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  • 51.
    Charalampopoulos, Dimitrios
    et al.
    UCL, England.
    Hermann, Julia M.
    Ulm Univ, Germany; German Ctr Diabet Res DZD, Germany.
    Svensson, Jannet
    Herlev Univ Hosp, Denmark.
    Skrivarhaug, Torild
    Oslo Univ Hosp, Norway.
    Maahs, David M.
    Stanford Univ, CA 94305 USA.
    Åkesson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Warner, Justin T.
    Childrens Hosp Wales, Wales.
    Holl, Reinhard W.
    Ulm Univ, Germany; German Ctr Diabet Res DZD, Germany.
    Birkebaek, Niels H.
    Aarhus Univ Hosp, Denmark.
    Drivvoll, Ann K.
    Oslo Univ Hosp, Norway.
    Miller, Kellee M.
    Jaeb Ctr Hlth Res, FL USA.
    Svensson, Ann-Marie
    Ctr Registers Reg Vastra Gotaland, Sweden.
    Stephenson, Terence
    University College London, London, U.K..
    Hofer, Sabine E.
    Med Univ Innsbruck, Austria.
    Fredheim, Siri
    Herlev University Hospital, Herlev, Denmark.
    Kummernes, Siv J.
    Oslo Univ Hosp, Norway.
    Foster, Nicole
    Jaeb Ctr Hlth Res, FL USA.
    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.
    Amin, Rakesh
    UCL, England.
    Rami-Merhar, Birgit
    Med Univ Vienna, Austria.
    Johansen, Anders
    Univ Copenhagen, Denmark.
    Dahl-Jorgensen, Knut
    Oslo Univ Hosp, Norway; Univ Oslo, Norway.
    Clements, Mark
    Childrens Mercy Hosp, MO 64108 USA; Univ Missouri Kansas City, MO USA; Univ Kansas, KS 66103 USA.
    Hanas, Ragnar
    NU Hosp Grp, Sweden; Univ Gothenburg, Sweden.
    Exploring Variation in Glycemic Control Across and Within Eight High-Income Countries: A Cross-sectional Analysis of 64,666 Children and Adolescents With Type 1 Diabetes2018In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 41, no 6, p. 1180-1187Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE International studies on childhood type 1 diabetes (T1D) have focused on whole-country mean HbA(1c) levels, thereby concealing potential variations within countries. We aimed to explore the variations in HbA(1c) across and within eight high-income countries to best inform international benchmarking and policy recommendations. RESEARCH DESIGN AND METHODS Data were collected between 2013 and 2014 from 64,666 children with T1D who were amp;lt; 18 years of age across 528 centers in Germany, Austria, England, Wales, U.S., Sweden, Denmark, and Norway. We used fixed-and random-effects models adjusted for age, sex, diabetes duration, and minority status to describe differences between center means and to calculate the proportion of total variation in HbA(1c) levels that is attributable to between-center differences (intraclass correlation [ICC]). We also explored the association between within-center variation and childrens glycemic control. RESULTS Sweden had the lowest mean HbA(1c) (59mmol/mol [7.6%]) and together with Norway and Denmark showed the lowest between-center variations (ICC amp;lt;= 4%). Germany and Austria had the next lowest mean HbA(1c) (61-62 mmol/mol [7.7-7.8%]) but showed the largest center variations (ICC similar to 15%). Centers in England, Wales, and the U.S. showed low-to-moderate variation around high mean values. In pooled analysis, differences between counties remained significant after adjustment for children characteristics and center effects (P value amp;lt; 0.001). Across all countries, children attending centers with more variable glycemic results had higher HbA(1c) levels (5.6mmol/mol [0.5%] per 5mmol/mol [0.5%] increase in center SD of HbA(1c) values of all children attending a specific center). CONCLUSIONS A tsimilar average levels of HbA(1c), countries display different levels of center variation. The distribution of glycemic achievement within countries should be considered in developing informed policies that drive quality improvement.

  • 52.
    Claesson, Ing-Marie
    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.
    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.
    Olhager, Elisabeth
    Lund Univ, Sweden.
    Oldin, Carin
    Reg Jonkoping Cty, 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.
    Effects of a gestational weight gain restriction program for obese women: Sibling pairs weight development during the first five years of life2018In: Sexual & Reproductive HealthCare, ISSN 1877-5756, E-ISSN 1877-5764, Vol. 17, p. 65-74Article in journal (Refereed)
    Abstract [en]

    Objectives: Successful gestational weight gain (GWG) restriction programs for obese (Body Mass Index (BMI) amp;gt;= 30 kg/m(2)) pregnant women, have not, so far, shown convincing effects on infants weight development. An intervention starting during the pregnancy might be too late and a pre-conceptional life style change may be preferable. Thus, the aim of this study was to follow children born to mothers who had participated in a weight gain restriction program during pregnancy, and make comparisons with their younger siblings. Study design and main outcome measures: An extended analysis of 262 children belonging to an intervention group and a control group. The effects of BMI at five years of age and weight-for-length/height development from two months of age until five years of age were assessed. Results: In the intervention group there was a difference in BMI at five years of age, between index boys and their younger sisters (p = 0.016). Mean BMI was lower among the boys compared with their younger female siblings. Regarding maternal GWG or the Swedish national reference data there was no difference between the index children and their younger siblings within the intervention or control groups or between younger siblings in the two groups. Conclusions: Maternal pre-conceptional lifestyle change may have a positive effect on the childs weight development during the five first years of age. However, the effect of participation in an extensive GWG restriction program when it comes to the impact on the offsprings weight development is still unclear and further research is required.

  • 53.
    Claesson, Ing-Marie
    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.
    Larsson, 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.
    Steen, Linda
    Univ Hosp, Norway.
    Alehagen, Siw
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    You just need to leave the room when you breastfeed: Breastfeeding experiences among obese women in Sweden – A qualitative study2018In: BMC Pregnancy and Childbirth, ISSN 1471-2393, E-ISSN 1471-2393, Vol. 18, no 1, article id 39Article in journal (Refereed)
    Abstract [en]

    Background

    The benefits of breastfeeding for the infant as well for the mother are well-known. It is recognized that obese (Body Mass Index ≥30 kg/m2) women may have less antenatal intention to breastfeed, and shortened duration of breastfeeding compared with normal-weight women. This may result in adverse short- and long-term health for both mother and child, such as a shortened lactational amenorrhoea and decreased protection against breast cancer for the women, and an increased risk for infectious diseases and overweight/obesity among the children. Therefore, it is important to gain more knowledge and understanding of obese women’s experiences of breastfeeding in order to attain good health care. Hence, the aim of this study was to identify and describe obese women’s experiences of breastfeeding.

    Methods

    This is an explorative study. Data was collected 2 – 18 months after childbirth through semi-structured face-to-face interviews with 11 obese women with breastfeeding experience. The interviews were recorded and transcribed verbatim. Thematic analysis was used.

    Results

    Three themes emerged from the data analysis: Breastfeeding - a part of motherhood, the challenges of breastfeeding, and support for breastfeeding. The women described an antenatal hope for breastfeeding, the body’s ability to produce milk fascinated them, and the breast milk was seen as the best way to feed the child and also as promoting the attachment between mother and child. Breastfeeding was described as a challenge even though it is natural. The challenges concerned technical difficulties such as the woman finding a good body position and helping the child to achieve an optimum grip of the nipple. Another challenge was the exposure of the body connected to public breastfeeding. Support of breastfeeding was described as the importance of being confirmed as an individual behind the obesity, rather than an individual with obesity, and to obtain enough professional breastfeeding support.

    Conclusions

    Breastfeeding was experienced as a natural part of being a mother. There were practical challenges for obese women concerning how to manage breastfeeding and how to handle the public exposure of the body. There was a need for realistic information about breastfeeding concerning both the child and the woman.

  • 54.
    Claesson, Ing-Marie
    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.
    Myrgård, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Wallberg, 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.
    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.
    Pregnant womens intention to breastfeed; their estimated extent and duration of the forthcoming breastfeeding in relation to the actual breastfeeding in the first year postpartum-A Swedish cohort study2019In: Midwifery, ISSN 0266-6138, E-ISSN 1532-3099, Vol. 76, p. 102-109Article in journal (Refereed)
    Abstract [en]

    Objectives: To investigate the prenatal intention to breastfeed and the estimated extent and duration of the forthcoming breastfeeding among nulliparous and multiparous women in different Body Mass Index (BMI) classes. Furthermore, in a sub-group we study the actual breastfeeding in relation to the prenatal intended extent and duration. Design: A prospective cohort study. Methods: A total of 775 pregnant women answered a questionnaire concerning their intention to breastfeed and how they estimated the extent and duration of the forthcoming breastfeeding. In a sub-group of 174 women, data from the actual breastfeeding were obtained. Findings: There was no difference concerning intention to breastfeed among underweight and normal weight women, overweight or obese nulliparous or multiparous women. Fewer multiparous women with BMI amp;lt;25 judged that the forthcoming breastfeeding would be partial, compared to multiparous women with overweight and obesity (p = 0.003). Furthermore, there was a significant difference within the group of nulliparous women concerning the prenatal intended extent and the actual breastfeeding at two weeks and five months postnatally (p = 0.000 and p = 0.041). There were more underweight and normal weight and overweight women who breastfed exclusively two weeks postnatally, compared with obese women. Additional, at five months postnatally there were more obese women who had ceased to breastfeed, than underweight and normal weight women. Conclusions: Among pregnant multiparous women there were more overweight and obese women who judged that the forthcoming breastfeeding would be partial, than pregnant underweight and normal weight women. The prenatal estimated extent of the forthcoming breastfeeding differed from the actually extent of breastfeeding among nulliparous women. Implications for practice: The antenatal breastfeeding information and education should be tailored to prepare every woman/couple, irrespective of maternal body composition for the forthcoming task and furthermore, the continuum of care, from antenatal care to Child Health Service should offer a supportive atmosphere to protect and promote breastfeeding (C) 2019 Elsevier Ltd. All rights reserved.

  • 55.
    Crespo-Felez, I.
    et al.
    University of Leon, Spain.
    Castaneda-Sampedro, A.
    University of Leon, Spain.
    Sanchez, D. I.
    University of Leon, Spain.
    Fernandez-Alegre, E.
    University of Leon, Spain.
    Alvarez-Rodriguez, Manuel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Dominguez, J. C.
    University of Leon, Spain.
    Morrell, J. M.
    Swedish University of Agriculture Science, Sweden.
    Martinez-Pastor, F.
    University of Leon, Spain; University of Leon, Spain.
    Effect of Single Layer Centrifugation Porcicoll (70%, 80% and 90%) or supplementation with reduced glutathione, seminal plasma and bovine serum albumin on frozen-thawed boar sperm2017In: Animal Reproduction Science, ISSN 0378-4320, E-ISSN 1873-2232, Vol. 187, p. 167-173Article in journal (Refereed)
    Abstract [en]

    Selecting the optimal sperm population is essential for success with reproductive techniques. Porcicoll (formerly Androcoll-P) is a colloid formulation for selection of high-quality boar spermatozoa by single layer centrifugation (SLC). To date, most studies have been carried out with fresh semen and large volumes. We carried out 2 experiments to test the use of Porcicoll for thawed boar semen in small volumes. In Experiment 1, cryopreserved semen doses were thawed, split in 200-pL aliquots and layered on 1 mL of Porcicoll 70%, 80% or 90%, or buffer without colloid. We assessed sperm recovery (the proportion of the loading dose that appeared in the pellet, %), and the physiology of the selected spermatozoa (flow cytometry: Viability, apoptotic changes, capacitation, mitochondrial activity, intracellular reactive oxygen species). The most suitable proportion was Porcicoll 80%, allowing acceptable sperm recovery (16.9 4.2%, compared to 70% (35.4% 3.0, p amp;lt; 0.001) and 90% (8.2% 3.0, P = 0.001), and improved quality (mitochondrial activity: Porcicoll 80%: 77.7 1% vs Control: 60.3 0.7%, P amp;lt; 0.05). In Experiment 2, we compared 3 supplements to Porcicoll 80%: 500 mM reduced glutathione (GSH), 20% seminal plasma (SP) and 0.5% bovine serum albumin (BSA). Supplementation with GSH or BSA did not cause relevant changes relative to Control. In contrast, SP induced membrane and acrosomal changes resembling capacitation, which might preclude its use in some applications, and decreased recovery (5.5% 1.9 vs. 24.3% 1.2 Control; P amp;lt; 0.001). However, it could be useful prior to other applications such as in vitro fertilisation. Overall, Porcicoll is an effective colloid for isolating a high-quality population from thawed boar sperm, 80% being a balanced option for good recovery and high quality. Supplements could be useful depending on the proposed use of the spermatozoa.

  • 56.
    Dahlberg, Johanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nelson, Marie
    Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Abrandt Dahlgren, Madeleine
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    Ten years of simulation-based shoulder dystocia training-impact on obstetric outcome, clinical management, staff confidence, and the pedagogical practice - a time series study2018In: BMC Pregnancy and Childbirth, ISSN 1471-2393, E-ISSN 1471-2393, Vol. 18, article id 361Article in journal (Refereed)
    Abstract [en]

    Background: To assess the impact of 10 years of simulation-based shoulder dystocia training on clinical outcomes, staff confidence, management, and to scrutinize the characteristics of the pedagogical practice of the simulation training. Methods: In 2008, a simulation-based team-training program (PROBE) was introduced at a medium sized delivery unit in Linkoping, Sweden. Data concerning maternal characteristics, management, and obstetric outcomes was compared between three groups; prePROBE (before PROBE was introduced, 2004-2007), early postPROBE (2008-2011) and late postPROBE (2012-2015). Staff responded to an electronic questionnaire, which included questions about self-confidence and perceived sense of security in acute obstetrical situations. Empirical data from the pedagogical practice was gathered through observational field notes of video-recordings of maternity care teams participating in simulation exercises and was further analyzed using collaborative video analysis. Results: The number of diagnosed shoulder dystocia increased from 0.9/1000 prePROBE to 1.8 and 2.5/1000 postPROBE. There were no differences in maternal characteristics between the groups. The rate of brachial plexus injuries in deliveries complicated with shoulder dystocia was 73% prePROBE compared to 17% in the late postPROBE group (p amp;gt; 0.05). The dominant maneuver to solve the shoulder dystocia changed from posterior arm extraction to internal rotation of the anterior shoulder between the pre and postPROBE groups. The staff questionnaire showed how the majority of the staff (48-62%) felt more confident when handling a shoulder dystocia after PROBE training. A model of facilitating relational reflection adopted seems to provide ways of keeping the collaboration and learning in the interprofessional team clearly focused. Conclusions: To introduce and sustain a shoulder dystocia training program for delivery staff improved clinical outcome. The impaired management and outcome of this rare, emergent and unexpectedly event might be explained by the learning effect in the debriefing model, clearly focused on the team and related to daily clinical practice.

