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  • 1.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Martinez-Serrano, Cristina
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Wright, Dominic
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Barranco, Isabel
    Univ Girona, Spain.
    Roca, Jordi
    Univ Murcia, Spain.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    The Transcriptome of Pig Spermatozoa, and Its Role in Fertility2020In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol. 21, no 5, article id 1572Article in journal (Refereed)
    Abstract [en]

    In the study presented here we identified transcriptomic markers for fertility in the cargo of pig ejaculated spermatozoa using porcine-specific micro-arrays (GeneChip((R)) miRNA 4.0 and GeneChip((R)) Porcine Gene 1.0 ST). We report (i) the relative abundance of the ssc-miR-1285, miR-16, miR-4332, miR-92a, miR-671-5p, miR-4334-5p, miR-425-5p, miR-191, miR-92b-5p and miR-15b miRNAs, and (ii) the presence of 347 up-regulated and 174 down-regulated RNA transcripts in high-fertility breeding boars, based on differences of farrowing rate (FS) and litter size (LS), relative to low-fertility boars in the (Artificial Insemination) AI program. An overrepresentation analysis of the protein class (PANTHER) identified significant fold-increases for C-C chemokine binding (GO:0019957): CCR7, which activates B- and T-lymphocytes, 8-fold increase), XCR1 and CXCR4 (with ubiquitin as a natural ligand, 1.24-fold increase), cytokine receptor activity (GO:0005126): IL23R receptor of the IL23 protein, associated to JAK2 and STAT3, 3.4-fold increase), the TGF-receptor (PC00035) genes ACVR1C and ACVR2B (12-fold increase). Moreover, two micro-RNAs (miR-221 and mir-621) were down- and up-regulated, respectively, in high-fertility males. In conclusion, boars with different fertility performance possess a wide variety of differentially expressed RNA present in spermatozoa that would be attractive targets as non-invasive molecular markers for predicting fertility.

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  • 2.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Ntzouni, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Wright, Dominic
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Khan, Kabirul Islam
    Chattogram Vet and Anim Sci Univ, Bangladesh.
    Lopez-Bejar, Manel
    Univ Autonoma Barcelona, Spain.
    Martinez-Serrano, Cristina
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Chicken seminal fluid lacks CD9-and CD44-bearing extracellular vesicles2020In: Reproduction in domestic animals, ISSN 0936-6768, E-ISSN 1439-0531Article in journal (Refereed)
    Abstract [en]

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

  • 3.
    Andersson White, Pär
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Jones, Michael P.
    Macquarie Univ, Australia.
    Faresjö, Tomas
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Inequalities in cardiovascular risks among Swedish adolescents (ABIS): a prospective cohort study2020In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 10, no 2, article id e030613Article in journal (Refereed)
    Abstract [en]

    Objectives To investigate if socioeconomic status (SES) is predictive of cardiovascular risk factors among Swedish adolescents. Identify the most important SES variable for the development of each cardiovascular risk factor. Investigate at what age SES inequality in overweight and obesity occurs. Design Longitudinal follow-up of a prospective birth cohort. Setting All Babies in Southeast Sweden (ABIS) study includes data from children born between October 1997 and October 1999 in five counties of south east Sweden. Participants A regional ABIS-study subsample from three major cities of the region n=298 adolescents aged 16-18 years, and prospective data from the whole ABIS cohort for overweight and obesity status at the ages 2, 5, 8 and 12 years (n=2998-7925). Outcome measures Blood pressure above the hypertension limit, overweight/obesity according to the International Obesity Task Force definition, low high-density lipoproteins (HDL) or borderline-high low-density lipoproteins according to National Cholesterol Education Program expert panel on cholesterol levels in children. Results For three out of four cardiovascular risk outcomes (elevated blood pressure, low HDL and overweight/obesity), there were increased risk in one or more of the low SES groups (p<0.05). The best predictor was parental occupational class (Swedish socioeconomic classification index) for elevated blood pressure (area under the receiver operating characteristic (ROC) curve 0.623), maternal educational level for overweight (area under the ROC curve 0.641) and blue-collar city of residence for low HDL (area under the ROC curve 0.641). SES-related differences in overweight/obesity were found at age 2, 5 and 12 and for obesity at age 2, 5, 8 and 12 years (all p<0.05). Conclusions Even in a welfare state like Sweden, SES inequalities in cardiovascular risks are evident already in childhood and adolescence. Intervention programmes to reduce cardiovascular risk based on social inequality should start early in life.

  • 4.
    Anderzen, Johan
    et al.
    Department of Paediatrics, County Hospital Ryhov, Jönköping, Sweden.
    Hermann, Julia M.
    Institute of Epidemiology and Medical Biometry, ZIBMT, Ulm University, Ulm, Germany, German Center for Diabetes Research (DZD), München‐Neuherberg, Germany.
    Samuelsson, Ulf
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Charalampopoulos, Dimitrios
    Great Ormond Street Institute of Child Health, University College London, London, UK.
    Svensson, Jannet
    Paediatric Department, CPH‐Direct, Herlev University Hospital, Herlev, Denmark.
    Skrivarhaug, Torild
    Division of Paediatric and Adolescent Medicine, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Froehlich-Reiterer, Elke
    Department of Paediatrics, Medical University of Graz, Graz, Austria.
    Maahs, David M.
    Division of Pediatric Endocrinology and Stanford Diabetes Research Center, Stanford, California, USA.
    Åkesson, Karin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Cty Hosp Ryhov, Sweden.
    Kapellen, Thomas
    University Children's Hospital Leipzig, Leipzig, Germany.
    Fritsch, Maria
    Department of Paediatrics, Medical University of Vienna, Vienna, Austria.
    Birkebaek, Niels H.
    Department of Paediatrics, Aarhus University Hospital, Aarhus, Denmark.
    Drivvoll, Ann K.
    Division of Paediatric and Adolescent Medicine, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Miller, Kellee
    Jaeb Center for Health Research, Tampa, Florida, USA.
    Stephenson, Terence
    Great Ormond Street Institute of Child Health, University College London, London, UK.
    Hofer, Sabine E.
    Department of Paediatrics, Medical University of Innsbruck, Innsbruck, Austria.
    Fredheim, Siri
    Paediatric Department, CPH‐Direct, Herlev University Hospital, Herlev, Denmark.
    Kummernes, Siv J.
    Division of Paediatric and Adolescent Medicine, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Foster, Nicole
    Jaeb Center for Health Research, Tampa, Florida, USA.
    Amin, Rakesh
    Great Ormond Street Institute of Child Health, University College London, London, UK.
    Hilgard, Doerte
    Pediatric Practice, Witten, Germany.
    Rami-Merhar, Birgit
    Department of Paediatrics, Medical University of Vienna, Vienna, Austria.
    Dahl-Jorgensen, Knut
    Division of Paediatric and Adolescent Medicine, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Clements, Mark
    Children's Mercy Hospital, Kansas City, Missouri, USA University of Missouri, Kansas City, Missouri, USA University of Kansas Medical Center, Kansas City, Kansas, USA.
    Hanas, Ragnar
    Department of Paediatrics, NU Hospital Group, Uddevalla, Sweden and the Sahlgrenska Academy, Institute of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden.
    Holl, Reinhard W.
    Institute of Epidemiology and Medical Biometry, ZIBMT, Ulm University, Ulm, Germany German Center for Diabetes Research (DZD), München‐Neuherberg, Germany.
    Warner, Justin T.
    Department of Paediatric Endocrinology and Diabetes, Children's Hospital for Wales, Cardiff, UK.
    International benchmarking in type 1 diabetes: Large difference in childhood HbA1c between eight high-income countries but similar rise during adolescence-A quality registry study2020In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448Article in journal (Refereed)
    Abstract [en]

    Objectives To identify differences and similarities in HbA1c levels and patterns regarding age and gender in eight high-income countries. Subjects 66 071 children and adolescents below18 years of age with type 1 diabetes for at least 3 months and at least one HbA1c measurement during the study period. Methods Pediatric Diabetes Quality Registry data from Austria, Denmark, England, Germany, Norway, Sweden, the United States, and Wales were collected between 2013 and 2014. HbA1c, gender, age, and duration were used in the analysis. Results Distribution of gender and age groups was similar in the eight participating countries. The mean HbA1c varied from 60 to 73 mmol/mol (7.6%-8.8%) between the countries. The increase in HbA1c between the youngest (0-9 years) to the oldest (15-17 years) age group was close to 8 mmol/mol (0.7%) in all countries (P < .001). Females had a 1 mmol/mol (0.1%) higher mean HbA1c than boys (P < .001) in seven out of eight countries. Conclusions In spite of large differences in the mean HbA1c between countries, a remarkable similarity in the increase of HbA1c from childhood to adolescence was found.

