripherally injected lipopolysaccharide. We show that IL-6R alpha on neural cells, peripheral nerves, and fine sensory afferents are dispensable for the lipopolysaccharide-induced fever, whereas IL-6R alpha in the brain endothelium plays an important role. Hence deletion of IL-6R alpha on brain endothelial cells strongly attenuated the febrile response, and also led to reduced induction of the prostaglandin synthesizing enzyme Cox-2 in the hypothalamus, the temperature-regulating center in the brain, as well as reduced expression of SOCS3, suggesting involvement of the STAT signaling pathway. Furthermore, deletion of STAT3 in the brain endothelium also resulted in attenuated fever. These data show that IL-6, when endogenously released during systemic inflammation, is pyrogenic by binding to IL-6R alpha on brain endothelial cells to induce prostaglandin synthesis in these cells, probably in concerted action with other peripherally released cytokines.

    Ort, förlag, år, upplaga, sidor
    Society for Neuroscience, 2014
    Nyckelord
    blood-brain barrier; cell-specific gene deletions; fever; interleukin-6; prostaglandins; STAT3
    Nationell ämneskategori
    Klinisk medicin
    Identifikatorer
    urn:nbn:se:liu:diva-113199 (URN)10.1523/JNEUROSCI.3520-14.2014 (DOI)000345923600013 ()25429137 (PubMedID)
    Anmärkning

    Funding Agencies|Swedish Medical Research Council; Swedish Cancer Foundation; European Research Council; Knut and Alice Wallenberg Foundation; Swedish Brain foundation; County CouncilO Ostergotland

    Tillgänglig från: 2015-01-13 Skapad: 2015-01-12 Senast uppdaterad: 2020-01-08
  • 22.
    Falk, Maja
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Nelson, Marie
    Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Blomberg, Marie
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    The impact of obstetric interventions and complications on womens satisfaction with childbirth a population based cohort study including 16,000 women2019Ingår i: BMC PREGNANCY AND CHILDBIRTH, Vol. 19, nr 1, artikel-id 494Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: As a quality marker and a tool for benchmarking between units, a visual analogue scale (VAS) (ranging from 1 to 10) to estimate womans satisfaction with childbirth was introduced in 2014. This study aimed to assess how obstetric interventions and complications affected womens satisfaction with childbirth. Methods: A retrospective cohort study including 16,775 women with an available VAS score who gave birth between January 2016 and December 2017. VAS score, maternal and obstetric characteristics were obtained from electronic medical records and crude and adjusted odds ratios (aOR) were calculated. Results: The total prevalence of dissatisfaction with childbirth (VAS 1-3) was 5.7%. The main risk factors for dissatisfaction with childbirth were emergency cesarean section, aOR 3.98 95% confidence interval (CI) 3.27-4.86, postpartum hemorrhage amp;gt;= 2000 ml, aOR 1.85 95%CI 1.24-2.76 and Apgar score amp;lt; 7 at five minutes, aOR 2.95 95%CI 1.95-4.47. The amount of postpartum hemorrhage showed a dose-response relation to dissatisfaction with childbirth. Moreover, labor induction, instrumental vaginal delivery, and obstetric anal sphincter injury were significantly associated with womens dissatisfaction with childbirth. A total number of 4429/21204 (21%) women giving birth during the study period had missing values on VAS. A comparison of characteristics between women with and without a recorded VAS score was performed. There were statistically significant differences in maternal age and maternal BMI between the study population and excluded women due to missing values on VAS. Moreover, 64% of the women excluded were multiparas, compared to 59% in the study population. Conclusions: Obstetric interventions and complications, including emergency cesareans section and postpartum hemorrhage, were significantly related to dissatisfaction with childbirth. Such events are common and awareness of these associations might lead to a more individualized care of women during and after childbirth.

  • 23.
    Fan, Chuanwen
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Sichuan Univ, Peoples R China; Collaborat Innovat Ctr Biotherapy, Peoples R China.
    Kopsida, Maria
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten.
    Liu, Youbin
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Sichuan Univ, Peoples R China; Collaborat Innovat Ctr Biotherapy, Peoples R China.
    Zhang, Hong
    Orebro Univ, Sweden.
    Gao, Jingfang
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Arbman, Gunnar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken ViN.
    Cao, Si-Yu-Wei
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Li, Yuan
    Sichuan Univ, Peoples R China; Collaborat Innovat Ctr Biotherapy, Peoples R China.
    Zhou, Zong-Guang
    Sichuan Univ, Peoples R China; Collaborat Innovat Ctr Biotherapy, Peoples R China.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Prognostic Heterogeneity of MRE11 Based on the Location of Primary Colorectal Cancer Is Caused by Activation of Different Immune Signals2020Ingår i: Frontiers in Oncology, ISSN 2234-943X, E-ISSN 2234-943X, Vol. 9, artikel-id 1465Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: MRE11 plays an important role in DNA damage response for the maintenance of genome stability, and is becoming a prognostic marker for cancers, including colorectal cancer (CRC). However, the correlations of MRE11 to prognosis and tumor-infiltrating inflammatory cells (TIICs) in different locations of CRC remains unclear. Methods: Among Swedish and TCGA-COREAD patients, we investigated the association of MRE11 expression, tumor-infiltrating inflammatory cells (TIICs) and microsatellite status with survival in right-sided colon cancer (RSCC) and left-sided colon and rectal cancer (LSCRC). The signaling of MRE11-related was further analyzed using weighted gene co-expression network analysis and ClueGO. Results: High MRE11 expression alone or combination of high MRE11 expression with high TIICs was related to favorable prognosis in LSCRC. Moreover, high MRE11 expression was associated with favorable prognosis in LSCRC with microsatellite stability. The relationships above were adjusted for tumor stage, differentiation, and/or TIICs. However, no such evidence was observed in RSCC. Several signaling pathways involving MRE11 were found to be associated with cell cycle and DNA repair in RSCC and LSCRC, whereas, the activation of the immune response and necrotic cell death were specifically correlated with LSCRC. Conclusions: High MRE11 expression is an independent prognostic marker in LSCRC and enhanced prognostic potency of combining high MRE11 with high TIICs in LSCRC, mainly due to differential immune signaling activated by MRE11 in RSCC and LSCRC, respectively.

  • 24.
    Faresjö, Tomas
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för prevention, rehabilitering och nära vård. Linköpings universitet, Medicinska fakulteten.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Wennerholm, Carina
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för omvårdnad och reproduktiv hälsa. Linköpings universitet, Medicinska fakulteten.
    Faresjö, Åshild
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för samhälle och hälsa. Linköpings universitet, Medicinska fakulteten.
    Nilsson, Hans
    Linköpings universitet, Institutionen för kultur och samhälle, Avdelningen för filosofi, historia, konst och religion.
    [Public health differences between »the twin cities« persist].2019Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 116, artikel-id FI6HArtikel i tidskrift (Refereegranskat)
    Abstract [sv]

    A decade ago, major public health differences between two neighboring, equal sized large Swedish cities, Norrköping and Linköping (»the Twin cities«) were revealed. These differences were considerable for cardiovascular mortality and life expectancy. An important finding was that cardiovascular mortality rates for men and women in the city of Norrköping were highest compared to other major Swedish cities. In this follow-up, a decade later, cardiovascular mortality rates are still highest for the Norrköping population in comparison to the largest Swedish cities. There are also still profound and major public health differences between these twin cities. The differences seem to persist over time. These differences could not be explained by differences in health care, but are rather reflecting different social history and socioeconomic and life style differences in these two cities.

