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  • 201.
    Pihl, Sofia
    et al.
    Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Uustal, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Hjertberg, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Blomberg, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Interobserver agreement in perineal ultrasound measurement of the anovaginal distance: a methodological study2018In: International Urogynecology Journal, ISSN 0937-3462, E-ISSN 1433-3023, Vol. 29, no 5, p. 697-701Article in journal (Refereed)
    Abstract [en]

    Objective outcome measures of the extent of laceration at delivery are needed. In this study we evaluated and describe here a method for learning perineal ultrasound measurement of the anovaginal distance (AVD). The learning period needed for examiners proficient in vaginal ultrasound examination and the interobserver agreement after reaching proficiency in AVD measurement were determined. The hypothesis was that the method is feasible to learn and reproducible for use in further research. The method was taught by an examiner experienced in perineal ultrasonography. The distance between the mucosal margin of the internal anal sphincter was measured with a vaginal probe. The studied examiners measured the AVD until similar results (+/- 5 mm) were achieved. The AVD in 40 women was then measured and documented by two examiners who were blinded to each others results. Interobserver agreement was calculated using the kappa score. Examiners with previous experience in vaginal ultrasonography had learned the method after performing five sets of comeasurements. The AVD measurements after the learning period showed almost perfect agreement (kappa = 0.87) between the examiners. The method for perineal ultrasound measurement of AVD was learned quickly with high interobserver agreement. The method is feasible to learn and reproducible for use in further research.

  • 202.
    Pihl, Sofia
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Uustal Fornell, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Blomberg, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Anovaginal distance and obstetric anal sphincter injury: a prospective observational study2019In: International Urogynecology Journal, ISSN 0937-3462, E-ISSN 1433-3023, Vol. 30, no 6, p. 939-944Article in journal (Refereed)
    Abstract [en]

    Introduction and Hypothesis

    No measurements are available for diagnosing the extent of obstetric lacerations. The primary aim of this study was to evaluate the relation between the anovaginal distance (AVD) measured with transperineal ultrasound immediately after delivery and external anal sphincter injury. A secondary aim was to assess whether the palpated perineal thickness was associated with the AVD.

    Methods

    A prospective observational study of 150 primiparous women at the University Hospital, Linköping, Sweden. After vaginal delivery, initial inspection and palpation of the perineal thickness were performed by the midwife. The women were then divided into subgroups depending on the degree of the suspected perineal laceration. Transperineal ultrasound of the AVD was performed by a physician. Diagnostics of the perineal laceration were done according to standard care.

    Results

    Women with an external sphincter injury had a shorter AVD and shorter palpatory perineal thickness compared with women without anal sphincter injury. No external sphincter injuries were diagnosed when the AVD and/or palpation height was > 20 mm. The mean AVD in the group with probable second-degree laceration (n = 85) was 18.8 mm (95% CI 17.8–19.8), in suspected third-degree laceration (n = 33) 15.7 mm (95% CI 13.7–17.7) and in probable third-degree laceration (n = 32) 11.8 mm (95% CI 9.7–13.9) (p < 0.001).

    Conclusions

    A short AVD could be a warning sign postpartum and should increase the awareness of possible external sphincter injury before suturing. An AVD of 20 mm seems to indicate a cutoff level of the occurrence of external sphincter injury, but this needs further evaluation.

  • 203.
    Ping Zhao, Lue
    et al.
    Fred Hutchinson Cancer Research Centre, WA 98109 USA; University of Washington, WA 98195 USA.
    Carlsson, Annelie
    Lund University, Sweden.
    Elding Larsson, Helena
    Lund University, Sweden.
    Forsander, Gun
    Sahlgrens University Hospital, Sweden.
    Ivarsson, Sten A.
    Lund University, Sweden.
    Kockum, Ingrid
    Karolinska Institute, Sweden.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Marcus, Claude
    Karolinska Institute, Sweden.
    Persson, Martina
    Karolinska University Hospital, Sweden.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Ortqvist, Eva
    Karolinska University Hospital, Sweden.
    Pyo, Chul-Woo
    Fred Hutchinson Cancer Research Centre, WA 98104 USA.
    Bolouri, Hamid
    University of Washington, WA 98195 USA.
    Zhao, Michael
    University of Washington, WA 98195 USA.
    Nelson, Wyatt C.
    Fred Hutchinson Cancer Research Centre, WA 98104 USA.
    Geraghty, Daniel E.
    Fred Hutchinson Cancer Research Centre, WA 98104 USA.
    Lernmark, Ake
    Lund University, Sweden.
    Building and validating a prediction model for paediatric type 1 diabetes risk using next generation targeted sequencing of class II HLA genes2017In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 33, no 8, article id e2921Article in journal (Refereed)
    Abstract [en]

    AimIt is of interest to predict possible lifetime risk of type 1 diabetes (T1D) in young children for recruiting high-risk subjects into longitudinal studies of effective prevention strategies. MethodsUtilizing a case-control study in Sweden, we applied a recently developed next generation targeted sequencing technology to genotype class II genes and applied an object-oriented regression to build and validate a prediction model for T1D. ResultsIn the training set, estimated risk scores were significantly different between patients and controls (P=8.12x10(-92)), and the area under the curve (AUC) from the receiver operating characteristic (ROC) analysis was 0.917. Using the validation data set, we validated the result with AUC of 0.886. Combining both training and validation data resulted in a predictive model with AUC of 0.903. Further, we performed a biological validation by correlating risk scores with 6 islet autoantibodies, and found that the risk score was significantly correlated with IA-2A (Z-score=3.628, Pamp;lt;0.001). When applying this prediction model to the Swedish population, where the lifetime T1D risk ranges from 0.5% to 2%, we anticipate identifying approximately 20 000 high-risk subjects after testing all newborns, and this calculation would identify approximately 80% of all patients expected to develop T1D in their lifetime. ConclusionThrough both empirical and biological validation, we have established a prediction model for estimating lifetime T1D risk, using class II HLA. This prediction model should prove useful for future investigations to identify high-risk subjects for prevention research in high-risk populations.

  • 204.
    Ramö Isgren, Anna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Kjölhede, Preben
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Blomberg, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Adverse Neonatal Outcomes in Overweight and Obese Adolescents Compared with Normal Weight Adolescents and Low Risk Adults2019In: Journal of Pediatric and Adolescent Gynecology, ISSN 1083-3188, E-ISSN 1873-4332, Vol. 32, no 2, p. 139-145Article in journal (Refereed)
    Abstract [en]

    Study Objective: To evaluate the association between maternal body mass index and neonatal outcomes in adolescents and to compare neonatal outcomes between overweight and obese adolescents and obstetric low-risk adult women. Design: Retrospective cohort study using data from the Swedish Medical Birth Register. Setting: Sweden. Participants: All 31,386 primiparous adolescents younger than 20 years of age and 178,844 "standard" women, defined as normal weight, obstetric low-risk adult women who delivered between 1992 and 2013. The adolescents were categorized according to weight and height in early pregnancy into body mass index groups according to the World Health Organization classification. Logistic regression models were used. Interventions and Main Outcome Measures: Neonatal outcomes in relation to maternal body mass index groups. Results: In the adolescents, 6109/31,386 (19.5%) and 2287/31,386 (7.3%) were overweight and obese, respectively. Compared with normal weight adolescents, overweight adolescents had a lower risk of having small for gestational age neonates, and higher risks for having neonates with macrosomia, and being large for gestational age and with Apgar score less than 7 at 5 minutes. The obese adolescents had increased risk for having neonates being large for gestational age (3.8% vs 1.3%; adjusted odds ratio [aOR], 2.97 [95% confidence interval (CI), 2.30-3.84]), with macrosomia ( amp;gt;4500 g) (4.6% vs 1.4%; aOR, 2.95 [95% CI, 2.33-3.73]), and with Apgar score less than 7 at 5 minutes (2.2% vs 1.1%; aOR, 1.98 [95% CI, 1.43-2.76]) than normal weight adolescents. Compared with the standard women, overweight and obese adolescents had overall more adverse neonatal outcomes. Conclusion: Overweight and obese adolescents had predominantly increased risks for adverse neonatal outcomes compared with normal weight adolescents and standard women.

  • 205.
    Ramö Isgren, Anna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Kjölhede, Preben
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Blomberg, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Obstetric Outcomes in Adolescents Related to Body Mass Index and Compared with Low-Risk Adult Women2017In: Journal of Women's Health, ISSN 1540-9996, E-ISSN 1931-843X, Vol. 26, no 5, p. 426-434Article in journal (Refereed)
    Abstract [en]

    Objective: To evaluate in adolescents the association between body mass index (BMI) and obstetric outcomes and to determine whether the outcomes in the BMI groups of adolescents differ from those of a low-risk population of adult women. Materials and Methods: This is a nationwide population-based register study. Obstetric outcomes of 31,386 singleton primiparous adolescents were evaluated in relation to BMI classes. Furthermore, the outcomes of the adolescents and 178,844 normal weight, nonsmoking, singleton primiparous women, 25-29 years old with no known comorbidity, defined as standard women, were compared. Multiple logistic regression models were used. Results are presented as crude odds ratios (ORs) or adjusted ORs and with a 95% confidence interval. Results: Compared with normal weight adolescents, obese adolescents had a lower chance of a normal vaginal delivery (VD)76% versus 85% [adjusted OR 0.61 (0.55-0.68)], a higher risk for acute cesarean section (CS)8.9% versus 4.5% [adjusted OR 2.45 (2.08-2.88)], and stillbirth0.7% versus 0.2% [adjusted OR 3.17 (1.74-5.77)]. Compared with standard women, overweight adolescents had a higher chance of a normal VD82% versus 75% [crude OR 1.53 (1.44-1.64)] and a lower risk for acute CS6.3% versus 7.1% [crude OR 0.85 (0.76-0.95)]. Obese adolescents had a lower risk for instrumental VD8% versus 13% [crude OR 0.61 (0.53-0.71)] and obstetric anal sphincter injury1% versus 3% [crude OR 0.38 (0.26-0.57)]. Conclusion: Several adverse obstetric outcomes were obesity related among adolescents. Overweight adolescents seemed to have better obstetric outcomes than standard women, something to consider when optimizing resources for women during pregnancy and delivery.

  • 206.
    Reid, G.
    et al.
    Lawson Health Research Institute, Canada; University of Western Ontario, Canada; University of Western Ontario, Canada.
    Abrahamsson, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Bailey, M.
    Ohio State University, OH 43210 USA; Nationwide Childrens Hospital, OH USA.
    Bindels, L. B.
    Catholic University of Louvain, Belgium.
    Bubnov, R.
    National Academic Science Ukraine, Ukraine.
    Ganguli, K.
    Massachusetts Gen Hospital Children, MA 02114 USA; Harvard Medical Sch, MA 02114 USA.
    Martoni, C.
    UAS Labs, WI 53718 USA.
    ONeill, C.
    University of Manchester, England.
    Savignac, H. M.
    Clasado Research Serv Ltd, England; 4D Pharma PLC, Scotland.
    Stanton, C.
    University of Coll Cork, Ireland.
    Ship, N.
    Bio K Pharma Inc, Canada.
    Surette, M.
    McMaster University, Canada.
    Tuohy, K.
    Fdn Edmund Mach, Italy.
    van Hemert, S.
    Winclove Probiot, Netherlands.
    How do probiotics and prebiotics function at distant sites?2017In: Beneficial Microbes, ISSN 1876-2883, E-ISSN 1876-2891, Vol. 8, no 4, p. 521-533Article in journal (Refereed)
    Abstract [en]

    The realisation that microbes regarded as beneficial to the host can impart effects at sites distant from their habitat, has raised many possibilities for treatment of diseases. The objective of a workshop hosted in Turku, Finland, by the International Scientific Association for Probiotics and Prebiotics, was to assess the evidence for these effects and the extent to which early life microbiome programming influences how the gut microbiota communicates with distant sites. In addition, we examined how probiotics and prebiotics might affect the skin, airways, heart, brain and metabolism. The growing levels of scientific and clinical evidence showing how microbes influence the physiology of many body sites, leads us to call for more funding to advance a potentially exciting avenue for novel therapies for many chronic diseases.

  • 207.
    Roepke, E. Rasmark
    et al.
    Malmo and Lund Univ, Sweden.
    Bruno, Valentina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Tor Vergata Univ Hosp, Italy; Tor Vergata Univ Hosp, Italy.
    Nedstrand, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Boij, Roland
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Strid, C. Petersson
    Kalmar Hosp, Sweden.
    Piccione, E.
    Tor Vergata Univ Hosp, Italy.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Svensson Arvelund, Judit
    Linköping University, Department of Clinical and Experimental Medicine, Division of Hematopoiesis and Developmental Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Rubér, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Low-molecular-weight-heparin increases Th1-and Th17-associated chemokine levels during pregnancy in women with unexplained recurrent pregnancy loss: a randomised controlled trial2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 12314Article in journal (Refereed)
    Abstract [en]

    Low-molecular-weight heparin (LMWH) is widely used to treat recurrent pregnancy loss (RPL) because of its anti-coagulant effects. Although in vitro studies have suggested additional immunological effects, these are debated. We therefore investigated whether LMWH could modulate immune responses in vivo during pregnancy of women with unexplained RPL. A Swedish open multi-centre randomised controlled trial included 45 women treated with tinzaparin and 42 untreated women. Longitudinally collected plasma samples were obtained at gestational weeks (gw) 6, 18, 28 and 34 and analysed by multiplex bead technology for levels of 11 cytokines and chemokines, chosen to represent inflammation and T-helper subset-associated immunity. Mixed linear models test on LMWH-treated and untreated women showed differences during pregnancy of the Th1-associated chemokines CXCL10 (p = 0.01), CXCL11 (p amp;lt; 0.001) and the Th17-associated chemokine CCL20 (p = 0.04), while CCL2, CCL17, CCL22, CXCL1, CXCL8, CXCL12, CXCL13 and IL-6 did not differ. Subsequent Students t-test showed significantly higher plasma levels of CXCL10 and CXCL11 in treated than untreated women at gw 28 and 34. The consistent increase in the two Th1-associated chemokines suggests a potential proinflammatory and unfavourable effect of LMWH treatment during later stages of pregnancy, when Th1 immunity is known to disrupt immunological tolerance.