  • 5.
    Andolf, E.
    et al.
    Karolinska Inst, Sweden.
    Bladh, Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Möller, Louise
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Sydsjö, Gunilla
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Prior placental bed disorders and later dementia: a retrospective Swedish register-based cohort study2020In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528Article in journal (Refereed)
    Abstract [en]

    Objective To investigate the association between a history of placental bed disorders and later dementia. Design Retrospective population-based cohort study. Setting Sweden. Sample All women giving birth in Sweden between 1973 and 1993 (1 128 709). Methods Women with and without placental bed disorders (hypertensive disorders of pregnancy including pre-eclampsia, fetal growth restriction, spontaneous preterm labour and birth, preterm premature rupture of membranes, abruptio placenta, late miscarriages) and other pregnancy complications were identified by means of the Swedish Medical Birth Register. International classification of disease was used. Data were linked to other National Registers. Participants were followed up until 2013. The Cox proportional hazards model was used to calculate hazard ratios for women with and without pregnancy complications and were adjusted for possible confounders. Main outcome measures Diagnosis of vascular dementia and non-vascular dementia. Results Adjusted for cardiovascular disease and socio-demographic factors, an increased risk of vascular dementia was shown in women with previous pregnancy-induced hypertension (Hazard ratio [HR] 1.88, 95% CI 1.32-2.69), pre-eclampsia (HR 1.63, 95% CI 1.23-2.16), spontaneous preterm labour and birth (HR 1.65, 95% CI 1.12-2.42) or preterm premature rupture of membranes (HR 1.60, 95% CI 1.08-2.37). No statistically significant increased risk was seen for other pregnancy complications or non-vascular dementia even though many of the point estimates indicated increased risks. Conclusions Women with placental bed disorders have a higher risk for vascular disease. Mechanisms behind the abnormal placentation remain elusive, although maternal constitutional factors, abnormal implantation as well as impaired angiogenesis have been suggested. Tweetable abstract Placental bed syndromes associated with vascular dementia even after adjusting for cardiovascular disease.

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  • 6.
    Barrett, Elizabeth
    et al.
    Univ Coll Dublin, Ireland; Childrens Univ Hosp, Ireland.
    Jacobs, Brian
    South London and Maudsley Hosp, England; European Union Med Specialists UEMS CAP, Belgium.
    Klasen, Henrikje
    Leiden Univ, Netherlands.
    Herguner, Sabri
    Child and Adolescent Psychiat, Turkey.
    Agnafors, Sara
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Banjac, Visnja
    Univ Clin Ctr Republ Srpska, Bosnia and Herceg.
    Bezborodovs, Nikita
    Riga Stradins Univ, Latvia.
    Cini, Erica
    East London Fdn Trust, England.
    Hamann, Christoph
    Univ Bern, Switzerland.
    Huscsava, Mercedes M.
    Med Univ Vienna, Austria.
    Kostadinova, Maya
    Univ Hosp Alexandrovska, Bulgaria; DNCC CAMHS, Ireland.
    Kramar, Yuliia
    TMA PSYCHIAT, Ukraine.
    Maravic, Vanja Mandic
    Inst Mental Hlth, Serbia.
    McGrath, Jane
    Cherry Orchard Hosp, Ireland.
    Molteni, Silvia
    Univ Pavia, Italy.
    Goretti Moron-Nozaleda, Maria
    Hosp Infantil Univ Nino Jesus, Spain.
    Mudra, Susanne
    Univ Med Ctr Hamburg Eppendorf, Germany.
    Nikolova, Gordana
    Univ Clin Psychiat, North Macedonia.
    Vorkas, Kallistheni Pantelidou
    Cypriot Soc Child and Adolescent Psychiat, Cyprus.
    Prata, Ana Teresa
    Hosp Dona Estefania, Portugal.
    Revet, Alexis
    Univ Toulouse III, France.
    Joseph, Judeson Royle
    Univ Hosp North Norway, Norway.
    Serbak, Reelika
    Tallinn Childrens Hosp, Estonia.
    Tomac, Aran
    CAMHS Clare, Ireland.
    Van den Steene, Helena
    Univ Antwerp, Belgium.
    Xylouris, Georgios
    Gen Childrens Hosp Agia Sophia, Greece.
    Zielinska, Anna
    Med Univ Warsaw, Poland.
    Hebebrand, Johannes
    Univ Duisburg Essen, Germany.
    The child and adolescent psychiatry: study of training in Europe (CAP-STATE)2020In: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165X, Vol. 29, no 1, p. 11-27Article in journal (Refereed)
    Abstract [en]

    There is great cultural diversity across Europe. This is reflected in the organisation of child and adolescent mental health (CAMH) services and the training of the respective professionals in different countries in Europe. Patients and their parents will want a high quality, knowledgeable, and skillful service from child and adolescent psychiatrists (CAPs) wherever they see them in Europe. A European comparison of training programs allows all stakeholders in different European countries to assess the diversity and to initiate discussions as to the introduction of improvements within national training programs. Major issues to be addressed in comparing child and adolescent psychiatric training programs across Europe include: (1) formal organisation and content of training programs and the relationship to adult psychiatry and paediatrics; (2) flexibility of training, given different trainee interests and that many trainees will have young families; (3) quality of governance of training systems; (4) access to research; and (5) networking. The Child and Adolescent Psychiatry-Study of Training in Europe (CAP-State) is a survey of training for child and adolescent psychiatrists (CAPs) across European countries. It aims to revisit and extend the survey carried out in 2006 by Karabekiroglu and colleagues. The current article is embedded in a special issue of European Child + Adolescent Psychiatry attempting to for the first time address training in CAP at the European and global levels. Structured information was sought from each of 38 European and neighboring countries (subsequently loosely referred to as Europe) and obtained from 31. The information was provided by a senior trainee or recently qualified specialist and their information was checked and supplemented by information from a senior child and adolescent psychiatry trainer. Results showed that there is a very wide range of provision of training in child and adolescent psychiatry in different countries in Europe. There remains very substantial diversity in training across Europe and in the degree to which it is subject to national oversight and governance. Some possible reasons for this variation are discussed and some recommendations made.

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

    The original article has been corrected.

  • 8.
    Borendal Wodlin, Ninnie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Risk Factors for Impaired Patient-Reported Satisfaction and Increased Length of Hospital Stay Following Hysterectomy on Benign Indications in Premenopausal Women: a Study From the Swedish National Register for Gynecological Surgery2020In: Geburtshilfe und Frauenheilkunde, ISSN 0016-5751, E-ISSN 1438-8804, Vol. 80, no 3, p. 288-299Article in journal (Refereed)
    Abstract [en]

    Introduction The aims of the study were to evaluate the impact of intra- and postoperative complications on satisfaction one year after hysterectomy for benign conditions, to determine risk factors for low patient satisfaction and to analyze whether complications were associated with the length of hospital stay. Material and Methods A retrospective study of 27938 women from the Swedish National Register for Gynecological Surgery undergoing hysterectomy for benign conditions between January 2004 and June 2016. Data were obtained from prospectively collected pre-, peri- and postoperative forms. Statistical analyses were performed using multivariable logistic regression models. Crude and adjusted odds ratios and 95% confidence intervals are presented. Results More than 90% were satisfied with the hysterectomy. Dissatisfaction was associated with complications. Pelvic pain as indication, preoperatively having less expectations to get rid of symptoms or being alleviated from surgery, and current smoking were also risk factors for low patient satisfaction. Vaginal and abdominal subtotal hysterectomies were associated with high satisfaction. Occurrence of complications intra- and postoperatively before discharge was associated with increased length of hospital stay, as well as occurrence and severity of complications reported after discharge from hospital. Conclusions Complications were strongly associated with lower patient satisfaction. Preoperative expectations of surgery, indication, mode of surgery and life-style factors had impact on the satisfaction. Patient-centered information to ensure realistic expectations and prevention of complications seem to be essential to gain optimal patient satisfaction with surgery.