  • 57.
    Dahm-Kähler, Pernilla
    et al.
    Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, Gothenburg, Sweden. Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Borgfeldt, Christer
    Department of Obstetrics and Gynecology, Skane University Hospital, Lund University, Lund, Sweden.
    Holmberg, Erik
    Regional Cancer Center Western Sweden, Sahlgrenska University Hospital, Gothenburg, Sweden. Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Staf, Christian
    Regional Cancer Center Western Sweden, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Falconer, Henrik
    Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
    Bjurberg, Maria
    Department of Clinical Sciences, Skåne University Hospital, Lund, 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.
    Rosenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Stålberg, Karin
    Department of Women's and Children's health Uppsala University, Uppsala, Sweden.
    Högberg, Thomas
    Department of Cancer Epidemiology, Lund University, Lund, 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. Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
    Population-based study of survival for women with serous cancer of the ovary, fallopian tube, peritoneum or undesignated origin - on behalf of the Swedish gynecological cancer group (SweGCG).2017In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 144, no 1, p. 167-173Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of the study was to determine survival outcome in patients with serous cancer in the ovary, fallopian tube, peritoneum and of undesignated origin.

    METHODS: Nation-wide population-based study of women≥18years with histologically verified non-uterine serous cancer, included in the Swedish Quality Registry for primary cancer of the ovary, fallopian tube and peritoneum diagnosed 2009-2013. Relative survival (RS) was estimated using the Ederer II method. Simple and multivariable analyses were estimated by Poisson regression models.

    RESULTS: Of 5627 women identified, 1246 (22%) had borderline tumors and 4381 had malignant tumors. In total, 2359 women had serous cancer; 71% originated in the ovary (OC), 9% in the fallopian tube (FTC), 9% in the peritoneum (PPC) and 11% at an undesignated primary site (UPS). Estimated RS at 5-years was 37%; for FTC 54%, 40% for OC, 34% for PPC and 13% for UPS. In multivariable regression analyses restricted to women who had undergone primary or interval debulking surgery for OC, FTC and PPC, site of origin was not independently associated with survival. Significant associations with worse survival were found for advanced stages (RR 2.63, P<0.001), moderate (RR 1.90, P<0.047) and poor differentiation (RR 2.20, P<0.009), neoadjuvant chemotherapy (RR1.33, P<0.022), residual tumor (RR 2.65, P<0.001) and platinum single (2.34, P<0.001) compared to platinum combination chemotherapy.

    CONCLUSION: Survival was poorer for serous cancer at UPS than for ovarian, fallopian tube and peritoneal cancer. Serous cancer at UPS needs to be addressed when reporting and comparing survival rates of ovarian cancer.

  • 58.
    Dietrich-Zagonel, Franciele
    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 Orthopaedics in Linköping.
    Hammerman, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Tätting, Love
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Dietrich, Fabricia
    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.
    Kozak Ljunggren, Monika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Parmis
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Eliasson, Pernilla T.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Stimulation of Tendon Healing With Delayed Dexamethasone Treatment Is Modified by the Microbiome2018In: American Journal of Sports Medicine, ISSN 0363-5465, E-ISSN 1552-3365, Vol. 46, no 13, p. 3281-3287Article in journal (Refereed)
    Abstract [en]

    Background:

    The immune system reflects the microbiome (microbiota). Modulation of the immune system during early tendon remodeling by dexamethasone treatment can improve rat Achilles tendon healing. The authors tested whether changes in the microbiota could influence the effect of dexamethasone treatment.

    Hypothesis:

    A change in microbiome would influence the response to dexamethasone on regenerate remodeling, specifically tendon material properties (peak stress).

    Study Design:

    Controlled laboratory study.

    Methods:

    Specific opportunist and pathogen-free female rats were housed separately (n = 41) or together with specific pathogen-free rats carrying opportunistic microbes such as Staphylococcus aureus (n = 41). After 6 weeks, all co-housed rats appeared healthy but now carried S aureus. Changes in the gut bacterial flora were tested by API and RapID biochemical tests. All rats (clean and contaminated) underwent Achilles tendon transection under aseptic conditions. Flow cytometry was performed 8 days postoperatively on tendon tissue. Sixty rats received subcutaneous dexamethasone or saline injections on days 5 through 9 after transection. The tendons were tested mechanically on day 12. The predetermined primary outcome was the interaction between contamination and dexamethasone regarding peak stress, tested by 2-way analysis of variance.

    Results:

    Dexamethasone increased peak stress in all groups but more in contaminated rats (105%) than in clean rats (53%) (interaction, P = .018). A similar interaction was found for an estimate of elastic modulus (P = .021). Furthermore, dexamethasone treatment reduced transverse area but had small effects on peak force and stiffness. In rats treated with saline only, contamination reduced peak stress by 16% (P = .04) and elastic modulus by 35% (P = .004). Contamination led to changes in the gut bacterial flora and higher levels of T cells (CD3+CD4+) in the healing tendon (P < .05).

    Conclusion:

    Changes in the microbiome influence tendon healing and enhance the positive effects of dexamethasone treatment during the early remodeling phase of tendon healing.

    Clinical Relevance:

    The positive effect of dexamethasone on early tendon remodeling in rats is strikingly strong. If similar effects could be shown in humans, immune modulation by a few days of systemic corticosteroids, or more specific compounds, could open new approaches to rehabilitation after tendon injury.

  • 59.
    Doumpas, Nikolaos
    et al.
    Univ Zurich, Switzerland.
    Lampart, Franziska
    Univ Zurich, Switzerland.
    Robinson, Mark D.
    Univ Zurich, Switzerland.
    Lentini, Antonio
    Univ Zurich, Switzerland.
    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.
    Cantù, Claudio
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Univ Zurich, Switzerland.
    Basler, Konrad
    Univ Zurich, Switzerland.
    TCF/LEF dependent and independent transcriptional regulation of Wnt/beta-catenin target genes2019In: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 38, no 2, article id e98873Article in journal (Refereed)
    Abstract [en]

    During canonical Wnt signalling, the activity of nuclear beta-catenin is largely mediated by the TCF/LEF family of transcription factors. To challenge this view, we used the CRISPR/Cas9 genome editing approach to generate HEK 293T cell clones lacking all four TCF/LEF genes. By performing unbiased whole transcriptome sequencing analysis, we found that a subset of beta-catenin transcriptional targets did not require TCF/LEF factors for their regulation. Consistent with this finding, we observed in a genome-wide analysis that beta-catenin occupied specific genomic regions in the absence of TCF/LEF. Finally, we revealed the existence of a transcriptional activity of beta-catenin that specifically appears when TCF/LEF factors are absent, and refer to this as beta-catenin-GHOST response. Collectively, this study uncovers a previously neglected modus operandi of beta-catenin that bypasses the TCF/LEF transcription factors.

  • 60.
    Duchén, Karel
    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.
    Lindberg, Anders
    Pfizer, Sweden.
    Kiplok, Kaire
    Pfizer, Sweden.
    Kriström, Berit
    Umeå University, Sweden.
    Using a spontaneous profile rather than stimulation test makes the KIGS idiopathic growth hormone deficiency model more accessible for clinicians2017In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 106, no 9, p. 1481-1486Article in journal (Refereed)
    Abstract [en]

    Aim: Children treated with a growth hormone (GH) for idiopathic growth hormone deficiency (IGHD) may be monitored with the first-year prediction model from the Pfizer International Growth Database (KIGS) using auxology, age, GH dose and the maximum GH concentration from a stimulation test (GH(max)stim). We tested the hypothesis that using a 12-hour spontaneous profile (GH(max)12h) would be as accurate. Methods: We studied 98 prepubertal Swedish children (78boys) aged2-12 years enrolled in KIGS. The first-year growth was predicted using the GH(max) from the GHprofile and a stimulation test, and both of these were compared separately with the observed growth response. Results: The increased height observed in the first year was 0.74 standard deviation scores (SDS), and the studentised residuals for the predicted and observed growth with GH(max)stim (-0.16 SDS) and GH(max)12h (-0.22) were similar. Individual predictions calculated with stimulated or spontaneous GH(max) showed a significant correlation (r = 0.80). Conclusion: We validated the KIGS IGHD prediction model and found that the stimulated GH(max) peak can be reliably replaced by the GH(max) 12h with similar accuracy. This makes the model more accessible for clinicians, who can then provide realistic expectations for the growth response during the first year of treatment.

  • 61.
    Dzidic, Majda
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. CSIC, Spain; FISABIO, Spain; CIBER ESP, Spain.
    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.
    Artacho, A.
    FISABIO, Spain; CIBER ESP, Spain.
    Collado, M. C.
    CSIC, Spain.
    Mira, A.
    FISABIO, Spain; CIBER ESP, Spain.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Oral microbiota maturation during the first 7 years of life in relation to allergy development2018In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 73, no 10, p. 2000-2011Article in journal (Refereed)
    Abstract [en]

    Background Allergic diseases have become a major public health problem in affluent societies. Microbial colonization early in life seems to be critical for instructing regulation on immune system maturation and allergy development in children. Even though the oral cavity is the first site of encounter between a majority of foreign antigens and the immune system, the influence of oral bacteria on allergy development has not yet been reported. Objective Methods We sought to determine the bacterial composition in longitudinally collected saliva samples during childhood in relation to allergy development. Illumina sequencing of the 16S rDNA gene was used to characterize the oral bacterial composition in saliva samples collected at 3, 6, 12, 24 months, and 7 years of age from children developing allergic symptoms and sensitization (n = 47) and children staying healthy (n = 33) up to 7 years of age. Results Conclusion Children developing allergic disease, particularly asthma, had lower diversity of salivary bacteria together with highly divergent bacterial composition at 7 years of age, showing a clearly altered oral microbiota in these individuals, likely as a consequence of an impaired immune system during infancy. Moreover, the relative amounts of several bacterial species, including increased abundance of Gemella haemolysans in children developing allergies and Lactobacillus gasseri and L. crispatus in healthy children, were distinctive during early infancy, likely influencing early immune maturation. Early changes in oral microbial composition seem to influence immune maturation and allergy development. Future experiments should test the probiotic potential of L. gasseri and L. crispatus isolates.

  • 62.
    Dzidic, Majda
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. FISABIO Fdn, Spain; Spanish National Research Council, Spain.
    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.
    Artacho, Alejandro
    FISABIO Fdn, Spain.
    Björksten, Bengt
    Karolinska Institute, Sweden.
    Collado, Maria Carmen
    Spanish National Research Council, Spain.
    Mira, Alex
    FISABIO Fdn, Spain.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Aberrant IgA responses to the gut microbiota during infancy precede asthma and allergy development2017In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 139, no 3, p. 1017-+Article in journal (Refereed)
    Abstract [en]

    Background: Although a reduced gut microbiota diversity and low mucosal total IgA levels in infancy have been associated with allergy development, IgA responses to the gut microbiota have not yet been studied. Objective: We sought to determine the proportions of IgA coating together with the characterization of the dominant bacteria, bound to IgA or not, in infant stool samples in relation to allergy development. Methods: A combination of flow cytometric cell sorting and deep sequencing of the 16S rDNA gene was used to characterize the bacterial recognition patterns by IgA in stool samples collected at 1 and 12 months of age from children staying healthy or having allergic symptoms up to 7 years of age. Results: The children with allergic manifestations, particularly asthma, during childhood had a lower proportion of IgA bound to fecal bacteria at 12months of age compared with healthy children. These alterations cannot be attributed to differences in IgA levels or bacterial load between the 2 groups. Moreover, the bacterial targets of early IgA responses (including coating of the Bacteroides genus), as well as IgA recognition patterns, differed between healthy children and children with allergic manifestations. Altered IgA recognition patterns in children with allergy were observed already at 1 month of age, when the IgA antibodies are predominantly maternally derived in breast-fed children. Conclusion: An aberrant IgAresponsiveness to the gutmicrobiota during infancy precedes asthma and allergy development, possibly indicating an impaired mucosal barrier function in allergic children.

  • 63.
    Dzidic, Majda
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. CSISP FISABIO, Spain; Inst Agrochem and Food Technol IATA CSIC, Spain.
    Collado, Maria C.
    Inst Agrochem and Food Technol IATA CSIC, Spain.
    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.
    Artacho, Alejandro
    CSISP FISABIO, Spain.
    Stensson, Malin
    Jonkoping Univ, Sweden.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Mira, Alex
    CSISP FISABIO, Spain.
    Oral microbiome development during childhood: an ecological succession influenced by postnatal factors and associated with tooth decay2018In: The ISME Journal, ISSN 1751-7362, E-ISSN 1751-7370, Vol. 12, no 9, p. 2292-2306Article in journal (Refereed)
    Abstract [en]

    Information on how the oral microbiome develops during early childhood and how external factors influence this ecological process is scarce. We used high-throughput sequencing to characterize bacterial composition in saliva samples collected at 3, 6, 12, 24 months and 7 years of age in 90 longitudinally followed children, for whom clinical, dietary and health data were collected. Bacterial composition patterns changed through time, starting with "early colonizers", including Streptococcus and Veillonella; other bacterial genera such as Neisseria settled after 1 or 2 years of age. Dental caries development was associated with diverging microbial composition through time. Streptococcus cristatus appeared to be associated with increased risk of developing tooth decay and its role as potential biomarker of the disease should be studied with species-specific probes. Infants born by C-section had initially skewed bacterial content compared with vaginally delivered infants, but this was recovered with age. Shorter breastfeeding habits and antibiotic treatment during the first 2 years of age were associated with a distinct bacterial composition at later age. The findings presented describe oral microbiota development as an ecological succession where altered colonization pattern during the first year of life may have long-term consequences for childs oral and systemic health.