  • 25.
    Fohlin, Helena
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för verksamhetsstöd och utveckling, Regionalt Cancercentrum.
    Bekkhus, Tove
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Sandström, Josefine
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten.
    Fornander, Tommy
    Karolinska Inst, Sweden.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Carstensen, John
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Medicinska fakulteten.
    Stål, Olle
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    RAB6C is an independent prognostic factor of estrogen receptor-positive/progesterone receptor-negative breast cancer2020Ingår i: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 19, nr 1, s. 52-60Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The majority of breast cancer tumors are estrogen receptor-positive (ER+) and can be treated with endocrine therapy. However, certain patients may exhibit a good prognosis without systemic treatment. The aim of the present study was to identify novel prognostic factors for patients with ER breast cancer tumors using gene copy data, and to investigate if these factors have prognostic value in subgroups categorized by progesterone receptor status (PR). Public data, including the whole genome gene copy data of 199 systemically untreated patients with ER+ tumors, were utilized in the present study. To assess prognostic value, patients were divided into two groups using the median gene copy number as a cut-off for the SNPs that were the most variable. One SNP was identified, which indicated that the Ras-related protein Rab-6C (RAB6C) gene may exhibit prognostic significance. Therefore, RAB6C protein expression was subsequently investigated in a second independent cohort, consisting of 469 systematically untreated patients (of which 310 were ER+) who received long term follow-up. In the public data set, a distant recurrence risk reduction of 55% was determined for copy numbers above the median value of RAB6C compared with numbers below [multivariable adjusted hazard ratio (HR), 0.45; 95% CI 0.28-0.72; P=0.001)]. It was also more pronounced in the ER+/PR- subgroup (HR, 0.15; 95% CI, 0.05-0.46; P=0.001). In the second cohort, patients of the ER+/PR- subgroup who exhibited high RAB6C expression had a reduced distant recurrence risk (HR, 0.17; 95% CI, 0.05-0.60; P=0.006). However, this was not identified among ER+/PR- tumors (HR, 1.31; 95% CI, 0.69-2.48; P=0.41). The results of the present study indicated that RAB6C serves as an independent prognostic factor of distant recurrence risk in systemically untreated patients with an ER+/PR- tumor.

  • 26.
    Gutefeldt, Kerstin
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Hedman, Christina
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Thyberg, Ingrid
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Bachrack Lindström, Margareta
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten.
    Arnqvist, Hans
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Spångeus, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Low health-related quality of life is strongly linked to upper extremity impairments in type 1 diabetes with a long duration2020Ingår i: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To compare health-related quality of life (HRQOL) in type 1 diabetes and non-diabetic controls and possible links to upper extremity impairments (UEIs). Prevalence of sick-leave and causes were investigated.

    Materials and methods: This Swedish population-based case-control study included type 1 diabetes patients <67 years old and with a diabetes duration ≥20 years. Participants completed a postal questionnaire including Short Form 36, and questions regarding UEIs, and sick-leave.

    Results: In total, 773 patients, aged 50 ± 10 years (diabetes duration 35 ± 10 years), and 708 non-diabetic controls, aged 54 ± 9 years, completed the study. Patients reported significantly lower HRQOL compared with controls. The difference was greatest for general health, vitality, and bodily pain. Patients with shoulder or hand but not finger impairments scored significantly lower than asymptomatic patients. The prevalence of sick leave was higher in patients vs. controls (23% vs. 9%, p < 0.001), and nearly half cited impairments from back, muscles, or joints as the main reason.

    Conclusions: Health-related quality of life is lower in type 1 diabetes than controls and in patients with shoulder and hand impairments than in asymptomatic. Musculoskeletal impairments (back/muscle/joints) have impact on work ability. Identification of UEIs is important for initiating preventative-, therapeutic-, and rehabilitative interventions.

    • Implications for rehabilitation
    • Upper extremity impairments (UEIs) that are common in type 1 diabetes, and associated with reduced health-related quality of life, should preferably be screened for on a regular basis along with other known diabetes complications.

    • Early identification of UEIs is important to improve health by initiating preventive as well as therapeutic multi-professional rehabilitative interventions.

    • Sick leave is higher in type 1 diabetes than in controls. Musculoskeletal impairments, including the back, muscles, and joints, are a common cause for sick leave warranting further studies.

  • 27.
    Henriksson, Pontus
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för samhälle och hälsa. Linköpings universitet, Medicinska fakulteten. Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
    Sandborg, Johanna
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för samhälle och hälsa. Linköpings universitet, Medicinska fakulteten. Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
    Blomberg, Marie
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Alexandrou, Christina
    Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
    Maddison, Ralph
    Institute for Physical Activity and Nutrition, Deakin University, Burwood, Australia.
    Silfvernagel, Kristin
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Psykologi.
    Henriksson, Hanna
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för samhälle och hälsa. Linköpings universitet, Medicinska fakulteten.
    Leppänen, Marja H
    Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden // Faculty of Sport and Health Sciences, University of Jyvaskyla, Jyvaskyla, Finland.
    Migueles, Jairo H
    Department of Physical and Sports Education, Faculty of Sport Sciences, University of Granada, Granada, Spain.
    Widman, Linnea
    Department of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Thomas, Kristin
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för samhälle och hälsa. Linköpings universitet, Medicinska fakulteten.
    Trolle Lagerros, Ylva
    Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Solna, Sweden // Obesity Center, Academic Specialist Center, Stockholm Health Services, Stockholm, Sweden.
    Löf, Marie
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för samhälle och hälsa. Linköpings universitet, Medicinska fakulteten.
    A Smartphone App to Promote Healthy Weight Gain, Diet, and Physical Activity During Pregnancy (HealthyMoms): Protocol for a Randomized Controlled Trial.2019Ingår i: JMIR Research Protocols, ISSN 1929-0748, E-ISSN 1929-0748, Vol. 8, nr 3, artikel-id e13011Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Excessive gestational weight gain is common and associated with adverse outcomes both in the short and long term. Although traditional lifestyle-based interventions have shown to mitigate excess gestational weight gain, little is known about whether mobile Health (mHealth) apps can promote healthy weight gain, diet, and physical activity during pregnancy.

    OBJECTIVE: The primary aim of the HealthyMoms trial is to determine the effectiveness of a smartphone app (HealthyMoms) for mitigating excess gestational weight gain during pregnancy. Secondary aims are to determine the effectiveness of the app on dietary habits, physical activity, body fatness, and glycemia during pregnancy.

    METHODS: HealthyMoms is a two-arm randomized controlled trial. Women are being recruited at routine visits at the maternity clinics in Linköping, Norrköping and Motala, Sweden. Women are randomized to the control or intervention group (n=150 per group). All women will receive standard care, and women in the intervention group will also receive the HealthyMoms smartphone app.

    RESULTS: Recruitment of participants to the trial was initiated in October 2017, and 190 women have so far completed the baseline measurement. The baseline measures are estimated to be finalized in December 2019, and the follow-up measures are estimated to be completed in June 2020.

    CONCLUSIONS: This project will evaluate a novel smartphone app intervention integrated with existing maternity health care. If successful, it has great potential to be implemented nationally in order to promote healthy weight gain and health behaviors during pregnancy.

    INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13011.

  • 28.
    Hindocha, Nishma
    et al.
    Zealand Univ Hosp, Denmark.
    Manhem, Filip
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Folktandvården.
    Bäckryd, Emmanuel
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för prevention, rehabilitering och nära vård. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Smärt och rehabiliteringscentrum.
    Bågesund, Mats
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Ice versus lidocaine 5% gel for topical anaesthesia of oral mucosa - a randomized cross-over study2019Ingår i: BMC Anesthesiology, ISSN 1471-2253, E-ISSN 1471-2253, Vol. 19, nr 1, artikel-id 227Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Topical anaesthesia is important to optimize pain control during dental injection. Our aim was to describe a new simple method for topical anaesthesia of oral mucosa and to compare the effectiveness of ice and lidocaine 5% gel for topical anaesthesia of oral mucosa. Methods: A total of 40 patients aged 10.7-19.5 years were included. The side and method of application were both randomized. Heart rate was recorded, and discomfort and pain were evaluated with a visual analogue scale (VAS). A paired t-test was used to compare mean values, a chi(2) test was used to compare proportions, and a Pearson correlation test was used to examine correlations between variables. Results: When ice was used, buccal injection VAS pain was rated lower (p = 0.044), and VAS discomfort was rated higher (p = 0.001), in comparison to when lidocaine 5% gel was used. There was no significant difference in relative heart rate change between ice and lidocaine 5% gel at either needle stick or injection. Lidocaine 5% gel produced a relative heart rate reduction after palatal injection (0.99 +/- 0.06) while buccal injection produced an increased relative heart rate (1.02 +/- 0.08) (p = 0.010). Unpleasant taste was more frequently reported when lidocaine 5% gel was used (p = 0.025). An application time of 1 min was sufficient for both ice and lidocaine 5% gel to achieve pain reduction from needle stick in buccal mucosa. Conclusion: The cheap and readily available described method using ice for topical anaesthesia of oral mucosa before dental injection is an effective alternative to lidocaine 5% gel.