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  • 9.
    Cambra, J. M.
    et al.
    Univ Murcia, Spain; Inst Biomed Res Murcia IMIB Arrixaca, Spain.
    Martinez-Serrano, Cristina
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Univ Murcia, Spain; Inst Biomed Res Murcia IMIB Arrixaca, Spain.
    Maside, C.
    Univ Murcia, Spain; Inst Biomed Res Murcia IMIB Arrixaca, Spain.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Martinez, E. A.
    Univ Murcia, Spain; Inst Biomed Res Murcia IMIB Arrixaca, Spain.
    Gil, M. A.
    Univ Murcia, Spain; Inst Biomed Res Murcia IMIB Arrixaca, Spain.
    Cuello, C.
    Univ Murcia, Spain; Inst Biomed Res Murcia IMIB Arrixaca, Spain.
    The cytokine platelet factor 4 successfully replaces bovine serum albumin for the in vitro culture of porcine embryos2020In: Theriogenology, ISSN 0093-691X, E-ISSN 1879-3231, Vol. 148, p. 201-207Article in journal (Refereed)
    Abstract [en]

    The cytokine platelet factor 4 (PF4) enhances differentiation and cell viability of different stem cells lines in vitro. This study investigated whether PF4 addition to customary pig embryo semi-defined culture media can improve their developmental outcome (Experiment 1) and ultimately replace the need for bovine serum albumin (BSA, Experiment 2). Experiment 1 added PF4 (100-1000 ng/mL, 0 = control) to NCSU-23 with 0.4 mg/mL BSA culturing 3430 presumptive zygotes. Experiment 2 added PF4 (100 -1000 ng/mL, 0 = Control-PVA) to a BSA-free medium (NCSU-23 with 0.3 mg/mL PVA) culturing 3820 presumptive zygotes. Zygote culture in NCSU-23 with 0.4 mg/mL BSA was used as overall control. All groups of Experiment 1 displayed similar rates of day 2-cleavage (range: 65.0 +/- 10.9 to 70.0 +/- 5.8%); of day 7-blastocyst rates (range: 46.6 +/- 10.0 to 56.4 +/- 8.2%) and of total day 7-blastocyst efficiency (range: 32.3 +/- 8.3 to 37.2 +/- 7.3%). Addition of PF4 did not affect total cell numbers of day 7 blastocysts (range: 44.1 +/- 23.2 to 50.5 +/- 26.4). In Experiment 2, PF4 accelerated embryo development, increasing (P < 0.01) blastocyst yield compared to 0-PF4, and blastocyst formation by day 5 adding PF4 100-500 ng/mL (range: 29.9 +/- 7.8 to 31.8 +/- 5.5%; P < 0.05) compared with BSA-control (17.2 +/- 8.2%) and PF4 1000 ng/mL (15.5 +/- 7.9%); showing similar blastocyst rates (range: 42.0 +/- 11.5 to 49.3 +/- 10.0%), total efficiency (28.0 +/- 8.2 to 32.3 +/- 7.1%) total cell numbers (range: 42.6 +/- 19.3 to 45.7 +/- 23.9) as BSA-controls. In conclusion, although PF4 did not show additive improvement under usual semi-defined, BSA-supplemented embryo media, it successfully replaced BSA sustaining porcine blastocyst production in chemically defined conditions. (C) 2019 Elsevier Inc. All rights reserved.

  • 10.
    Carlhäll, Sara
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Kallen, Karin
    Lund Univ, Sweden.
    Blomberg, Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    The effect of maternal body mass index on duration of induced labor2020In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412Article in journal (Refereed)
    Abstract [en]

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

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  • 11.
    Carlsson, Annelie
    et al.
    Lund Univ, Sweden.
    Shepherd, Maggie
    Univ Exeter, England.
    Ellard, Sian
    Univ Exeter, England; Royal Devon and Exeter NHS Fdn Trust, England.
    Weedon, Michael
    Univ Exeter, England.
    Lernmark, Ake
    Lund Univ, Sweden.
    Forsander, Gun
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Colclough, Kevin
    Royal Devon and Exeter NHS Fdn Trust, England.
    Brahimi, Qefsere
    Lund Univ, Sweden.
    Valtonen-Andre, Camilla
    Univ and Reg Labs Reg, Sweden.
    Ivarsson, Sten A.
    Lund Univ, Sweden.
    Elding Larsson, Helena
    Lund Univ, Sweden.
    Samuelsson, Ulf
    Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Ortqvist, Eva
    Karolinska Inst, Sweden.
    Groop, Leif
    Univ Helsinki, Finland.
    Ludvigsson, Johnny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Marcus, Claude
    Karolinska Inst, Sweden.
    Hattersley, Andrew T.
    Univ Exeter, England.
    Absence of Islet Autoantibodies and Modestly Raised Glucose Values at Diabetes Diagnosis Should Lead to Testing for MODY: Lessons From a 5-Year Pediatric Swedish National Cohort Study2020In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 43, no 1, p. 82-89Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 12.
    Dedrick, Sandra
    et al.
    Boston Coll, MA 02167 USA.
    Sundaresh, Bharathi
    Boston Coll, MA 02167 USA.
    Huang, Qian
    Boston Coll, MA 02167 USA.
    Brady, Claudia
    Boston Coll, MA 02167 USA.
    Yoo, Tessa
    Boston Coll, MA 02167 USA.
    Cronin, Catherine
    Boston Coll, MA 02167 USA.
    Rudnicki, Caitlin
    Boston Coll, MA 02167 USA.
    Flood, Michael
    Boston Coll, MA 02167 USA.
    Momeni, Babak
    Boston Coll, MA 02167 USA.
    Ludvigsson, Johnny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Altindis, Emrah
    Boston Coll, MA 02167 USA.
    The Role of Gut Microbiota and Environmental Factors in Type 1 Diabetes Pathogenesis2020In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 11, article id 78Article, review/survey (Refereed)
    Abstract [en]

    Type 1 Diabetes (T1D) is regarded as an autoimmune disease characterized by insulin deficiency resulting from destruction of pancreatic beta-cells. The incidence rates of T1D have increased worldwide. Over the past decades, progress has been made in understanding the complexity of the immune response and its role in T1D pathogenesis, however, the trigger of T1D autoimmunity remains unclear. The increasing incidence rates, immigrant studies, and twin studies suggest that environmental factors play an important role and the trigger cannot simply be explained by genetic predisposition. Several research initiatives have identified environmental factors that potentially contribute to the onset of T1D autoimmunity and the progression of disease in children/young adults. More recently, the interplay between gut microbiota and the immune system has been implicated as an important factor in T1D pathogenesis. Although results often vary between studies, broad compositional and diversity patterns have emerged from both longitudinal and cross-sectional human studies. T1D patients have a less diverse gut microbiota, an increased prevalence of Bacteriodetes taxa and an aberrant metabolomic profile compared to healthy controls. In this comprehensive review, we present the data obtained from both animal and human studies focusing on the large longitudinal human studies. These studies are particularly valuable in elucidating the environmental factors that lead to aberrant gut microbiota composition and potentially contribute to T1D. We also discuss how environmental factors, such as birth mode, diet, and antibiotic use modulate gut microbiota and how this potentially contributes to T1D. In the final section, we focus on existing recent literature on microbiota-produced metabolites, proteins, and gut virome function as potential protectants or triggers of T1D onset. Overall, current results indicate that higher levels of diversity along with the presence of beneficial microbes and the resulting microbial-produced metabolites can act as protectors against T1D onset. However, the specifics of the interplay between host and microbes are yet to be discovered.