  • 64.
    Díaz, Martín D.
    et al.
    Laboratorio de Enfermedades del Sistema Inmune y Oncología. Departamento de Medicina. Universidad de Alcalá. Alcalá de Henares, Madrid, Spain.
    Barcenilla Rodríguez, 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.
    Úbeda, Cantera M.
    Laboratorio de Enfermedades del Sistema Inmune y Oncología. Departamento de Medicina. Universidad de Alcalá. Alcalá de Henares, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd). Instituto de Salud Carlos III, Madrid, Spain.
    Muñoz, Zamarrón L.
    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd). Instituto de Salud Carlos III, Madrid, Spain.
    Self-reactivity and autoimmunity [Autorreactividad y autoinmunidad]2017In: Medicine (Spain), ISSN 0304-5412, Vol. 12, no 24, p. 1418-1427Article in journal (Refereed)
    Abstract [en]

    Definition of Autoimmunity and autoimmune diseases

    Autoimmunity is an immune response against one or several self-antigens. Autoimmune diseases are the result of damage or loss of physiological function in organs and tissues due to an autoimmune response. This specific recognition is mediated by cells of the adaptive immune system, i.e., T and B lymphocytes, while in the mechanisms of damage also participate cells and molecules of the innate immune system.

    Features of the autoimmune diseases

    Autoimmune diseases are chronic and often progressive. The persistence of the antigen, antigen-specific memory T and B cells and the powerful inflammatory mechanisms of amplification are pathogenetic mechanisms that perpetuate the disease.

    Immune tolerance

    The mechanisms of tolerance are essential for the control of the autoreactivity, mainly in the periphery by T lymphocytes. These mechanisms are typically divided into central tolerance, peripheral tolerance and tolerance mediated by regulatory T cells (Tregs).

    Etiology of the autoimmune diseases

    The etiology of the autoimmune diseases is not evident, although it seems clear that it is multifactorial. The genetic propensity is an important factor and certain sets of alleles of genes can predispose to the disease. In addition, environmental factors as the infection and the tissue injury seem fundamental in its development.

  • 65.
    Elenis, Evangelia
    et al.
    Uppsala Univ, Sweden.
    Skalkidou, Alkistis
    Uppsala Univ, 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.
    Stavreus-Evers, Anneli
    Uppsala Univ, Sweden.
    Akerud, Helena
    Uppsala Univ, Sweden.
    HRG C633T polymorphism and risk of gestational hypertensive disorders: a pilot study2018In: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 19, article id 44Article in journal (Refereed)
    Abstract [en]

    Background: Preeclampsia and gestational hypertensive disorders are thought to occur due to endothelial cell dysfunction and abnormal placentation, triggered by angiogenesis-related factors yet undetermined. The aim of this study was to investigate whether a genetic polymorphism (SNP) of Histidine-rich glycoprotein (HRG), HRG C633T SNP, is associated with gestational hypertensive disorders. Methods: It was performed a nested case-control study from the BASIC Cohort of Uppsala University Hospital comprising 92 women diagnosed with gestational hypertensive disorders without other comorbidities and 200 women with full term uncomplicated pregnancies, all genotyped regarding HRG C633T SNP. Results: The genetic analysis of the study sample showed that C/C genotype was more prevalent among controls. The presence of the T-allele showed a tendency towards an increased risk of gestational hypertensive disorders. After clustering the study participants based on their genotype, it was observed that the odds for gestational hypertensive disorders among heterozygous C/T or homozygous T/T carriers were higher compared to homozygous C/C carriers [OR 1.72, 95% CI (1.04-2.84)]. The association remained significant even after adjustment for maternal age, BMI and parity. Conclusions: The HRG C633T genotype seems to be associated with gestational hypertensive disorders, and as part of a greater algorithm, might contribute in the future to the prediction of the individual susceptibility to the condition.

  • 66.
    Elmerstig, Eva
    et al.
    Malmö University, Sweden.
    Wijma, Barbro
    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.
    Årestedt, Kristofer
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Linnaeus University, Sweden.
    Swahnberg, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linnaeus University, Sweden.
    Being "Good in Bed"Body Concerns, Self-Perceptions, and Gender Expectations Among Swedish Heterosexual Female and Male Senior High-School Students2017In: Journal of sex & marital therapy, ISSN 0092-623X, E-ISSN 1521-0715, Vol. 43, no 4, p. 326-342Article in journal (Refereed)
    Abstract [en]

    We investigated gender differences regarding body perceptions, self-perceptions, values and expectations in sexual situations, and factors associated with expectations, among Swedish heterosexual female and male high-school students. A total of 2,765 students (aged 18 to 22) completed questionnaires. Women reported lower satisfaction with themselves and their body appearance (p amp;lt; 0.001), and felt more inferior to their partner (p amp;lt; 0.001). Men felt more superior to their partner, and felt higher expectations (p amp;lt; 0.001). Male sex, difficulty saying no to sex, dissatisfaction with the body, feeling inferior or superior to partner, and considering partners satisfaction as more important, were all associated with feeling expectations during sex.

  • 67.
    Enander, Rebecka
    et al.
    SkaS Hosp Grp, Sweden.
    Adolfsson, Peter
    Hosp Halland, Sweden; Univ Gothenburg, Sweden.
    Bergdahl, Torun
    SkaS Hosp Grp, Sweden.
    Forsander, Gun
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, 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, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Hanas, Ragnar
    Univ Gothenburg, Sweden; NU Hosp Grp, Sweden.
    Beta cell function after intensive subcutaneous insulin therapy or intravenous insulin infusion at onset of type 1 diabetes in children without ketoacidosis2018In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, no 6, p. 1079-1085Article in journal (Refereed)
    Abstract [en]

    Background

    Our aim was to see if IV insulin therapy at diagnosis preserves beta‐cell function better than multiple subcutaneous (SC) injections.

    Methods

    Fifty‐four children 9.9 ± 3.5 years (range 2.8‐14.9) without ketoacidosis were included in a 2 years, randomized multicenter study with insulin SC or 48 to 72 hours IV initially. Thirty‐three (61%) were boys, 22 (41%) were pubertal. Forty‐eight subjects completed 12 months follow‐up and 43 completed 24 months. At 1, 6, 12, and 24 months, hemoglobin A1c (HbA1c), C‐peptide and insulin/kg/24 h were measured. At 24 months, a mixed‐meal tolerance test (MMTT) was performed.

    Results

    HbA1c at diagnosis was 10.7%, (93 mmol/mol) for IV, 10.7%, (94 mmol/mol) for SC. During the first 2 full days of insulin therapy, mean plasma glucose was 8.2 mmol/L for IV, 9.5 for SC (P = .025). Mean insulin dose was 1.5 U/kg/d for IV vs 1.0 for SC (P = .001). Sixteen (7 in IV, 9 in SC group) started with insulin pumps during the follow‐up. At 24 months, we saw no significant differences: HbA1c (7.5%, 58 mmol/mol, for IV, 7.2%, 55 mmol/mol, for SC; ns), insulin doses (0.79 vs 0.88 U/kg/d; ns), fasting C‐peptide (0.08 vs 0.12 nmol/L; ns), maximal MMTT response (0.19 vs 0.25 nmol/L; ns) and AUC (18.26 vs 23.9 nmol/L*min; ns). Peak C‐peptide >0.2 nmol/L in the combined IV and SC groups correlated significantly with HbA1c and C‐peptide at onset in a multiple regression.

    Conclusion

    Residual beta cell function at 2 years seems to be independent from initial insulin regimens but related to HbA1c and C‐peptide at onset.

  • 68.
    Enblom, Anna
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Institutionen för klinisk neurovetenskap, Osher centrum för integrativ medicin, Karolinska Institutet, Stockholm, Sweden.
    Steineck, Gunnar
    Institutionen för onkologi-patologi, Karolinska Institutet, Stockholm; Institutionen för kliniska vetenskaper, avdelning för onkologi, Sahlgrenska akademin, Göteborgs universitet, Göteborg, 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.
    Börjeson, Sussanne
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Medical and Health Sciences, Division of Nursing Science.
    Reduced Need for Rescue Antiemetics and Improved Capacity to Eat in Patients Receiving Acupuncture Compared to Patients Receiving Sham Acupuncture or Standard Care during Radiotherapy.2017In: Evidence-based Complementary and Alternative Medicine, ISSN 1741-427X, E-ISSN 1741-4288, Vol. 2017, article id 5806351Article in journal (Refereed)
    Abstract [en]

    Objective. To evaluate if consumption of emesis-related care and eating capacity differed between patients receiving verum acupuncture, sham acupuncture, or standard care only during radiotherapy. Methods. Patients were randomized to verum (n = 100) or sham (n = 100) acupuncture (telescopic blunt sham needle) (median 12 sessions) and registered daily their consumption of antiemetics and eating capacity. A standard care group (n = 62) received standard care only and delivered these data once. Results. More patients in the verum (n = 73 of 89 patients still undergoing radiotherapy; 82%, Relative Risk (RR) 1.23, 95% Confidence Interval (CI) 1.01-1.50) and the sham acupuncture group (n = 79 of 95; 83%, RR 1.24, CI 1.03-1.52) did not need any antiemetic medications, as compared to the standard care group (n = 42 out of 63; 67%) after receiving 27 Gray dose of radiotherapy. More patients in the verum (n = 50 of 89; 56%, RR 1.78, CI 1.31-2.42) and the sham acupuncture group (n = 58 of 94 answering patients; 62%, RR 1.83, CI 1.20-2.80) were capable of eating as usual, compared to the standard care group (n = 20 of 63; 39%). Conclusion. Patients receiving acupuncture had lower consumption of antiemetics and better eating capacity than patients receiving standard antiemetic care, plausible by nonspecific effects of the extra care during acupuncture.

  • 69.
    Falconer, Henrik
    et al.
    Karolinska Inst, Sweden.
    Palsdottir, Kolbrun
    Karolinska Inst, Sweden.
    Stalberg, Karin
    Uppsala Univ, Sweden.
    Dahm-Kahler, Pernilla
    Sahlgrens Acad, Sweden.
    Ottander, Ulrika
    Umea Univ, Sweden.
    Lundin, Evelyn
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Wijk, Lena
    Orebro Univ, Sweden.
    Kimmig, Rainer
    Univ Hosp Duisburg Essen, Germany.
    Jensen, Pernille Tine
    Aarhus Univ, Denmark.
    Eriksson, Ane Gerda Zahl
    Univ Oslo, Norway.
    Maenpaa, Johanna
    Tampere Univ, Finland.
    Persson, Jan
    Lund Univ Hosptial, Sweden.
    Salehi, Sahar
    Karolinska Inst, Sweden.
    Robot-assisted approach to cervical cancer (RACC): an international multi-center, open-label randomized controlled trial2019In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 29, no 6, p. 1072-1076Article in journal (Refereed)
    Abstract [en]

    Background Radical hysterectomy with pelvic lymphadenectomy represents the standard treatment for early-stage cervical cancer. Results from a recent randomized controlled trial demonstrate that minimally invasive surgery is inferior to laparotomy with regards to disease-free and overall survival. Primary Objective To investigate the oncologic safety of robot-assisted surgery for early-stage cervical cancer as compared with standard laparotomy. Study Hypothesis Robot-assisted laparoscopic radical hysterectomy is non-inferior to laparotomy in regards to recurrence-free survival with the advantage of fewer post-operative complications and superior patient-reported outcomes. Trial Design Prospective, multi-institutional, international, open-label randomized clinical trial. Consecutive women with early-stage cervical cancer will be assessed for eligibility and subsequently randomized 1:1 to either robot-assisted laparoscopic surgery or laparotomy. Institutional review board approval will be required from all participating institutions. The trial is coordinated from Karolinska University Hospital, Sweden. Major Inclusion/Exclusion Criteria Women over 18 with cervical cancer FIGO (2018) stages IB1, IB2, and IIA1 squamous, adenocarcinoma, or adenosquamous will be included. Women are not eligible if they have evidence of metastatic disease, serious co-morbidity, or a secondary invasive neoplasm in the past 5 years. Primary Endpoint Recurrence-free survival at 5 years between women who underwent robot-assisted laparoscopic surgery versus laparotomy for early-stage cervical cancer. Sample Size The clinical non-inferiority margin in this study is defined as a 5-year recurrence-free survival not worsened by amp;gt;7.5%. With an expected recurrence-free survival of 85%, the study needs to observe 127 events with a one-sided level of significance (alpha) of 5% and a power (1-beta) of 80%. With 5 years of recruitment and 3 years of follow-up, the necessary number of events will be reached if the study can recruit a total of 768 patients. Estimated Dates for Completing Accrual and Presenting Results Trial launch is estimated to be May 2019 and the trial is estimated to close in May 2027 with presentation of data shortly thereafter.