  • 29.
    Huoman, Johanna
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten.
    Papapavlou, Georgia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten.
    Pap, Anna
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten.
    Alm, Johan
    Karolinska Institutet, Department of Clinical Science and Education, Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden.
    Nilsson, Lennart J
    Region Östergötland, Hjärt- och Medicincentrum, Allergicentrum US. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Jenmalm, Maria C
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten.
    Sublingual immunotherapy alters salivary IgA and systemic immune mediators in timothy allergic children.2019Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 30, nr 5, s. 522-530Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Immunomodulatory effects of sublingual immunotherapy on systemic and mucosal mediators in allergic children are largely unexplored. The aim of this study was to investigate allergy-related cytokine and chemokine levels, as well as IgA-responses upon a 3-year treatment with timothy grass pollen sublingual immunotherapy in children with allergic rhinoconjunctivitis.

    METHODS: From children included in the GRAZAX® Asthma Prevention study, blood and saliva samples were analyzed at inclusion, after 3 years of treatment, and 2 years after treatment ending. By means of Luminex and ELISA methodologies, allergy-related cytokines and chemokines were measured in plasma samples and allergen-stimulated peripheral blood mononuclear cell supernatants. Furthermore, studies of total, secretory, and Phl p 1-specific salivary IgA antibodies were performed using the same methods.

    RESULTS: GRAZAX® -treated children exhibited significantly higher levels of Phl p 1-specific salivary IgA and serum IgG4 , along with significantly lower skin prick test positivity, after 3 years of treatment and 2 years after treatment cessation. Additionally, plasma levels of the Th1-associated chemokines CXCL10 and CXCL11 were significantly higher in treated than untreated children at these time points. Timothy-induced ratios of IL-5/IL-13 over IFN-γ were significantly decreased after 3 years with active treatment, as were symptoms of allergic rhinitis in terms of both severity and visual analogue scale scores. However, no consistent correlations were found between the clinical outcomes and immunologic parameters.

    CONCLUSION: Phleum pratense sublingual immunotherapy in grass pollen allergic children modulates the immune response in the oral mucosa as well as systemically-by increasing Th1-responses, decreasing Th2-responses, and inducing immunoregulatory responses-all signs of tolerance induction.

  • 30.
    Håkansson, Irene
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken i Linköping.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken i Linköping.
    Dahle, Charlotte
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Ekdahl, Kristina N.
    Centre of Biomaterials Chemistry, Linnaeus University, Kalmar, Sweden ; Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
    Complement activation in cerebrospinal fluid in clinically isolated syndrome and early stages of relapsing remitting multiple sclerosis2020Ingår i: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 340, artikel-id 577147Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To assess if markers of complement activation are associated with disease activity, C1q, C3, C3a and sC5b-9 levels in plasma and cerebrospinal fluid (CSF) were determined in 41 patients with clinically isolated syndrome (CIS) or remitting multiple sclerosis (RRMS), in a prospective longitudinal four-year cohort study. C1q in CSF (CSF-C1q) was significantly higher in patients than in controls. Baseline CSF-C1q and CSF-C3a correlated with several neuroinflammatory markers and neurofilament light chain levels. Baseline CSF-C3a correlated with the number of T2 lesions at baseline and new T2 lesions during follow-up. Baseline CSF-C3a was also significantly higher in patients with (n = 21) than in patients without (n = 20) signs of disease activity according to the NEDA-3 concept during one year of follow-up (p ≀ .01) Study results support that complement activation is involved in MS pathophysiology and that CSF-C3a carries prognostic information.

  • 31.
    Jakobsen, Lasse H.
    et al.
    Aalborg Univ Hosp, Denmark; Aalborg Univ, Denmark.
    Ellin, Fredrik
    Lund Univ, Sweden.
    Smeland, Knut B.
    Oslo Univ Hosp, Norway.
    Wasterlid, Tove
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Christensen, Jacob H.
    Odense Univ Hosp, Denmark.
    Jorgensen, Judit M.
    Aarhus Univ Hosp, Denmark.
    Josefsson, Par L.
    Herlev Hosp, Denmark.
    Ovlisen, Andreas K.
    Aalborg Univ Hosp, Denmark; Aalborg Univ, Denmark.
    Holte, Harald
    Oslo Univ Hosp, Norway; Oslo Univ Hosp, Norway.
    Blaker, Yngvild N.
    Oslo Univ Hosp, Norway; Oslo Univ Hosp, Norway.
    Grauslund, Jacob H.
    Roskilde Sygehus, Denmark.
    Bjorn, Jon
    Rigshosp, Denmark.
    Molin, Daniel
    Uppsala Univ, Sweden.
    Lagerlof, Ingemar
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Smedby, Karin E.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Colvin, Katherine
    Sir Charles Gairdner Hosp, Australia.
    Thanarajasingam, Gita
    Mayo Clin, MN USA.
    Maurer, Matthew J.
    Mayo Clin, MN USA.
    Habermann, Thomas M.
    Mayo Clin, MN USA.
    Song, Kevin W.
    BC Canc, Canada.
    Zhu, Katie Y.
    BC Canc, Canada.
    Gerrie, Alina S.
    BC Canc, Canada.
    Cheah, Chan Y.
    Sir Charles Gairdner Hosp, Australia; Pathwest Lab Med WA, Australia; Univ Western Australia, Australia.
    El-Galaly, Tarec C.
    Aalborg Univ Hosp, Denmark; Aalborg Univ, Denmark.
    Minimal relapse risk and early normalization of survival for patients with Burkitt lymphoma treated with intensive immunochemotherapy: an international study of 264 real-world patients2020Ingår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Non-endemic Burkitt lymphoma (BL) is a rare germinal centre B-cell-derived malignancy with the genetic hallmark of MYC gene translocation and with rapid tumour growth as a distinct clinical feature. To investigate treatment outcomes, loss of lifetime and relapse risk in adult BL patients treated with intensive immunochemotherapy, retrospective clinic-based and population-based lymphoma registries from six countries were used to identify 264 real-world patients. The median age was 47 years and the majority had advanced-stage disease and elevated LDH. Treatment protocols were R-CODOX-M/IVAC (47%), R-hyper-CVAD (16%), DA-EPOCH-R (11%), R-BFM/GMALL (25%) and other (2%) leading to an overall response rate of 89%. The two-year overall survival and event-free survival were 84% and 80% respectively. For patients in complete remission/unconfirmed, the two-year relapse risk was 6% but diminished to 0 center dot 6% for patients reaching 12 months of post-remission event-free survival (pEFS12). The loss of lifetime for pEFS12 patients was 0 center dot 4 (95% CI: -0 center dot 7 to 2) months. In conclusion, real-world outcomes of adult BL are excellent following intensive immunochemotherapy. For pEFS12 patients, the relapse risk was low and life expectancy similar to that of a general population, which is important information for developing meaningful follow-up strategies with increased focus on survivorship and less focus on routine disease surveillance.

  • 32.
    Jerlstrom, Tomas
    et al.
    Orebro Univ, Sweden.
    Chen, Ruoqing
    Orebro Univ, Sweden; Karolinska Inst, Sweden.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Andren, Ove
    Orebro Univ, Sweden.
    Strock, Viveka
    Sahlgrens Univ Hosp, Sweden; Sahlgrens Acad, Sweden.
    Aljabery, Firas A. S.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Hosseini, Abolfazl
    Karolinska Inst, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Malmstrom, Per-Uno
    Inst Surg Sci, Sweden.
    Ullen, Anders
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Gardmark, Truls
    Danderyd Hosp, Sweden.
    Fall, Katja
    Orebro Univ, Sweden; Karolinska Inst, Sweden.
    No increased risk of short-term complications after radical cystectomy for muscle-invasive bladder cancer among patients treated with preoperative chemotherapy: a nation-wide register-based study2020Ingår i: World journal of urology, ISSN 0724-4983, E-ISSN 1433-8726, Vol. 38, nr 2, s. 381-388Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose Preoperative chemotherapy is underused in conjunction with radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) due to concerns for complications and delay of surgery. Prospective data on short-term complications from population-based settings with frequent use of preoperative chemotherapy and standardised reporting of complications is lacking. Methods We identified 1,340 patients who underwent RC between 2011 and 2015 in Sweden due to MIBC according to the Swedish Cystectomy Register. These individuals were followed through linkages to several national registers. Propensity score adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for complications and death within 90 days of surgery, comparing patients receiving preoperative chemotherapy or not. Results Minimum two cycles of preoperative chemotherapy were given to 519 (39%) of the patients, who on average tended to be younger, have higher education, better physical status, and more advanced bladder cancer than patients not receiving chemotherapy. After adjusting for these and other parameters, there was no association between treatment with preoperative chemotherapy and short-term complications (OR 1.06 95% CI 0.82-1.39) or mortality (OR 0.75 95% CI 0.36-1.55). We observed a risk reduction for gastrointestinal complications among patients who received preoperative chemotherapy compared with those who did not (OR 0.49 95% CI 0.30-0.81). Conclusion This nation-wide population-based observational study does not suggest that preoperative chemotherapy, in a setting with high utilisation of such treatment, is associated with an increased risk of short-term complications in MIBC patients treated with radical cystectomy.