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  • 13.
    Douvlataniotis, Karolos
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Bensberg, Maike
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Lentini, Antonio
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Gylemo, Björn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Nestor, Colm
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    No evidence for DNA N-6-methyladenine in mammals2020In: Science Advances, E-ISSN 2375-2548, Vol. 6, no 12, article id eaay3335Article in journal (Refereed)
    Abstract [en]

    N-6-methyladenine (6mdA) is a widespread DNA modification in bacteria. More recently, 6mdA has also been characterized in mammalian DNA. However, measurements of 6mdA abundance and profiles are often very dissimilar between studies, even when performed on DNA from identical mammalian cell types. Using comprehensive bioinformatics analyses of published data and novel experimental approaches, we reveal that efforts to assay 6mdA in mammals have been severely compromised by bacterial contamination, RNA contamination, technological limitations, and antibody nonspecificity. These complications render 6mdA an exceptionally problematic DNA modification to study and have resulted in erroneous detection of 6mdA in several mammalian systems. Together, our results strongly imply that the evidence published to date is not sufficient to support the presence of 6mdA in mammals.

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  • 14.
    Forsberg, Anna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Huoman, Johanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Söderholm, Simon
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. 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.
    Nilsson, Lennart
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    Abrahamsson, Thomas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Ernerudh, Jan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Gustafsson, Mika
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Jenmalm, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Pre- and postnatal Lactobacillus reuteri treatment alters DNA methylation of infant T helper cells2020In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038Article in journal (Refereed)
    Abstract [en]

    Background Perinatal childhood exposures, including probiotic supplementation, may affect epigenetic modifications and impact on immune maturation and allergy development. The aim of this study was to assess the effects of pre- and postnatal Lactobacillus reuteri supplementation on DNA methylation in relation to immune maturation and allergy development. Methods DNA methylation patterns were investigated for allergy-related T helper subsets using a locus-specific method and at a genome-wide scale using the Illumina 450K array. From a randomised, double-blind, placebo-controlled allergy prevention trial with pre- and postnatal probiotic supplementation, CD4+ T helper cells were obtained at birth (from cord blood), and 12 and 24 months of age (total (placebo/probiotics); locus-specific method: CB = 32 (17/15), 12 months = 24 (9/15), 24 months = 35 (15/20); Illumina: CB = 19 (10/9), 12 months = 10 (6/4), 24 months = 19(11/8)). Results Comparing probiotics to placebo, the greatest genome-wide differential DNA methylation was observed at birth, where the majority of sites were hypomethylated, indicating transcriptional accessibility in the probiotic group. Bioinformatic analyses, including network analyses, revealed a module containing 91 genes, enriched for immune-related pathways such as chemotaxis, PI3K-Akt, MAPK and TGF-beta signalling. A majority of the module genes were associated with atopic manifestations (OR = 1.43, P = 2.4 x 10(-6)), and a classifier built on this model could predict allergy development (AUC = 0.78, P = 3.0 x 10(e-3)). Pathways such as IFN-gamma signalling and T-cell activation were more hypermethylated at birth compared with later in life in both intervention groups over time, in line with DNA methylation patterns in the IFNG locus obtained by the locus-specific methodology. Conclusion Maternal L. reuteri supplementation during pregnancy alters DNA methylation patterns in CD4+ T cells towards enhanced immune activation at birth, which may affect immune maturation and allergy development.

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  • 15.
    Gawel, Danuta
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Serra I 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 Biomedical and Clinical Sciences, 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 Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Hjortswang, Henrik
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Karlsson, Jan-Erik
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Köpsen, 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 Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Li, Xinxiu
    Linköping University, Department of Biomedical and Clinical Sciences, 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 Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Schäfer, Samuel
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Seifert, Oliver
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Sonmez, Ceylan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. 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
    Not Found:Linkoping Univ, Dept Phys Chem and Biol, Bioinformat, Linkoping, Sweden.
    Åkesson, Karin
    Linköping University, Department of Biomedical and Clinical Sciences, 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; MIT, MA 02139 USA; 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 Biomedical and Clinical Sciences, 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 Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Correction: A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases (vol 11, 47, 2019)2020In: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 12, no 1, article id 37Article in journal (Refereed)
    Abstract [en]

    An amendment to this paper has been published and can be accessed via the original article.

  • 16.
    Ginstman, Charlotte
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Kopp Kallner, Helena
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Fagerberg-Silwer, Johanna
    Danderyd Hosp, Sweden.
    Carlsson, Björn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Drug Research. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
    Ärlemalm, Andreas
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Böttiger, Ylva
    Linköping University, Department of Biomedical and Clinical 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 Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Pharmacokinetics of Oral Levonorgestrel in Women After Roux-en-Y Gastric Bypass Surgery and in BMI-Matched Controls2020In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428Article in journal (Refereed)
    Abstract [en]

    Background

    Women are advised to primarily use non-oral contraceptive alternatives after Roux-en-Y gastric bypass since it is not known if the surgery affects the pharmacokinetics of oral contraceptives.

    Methods

    This is a multi-center, open label, phase 2 pharmacokinetic study performed at the University Hospital of Linköping and the Clinical Trials Center, Department of Obstetrics and Gynecology, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden. Fifteen women aged 18–40 years who had previously undergone Roux-en-Y gastric bypass surgery and reached a BMI < 30 were included. Fifteen BMI-matched women with no previous history of Roux-en-Y gastric bypass surgery served as a control group. After administration of a single dose of a combined oral contraceptive containing 0.03 mg ethinylestradiol/0.15 mg levonorgestrel, serum levonorgestrel concentrations were determined during a 24-h period using ultra performance liquid chromatography/tandem mass spectrometry. The area under the plasma concentration time curve of levonorgestrel (AUC0–24h) was the main outcome measure.

    Results

    There were no significant differences in the studied pharmacokinetic parameters, AUC0–24h, total AUC, peak serum concentration (Cmax), time to peak serum concentrations (Tmax), apparent oral clearances of levonorgestrel (CLoral), or terminal half-lives (t½) between the groups.

    Conclusion

    This is to our knowledge the first study to evaluate the pharmacokinetics of oral levonorgestrel in women with a BMI < 30 at least 1 year after RYGB compared with a BMI-matched group of women. We could not find any significant pharmacokinetic differences between the groups, suggesting that oral levonorgestrel may be used in non-obese women after Roux-en-Y gastric bypass once a stable body weight has been reached.

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  • 17.
    Jung Lee, Eun Jung
    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. Yonsei Univ, South Korea.
    Lilja, Sandra
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Li, Xinxiu
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Schäfer, Samuel
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Zhang, Huan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Benson, Mikael
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Bulk and single cell transcriptomic data indicate that a dichotomy between inflammatory pathways in peripheral blood and arthritic joints complicates biomarker discovery2020In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 127, article id 154960Article in journal (Refereed)
    Abstract [en]