  • 208.
    Rosenberg, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Kjölhede, Preben
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Staf, Christian
    Reg Canc Ctr, Sweden; Sahlgrens Univ Hosp, Sweden.
    Bjurberg, Maria
    Skane Univ Hosp, Sweden.
    Borgfeldt, Christer
    Lund Univ, Sweden.
    Dahm-Kahler, Pernilla
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Hellman, Kristina
    Karolinska Inst, Sweden.
    Hjerpe, Elisabet
    Karolinska Inst, Sweden.
    Holmberg, Erik
    Reg Canc Ctr, Sweden; Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Stalberg, Karin
    Uppsala Univ, Sweden.
    Tholander, Bengt
    Uppsala Univ, Sweden.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Hogberg, Thomas
    Lund Univ, Sweden.
    Data quality in the Swedish Quality Register of Gynecologic Cancer - a Swedish Gynecologic Cancer Group (SweGCG) study2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 3, p. 346-353Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of this study is to evaluate the quality of data on endometrial (EC) and ovarian, fallopian tube, peritoneal, abdominal or pelvic cancers (OC) registered in the Swedish Quality Register of Gynecologic Cancer (SQRGC).Method: A random sample of 500 patients was identified in the SQRGC and their medical charts were reviewed for re-abstraction of 31 selected core variables by an independent validator. The data in the SQRGC and the re-abstracted data were compared. The data were collected from 25 hospitals evenly distributed throughout Sweden. The main outcomes were comparability, timeliness, completeness and validity. Coverage was compared with the National Cancer Register (NCR). Timeliness was defined as the speed of registration i.e. when patients were registered in the SQRGC relative to date of diagnosis. Internationally accepted coding systems for stage, grading and histologic type were used ensuring a high degree of comparability. Correlations were estimated using Pearsons correlation coefficient and Cohens kappa coefficient.Results: The completeness was 95%. The timeliness was 88-91% within 12 months of diagnosis. The median degree of agreement between re-abstracted data and data in the SQRGC was 82.1%, with a median kappa value of 0.73 for ordinate variables and a median Pearsons correlation coefficient of 0.96. The agreements for the type of surgery were 76% (95% CI 70-81%; kappa 0.49) and type of primary treatment 90% (95% CI 87-94%; kappa 0.85) in OC and in EC 88% (95% CI 84-93%; kappa 0.84). The agreements for the FIGO stage were in OC and EC 74% (95% CI 68-80%; kappa 0.69) and 87% (95% CI 82-91%; kappa 0.79), respectively.Conclusions: The data in the Swedish Quality Register for Gynecologic Cancer are of adequate quality in order to be used as a basis for research and to evaluate possible differences in treatment, lead times and treatment results.

  • 209.
    Russell, Jordan T.
    et al.
    Univ Florida, FL 32611 USA.
    Roesch, Luiz F. W.
    Univ Fed Pampa, Brazil.
    Ördberg, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Ilonen, Jorma
    Univ Turku, Finland; Turku Univ Hosp, Finland.
    Atkinson, Mark A.
    Univ Florida, FL 32610 USA.
    Schatz, Desmond A.
    Univ Florida, FL 32610 USA.
    Triplett, Eric W.
    Univ Florida, FL 32611 USA.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Genetic risk for autoimmunity is associated with distinct changes in the human gut microbiome2019In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, article id 3621Article in journal (Refereed)
    Abstract [en]

    Susceptibility to many human autoimmune diseases is under strong genetic control by class II human leukocyte antigen (HLA) allele combinations. These genes remain by far the greatest risk factors in the development of type 1 diabetes and celiac disease. Despite this, little is known about HLA influences on the composition of the human gut microbiome, a potential source of environmental influence on disease. Here, using a general population cohort from the All Babies in Southeast Sweden study, we report that genetic risk for developing type 1 diabetes autoimmunity is associated with distinct changes in the gut microbiome. Both the core microbiome and beta diversity differ with HLA risk group and genotype. In addition, protective HLA haplotypes are associated with bacterial genera Intestinibacter and Romboutsia. Thus, general population cohorts are valuable in identifying potential environmental triggers or protective factors for autoimmune diseases that may otherwise be masked by strong genetic control.

  • 210.
    Samuelsson, Ulf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Åkesson, Karin
    Cty Hosp Ryhov, Sweden; Jonkoping Univ, Sweden.
    Peterson, Anette
    Jonkoping Univ, Sweden; Jonkoping Univ, Sweden.
    Hanas, Ragnar
    Uddevalla Cent Hosp, Sweden; Univ Gothenburg, Sweden.
    Hanberger, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Continued improvement of metabolic control in Swedish pediatric diabetes care2018In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, no 1, p. 150-157Article in journal (Refereed)
    Abstract [en]

    Background: To prospectively investigate if the grand mean HbA1c and the differences in mean HbA1c between centers in Sweden could be reduced, thereby improving care delivered by pediatric diabetes teams. Methods: We used an 18-month quality improvement collaborative (QIC) together with the Swedish pediatric diabetes quality registry (SWEDIABKIDS). The first program (IQ-1), started in April 2011 and the second (IQ-2) in April 2012; together they encompassed 70% of Swedish children and adolescents with diabetes. Results: The proportion of patients in IQ-1 with a mean HbA1c amp;lt;7.4% (57 mmol/mol) increased from 26.4% before start to 35.9% at 36 months (P amp;lt; .001), and from 30.2% to 37.2% (P amp;lt; .001) for IQ-2. Mean HbA1c decreased in both participating and non-participating (NP) centers in Sweden, thereby indicating an improvement by a spatial spill over effect in NP centers. The grand mean HbA1c decreased by 0.45% (4.9 mmol/mol) during 36 months; at the end of 2014 it was 7.43% (57.7 mmol/mol) (P amp;lt; .001). A linear regression model with the difference in HbA1c before start and second follow-up as dependent variable showed that QIC participation significantly decreased mean HbA1c both for IQ-1 and IQ-2. The proportion of patients with high HbA1c values (amp;gt;8.7%, 72 mmol/mol) decreased significantly in both QICs, while it increased in the NP group. Conclusions: The grand mean HbA1c has decreased significantly in Sweden from 2010 to 2014, and QICs have contributed significantly to this decrease. There seems to be a spatial spill-over effect in NP centers.

  • 211.
    Sandestig, Anna
    et al.
    Region Östergötland, Center for Diagnostics, Clinical genetics.
    Gréen, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Jonasson, Jon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Vogt, Hartmut
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Wahlström, Johan
    Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Pepler, Alexander
    Department of CeGaT GmbH, Tübingen, Germany.
    Ellnebo, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Biskup, Saskia
    Department of CeGaT GmbH, Tübingen, Germany.
    Stefanova, Margarita
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Could Dissimilar Phenotypic Effects of ACTB Missense Mutations Reflect the Actin Conformational Change?: Two Novel Mutations and Literature Review2019In: Molecular Syndromology, ISSN 1661-8769, E-ISSN 1661-8777, Vol. 9, no 5, p. 259-265Article in journal (Refereed)
    Abstract [en]

    The beta-actin gene encodes 1 of 6 different actin proteins. De novo heterozygous missense mutations in ACTB have been identified in patients with Baraitser-Winter syndrome (BRWS) and also in patients with developmental disorders other than BRWS, such as deafness, dystonia, and neutrophil dysfunction. We describe 2 different novel de novo missense ACTB mutations, c.208Camp;gt;G (p.Pro70Ala) and c.511Camp;gt;T (p.Leu171Phe), found by trio exome sequencing analysis of 2 unrelated patients: an 8-year-old boy with a suspected BRWS and a 4-year-old girl with unclear developmental disorder. The mutated residue in the first case is situated in the actin H-loop, which is involved in actin polymerization. The mutated residue in the second case (p.Leu171Phe) is found at the actin barbed end in the W-loop, important for binding to profilin and other actin-binding molecules. While the boy presented with a typical BRWS facial appearance, the girl showed facial features not recognizable as a BRWS gestalt as well as ventricular arrhythmia, cleft palate, thrombocytopenia, and gray matter heterotopia. We reviewed previously published ACTB missense mutations and ascertained that a number of them do not cause typical BRWS. By comparing clinical and molecular data, we speculate that the phenotypic differences found in ACTB missense mutation carriers might supposedly be dependent on the conformational change of ACTB.

  • 212.
    Shalek, Alex K.
    et al.
    MIT, MA USA; Broad Institute MIT and Harvard, MA 02142 USA; Ragon Institute Massachusetts Gen Hospital MIT and Harvard, MA 02139 USA.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    Single-cell analyses to tailor treatments2017In: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 9, no 408, article id eaan4730Article in journal (Other academic)
    Abstract [en]

    Single-cell RNA-seq could play a key role in personalized medicine by facilitating characterization of cells, pathways, and genes associated with human diseases such as cancer.

  • 213.
    Sharma, Sumit
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Carlsson, Beatrice
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Czako, Rita
    Baylor Coll Med, TX 77030 USA; Baylor Coll Med, TX 77030 USA.
    Vene, Sirkka
    Public Health Agency Sweden, Sweden.
    Haglund, Mats
    County Hospital Kalmar, Sweden.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Larson, Goran
    University of Gothenburg, Sweden.
    Hammarstrom, Lennart
    Karolinska Institute, Sweden.
    Sosnovtsev, Stanislav V.
    NIAID, MD 20892 USA.
    Atmar, Robert L.
    Baylor Coll Med, TX 77030 USA; Baylor Coll Med, TX 77030 USA.
    Green, Kim Y.
    NIAID, MD 20892 USA.
    Estes, Mary K.
    Baylor Coll Med, TX 77030 USA; Baylor Coll Med, TX 77030 USA.
    Svensson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Human Sera Collected between 1979 and 2010 Possess Blocking-Antibody Titers to Pandemic GII.4 Noroviruses Isolated over Three Decades2017In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 91, no 14, article id UNSP e00567Article in journal (Refereed)
    Abstract [en]

    The emergence of pandemic GII.4 norovirus (NoV) strains has been proposed to occur due to changes in receptor usage and thereby to lead to immune evasion. To address this hypothesis, we measured the ability of human sera collected between 1979 and 2010 to block glycan binding of four pandemic GII. 4 noroviruses isolated in the last 4 decades. In total, 268 sera were investigated for 50% blocking titer (BT50) values of virus-like particles (VLPs) against pig gastric mucin (PGM) using 4 VLPs that represent different GII. 4 norovirus variants identified between 1987 and 2012. Pre- and postpandemic sera (sera collected before and after isolation of the reference NoV strain) efficiently prevented binding of VLP strains MD145 (1987), Grimsby (1995), and Houston (2002), but not the Sydney (2012) strain, to PGM. No statistically significant difference in virus-blocking titers was observed between pre- and postpandemic sera. Moreover, paired sera showed that blocking titers of amp;gt;= 160 were maintained over a 6-year period against MD145, Grimsby, and Houston VLPs. Significantly higher serum blocking titers (geometric mean titer [GMT], 1,704) were found among IgA-deficient individuals than among healthy blood donors (GMT, 90.9) (P amp;lt; 0.0001). The observation that prepandemic sera possess robust blocking capacity for viruses identified decades later suggests a common attachment factor, at least until 2002. Our results indicate that serum IgG possesses antibody-blocking capacity and that blocking titers can be maintained for at least 6 years against 3 decades of pandemic GII. 4 NoV. IMPORTANCE Human noroviruses (NoVs) are the major cause of acute gastroenteritis worldwide. Histo-blood group antigens (HBGAs) in saliva and gut recognize NoV and are the proposed ligands that facilitate infection. Polymorphisms in HBGA genes, and in particular a nonsense mutation in FUT2 (G428A), result in resistance to global dominating GII. 4 NoV. The emergence of new pandemic GII. 4 strains occurs at intervals of several years and is proposed to be attributable to epochal evolution, including amino acid changes and immune evasion. However, it remains unclear whether exposure to a previous pandemic strain stimulates immunity to a pandemic strain identified decades later. We found that prepandemic sera possess robust virus-blocking capacity against viruses identified several decades later. We also show that serum lacking IgA antibodies is sufficient to block NoV VLP binding to HBGAs. This is essential, considering that 1 in every 600 Caucasian children is IgA deficient.

  • 214.
    Sharma, Surendra
    et al.
    Department of Pediatrics, Women and Infants Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USA.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Obituary: Leif Matthiesen, MD, PhD (1954‐2017)2017In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 78, no 4, article id e12740Article in journal (Other academic)
    Abstract [en]

    Leif Matthiesen, an evergreen member and supporter of the American Society for Reproductive Immunology (ASRI), died on April 29, 2017, following a hard fought battle with glioblastoma. We all hoped that Leif being a fearless person and a fun‐loving physician scientist would beat all the odds against this dreaded disease and come out of it with flying colors. Alas, our hopes were given a serious thought by the Almighty. We as a community of friends and scientific colleagues are saddened by the loss of such a wonderful human being and a noteworthy member of the ASRI.