  • 70.
    Fernlund, Eva
    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. Lund University, Sweden.
    Gyllenhammar, T.
    Lund University, Sweden.
    Jablonowski, R.
    Lund University, Sweden.
    Carlsson, M.
    Lund University, Sweden.
    Larsson, A.
    Uppsala University, Sweden.
    Arnlov, J.
    Uppsala University, Sweden; Karolinska Institute, Sweden.
    Liuba, P.
    Lund University, Sweden.
    Serum Biomarkers of Myocardial Remodeling and Coronary Dysfunction in Early Stages of Hypertrophic Cardiomyopathy in the Young2017In: Pediatric Cardiology, ISSN 0172-0643, E-ISSN 1432-1971, Vol. 38, no 4, p. 853-863Article in journal (Refereed)
    Abstract [en]

    Hypertrophic cardiomyopathy (HCM) remains the leading cause of sudden cardiac death in the young. Early markers for HCM are important to identify individuals at risk. The aim of this study was to investigate novel serum biomarkers reflecting myocardial remodeling, microfibrosis, and vascular endotheliopathy in the early stages of familial HCM in young patients. Twenty-three HCM patients, 16 HCM-risk individuals, and 66 controls (median 15 years) underwent echocardiography and serum analysis for cathepsin S, endostatin, myostatin, type I collagen degradation marker (ICTP), matrix metalloproteinase (MMP)-9, vascular endothelial growth factor receptor (VEGFR)-1, and vascular and intercellular adhesion molecules (VCAM, ICAM). In a subset of the population, global myocardial perfusion was performed by magnetic resonance imaging. Cathepsin S (p = 0.0009), endostatin (p amp;lt; 0.0001), MMP-9 (p = 0.008), and VCAM (p = 0.04) were increased in the HCM group and correlated to left ventricular mass index and mitral E/e (p amp;lt; 0.01). In the HCM-risk group, myostatin was decreased (p = 0.004), whereas ICAM was increased (p = 0.002). Global perfusion was decreased in the HCM group (p amp;lt; 0.05) versus controls. Endostatin and mitral E/e correlated inversely to myocardial perfusion (p aeamp;lt;currencyamp;gt; 0.05). This is the first study demonstrating adverse changes in biomarkers reflecting myocardial matrix remodeling, microfibrosis, and vascular endotheliopathy in early stage of hypertrophic cardiomyopathy in the young.

  • 71.
    Fernlund, Eva
    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. Lund University, Sweden.
    Wålinder Österberg, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Kuchinskaya, Ekaterina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Gustafsson, Mikael
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Jansson, Kjell
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Gunnarsson, Cecilia
    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. Region Östergötland, Center for Business support and Development.
    Novel Genetic Variants in BAG3 and TNNT2 in a Swedish Family with a History of Dilated Cardiomyopathy and Sudden Cardiac Death2017In: Pediatric Cardiology, ISSN 0172-0643, E-ISSN 1432-1971, Vol. 38, no 6, p. 1262-1268Article in journal (Refereed)
    Abstract [en]

    Familial dilated cardiomyopathy is a rare cause of dilated cardiomyopathy (DCM), especially in childhood. Our aim was to describe the clinical course and the genetic variants in a family where the proband was a four-month-old infant presenting with respiratory problems due to DCM. In the family, there was a strong family history of DCM and sudden cardiac death in four generations. DNA was analyzed initially from the deceased girl using next-generation sequencing including 50 genes involved in cardiomyopathy. A cascade family screening was performed in the family after identification of the TNNT2 and the BAG3 variants in the proband. The first-degree relatives underwent clinical examination including biochemistry panel, cardiac ultrasound, Holter ECG, exercise stress test, and targeted genetic testing. The index patient presented with advanced DCM. After a severe clinical course, the baby had external left ventricular assist as a bridge to heart transplantation. 1.5 months after transplantation, the baby suffered sudden cardiac death (SCD) despite maximal treatment in the pediatric intensive care unit. The patient was shown to carry two heterozygous genetic variants in the TNNT2 gene [TNNT2 c.518G amp;gt; A(p.Arg173Gln)] and BAG3 [BAG3 c.785C amp;gt; T(p.Ala262Val)]. Two of the screened individuals (two females) appeared to carry both the familial variants. All the individuals carrying the TNNT2 variant presented with DCM, the two adult patients had mild or moderate symptoms of heart failure and reported palpitations but no syncope or presyncopal attacks prior to the genetic diagnosis. The female carriers of TNNT2 and BAG3 variants had more advanced DCM. In the family history, there were three additional cases of SCD due to DCM, diagnosed by autopsy, but no genetic analysis was possible in these cases. Our findings suggest that the variants in TNNT2 and BAG3 are associated with a high propensity to life-threatening cardiomyopathy presenting from childhood and young adulthood.

  • 72.
    Fernández-Gago, Rocío
    et al.
    Department of Medicine, Surgery and Veterinary Anatomy, University of León, 24071 León, Spain.
    Alvarez-Rodriguez, Manuel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Alonso, Marta E
    Department of Animal Production, University of León, 24071 León, Spain.
    González, J Ramiro
    Department of Medicine, Surgery and Veterinary Anatomy, University of León, 24071 León, Spain.
    Alegre, Beatriz
    Department of Medicine, Surgery and Veterinary Anatomy, University of León, 24071 León, Spain.
    Domínguez, Juan C
    Department of Medicine, Surgery and Veterinary Anatomy, University of León, 24071 León, Spain.
    Martínez-Pastor, Felipe
    INDEGSAL (Institute for Animal Health and Cattle Development), University of León, 24071 León, Spain /Molecular Biology (Cell Biology), University of León, 24071 León, Spain/ .
    Thawing boar semen in the presence of seminal plasma improves motility, modifies subpopulation patterns and reduces chromatin alterations.2017In: Reproduction, fertility, and development, ISSN 1031-3613, Vol. 29, no 8, p. 1576-1584Article in journal (Refereed)
    Abstract [en]

    Seminal plasma could have positive effects on boar semen after thawing. In the present study we investigated changes in the motility and chromatin structure in spermatozoa over 4h incubation (37°C) of boar semen thawed in the presence of 0%, 10% or 50% seminal plasma from good-fertility boars. Cryopreserved doses were used from seven males, three of which were identified as susceptible to post-thawing chromatin alterations. Motility was analysed by computer-aided sperm analysis every hour, and data were used in a two-step clustering, yielding three subpopulations of spermatozoa (slow non-linear, fast non-linear, fast linear). Chromatin structure was analysed using a sperm chromatin structure assay and flow cytometry to determine the DNA fragmentation index (%DFI) as a percentage, the standard deviation of the DFI (SD-DFI) and the percentage of high DNA stainability (%HDS), indicating chromatin compaction. Thawing without seminal plasma resulted in a rapid loss of motility, whereas seminal plasma helped maintain motility throughout the incubation period and preserved the subpopulation comprising fast and linear spermatozoa. The incidence of chromatin alterations was very low in samples from non-susceptible males, whereas samples from males susceptible to post-thawing chromatin alterations exhibited marked alterations in%DFI and%HDS. Seminal plasma partly prevented these alterations in samples from susceptible males. Overall, 50% seminal plasma was the most efficient concentration to protect motility and chromatin. Some changes were concomitant with physiological events reported previously (e.g., semen thawed with 50% seminal plasma increased the production of reactive oxygen species and yielded higher fertility after AI). Thawing in the presence of seminal plasma could be particularly useful in the case of samples susceptible to post-thawing chromatin damage.

  • 73.
    Forsander, G.
    et al.
    Univ Gothenburg, Sweden.
    Stallknecht, S.
    Incentive, Denmark.
    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, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Marcus, C.
    Karolinska Inst, Sweden.
    Bogelund, M.
    Incentive, Denmark.
    Preferences for treatment among adolescents with Type 1 diabetes: a national study using a discrete choice experiment model2018In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 35, no 5, p. 621-629Article in journal (Refereed)
    Abstract [en]

    AimTo test the possibility of using a discrete choice experiment model, on a national level in adolescents with Type 1 diabetes, in order to obtain a better understanding of drivers of and barriers to diabetes self-care. MethodsA survey instrument was constructed and tested on a small group of the target population: adolescents aged 15 to amp;lt;18 years with Type 1 diabetes. All individuals in Sweden belonging to this target group (N=2112) were then identified via the Swedish paediatric diabetes quality registry SWEDIABKIDS, and were sent an invitation to answer an online questionnaire. A valid response for the discrete choice experiment analyses was achieved from 431 individuals. ResultsThe included respondents were not statistically different from non-participants in terms of age and duration of diabetes, but more young women entered the study and the participants had (on average) a significantly lower HbA(1c) value than the non-participants. Participants regarded as undesirable both non-severe hypoglycaemic events (day and night) and hyperglycaemic events. Avoiding weight gain and even achieving weight loss were the most important aspects among female respondents, who were willing to trade off a substantial level of glycaemic control [13 mmol/mol (1.2%)] to avoid a weight gain of 3 kg. Hypothetical equipment improvements were desired. ConclusionsThe responses may provide useful indications of the aspects that the respondents would prioritize given a real-life dilemma. For treatment effects, stratification along gender lines was important, whereas the treatment administration aspects were stratified according to treatment type because these aspects are closely related.

  • 74.
    Forsander, Gun
    et al.
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Bogelund, Mette
    Incentive, Denmark.
    Haas, Josephine
    Karolinska Institute, 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.
    Adolescent life with diabetes-Gender matters for level of distress. Experiences from the national TODS study2017In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 18, no 7, p. 651-659Article in journal (Refereed)
    Abstract [en]

    Objective: To examine the relationship between diabetes distress and gender, and the association with glycemic control, social support, health behaviors, and socio-economic status. Methods: All adolescents, aged 15 to 18 years, in the national, pediatric diabetes registry SWE-DIABKIDS with type 1 diabetes were invited to complete an online questionnaire. A total of 2112 teenagers were identified. Results: 453 complete responses were valid for analyses. Young women scored significantly higher on the distress-screening instrument DDS-2. Almost half of the female respondents exhibited moderate to severe diabetes distress-more than twice the proportion than among male respondents (44% vs 19%). Females reported twice as high scores on the fear of hypoglycemia scale (P amp;lt; 0.0001) and had a higher HbA1c value than males (P amp;lt; 0.0001). Gender was highly correlated with distress level even when controlling for multiple factors that may affect distress (parameter(female) = 0.4, P = 0.0003). Particular social problems were highly significant, that is, those who trust that their parents can handle their diabetes when necessary were significantly less distressed than others (P = 0.018). Higher HbA1c levels were associated with higher distress scores (P = 0.0005 [female], P = 0.0487 [male]). Conclusions: Diabetes-related distress is a great burden for adolescents living with diabetes. Actively involved family and friends may reduce diabetes distress, but female adolescents appear to be particularly vulnerable and may need extra focus and support. Our findings indicate that pediatric diabetes teams working with teenagers must intensify the care during this vulnerable period of life in order to reduce the risk of both psychological and vascular complications in young adults.

  • 75.
    Forsgren, Lars
    et al.
    Umeå universitet, Umeå, Sweden.
    Sundelin, Heléne
    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.
    Sveinsson, Olafur
    Neurologiska kliniken, Stockholm, Sweden.
    Epilepsins orsaker, förekomst och prognos [Epilepsy: incidens, prevalens and causes]2018In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115Article, review/survey (Refereed)
    Abstract [en]

    Epilepsy affects people in all ages with the highest incidence in small children, particularly before age one year, and in elderly aged 65 years and older. In Sweden, between 4500-5000 persons develop epilepsy annually. Based on studies from North America and Europe, including the Nordic countries, the number of people with active epilepsy in Sweden is between 60000-70000. The lifetime risk for epilepsy up to age 85 years is 4-5 %, i.e. approximately every 25th person. The new epilepsy classification divides etiology into the following groups: structural, genetic, infectious, metabolic, immune and unknown. The majority (70%) of people with epilepsy eventually become seizure free. Epilepsy increases the risk of psychosocial problems and accidents. People with epilepsy have up to a 3-fold increase in mortality, mainly due to the underlying causes and epilepsy related deaths, e.g. status epilepticus, SUDEP and accidents. Somatic, psychiatric and neuropsychiatric comorbidities are common in epilepsy.

  • 76.
    Gawel, Danuta R.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Identification of genes and regulators that are shared across T cell associated diseases2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Genome-wide association studies (GWASs) of hundreds of diseases and millions of patients have led to the identification of genes that are associated with more than one disease. The aims of this PhD thesis were to a) identify a group of genes important in multiple diseases (shared disease genes), b) identify shared up-stream disease regulators, and c) determine how the same genes can be involved in the pathogenesis of different diseases. These aims have been tested on CD4+ T cells because they express the T helper cell differentiation pathway, which was the most enriched pathway in analyses of all disease associated genes identified with GWASs.

    Combining information about known gene-gene interactions from the protein-protein interaction (PPI) network with gene expression changes in multiple T cell associated diseases led to the identification of a group of highly interconnected genes that were miss-expressed in many of those diseases – hereafter called ‘shared disease genes’. Those genes were further enriched for inflammatory, metabolic and proliferative pathways, genetic variants identified by all GWASs, as well as mutations in cancer studies and known diagnostic and therapeutic targets. Taken together, these findings supported the relevance of the shared disease genes.

    Identification of the shared upstream disease regulators was addressed in the second project of this PhD thesis. The underlying hypothesis assumed that the determination of the shared upstream disease regulators is possible through a network model showing in which order genes activate each other. For that reason a transcription factor–gene regulatory network (TF-GRN) was created. The TF-GRN was based on the time-series gene expression profiling of the T helper cell type 1 (Th1), and T helper cell type 2 (Th2) differentiation from Native T-cells. Transcription factors (TFs) whose expression changed early during polarization and had many downstream predicted targets (hubs) that were enriched for disease associated single nucleotide polymorphisms (SNPs) were prioritised as the putative early disease regulators. These analyses identified three transcription factors: GATA3, MAF and MYB. Their predicted targets were validated by ChIP-Seq and siRNA mediated knockdown in primary human T-cells. CD4+ T cells isolated from seasonal allergic rhinitis (SAR) and multiple sclerosis (MS) patients in their non-symptomatic stages were analysed in order to demonstrate predictive potential of those three TFs. We found that those three TFs were differentially expressed in symptom-free stages of the two diseases, while their TF-GRN{predicted targets were differentially expressed during symptomatic disease stages. Moreover, using RNA-Seq data we identified a disease associated SNP that correlated with differential splicing of GATA3.