    Background: Unbiased studies using different genome-wide methods have identified several novel biomarkers for diagnosis and treatment response in Rheumatoid Arthritis (RA). However, clinical translation has proven difficult. Here, we hypothesized that one reason could be that inflammatory responses in peripheral blood are different from those in the arthritic joint. Methods: We performed meta-analysis of gene expression microarray data from synovium, whole blood cells (WBC), peripheral blood mononuclear cells (PBMC), and CD4+ T cells from patients with RA and healthy controls in order to identify overlapping pathways, upstream regulators and potential biomarkers. We also analyzed single cell RNA-sequencing (scRNA-seq) data from peripheral blood and whole joints from a mouse model of antigen-induced arthritis. Results: Analyses of two profiling data sets from synovium from RA patients and healthy controls all showed significant activation of pathways with known pathogenic relevance, such as the Th1 pathway, the role of NFAT in regulation of the immune response, dendritic cell maturation, iCOS-iCOSL signaling in T helper cells, Fc gamma receptor-mediated phagocytosis, interferon signaling, Cdc42 signaling, and cytotoxic T lymphocyte-mediated apoptosis. The most activated upstream regulators included TNF, an important drug target, as well as IFN-gamma and CD40LG, all of which are known to play important pathogenic roles in RA. The differentially expressed genes from synovium included several potential biomarkers, such as CCL5, CCL13, CCL18, CX3CL1, CXCL6, CXCL9, CXCL10, CXCL13, ILLS, IL32, IL1RN, SPP1, and TNFSF11. By contrast, microarray studies of WBC, PBMC and CD4+ T cells showed variable pathways and limited pathway overlap with synovium. Similarly, scRNA-seq data from a mouse model of arthritis did not support that inflammatory responses in peripheral blood reflect those in the arthritic joints. These data showed pathway overlap between mouse joint cells and synovium from patients with RA, but not with cells in peripheral blood. Conclusions: Our findings indicate a dichotomy between gene expression changes, pathways, upstream regulators and biomarkers in synovium and cell types in peripheral blood, which complicates identification of biomarkers in blood.

  • 18.
    Li, Xinxiu
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Jung Lee, Eun Jung
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Yonsei Univ, South Korea.
    Gawel, Danuta
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Lilja, Sandra
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Schäfer, Samuel
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Zhang, Huan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Benson, Mikael
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Meta-Analysis of Expression Profiling Data Indicates Need for Combinatorial Biomarkers in Pediatric Ulcerative Colitis2020In: Journal of Immunology Research, ISSN 2314-8861, E-ISSN 2314-7156, Vol. 2020, article id 8279619Article in journal (Refereed)
    Abstract [en]

    Background. Unbiased studies using different genome-wide methods have identified a great number of candidate biomarkers for diagnosis and treatment response in pediatric ulcerative colitis (UC). However, clinical translation has been proven difficult. Here, we hypothesized that one reason could be differences between inflammatory responses in an inflamed gut and in peripheral blood cells. Methods. We performed meta-analysis of gene expression microarray data from intestinal biopsies and whole blood cells (WBC) from pediatric patients with UC and healthy controls in order to identify overlapping pathways, predicted upstream regulators, and potential biomarkers. Results. Analyses of profiling datasets from colonic biopsies showed good agreement between different studies regarding pathways and predicted upstream regulators. The most activated predicted upstream regulators included TNF, which is known to have a key pathogenic and therapeutic role in pediatric UC. Despite this, the expression levels of TNF were increased in neither colonic biopsies nor WBC. A potential explanation was increased expression of TNFR2, one of the membrane-bound receptors of TNF in the inflamed colon. Further analyses showed a similar pattern of complex relations between the expression levels of the regulators and their receptors. We also found limited overlap between pathways and predicted upstream regulators in colonic biopsies and WBC. An extended search including all differentially expressed genes that overlapped between colonic biopsies and WBC only resulted in identification of three potential biomarkers involved in the regulation of intestinal inflammation. However, two had been previously proposed in adult inflammatory bowel diseases (IBD), namely, MMP9 and PROK2. Conclusions. Our findings indicate that biomarker identification in pediatric UC is complicated by the involvement of multiple pathways, each of which includes many different types of genes in the blood or inflamed intestine. Therefore, further studies for identification of combinatorial biomarkers are warranted. Our study may provide candidate biomarkers for such studies.

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  • 19.
    Lichtenstein Liljeblad, Karin
    et al.
    Karolinska Inst, Sweden; Danderyd Hosp, Sweden.
    Kopp Kallner, Helena
    Karolinska Inst, Sweden; Danderyd Hosp, Sweden.
    Brynhildsen, Jan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Risk of abortion within 1-2 years after childbirth in relation to contraceptive choice: a retrospective cohort studyIn: European journal of contraception & reproductive health care, ISSN 1362-5187, E-ISSN 1473-0782Article in journal (Refereed)
    Abstract [en]

    Objectives: The primary objective of the study was to investigate whether the choice of long-acting reversible contraception (LARC) was associated with the risk of abortion over a period of 24 months postpartum. The secondary objective was to analyse whether other significant factors were affecting the risk of abortion during this period. Methods: In this retrospective cohort study, we analysed 11,066 women who had delivered in three Swedish cities during 2013 and 2014. Demographic and medical variables were obtained from medical records. Attendance at the postpartum visit, choice of postpartum contraception and history of abortion was noted. Logistic regression analysis was performed to assess factors associated with the risk of abortion. The main outcome measure was the proportion of women with abortion up to 24 months postpartum. Results: Data from 11,066 women were included in the final analysis. Within 12-24 months after delivery 2.5% of women had an abortion. The choice of LARC after childbirth reduced the risk of subsequent abortion (odds ratio 0.74; 95% confidence interval [CI] 0.60, 0.91; p = .005). Smoking, age amp;lt;25 years and have had a previous abortion significantly increased the risk of abortion during follow-up, whereas exclusive breastfeeding decreased the risk. Conclusions: Increasing the proportion of women who choose LARC postpartum could decrease the risk of abortion for up to 2 years after childbirth.

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  • 20.
    Lindblad, Maria
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Dept Orthoped, Sweden.
    Josefsson, Ann
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Bladh, Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Sydsjö, Gunilla
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Johansson, Torsten
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Dept Orthoped, Sweden.
    Risk factors during pregnancy and delivery for the development of Perthes disease, a nationwide Swedish study of 2.1 million individuals2020In: BMC Pregnancy and Childbirth, ISSN 1471-2393, E-ISSN 1471-2393, BMC PREGNANCY AND CHILDBIRTH, Vol. 20, no 1, article id 192Article in journal (Refereed)
    Abstract [en]

    Background

    To ascertain or disprove a correlation between suboptimal birth characteristics, breech position at delivery and development of Perthes’ disease.

    Methods

    Study material was collected from nationwide registers regarding diagnoses, birth statistics and delivery data. As study population were included children with a diagnosis code for Perthes’ disease who were alive and living in Sweden at age 13. Children with missing birth statistics were excluded. All children with no Perthes’ disease diagnosis were used as control group. Both single and multiple logistical regression analyses were used to calculate OR for the included characteristics.

    Results

    Children in breech position had a higher risk for developing Perthes’ disease. Children with Perthes’ disease had also a higher probability of having been born pre-term, very pre-term or post-term. Lower than normal birth weight and a lower Apgar-score were also associated with Perthes’ disease.

    Conclusions

    There is a correlation between breech birth and development of Perthes’ disease. There is also correlation to suboptimal birth characteristics. Despite our findings this should not be used for screening of Perthes’ disease as the percentage of children who actually develop it is very low. Also, as of yet there is no possibility to diagnose Perthes’ disease before the presence of skeletal changes. Our findings could be important in finding the cause of Perthes’ disease and therefore developing better diagnostics, treatment and prevention.

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  • 21.
    Ludvigsson, Johnny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Autoantigen Treatment in Type 1 Diabetes: Unsolved Questions on How to Select Autoantigen and Administration Route2020In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol. 21, no 5, article id 1598Article, review/survey (Refereed)
    Abstract [en]

    Autoantigen treatment has been tried for the prevention of type 1 diabetes (T1D) and to preserve residual beta-cell function in patients with a recent onset of the disease. In experimental animal models, efficacy was good, but was insufficient in human subjects. Besides the possible minor efficacy of peroral insulin in high-risk individuals to prevent T1D, autoantigen prevention trials have failed. Other studies on autoantigen prevention and intervention at diagnosis are ongoing. One problem is to select autoantigen/s; others are dose and route. Oral administration may be improved by using different vehicles. Proinsulin peptide therapy in patients with T1D has shown possible minor efficacy. In patients with newly diagnosed T1D, subcutaneous injection of glutamic acid decarboxylase (GAD) bound to alum hydroxide (GAD-alum) can likely preserve beta-cell function, but the therapeutic effect needs to be improved. Intra-lymphatic administration may be a better alternative than subcutaneous administration, and combination therapy might improve efficacy. This review elucidates some actual problems of autoantigen therapy in the prevention and/or early intervention of type 1 diabetes.