  • 215.
    Simona Chisalita, Ioana
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Insulin-Like Growth Factor-1 at Diagnosis and during Subsequent Years in Adolescents with Type 1 Diabetes2018In: Journal of Diabetes Research, ISSN 2314-6745, E-ISSN 2314-6753, article id 8623560Article in journal (Refereed)
    Abstract [en]

    Background. Type 1 diabetes (T1D) in adolescents is associated with alterations in the insulin-like factor system probably caused both by a deranged metabolism and insulinopenia in the portal vein.

    Objective. To study how the circulating IGF-1 is affected at diagnosis and during subsequent years in adolescents with T1D.

    Methods. Ten girls and ten boys with type 1 diabetes (T1D), aged 13.0 +/- 1.4 (mean +/- SD) years at diagnosis, took part in the study. Blood samples were drawn at diagnosis and after 3, 9, 18, and 48 months. HbA1c, total IGF-1, and C-peptide were measured.

    Results. At diagnosis, the patients had high HbA1c, low IGF-1, and measurable C-peptide. After the start of insulin treatment, maximal improvement in glycemic control and IGF-1 occurred within 3 months and then both tended to deteriorate, that is, HbA1c to increase and IGF-1 to decrease. C-peptide decreased with time, and after 4 years, half of the patients were C-peptide negative. At diagnosis, C-peptide correlated positively to IGF-1 (r = 0 50; p amp;lt; 0 03). C-peptide correlated negatively with insulin dose (U/kg) after 18 and 48 months from diagnosis (r = -0 48; p amp;lt; 0 03 and r = -0 72; p amp;lt; 0 001, resp.).

    Conclusions. In conclusion, our results show that in newly diagnosed adolescents with type 1 diabetes and deranged metabolism, the IGF-1 level is low and rapidly improves with insulin treatment but later tends to decrease concomitantly with declining endogenous insulin secretion.

  • 216.
    Stalberg, Karin
    et al.
    Uppsala Univ, Sweden.
    Bjurberg, Maria
    Skane Univ Hosp Lund, Sweden; Lund Univ, Sweden.
    Borgfeldt, Christer
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Carlson, Joseph
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Dahm-Kahler, Pernilla
    Gothenburg Univ, Sweden.
    Floter-Radestad, Angelique
    Karolinska Inst, Sweden.
    Hellman, Kristina
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Hjerpe, Elisabet
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Holmberg, Erik
    Sahlgrens Acad, Sweden; Sahlgrens Univ Hosp, Sweden.
    Kjölhede, Preben
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Marcickiewicz, Janusz
    Reg Canc Ctr Vast, Sweden; Hallands Hosp Varberg, Sweden.
    Rosenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Tholander, Bengt
    Uppsala Univ, Sweden.
    Åvall Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Hogberg, Thomas
    Lund Univ, Sweden.
    Lymphovascular space invasion as a predictive factor for lymph node metastases and survival in endometrioid endometrial cancer - a Swedish Gynecologic Cancer Group (SweGCG) studyIn: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226XArticle in journal (Refereed)
    Abstract [en]

    Background: The aim of this study is to evaluate the impact of lymphovascular space invasion (LVSI) on the risk of lymph node metastases and survival in endometrioid endometrial adenocarcinoma. Material and methods: As regard the study design, this is a cohort study based on prospectively recorded data. Patients with endometrioid endometrial adenocarcinoma registered in the Swedish Quality Registry for Gynecologic Cancer 2010-2017 with FIGO stages I-III and verified nodal status were identified (n = 1587). LVSI together with established risk factors, namely DNA ploidy, FIGO grade, myometrial invasion and age, were included in multivariable regression analyses with lymph node metastases as the dependent variable. Associations between the risk factors and overall and relative survival were included in multivariable models. Estimates of risk ratios (RR), hazard ratios (HR), excess mortality rate ratios (EMR), and 95% confidence intervals (95% CI) were calculated. Results: The presence of LVSI presented the strongest association with lymph node metastases (RR = 5.46, CI 3.69-8.07, p amp;lt; .001) followed by deep myometrial invasion (RR = 1.64, CI 1.13-2.37). In the multivariable survival analyses, LVSI (EMR = 7.69, CI 2.03-29.10,) and non-diploidy (EMR = 3.23, CI 1.25-8.41) were associated with decreased relative survival. In sub-analyses including only patients with complete para-aortic and pelvic lymphadenectomy and negative lymph nodes (n = 404), only LVSI (HR = 2.50, CI 1.05-5.98) was associated with a worsened overall survival. Conclusion: This large nationwide study identified LVSI as the strongest independent risk factor for lymph node metastases and decreased survival in patients with endometrioid adenocarcinomas. Moreover, decreased overall survival was also seen in patients with LVSI-positive tumors and negative lymph nodes, indicating that hematogenous dissemination might also be important.

  • 217.
    Stenfelt, Camilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Fertilitetsctr Stockholm, Sweden.
    Armuand, Gabriela
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Wanggren, Kjell
    Karolinska Inst, Sweden.
    Skoog Svanberg, Agneta
    Uppsala Univ, Sweden.
    Sydsjö, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Attitudes toward surrogacy among doctors working in reproductive medicine and obstetric care in Sweden2018In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 97, no 9, p. 1114-1121Article, review/survey (Refereed)
    Abstract [en]

    IntroductionThe aim of this study was to investigate attitudes and opinions towards surrogacy among physicians working within obstetrics and reproductive medicine in Sweden. Material and methodsPhysicians working within medically assisted reproduction (MAR), antenatal care and obstetrics were invited to participate in a cross-sectional nationwide survey study. The study-specific questionnaire measured attitudes and experiences in three domains: attitudes towards surrogacy, assessment of prospective surrogate mothers, and antenatal and obstetric care for surrogate mothers. ResultsOf the 103 physicians who participated (response rate 74%), 63% were positive or neutral towards altruistic surrogacy being introduced in Sweden. However, only 28% thought that it should be publicly financed. Physicians working at fertility clinics were more positive towards legalization as well as public financing of surrogacy compared than were those working within antenatal and delivery care. The majority of the physicians agreed that surrogacy involves the risk of exploitation of womens bodies (60%) and that there is a risk that the commissioning couple might pay the surrogate mother under the table (82%). They also expressed concerns about potential surrogate mothers not being able to understand fully the risks of entering pregnancy on behalf of someone else. ConclusionThere is a relatively strong support among physicians working within obstetrics and reproductive medicine for the introduction of surrogacy in Sweden. However, the physicians expressed concerns about the surrogate mothers health as well as the risk of coercion. Further discussions about legalization of surrogacy should include views from individuals within a wide field of different medical professions and laymen.

  • 218.
    Stenhammar, Lars
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Högberg, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Browaldh, Lars
    Sachsska Childrens Hospital, Sweden.
    Eriksson, Mats
    Uddevalla Central Hospital, Sweden.
    Tjellström, Bo
    Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping. Karolinska Institute, Sweden.
    John Walker-Smith: the father of European paediatric gastroenterology2018In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 107, no 2, p. 219-222Article in journal (Other academic)
    Abstract [en]

    The rapid development of paediatrics during the latter half of the 20th century led to organ‐specific subspecialities being established. One of these was paediatric gastroenterology, which was pioneered by enthusiasts at university departments during the 1960s and 1970s 1, 2. In 1975, the first two European paediatric gastroenterology textbooks appeared in English – ‘Paediatric Gastroenterology’ – edited by Charlotte Anderson and Valerie Burke and – ‘Diseases of the Small Intestine in Childhood’ – by John Walker‐Smith 3. Charlotte Anderson (1915–2002) was professor of paediatrics and child health and director of the Institute of Child Health at the University of Birmingham in the United Kingdom. Dr John Walker‐Smith (Fig. 1) was a London‐based consultant paediatrician and senior lecturer at the Medical College of St. Bartholomew′s Hospital (Barts) and the Queen Elizabeth Hospital for Children and later professor of paediatric gastroenterology at the Royal Free School of Medicine and Royal Free Hospital. He is now an emeritus professor. If we consider Charlotte Anderson to be the mother of European Paediatric Gastroenterology, then John Walker‐Smith is certainly the father....

  • 219.
    Strollo, Rocky
    et al.
    Univ Campus Biomed Roma, Italy.
    Vinci, Chiara
    Univ Campus Biomed Roma, Italy; Queen Mary Univ London, England.
    Napoli, Nicola
    Univ Campus Biomed Roma, Italy; IRCCS Ist Ortoped Galeazzi, Italy.
    Fioriti, Elvira
    Univ Campus Biomed Roma, Italy.
    Maddaloni, Ernesto
    Univ Campus Biomed Roma, Italy.
    Åkerman, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Casas, Rosaura
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Pozzilli, Paolo
    Univ Campus Biomed Roma, Italy; Queen Mary Univ London, England.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Nissim, Ahuva
    Queen Mary Univ London, England.
    Antibodies to oxidized insulin improve prediction of type 1 diabetes in children with positive standard islet autoantibodies2019In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, DIABETES-METABOLISM RESEARCH AND REVIEWS, Vol. 35, no 4, article id e3132Article in journal (Refereed)
    Abstract [en]

    Background

    Antibodies to posttranslationally modified insulin (oxPTM‐INS‐Ab) are a novel biomarker of type 1 diabetes (T1D). Here, we evaluated whether oxPTM‐INS‐Ab can improve T1D prediction in children with positive standard islet autoantibodies (AAB).

    Methods

    We evaluated sensitivity, specificity, accuracy, and risk for progression to T1D associated with oxPTM‐INS‐Ab and the standard islet AAB that include insulin (IAA), GAD (GADA), and tyrosine phosphatase 2 (IA‐2A) in a cohort of islet AAB‐positive (AAB+) children from the general population (median follow‐up 8.8 years).

    Results

    oxPTM‐INS‐Ab was the most sensitive and specific autoantibody biomarker (74% sensitivity, 91% specificity), followed by IA‐2A (71% sensitivity, 91% specificity). GADA and IAA showed lower sensitivity (65% and 50%, respectively) and specificity (66% and 68%, respectively). Accuracy (AUC of ROC) of oxPTM‐INS‐Ab was higher than GADA and IAA (P = 0.003 and P = 0.017, respectively), and similar to IA‐2A (P = 0.896). oxPTM‐INS‐Ab and IA‐2A were more effective than IAA for detecting progr‐T1D when used as second‐line biomarker in GADA+ children. Risk for diabetes was higher (P = 0.03) among multiple AAB+ who were also oxPTM‐INS‐Ab+ compared with those who were oxPTM‐INS‐Ab–. Importantly, when replacing IAA with oxPTM‐INS‐Ab, diabetes risk increased to 100% in children with oxPTM‐INS‐Ab+ in combination with GADA+ and IA‐2A+, compared with 84.37% in those with IAA+, GADA+, and IA‐2A+ (P = 0.04).

    Conclusions

    Antibodies to oxidized insulin (oxPTM‐INS‐Ab), compared with IAA which measure autoantibodies to native insulin, improve T1D risk assessment and prediction accuracy in AAB+ children.

  • 220.
    Strollo, Rocky
    et al.
    University of Campus Biomed Roma, Italy.
    Vinci, Chiara
    University of Campus Biomed Roma, Italy; Queen Mary University of London, England.
    Napoli, Nicola
    University of Campus Biomed Roma, Italy; IRCCS Ist Ortoped Galeazzi, Italy.
    Pozzilli, Paolo
    University of Campus Biomed Roma, Italy; Queen Mary University of London, England.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Nissim, Ahuva
    Queen Mary University of London, England.
    Antibodies to post-translationally modified insulin as a novel biomarker for prediction of type 1 diabetes in children2017In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, no 8, p. 1467-1474Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis We have shown that autoimmunity to insulin in type 1 diabetes may result from neoepitopes induced by oxidative post-translational modifications (oxPTM). Antibodies specific to oxPTM-insulin (oxPTM-INS-Ab) are present in most newly diagnosed individuals with type 1 diabetes and are more common than autoantibodies to native insulin. In this study, we investigated whether oxPTM-INS-Ab are present before clinical onset of type 1 diabetes, and evaluated the ability of oxPTM-INS-Ab to identify children progressing to type 1 diabetes. Methods We used serum samples collected longitudinally from the All Babies in Southeast Sweden (ABIS) cohort tested for the gold standard islet autoantibodies to insulin (IAA), GAD (GADA), tyrosine phosphatase 2 (IA-2A) and zinc transporter 8 (ZnT8A). We studied 23 children who progressed to type 1 diabetes (progr-T1D) and 63 children who did not progress to type 1 diabetes (NP) after a median follow-up of 10.8 years (interquartile range 7.7-12.8). Of the latter group, 32 were positive for one or more islet autoantibodies (NP-AAB(+)). oxPTM-INS-Ab to insulinmodified by (OH)-O-center dot or HOCl were measured by our developed ELISA platform. Results Antibodies to at least one oxPTM-INS were present in 91.3% of progr-T1D children. oxPTM-INS-Ab co-existed with GADA, IA-2A, IAA or ZnT8A in 65.2%, 56.5%, 38.9% and 33.3% progr-T1D children, respectively. In addition, oxPTM-INS-Ab were present in 17.4%, 26.1%, 38.9% and 41.6% of progr-T1D children who were negative for GADA, IA-2A, IAA and ZnT8A, respectively. (OH)-O-center dot-INS-Ab were more common in progr-T1D children than in NP-AAB+ children (82.6% vs 19%; p amp;lt; 0.001) and allowed discrimination between progr-T1D and NP-AAB(+) children with 74% sensitivity and 91% specificity. None of the NP-AAB(-) children were positive for oxPTM-INS-Ab. Conclusions/interpretation oxPTM-INS-Ab are present before the clinical onset of type 1 diabetes and can identify children progressing to type 1 diabetes.