    A limitation of the above study is that it concentrated on TFs as main regulators in cells, excluding other potential regulators such as microRNAs. To this end, a microRNA{gene regulatory network (mGRN) of human CD4+ T cell differentiation was constructed. Within this network, we defined regulatory clusters (groups of microRNAs that are regulating groups of mRNAs). One regulatory cluster was differentially expressed in all of the tested diseases, and was highly enriched for GWAS SNPs. Although the microRNA processing machinery was dynamically upregulated during early T-cell activation, the majority of microRNA modules showed specialisation in later time-points.

    In summary this PhD thesis shows the relevance of shared genes and up-stream disease regulators. Putative mechanisms of why shared genes can be involved in pathogenesis of different diseases have also been demonstrated: a) differential gene expression in different diseases; b) alternative transcription factor splicing variants may affect different downstream gene target group; and c) SNPs might cause alternative splicing.

    List of papers
    1. Integrated genomic and prospective clinical studies show the importance of modular pleiotropy for disease susceptibility, diagnosis and treatment
    Open this publication in new window or tab >>Integrated genomic and prospective clinical studies show the importance of modular pleiotropy for disease susceptibility, diagnosis and treatment
    Show others...
    2014 (English)In: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 6, no 17Article in journal (Refereed) Published
    Abstract [en]

    Background: Translational research typically aims to identify and functionally validate individual, disease-specific genes. However, reaching this aim is complicated by the involvement of thousands of genes in common diseases, and that many of those genes are pleiotropic, that is, shared by several diseases. Methods: We integrated genomic meta-analyses with prospective clinical studies to systematically investigate the pathogenic, diagnostic and therapeutic roles of pleiotropic genes. In a novel approach, we first used pathway analysis of all published genome-wide association studies (GWAS) to find a cell type common to many diseases. Results: The analysis showed over-representation of the T helper cell differentiation pathway, which is expressed in T cells. This led us to focus on expression profiling of CD4(+) T cells from highly diverse inflammatory and malignant diseases. We found that pleiotropic genes were highly interconnected and formed a pleiotropic module, which was enriched for inflammatory, metabolic and proliferative pathways. The general relevance of this module was supported by highly significant enrichment of genetic variants identified by all GWAS and cancer studies, as well as known diagnostic and therapeutic targets. Prospective clinical studies of multiple sclerosis and allergy showed the importance of both pleiotropic and disease specific modules for clinical stratification. Conclusions: In summary, this translational genomics study identified a pleiotropic module, which has key pathogenic, diagnostic and therapeutic roles.

    Place, publisher, year, edition, pages
    BioMed Central, 2014
    National Category
    Clinical Medicine Basic Medicine
    Identifiers
    urn:nbn:se:liu:diva-106873 (URN)10.1186/gm534 (DOI)000334631300002 ()
    Available from: 2014-05-28 Created: 2014-05-23 Last updated: 2018-04-10
    2. A validated gene regulatory network and GWAS identifies early regulators of T cell-associated diseases
    Open this publication in new window or tab >>A validated gene regulatory network and GWAS identifies early regulators of T cell-associated diseases
    Show others...
    2015 (English)In: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 7, no 313, article id 313ra178Article in journal (Refereed) Published
    Abstract [en]

    Early regulators of disease may increase understanding of disease mechanisms and serve as markers for presymptomatic diagnosis and treatment. However, early regulators are difficult to identify because patients generally present after they are symptomatic. We hypothesized that early regulators of T cell-associated diseases could be found by identifying upstream transcription factors (TFs) in T cell differentiation and by prioritizing hub TFs that were enriched for disease-associated polymorphisms. A gene regulatory network (GRN) was constructed by time series profiling of the transcriptomes and methylomes of human CD4(+) T cells during in vitro differentiation into four helper T cell lineages, in combination with sequence-based TF binding predictions. The TFs GATA3, MAF, and MYB were identified as early regulators and validated by ChIP-seq (chromatin immunoprecipitation sequencing) and small interfering RNA knockdowns. Differential mRNA expression of the TFs and their targets in T cell-associated diseases supports their clinical relevance. To directly test if the TFs were altered early in disease, T cells from patients with two T cell-mediated diseases, multiple sclerosis and seasonal allergic rhinitis, were analyzed. Strikingly, the TFs were differentially expressed during asymptomatic stages of both diseases, whereas their targets showed altered expression during symptomatic stages. This analytical strategy to identify early regulators of disease by combining GRNs with genome-wide association studies may be generally applicable for functional and clinical studies of early disease development.

    Place, publisher, year, edition, pages
    AMER ASSOC ADVANCEMENT SCIENCE, 2015
    National Category
    Biological Sciences Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-123522 (URN)10.1126/scitranslmed.aad2722 (DOI)000365237400003 ()26560356 (PubMedID)
    Note

    Funding Agencies|Cancer fund, Swedish Medical Research Council [K2013-61X-22310-01-04, 2012-3168]; Academy of Finland Centre of Excellence in Molecular Systems Immunology and Physiology Research [250114]; Sigrid Juselius Foundation; Generalitat de Catalunya AGAUR [2014-SGR364]; Spanish Association Against Cancer; Spanish Ministry of Health ISCIII FIS [PI12/01528]; RTICC [RD12/0036/0008]

    Available from: 2015-12-22 Created: 2015-12-21 Last updated: 2018-04-10Bibliographically approved
  • 77.
    Gawel, Danuta
    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.
    Serra-Musach, Jordi
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Lilja, Sandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Aagesen, Jesper
    Reg Jonkoping Cty, Sweden.
    Arenas, Alex
    Univ Rovira and Virgili, Spain.
    Asking, Bengt
    Reg Jonkoping Cty, Sweden.
    Bengner, Malin
    Reg Jonkoping Cty, Sweden.
    Bjorkander, Janne
    Reg Jonkoping Cty, Sweden.
    Biggs, Sophie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. 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.
    Hjortswang, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Karlsson, Jan-Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Köpsén, Mattias
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Jung Lee, Eun Jung
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Yonsei Univ, South Korea.
    Lentini, Antonio
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Li, Xinxiu
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Magnusson, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Martinez, David
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Matussek, Andreas
    Reg Jonkoping Cty, Sweden; Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    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.
    Schafer, Samuel
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Seifert, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Sonmez, Ceylan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Stjernman, Henrik
    Reg Jonkoping Cty, Sweden.
    Tjärnberg, Andreas
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Wu, Simon
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Åkesson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Shalek, Alex K.
    MIT, MA 02139 USA; Broad Inst MIT and Harvard, MA 02142 USA; Ragon Inst MGH MIT and Harvard, MA USA.
    Stenmarker, Margaretha
    Reg Jonkoping Cty, Sweden; Inst Clin Sci, Sweden.
    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.
    Gustafsson, Mika
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    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, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases2019In: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 11, article id 47Article in journal (Refereed)
    Abstract [en]

    Background

    Genomic medicine has paved the way for identifying biomarkers and therapeutically actionable targets for complex diseases, but is complicated by the involvement of thousands of variably expressed genes across multiple cell types. Single-cell RNA-sequencing study (scRNA-seq) allows the characterization of such complex changes in whole organs.

    Methods

    The study is based on applying network tools to organize and analyze scRNA-seq data from a mouse model of arthritis and human rheumatoid arthritis, in order to find diagnostic biomarkers and therapeutic targets. Diagnostic validation studies were performed using expression profiling data and potential protein biomarkers from prospective clinical studies of 13 diseases. A candidate drug was examined by a treatment study of a mouse model of arthritis, using phenotypic, immunohistochemical, and cellular analyses as read-outs.

    Results

    We performed the first systematic analysis of pathways, potential biomarkers, and drug targets in scRNA-seq data from a complex disease, starting with inflamed joints and lymph nodes from a mouse model of arthritis. We found the involvement of hundreds of pathways, biomarkers, and drug targets that differed greatly between cell types. Analyses of scRNA-seq and GWAS data from human rheumatoid arthritis (RA) supported a similar dispersion of pathogenic mechanisms in different cell types. Thus, systems-level approaches to prioritize biomarkers and drugs are needed. Here, we present a prioritization strategy that is based on constructing network models of disease-associated cell types and interactions using scRNA-seq data from our mouse model of arthritis, as well as human RA, which we term multicellular disease models (MCDMs). We find that the network centrality of MCDM cell types correlates with the enrichment of genes harboring genetic variants associated with RA and thus could potentially be used to prioritize cell types and genes for diagnostics and therapeutics. We validated this hypothesis in a large-scale study of patients with 13 different autoimmune, allergic, infectious, malignant, endocrine, metabolic, and cardiovascular diseases, as well as a therapeutic study of the mouse arthritis model.

    Conclusions

    Overall, our results support that our strategy has the potential to help prioritize diagnostic and therapeutic targets in human disease.

  • 78.
    Gebhardt, Anja J.
    et al.
    Karolinska Institute, 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.
    Skoog Svanberg, Agneta
    Uppsala University, Sweden.
    Indekeu, Astrid
    Karolinska Institute, Sweden.
    Lampic, Claudia
    Karolinska Institute, Sweden.
    Parenting stress and its association with perceived agreement about the disclosure decision in parents following donor conception2017In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 96, no 8, p. 968-975Article in journal (Refereed)
    Abstract [en]

    IntroductionFor many donor-conceiving heterosexual parents, the process of deciding whether and what to tell children about their genetic origin is challenging. We hypothesized that incomplete couple agreement about disclosure could be associated with parenting stress. The aim of the study was to investigate: (1) parenting stress levels among heterosexual parents of young children following gamete donation and (2) whether parenting stress is related to perceived agreement about disclosure of the donor conception to the children. Material and methodsThis study is part of the longitudinal multicenter Swedish Study on Gamete Donation and included a total of 213 heterosexual parents with children aged 1-4years following oocyte donation (n=103) and sperm donation (n=110). Parents individually completed a questionnaire that included validated instruments on parenting stress (SPSQ) and relationship quality (ENRICH), as well as a study-specific measure on disclosure agreement. Multiple regression analysis was applied. ResultsIncomplete couple agreement on disclosure to the children was not statistically significantly associated with increased levels of parenting stress. Relationship satisfaction consistently and significantly accounted for variation in parenting stress levels, indicating that relationship satisfaction had a buffering impact on parenting stress. ConclusionsParental stress does not appear to be negatively influenced by incomplete couple agreement about disclosure to children. As children grow up, reaching agreement about what to tell the child about the donor conception might become more relevant for couples stress related to parenthood.

  • 79.
    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.
    Contraception in women with obesity with special reference to gastric bypass surgery2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: The prevalence of obesity is increasing worldwide. The treatment of morbid obesity is dominated by bariatric surgery, for example Roux-en-Y gastric bypass (RYGB) surgery. If other contraceptive options are available, women with obesity should not be prescribed combined hormonal contraceptives due to the obesity-related increased risk of venous thromboembolism. Women are advised not to become pregnant during the first 12-18 months after RYGB surgery. There is a lack of knowledge of what type of contraceptive methods women with obesity are prescribed and whether they experience more or different side effects compared to normal-weight women. It is not known if the absorption and pharmacokinetic profile of progestins are affected by RYGB. The aim of this thesis was to investigate the pattern of contraceptive use in women with obesity, what type of contraceptive counselling was given to women in relation to RYGB, and whether the pharmacokinetics of two different progestins were affected by RYGB surgery.

    Material and Methods: Paper I is a retrospective cohort study analysing the patterns of contraceptive prescription, adverse effects, duration of treatment, reasons for discontinuation and bleeding pattern in 371 women with obesity compared with 744 normal-weight women. Medical records were scrutinised from 1 Jan 2010 until 31 Dec 2014. Paper II is based on a questionnaire sent to 987 women who had undergone RYGB during 2010. The questionnaire concerned preoperative and present contraceptive use, contraceptive counselling in relation to surgery and what type of recommendations they had received regarding pregnancy after RYGB. Papers III and IV are experimental studies investigating the pharmacokinetics of desogestrel (etonogestrel) and levonorgestrel in relation to RYGB.

    Results and conclusions: The most commonly prescribed contraceptive method for women with obesity was the progestin-only pill but many women with obesity were prescribed combined hormonal contraceptives despite the current recommendations of cautious prescription of oestrogen-containing methods. There were no differences in adherence to contraceptive method between women with obesity and normal-weight women. Despite the uncertainties regarding absorption, almost 10 % of women continued using oral contraceptives after RYGB. Nearly 40% were not aware of the recommendation to avoid pregnancy in the first year after RYGB and almost one third did not use any contraception during this period. This could be due to a lack of information or that the women did not retain the given information to avoid pregnancy. We found no clinically significant differences in the steady state pharmacokinetics of desogestrel before compared with after RYGB, or in single dose pharmacokinetics of levonorgestrel in women with BMI< 30 having undergone RYGB compared with BMI-matched non-operated women. This suggests that oral contraceptives containing desogestrel and levonorgestrel might be used after RYGB surgery.