  • 33.
    Kallner, Anders
    et al.
    Karolinska Univ Hosp, Sweden.
    Petersmann, Astrid
    Univ Med, Germany; Univ Med, Germany.
    Nauck, Matthias
    Univ Med, Germany.
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Measurement repeatability profiles of eight frequently requested measurands in clinical chemistry determined by duplicate measurements of patient samples2020Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Measurement uncertainties in clinical chemistry are commonly regarded as heteroscedastic - having a constant relative standard deviation irrespective of the concentration of the measurand. The uncertainty is usually determined at two concentrations using stabilized control materials and assumed to represent the analytical goal. The purpose of the present study was to use duplicates of unselected patient samples to calculate the absolute and relative repeatability component of the intra-laboratory measurement uncertainty from duplicates, using the Dahlberg formula and analysis of variance components. Estimates were made at five different concentration intervals of ALT, AST, Calcium, Cholesterol, Creatinine, CRP, Triglycerides and TSH covering the entire concentration interval of the patient cohort. This partioning allows detailing their repeatability profiles. The calculations of the profiles were based on randomly selected results from sets of duplicates ranging from 12,000 to 65,000 pairs. The repeatability of the measurands showed substantial variability within the measuring interval. Therefore, characterizing imprecision profiles as purely homo- or heteroscedastic or by a single number may not be optimal for the intended use. The present data make a case for nuancing the evaluation of analytical goals and minimal differences of measurement results by establishing uncertainty profiles under repeatability conditions, using natural patient samples.

  • 34.
    Kallner, Anders
    et al.
    Karolinska Univ Hosp, Sweden.
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Repeatability imprecision from analysis of duplicates of patient samples and control materials2020Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Measurement imprecision is usually calculated from measurement results of the same stabilized control material(s) obtained over time, and is therefore, principally, only valid at the concentration(s) of the selected control material(s). The resulting uncertainty has been obtained under reproducibility conditions and corresponds to the conventional analytical goals. Furthermore, the commutability of the control materials used determines whether the imprecision calculated from the control materials reflects the imprecision of measuring patient samples. Imprecision estimated by measurements of patient samples uses fully commutable samples, freely available in the laboratories. It is commonly performed by calculating the results of routine patient samples measured twice each. Since the duplicates are usually analysed throughout the entire concentration interval of the patient samples processed in the laboratory, the result will be a weighted average of the repeatability imprecision measured in the chosen measurement intervals or throughout the entire interval of concentrations encountered in patient care. In contrast, the uncertainty derived from many measurements of control materials over periods of weeks is usually made under reproducibility conditions. Consequently, the repeatability and reproducibility imprecision play different roles in the inference of results in clinical medicine. The purpose of the present review is to detail the properties of the imprecision calculated by duplicates of natural samples, to explain how it differs from imprecision calculated from single concentrations of control materials, and to elucidate what precautions need to be taken in case of bias, e.g. due to carry-over effects.

  • 35.
    Korsgren, Olle
    et al.
    Uppsala University, Uppsala, Sweden.
    Skog, Oskar
    Uppsala University, Uppsala, Sweden.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Teplizumab in Relatives at Risk for Type 1 Diabetes.2019Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 381, nr 19, s. 1879-1880, artikel-id 10.1056/NEJMc1912500#sa3Artikel i tidskrift (Refereegranskat)
  • 36.
    Lagali, Neil
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för logopedi, otorhinolaryngologi och audiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM. Sorlandet Hosp Arendal, Norway.
    Wowra, Bogumil
    Med Univ Silesia, Poland.
    Fries, Fabian Norbert
    UKS, Germany.
    Latta, Lorenz
    UKS, Germany.
    Moslemani, Kayed
    UKS, Germany.
    Utheim, Tor Paaske
    Sorlandet Hosp Arendal, Norway; Oslo Univ Hosp, Norway.
    Wylegala, Edward
    Med Univ Silesia, Poland.
    Seitz, Berthold
    UKS, Germany.
    Kasmann-Kellner, Barbara
    UKS, Germany.
    PAX6 Mutational Status Determines Aniridia-Associated Keratopathy Phenotype2020Ingår i: Ophthalmology (Rochester, Minn.), ISSN 0161-6420, E-ISSN 1549-4713, Vol. 127, nr 2, s. 273-275Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    n/a

  • 37.
    Lee, Mary R.
    et al.
    NIAAA, MD 20892 USA; NIDA, MD 20892 USA.
    Tapocik, Jenica D.
    NIDA, MD 20892 USA.
    Ghareeb, Mwlod
    Univ Rhode Isl, RI 02881 USA.
    Schwandt, Melanie L.
    NIAAA, MD USA.
    Dias, Alexandra A.
    NIAAA, MD 20892 USA; NIDA, MD 20892 USA.
    Le, April N.
    NIAAA, MD 20892 USA; NIDA, MD 20892 USA.
    Cobbina, Enoch
    Univ Rhode Isl, RI 02881 USA.
    Farinelli, Lisa A.
    NIAAA, MD 20892 USA; NIDA, MD 20892 USA.
    Bouhlal, Sofia
    NIAAA, MD 20892 USA; NIDA, MD 20892 USA.
    Farokhnia, Mehdi
    NIAAA, MD 20892 USA; NIDA, MD 20892 USA.
    Heilig, Markus
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Psykiatriska kliniken inkl beroendekliniken. NIDA, MD 20892 USA.
    Akhlaghi, Fatemeh
    Univ Rhode Isl, RI 02881 USA.
    Leggio, Lorenzo
    NIAAA, MD 20892 USA; NIDA, MD 20892 USA; Brown Univ, RI 02912 USA.
    The novel ghrelin receptor inverse agonist PF-5190457 administered with alcohol: preclinical safety experiments and a phase 1b human laboratory study2020Ingår i: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 25, nr 2, s. 461-475Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Rodent studies indicate that ghrelin receptor blockade reduces alcohol consumption. However, no ghrelin receptor blockers have been administered to heavy alcohol drinking individuals. Therefore, we evaluated the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and behavioral effects of a novel ghrelin receptor inverse agonist, PF-5190457, when co-administered with alcohol. We tested the effects of PF-5190457 combined with alcohol on locomotor activity, loss-of-righting reflex (a measure of alcohol sedative actions), and on blood PF-5190457 concentrations in rats. Then, we performed a single-blind, placebo-controlled, within-subject human study with PF-5190457 (placebo/0 mg b.i.d., 50 mg b.i.d., 100 mg b.i.d.). Twelve heavy drinkers during three identical visits completed an alcohol administration session, subjective assessments, and an alcohol cue-reactivity procedure, and gave blood samples for PK/PD testing. In rats, PF-5190457 did not interact with the effects of alcohol on locomotor activity or loss-of-righting reflex. Alcohol did not affect blood PF-5190457 concentrations. In humans, all adverse events were mild or moderate and did not require discontinuation or dose reductions. Drug dose did not alter alcohol concentration or elimination, alcohol-induced stimulation or sedation, or mood during alcohol administration. Potential PD markers of PF-5190457 were acyl-to-total ghrelin ratio and insulin-like growth factor-1. PF-5190457 (100 mg b.i.d.) reduced alcohol craving during the cue-reactivity procedure. This study provides the first translational evidence of safety and tolerability of the ghrelin receptor inverse agonist PF-5190457 when co-administered with alcohol. PK/PD/behavioral findings support continued research of PF-5190457 as a potential pharmacological agent to treat alcohol use disorder.