  • 221.
    Stukenborg, J. -B.
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Alves-Lopes, J. P.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Kurek, M.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Albalushi, H.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; Sultan Qaboos Univ, Oman.
    Reda, A.
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden; Katholieke Univ Leuven, Belgium.
    Keros, V.
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Tohonen, V.
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Bjarnason, R.
    Landspitali Univ Hosp, Iceland; Univ Iceland, Iceland.
    Romerius, P.
    Lund Univ, Sweden.
    Sundin, M.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Nystrom, U. Noren
    Umea Univ, Sweden.
    Langenskiold, C.
    Queen Silvia Childrens Hosp, Sweden.
    Vogt, Hartmut
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Henningsohn, L.
    Karolinska Inst, Sweden.
    Mitchell, R. T.
    Univ Edinburgh, Scotland; Edinburgh Royal Hosp Sick Children, Scotland.
    Soder, O.
    Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Petersen, C.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Jahnukainen, K.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; Univ Helsinki, Finland.
    Spermatogonial quantity in human prepubertal testicular tissue collected for fertility preservation prior to potentially sterilizing therapy2018In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 33, no 9, p. 1677-1683Article in journal (Refereed)
    Abstract [en]

    STUDY QUESTION

    Does chemotherapy exposure (with or without alkylating agents) or primary diagnosis affect spermatogonial quantity in human prepubertal testicular tissue?

    SUMMARY ANSWER

    Spermatogonial quantity is significantly reduced in testes of prepubertal boys treated with alkylating agent therapies or with hydroxyurea for sickle cell disease.

    WHAT IS KNOWN ALREADY

    Cryopreservation of spermatogonial stem cells, followed by transplantation into the testis after treatment, is a proposed clinical option for fertility restoration in children. The key clinical consideration behind this approach is a sufficient quantity of healthy cryopreserved spermatogonia. However, since most boys with malignancies start therapy with agents that are not potentially sterilizing, they will have already received some chemotherapy before testicular tissue cryopreservation is considered.

    STUDY DESIGN, SIZE, DURATION

    We examined histological sections of prepubertal testicular tissue to elucidate whether chemotherapy exposure or primary diagnosis affects spermatogonial quantity. Quantity of spermatogonia per transverse tubular cross-section (S/T) was assessed in relation to treatment characteristics and normative reference values in histological sections of paraffin embedded testicular tissue samples collected from 32 consecutive boy patients (aged 6.3 ± 3.8 [mean ± SD] years) between 2014 and 2017, as part of the NORDFERTIL study, and in 14 control samples (from boys aged 5.6 ± 5.0 [mean ± SD] years) from an internal biobank.

    PARTICIPANTS/MATERIALS, SETTING, METHODS

    Prepubertal boys in Sweden, Finland and Iceland who were facing treatments associated with a very high risk of infertility, were offered the experimental procedure of testicular cryopreservation. Exclusion criteria were testicular volumes >10 ml and high bleeding or infection risk. There were 18 patients with a diagnosis of malignancy and 14 patients a non-malignant diagnosis. While 20 patients had the testicular biopsy performed 1–45 days after chemotherapy, 12 patients had not received any chemotherapy. In addition, 14 testicular tissue samples of patients with no reported testicular pathology, obtained from the internal biobank of the Department of Pathology at Karolinska University Hospital, were included as control samples in addition to reference values obtained from a recently published meta-analysis. The quantity of spermatogonia was assessed by both morphological and immunohistochemical analysis.

    MAIN RESULTS AND THE ROLE OF CHANCE

    The main finding was a significant reduction in spermatogonial cell counts in boys treated with alkylating agents or with hydroxyurea for sickle cell disease. The mean S/T values in boys exposed to alkylating agents (0.2 ± 0.3, n = 6) or in boys with sickle cell disease and exposed to hydroxyurea (0.3 ± 0.6, n = 6) were significantly lower (P = 0.003 and P = 0.008, respectively) than in a group exposed to non-alkylating agents or in biobank control samples (1.7 ± 1.0, n = 8 and 4.1 ± 4.6, n = 14, respectively). The mean S/T values of the testicular tissue samples included in the biobank control group and the patient group exposed to non-alkylating agents were within recently published normative reference values.

    LIMITATIONS, REASONS FOR CAUTION

    Normal testicular tissue samples included in this study were obtained from the internal biobank of Karolinska University Hospital. Samples were considered normal and included in the study if no testicular pathology was reported in the analysed samples. However, detailed information regarding previous medical treatments and testicular volumes of patients included in this biobank were not available.

    WIDER IMPLICATIONS OF THE FINDINGS

    This study summarizes, for the first time, spermatogonial quantity in a prepubertal patient cohort just before and after potentially sterilizing treatments. Boys facing cancer and cytotoxic therapies are regarded as the major group who will benefit from novel fertility preservation techniques. There are no previous reports correlating spermatogonial quantity to cumulative exposure to alkylating agents and anthracyclines (non-alkylating agents) and no information about the timing of cytotoxic exposures among this particular patient cohort. For prepubertal boys in whom fertility preservation is indicated, testicular tissue should be obtained before initiation of chemotherapy with alkylating agents, whilst for those with sickle cell disease and treated with hydroxyurea, this approach to fertility preservation may not be feasible.

    STUDY FUNDING/COMPETING INTEREST(S)

    This study was supported by grants from The Swedish Childhood Cancer Foundation (PR2016-0124; TJ2016-0093; PR2015-0073, TJ2015-0046) (J.-B.S. and K.J.), the Jane and Dan Olssons Foundation (2016-33) (J.-B.S.), the Finnish Cancer Society (K.J.), the Foundation for Paediatric Research (J.-B.S.), Kronprinsessan Lovisas Förening För Barnasjukvård/ Stiftelsen Axel Tielmans Minnesfond, Samariten Foundation (J.-B.S.), the Väre Foundation for Paediatric Cancer Research (K.J.) and the Swedish Research Council (2012-6352) (O.S.). R.T.M. was supported by a Wellcome Trust Fellowship (09822). J.P.A.-L. and M.K. were supported by the ITN Marie Curie program ‘Growsperm’ (EU-FP7-PEOPLE-2013-ITN 603568). The authors declare no conflicts of interest.

  • 222.
    Stålberg, Karin
    et al.
    Uppsala University, Sweden.
    Kjölhede, Preben
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Bjurberg, M.
    Skånes University of Sjukhus, Sweden; Lund University, Sweden.
    Borgfeldt, C.
    Lund University, Sweden.
    Dahm-Kahler, P.
    University of Gothenburg, Sweden.
    Falconer, H.
    Karolinska Institute, Sweden.
    Holmberg, E.
    Sahlgrens University Hospital, Sweden; Gothenburg University, Sweden.
    Staf, C.
    Sahlgrens University Hospital, Sweden.
    Tholander, B.
    Uppsala University Hospital, Sweden.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Karolinska Institute, Sweden.
    Rosenberg, Per
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences.
    Högberg, T.
    Lund University, Sweden.
    Risk factors for lymph node metastases in women with endometrial cancer: A population-based, nation-wide register studyOn behalf of the Swedish Gynecological Cancer Group2017In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 140, no 12, p. 2693-2700Article in journal (Refereed)
    Abstract [en]

    The role of lymphadenectomy in the management of early endometrial cancer remains controversial. In the recent ESMO-ESGO-ESTRO guidelines, lymphadenectomy is recommended for patients with endometrioid adenocarcinoma Grade 3 with deep myometrial invasion, but complete agreement was not achieved. In Sweden, DNA aneuploidy has been included as a high-risk factor. The aim of our study was to evaluate the impact of tumor histology, FIGO grade, DNA ploidy and myometrial invasion (MI) on occurrence of lymph node metastasis (LNM) in patients with endometrial cancer. The study design is a retrospective cohort study based on prospectively recorded register data. Endometrial cancer patients registered in the Swedish Quality Registry for Gynecologic Cancer 2010-2015 with FIGO Stages I-III and verified nodal status were included. Data on DNA ploidy, histology, FIGO grade and MI were included in multivariable log-binomial regression analyses with LNM as dependent variable. 1,165 cases fulfilled the inclusion criteria. The multivariable analyses revealed increased risk of LNM in patients with tumors with MI50% (risk ratio [RR]=4.1; 95% confidence interval [CI] 3.0-5.6), nonendometrioid compared to endometrioid histology (RR 1.8; CI 1.4-2.4) and FIGO Grade 3 compared to Grade 1-2 tumors (RR 1.5; CI 1.1-2.0). No statistically significant association between DNA ploidy status and LNM was detected. This population-based, nation-wide study in women with endometrial cancer confirms a strong association between MI50%, nonendometrioid histology and FIGO Grade 3, respectively, and LNM. DNA ploidy should not be included in the preoperative decision making of removing nodes or not. Whats new? Whether lymphadenectomy is beneficial for women with endometrial cancer remains uncertain. Moreover, additional studies are needed to explore factors that reliably predict lymph node metastasis (LNM). Here, multiple factors, including tumor histology, grade of differentiation and DNA aneuploidy, were evaluated for associations with LNM risk in women with endometrial cancer and verified lymph node status. Most significantly, deep myometrial invasion in tumors increased LNM risk fourfold, whereas DNA ploidy had essentially no impact on LNM risk. The findings confirm the predictive relevance of myometrial invasion, histology and grade reported in previous single-center and multicenter studies.

  • 223.
    Sun, Kwang-Hsiao
    et al.
    Nanjing University, Peoples R China.
    Liu, Zhao
    Nanjing University, Peoples R China.
    Liu, Chang-Jian
    Nanjing University, Peoples R China.
    Yu, Tong
    Nanjing University, Peoples R China.
    Zhou, Min
    Nanjing University, Peoples R China.
    Liu, Cheng
    Nanjing University, Peoples R China.
    Ran, Feng
    Nanjing University, Peoples R China.
    Pan, Li-Jia
    Nanjing University, Peoples R China.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    In vivo study of alginate hydrogel conglutinating cells to polycaprolactone vascular scaffolds fabricated by electrospinning2017In: Journal of Biomedical Materials Research. Part B - Applied biomaterials, ISSN 1552-4973, E-ISSN 1552-4981, Vol. 105, no 8, p. 2443-2454Article in journal (Refereed)
    Abstract [en]

    Objective The aim of this study was to explore an innovative cell-seeding technology applied on artificial vascular scaffolds. Methods Scaffolds were fabricated by electrospinning polycaprolactone (PCL) and seeded with rat endothelial progenitor cells differentiated from adipose-derived stem cells. Then, we modified the PCL scaffolds through the use of alginate hydrogel conglutinating cells (AHCC), a blank alginate hydrogel coating (BAHC), and natural sedimentation seeding cells (NSSC). The blank PCL (BP) scaffolds without any modifications were considered the blank control group. After modification, the scaffolds were implanted in a rat model. The implanted scaffolds were harvested and observed using histological and immunohistochemical methods and scanning electron microscopy (SEM) at 1, 2, and 4weeks after implantation, respectively. Results The best regeneration and configuration of the endothelium tissue and the most similar morphology to that of natural endangium was observed qualitatively in the AHCC scaffolds. The BP scaffolds had qualitatively the worst regeneration and configuration and the most dissimilar morphology at the same time point. In the AHCC group, cells could adhere directly on the inner surface of the vascular scaffolds, eliminating the time delay via the NSSC method prior to cell adhesion. Conclusion AHCC are an effective method for seeding cells on vascular scaffolds and can eliminate the time delay for cell adhesion. (C) 2016 Wiley Periodicals, Inc.

  • 224.
    Sundelin, Heléne
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Chang, Zheng
    Karolinska Inst, Sweden.
    Larsson, Henrik
    Karolinska Inst, Sweden.
    Lichtenstein, Paul
    Karolinska Inst, Sweden.
    Almqvist, Catarina
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Tomson, Torbjorn
    Karolinska Inst, Sweden.
    Ludvigsson, Jonas F.
    Karolinska Inst, Sweden; Orebro Univ Hosp, Sweden; Univ Nottingham, England; Columbia Univ, NY USA.
    Epilepsy, antiepileptic drugs, and serious transport accidents A nationwide cohort study2018In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 90, no 13, p. E1111-+Article in journal (Refereed)
    Abstract [en]

    Objectives To investigate the association between epilepsy and antiepileptic drugs and serious transport accidents requiring emergency care or resulting in death.

    Methods We identified 29,220 individuals 18 years or older with epilepsy without cerebral palsy or intellectual disability and 267,637 matched controls using Swedish registers. This nationwide cohort was followed from 2006 to 2013 for serious transport accidents. We used Cox regression to analyze the risk of serious transport accidents between individuals with epilepsy and matched controls, and then stratified Cox regression to compare the risk during periods of medication with the risk during nonmedication period within the same individual with epilepsy. We adjusted for civil status, employment, education, living area, psychiatric disorders prior to the start of follow-up, and psychotropic medication.