    List of papers
    1. Contraceptive Use Before and After Gastric Bypass: a Questionnaire Study
    Open this publication in new window or tab >>Contraceptive Use Before and After Gastric Bypass: a Questionnaire Study
    2015 (English)In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 25, no 11, p. 2066-2070Article in journal (Refereed) Published
    Abstract [en]

    At present, women are recommended to avoid pregnancy 12-18 months after bariatric surgery. Our aim in this study was to describe patterns of contraceptive use before and after gastric bypass in Sweden, and to describe the contraceptive counseling given preoperatively to women undergoing gastric bypass. In October 2012, a questionnaire was sent to 1000 Swedish women who all had undergone gastric bypass during 2010. The women had been included in the Scandinavian Obesity Surgery Register at time of surgery. The main outcome measures were patterns of use of contraception before and after bariatric surgery. The response rate was 57 %. The most commonly used contraceptive methods were intrauterine devices, 29 % preoperatively and 26 % postoperatively even though there was a postoperative switch from the copper intrauterine device to the levonorgestrel intrauterine system. Thirty percent did not use any contraceptive during the first 12 months after surgery. Sixty percent of the responders were aware of the recommendations to avoid pregnancy after surgery. Many women who undergo bariatric surgery are not using any contraceptive method despite the recommendation that they should avoid pregnancy for at least 12 months. There is a great need to improve contraceptive counseling for this growing group of women.

    Place, publisher, year, edition, pages
    SPRINGER, 2015
    Keywords
    Gastric bypass; Pregnancy; Contraception; Obesity
    National Category
    Obstetrics, Gynecology and Reproductive Medicine
    Identifiers
    urn:nbn:se:liu:diva-122518 (URN)10.1007/s11695-015-1641-7 (DOI)000362578700048 ()25744304 (PubMedID)
    Note

    Funding Agencies|Bayer AB, Sweden

    Available from: 2015-11-09 Created: 2015-11-06 Last updated: 2019-05-02
    2. Plasma concentrations of etonogestrel in women using oral desogestrel before and after Roux-en-Y gastric bypass surgery: a pharmacokinetic study
    Open this publication in new window or tab >>Plasma concentrations of etonogestrel in women using oral desogestrel before and after Roux-en-Y gastric bypass surgery: a pharmacokinetic study
    Show others...
    2019 (English)In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 126, no 4, p. 486-492Article in journal (Refereed) Published
    Abstract [en]

    Objective

    To investigate whether Roux‐en‐Y gastric bypass (RYGB) affects oral desogestrel (etonogestrel) pharmacokinetics.

    Design

    Single centre, open label, phase‐2 pharmacokinetic study.

    Setting

    University hospital of Linköping, Sweden.

    Population

    Fourteen women with planned RYGB surgery were included; nine women aged 18–45 years using 75 micrograms desogestrel completed the study.

    Methods

    Steady‐state etonogestrel pharmacokinetic (PK) parameters were measured on three occasions for each individual (at 8 ± 6 weeks before surgery, and at 12 ± 2 and 52 ± 2 weeks after surgery). Each patient served as her own control. On each occasion, serum samples were collected during a 24‐hour period and etonogestrel concentrations were determined with ultra‐performance liquid chromatography/tandem mass spectrometry.

    Main outcome measures

    Area under the plasma concentration time curve of etonogestrel (AUC0–24 hours).

    Results

    All women had significant postoperative weight loss. There were no significant differences in AUC0–24 hours, terminal half‐lives (t½), time to peak serum concentrations (Tmax), or apparent oral clearances of etonogestrel (CLoral) before and after gastric bypass surgery on any occasion. Peak serum concentrations (Cmax) increased after 52 ± 2 weeks compared with preoperative values (0.817 ng/ml versus 0.590 ng/ml, P = 0.024).

    Conclusion

    To our knowledge, this is the first study to investigate the effects on desogestrel pharmacokinetics after RYGB. This study did not reveal any clinically significant changes in etonogestrel pharmacokinetics, suggesting that oral desogestrel may be used by women after RYGB surgery. The sample size was limited, however, and therefore the results should be interpreted cautiously.

    Place, publisher, year, edition, pages
    Wiley-Blackwell Publishing Inc., 2019
    Keywords
    Contraceptives; desogestrel; etonogestrel; gastric bypass surgery; hormonal contraception; obesity; oral contraceptives; pharmacokinetic; Roux-en-Y gastric bypass
    National Category
    Obstetrics, Gynecology and Reproductive Medicine
    Identifiers
    urn:nbn:se:liu:diva-154831 (URN)10.1111/1471-0528.15511 (DOI)000458702400012 ()30347490 (PubMedID)2-s2.0-85056623277 (Scopus ID)
    Note

    Funding Agencies|county council of Ostergotland (ALF)

    Available from: 2019-03-07 Created: 2019-03-07 Last updated: 2019-07-05Bibliographically approved
  • 80.
    Ginstman, Charlotte
    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.
    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.
    Authors reply re: Plasma concentrations of etonogestrel in obese women using oral desogestrel before and after Roux-en-Y gastric bypass surgery: a pharmacokinetic study2019In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 126, no 5, p. 677-677Article in journal (Other academic)
    Abstract [en]

    n/a

  • 81.
    Ginstman, Charlotte
    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.
    Frisk, Jessica
    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 Surgery in Norrköping.
    Carlsson, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Ärlemalm, A.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    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.
    Plasma concentrations of etonogestrel in women using oral desogestrel before and after Roux-en-Y gastric bypass surgery: a pharmacokinetic study2019In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 126, no 4, p. 486-492Article in journal (Refereed)
    Abstract [en]

    Objective

    To investigate whether Roux‐en‐Y gastric bypass (RYGB) affects oral desogestrel (etonogestrel) pharmacokinetics.

    Design

    Single centre, open label, phase‐2 pharmacokinetic study.

    Setting

    University hospital of Linköping, Sweden.

    Population

    Fourteen women with planned RYGB surgery were included; nine women aged 18–45 years using 75 micrograms desogestrel completed the study.

    Methods

    Steady‐state etonogestrel pharmacokinetic (PK) parameters were measured on three occasions for each individual (at 8 ± 6 weeks before surgery, and at 12 ± 2 and 52 ± 2 weeks after surgery). Each patient served as her own control. On each occasion, serum samples were collected during a 24‐hour period and etonogestrel concentrations were determined with ultra‐performance liquid chromatography/tandem mass spectrometry.

    Main outcome measures

    Area under the plasma concentration time curve of etonogestrel (AUC0–24 hours).

    Results

    All women had significant postoperative weight loss. There were no significant differences in AUC0–24 hours, terminal half‐lives (t½), time to peak serum concentrations (Tmax), or apparent oral clearances of etonogestrel (CLoral) before and after gastric bypass surgery on any occasion. Peak serum concentrations (Cmax) increased after 52 ± 2 weeks compared with preoperative values (0.817 ng/ml versus 0.590 ng/ml, P = 0.024).

    Conclusion

    To our knowledge, this is the first study to investigate the effects on desogestrel pharmacokinetics after RYGB. This study did not reveal any clinically significant changes in etonogestrel pharmacokinetics, suggesting that oral desogestrel may be used by women after RYGB surgery. The sample size was limited, however, and therefore the results should be interpreted cautiously.

  • 82.
    Grundström, Hanna
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Norrköping.
    Alehagen, Siw
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Berterö, Carina
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Kjölhede, Preben
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Impact of Pelvic Pain and Endometriosis on Patient-Reported Outcomes and Experiences of Benign Hysterectomy: A Study from the Swedish National Register for Gynecological Surgery2018In: Journal of Women's Health, ISSN 1540-9996, E-ISSN 1931-843X, Vol. 27, no 5, p. 691-698Article in journal (Refereed)
    Abstract [en]

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

  • 83.
    Grundström, Hanna
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Norrköping.
    Gerdle, Björn
    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.
    Alehagen, Siw
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Berterö, Carina
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Arendt-Nielsen, Lars
    Center for Sensory‐Motor Interactions, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark.
    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.
    Reduced pain thresholds and signs of sensitization in women with persistent pelvic pain and suspected endometriosis2019In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 98, no 3, p. 327-336Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Endometriosis is a gynecological disorder that may cause considerable pelvic pain in women of fertile age. Determining pain mechanisms is necessary in order to optimize the treatment of the disease. The objective of the study was to evaluate pain thresholds in women with persistent pelvic pain with and without confirmed endometriosis, and healthy, unaffected controls, and analyze how pain thresholds in these cohorts related to duration of pelvic pain, quality of life, and symptoms of anxiety and depression.

    MATERIAL AND METHODS: Pain thresholds for heat, cold and pressure were assessed with quantitative sensory testing on six locations on a reference group of 55 healthy women and on 37 women with persistent pelvic pain who had been admitted for diagnostic laparoscopy on the suspicion of endometriosis. Validated instruments were applied to assess quality of life and symptoms of anxiety and depression. Data were analyzed by means of uni- and multivariate analysis of variance and Spearman's rank-order correlation.

    RESULTS: The women with persistent pelvic pain had significantly lower pain thresholds compared with the reference women. In the women with pain, no differences were observed in pain thresholds between women with (n = 13) and women without (n = 24) biopsy-proven endometriosis. The duration of pelvic pain correlated significantly positively with reduced pain thresholds, ie, the longer the duration, the more sensitization. In the persistent pelvic pain group, pain thresholds for heat correlated significantly with the Short Form Health Survey 36 dimension of bodily pain, and thresholds for cold correlated with Short Form Health Survey 36 bodily pain and with symptoms of depression.

    CONCLUSIONS: Our results showed widespread alterations in pain thresholds in women with persistent pelvic pain that are indicative of central sensitization and a time-dependent correlation. Women with pelvic pain and suspicion of endometriosis should probably be treated more thoroughly to prevent or at least minimize the concomitant development of central sensitization.

    The full text will be freely available from 2019-11-25 12:48
  • 84.
    Grundström, Hanna
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Norrköping.
    Larsson, Britt
    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.
    Arendt-Nielsen, Lars
    Aalborg Univ, Denmark.
    Gerdle, Björn
    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.
    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.
    Associations between pain thresholds for heat, cold and pressure, and Pain Sensitivity Questionnaire scores in healthy women and in women with persistent pelvic pain2019In: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149Article in journal (Refereed)
    Abstract [en]

    Background

    The Pain Sensitivity Questionnaire (PSQ) is a self‐rating instrument developed as a time‐ and cost‐saving alternative to quantitative sensory testing (QST). The aims of the study were to assess (a) the associations between PSQ scores and QST in women with persistent pelvic pain and in pain‐free controls and (b) to what extent demographic variables and psychological distress influenced PSQ scores.

    Methods

    Fifty‐five healthy women and 37 women with persistent pelvic pain participated. All filled in the PSQ and Hospital Anxiety and Depression Scale and had QST (heat, cold and pressure pain thresholds) performed on six locations on the body. Information on age, body mass index, smoking habits and pain duration were collected. Principal component analysis and orthogonal partial least square regressions were used.

    Results

    The patients scored significantly higher on PSQ than the controls. Significant multivariate correlations between pain thresholds and PSQ scores were found only in the patient group. In the patient group, the heat and cold pain thresholds correlated more strongly with PSQ scores than the pressure pain threshold.

    Conclusions

    The PSQ score was significantly higher in pelvic pain patients, and correlations between QSTs and the PSQ were only found for patients.

    Significance

    The PSQ reflects pain sensitivity in women with PPP and can be used as a non‐invasive and painless way to assess this condition in clinical practice.

  • 85.
    Gunnarsson, Rebeqa
    et al.
    Lund Univ, Sweden.
    Dilorenzo, Sebastian
    Uppsala Univ, Sweden; Uppsala Univ, Sweden.
    Lundin-Strom, Kristina B.
    Lund Univ, Sweden.
    Olsson, Linda
    Lund Univ, Sweden; Dept Clin Genet and Pathol, Sweden.
    Biloglav, Andrea
    Lund Univ, Sweden.
    Lilljebjorn, Henrik
    Lund Univ, Sweden.
    Rissler, Marianne
    Lund Univ, Sweden.
    Wahlberg, Per
    Uppsala Univ, Sweden.
    Lundmark, Anders
    Uppsala Univ, Sweden.
    Castor, Anders
    Skane Univ Hosp, Sweden.
    Behrendtz, Mikael
    Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus. Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Fioretos, Thoas
    Lund Univ, Sweden; Dept Clin Genet and Pathol, Sweden.
    Paulsson, Kajsa
    Lund Univ, Sweden.
    Isaksson, Anders
    Uppsala Univ, Sweden.
    Johansson, Bertil
    Lund Univ, Sweden; Dept Clin Genet and Pathol, Sweden.
    Mutation, methylation, and gene expression profiles in dup(1q)-positive pediatric B-cell precursor acute lymphoblastic leukemia2018In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 32, no 10, p. 2117-2125Article in journal (Refereed)
    Abstract [en]

    High-throughput sequencing was applied to investigate the mutation/methylation patterns on 1q and gene expression profiles in pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL) with/without (w/wo) dup(1q). Sequencing of the breakpoint regions and all exons on 1q in seven dup(1q)-positive cases revealed non-synonymous somatic single nucleotide variants (SNVs) in BLZF1, FMN2, KCNT2, LCE1C, NES, and PARP1. Deep sequencing of these in a validation cohort w (n = 17)/wo (n = 94) dup(1q) revealed similar SNV frequencies in the two groups (47% vs. 35%; P = 0.42). Only 0.6% of the 36,259 CpGs on 1q were differentially methylated between cases w (n = 14)/wo (n = 13) dup(1q). RNA sequencing of high hyperdiploid (HeH) and t(1;19)(q23;p13)-positive cases w (n = 14)/wo (n = 52) dup(1q) identified 252 and 424 differentially expressed genes, respectively; only seven overlapped. Of the overexpressed genes in the HeH and t(1;19) groups, 23 and 31%, respectively, mapped to 1q; 60-80% of these encode nucleic acid/protein binding factors or proteins with catalytic activity. We conclude that the pathogenetically important consequence of dup(1q) in BCP ALL is a gene-dosage effect, with the deregulated genes differing between genetic subtypes, but involving similar molecular functions, biological processes, and protein classes.