  • 38.
    Li, Jun
    et al.
    Univ Med Ctr Hamburg Eppendorf, Germany.
    Moustafa, Mohamed
    Univ Padua, Italy.
    Linecker, Michael
    Univ Hosp Zurich, Switzerland.
    Lurje, Georg
    Univ Hosp RWTH Aachen, Germany.
    Capobianco, Ivan
    Univ Hosp Tuebingen, Germany.
    Baumgart, Janine
    Univ Hosp Mainz, Germany.
    Ratti, Francesca
    Osped San Raffaele, Italy.
    Rauchfuss, Falk
    Univ Hosp Jena, Germany.
    Balci, Deniz
    Ankara Univ, Turkey.
    Fernandes, Eduardo
    Univ Fed Rio de Janeiro, Brazil; Sao Lucas Hosp Copacabana, Brazil.
    Montalti, Roberto
    Federico II Univ Hosp, Italy.
    Robles-Campos, Ricardo
    Virgen Arrixaca Hosp, Spain.
    Björnsson, Bergthor
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Topp, Stefan A.
    Univ Hosp Dusseldorf, Germany.
    Fronek, Jiri
    Inst Clin and Expt Med, Czech Republic; Charles Univ Prague, Czech Republic.
    Liu, Chao
    Sun Yat Sen Univ, Peoples R China.
    Wahba, Roger
    Univ Hosp Cologne, Germany.
    Bruns, Christiane
    Univ Hosp Cologne, Germany.
    Brunner, Stefan M.
    Univ Med Ctr Regensburg, Germany.
    Schlitt, Hans J.
    Univ Med Ctr Regensburg, Germany.
    Heumann, Asmus
    Univ Med Ctr Hamburg Eppendorf, Germany.
    Stueben, Bjoern-Ole
    Univ Med Ctr Hamburg Eppendorf, Germany.
    Izbicki, Jakob R.
    Univ Med Ctr Hamburg Eppendorf, Germany.
    Bednarsch, Jan
    Univ Hosp RWTH Aachen, Germany.
    Gringeri, Enrico
    Univ Padua, Italy.
    Fasolo, Elisa
    Univ Padua, Italy.
    Rolinger, Jens
    Univ Hosp Tuebingen, Germany.
    Kristek, Jakub
    Inst Clin and Expt Med, Czech Republic; Charles Univ Prague, Czech Republic.
    Hernandez-Alejandro, Roberto
    Univ Rochester, NY USA.
    Schnitzbauer, Andreas
    Univ Hosp Frankfurt, Germany.
    Nuessler, Natascha
    Munchen Klin Neuperlach, Germany.
    Schoen, Michael R.
    Klinikum Karlsruhe, Germany.
    Voskanyan, Sergey
    AI Burnazyan Russian State Sci Ctr FMBC FMBA, Russia.
    Petrou, Athanasios S.
    Nicosia Teaching Hosp, Cyprus.
    Hahn, Oszkar
    Semmelweis Univ, Hungary.
    Soejima, Yuji
    Shinshu Univ, Japan.
    Vicente, Emilio
    San Pablo Univ CEU, Spain.
    Castro-Benitez, Carlos
    Univ Paris Saclay, France.
    Adam, Rene
    Univ Paris Saclay, France.
    Tomassini, Federico
    Univ Ghent, Belgium.
    Troisi, Roberto Ivan
    Univ Ghent, Belgium; Univ Naples Federico II, Italy.
    Kantas, Alexandros
    Semmelweis Univ Budapest, Germany.
    Oldhafer, Karl Juergen
    Semmelweis Univ Budapest, Germany.
    Ardiles, Victoria
    Italian Hosp Buenos Aires, Argentina.
    de Santibanes, Eduardo
    Italian Hosp Buenos Aires, Argentina.
    Malago, Massimo
    UCL, England.
    Clavien, Pierre-Alain
    Univ Hosp Zurich, Switzerland.
    Vivarelli, Marco
    Polytech Univ Marche, Italy.
    Settmacher, Utz
    Univ Hosp Jena, Germany.
    Aldrighetti, Luca
    Osped San Raffaele, Italy.
    Neumann, Ulf
    Univ Hosp RWTH Aachen, Germany.
    Petrowsky, Henrik
    Univ Hosp Zurich, Switzerland.
    Cillo, Umberto
    Univ Padua, Italy.
    Lang, Hauke
    Univ Hosp Mainz, Germany.
    Nadalin, Silvio
    Univ Hosp Tuebingen, Germany.
    ALPPS for Locally Advanced Intrahepatic Cholangiocarcinoma: Did Aggressive Surgery Lead to the Oncological Benefit? An International Multi-center Study2020Ingår i: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background ALPPS is found to increase the resectability of primary and secondary liver malignancy at the advanced stage. The aim of the study was to verify the surgical and oncological outcome of ALPPS for intrahepatic cholangiocarcinoma (ICC). Methods The study cohort was based on the ALPPS registry with patients from 31 international centers between August 2009 and January 2018. Propensity score matched patients receiving chemotherapy only were selected from the SEER database as controls for the survival analysis. Results One hundred and two patients undergoing ALPPS were recruited, 99 completed the second stage with median inter-stage duration of 11 days. The median kinetic growth rate was 23 ml/day. R0 resection was achieved in 87 (85%). Initially high rates of morbidity and mortality decreased steadily to a 29% severe complication rate and 7% 90-day morbidity in the last 2 years. Post-hepatectomy liver failure remained the main cause of 90-day mortality. Multivariate analysis revealed insufficient future liver remnant at the stage-2 operation (FLR2) to be the only risk factor for severe complications (OR 2.91, p = 0.02). The propensity score matching analysis showed a superior overall survival in the ALPPS group compared to palliative chemotherapy (median overall survival: 26.4 months vs 14 months; 1-, 2-, and 3-year survival rates: 82.4%, 70.5% and 39.6% vs 51.2%, 21.4% and 11.3%, respectively, p amp;lt; 0.01). The survival benefit, however, was not confirmed in the subgroup analysis for patients with insufficient FLR2 or multifocal ICC. Conclusion ALPPS showed high efficacy in achieving R0 resections in locally advanced ICC. To get the most oncological benefit from this aggressive surgery, ALPPS would be restricted to patients with single lesions and sufficient FLR2.

  • 39.
    Lin, Chung-Ying
    et al.
    Hong Kong Polytech Univ, Peoples R China.
    Cheng, Andy S. K.
    Hong Kong Polytech Univ, Peoples R China.
    Nejati, Babak
    Tabriz Univ Med Sci, Iran.
    Imani, Vida
    Tabriz Univ Med Sci, Iran.
    Ulander, Martin
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurofysiologiska kliniken US.
    Browall, Maria
    Jonkoping Univ, Sweden.
    Griffiths, Mark D.
    Nottingham Trent Univ, England.
    Broström, Anders
    Region Östergötland, Sinnescentrum, Neurofysiologiska kliniken US. Jonkoping Univ, Sweden.
    Pakpour, Amir H.
    Jonkoping Univ, Sweden; Qazvin Univ Med Sci, Iran.
    A thorough psychometric comparison between Athens Insomnia Scale and Insomnia Severity Index among patients with advanced cancer2020Ingår i: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 29, nr 1, artikel-id e12891Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    For patients with cancer, sleep disturbance is commonplace. Using classical test theory and Rasch analyses, the present study compared two commonly used psychometric instruments for insomnia - Athens Insomnia Scale and Insomnia Severity Index - among patients with advanced cancer. Through convenience sampling, patients with cancer at stage III or IV (n = 573; 326 males; mean age = 61.3 years; SD = 10.7) from eight oncology units of university hospitals in Iran participated in the study. All the participants completed the Athens Insomnia Scale, Insomnia Severity Index, Edmonton Symptom Assessment Scale, Hospital Anxiety and Depression Scale, General Health Questionnaire-12, Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index. Additionally, 433 participants wore an Actigraph device for two continuous weekdays. Classical test theory and Rasch analysis both supported the construct validity for Athens Insomnia Scale (factor loadings from confirmatory factor analysis = 0.61-0.87; test-retest reliability = 0.72-0.82; infit mean square = 0.81-1.17; outfit MnSq = 0.79-1.14) and for Insomnia Severity Index (factor loadings from confirmatory factor analysis = 0.61-0.81; test-retest reliability = 0.72-0.82; infit mean square = 0.72-1.14; outfit mean square = 0.76-1.11). Both Athens Insomnia Scale and Insomnia Severity Index had significant associations with Edmonton Symptom Assessment Scale, Hospital Anxiety and Depression Scale, General Health Questionnaire-12, Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index, as well as having good sensitivity and specificity. Significant differences in the actigraphy measure were found between insomniacs and non-insomniacs based on Athens Insomnia Scale or Insomnia Severity Index score. With promising results, healthcare providers can use either Athens Insomnia Scale or Insomnia Severity Index to understand the insomnia of patients with advanced cancer.