    Results Compared to matched controls, individuals with epilepsy were at increased risk of serious transport accidents (hazard ratio [HR] 1.37; 95% confidence interval [CI] 1.29–1.46). There were increased risks of pedestrian accidents (HR 2.24, 95% CI 1.69–2.97), bicycle accidents (HR 1.68, 95% CI 1.49–1.89) and car accidents (HR 1.31, 95% CI 1.19–1.44). However, among patients with a diagnosis of epilepsy, use of antiepileptic drugs did not influence the risk of serious transport accidents in population-level comparisons (HR 0.97; 95% CI 0.85–1.11) or within-individual comparisons (HR 0.99; 95% CI 0.69–1.42).

    Conclusion Serious transportation accidents were more common in individuals with epilepsy, but this risk was independent of use of antiepileptic drugs.

  • 225.
    Sundelin, Heléne
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Ludvigsson, Jonas F.
    Stockholm, Sweden.
    Author response: Autism and epilepsy: A population-based nationwide cohort study2017In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 88, no 1Article in journal (Other academic)
    Abstract [en]

    n/a

  • 226.
    Sundelin, Heléne
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus. Orebro Univ, Sweden.
    Stephansson, Olof
    Karolinska Univ Hosp and Inst, Sweden; Univ Calif Berkeley, CA 94720 USA.
    Hultman, Christina M.
    Karolinska Inst, Sweden; Icahn Sch Med Mt Sinai, NY 10029 USA.
    Ludvigsson, Jonas F.
    Karolinska Inst, Sweden; Orebro Univ Hosp, Sweden; Univ Nottingham, England; Columbia Univ, NY USA.
    Pregnancy outcomes in women with autism: a nationwide population-based cohort study2018In: Clinical Epidemiology, ISSN 1179-1349, E-ISSN 1179-1349, Vol. 10, p. 1817-1826Article in journal (Refereed)
    Abstract [en]

    Background: The consequences of autism in pregnancy outcomes have not been explored before, although it is of crucial importance because of the frequent comorbidities and medication in this group of women. Objectives: To estimate the risk of adverse pregnancy outcomes in women diagnosed with autism. Design: Nationwide population-based cohort study. Setting: Sweden. Participants: Singleton births identified in the Swedish Medical Birth Registry, 2006-2014. A total of 2,198 births to women diagnosed with autism registered in the Swedish National Patient Registry were compared to 877,742 singleton births to women without such a diagnosis. Main outcome and measures: Preterm delivery. Secondary measures were cesarean delivery (emergency and elective), Apgar score amp;lt;7 at 5 minutes, small for gestational age, large for gestational age, stillbirth, gestational diabetes, and preeclampsia. ORs were calculated through logistic regression, adjusted for maternal age at delivery, maternal country of birth, smoking, maternal body mass index, parity, calendar year of birth, and psychotropic and antiepileptic medication during pregnancy. Results: Women with autism were at increased risk of preterm birth (OR=1.30; 95% CI=1.10-1.54), especially medically indicated preterm birth (OR=1.41; 95% CI=1.08-1.82), but not with spontaneous preterm birth. Maternal autism was also associated with an increased risk of elective cesarean delivery (OR=1.44; 95% CI=1.25-1.66) and preeclampsia (OR=1.34; 95% CI=1.08-1.66), but not with emergency cesarean delivery, low Apgar score (amp;lt;7), large for gestational age, gestational diabetes, and stillbirth. In women with medication during pregnancy, there was no increased risk of adverse pregnancy outcome except for induction of delivery (OR=1.33; 95% CI=1.14-1.55). Conclusion and relevance: Maternal autism is associated with preterm birth, likely due to an increased frequency of medically indicated preterm births, but also with other adverse pregnancy outcomes, suggesting a need for extra surveillance during prenatal care.

  • 227.
    Sundell, Micaela
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Ginstman, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Månsson, Agnes
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Forslund, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Brynhildsen, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Patterns of prescription and discontinuation of contraceptives for Swedish women with obesity and normal-weight women2019In: European journal of contraception & reproductive health care, ISSN 1362-5187, E-ISSN 1473-0782Article in journal (Refereed)
    Abstract [en]

    Purpose: This study aimed to explore the prescription of different contraceptive methods to Swedish women with obesity and to compare the pattern of prescription and adherence to treatment between this group and normal-weight women. Materials and methods: This study included 371 women with obesity and 744 matched normal-weight women, aged 18-40. Medical records were scrutinised for the period 1 January 2010 to 31 December 2014. The retrieved variables included: background characteristics, prescribed contraceptive methods, adverse effects, duration of treatment, reason for discontinuation and bleeding pattern. Result: Progestin-only pills were mainly prescribed to women with obesity (44% vs. 20%, p = 0.001) whereas combined hormonal contraception was mainly prescribed to normal-weight women (60% vs. 21%, p amp;lt; 0.0001). Thirty-three percent vs. 25% (p = 0.003) discontinued their contraceptive method within 1 year. The most commonly declared reason for discontinuation was bleeding disturbance (14.7% vs. 9.6%, p = 0.008). Conclusion: The most commonly prescribed contraceptive method in women with obesity was progestin-only pills, but surprisingly many women with obesity were prescribed combined hormonal contraception despite current Swedish and European guidelines. Incident users with obesity were significantly more likely to discontinue their contraceptive method within the first year of the study period, compared with incident normal-weight users.

  • 228.
    Sundqvist, Tommy
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Stenhammar, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Tjellström, Bo
    Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping. Karolinska Institute, Sweden.
    Magnusson, Karl-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Forslund, Tony
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Högberg, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Oral immunoglobulin treatment improved intestinal permeability in children with active Crohns disease2017In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 106, no 4, p. 647-653Article in journal (Refereed)
    Abstract [en]

    Aim: Crohns disease (CD) is a chronic mucosal inflammation that affects the intestinal barrier function, for example, by altering the intestinal permeability. This pilot clinical study investigated the impact of oral human immunoglobulin (OHIG) treatment on permeability characteristics in children with active luminal Crohns disease. Methods: The study was performed at the Department of Paediatrics, Norrkoping Hospital, Sweden. Intestinal permeability was studied in three boys aged 13, 15 and 18 years with active CD, before and after a six-week treatment programme with OHIG, using different-sized polyethylene glycols as the test molecules. Three age-and sex-matched children with active CD treated with exclusive enteral nutrition (EEN) were also studied. Results: OHIG and EEN resulted in virtually similar reductions in the signs and symptoms of mucosal inflammation. However, OHIG, unlike EEN, appeared to normalise mucosal transfer leading to a normalisation of the maximum permeation of the small PEG molecules, as well as less restrictions of the larger PEG molecules. Conclusion: Our study found that OHIG appeared to normalise the mucosal barrier. This suggests that it could offer a new additional and versatile treatment for paediatric CD patients, with a minimal risk of adverse effects.

  • 229.
    Sydsjö, Gunilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Agnafors, Sara
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Bladh, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Josefsson, Ann
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Anxiety in women - a Swedish national three-generational cohort study2018In: BMC Psychiatry, ISSN 1471-244X, E-ISSN 1471-244X, Vol. 18, article id 168Article in journal (Refereed)
    Abstract [en]

    Background: Findings from animal and human studies indicate that anxiety and stress have a negative influence on the child and mother. The aim of this study was to explore the risk for having an anxiety diagnosis and the impact of the diagnosis in a three generational perspective. Methods: The information was retrieved from Swedish population-based registries. All women who gave birth between 1973 and 1977 (n 169,782), their daughters (n 244,152), and subsequently also the offspring of the daughters (n 381,953) were followed until 2013. Results: We found that 4% of the mothers and 6% of the grandmothers had been diagnosed with anxiety. Women who had mothers with an anxiety disorder were more than twice as likely to have an anxiety disorder themselves compared to all other women (OR = 2.20, 95% CI = 2.04-2.30). In the third generation, the children born to mothers with an anxiety disorder, the odds ratio of being diagnosed with anxiety was more than twice as high than for the rest of the population (OR = 2.54, 95% CI = 2.01-3.20). If both the mother and the grandmother had had an anxiety disorder the odds ratio for the child having a diagnosis of anxiety was three times higher (OR = 3.11, 95% CI = 2.04-4.75). Anxiety diagnosis in the two previous generations also increased the likelihood of the child having either more than two inpatient visits or more than 10 outpatient visits (OR = 2.64, 95% CI = 2.40-2.91 and OR = 2.21, 95% CI = 2.01-2.43, respectively). Conclusions: The intergenerational effect on anxiety is high. In order to minimize the risk for further transmission of anxiety disorders, increased awareness and generous use of effective treatment regimes might be of importance.

  • 230.
    Sydsjö, Gunilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Lindell Pettersson, Malin
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Bladh, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Skoog Svanberg, Agneta
    Uppsala Univ, Sweden.
    Lampic, Claudia
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Nedstrand, Elizabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Evaluation of risk factors’ importance on adverse pregnancy and neonatal outcomes in women aged 40 years or older2019In: BMC Pregnancy and Childbirth, ISSN 1471-2393, E-ISSN 1471-2393, Vol. 19, article id 92Article in journal (Refereed)
    Abstract [en]

    Background

    Women of advanced age (40 years or older) are generally, at risk for pregnancy and delivery related problems. In addition, there is limited knowledge on being of advanced age and having been given Assisted Reproductive Treatment (ART) and its association with negative obstetric outcomes. Therefore, data from the Swedish Medical Birth Register was used to investigate pregnancy and neonatal outcomes for women aged 40 or more who had given birth. The secondary aim was to compare the obstetric outcomes of women who had used ART and women who had not undergoneART while adjusting for marital status across the age groups.

    Method

    Women of advanced age who had given birth in Sweden during 2007–2012 formed the index group, n = 37,558; a reference group of women comprised 71,472 women under the age of 40. An additional subgroup of women aged 45 or older when giving birth was also formed, n = 2229. The obstetric and neonatal data for all the women was derived from national register data.

    Results

    Women of advanced age were more often single, had undergone ART, and more often experienced adverse obstetric outcomes than did younger women. The neonate’s health was also more often adversely affected expressed as being born with low birth weight and Small for Gestational Age (SGA), having lower Apgar scores, and having more health problems during the first week compared to the reference group.

    Conclusions

    Women who are approaching the upper limit of fecundity are at greater risk for having children who are preterm and SGA. The adverse effects of being preterm and SGA may have negative long-term effects, not only on the children but also on the mothers. This needs to be addressed more frequently in a clinical setting when advising women of all ages on pregnancy and ART treatment.

  • 231.
    Sydsjö, Gunilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Skoog Svanberg, Agneta
    Uppsala Univ, Sweden.
    Lampic, Claudia
    Karolinska Inst, Sweden.
    Cross-border surrogacy: Experiences of heterosexual and gay parents in Sweden2019In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 98, no 1, p. 68-76Article in journal (Refereed)
    Abstract [en]

    Introduction Surrogacy is a controversial method of assisted reproduction that is not permitted in many countries. While there is some evidence that families following surrogacy seem to fare well, there is limited knowledge about the experiences of parents who turn to cross-border surrogacy. The aim of the present study was therefore to investigate the experiences of heterosexual parents and gay fathers who chose cross-border surrogacy to have a child. Material and methods This cross-sectional survey describes the experiences of 30 families (18 heterosexual parent and 12 gay father families). Participants were recruited through a website for a Swedish surrogacy interest group. The participants were requested individually to complete a postal questionnaire including study-specific questions on their experiences of disclosure and the Swedish Parenting Stress Questionnaire. Results All couples but one were still living together and had a child (3 months to 5 years). Parenting stress levels were generally low and were not related to sexual orientation. While almost all parents were open about the childs mode of conception in contacts with health care, gay fathers were significantly more open about using surrogacy in contacts with preschool (P = 0.004) and child recreational activities (P = 0.005) compared with heterosexual parents. A majority described being treated positively or "as any other parent" in these contexts. Conclusions Heterosexual and gay parents reported low levels of parenting stress and generally experienced positive or neutral reactions to their parenthood in contacts with healthcare providers, in preschool, and in the childs recreational activities.

  • 232.
    Sydsjö, Gunilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Törnblom, Pia
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Gäddlin, Per-Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Finnström, Orvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Leijon, Ingemar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Nelson Follin, Nina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus. Karolinska Univ Hosp, Sweden.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Hammar, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Women born with very low birth weight have similar menstrual cycle pattern, pregnancy rates and hormone profiles compared with women born at term2019In: BMC Women's Health, ISSN 1472-6874, E-ISSN 1472-6874, Vol. 19, no 1, article id 56Article in journal (Refereed)
    Abstract [en]

    Background

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

    Aim

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

    Methods

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

    Results

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

    Conclusion

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

  • 233.
    Tavira Iglesias, Beatriz
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Barcenilla, Hugo
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Wahlberg, Jeanette
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Achenbach, Peter
    Tech Univ Munich, Germany.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Casas, Rosaura
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Intralymphatic Glutamic Acid Decarboxylase-Alum Administration Induced Th2-Like-Specific Immunomodulation in Responder Patients: A Pilot Clinical Trial in Type 1 Diabetes2018In: Journal of Diabetes Research, ISSN 2314-6745, E-ISSN 2314-6753, article id 9391845Article in journal (Refereed)
    Abstract [en]

    GAD-alum given into lymph nodes to type 1 diabetes patients participating in an open-label pilot trial resulted in preservation of C-peptide similar to promising results from other trials. Here, we compared the immunomodulatory effect of giving GAD-alum directly into lymph nodes versus that induced by subcutaneous administration. Samples from T1D patients (n = 6) who received 4 mu g GAD-alum into lymph nodes (LNs), followed by two booster injections one month apart, and from patients (n = 6) who received two subcutaneous injections (SC) (20 mu g) given one month apart were compared. GADA, IA-2A, GADA subclasses, IgE, GAD(65)-induced cytokines, PBMC proliferation, and T cell markers were analyzed. Lower doses of GAD-alum into LN induced higher GADA levels than SC injections and reduced proliferation and IgG1 GADA subclass, while enhancing IgG2, IgG3, and IgG4. The cytokine profile was dominated by the Th2-associated cytokine IL-13, and GAD(65) stimulation induced activated CD4 T cells. Patients responding clinically best account for most of the immunological changes. In contrast, SC treatment resulted in predominant IgGI, predominant IFN-gamma, higher proliferation, and activated CD4 and CD8 cells. Patients from the LN group with best metabolic outcome seemed to have common immune correlates related to the treatment.