  • 22.
    Magnusson, Louise
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Uppsala Univ, Sweden.
    Barcenilla, Hugo
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Pihl, Mikael
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Bensing, Sophie
    Karolinska Inst, Sweden.
    Espes, Daniel
    Uppsala Univ, Sweden; Uppsala Univ, Sweden.
    Carlsson, Per-Ola
    Uppsala Univ, Sweden; Uppsala Univ, Sweden.
    Casas, Rosaura
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Mass Cytometry Studies of Patients With Autoimmune Endocrine Diseases Reveal Distinct Disease-Specific Alterations in Immune Cell Subsets2020In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 11, article id 288Article in journal (Refereed)
    Abstract [en]

    Although there is evidence that autoimmune diseases share similar immunogenetic mechanisms, studies comparing peripheral CD45(+) cells from patients with autoimmune endocrine diseases in parallel are limited. In this study, we applied high-dimensional single-cell mass cytometry to phenotypically characterize PBMC from patients with new-onset (N-T1D) and long-standing type 1 diabetes, Hashimotos thyroiditis (HT), Graves disease and autoimmune Addisons disease (AD), as well as healthy controls. The frequency of CD20(lo)CD27(hi)CD38(hi)HLA-DRint plasmablasts, CD86(+)CD14(lo)CD16(+) non-classical monocytes and two subsets of CD56(dim)HLA-DR+IFN-gamma(+) NK cells were increased in patients with HT. Subsets of CD56(dim)CD69(+)HLA-DR- NK cells and CD8(+) TEMRA cells, both expressing IFN-gamma, were expanded and reduced, respectively, in the N-T1D group. In addition, patients with AD were characterized by an increased percentage of central memory CD8(+) T cells that expressed CCR4, GATA3, and IL-2. We demonstrate that patients with N-T1D, HT, and AD had altered frequencies of distinct subsets within antigen-presenting and cytotoxic cell lineages. Previously unreported alterations of specific cell subsets were identified in samples from patients with HT and AD. Our study might contribute to a better understanding of shared and diverging immunological features between autoimmune endocrine diseases.

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  • 23.
    Malmborg, Agota
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Brynte, Louise
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Falk, Gabriella
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Brynhildsen, Jan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Hammar, Mats
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Berterö, Carina
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Nursing Sciences and Reproductive Health. Linköping University, Faculty of Medicine and Health Sciences.
    Sexual function changes attributed to hormonal contraception use - a qualitative study of women experiencing negative effects2020In: European journal of contraception & reproductive health care, ISSN 1362-5187, E-ISSN 1473-0782Article in journal (Refereed)
    Abstract [en]

    Objective: To increase the understanding of women who experience negative effects on sexual function when using hormonal contraception. Methods: We performed 24 in-depth interviews with women who had previously experienced negative sexual function effects while using hormonal contraceptives. The thematic analysis method was used. Results: After experience comes insight, Lubrication and desire go hand in hand, Mental wellbeing comes before desire and The contraceptive counsellor potentially facilitates insight and decision-making were the main themes found in the study. Conclusions: This selected group of women described lubrication difficulties and decreased sexual desire associated with both contraceptive use and the menstrual cycle. Contraceptive use became easier with age and with better understanding. The contraceptive counsellor could facilitate the process. Further choice between hormonal or non-hormonal contraceptive methods depended primarily on experienced adverse effects on mood, and secondarily on sexual function, weighed against the advantages or disadvantages experienced during the persons own menstrual cycle.

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  • 24.
    Martinez, Cristina A
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Rubér, Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Rodriguez-Martinez, Heriberto
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health.
    Alvarez-Rodriguez, Manuel
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health.
    Pig Pregnancies after Transfer of Allogeneic Embryos Show a Dysregulated Endometrial/Placental Cytokine Balance: A Novel Clue for Embryo Death?2020In: Biomolecules, E-ISSN 2218-273X, Vol. 10, no 4, article id E554Article in journal (Refereed)
    Abstract [en]

    Pig embryo transfer (ET) is burdened by high embryo mortality, with cytokines playing a significant role in recruitment of immune cells during embryo attachment and placentation. We hereby tested if their levels in endometrium and placenta from sows carrying hemi-allogeneic (artificially inseminated sows; C+ positive control) or allogeneic embryos (sows subjected to ET; ET) during peri-implantation (D18) or post-implantation (D24) are suitable mirrors of embryo rejection or tolerance after ET. Non-pregnant sows (C-) were used as negative controls. A set of cytokines was assayed in the tissues through multiplexed microsphere-based flow cytometry (Luminex xMAP, Millipore. USA). Fewer (58.7%. p < 0.003) conceptuses were recovered at D24 after ET compared to C+ (80.9%); with more than 20% of the ET conceptuses being developmentally delayed. Cytokine levels shifted during implantation. Anti-inflammatory IL-10 levels were significantly (p < 0.05) lower in ET sows compared to C+ at D24 of pregnancy. The C+ controls (carrying hemi-allogeneic embryos) consistently showed higher levels of pro-inflammatory TNF-α, IFN-γ, and IL-2 cytokines at D18 and IL-1α at D24, compared to the ET group. This clear dysregulation of pro- and anti-inflammatory cytokine levels in sows subjected to ET could be associated with an impaired maternal immune tolerance, explaining the high embryonic mortality of ET programs.

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  • 25.
    Martinez-Serrano, Cristina
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Alvarez-Rodriguez, Manuel
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Wright, Dominic
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Does the Pre-Ovulatory Pig Oviduct Rule Sperm Capacitation In Vivo Mediating Transcriptomics of Catsper Channels?2020In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol. 21, no 5, article id 1840Article in journal (Refereed)
    Abstract [en]

    Spermatozoa need to conduct a series of biochemical changes termed capacitation in order to fertilize. In vivo, capacitation is sequentially achieved during sperm transport and interaction with the female genital tract, by mechanisms yet undisclosed in detail. However, when boar spermatozoa are stored in the tubal reservoir pre-ovulation, most appear to be in a non-capacitated state. This study aimed at deciphering the transcriptomics of capacitation-related genes in the pig pre-ovulatory oviduct, following the entry of semen or of sperm-free seminal plasma (SP). Ex-vivo samples of the utero-tubal junction (UTJ) and isthmus were examined with a microarray chip (GeneChip((R)) Porcine Gene 1.0 ST Array, Thermo Fisher Scientific) followed by bioinformatics for enriched analysis of functional categories (GO terms) and restrictive statistics. The results confirmed that entry of semen or of relative amounts of sperm-free SP modifies gene expression of these segments, pre-ovulation. It further shows that enriched genes are differentially associated with pathways relating to sperm motility, acrosome reaction, single fertilization, and the regulation of signal transduction GO terms. In particular, the pre-ovulation oviduct stimulates the Catsper channels for sperm Ca2+ influx, with AKAPs, CATSPERs, and CABYR genes being positive regulators while PKIs and CRISP1 genes appear to be inhibitors of the process. We postulate that the stimulation of PKIs and CRISP1 genes in the pre-ovulation sperm reservoir/adjacent isthmus, mediated by SP, act to prevent premature massive capacitation prior to ovulation.