  • 40.
    Lindberg, Oscar
    et al.
    Region Östergötland, Sinnescentrum, Anestesi- och intensivvårdskliniken US (ANOPIVA).
    de Geer, Lina
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Chew, Michelle
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Anestesi- och intensivvårdskliniken US (ANOPIVA).
    Nonadherence to antibiotic guidelines in patients admitted to ICU with sepsis is associated with increased mortality A registry-based, retrospective cohort study2020Ingår i: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 37, nr 2, s. 113-120Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND Early appropriate antibiotic therapy is an important component of the Surviving Sepsis Guidelines bundles that are associated with decreased in-hospital mortality. National antibiotic guidelines for the treatment of sepsis in Sweden have been available since 2008. Compliance with these guidelines is largely unknown, and whether it translates to improved patient outcome has not been studied. OBJECTIVE To assess mortality and its relationship to compliance with Swedish antibiotic guidelines. A secondary aim was to assess the effect of timing of antibiotic administration and mortality. DESIGN A registry-based, retrospective cohort study. Registry data were supplemented by manual extraction of data on antibiotic treatment from patient charts. The association between guideline compliance and mortality was evaluated using multivariable analysis. Three levels of compliance were predefined: full compliance - correct antibiotics and dose; partial compliance - correct antibiotic but wrong dose and/or wrong initial antibiotic but corrected within 24 h and/or wrong combination in a combined regime that is at least one antibiotic not in line with the national antibiotic guideline; no compliance - incorrect antibiotic. SETTING Two general ICUs in Sweden between 1 January 2011 and 31 December 2015. PATIENTS Seven hundred and thirteen patients over the age of 18 with severe sepsis or septic shock identified through the Swedish ICU Registry. MAIN OUTCOME MEASURES The primary outcome was 30-day mortality. RESULTS Full compliance was observed in 47.0% of patients, partial compliance in 36.0%, and no compliance in 17.0%. Lack of compliance was independently associated with increased risk of 30-day mortality: the adjusted hazard ratio was 1.86 (95% CI 1.34 to 2.58 P amp;lt; 0.001) for partial compliance and 2.18 (95% CI 1.34 to 3.40 P amp;lt; 0.001) for no compliance. The time to first antibiotic administration was not associated with mortality. CONCLUSION Less than half of the patients with severe sepsis and septic shock received antibiotics according to Swedish national guidelines. Full compliance with the guidelines was associated with decreased mortality. The results of this study show that a strict approach to guideline compliance seems to be beneficial: half measures and inadequate doses should be avoided.

  • 41.
    Ludvigsson, Johnny
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Andersson-White, P
    Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Guerrero-Bosagna, C
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi.
    Toxic metals in cord blood and later development of Type 1 diabetes.2019Ingår i: Pediatric dimensions, ISSN 2397-950X, Vol. 4, nr 2Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The incidence of type 1 diabetes (T1D) has increased explained by changes in environment or lifestyle. In modern society dissemination of heavy metals has increased. As the autoimmune process usually starts already, we hypothesized that exposure to toxic metals during fetal life might contribute to development of T1D in children. We analysed arsenic (AS), aluminium (Al), cadmium (Cd), lithium (Li), mercury (Hg), lead (Pb), in cord blood of 20 children who later developed T1D (probands), and in 40 age-and sex-matched controls. Analysis of heavy metals in cord blood was performed by ALS Scandinavia AB (Luleå, Sweden) using the 'ultrasensitive inductively coupled plasma sector field mass spectrometry method' (ICP-SFMS) after acid digestion with HNO3. Most children had no increased concentrations of the metals in cord blood. However, children who later developed T1D had more often increased concentrations (above limit of detection; LOD) of aluminium (p = 0.006) in cord blood than the non-diabetic controls, and also more often mercury and arsenic (n.s). Our conclusion is that exposure to toxic metals during pregnancy might be one among several contributing environmental factors to the disease process if confirmed in other birth cohort trials.

  • 42.
    Lund Hansen, Stine
    et al.
    Univ Copenhagen, Denmark.
    Johansen, Sys Stybe
    Univ Copenhagen, Denmark.
    Nielsen, Marie Katrine Klose
    Univ Copenhagen, Denmark.
    Nilsson, Gunnel
    Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Kronstrand, Robert
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Distribution of zopiclone and main metabolites in hair following a single dose2020Ingår i: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 306, artikel-id 110074Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In forensic investigations, such as drug-facilitated crimes, reference values are useful for interpretation of hair results. The aim of this study was to establish levels of zopiclone and two main metabolites, N-desmethylzopiclone and zopiclone N-oxide, in hair after the administration of a single dose of zopiclone, as very limited data are published. A controlled study was performed, where 16 volunteers consumed either 5 or 10 mg zopiclone. Hair was sampled prior to consumption and 14, 30, 60, and 120 days after intake. The deposition of drug in hair segments of all sampling time points was followed in small hair segments of 5-mm, using a validated ultra-high performance liquid chromatography-tandem mass spectrometry method. In all participants, hair segments corresponding to the time of intake were positive for zopiclone, but also with lower concentrations in the neighbouring segments. The highest zopiclone concentrations were detected in samples collected 30 or 60 days after intake. For all sampling time points maximum values for the 5-mg dose ranged from 5.0-370 pg/mg for zopiclone and 5.4 to 300 pg/mg for N-desmethylzopiclone, where the maximum values for the 10-mg dose ranged from 17 to 590 pg/mg for zopiclone and 25-410 pg/mg for N-desmethylzopiclone for all sampling time points. No significant difference in concentrations was found between the two dosing groups for either zopiclone or N-desmethylzopiclone. Almost half of the participants showed lower levels 14 days after intake than in the later sampling time points. The metabolite to parent drug ratio of N-desmethylzopiclone to zopiclone varied from 0.6 to 3.4 (median = 1.2) for the maximum levels of all sampling time points. N-desmethylzopiclone are suggested to serve as an additional marker to confirm the intake of zopiclone. Traces of zopiclone N-oxide were detected in hair from only eight participants. This study showed, that it was possible to follow zopiclone and N-desmethylzopiclone in hair for 4 months even though the drugs was divided into several segments in the latest collected hair samples, and no obvious wash-out effect between the sampling time points by e.g. personal hygiene could be discerned because the cumulated amount at each sampling time point was similar. We conclude that the analysis of short segments e.g. segments of 5-mm can help determine the time of a single intake of zopiclone and that obtaining a sample 1-2 months after a drug exposure provide the best conditions to detect and interpret the results. (C) 2019 Elsevier B.V. All rights reserved.