  • 234.
    Tavira Iglesias, Beatriz
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Chéramy, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Axelsson Chéramy, Stina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Åkerman, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Casas, Rosaura
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Effect of simultaneous vaccination with H1N1 and GAD-alum on GAD(65)-induced immune response2017In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, no 7, p. 1276-1283Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis A European Phase III trial of GAD formulated with aluminiumhydroxide (GAD-alum) failed to reach its primary endpoint (preservation of stimulated C-peptide secretion from baseline to 15 months in type 1 diabetes patients), but subgroup analysis showed a clinical effect when participants from Nordic countries were excluded, raising concern as to whether the mass vaccination of the Swedish and Finnish populations with the Pandemrix influenza vaccine could have influenced the study outcomes. In the current study, we aimed to assess whether Pandemrix vaccination affects the specific immune responses induced by GAD-alum and the C-peptide response. Methods In this secondary analysis, we analysed data acquired from the Swedish participants in the Phase III GAD-alum trial who received subcutaneous GAD-alum vaccination (two doses, n = 43; four doses, n = 46) or placebo (n = 48). GAD autoantibodies (GADA) and H1N1 autoantibodies, GAD(65)-induced cytokine secretion and change in fasting and stimulated C-peptide levels from baseline to 15 months were analysed with respect to the relative time between H1N1 vaccination and the first injection of GAD-alum. Results GADA levels at 15 months were associated with the relative time between GAD-alum and Pandemrix administration in participants who received two doses of the GAD-alum vaccine (p = 0.015, r = 0.4). Both in participants treated with two doses and four doses of GAD-alum, GADA levels were higher when the relative time between vaccines was amp;gt;= 210 days (p amp;lt; 0.05). In the group that received two doses of GAD-alum, levels of several GAD(65)-induced cytokines were higher in participants who received the H1N1 vaccination and the first GADalum injection at least 150 days apart, and the change in fasting and stimulated C-peptide at 15 months was associated with the relative time between vaccines. Neither of these effects were observed in individuals who received four doses of GAD-alum. Conclusions/interpretation In individuals who received two doses of GAD-alum, receiving the Pandemrix vaccine closer to the first GAD-alum injection, i.e. amp;lt; 150 days, seemed to affect both GAD(65)-induced immune response and C-peptide preservation.

  • 235.
    Thomson, John P.
    et al.
    MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, The University of Edinburgh, Crewe Road, Edinburgh, UK.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Meehan, Richard R.
    MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, The University of Edinburgh, Crewe Road, Edinburgh, UK.
    5-Hydroxymethylcytosine Profiling in Human DNA2017In: Population Epigenetics: Methods and Protocols / [ed] Paul Haggarty; Kristina Harrison, Humana Press, 2017, Vol. 1589, p. 89-98Chapter in book (Refereed)
    Abstract [en]

    Since its "re-discovery" in 2009, there has been significant interest in defining the genome-wide distribution of DNA marked by 5-hydroxymethylation at cytosine bases (5hmC). In recent years, technological advances have resulted in a multitude of unique strategies to map 5hmC across the human genome. Here we discuss the wide range of approaches available to map this modification and describe in detail the affinity based methods which result in the enrichment of 5hmC marked DNA for downstream analysis.

  • 236.
    Tordön, Rikard
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences.
    Svedin, Carl Göran
    Linköping University, Department of Clinical and Experimental Medicine, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Fredlund, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Jonsson, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Pribe, Gisela
    Linköping University, Department of Clinical and Experimental Medicine, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences.
    Sydsjö, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Background, experience of abuse, and mental health among adolescents in out-of-home care: a cross-sectional study of a Swedish high school national sample2019In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 73, no 1, p. 16-23Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To compare experiences for adverse events, especially sexual abuse, and mental health in a group of high school students in out-of-home care with a representative sample of peers of the same age and similar educational attainment living with their parents.

    MATERIALS AND METHODS: A sample of 5839 students in the third year of Swedish high school, corresponding to a response rate of 59.7%, answered a study specific questionnaire. Data from 41 students living in out-of-home care were compared with data from peers not in out-of-home care in a cross-sectional analyze.

    RESULTS: Students in out-of-home care had more often an immigrant background and a non-heterosexual orientation, had more often experienced physical and penetrative sexual abuse, and more often sought healthcare for mental problems. Disclosure of sexual abuse was less common, and acts of persuasion or adults' use of their social position was more common among students in out-of-home care.

    CONCLUSIONS: Even where the protective factor 'senior educational attainment' is present, risks for abuse and poor mental health are evident for adolescents in out-of-home care. Disclosure of adversity, when it has occurred, ought to be higher among these adolescents with regular contact with social services, but our findings indicate tendencies for the opposite. We therefore suggest routines to be established to screen for adverse life events and mental health actively, along with general and systematic assessments of adversity and mental health during care.

  • 237.
    van Ettinger-Veenstra, Helene M
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Widen, Carin
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Karlsson, Thomas
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Leijon, Ingemar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Nelson Follin, Nina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping. Karolinska University Hospital, Sweden.
    Neuroimaging of decoding and language comprehension in young very low birth weight (VLBW) adolescents: Indications for compensatory mechanisms2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 10, article id e0185571Article in journal (Refereed)
    Abstract [en]

    In preterm children with very low birth weight (VLBW amp;lt;= 1500 g), reading problems are often observed. Reading comprehension is dependent on word decoding and language comprehension. We investigated neural activation-within brain regions important for reading-related to components of reading comprehension in young VLBW adolescents in direct comparison to normal birth weight (NBW) term-born peers, with the use of functional magnetic resonance imaging (fMRI). We hypothesized that the decoding mechanisms will be affected by VLBW, and expect to see increased neural activity for VLBW which may be modulated by task performance and cognitive ability. The study investigated 13 (11 included in fMRI) young adolescents (ages 12 to 14 years) born preterm with VLBW and in 13 NBW controls (ages 12-14 years) for performance on the Block Design and Vocabulary subtests of the Wechsler Intelligence Scale for Children; and for semantic, orthographic, and phonological processing during an fMRI paradigm. The VLBW group showed increased phonological activation in left inferior frontal gyrus, decreased orthographic activation in right supramarginal gyrus, and decreased semantic activation in left inferior frontal gyrus. Block Design was related to altered right-hemispheric activation, and VLBW showed lower WISC Block Design scores. Left angular gyrus showed activation increase specific for VLBW with high accuracy on the semantic test. Young VLBW adolescents showed no accuracy and reaction time performance differences on our fMRI language tasks, but they did exhibit altered neural activation during these tasks. This altered activation for VLBW was observed as increased activation during phonological decoding, and as mainly decreased activation during orthographic and semantic processing. Correlations of neural activation with accuracy on the semantic fMRI task and with decreased WISC Block Design performance were specific for the VLBW group. Together, results suggest compensatory mechanisms by recruiting additional brain regions upon altered neural development of decoding for VLBW.

  • 238.
    Verder, Henrik
    et al.
    Holbaek University Hospital, Denmark.
    Heiring, Christian
    University of Copenhagen, Denmark.
    Clark, Howard
    University of Southampton, England.
    Sweet, David
    Royal Matern Hospital, North Ireland.
    Jessen, Torben E.
    Holbaek University Hospital, Denmark.
    Ebbesen, Finn
    Aalborg University, Denmark.
    Bjoerklund, Lars J.
    Skåne University Hospital, Sweden; Lund University, Sweden.
    Andreasson, Bengt
    Skåne University Hospital, Lund, Sweden.
    Bender, Lars
    Aalborg University, Denmark.
    Bertelsen, Aksel
    Holbaek University Hospital, Holbaek, Denmark.
    Dahl, Marianne
    University of Southen, Denmark.
    Eschen, Christian
    Holbaek University Hospital, Holbaek, Denmark.
    Fenger-Gron, Jesper
    University of Soouthern, Denmark.
    Hoffmann, Stine F.
    University of Copenhagen, Denmark.
    Hoeskuldsson, Agnar
    Holbaek University Hospital, Denmark.
    Bruusgaard-Mouritsen, Maria
    Holbaek University Hospital, Denmark.
    Lundberg, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Postle, Anthony D.
    University of Southampton, England.
    Schousboe, Peter
    Holbaek University Hospital, Denmark.
    Schmidt, Peter
    University of Copenhagen, Denmark.
    Stanchev, Hristo
    Naestved University Hospital, Denmark.
    Sorensen, Lars
    Holbaek University Hospital, Denmark.
    Rapid test for lung maturity, based on spectroscopy of gastric aspirate, predicted respiratory distress syndrome with high sensitivity2017In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 106, no 3, p. 430-437Article in journal (Refereed)
    Abstract [en]

    Aim: Respiratory distress syndrome (RDS) is a major cause of mortality and morbidity in premature infants. By the time symptoms appear, it may already be too late to prevent a severe course, with bronchopulmonary dysplasia or mortality. We aimed to develop a rapid test of lung maturity for targeting surfactant supplementation. Methods: Concentrations of the most surface-active lung phospholipid dipalmitoylphosphatidylcholine and sphingomyelin in gastric aspirates from premature infants were measured by mass spectrometry and expressed as the lecithin/sphingomyelin ratio (L/S). The same aspirates were analysed with mid-infrared spectroscopy. Subsequently, L/S was measured in gastric aspirates and oropharyngeal secretions from another group of premature infants using spectroscopy and the results were compared with RDS development. The 10-minute analysis required 10 mu L of aspirate. Results: An L/S algorithm was developed based on 89 aspirates. Subsequently, gastric aspirates were sampled in 136 infants of 24-31 weeks of gestation and 61 (45%) developed RDS. The cut-off value of L/S was 2.2, sensitivity was 92%, and specificity was 73%. In 59 cases, the oropharyngeal secretions had less valid L/S than gastric aspirate results. Conclusion: Our rapid test for lung maturity, based on spectroscopy of gastric aspirate, predicted RDS with high sensitivity.

  • 239.
    Vicente-Carrillo, Alejandro
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Álvarez-Rodríguez, Manuel
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health.
    Rodríguez-Martínez, Heriberto
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health.
    The CatSper channel modulates boar sperm motility during capacitation.2017In: Reproductive biology, ISSN 2300-732X, Vol. 17, no 1, p. 69-78Article in journal (Refereed)
    Abstract [en]

    The cation channel of sperm (CatSper) comprises four transmembrane subunits specifically expressed in human, equine, murine and ovine spermatozoa, apparently implicated in capacitation, hyperactivation and acrosome exocytosis. Western blotting and immunocytochemistry showed hereby that CatSper subunits are also present in boar spermatozoa, primarily over the sperm neck, tail and cytoplasmic droplets; albeit CatSper -1 presented in addition some distribution over the membrane of the acrosome and CatSper -2 and -4 over the membrane of the post-acrosome. The role of the Catsper channel in boar spermatozoa was investigated by extending the spermatozoa in media containing different calcium (Ca(2+)) availability and exposure to the capacitation-trigger bicarbonate, to progesterone or CatSper inhibitors (Mibefradil and NNC 55-0396), separately or sequentially, at physiological and toxicological doses. Extracellular Ca(2+) availability, combined with bicarbonate exposure (capacitation-inducing conditions) decreased sperm motility, similarly to when spermatozoa incubated in capacitation-inducing conditions was exposed to Mibefradil and NNC 55-0396. Exposure of these spermatozoa to progesterone did not cause significant changes in sperm motility and nor did it revert its decrease induced by CatSper antagonists. In conclusion, the CatSper channel regulates sperm motility during porcine capacitation-related events in vitro.