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  • 26.
    Moltubak, Elin
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Cty Hosp Ryhov, Sweden.
    Landerholm, Kalle
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Cty Hosp Ryhov, Sweden.
    Blomberg, Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Redéen, Stefan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Andersson, Roland
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Cty Hosp Ryhov, Sweden.
    Major Variation in the Incidence of Appendicitis Before, During and After Pregnancy: A Population-Based Cohort Study2020In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323Article in journal (Refereed)
    Abstract [en]

    Background Previous studies indicate a low incidence of appendicitis in third-trimester pregnancy, suggesting a protecting effect of pregnancy. This large population-based cohort study analyzes the association of appendicitis with pregnancy in more detail. The aim of the study was to investigate the incidence of appendicitis and negative appendectomy before, during and after pregnancy. Methods Cross-linking between two Swedish health registries provided data on appendectomy for all women in Sweden giving birth between 1973 and 2013. We analyzed the incidence rates (IR) of perforated and non-perforated appendicitis and negative appendectomy before, during and after pregnancy, and secular trends during the study period. Standardized incidence ratios (SIR) were estimated using age-, sex- and period-specific IR from the background population in Sweden. Results Some 3,888,452 pregnancies resulted in birth during the study period. An appendectomy was registered for 27,575 women in the interval starting one year before and ending two years after pregnancy. The incidence of appendicitis varied substantially during and after pregnancy. SIR for perforated appendicitis was 0.47 (95% CI 0.38-0.59) in the third trimester, 3.89 (2.92-5.18) peripartum, 2.20 (1.89-2.55) in the puerperium and 1.27 (1.19-1.36) in the year postpartum. The pattern was similar for non-perforated appendicitis. Negative appendectomy decreased postpartum. Incidence rate of non-perforated appendicitis and negative appendectomy decreased for both pregnant and non-pregnant women during the study period. Conclusions The findings in this study suggest a protecting effect of pregnancy on the development of appendicitis, which is followed by a rebound effect after birth.

  • 27.
    Najafi, Davood
    et al.
    Baqiyatallah University of Medical Sciences, Tehran, Iran.
    Taheri, Ramezan Ali
    Baqiyatallah University of Medical Sciences, Tehran, Iran.
    Najafi, Abouzar
    University of Tabriz, Tabriz, Iran.
    Shamsollahi, Mohammad
    University of Tabriz, Tabriz, Iran.
    Alvarez-Rodriguez, Manuel
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
    Effect of astaxanthin nanoparticles in protecting the post-thawing quality of rooster sperm challenged by cadmium administration.2020In: Poultry Science, ISSN 0032-5791, E-ISSN 1525-3171, Vol. 99, no 3, p. 1678-1686, article id S0032-5791(19)57917-2Article in journal (Refereed)
    Abstract [en]

    The protective role of astaxanthin nanoparticles (Ast NPs, 25 mg/kg p.o) against cadmium (Cd, 1 mg/100 g b.w. SC), a known inductor of lipid peroxidation and changes in the antioxidant defense system in the Ross 308 breeder roosters sperm, was examined. Sperm motility (computer-assisted sperm motility analysis), membrane integrity (hypoosmotic swelling test), viability, total abnormality, and enzymatic parameters were assessed after thawing. The testis/body weight (mg/kg) ratio and HE staining results of testis were also performed. The obtained results showed that Cd induced detrimental effects on testis and sperm, while Cd treated by Ast NPs (Cd Ast) diminished this change compared to the Cd group. Cd-treated group resulted in significantly (P < 0.05) lowest total (37.29 ± 2.46) and progressive (5.84 ± 0.47) motility and decreased antioxidant enzyme activity (CAT, TAC, and GPx), as well as producing a significant (P < 0.05) decrease in testis weight (mg) compared to the control group. Treatment with Ast NPs (Ast NPs + Cd) had reversed Cd-induced changes in the antioxidant defense system and significantly prevented Cd-induced testis damage. In conclusion, the results of our work suggest that Ast NPs at 25 mg/kg act as a potent antioxidant in protecting rooster testes against oxidative stress induced by Cd.

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  • 28.
    Oppi, Sara
    et al.
    Univ Zurich, Switzerland.
    Nusser-Stein, Stefanie
    Univ Zurich, Switzerland.
    Blyszczuk, Przemyslaw
    Univ Hosp Zurich, Switzerland; Jagiellonian Univ, Poland.
    Wang, Xu
    Shanghai Jiao Tong Univ, Peoples R China.
    Jomard, Anne
    Swiss Fed Inst Technol, Switzerland; Univ Hosp Zurich, Switzerland.
    Marzolla, Vincenzo
    Univ Zurich, Switzerland; IRCCS San Raffaele Pisana, Italy.
    Yang, Kangmin
    Univ Zurich, Switzerland.
    Velagapudi, Srividya
    Univ Zurich, Switzerland.
    Ward, Liam
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Yuan, Ximing
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Geiger, Martin A.
    Univ Estadual Campinas, Brazil.
    Guillaumon, Ana T.
    Univ Estadual Campinas, Brazil.
    Othman, Alaa
    Univ Hosp Zurich, Switzerland.
    Hornemann, Thorsten
    Univ Hosp Zurich, Switzerland.
    Rancic, Zoran
    Univ Hosp Zurich, Switzerland.
    Ryu, Dongryeol
    Sungkyunkwan Univ, South Korea.
    Oosterveer, Maaike H.
    Univ Groningen, Netherlands.
    Osto, Elena
    Univ Zurich, Switzerland; Swiss Fed Inst Technol, Switzerland; Univ Hosp Zurich, Switzerland.
    Luscher, Thomas F.
    Univ Zurich, Switzerland; Royal Brompton and Harefield Hosp Trust, England; Imperial Coll London, England.
    Stein, Sokrates
    Univ Zurich, Switzerland.
    Macrophage NCOR1 protects from atherosclerosis by repressing a pro-atherogenic PPAR gamma signature2020In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 41, no 9, p. 995-1005Article in journal (Refereed)
    Abstract [en]

    Aims Nuclear receptors and their cofactors regulate key pathophysiological processes in atherosclerosis development. The transcriptional activity of these nuclear receptors is controlled by the nuclear receptor corepressors (NCOR), scaffolding proteins that form the basis of large corepressor complexes. Studies with primary macrophages demonstrated that the deletion of Ncor1 increases the expression of atherosclerotic molecules. However, the role of nuclear receptor corepressors in atherogenesis is unknown. Methods and results We generated myeloid cell-specific Ncor1 knockout mice and crossbred them with low-density lipoprotein receptor and results (Ldlr) knockouts to study the role of macrophage NCOR1 in atherosclerosis. We demonstrate that myeloid cellspecific deletion of nuclear receptor corepressor 1 (NCOR1) aggravates atherosclerosis development in mice. Macrophage Ncorl-deficiency leads to increased foam cell formation, enhanced expression of pro-inflammatory cytokines, and atherosclerotic lesions characterized by larger necrotic cores and thinner fibrous caps. The immunometabolic effects of NCOR1 are mediated via suppression of peroxisome proliferator-activated receptor gamma (PPAR gamma) target genes in mouse and human macrophages, which lead to an enhanced expression of the CD36 scavenger receptor and subsequent increase in oxidized low-density lipoprotein uptake in the absence of NCOR1. Interestingly, in human atherosclerotic plaques, the expression of NCOR1 is reduced whereas the PPAR gamma signature is increased, and this signature is more pronounced in ruptured compared with non-ruptured carotid plaques. Conclusions Our findings show that macrophage NCOR1 blocks the pro-atherogenic functions of PPAR gamma in atherosclerosis and suggest that stabilizing the NCOR1-PPAR gamma binding could be a promising strategy to block the pro-atherogenic functions of plaque macrophages and lesion progression in atherosclerotic patients.

  • 29.
    Ostman-Smith, Ingegerd
    et al.
    Gothenburg Univ, Sweden; Queen Silvia Childrens Hosp, Sweden.
    Javidgonbadi, Davood
    Northern Alvsborg Cty Hosp, Sweden.
    Fernlund, Eva
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Concerns About the HCM Risk-Kids Study2020In: JAMA cardiology, ISSN 2380-6583, E-ISSN 2380-6591, Vol. 5, no 3, p. 362-362Article in journal (Other academic)
    Abstract [en]

    n/a

  • 30.
    Samuelsson, John
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Samuelsson, Ulf
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Hanberger, Lena
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Nursing Sciences and Reproductive Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Bladh, Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Åkesson, Karin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Poor metabolic control in childhood strongly correlates to diabetes-related premature death in persons <30 years of age-A population-based cohort study2020In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448Article in journal (Refereed)
    Abstract [en]

    Background/objective

    The importance of metabolic control in childhood regarding excess risk of death in young persons has not been well studied. This registry‐based study aimed to investigate mortality rates and cause of death related to metabolic control in young persons (≤29 years) in Sweden with type 1 diabetes.