  • 43.
    MacRitchie, Jennifer
    et al.
    Western Sydney Univ, Australia.
    Breaden, Matthew
    Western Sydney Univ, Australia.
    Milne, Andrew J.
    Western Sydney Univ, Australia.
    Mcintyre, Sarah
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten. Western Sydney Univ, Australia.
    Cognitive, Motor and Social Factors of Music Instrument Training Programs for Older Adults Improved Wellbeing2020Ingår i: Frontiers in Psychology, ISSN 1664-1078, E-ISSN 1664-1078, Vol. 10, artikel-id 2868Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Given emerging evidence that learning to play a musical instrument may lead to a number of cognitive benefits for older adults, it is important to clarify how these training programs can be delivered optimally and meaningfully. The effective acquisition of musical and domain-general skills by later-life learners may be influenced by social, cultural and individual factors within the learning environment. The current study examines the effects of a 10-week piano training program on healthy older adult novices cognitive and motor skills, in comparison to an inactive waitlisted control group. Fifteen participants completed piano training led by a music facilitator in small groups (max n = 4 per lesson class; two experimental, two waitlisted control groups). Data was collected using an explanatory sequential design: quantitative data from a battery of cognitive and motor tests was collected pre/post-test on all participants, with further post-test data from the waitlisted control group (n = 7). Qualitative data included weekly facilitator observations, participant practice diaries, and an individual, semi-structured, post-experiment interview. Bayesian modelling demonstrated moderate evidence of a strong positive impact of training on part A of the Trail Making test (TMT), indicating improved visuo-motor skills. Moderate evidence for negative impacts of training on part B of the Trail Making Test (and difference score delta) was also found, suggesting no benefit of cognitive switching. Qualitative results revealed that the group learning environment motivated participants to play in musical ensembles and to socialize. Motivation was optimal when all participants were happy with the chosen repertoire (participants reported they were motivated by learning to play familiar music) and when the facilitator observed that groups had formed cohesive bonds. Informed by these factors, exploratory analyses demonstrated strong evidence that a participants lesson class had an impact on post-test scores (TMT part A). These results not only demonstrate the extent of cognitive benefits of a short-term piano training intervention for older adults, but also the importance of considering the group dynamics in the learning environment.

  • 44.
    Magnusson, Per
    et al.
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Nilsen, Per
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Schedvin, Göran
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Appropriate Use of Vitamin D Assessments in Primary Health Care: Impact of New Strategies for the Introduction and Follow-Up of Analyses in Östergötland2019Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 116, nr 14, artikel-id FFPXArtikel i tidskrift (Refereegranskat)
  • 45.
    Makitie, Riikka E.
    et al.
    Univ Helsinki, Finland; Imperial Coll London, England.
    Kampe, Anders
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Costantini, Alice
    Karolinska Inst, Sweden.
    Alm, Jessica J.
    Karolinska Inst, Sweden.
    Magnusson, Per
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Makitie, Outi
    Univ Helsinki, Finland; Karolinska Inst, Sweden; Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; Univ Helsinki, Finland; Univ Helsinki, Finland; Helsinki Univ Hosp, Finland.
    Biomarkers in WNT1 and PLS3 Osteoporosis: Altered Concentrations of DKK1 and FGF232020Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recent advancements in genetic research have uncovered new forms of monogenic osteoporosis, expanding our understanding of the molecular pathways regulating bone health. Despite active research, knowledge on the pathomechanisms, disease-specific biomarkers, and optimal treatment in these disorders is still limited. Mutations in WNT1, encoding a WNT/beta-catenin pathway ligand WNT1, and PLS3, encoding X chromosomally inherited plastin 3 (PLS3), both result in early-onset osteoporosis with prevalent fractures and disrupted bone metabolism. However, despite marked skeletal pathology, conventional bone markers are usually normal in both diseases. Our study aimed to identify novel bone markers in PLS3 and WNT1 osteoporosis that could offer diagnostic potential and shed light on the mechanisms behind these skeletal pathologies. We measured several parameters of bone metabolism, including serum dickkopf-1 (DKK1), sclerostin, and intact and C-terminal fibroblast growth factor 23 (FGF23) concentrations in 17 WNT1 and 14 PLS3 mutation-positive subjects. Findings were compared with 34 healthy mutation-negative subjects from the same families. Results confirmed normal concentrations of conventional metabolic bone markers in both groups. DKK1 concentrations were significantly elevated in PLS3 mutation-positive subjects compared with WNT1 mutation-positive subjects (p amp;lt; .001) or the mutation-negative subjects (p = .002). Similar differences were not seen in WNT1 subjects. Sclerostin concentrations did not differ between any groups. Both intact and C-terminal FGF23 were significantly elevated in WNT1 mutation-positive subjects (p = .039 and p = .027, respectively) and normal in PLS3 subjects. Our results indicate a link between PLS3 and DKK1 and WNT1 and FGF23 in bone metabolism. The normal sclerostin and DKK1 levels in patients with impaired WNT signaling suggest another parallel regulatory mechanism. These findings provide novel information on the molecular networks in bone. Extended studies are needed to investigate whether these biomarkers offer diagnostic value or potential as treatment targets in osteoporosis. (c) 2020 American Society for Bone and Mineral Research.

  • 46.
    Marshall, Andrew G.
    et al.
    Univ Liverpool, England; Liverpool John Moores Univ, England; Walton Ctr NHS Fdn Trust, England.
    Sharma, Manohar L.
    Walton Ctr NHS Fdn Trust, England.
    Marley, Kate
    Aintree Univ Hosp NHS Fdn Trust, England.
    Olausson, Håkan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurofysiologiska kliniken US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Aintree Univ Hosp NHS Fdn Trust, England.
    McGlone, Francis P.
    Liverpool John Moores Univ, England; Univ Liverpool, England.
    Spinal signalling of C-fiber mediated pleasant touch in humans2019Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 8, artikel-id e51642Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    C-tactile afferents form a distinct channel that encodes pleasant tactile stimulation. Prevailing views indicate they project, as with other unmyelinated afferents, in lamina I-spinothalamic pathways. However, we found that spinothalamic ablation in humans, whilst profoundly impairing pain, temperature and itch, had no effect on pleasant touch perception. Only discriminative touch deficits were seen. These findings preclude privileged C-tactile-lamina I-spinothalamic projections and imply integrated hedonic and discriminative spinal processing from the body.

  • 47.
    Nätt, Daniel
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Örtegren Kugelberg, Unn
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Casas, Eduard
    Josep Carreras Leukaemia Res Inst IJC, Spain.
    Nedstrand, Elizabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Zalavary, Stefan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Henriksson, Pontus
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Karolinska Inst, Sweden.
    Nijm, Carola
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Jaderquist, Julia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Sandborg, Johanna
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Karolinska Inst, Sweden.
    Flinke Carlsson, Eva
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Ramesh, Rashmi
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Örkenby, Lovisa
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Appelkvist, Filip
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelning för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Lingg, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelning för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Guzzi, Nicola
    Lund Univ, Sweden.
    Bellodi, Cristian
    Lund Univ, Sweden.
    Löf, Marie
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Karolinska Inst, Sweden.
    Vavouri, Tanya
    Josep Carreras Leukaemia Res Inst IJC, Spain.
    Öst, Anita
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Human sperm displays rapid responses to diet2019Ingår i: PLoS biology, ISSN 1544-9173, E-ISSN 1545-7885, Vol. 17, nr 12, artikel-id e3000559Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The global rise in obesity and steady decline in sperm quality are two alarming trends that have emerged during recent decades. In parallel, evidence from model organisms shows that paternal diet can affect offspring metabolic health in a process involving sperm tRNA-derived small RNA (tsRNA). Here, we report that human sperm are acutely sensitive to nutrient flux, both in terms of sperm motility and changes in sperm tsRNA. Over the course of a 2-week diet intervention, in which we first introduced a healthy diet followed by a diet rich in sugar, sperm motility increased and stabilized at high levels. Small RNA-seq on repeatedly sampled sperm from the same individuals revealed that tsRNAs were up-regulated by eating a high-sugar diet for just 1 week. Unsupervised clustering identified two independent pathways for the biogenesis of these tsRNAs: one involving a novel class of fragments with specific cleavage in the T-loop of mature nuclear tRNAs and the other exclusively involving mitochondrial tsRNAs. Mitochondrial involvement was further supported by a similar up-regulation of mitochondrial rRNA-derived small RNA (rsRNA). Notably, the changes in sugar-sensitive tsRNA were positively associated with simultaneous changes in sperm motility and negatively associated with obesity in an independent clinical cohort. This rapid response to a dietary intervention on tsRNA in human sperm is attuned with the paternal intergenerational metabolic responses found in model organisms. More importantly, our findings suggest shared diet-sensitive mechanisms between sperm motility and the biogenesis of tsRNA, which provide novel insights about the interplay between nutrition and male reproductive health.