  • 240.
    Vikström, Josefin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Josefsson, Ann
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health.
    Hammar, Mats
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health.
    Bladh, Marie
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health.
    Sydsjö, Gunilla
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health.
    Risk of postpartum psychosis after IVF treatment: a nationwide case-control study2017In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 32, no 1, p. 139-146Article in journal (Refereed)
    Abstract [en]

    STUDY QUESTION: Is the risk of postpartum psychosis (PPP) increased in women who give birth after IVF treatment compared to after spontaneous conception? SUMMARY ANSWER: The risk of PPP is not higher in the group of women who give birth after IVF treatment compared with women who give birth after spontaneous conception. WHAT IS KNOWN ALREADY: Women who conceive using IVF treatment can experience higher levels of pregnancy-specific distress and are at increased risk of pre-eclampsia, an immune-related condition which in turn has been linked to PPP, as well as other pregnancy and delivery complications, which also serve as PPP risk factors. It is not known whether the risk of PPP is increased in women who have conceived using IVF treatment. STUDY DESIGN, SIZE, DURATION: A nationwide, register-based, case-control study of all primiparous women who had given birth after IVF treatment between 1988 and 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: Information about 10 412 women was collected from the Swedish IVF register. A control group of women who had given birth after spontaneous conception was selected from the Swedish Medical Birth Register (n = 18 624). PPP diagnoses, identified using ICD-10 diagnostic codes F20-31 and F531 the first year postpartum, were collected from the National Patient Register. Associations between PPP and IVF/spontaneous conception were evaluated using chi-square tests and logistic regression analyses while controlling for known risk factors of PPP. MAIN RESULTS AND THE ROLE OF CHANCE: There were no differences in PPP prevalence between the IVF group and the control group (0.3%, n = 29 versus 0.4%, n = 77) in the chi-square analysis (P = 0.169) or the multiple logistic regression analyses (P = 0.646; odds ratio (OR): 1.178; 95% CI: 586-2.365). No associations between pregnancy or delivery complications and PPP were found. A history of any psychiatric disorder (P amp;lt; 0.001; OR = 40.7; 95% CI = 23.9-69.5), or specifically a psychotic (P amp;lt; 0.001; OR = 324.1; 95% CI = 131.3-800.0), bipolar (P amp;lt; 0.001; OR = 516.1; 95% CI = 264.3-1008.1), depressive (P amp;lt; 0.001; OR = 27.5; 95% CI = 16.2-46.5), anxiety (P amp;lt; 0.001; OR = 12.9; 95% CI = 7.4-22.6) or personality disorder (P amp;lt; 0.001; OR = 27.3; CI = 11.8-63.0), all significantly increased the risk of PPP. LIMITATIONS REASONS FOR CAUTION: PPP is a rare condition, hence the number of individuals was small. Since all women for whom information was available from all registers were included, it was not possible to further increase the power of the study using this design. WIDER IMPLICATIONS OF THE FINDINGS: Since this study is the first to examine risk of PPP after IVF treatment, more studies are needed to verify these results. The generalizability is restricted to primiparous women in western countries. This study confirms the results of previous studies in showing a history of mental illness to be the major risk factor for PPP.

  • 241.
    Vikström, Josefin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Sydsjö, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Hammar, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Bladh, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Josefsson, Ann
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health.
    Risk of postnatal depression or suicide after in vitro fertilisation treatment: a nationwide case–control study2017In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 124, no 3, p. 435-442Article in journal (Refereed)
    Abstract [en]

    Objective

    To examine whether women who undergo in vitro fertilisation (IVF) treatment are at greater risk of postnatal suicide or postnatal depression (PND) requiring psychiatric care, compared with women who conceive spontaneously.

    Design

    Case–control study using data from national registers.

    Setting

    Sweden during the period 2003–2009.

    Population

    Cases were 3532 primiparous women who had given birth following IVF treatment. An aged-matched control group of 8553 mothers was randomly selected from the medical birth register.

    Methods

    Logistic regression analyses were performed with PND as the outcome, and with known risk factors of PND as well as IVF/spontaneous birth as covariates.

    Main outcome measures

    Postnatal depression (PND), defined as diagnoses F32–F39 of the tenth edition of the International Classification of Diseases (ICD–10), within 12 months of childbirth.

    Results

    Initial analyses showed that PND was more common in the control group than in the IVF group (0.8 versus 0.4%; P = 0.04); however, these differences disappeared when confounding factors were controlled for. A history of any psychiatric illness (P = 0.000; odds ratio, OR = 25.5; 95% confidence interval, 95% CI = 11.7–55.5), any previous affective disorder (P = 0.000; OR = 26.0; 95% CI = 10.5–64.0), or specifically a personality disorder (P = 0.028; OR = 3.8; 95% CI = 1.2–12.7) increased the risk of PND. No woman in either group committed suicide during the first year after childbirth.

    Conclusions

    Whereas mothers who receive IVF treatment are not at increased risk of PND, the risk is increased among mothers with a history of mental illness. Tweetable abstract A Swedish study on 3532 women showed that IVF treatment does not increase the risk of postnatal depression.

  • 242.
    Wang, Hui
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. University of Texas MD Anderson Cancer Centre, TX 77030 USA.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    GAB2 regulates type 2 T helper cell differentiation in humans2017In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 96, p. 234-237Article in journal (Refereed)
    Abstract [en]

    Th2 cell differentiation involves complex changes in expression of multiple genes, many of which have poorly characterized roles. In a gene expression microarray analysis of human primary CD4(+) effector T subsets, we identified that an adaptor protein, GAB2, was preferentially expressed in human Th2 cells. The role of GAB2 in human Th2 cells is unknown. Through analysis of primary and in vitro differentiated human T effector subsets, we confirmed that human Th2 cells preferentially expressed GAB2. Further analysis of public gene expression microarray data of STAT6-knockdowned Th2 cells indicated that GAB2 expression was regulated by IL-4 and STAT6. Both siRNA knockdown and ectopic expression of GAB2 in activated T cells showed that GAB2 positively regulated IL-4 and IL-13 expression in human Th2 cells. We hence identified the adaptor protein, GAB2, as an important novel regulator of the human Th2 immune response.

  • 243.
    Ward, Liam
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Sex differences in atherosclerosis and exercise effects2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Cardiovascular disease (CVD) is the leading cause of death globally, with atherosclerosis being the main cause of cardiovascular diseases. Atherosclerosis is an inflammatory disease of the blood vessel wall, which over time will cause thickening and hardening of the vessel wall. Atherosclerosis can result in catastrophic vascular events, such as myocardial infarction and stroke. There are distinct sex differences in CVD mortality at different ages, before menopause women have a lower mortality of CVD in comparison to men, which equalises after menopause. In addition to sex differences in the incidence of CVD, there are also distinct sex differences in the phenotype of atherosclerotic plaques, with men generally developing more severe and vulnerable plaques that are at risk of rupture.

    This thesis aimed to investigate the sex differences in atherosclerosis, in particular how the proteome and pathophysiology differs. In addition, we sought to investigate the potential benefit of an exercise programme, in reducing CVD risks, using a randomised controlled trial including postmenopausal women.

    Sex differences in atherosclerosis were first investigated via proteomic analysis of human carotid endarterectomy samples. Initially, five intraplaque biopsies were taken from distinct atheroma regions, including; internal control, fatty streak, plaque shoulder, plaque centre, and fibrous cap. Protein extracts from these biopsies were subjected to analysis by mass spectrometry. The novel sampling method was successful in reducing the effect of plaque heterogeneity, a limitation in previous proteomic studies of atherosclerosis, and a number of previously unreported proteins were identified in human carotid atheroma. In addition to this, with the inclusion of multivariate statistical modelling, it was found that 43 proteins significantly discriminated the carotid atheroma between men and women. These proteins were grouped by function, and it was found that atheroma from men was associated with the increased abundance of inflammatory response proteins, including phospholipase-A2 membrane associated and lysozyme C, and atheroma from women was associated with increased abundance of blood coagulation, complement activation, and transport proteins, notably including; antithrombin-III, coagulation factor XII, and afamin. In addition, differences were also ii observed in the abundance of iron metabolism related proteins. These sex differences were further expanded upon from a pathophysiological perspective. Immunohistochemistry stainings of ferritin and transferrin receptor 1 were found significantly increased in the atheroma from men. Moreover, the levels of plasma haemoglobin were also significantly increased in men and were associated with the development of more vulnerable and severe plaque types. The more vulnerable and severe plaque types were also associated with significantly greater macrophage infiltration. In summary, these results are indicative of men developing atheroma with greater inflammation that are more vulnerable, due to increased iron and inflammatory proteins and macrophage infiltration, whereas atheroma from women develop with less inflammation and a more stable phenotype.

    The randomised controlled clinical trial aimed at investigating the effects of resistance training (RT), over a 15-week period, in postmenopausal women. Plasma samples were obtained at week-0 and week-15 of the study period, and analyses were performed primarily using a series of immunoassays. Results showed that women participating in RT, with good compliance, were associated with significant decreases in plasma levels of ferritin, lipids, and inflammatory adipokines. These results suggest that the use of regular RT may be a beneficial intervention in reducing the levels of body iron, lipids, and inflammation, all of which are risk factors for the development of CVD. However, validation studies are required in a larger cohort of postmenopausal women, in addition to the inclusion or complementary studies in middle-aged men.

    In summary, the works included in this thesis further expand on the current knowledge of sex differences in atherosclerosis, and also provides information on the potential of an exercise intervention to beneficially reduces the effects of known risk factors of CVD.

    List of papers
    1. Distinctive proteomic profiles among different regions of human carotid plaques in men and women
    Open this publication in new window or tab >>Distinctive proteomic profiles among different regions of human carotid plaques in men and women
    Show others...
    2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 26231Article in journal (Refereed) Published
    Abstract [en]

    The heterogeneity of atherosclerotic tissue has limited comprehension in proteomic and metabolomic analyses. To elucidate the functional implications, and differences between genders, of atherosclerotic lesion formation we investigated protein profiles from different regions of human carotid atherosclerotic arteries; internal control, fatty streak, plaque shoulder, plaque centre, and fibrous cap. Proteomic analysis was performed using 2-DE with MALDI-TOF, with validation using nLC-MS/MS. Protein mapping of 2-DE identified 52 unique proteins, including 15 previously unmapped proteins, of which 41 proteins were confirmed by nLC-MS/MS analysis. Expression levels of 18 proteins were significantly altered in plaque regions compared to the internal control region. Nine proteins showed site-specific alterations, irrespective of gender, with clear associations to extracellular matrix remodelling. Five proteins display gender-specific alterations with 2-DE, with two alterations validated by nLC-MS/MS. Gender differences in ferritin light chain and transthyretin were validated using both techniques. Validation of immunohistochemistry confirmed significantly higher levels of ferritin in plaques from male patients. Proteomic analysis of different plaque regions has reduced the effects of plaque heterogeneity, and significant differences in protein expression are determined in specific regions and between genders. These proteomes have functional implications in plaque progression and are of importance in understanding gender differences in atherosclerosis.

    Place, publisher, year, edition, pages
    NATURE PUBLISHING GROUP, 2016
    National Category
    Biochemistry and Molecular Biology
    Identifiers
    urn:nbn:se:liu:diva-129495 (URN)10.1038/srep26231 (DOI)000376554600001 ()27198765 (PubMedID)
    Note

    Funding Agencies|Swedish Heart Lung Foundation; Linkoping University Hospital Research foundation; Swedish Institute; China Scholarship Council

    Available from: 2016-06-20 Created: 2016-06-20 Last updated: 2019-04-17
    2. Proteomics and multivariate modelling reveal sex-specific alterations in distinct regions of human carotid atheroma
    Open this publication in new window or tab >>Proteomics and multivariate modelling reveal sex-specific alterations in distinct regions of human carotid atheroma
    2018 (English)In: Biology of Sex Differences, ISSN 2042-6410, Vol. 9, article id 54Article in journal (Refereed) Published
    Abstract [en]

    BackgroundAtherosclerotic lesions are comprised of distinct regions with different proteomic profiles. Men and women develop differences in lesion phenotype, with lesions from women generally being more stable and less prone to rupture. We aimed to investigate the differences in proteomic profiles between sexes, including distinct lesion regions, to identify altered proteins that contribute to these differences observed clinically.MethodsCarotid endarterectomy samples (ten men/ten women) were obtained, and intraplaque biopsies from three distinct regions (internal control, fatty streak and plaque) were analysed by tandem-mass spectrometry. Multivariate statistical modelling, using orthogonal partial least square-discriminant analysis, was used to discriminate the proteomes between men and women.ResultsMultivariate discriminant modelling revealed proteins from 16 functional groups that displayed sex-specific associations. Additional statistics revealed ten proteins that display region-specific alterations when comparing sexes, including proteins related to inflammatory response, response to reactive oxygen species, complement activation, transport and blood coagulation. Transport protein afamin and blood coagulation proteins antithrombin-III and coagulation factor XII were significantly increased in plaque region from women. Inflammatory response proteins lysozyme C and phospholipase A2 membrane-associated were significantly increased in plaque region from men. Limitations with this study are the small sample size, limited patient information and lack of complementary histology to control for cell type differences between sexes.ConclusionsThis pilot study, for the first time, utilises a multivariate proteomic approach to investigate sexual dimorphism in human atherosclerotic tissue, and provides an essential proteomic platform for further investigations to help understand sexual dimorphism and plaque vulnerability in atherosclerosis.