  • 86.
    Hammar, Mats
    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.
    Larsson, Erika
    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.
    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.
    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.
    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.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Sydsjö, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    A long-term follow-up study of men born with very low birth weight and their reproductive hormone profile2018In: Systems biology in reproductive medicine, ISSN 1939-6376, Vol. 64, no 3, p. 207-215Article in journal (Refereed)
    Abstract [en]

    Environmental factors during the fetal period may adversely affect reproductive functions in men being born with very low birth weight (VLBW, <1500 g). The objective of this prospective, controlled cohort study was to investigate if VLBW men have an altered reproductive hormone profile compared with men born at term. The study group initially consisted of all VLBW boys live-born between 1 February 1987 and 30 April 1988 in the south-east region of Sweden (n = 47). A control child was chosen born at term, at the same hospital, with the same parity, without malformations, and next in order after each VLBW child who survived the first four weeks (n = 45). The present follow-up was performed when the men were 26-28 years of age and included measurements of serum hormone levels, hair testosterone concentration, and anthropometric data. Also life-style questionnaires were collected from 26 VLBW men and 19 controls. The VLBW group (n = 26) had higher median levels of serum estradiol, 84.5 pmol/L than controls (n = 19), 57.5 pmol/L (p = 0.008). There was no significant correlation between serum estradiol and BMI (r = 0.06, p = 0.74). There were no differences in other hormone levels or the reproductive pattern between the groups. In conclusion, even though there was a statistically significant difference in estradiol levels between the groups, both groups had low normal mean levels of questionable clinical significance. The reproductive pattern was similar in the two groups and in this study being born VLBW does not seem to affect these measured aspects of reproduction.

    ABBREVIATIONS: ADHD: attention deficit hyperactive disorder; AGA: average for gestational age; BMI: body mass index; CP: cerebral palsy; DHT: dihydrotestosterone; FSH: follicle stimulating hormone; LBW: low birth weight; LH: luteinizing hormone; SAD: sagittal abdominal diameter; SGA: small for gestational age; SHBG: sex hormone binding globulin; TSH: thyroid stimulating hormone; T3: triiodothyronine; T4: thyroxin; VLBW: very low birth weight.

  • 87.
    Hanberger, Lena
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    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, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Holl, Reinhard W.
    Univ Ulm, Germany; German Inst Diabet Res, Germany.
    Froehlich-Reiterer, Elke
    Med Univ Graz, Austria.
    Åkesson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden; Jonkoping Univ, Sweden.
    Hofer, Sabine
    Med Univ Innsbruck, Austria.
    Type 1 diabetes during adolescence: International comparison between Germany, Austria, and Sweden2018In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, no 3, p. 506-511Article in journal (Refereed)
    Abstract [en]

    Objectives: By using pediatric diabetes quality registries in Austria, Germany, and Sweden treatment of type 1 diabetes and the outcome of care during the vulnerable adolescence period were compared. Methods: Data in DPV, broadly used in Austria and Germany, and Swediabkids used in Sweden, from clinical visits in the year 2013 on 14 383 patients aged 11 to 16 years regarding hemoglobin A1c (HbA1c), insulin regimen, body mass index (BMI)-SD score (SDS), blood pressure, hypoglycemia, ketoacidosis, and smoking habits were analyzed. Results: Patients in Sweden had fewer clinical visits per year (P amp;lt; .05), lower insulin dose per kg (P amp;lt; .001), and lower proportion of fast acting insulin compared with Germany and Austria (P amp;lt; .001). The proportion of pump users was higher in Sweden (P amp;lt; .001). Patients in Sweden had lower mean HbA1c levels (Austria: 64 mmol/mol, Germany: 63 mmol/mol, and Sweden: 61 mmol/mol [8.0%, 7.9%, and 7.7%, respectively]; P amp;lt; .001). The frequency of severe hypoglycemia was higher in Sweden while it was lower for ketoacidosis (3.3% and 1.1%, respectively) than in Austria (1.1% and 5.3%) and Germany (2.0% and 4.4%) (P amp;lt; .001). Girls in all 3 countries had higher HbA1c and BMI-SDS than boys. Conclusions: Sharing data between diabetes registries and nations enables us to better understand differences in diabetes outcome between countries. In this particular comparison, pediatric patients with diabetes in Sweden were more often treated with insulin pump, had lower HbA1c levels and a higher rate of severe hypoglycemia. Patients in Austria and Germany used rapid acting insulin analogs more often and had a lower rate of ketoacidosis.

  • 88.
    Hellberg, Sandra
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Bhai Mehta, Ratnesh
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Forsberg, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    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.
    Winqvist, Ola
    Karolinska Inst, Sweden.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. 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.
    Maintained thymic output of conventional and regulatory T cells during human pregnancy2019In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 143, no 2, p. 771-775.e7Article in journal (Other academic)
    Abstract [en]

    n/a

  • 89.
    Heyne, David
    et al.
    Leiden Univ, Netherlands.
    Gren Landell, 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.
    Melvin, Glenn
    Monash Univ, Australia.
    Gentle-Genitty, Carolyn
    Indiana Univ, IN 47405 USA.
    Differentiation Between School Attendance Problems: Why and How?2019In: Cognitive and Behavioral Practice, ISSN 1077-7229, E-ISSN 1878-187X, Vol. 26, no 1, p. 8-34Article in journal (Refereed)
    Abstract [en]

    School attendance problems (SAPs) are heterogeneous with respect to etiology and presentation. The long history of conceptualizing SAPs has led to a vast array of terms and definitions as well as different perspectives on the most helpful approach to classification. For educators, practitioners, researchers, and policymakers, this presents a challenge in understanding, assessing, and intervening with SAPs. This paper outlines evolution in the conceptualization of SAPs, focusing on two contemporary approaches to differentiating between them. One approach draws on the longstanding differentiation between SAP types labeled school refusal, truancy, and school withdrawal. A fourth type of SAP, labeled school exclusion, is also considered. The other approach focuses on the function of absenteeism, measured via the School Refusal Assessment Scale (SRAS). Anecdotal and scientific support for the SAP typology is presented, along with the benefits and shortcomings of the SRAS approach to differentiation. The paper offers suggestions for how to differentiate between SAPs and introduces the SNACK, a brief screening measure that permits differentiation by SAP type.

  • 90.
    Hjerpe, Elisabet
    et al.
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Staf, Christian
    Sahlgrens Univ Hosp, Sweden.
    Dahm-Kahler, Pernilla
    Sahlgrens Univ Hosp, Sweden.
    Stalberg, Karin
    Uppsala Univ, Sweden.
    Bjurberg, Maria
    Skåne Univ Hosp, Sweden; Lund Univ, Sweden.
    Holmberg, Erik
    Sahlgrens Univ Hosp, Sweden; Sahlgrens Acad, Sweden.
    Borgfeldt, Christer
    Skåne Univ Hosp, Sweden; Lund Univ, Sweden.
    Tholander, Bengt
    Uppsala Univ Hosp, Sweden.
    Hellman, Kristina
    Karolinska Univ Hosp, Sweden; Karolinska Inst, 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.
    Högberg, Thomas
    Lund Univ, Sweden.
    Rosenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    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 Inst, Sweden.
    Lymph node metastases as only qualifier for stage IV serous ovarian cancer confers longer survival than other sites of distant disease - a Swedish Gynecologic Cancer Group (SweGCG) study2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 3, p. 331-337Article in journal (Refereed)
    Abstract [en]

    Background: The International Federation of Gynecology and Obstetrics (FIGO) ovarian cancer staging system includes no sub-stage for lymph nodes (LN) as only distant disease manifestation. We explore the prognostic implication of LN as only stage IV classifier in serous ovarian cancer.Method: This is a nation-wide, population-based study on 551 women with serous stage IV cancers diagnosed between 2009-2014. We compare overall survival (OS) in women with LN as only distant metastatic site to those with pleural metastases only and to patients with other/multiple stage IV manifestations. Cox regression models were used for uni- and multivariable estimations.Results: Of 551stage IV cases, distant metastatic site was registered in 433. Median OS for women with LN (n=51) was 41.4 months, compared to 25.2 and 26.8 months for patients with pleural (n=195) or other/multiple (n=187) distant metastases (p=.0007). The corresponding five-year survival rates were 32, 11 and 22%, respectively. Multivariable analyzes confirmed shorter survival for women with pleural (HR 2.99, p=.001) or other/multiple distant sites (HR 2.67, p=.007), as compared to LN cases. LN only patients lived 9.1 months longer after primary than after interval surgery, but this difference was not significant (p=.245).Conclusion: Women with stage IV serous ovarian cancer having lymph nodes as only distant metastatic site live longer than other stage IV patients.

  • 91.
    Hjertberg, Linda
    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, 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.
    Pihl, Sofia
    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.
    Maternal Body Mass Index and Anovaginal Distance in Active Phase of Term Labor2018In: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, article id 1532949Article in journal (Refereed)
    Abstract [en]

    Introduction. To evaluate if there was a difference in the anovaginal distance (AVD) measured by transperineal ultrasound between obese and normal weight women. Material and Methods. A prospective observational study including 207 primiparous women at term in first stage of labor. Transperineal ultrasound with a vaginal probe was used to measure the AVD. Maternal, pregnancy, and delivery characteristics potentially associated with perineal thickness were extracted from womans medical records. The participants were divided into three BMI groups based on maternal weight in early pregnancy: normal weight (BMI amp;lt; 25), overweight (BMI 25-29.9), and obesity (BMI amp;gt;= 30). Obese and overweight women were compared with normal weight women regarding the AVD. Results. The mean AVD was 24.3, 24.9, and 27.0 mm in the normal weight, overweight, and obesity group, respectively. There were no group differences in background characteristics. The AVD was significantly longer in obese women compared with normal weight women (p = 0.018). Conclusions. The observed longer AVD in obese women might be protective of the anal sphincter complex, explaining lower rates of anal sphincter injuries in this group. Further studies are indicated to evaluate whether the length of the AVD plays a role in the risk assessment of obstetric anal sphincter injury.

  • 92.
    Höglund, Markus
    et al.
    Region Östergötland, Public Dental Health Care, Orofacial Medicine/Hospital Dentistry Linköping. Karolinska Inst, Sweden.
    Bågesund, 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, Public Dental Health Care.
    Shahnavaz, Shervin
    Karolinska Inst, Sweden.
    Wardh, Inger
    Karolinska Inst, Sweden; Acad Ctr Geriatr Dent, Sweden.
    Evaluation of the ability of dental clinicians to rate dental anxietyIn: European Journal of Oral Sciences, ISSN 0909-8836, E-ISSN 1600-0722Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to evaluate the ability of dental clinicians to rate dental anxiety. A total of 104 clinicians from 24 public dental clinics in the Region of ostergotland, Sweden, examined 1,128 adult patients undergoing their regular dental examination. The patients rated their dental anxiety using the Modified Dental Anxiety Scale and a Visual Analogue Scale. After the examination, the clinicians rated the patients levels of dental anxiety on a Visual Analogue Scale. The correlation (r(s)) between the clinicians and patients ratings of dental anxiety was 0.45. Among highly dentally anxious patients, there was no correlation between clinicians and patients ratings. Dental clinicians rated dental anxiety lower than their patients did, especially if the patients were highly anxious. The ability of clinicians to rate dental anxiety was better when the clinician was older and the patient was older. There was an inverse association between clinicians confidence and their ability to rate a patients dental anxiety. In conclusion, clinicians are unsuccessful in identifying a dentally anxious patient without the concurrent use of patient self-assessment tools. A Visual Analogue Scale is a suitable screening tool in general practice for detection of dental anxiety.

  • 93.
    Ingberg, Edvin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Orebro Univ, Sweden.
    Dock, Hua
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Theodorsson, Annette
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Ström, Jakob O.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Orebro Univ, Sweden.
    Effect of laser Doppler flowmetry and occlusion time on outcome variability and mortality in rat middle cerebral artery occlusion: inconclusive results2018In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 19, article id 24Article in journal (Refereed)
    Abstract [en]

    Background: Stroke is among the leading causes of death and disability. Although intense research efforts have provided promising treatment options in animals, most clinical trials in humans have failed and the therapeutic options are few. Several factors have been suggested to explain this translational difficulty, particularly concerning methodology and study design. Consistent infarcts and low mortality might be desirable in some, but not all, studies. Here, we aimed to investigate whether the use of laser Doppler flowmetry (LDF) and the occlusion time (60 vs. 45 min) affected outcome variability and mortality in a rat stroke model. Eighty ovariectomized female Wistar rats were subjected to ischemic stroke using intraluminal filament middle cerebral artery occlusion with or without LDF and with occlusion times of 45 or 60 min. Outcome was evaluated by triphenyl tetrazolium chloride staining of brain slices to measure infarct size and a modified sticky tape test. Results: Neither LDF nor occlusion times of 45 versus 60 min significantly affected mortality, outcome variability or outcome severity. Conclusions: Due to the unexpectedly high mortality and variability the statistical power was very low and thus the results were inconclusive.

  • 94.
    Iso-Touru, Terhi
    et al.
    Nat Resources Inst Finland Luke, Finland.
    Wurmser, Christine
    Tech Univ Munich, Germany.
    Venhoranta, Heli
    Univ Helsinki, Finland.
    Hiltpold, Maya
    Swiss Fed Inst Technol, Switzerland.
    Savolainen, Tujia
    Univ Helsinki, Finland.
    Sironen, Anu
    Nat Resources Inst Finland Luke, Finland.
    Fischer, Konrad
    Tech Univ Munich, Germany.
    Flisikowski, Krzysztof
    Tech Univ Munich, Germany.
    Fries, Ruedi
    Tech Univ Munich, Germany.
    Vicente Carrillo, Alejandro
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Alvarez-Rodriguez, Manuel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Nagy, Szabolcs
    Univ Pannonia, Hungary.
    Mutikainen, Mervi
    Nat Resources Inst Finland Luke, Finland.
    Peippo, Jaana
    Nat Resources Inst Finland Luke, Finland.
    Taponen, Juhani
    Univ Helsinki, Finland.
    Sahana, Goutam
    Aarhus Univ, Denmark.
    Guldbrandtsen, Bernt
    Aarhus Univ, Denmark.
    Simonen, Henri
    VikingGenet, Finland.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Andersson, Magnus
    Univ Helsinki, Finland.
    Pausch, Hubert
    Swiss Fed Inst Technol, Switzerland.
    A splice donor variant in CCDC189 is associated with asthenospermia in Nordic Red dairy cattle2019In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 20, no 1, article id 286Article in journal (Refereed)
    Abstract [en]

    Background

    Cattle populations are highly amenable to the genetic mapping of male reproductive traits because longitudinal data on ejaculate quality and dense microarray-derived genotypes are available for thousands of artificial insemination bulls. Two young Nordic Red bulls delivered sperm with low progressive motility (i.e., asthenospermia) during a semen collection period of more than four months. The bulls were related through a common ancestor on both their paternal and maternal ancestry. Thus, a recessive mode of inheritance of asthenospermia was suspected.