    Methods

    All 12 652 subjects registered in the Swedish pediatric diabetes quality register, from 2006 to 2014, were included. Data were merged with the Swedish Cause of Death Register. Standardized mortality rates were calculated using the official Swedish population register.

    Results

    Of 68 deaths identified, 38.2% of the deaths were registered as being due to diabetes whereof the major cause of death was acute complications. Overall standardized mortality ratio was 2.7 (2.1‐3.4, 95% CI). Subjects who died from diabetes had a mean HbA1c of 74 ± 19 mmol/mol (8.9 ± 1.7%) during childhood vs 62 ± 12 mmol/mol (7.8 ± 1.1%) in those still alive (P < .001).

    Conclusions

    In this nationwide cohort of young subjects with type 1 diabetes, there was a high mortality rate compared to the general population. Mean HbA1c in childhood was significantly higher in those who died from diabetes, compared to subjects who were still alive. To decrease mortality in young persons with type 1 diabetes it is essential not only to achieve but also to maintain a good metabolic control during childhood and adolescence.

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  • 31.
    Sluijs, Anne-Marie
    et al.
    Leiden Univ, Netherlands.
    Cleiren, Marc P. H. D.
    Leiden Univ, Netherlands.
    van Lith, Jan M. M.
    Leiden Univ, Netherlands.
    Wijma, Barbro
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Wijma, Klaas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Is fear of childbirth related to the womans preferred location for giving birth? A Dutch low-risk cohort study2020In: Birth, ISSN 0730-7659, E-ISSN 1523-536X, Vol. 47, no 1, p. 144-152Article in journal (Refereed)
    Abstract [en]

    Background In The Netherlands, women with low-risk pregnancy are routinely given the option of home birth, providing a unique opportunity to study the relationship between fear of childbirth (FOC) and preference for childbirth location, and whether women experience higher FOC when the actual location differs from their preference. Methods In this prospective cohort study, 331 nulliparous and parous women completed a questionnaire at gestational week 30 (T1) and two months postpartum (T2). FOC was assessed using versions A (T1) and B (T2) of the Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ). Results At T1, women who preferred home birth had significantly lower FOC compared with women who preferred a hospital birth (mean +/- SD W-DEQ scores: 55 +/- 19.8 and 64 +/- 18.3, respectively, P amp;lt; .01). About 28% of women who responded at T2 gave birth at home. Congruence between the preferred and actual childbirth location was not predictive of FOC assessed at T2 when adjusted for obstetric and psychological variables. In an extended analysis, we found that except for prepartum FOC, the following variables also correlated with postpartum FOC: being referred because of complications and poor neonatal condition. Conclusions Compared to women who prefer hospital birth, women who prefer home birth have lower prepartum and postpartum FOC. Giving birth at a location other than the preferred location does not appear to affect postpartum FOC. Whether giving birth at home or in the hospital, caregivers should pay extra attention to women with high FOC because they are vulnerable to postpartum FOC, especially after a complicated birth and referral.

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  • 32.
    Tordön, Rikard
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences.
    Bladh, Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Svedin, Carl Göran
    Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Sydsjö, Gunilla
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Challenging intellectual, behavioral and educational prerequisites for interventions aimed at school aged children in foster care. A compilation of Swedish test results2020In: Children and youth services review, ISSN 0190-7409, E-ISSN 1873-7765, Vol. 108, article id 104598Article in journal (Refereed)
    Abstract [en]

    Children in foster care constitute a vulnerable group with higher risks for exposure to poorer health, adverse experiences during childhood and poor performance in school. School success is considered one of the most important factors to prevent future adversity and there is a growing interest in society for school results for children in foster care or other out-of-home care arrangements. The purpose of this study was to outline prerequisites for interventions aimed at school performance for children in foster care, related to those in normal population studies. In this study assessments of intelligence, literacy and numeracy skills, mental and behavioral conditions were compiled from 856 children in foster care, between preschool class and 7th grade from 22 Swedish municipalities. Results show lower scores in intelligence, most prominent in working memory, adaptive behavior, literacy and numeracy, and more behavioral problems. Ingroup comparisons showed less favorable scores for boys than girls in general, except in mathematics. These findings call for a need to adapt learning conditions in school by individual assessments of children in out-of-home care, rather than assuming age-typical prerequisites.

    The full text will be freely available from 2022-11-22 12:38
  • 33.
    Tordön, Rikard
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid.
    Bladh, Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Sydsjö, Gunilla
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Svedin, Carl Göran
    Ersta Sköndal Bräcke University College, Stockholm, Sweden.
    Improved Intelligence, Literacy and Mathematic Skills Following School-Based Intervention for Children in Foster Care2020In: Frontiers in Psychology, ISSN 1664-1078, E-ISSN 1664-1078, Vol. 11Article in journal (Refereed)
    Abstract [en]

    Interventions aimed at improving school performance for children in foster care are few and are generally not implemented. By preventing failure in school, the prospect of reducing the risk for future poor health, substance abuse, unemployment, and other detrimental social conditions are met. This paper focuses on the change of preconditions for compulsory school performance in out-of-home care children, following an intervention called “Skolfam” that aims to improve school performance by individual assessments and school-based interventions. In this study, data were compiled from prospective repeated tests of 475 children in foster care in Sweden. Educational preconditions were analysed for compulsory school performance, such as intelligence (WISC-IV), psychosocial (SDQ) and adaptive behavior (ABAS-II), literacy (Reading Chains) and mathematical skills (Magne Mathematic Diagnoses) before and after the first 2 years of the “Skolfam” intervention. All tests were age-standardized and performed by experienced professionals. The results showed improved skills in complex aspects of literacy, mathematics, and cognitive performance, but no improvement in less complex literacy skills, adaptive behavior or mental health symptoms. In conclusion, higher-order cognitive functions can develop positively when appropriate school support is provided. Affective function, adaptive behavior, and psychosocial well-being present a more pervasive challenge for children in foster care. Implications for future research, practice in social services, and school is that further development of methods to aid future prospects for children in out-of-home care should aim to improve both cognitive higher-order executive-, and affective functions.

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  • 34.
    Álvarez-Rodríguez, Manuel
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Martinez, Cristina
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Wright, Dominic
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Rodríguez-Martinez, Heriberto
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    The role of semen and seminal plasma in inducing large-scale genomic changes in the female porcine peri-ovulatory tract2020In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 10, no 1, article id 5061Article in journal (Refereed)
    Abstract [en]

    Semen modifies the expression of genes related to immune function along the porcine female internal genital tract. Whether other pathways are induced by the deposition of spermatozoa and/or seminal plasma (SP), is yet undocumented. Here, to determine their relative impact on the uterine and tubal transcriptomes, microarray analyses were performed on the endocervix, endometrium and endosalpinx collected from pre-ovulatory sows 24 h after either mating or artificial insemination (AI) with specific ejaculate fractions containing spermatozoa or sperm-free SP. After enrichment analysis, we found an overrepresentation of genes and pathways associated with sperm transport and binding, oxidative stress and cell-to-cell recognition, such as PI3K-Akt, FoxO signaling, glycosaminoglycan biosynthesis and cAMP-related transcripts, among others. Although semen (either after mating or AI) seemed to have the highest impact along the entire genital tract, our results demonstrate that the SP itself also modifies the transcriptome. The detected modifications of the molecular profiles of the pre/peri-ovulatory endometrium and endosalpinx suggest an interplay for the survival, transport and binding of spermatozoa through, for instance the up-regulation of the Estrogen signaling pathway associated with attachment and release from the oviductal reservoir.

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