    Place, publisher, year, edition, pages
    BMC, 2018
    Keywords
    Afamin; Atherosclerosis; Lysozyme C; Mass spectrometry; Serine protease inhibitors; Vulnerability
    National Category
    Medical Genetics
    Identifiers
    urn:nbn:se:liu:diva-153822 (URN)10.1186/s13293-018-0217-3 (DOI)000454616000001 ()30594242 (PubMedID)
    Note

    Funding Agencies|Swedish Heart Lung Foundation; Torsten and Ragnar Soderbergs Foundation; Stroke Foundation; Olle Engkvist Foundation; Swedish Gamla Tjanarinnor Foundation; Linkoping University Hospital Research Fund

    Available from: 2019-01-11 Created: 2019-01-11 Last updated: 2019-05-02
    3. Carotid Atheroma From Men Has Significantly Higher Levels of Inflammation and Iron Metabolism Enabled by Macrophages
    Open this publication in new window or tab >>Carotid Atheroma From Men Has Significantly Higher Levels of Inflammation and Iron Metabolism Enabled by Macrophages
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    2018 (English)In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 49, no 2, p. 419-425Article in journal (Refereed) Published
    Abstract [en]

    Background and Purpose-Men differ from women in the manifestation of atherosclerosis and iron metabolism. Intraplaque hemorrhage and hemoglobin (Hb) catabolism by macrophages are associated with atherosclerotic lesion instability. The study aims were to investigate sex differences in (1) lesion severity in relation to blood Hb, (2) iron homeostasis in human carotid plaques, and (3) macrophage polarization within atheroma. Methods-The carotid artery samples from 39 men and 23 women were immunostained with cell markers for macrophages, smooth muscle cells, ferritin, and TfR1 (transferrin receptor 1), which were further analyzed according to sex in relation to iron, Hb, and lipids in circulation. Additionally, samples of predefined regions from human carotid atherosclerotic lesions, including internal controls, were used for proteomic analysis by mass spectrometry. Results-Male patients, compared with women, had larger necrotic cores and more plaque rupture, which were associated with higher levels of Hb. Atheroma of male patients had significantly higher levels of Hb in circulation and CD68 macrophages, ferritin, and TfR1 in lesions. CD68 macrophages were significantly correlated with ferritin and TfR1. Plaques from male patients comparatively possessed higher levels of inflammatory macrophage subsets, CD86 (M1) and CD163 (M2), but lower levels of STF (serotransferrin) and HPX (hemopexin). Conclusions-Male patients with carotid atheroma had more advanced and ruptured lesions associated with significantly higher levels of inflammatory macrophage infiltration and high iron stores in the blood and in their plaques. These findings help to understand sex differences and iron metabolism in atherosclerosis and factors related to atheroma progression.

    Place, publisher, year, edition, pages
    LIPPINCOTT WILLIAMS & WILKINS, 2018
    Keywords
    atherosclerosis; ferritins; hemoglobins; hemopexin; macrophages; male
    National Category
    Neurology
    Identifiers
    urn:nbn:se:liu:diva-144876 (URN)10.1161/STROKEAHA.117.018724 (DOI)000422928000035 ()29284736 (PubMedID)
    Note

    Funding Agencies|Swedish Heart-Lung Foundation; Torsten and Ragnar Soderbergs Foundation; Stroke Foundation; Olle Engkvist Foundation; Swedish Gamla Tjanarinnor Foundation; Linkoping University; Linkoping University Hospital Research Fund

    Available from: 2018-02-09 Created: 2018-02-09 Last updated: 2019-05-02
  • 244.
    Ward, Liam
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Ljunggren, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Li, Wei
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Yuan, Ximing
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Exposure to atheroma-relevant 7-oxysterols causes proteomic alterations in cell death, cellular longevity, and lipid metabolism in THP-1 macrophages2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 3, article id e0174475Article in journal (Refereed)
    Abstract [en]

    The 7-oxysterols are recognised as strong enhancers of inflammatory processes in foamy macrophages. Atheroma-relevant 7-oxysterol mixtures induce a mixed type of cell death in macrophages, and trigger cellular oxidative stress responses, which mimic oxidative exposures observed in atherosclerotic lesions. However, the macrophage proteome has not previously been determined in the 7-oxysterol treated cell model. The aim of the present study was to determine the specific effects of an atheroma-relevant 7-oxysterol mixture on human macrophage proteome. Human THP-1 macrophages were exposed to an atheroma-relevant mixture of 7 beta-hydroxycholesterol and 7-ketocholesterol. Two-dimensional gel electrophoresis and mass spectrometry techniques were used to analyse the alterations in macrophage proteome, which resulted in the identification of 19 proteins with significant differential expression upon oxysterol loading; 8 increased and 11 decreased. The expression patterns of 11 out of 19 identified significant proteins were further confirmed by tandemmass spectrometry, including further validation of increased histone deacetylase 2 and macrophage scavenger receptor types I and II expressions by western blot analysis. Identified proteins with differential expression in the cell model have been associated with i) signalling imbalance in cell death and cellular longevity; ii) lipid uptake and metabolism in foam cells; and iii) inflammatory proteins. The presented findings highlight a new proteomic platform for further studies into the functional roles of macrophages in atherosclerosis, and present a cell model for future studies to modulate the macrophage proteome by potential anti-atherosclerotic agents.

  • 245.
    Ward, Liam
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Olausson, Patrik
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Li, Wei
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Yuan, Ximing
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Proteomics and multivariate modelling reveal sex-specific alterations in distinct regions of human carotid atheroma2018In: Biology of Sex Differences, ISSN 2042-6410, Vol. 9, article id 54Article in journal (Refereed)
    Abstract [en]

    BackgroundAtherosclerotic lesions are comprised of distinct regions with different proteomic profiles. Men and women develop differences in lesion phenotype, with lesions from women generally being more stable and less prone to rupture. We aimed to investigate the differences in proteomic profiles between sexes, including distinct lesion regions, to identify altered proteins that contribute to these differences observed clinically.MethodsCarotid endarterectomy samples (ten men/ten women) were obtained, and intraplaque biopsies from three distinct regions (internal control, fatty streak and plaque) were analysed by tandem-mass spectrometry. Multivariate statistical modelling, using orthogonal partial least square-discriminant analysis, was used to discriminate the proteomes between men and women.ResultsMultivariate discriminant modelling revealed proteins from 16 functional groups that displayed sex-specific associations. Additional statistics revealed ten proteins that display region-specific alterations when comparing sexes, including proteins related to inflammatory response, response to reactive oxygen species, complement activation, transport and blood coagulation. Transport protein afamin and blood coagulation proteins antithrombin-III and coagulation factor XII were significantly increased in plaque region from women. Inflammatory response proteins lysozyme C and phospholipase A2 membrane-associated were significantly increased in plaque region from men. Limitations with this study are the small sample size, limited patient information and lack of complementary histology to control for cell type differences between sexes.ConclusionsThis pilot study, for the first time, utilises a multivariate proteomic approach to investigate sexual dimorphism in human atherosclerotic tissue, and provides an essential proteomic platform for further investigations to help understand sexual dimorphism and plaque vulnerability in atherosclerosis.

  • 246.
    Wejryd, Erik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Generó, Magali Marti
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Marchini, Giovanna
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Werme, Anna
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Jonsson, Baldvin
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Landberg, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Abrahamsson, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Low Diversity of Human Milk Oligosaccharides is Associated with Necrotising Enterocolitis in Extremely Low Birth Weight Infants2018In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 10, no 10, article id 1556Article in journal (Refereed)
    Abstract [en]

    Difference in human milk oligosaccharides (HMO) composition in breast milk may be one explanation why some preterm infants develop necrotizing enterocolitis (NEC) despite being fed exclusively with breast milk. The aim of this study was to measure the concentration of 15 dominant HMOs in breast milk during the neonatal period and investigate how their levels correlated to NEC, sepsis, and growth in extremely low birth weight (ELBW; amp;lt;1000 g) infants who were exclusively fed with breast milk. Milk was collected from 91 mothers to 106 infants at 14 and 28 days and at postmenstrual week 36. The HMOs were analysed with high-performance anion-exchange chromatography with pulsed amperometric detection. The HMOs diversity and the levels of Lacto-N-difucohexaose I were lower in samples from mothers to NEC cases, as compared to non-NEC cases at all sampling time points. Lacto-N-difucohexaose I is only produced by secretor and Lewis positive mothers. There were also significant but inconsistent associations between 3-sialyllactose and 6-sialyllactose and culture-proven sepsis and significant, but weak correlations between several HMOs and growth rate. Our results suggest that the variation in HMO composition in breast milk may be an important factor explaining why exclusively breast milk fed ELBW infants develop NEC.

  • 247.
    Wejryd, Erik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Marchini, Giovanna
    Department of Neonatology, Astrid Lindgren Children's Hospital, Karolinska University Hospital and Institute, Stockholm, Sweden.
    Frimmel, Veronica
    Department of Neonatology, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
    Jonsson, Baldvin
    Department of Neonatology, Astrid Lindgren Children's Hospital, Karolinska University Hospital and Institute, Stockholm, Sweden.
    Abrahamsson, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Probiotics promoted head growth in extremely low birthweight infants in a double-blind placebo-controlled trial2019In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 108, no 1, p. 62-69Article in journal (Refereed)
    Abstract [en]

    Aim

    This study evaluated if oral supplementation with the probiotic bacterium Lactobacillus reuteri DSM 17938 improved enteral feeding tolerance and growth rates in extremely low birthweight (ELBW) infants.

    Method

    A randomised, double‐blind, placebo‐controlled trial comprising 134 ELBW (<1000 g) infants born before gestational week 28 + 0. Daily supplementation of Lreuteri (1.25 × 108 bacteria/day) or placebo started within 3 days and continued until gestational week 36 + 0. Primary outcome was feeding tolerance and secondary outcome growth rate calculated as z‐score development.

    Results

    Feeding tolerance was similar in the probiotic and placebo group. Time to full enteral feeds was 15 days in both groups. The z‐score of the head circumference decreased in both groups from birth to day 28 of life, but it decreased less in the L. reuteri group compared to the placebo group: −1.2 SD (95% CI: −1.4 to −1.0) versus −1.7 SD (95% CI: −2.0 to −1.5; p = 0.001). Other growth parameters were similar in the study groups.

    Conclusion

    Lactobacillus reuteri did not reduce time to reach full enteral feeds in ELBW infants. The L. reuteri supplemented infants, however, had a better growth rate of the head during the first month of life.

  • 248.
    West, Janne
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Romu, Thobias
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV). Adv MR Analyt AB, Linkoping, Sweden.
    Thorell, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Sweden.
    Lindblom, Hanna
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Berin, Emilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Spetz Holm, Anna-Clara
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Lindh Åstrand, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Karlsson, Anette
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Borga, Magnus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV). Adv MR Analyt AB, Linkoping, Sweden.
    Hammar, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV). Adv MR Analyt AB, Linkoping, Sweden.
    Precision of MRI-based body composition measurements of postmenopausal women2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 2, article id e0192495Article in journal (Refereed)
    Abstract [en]

    Objectives To determine precision of magnetic resonance imaging (MRI) based fat and muscle quantification in a group of postmenopausal women. Furthermore, to extend the method to individual muscles relevant to upper-body exercise. Materials and methods This was a sub-study to a randomized control trial investigating effects of resistance training to decrease hot flushes in postmenopausal women. Thirty-six women were included, mean age 56 +/- 6 years. Each subject was scanned twice with a 3.0T MR-scanner using a whole-body Dixon protocol. Water and fat images were calculated using a 6-peak lipid model including R2*-correction. Body composition analyses were performed to measure visceral and subcutaneous fat volumes, lean volumes and muscle fat infiltration (MFI) of the muscle groups thigh muscles, lower leg muscles, and abdominal muscles, as well as the three individual muscles pectoralis, latissimus, and rhomboideus. Analysis was performed using a multi-atlas, calibrated water-fat separated quantification method. Liver-fat was measured as average proton density fat-fraction (PDFF) of three regions-of-interest. Precision was determined with Bland-Altman analysis, repeatability, and coefficient of variation. Results All of the 36 included women were successfully scanned and analysed. The coefficient of variation was 1.1% to 1.5% for abdominal fat compartments (visceral and subcutaneous), 0.8% to 1.9% for volumes of muscle groups (thigh, lower leg, and abdomen), and 2.3% to 7.0% for individual muscle volumes (pectoralis, latissimus, and rhomboideus). Limits of agreement for MFI was within +/- 2.06% for muscle groups and within +/- 5.13% for individual muscles. The limits of agreement for liver PDFF was within +/- 1.9%. Conclusion Whole-body Dixon MRI could characterize a range of different fat and muscle compartments with high precision, including individual muscles, in the study-group of postmenopausal women. The inclusion of individual muscles, calculated from the same scan, enables analysis for specific intervention programs and studies.

  • 249.
    Westermark, Gunilla T.
    et al.
    Uppsala University, Sweden.
    Krogvold, Lars
    Oslo University Hospital, Norway; University of Oslo, Norway.
    Dahl-Jorgensen, Knut
    Oslo University Hospital, Norway; University of Oslo, Norway.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Islet amyloid in recent-onset type 1 diabetes-the DiViD study2017In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 3, p. 201-203Article in journal (Other academic)
    Abstract [en]

    n/a

  • 250.
    Wijma, Barbro
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Persson, Alma
    Linköping University, Department of Thematic Studies, The Department of Gender Studies. Linköping University, Faculty of Arts and Sciences.
    Ockander, Marlene
    Jönköping Academy for Improvement of Health and Welfare, Jönköping University.
    Brüggemann, Jelmer
    Linköping University, Department of Thematic Studies, Technology and Social Change. Linköping University, Faculty of Arts and Sciences.
    Kränkningar i vården är vanligt förekommande: Viktigt med aktivt arbete mot att patienter kränks2019In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, p. 1-6Article in journal (Other academic)
    Abstract [sv]

    Trots goda intentioner hos vårdpersonal upplever patienter ofta möten i vården som misslyckade. Det kan vara möten där patienten har fått en helt korrekt medicinsk behandling, men av andra anledningar upplever sig kränkt eller överkörd. Ofta lägger vårdgivare inte ens märke till att det sker. Om patienten i efterhand försöker få upprättelse är det heller inte säkert att ett sådant samtal når sitt syfte. Ämnet kränkningar i vården är tabubelagt och känslomässigt laddat. För att ge legitimitet åt insatser att hjälpa personal att motverka kränkningar behövs därför en god kunskapsbas.

    Med denna utgångspunkt startades för 20 år sedan ett nytt forskningsfält om kränkningar i vården vid enheten för genus och medicin, Linköpings universitet. I denna artikel redovisar forskargruppen några av sina resultat och lärdomar.

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