    Results

    Both bulls were genotyped at 54,001 SNPs using the Illumina BovineSNP50 Bead chip. A scan for autozygosity revealed that they were identical by descent for a 2.98 Mb segment located on bovine chromosome 25. This haplotype was not found in the homozygous state in 8557 fertile bulls although five homozygous haplotype carriers were expected (P = 0.018). Whole genome-sequencing uncovered that both asthenospermic bulls were homozygous for a mutation that disrupts a canonical 5′ splice donor site of CCDC189 encoding the coiled-coil domain containing protein 189. Transcription analysis showed that the derived allele activates a cryptic splice site resulting in a frameshift and premature termination of translation. The mutated CCDC189 protein is truncated by more than 40%, thus lacking the flagellar C1a complex subunit C1a-32 that is supposed to modulate the physiological movement of the sperm flagella. The mutant allele occurs at a frequency of 2.5% in Nordic Red cattle.

    Conclusions

    Our study in cattle uncovered that CCDC189 is required for physiological movement of sperm flagella thus enabling active progression of spermatozoa and fertilization. A direct gene test may be implemented to monitor the asthenospermia-associated allele and prevent the birth of homozygous bulls that are infertile. Our results have been integrated in the Online Mendelian Inheritance in Animals (OMIA) database (https://omia.org/OMIA002167/9913/).

  • 95.
    Ivars, Katrin
    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 of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Nelson, 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. Department of Quality and Patient Safety, Karolinska University Hospital, Stockholm, Sweden.
    Theodorsson, Annette
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Ström, Jakob O.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Department of Neurology, Faculty of Medicine and Health, University of Örebro, Örebro, Sweden.
    Mörelius, Evalotte
    Linköping University, Department of Social and Welfare Studies, 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.
    Development of salivary cortisol circadian rhythm in preterm infants2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 8, article id e0182685Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To investigate at what age preterm infants develop a salivary cortisol circadian rhythm and identify whether it is dependent on gestational age and/or postnatal age. To evaluate whether salivary cortisol circadian rhythm development is related to behavioral regularity. To elucidate salivary cortisol levels in preterm infants during the first year of life.

    METHODS: This prospective, longitudinal study included 51 preterm infants. 130 healthy full-term infants served as controls. Monthly salivary cortisol levels were obtained in the morning (07:30-09:30), at noon (10:00-12:00), and in the evening (19:30-21:30), beginning at gestational age week 28-32 and continuing until twelve months corrected age. Behavioral regularity was studied using the Baby Behavior Questionnaire.

    RESULTS: A salivary cortisol circadian rhythm was established by one month corrected age and persisted throughout the first year. The preterm infants showed a cortisol pattern increasingly more alike the full-term infants as the first year progressed. The preterm infants increase in behavioral regularity with age but no correlation was found between the development of salivary cortisol circadian rhythm and the development of behavior regularity. The time to establish salivary cortisol circadian rhythm differed between preterm and full-term infants according to postnatal age (p = 0.001) and was dependent on gestational age. Monthly salivary cortisol levels for preterm infants from birth until twelve months are presented. Additional findings were that topical corticosteroid medication was associated with higher concentrations of salivary cortisol (p = 0.02) and establishment of salivary cortisol circadian rhythm occurred later in infants treated with topical corticosteroid medication (p = 0.02).

    CONCLUSIONS: Salivary cortisol circadian rhythm is established by one month corrected age in preterm infants. Establishment of salivary cortisol circadian rhythm is related to gestational age rather than to postnatal age. Salivary cortisol circadian rhythm development is not related to behavioral regularity.

  • 96.
    Johansson, Torsten
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Department Orthopaed, Sweden.
    Lindblad, Maria
    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 Orthopaedics in Norrköping.
    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
    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.
    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.
    Incidence of Perthes disease in children born between 1973 and 1993: A Swedish nationwide cohort study of 2.1 million individuals2017In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 88, no 1, p. 96-100Article in journal (Refereed)
    Abstract [en]

    Background and purpose - The incidence of Perthes disease as reported in the literature varies widely between and within countries. The etiology of the disease is still unknown. Both environmental and genetic factors have been suggested to play a part in either causing the disease or increasing the susceptibility of an individual. We determined the incidence of Perthes disease in Sweden and investigated possible relationships to parental socioeconomic status, ethnicity, marital status, mothers age when giving birth, parity, number of siblings, and smoking habits. Patients and methods - Six Swedish population-based registers were used, together covering all children born in Sweden from 1973 through 1993. Results - The incidence of Perthes disease in Sweden was 9.3 per 100,000 subjects. The ratio between boys and girls was 3.1:1. The educational level of the father and the mother of a child with Perthes disease was lower than in the controls. The incidence was lower when the fathers were in the highest income bracket (above the 90(th) percentile). A higher proportion of parents of Nordic lineage had children with Perthes disease than parental pairs with one or both who were not of such lineage. Interpretation - This study confirms that there is an association between the incidence of Perthes disease and the socioeconomic status of the parents.

  • 97.
    Jonsdottir, Berglind
    et al.
    Department of Clinical Sciences, Lund University, Skåne University Hospital Malmö, Sweden.
    Larsson, Christer
    Department of Laboratory Medicine, Lund University, Lund. Sweden.
    Carlsson, Annelie
    Department of Pediatrics, Lund University, Skåne University Hospital, Lund, Sweden.
    Forsander, Gun
    Department of Pediatrics, The Queen Silvia Children´s Hospital, Gothenburg, Sweden.
    Ivarsson, Sten Anders
    Department of Clinical Sciences, Lund University, Skåne University Hospital Malmö, Sweden.
    Lernmark, Åke
    Department of Clinical Sciences, Lund University, Skåne University Hospital Malmö, Sweden.
    Ludvigsson, Johnny
    Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics 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.
    Marcus, Claude
    Division of Pediatrics, Department of Clinical Science, Intervention and Technology Karolinska Institute, Stockholm, 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.
    Örtqvist, Eva
    Pediatric Endocrinology Unit, Department of Woman and Child Health, Karolinska Institute, Stockholm, Sweden.
    Elding Larsson, Helena
    Department of Clinical Sciences, Lund University, Skåne University Hospital Malmö, Sweden.
    Thyroid and islet autoantibodies predict autoimmune thyroid disease already at Type 1 diabetes diagnosis.2017In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 102, no 4, p. 1277-1285Article in journal (Refereed)
    Abstract [en]

    CONTEXT: Screening of autoimmune thyroid disease in children and young adults with Type 1 diabetes is important but vary greatly between clinics.

    OBJECTIVE: The aim was to determine the predictive value of thyroid autoantibodies, thyroid function, islet autoantibodies, and HLA- DQ at diagnosis of Type 1 diabetes for autoimmune thyroid disease during subsequent follow-up.

    SETTING: 43 Paediatric Endocrinology units Sweden. Design, patients and main outcome measures: At diagnosis of Type 1 diabetes, samples from 2433 children were analysed for autoantibodies against thyroid peroxidase (TPOAb), thyroglobulin (TGAb), glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma-associated protein-2 (IA-2A), and the three variants of the zinc transporter 8 (ZnT8W/R/QA) as well as HLA-DQA1-B1 genotypes and thyroid function. After 5.1-9.5 years disease duration, children treated with thyroxine were identified in the Swedish National Board of Health and Welfare Prescribed Drug Register.

    RESULTS: Thyroxine had been prescribed to 6% (147/2433; 66% girls). In patients below 5 years, female gender (HR=4.60, p=0.008) and GADA (HR=5.80, p=0.02) were significant predictors. In patients 5-10 years, TPOAb (HR=20.56, p<0.0001), TGAb (HR=3.40, p=0.006) and TSH outside the reference limit (HR=3.64, p<0.001) were predictors while in the 10-15 year olds, TPOAb (HR=17.00, p<0.001) and TSH outside the reference limit (HR=4.11, p<0.001) predicted future thyroxine prescription.

    CONCLUSION: In addition to TPOAb and TSH, positive GADA tested at the diagnosis of type 1 diabetes is important for the prediction of autoimmune thyroid disease in children below 5 years of age.

  • 98.
    Kempe, Per
    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. Cty Hosp Sundsvall, Sweden.
    Eklund, Daniel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Hallin, Agnes
    Not Found:Linkoping Univ, Dept Clin and Expt Med, SE-58185 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.
    Olsson, Tomas
    Karolinska Inst, Sweden.
    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.
    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.
    Immune profile in relation to sex steroid cyclicity in healthy women and women with multiple sclerosis2018In: Journal of Reproductive Immunology, ISSN 0165-0378, E-ISSN 1872-7603, Vol. 126, p. 53-59Article in journal (Refereed)
    Abstract [en]

    To prospectively study systemic in vivo immunological effects of sex hormones, using different phases of oral combined hormonal contraceptives (CHC), and the natural menstrual cycles in both healthy women and in women with multiple sclerosis (MS), blood samples from sixty female MS patients and healthy controls with and without CHC were drawn in high and low estrogenic/progestogenic phases. Expression of Th-associated genes in blood cells was determined by qPCR and a panel of cytokines and chemokines was measured in plasma. High hormone level phases were associated with increases in Th1 (TBX21) and Th2 (GATA3) associated markers, as well as the B cell-associated chemokine CXCL13, while the inhibitory regulator CTLA-4 was decreased. These changes were not observed in MS patients, of whom most were treated with immunomodulatory drugs. Our data indicate immune activating properties in vivo of high steroid sex hormone levels during both CHC and normal menstrual cyclicity.

  • 99.
    Kernell, Kristina
    et al.
    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.
    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.
    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.
    Birth characteristics of women with Marfan syndrome, obstetric and neonatal outcomes of their pregnancies-A nationwide cohort and case-control study2017In: European Journal of Obstetrics, Gynecology, and Reproductive Biology, ISSN 0301-2115, E-ISSN 1872-7654, Vol. 215, p. 106-111Article in journal (Refereed)
    Abstract [en]

    Objective: The aim was to investigate birth characteristics, obstetric and neonatal outcomes of the first childbirth in women with Marfan syndrome by use of Swedish national registers since pregnancy-related outcomes in women with Marfan syndrome have only been sparsely investigated. Study design: In this national population-based cohort study and matched case-control study of Swedish women born 1973-1993, women with Marfan syndrome (n =273) were compared to women without the condition (n = 1 017 265). The study population was followed until 2013. A total of 364 553 mother -firstborn-offspring pairs were analyzed. Sixty-one women with Marfan syndrome became mothers. Women with Marfan syndrome were also compared to 543 healthy controls. Results: Women with Marfan syndrome were more often born preterm (p amp;lt; 0.001), small-for-gestational age (p amp;lt; 0.001), and delivered by cesarean section (p = 0.001). Women with Marfan syndrome had no increased risk of giving birth by cesarean section (p = 0.079). No increased neonatal risks in their children were found. Women with Marfan syndrome were less likely to give birth than those without (p amp;lt; 0.001). There were no maternal deaths. Conclusions: Women with Marfan syndrome were more likely to be born preterm, SGA and by cesarean section. These increased risks of preterm birth and SGA babies were not found in connection with their own first childbirth. Pregnancies with known fetal Marfan syndrome have to be carefully monitored. The results are important for obstetricians giving preconception counseling and treating women with Marfan syndrome. Further studies are needed to evaluate risks during pregnancy and long-term effects of pregnancy on the cardiovascular status of women with Marfan syndrome. (C) 2017 Elsevier B.V. All rights reserved.

  • 100.
    Kilander, Helena
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Berterö, Carina
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Eksjo Nassjo Hosp, Sweden.
    Thor, Johan
    Jonkoping Univ, Sweden.
    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.
    Alehagen, Siw
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Womens experiences of contraceptive counselling in the context of an abortion - An interview study2018In: Sexual & Reproductive HealthCare, ISSN 1877-5756, E-ISSN 1877-5764, Vol. 17, p. 103-107Article in journal (Refereed)
    Abstract [en]

    Objective: To identify and understand womens lived experiences of contraceptive counselling given at the same time as abortion counselling. Methods: We interviewed 13 women aged 20-39 who had experienced an abortion and the related counselling. The women were recruited from five hospitals in Sweden. Interviews were analysed using an interpretative phenomenological approach. Results: We identified two themes: need for respectful counselling and needs for guidance and access to contraceptives. The essence "Being in a state of limbo and feeling sceptical" was coalesced from the themes. The women described a state of limbo, as being caught in an unwanted and emotionally charged situation. They reported that respectful counselling and meeting a skilled health professional helped to dispel their scepticism and influenced their plans for contraceptive use post abortion. Furthermore, women who wanted an intrauterine device described difficulties in access post abortion. Conclusion: The women seem to have a limited receptivity to contraceptive counselling when they have an unwanted pregnancy and are sceptical about contraceptives. Women, who experience respect in the counselling, report being helped in contraceptive decision-making. To receive respectful counselling and to have good access to intrauterine devices emerged as central needs among women at the time of an abortion.

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