  • 48.
    Ousdal, Olga Therese
    et al.
    Haukeland Hosp, Norway.
    Argyelan, Miklos
    Feinstein Inst Med Res, NY USA.
    Narr, Katherine L.
    Univ Calif Los Angeles, CA 90024 USA.
    Abbott, Christopher
    Univ New Mexico, NM 87131 USA.
    Wade, Benjamin
    Univ Calif Los Angeles, CA 90024 USA.
    Vandenbulcke, Mathieu
    Katholieke Univ Leuven, Belgium.
    Urretavizcaya, Mikel
    Univ Barcelona, Spain; Univ Barcelona, Spain; Carlos III Hlth Inst, Spain.
    Tendolkar, Indira
    Radboud Univ Nijmegen, Netherlands; Ctr Cognit Neuroimaging, Netherlands; Univ Duisburg Essen, Germany; Univ Duisburg Essen, Germany.
    Takamiya, Akihiro
    Keio Univ, Japan; Komagino Hosp, Japan.
    Stek, Max L.
    Geestelijke GezondheidsZorg InGeest Specialized M, Netherlands; Vrije Univ Amsterdam, Netherlands.
    Soriano-Mas, Carles
    Univ Barcelona, Spain; Univ Autonoma Barcelona, Spain; Carlos III Hlth Inst, Spain.
    Redlich, Ronny
    Univ Munster, Germany.
    Paulson, Olaf B.
    Rigshosp, Denmark; Univ Copenhagen, Denmark.
    Oudega, Mardien L.
    Geestelijke GezondheidsZorg InGeest Specialized M, Netherlands; Vrije Univ Amsterdam, Netherlands.
    Opel, Nils
    Univ Munster, Germany; Univ Munster, Germany.
    Nordanskog, Pia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Kishimoto, Taishiro
    Keio Univ, Japan.
    Kämpe, Robin
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten.
    Jorgensen, Anders
    Rigshosp, Denmark.
    Hanson, Lars G.
    Tech Univ Denmark, Denmark; Copenhagen Univ Hosp, Denmark.
    Hamilton, Paul
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Espinoza, Randall
    Univ Calif Los Angeles, CA 90024 USA.
    Emsell, Louise
    Katholieke Univ Leuven, Belgium.
    van Eijndhoven, Philip
    Radboud Univ Nijmegen, Netherlands; Ctr Cognit Neuroimaging, Netherlands.
    Dols, Annemieke
    Geestelijke GezondheidsZorg InGeest Specialized M, Netherlands; Vrije Univ Amsterdam, Netherlands.
    Dannlowski, Udo
    Univ Munster, Germany.
    Cardoner, Narcis
    Univ Autonoma Barcelona, Spain; Carlos III Hlth Inst, Spain; Univ Hosp Parc Tauli I3PT, Spain.
    Bouckaert, Filip
    Katholieke Univ Leuven, Belgium.
    Anand, Amit
    Cleveland Clin, OH 44106 USA.
    Bartsch, Hauke
    Univ Calif Los Angeles, CA USA; Ctr Multimodal Imaging and Genet, CA USA; Univ Calif San Diego, CA 92093 USA.
    Kessler, Ute
    Haukeland Hosp, Norway; Univ Bergen, Norway.
    Oedegaard, Ketil J.
    Haukeland Hosp, Norway; Univ Bergen, Norway.
    Dale, Anders M.
    Univ Calif Los Angeles, CA USA; Ctr Multimodal Imaging and Genet, CA USA; Univ Calif San Diego, CA 92093 USA; Univ Calif San Diego, CA 92093 USA.
    Oltedal, Leif
    Haukeland Hosp, Norway; Univ Bergen, Norway.
    Brain Changes Induced by Electroconvulsive Therapy Are Broadly Distributed2020Ingår i: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 87, nr 5, s. 451-461Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Electroconvulsive therapy (ECT) is associated with volumetric enlargements of corticolimbic brain regions. However, the pattern of whole-brain structural alterations following ECT remains unresolved. Here, we examined the longitudinal effects of ECT on global and local variations in gray matter, white matter, and ventricle volumes in patients with major depressive disorder as well as predictors of ECT-related clinical response. METHODS: Longitudinal magnetic resonance imaging and clinical data from the Global ECT-MRI Research Collaboration (GEMRIC) were used to investigate changes in white matter, gray matter, and ventricle volumes before and after ECT in 328 patients experiencing a major depressive episode. In addition, 95 nondepressed control subjects were scanned twice. We performed a mega-analysis of single subject data from 14 independent GEMRIC sites. RESULTS: Volumetric increases occurred in 79 of 84 gray matter regions of interest. In total, the cortical volume increased by mean +/- SD of 1.04 +/- 1.03% (Cohens d = 1.01, p amp;lt; .001) and the subcortical gray matter volume increased by 1.47 +/- 1.05% (d = 1.40, p amp;lt; .001) in patients. The subcortical gray matter increase was negatively associated with total ventricle volume (Spearmans rank correlation rho = -.44, p amp;lt; .001), while total white matter volume remained unchanged (d = -0.05, p = .41). The changes were modulated by number of ECTs and mode of electrode placements. However, the gray matter volumetric enlargements were not associated with clinical outcome. CONCLUSIONS: The findings suggest that ECT induces gray matter volumetric increases that are broadly distributed. However, gross volumetric increases of specific anatomically defined regions may not serve as feasible biomarkers of clinical response.

  • 49.
    Pham, Tuan
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Prince Mohammad Bin Fahd Univ, Saudi Arabia.
    Fan, Chuanwen
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Sichuan Univ, Peoples R China.
    Pfeifer, Daniella
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten.
    Zhang, Hong
    Orebro Univ, Sweden.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Image-Based Network Analysis of DNp73 Expression by Immunohistochemistry in Rectal Cancer Patients2020Ingår i: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 10, artikel-id 1551Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Rectal cancer is a disease characterized with tumor heterogeneity. The combination of surgery, radiotherapy, and chemotherapy can reduce the risk of local recurrence. However, there is a significant difference in the response to radiotherapy among rectal cancer patients even they have the same tumor stage. Despite rapid advances in knowledge of cellular functions affecting radiosensitivity, there is still a lack of predictive factors for local recurrence and normal tissue damage. The tumor protein DNp73 is thought as a biomarker in colorectal cancer, but its clinical significance is still not sufficiently investigated, mainly due to the limitation of human-based pathology analysis. In this study, we investigated the predictive value of DNp73 in patients with rectal adenocarcinoma using image-based network analysis.

    Methods: The fuzzy weighted recurrence network of time series was extended to handle multi-channel image data, and applied to the analysis of immunohistochemistry images of DNp73 expression obtained from a cohort of 25 rectal cancer patients who underwent radiotherapy before surgery. Two mathematical weighted network properties, which are the clustering coefficient and characteristic path length, were computed for the image-based networks of the primary tumor (obtained after operation) and biopsy (obtained before operation) of each cancer patient.

    Results: The ratios of two weighted recurrence network properties of the primary tumors to biopsies reveal the correlation of DNp73 expression and long survival time, and discover the non-effective radiotherapy to a cohort of rectal cancer patients who had short survival time.

    Conclusion: Our work contributes to the elucidation of the predictive value of DNp73 expression in rectal cancer patients who were given preoperative radiotherapy. Mathematical properties of fuzzy weighted recurrence networks of immunohistochemistry images are not only able to show the predictive factor of DNp73 expression in the patients, but also reveal the identification of non-effective application of radiotherapy to those who had poor overall survival outcome.

  • 50.
    Pinto, Bernardo Bollen
    et al.
    Geneva Univ Hosp, Switzerland; Geneva Perioperat Basic Translat and Clin Res Grp, Switzerland.
    Chew, Michelle
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Anestesi- och intensivvårdskliniken US (ANOPIVA).
    Buse, Giovanna Lurati
    Univ Hosp Dusseldorf, Germany.
    Walder, Bernhard
    Geneva Univ Hosp, Switzerland; Geneva Perioperat Basic Translat and Clin Res Grp, Switzerland.
    The concept of peri-operative medicine to prevent major adverse events and improve outcome in surgical patients A narrative review2019Ingår i: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 36, nr 12, s. 889-903Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Peri-operative Medicine is the patient-centred and value-based multidisciplinary peri-operative care of surgical patients. Peri-operative stress, that is the collective response to stimuli occurring before, during and after surgery, is, together with pre-existing comorbidities, the pathophysiological basis of major adverse events. The ultimate goal of Perioperative Medicine is to promote high quality recovery after surgery. Clinical! scores and/or biomarkers should be used to identify patients at high risk of developing major adverse events throughout the peri-operative period. Allocation of high-risk patients to specific care pathways with peri-operative organ protection, close surveillance and specific early interventions is likely to improve patient-relevant outcomes, such as disability, health-related quality of life and mortality.

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